NTA Level 5 • Semester 2 • PST05207

Quality Assurance of Pharmaceutical Products – Complete Full Notes

Complete educational source text in one page

Completeness safeguard: this page keeps the complete educational module/source wording in one place so learning material is not lost when browsing topic by topic. Presenter/tutor metadata is intentionally excluded.

UNITED REPUBLIC OF TANZANIA

Ministry of Health, Community

Development, Gender, Elderly and

Children

PST 05207

Quality Assurance of

Pharmaceutical Products

NTA Level 5 Semester 2

Facilitator Guide

March 2019

Table of Contents

Background ………………………………………………………………………………………………………………. iv

Introduction ……………………………………………………………………………………………………………..viii

Abbreviations/Acronyms …………………………………………………………………………………………….. x

Session 1: Introduction to Good Manufacturing Practices: ………………………………………………. 1

Session 2: Components of GMP …………………………………………………………………………………… 7

Session 3: GMP -Personnel requirements……………………………………………………………………. 13

Session 4: GMP Requirements on Raw Materials …………………………………………………………. 20

Session 5: GMP Documentations Requirements …………………………………………………………… 31

Session 6: GMP Equipments Requirements …………………………………………………………………. 38

Session 7: Quality Control and Assurance in Relation to Preparation of Pharmaceutical

Products…………………………………………………………………………………………………………………… 45

Session 8: The Operating Principles of Equipments and Machines …………………………………. 56

Session 9: Standard Operating Procedures for Equipments and Machines ……………………….. 67

Session 10: Preventive Maintenance Procedures for Equipments and Machines……………….. 72

Session 11: Procedures for Quality Testing of Pharmaceutical Products ………………………….. 79

iii

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Background

There is currently an ever-increasing demand for pharmaceutical personnel in Tanzania.

This is due to expanding investment in public and private pharmaceutical sector. Shortage of

trained pharmaceutical human resource contributes to poor quality of pharmaceutical

services and low access to medicines in the country (GIZ, 2012).

Through Public-Private-Partnership (PPP) the Pharmacy Council (PC) together with

Development Partners (DPs) in Germany and Pharmaceutical Training Institutions (PTIs)

worked together to address the shortage of human resource for pharmacy by designing a

project named “Supporting Training Institutions for Improved Pharmaceutical Services in

Tanzania” in order to improve quality and capacity of PTIs in training.

CSSC prepared a Multi-actor Partnership (MAP) project proposal on how to sustain and

strengthen health care in Tanzania through improvement of pharmaceutical training and an

inter-institutional coordination of actors. This will harmonize and improve access to quality

pharmaceutical service in Tanzania.

The project has a various key stakeholders like; CSSC, NACTE, PC, TCU, CEDHA and

Pharmaceutical Training Institutions (PTIs). Through this project, few PTIs will receive

infrastructural improvements to increase the quantitative and qualitative capacities (CUHAS,

RUCU and KSP). Furthermore this project will train Pharmaceutical tutors from different

PTIs on teaching and assessment methods in Tanzania and thus improved health delivery

through increased qualified human resource.

It was also observed that in the previous stakeholder‟s meetings there was a need for the

development of training manuals and assessment plans for NTA Level 5 & 6, in order to

support the establishment and implementation of the curriculum in PTIs. During MAP kick-

off workshop done in February 2018, Stakeholders agreed that there was a need for

development of the said manuals and it was among the highest priority in Pharmacy

education in Tanzania. Therefore this project aims at developing facilitator‟s guide and

assessment plans for NTA Level 5 & 6.

Pharmacy Council, CSSC and action medeor developed the Terms of Reference and selected

a qualified service provider with experience in material development to develop the

mentioned training manuals and assessment plan. Centre for Educational Development in

Health Arusha (CEDHA) was selected and offered a contract to develop Facilitators guide for

NTA level 5 & 6 and assessment plan.

Centre for Educational Development in Health Arusha (CEDHA) was offered a leading role

with the instructions to include experts who have developed teaching materials for NTA

Level 4. These experts are primarily experienced pharmaceutical and non-pharmaceutical

tutors.

The mode of operation used by CEDHA to develop facilitators guide and assessment plan

was participatory approach which included a number of activities through various workshops

such as planning, and orientation of material development. After these preliminary

workshops, experts developed materials individually and in-groups. Thereafter, developed

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

draft materials were reviewed, edited and formatted and draft one was finalized and shared to

stakeholders for inputs.

Finally, CEDHA submitted the finalized Facilitator‟s guides and assessment plans for NTA

level 5 and 6 to CSSC for endorsement, printing, dissemination and sharing with relevant

authorities.

There are 11 modules for NTA level 5 making 11 facilitator guides including one practicum

guide.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Acknowledgment

The development of standardized training materials of a competence-based curriculum for

pharmaceutical sciences has been accomplished through involvement of different

stakeholders.

Special thanks go to the Pharmacy Council for spearheading the harmonization of training

materials in the pharmacy after noticing that training institutions in Tanzania were using

different curricula and train their students differently.

I would also like to extend my gratitude to Christian Social Service Commission (CSSC) for

their tireless efforts to mobilize funds from development partners (German Ministry of Industry

and action medeor). It is through the implementation of the Multi-Actors Partnership (MAP)

project, CSSC has been able to provide the financial and technical support needed during the

development of this training material.

Many thanks go to the Centre for Educational Development in Health Arusha (CEDHA)

experts on health material development and training who coordinated the development of

these module sessions particularly Ms. Diana H. Gamuya for her commitment in coordinating

and facilitating the planning and development to its completion.

Particular acknowledgements are sent to Mr. Dickson Mtalitinya and Members from the

secretariat of National Council for Technical Education (NACTE) for facilitating and

providing their expertise to the success of this work.

It will be unfair if I will not recognize the efforts and contributions of all CEDHA supportive

staff that made this process a success; accountant, secretary, drivers and printers

Finally, I very much appreciate the contributions of the tutors and content experts

representing PTIs, hospitals, and other health training institutions. Their participation in

meetings and workshops, and their input in the development of this training

manual/facilitators guide have been invaluable.

These participants are listed with our gratitude below:

Ms. Elizabeth Shekalaghe Registrar, Pharmacy Council of Tanzania

Dr. Fadhili Lyimo Assistant Director Allied Health,MoHCDGEC

Dr. Catherine Jincen Acting Principal, CEDHA

Dr. Sungwa N. Kabissi Project Manager – MAP, CSSC

Ms. Diana H. Gamuya CEDHA

Ms. Grace Mallange PC

Ms. Emily Mwakibolwa Pharmacy Council

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Ms. Tumaini H. Lyombe MUHAS

Ms. Dilisi J. Makawia KSP

Director of Human Resources Development

Ministry of Health, Community Development, Gender, Elderly and Children

vii

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Introduction

Module Overview

This module content is a guide for tutors of Pharmaceutical schools for training of students.

The session contents are based on sub-enabling outcomes and their related tasks of the

curriculum for Basic Technician Course in Pharmaceutical Sciences. The module sub-

enabling outcomes and their related tasks are as shown in the curriculum for Basic

Technician Certificate Course in Pharmaceutical Sciences (NTA Level 5).

Target Audience

This module is intended for use primarily by tutors of pharmaceutical schools. The module‟s

sessions give guidance on the time, activities and provide information on how to teach the

session. The sessions include different activities which focus on increasing students‟

knowledge, skills and attitudes.

Organization of the Module

The module consists of 11 (eleven) sessions; each session is divided into several parts as

indicated below:

• Session Title: The name of the session

• Total Session Time: The estimated time for teaching the session, indicated in minutes

• Pre-requisites: A module or session which needs to be covered before teaching the

session.

• Learning Tasks: Statements which indicate what the student is expected to learn by the

end of the session

• Resources Needed: All resources needed for the session are listed including handouts

and worksheets

• Session Overview: The session overview box lists the steps, time for each step, the

activity or method used in each step and the step title

• Session Content: All the session contents are divided into steps. Each step has a heading

and an estimated time to teach that step as shown in the overview box. Also, this section

includes instructions for the tutor and activities with their instructions to be done during

teaching of the contents

• Key Points: Key messages for concluding the session contents at the end of a session

This step summarizes the main points and ideas from the session, based on the learning

tasks of the session

• Evaluation: The last section of the session consists of short questions based on the

learning tasks to check the understanding of students.

• Handouts: Additional information which can be used in the classroom while teaching or

later for students‟ further learning. Handouts are used to provide extra information related

to the session topic that cannot fit into the session time. Handouts can be used by the

students to study material on their own and to refer to them after the session. Sometimes,

a handout will have questions or an exercise for the participants including the answers to

the questions.

viii

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Instructions for Use and Facilitators Preparation

• Tutors are expected to use the module as a guide to train students in the classroom and

skills laboratory

• The contents of the modules are the basis for teaching and learning process.

• Use the session contents as a guide

• The tutors are therefore advised to read each session and the relevant handouts and

worksheets as preparation before facilitating the session

• Tutors need to prepare all the resources, as indicated in the resource section or any other

item, for an effective teaching and learning process

• Plan a schedule (timetable) of the training activities

• Facilitators are expected to be innovative to make the teaching and learning process

effective

• Read the sessions before facilitation; make sure you understand the contents in order to

clarify points during facilitation

• Time allocated is estimated, but you are advised to follow the time as much as possible,

and adjust as needed

• Use session activities and exercises suggested in the sessions as a guide

• Always involve students in their own learning. When students are involved, they learn

more effectively

• Facilitators are encouraged to use real life examples to make learning more realistic

• Make use of appropriate reference materials and teaching resources available locally

Preparation with Handouts and Worksheets

• Go through the session and identify handouts and worksheets needed for the session

• Reproduce pages of these handouts and worksheets for student use while teaching the

session. This will enable students to refer to handouts and worksheets during the session

in the class. You can reproduce enough copies for students or for sharing

• Give clear instructions to students on the student activity in order for the students to

follow the instructions of the activity

• Refer students to the specific page in the student manual as instructed in the facilitator

guide

Using Students Manual When Teaching

• The student manual is a document which has the same content as the facilitator guide,

which excludes facilitator instructions and answers for exercises.

• The student manual is for assisting students to learn effectively and acts as a reference

document during and after teaching the session.

• Some of the activities included in facilitator guide are in the student manual without

facilitator instructions.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Abbreviations/Acronyms

ALCOA Attribute ,legible, contemporaneous, original, and accurate

API Active pharmaceutical ingredient

BHT Butyl hydroxyl toluene

CO2 carbon dioxide

DPD N,N, diethyl-p-phenylene-diamine

FTIR Fourier transfer infrared spectroscopy

GC Gas chromatography

GCP Good clinical practice

GDocP Good documentation practices

GLP Good laboratory practice

GMP Good manufacturing practice

HPLC High performance liquid chromatograph

HPMC Hydroxy propyl-methyl cellulose

LAF Laminar air flow

MLT Microbial limit test

OOS Out of specification

P.S.I Pounds per square inch

PM Preventive maintenance

QA Quality assurance

QC Quality control

RH Relative humidity

RO Reverse osmosis

SLS Sodium lauryl sulphate

SOP Standard operating procedures

TDT Thermal death time

TLC Thin layer chromatograph

U.S.P United States Pharmacopoeia

UV Ultraviolet light

WHO World health organization

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 1: Introduction to Good Manufacturing Practices:

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Give the overview of Good Manufacturing Practice

• Define GMP

• List principles of Good Manufacturing Practice

• Explain the importance of Good Manufacturing Practice in pharmaceutical

Manufacturing

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

2 10 minutes Presentation Overview of Good Manufacturing Practice

3 05 minutes Presentation Definition of GMP

30 minutes Brainstorming

4 Principles of GMP

Presentation

60 minutes Importance of GMP in pharmaceutical

5 Presentation Manufacturing

05 minutes Presentation Key points

05 minutes Presentation

7 Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Overview of Good Manufacturing Practice (10 minutes)

• The first World health organization (WHO) drafts text on good manufacturing practices

(GMP) was prepared in 1967 by a group of consultants at the request of the Twentieth

World Health Assembly.

• In 1969, when the World Health Assembly recommended the first version of the WHO

Certification Scheme on the Quality of Pharmaceutical Products Moving in International

Commerce, it accepted at the same time the GMP text as an integral part of the Scheme.

• The guide to GMP shall be used as a standard to justify GMP status, which constitutes

one of the elements of the WHO Certification Scheme on the Quality of Pharmaceutical

Products Moving in International Commerce, through the assessment of applications for

manufacturing authorizations and as a basis for the inspection of manufacturing facilities.

• It may also be used as training material for government drug inspectors, as well as for

production, quality control and quality assurance personnel in the industry.

STEP 3: Definition of Good Manufacturing Practices (5 minutes)

• Good Manufacturing Practices

o Good Manufacturing Practice is that part of Quality Assurance which ensures that

pharmaceutical products are consistently produced and controlled to the quality

standards appropriate to their intended use and as required by the marketing

authorization or product specification.

QUALITY ASSURANCE

Good Manufacturing Practices QUALITY CONTROL

(GMP)

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

STEP 4: Principles of GMP (30 minutes)

Activity: Brainstorming (5 minutes)

ASK students to brainstorm on the following question

• What are the principles of GMP?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• The following are the Principles of Good Manufacturing Practices: GMP is concerned

with both production and quality control. The basic principles /essential elements are:

o Quality assurance

o Good manufacturing practices for pharmaceutical products

o Sanitation and hygiene

o Qualification and validation

o Complaints

o Product recalls

o Contract production and analysis

o Self-inspection and quality audits

o Personnel

o Training

o Personal hygiene

o Premises

o Equipment

o Materials

o Documentation

o Good practices in production

o Good practices in quality control

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

STEP 5: Importance of GMP in pharmaceutical manufacturing

(60minutes)

Activity: Buzzing (10 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

•What are the importances of GMP in pharmaceutical manufacturing?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Manufacture of pharmaceutical products involve operations of purchase of materials,

production, quality control, release, storage, shipment of finished products and the related

controls. Such operations need to be carried out according to Good Manufacturing

Practices (GMP) that forms an important part of a comprehensive system of quality

assurance. Adherence to GMP ensures that pharmaceutical products are manufactured to

meet quality standards required for their intended use.

• Good manufacturing practice is that part of quality assurance which ensures that products

are consistently produced and controlled to the quality standards appropriate to their

intended use and as required by the marketing authorization.

• GMP is aimed primarily at diminishing the risks inherent in any pharmaceutical

production.

• Such risks are essentially of two types: cross-contamination (in particular of unexpected

contaminants) and mix-ups (confusion) caused by, for example, false labels being put on

containers. It is required that:

o All manufacturing processes are clearly defined, systematically reviewed in the light

of experience, and shown to be capable of consistently manufacturing pharmaceutical

products of the required quality that comply with their specifications;

o Qualification and validation are performed.

o All necessary resources are provided, including ,

 Appropriately qualified and trained personnel.

 Adequate premises and space.

 Suitable equipment and services.

 Appropriate materials, containers and labels

 Approved procedures and instructions.

 Suitable storage and transport.

 Adequate personnel, laboratories and equipment for in- process

o Instructions and procedures are written in clear and unambiguous language

specifically applicable to the facilities provided.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o Operators are trained to carry out procedures correctly.

o Records covering manufacture and distribution, which enable the complete history of

a batch to be traced, are retained in a comprehensible and accessible form.

o The proper storage and distribution of the products minimizes any risk to their

quality.

o A system is available to recall any batch of product from sale or supply.

o Complaints about marketed products are examined; the causes of quality defects

investigated, and appropriate measures taken in respect of the defective products

to prevent recurrence.

• Why is GMP important?

o Poor quality medicines are not only a health hazard, but a waste of money for both

governments and individual consumers.

o Poor quality medicines can damage health

o A poor quality medicine may contain toxic substances that have been unintentionally

added.

o A medicine that contains little or none of the claimed ingredient will not have the

intended therapeutic effect.

o GMP helps boost pharmaceutical export opportunities:

o Most countries will only accept import and sale of medicines that have been

manufactured to internationally recognized GMP.

o Governments seeking to promote their countries' export of pharmaceuticals can do so

by making GMP mandatory for all pharmaceutical production and by training their

inspectors in GMP requirement

STEP 6: Key Points (5 minutes)

• GMP is aimed primarily at diminishing the risks inherent in any pharmaceutical

manufacturing.

• The risks inherent in any pharmaceutical manufacturing include; cross-contamination

(in particular of unexpected contaminants) and mix-ups (confusion) caused by, for

example, false labels being put on containers.

STEP 7: Evaluation (5 minutes)

• What is Good Manufacturing Practice as in regard to pharmaceutical manufacturing?

• What are the basic principles of GMP

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

Signore, A. A., & Jacobs, T. (2017). Good design practices for GMP pharmaceutical

facilities. Boca Raton, Fl.: CRC Press.

amm, G., hler, . . Manual for decentralized infusion production: Infusion Unit

Project, Tanzania. Erscheinungsort nicht ermittelbar: Verlag nicht ermittelbar.

Lund, W. (2009). The pharmaceutical codex: Principles and practice of pharmaceutics. New

Delhi: CBS.

Tanzania Foods and Drug Authority (2017). Guidelines for production of extemporaneous

formulations and Hospital based sterile preparations,

Aulton, M. E., & Taylor, K. (2018). Aulton s pharmaceutics: The design and manufacture of

medicines. Edinburgh: Elsevier.

Gad, S. C. (2008). Pharmaceutical manufacturing handbook production and processes.

Hoboken, NJ: Wiley-Interscience.

United States pharmacopoeia. (2004). Montvale, NJ: Medical Economics.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 2: Components of GMP

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• List components of GMP

• Explain General premises requirements of GMP

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board, chalk and whiteboard markers

• Computer and LCD Projector

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

2 05 minutes Presentation Overview of GMP Components

3 20 minutes Presentation Components of GMP

80 minutes Presentation

4 General Premise Requirements of GMP

Group Discussion

5 05 minutes Presentation Key points

05 minutes Presentation

6 Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Overview of GMP Components (5 minutes)

• Good manufacturing practice (GMP) is a vital component of quality assurance which

helps to ensure that pharmaceutical products are consistently produced with the quality

standards appropriate for their intended use

• GMP defines quality measures for both production and quality control and defines

general measures to ensure that processes necessary for production and testing are clearly

defined , validated reviewed and documented and that the personnel, premises and

material are suitable for the production of pharmaceuticals and biological including

vaccines.

STEP 3: Components of GMP (20 minutes)

The following are components of GMP:

• Premises of good design, which are regularly monitored.

• Equipment of appropriate design and which are well maintained.

• Personnel who are well trained and motivated.

• Quality control of raw materials.

• Quality control of finished products

• Written procedures & other documentation

• Packaging and labelling control.

STEP 4: General Premise Requirements (80 minutes)

Activity: Brainstorming (5minutes)

ASK students to brainstorm on the following question for 5 minutes

• What is a premise as in regards to GMP?

ALLOW students to brain storm for 5minutes

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• By definition Premises include land, buildings, structures, basements and vessels and in

relation to any building includes a part of a building and any cartilage, forecourt, yard, or

place of storage used in connection with building or part of that building; and in relation

to ''vessel'', means ship, boat, air craft, and includes a carriage or receptacle of any kind,

whether open or closed. (TFDC Act 2003).

• Premises requirements:

o The land and buildings where the manufacturing operations are located must

contribute towards the quality of the products. They do this by avoiding the risks of

contamination, permitting effective cleaning and maintenance, minimizing the build-

up of dirt and dust and preventing quality defects. .

o The geography of the chosen location can have a considerable impact upon the design

of facilities. Is the location subject to earthquake hazards? Does it experience

flooding regularly – during the monsoon season? What precautions need to be taken

regarding continuity of supply of services?

o The climate of the area is also important. If the company will be handling, for

example, gelatine capsules then humidity are of great concern. If the company has a

lot of goods requiring temperature or humidity controls in transport, and the goods

have to sit on the dockside for weeks waiting for a boat to arrive, there may be a

problem with the quality of the products. The company may need to rent

temperature-controlled storage. If it does, how will it check the quality of that

storage?

• The factory may have to seek some expensive design solutions to overcome the problems

that arise. Does the process make a lot of noise, for example? If it does and the location

is close to neighbours, then the company may be forced into expensive soundproofing.

• The neighbourhood is also important. If the company is to be located next to a steel mill

then the design precautions that it will have to take, and the level of maintenance that it

will have to undertake, will be very different than if it is in a rural setting. If the

neighbours change, the company will need to take appropriate measures to handle the

situation correctly.

• The company is also required to take measures that prevent the factory polluting the

surrounding area with product or by-products from its manufacturing processes.

• A site inspection is useful before building commences to ensure that the area is suitable

for the construction of a pharmaceutical factory

• How do we achieve good conditions in the factory?

o The layout and design of premises must aim to minimize the risk of errors and permit

effective cleaning and maintenance in order to avoid cross-contamination, build-up of

dust or dirt, and, in general, any adverse effect on the quality of products.

o Premises should be carefully maintained, and it should be ensured that repair and

maintenance operations do not present any hazard to the quality of products.

o Electrical supply, lighting, temperature, humidity and ventilation should be

appropriate and such that they do not adversely affect, directly or indirectly, either the

pharmaceutical products during their manufacture and storage, or the accurate

functioning of equipment.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o Premises should be designed to ensure the logical flow of materials and personnel

corresponding to the sequence of the operations and to the requisite cleanliness levels.

o Interior surfaces (walls, floors and ceilings) should be smooth and free from cracks

and open joints, should not shed particulate matter, and should permit easy and

effective cleaning and, if necessary, disinfection.

o Facilities for changing and storing clothes and for washing and toilet purposes should

be easily accessible and appropriate for the number of users. Toilets should not

communicate directly with production or storage areas.

o Interior surfaces (walls, floors and ceilings) should be smooth and free from cracks

and open joints, should not shed particulate matter, and should permit easy and

effective cleaning and, if necessary, disinfection.

o Facilities for changing and storing clothes and for washing and toilet purposes should

be easily accessible and appropriate for the number of users. Toilets should not

communicate directly with production or storage areas.

o Printed packaging materials are considered critical to the conformity of the

pharmaceutical product to its labeling and special attention should be paid to sampling

and the safe and secure storage of these materials.

o There should normally be a separate sampling area for starting materials. (If sampling

is performed in the storage area, it should be conducted in such a way as to prevent

contamination or cross contamination.)

o Highly active and radioactive materials, narcotics, other dangerous drugs, and

substances presenting special risks of abuse, fire or explosion should be stored in safe

and secure areas.

o The weighing of starting materials should be carried out in separate weighing areas

designed for that use, for example with provisions for dust control. Such areas may be

part of either storage or production areas.

o Pipe work, light fittings, ventilation points and other services should be designed and

sited to avoid the creation of recesses that are difficult to clean. As far as possible, for

maintenance purposes, they should be accessible from outside the manufacturing

areas.

o Production areas should be effectively ventilated, with air control facilities (including

filtration of air to a sufficient level to prevent contamination and cross-contamination,

o Production areas have control of temperature and, where necessary, humidity.

o Drains should be of adequate size and designed and equipped to prevent back-flow.

Open channels should be avoided where possible, but if they are necessary they

should be shallow to facilitate cleaning and disinfection.

o Quality control laboratories should be separated from production areas. Areas where

biological, microbiological or radioisotope test methods are employed should be

separated from each other.

o Quality control laboratories should be designed to suit the operations to be carried out

in them. Sufficient space should be given to avoid mix-ups and cross-contamination.

There should be adequate suitable storage space for samples, reference standards (if

necessary, with cooling), solvents, reagents and records.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o The design of the laboratories should take into account the suitability of construction

materials, prevention of fumes and ventilation. There should be separate air supply to

laboratories and production areas. Separate air-handling units and other provisions are

needed for biological, microbiological and radioisotope laboratories.

o A separate room may be needed for instruments to protect them against electrical

interference, vibration, contact with excessive moisture and other external factors, or

where it is necessary to isolate the instruments.

STEP 5: Key Points (5 minutes)

• Components of GMP includePersonnel who are well trained and motivated, Quality

control of raw materials.

o Quality control of finished products

o Written procedures & other documentation

• Premises include land, buildings, structures, basements and vessels and in relation to any

building include a part of a building and any cartilage, forecourt, yard.

• Premise requirements include, geographical location, the climate of the area , and

neighbourhood

STEP 6: Evaluation (5 minutes)

• Mention components of GMP?

• What are the premises requirements in GMP?

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

Signore, A. A., & Jacobs, T. (2017). Good design practices for GMP pharmaceutical

facilities. Boca Raton, Fl.: CRC Press.

Lund, W. (2009). The pharmaceutical codex: Principles and practice of pharmaceutics. New

Delhi: CBS.

Rawlins E.A, Editor: 1977 Bentley’s Textbook of Pharmaceutics, 8th Ed. Baillie're Tindall.

London

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 3: GMP -Personnel requirements

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• List general possible issues related to personnel in GMP

• List general principles related to personnel in GMP

• Explain requirements for key personnel in GMP

• Review the training of personnel in GMP

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• Pointer

• LCD Projector and computer.

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

35 minutes Presentation General Possible Issues Related to Personnel

Buzzing in GMP

30 minutes General Principles Related to Personnel in

3 Presentation

GMP

30 minutes Presentation

4 Requirements for Key Personnel in GMP

Brainstorming

5 10 minutes Presentation Reviewing the Training for Personnel in GMP

6 05 minutes Presentation Key Points

7 05 minutes Presentation Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: General Possible Issues Related to Personnel in GMP ( 35

minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What are general possible issues related to personnel in GMP?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• The general possible issues related to personnel in GMP are:

o In a company the issues will be around a lack of skills and resources to comply with

all the requirements of GMP:

 Limited staff numbers may mean that people are under pressure to perform. They

may be trying to do too much. There may be a lack of deputies during times of

illness or holidays.

 Recruited staff may have inadequate qualifications.

 Recruited staff may have inadequate experience or experience in an inappropriate

area. Sometimes the owner recruits relatives who are inadequately qualified or

experienced.

 The owner may interfere with quality decisions, particularly if orders are required

urgently or are very valuable. Senior staff may have difficulty in combating this,

since it may cost them their jobs.

 Smaller companies may have no means to develop training materials to educate

their staff in the requirements of GMP. They do not become members of the local

manufacturers‟ association because of cost. They do not then have access to

training programmes that are available through the association.

 Subsidiaries of multinational companies may claim that company procedures or

standards take precedence over local legislation. If this is claimed, it will be most

unusual since all multinationals require local companies to conform first to local

legislation. It will be worth exploring with the company what benefits are obtained

by not conforming to local legislation.

 Large organizations often move people around through promotion, training,

recruitment or relocation. In so doing they can lose sight of the requirements of

GMP. Managers can be promoted into positions for which they are not qualified or

experienced.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

 Companies may not keep adequate training records even though people are

apparently undergoing training.

 As with small companies, large companies may have personnel policies that

penalize people. The problem is that if people are not going to be paid when sick

or injured, they may work on under circumstances that create a risk to the product.

STEP 3: General Principles Related to Personnel in GMP ( 30 minutes)

The following are principles related to personnel in GMP:

• For successful and good quality pharmaceutical production, it is essential to have people

with sufficient knowledge and experience to undertake the work. They must have the

authority and the means to do that work, and there must be enough of them available to

carry out tasks effectively.

• It is most important that the people that are recruited are selected from a group that can

meet the requirements.

• It is not recommended to recruit people to work in manufacturing areas if they are unable

to read the instructions for their safety and for product quality. A medical examination

should be included during the recruitment processes. Operators working with cytotoxic

products may need blood tests at the time of recruitment and at six monthly intervals

thereafter.

• Operators who will work on visual inspection processes should also undertake an eye test

at the time of recruitment with a regular check on a periodic basis afterwards.

• A major and most common problem is that of insufficient people available to do the

work. It is of little value having just one person well qualified and experienced, with no

backup staff. What then happens in the case of sickness or holiday? This can be a very

difficult area, and one which is harder for smaller companies than a multinational

company or similar.

• Another issue that often surfaces is the employment of a well-qualified, but inexperienced

person to manage, for example, quality. An illustration of this is the recruitment by the

owner of a small company of a relative — who is newly qualified, but completely

inexperienced to run a laboratory or manufacturing area.

• The duties incumbent upon any one individual should not be so extensive that he/she

cannot cope, resulting in a risk to quality of the product.

• Staff must have a clear job description which tells them and the rest of the company what

their role is, what their responsibilities are and what authority they have to carry out their

tasks. The company should also have a written organization chart. The combination of

organization chart and written job descriptions enables the company to see quickly

whether there are any gaps or whether there are any areas of overlap, owing to too many

people being involved. The organization chart should make clear and ensure the

independence of QA/QC from production.

• Personnel involved in QA/QC must have the authority to carry out their responsibilities.

This is very easy to say and sometimes not so easy to ensure. Problems can emerge in

every size of company, from small private companies to very large multinational

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

enterprises. They arise because of a combination of human interactions, and the pressures

placed on people by the business considerations

• All personnel involved with materials and products should receive GMP training. This

training should commence upon recruitment and continue throughout employment. The

training should be appropriate to their needs and position within the company, and should

include training in hygiene standards.

• Personnel policies should be designed to encourage people to support the development

and maintenance of high quality standards in all work performed.

• The company should prevent people who have not been properly trained from entering

any production, storage or quality control area without strict supervision. For example: it

should not be the case that people from accounts are allowed to walk through the factory

to get to the warehouse to pick up or deliver invoices. Access to all other areas of the

company should be organized so that no entry to production, storage or laboratory areas is

necessary (see Premises).

STEP 4: Requirements for Key Personnel in GMP (30 minutes)

Activity: Brainstorming (5 minutes)

ASK students to brainstorm on the following question:

• What are requirements for key personnel in GMP?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Key personnel include the following

o The heads of production,

o Quality control personnel

o Sales and distribution personnel

o Authorized person who releases product for sale

• Normally they should all be full-time positions.

• The heads of production and quality control should not report to one another (although they may

both report to a technical director) but may share certain responsibilities.

• In large organizations, it may be necessary to delegate some of the functions; however, the

responsibility cannot be delegated.

• The principle is that there must be independence of quality control from production.

• These key personnel must have the education and experience which is appropriate to their positions.

• Heads of Production and Quality Control should be independent of each other

• Should possess appropriate qualifications Scientific education such as:

 chemistry or biochemistry

 chemical engineering

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

 microbiology

 pharmaceutical sciences and technology

 pharmacology and toxicology

 physiology; or

 other related science subjects relevant to the responsibilities to be undertaken

• The WHO GMP text part one, section 9.7 refers to some of the acceptable qualifications of key

personnel and it goes into a lot of detail.

• Key personnel should first of all have the educational background specified by local legislation

and with the requirements set out in company policy. This will include a combination of

chemistry, biochemistry, chemical engineering, microbiology, pharmaceutical sciences and

technology, pharmacology and toxicology, physiology or other related science subjects relevant to

the responsibilities to be undertaken.

• In particular, the GMP text talks about gaining experience not in a haphazard way, but under

specific guidance of an expert. This is in order to equip personnel with an ability to take difficult

decisions in a professional and scientific way, and to resolve the problems encountered in

manufacturing and quality control.

• It is clear, therefore, that we are talking about professionals who have had a practical as well as an

academic training.

• They should also continue to have training in their area of expertise.

• There are others who play an important role in the operation of the factory, for example, engineers.

Engineers are crucial to the maintenance and operation of the facility and equipment, in particular,

for the processes of planned preventative maintenance and validation.

• Should possess appropriate experience

o Practical experience

o Manufacture and quality assurance

o Preparatory period under professional guidance sometimes needed

o Education and experience should enable personnel to take difficult decisions in an independent,

professional and scientific way resolve the problems encountered in manufacturing and QC

• Personnel should also possess appropriate experience including practical experience in the

manufacture and quality assurance of pharmaceutical products. It is common and recommended,

that there should be a preparatory period under professional guidance for new employees.

• Education and experience should enable personnel to take difficult decisions in an independent,

professional and scientific way, and to resolve the problems encountered in manufacturing and

QC.

STEP 5: Reviewing the Training for Personnel in GMP (10 minutes)

The following are the key points for reviewing training for personnel in GMP

• Training, in accordance with a written, approved programme

• All personnel whose duties take them into production areas; or Into control laboratories;

and For others whose activities could affect the quality of the product including technical,

maintenance and cleaning personnel

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• Induction and continuing training

o On theory and practice of GMP and their duties

o Training records should be kept

o Practical effectiveness checked

o Training before undertaking any new task

• Specific training for staff in special areas, e.g. Where contamination is a hazard,

Including clean areas; or Areas where highly active, toxic, infectious, sensitizing materials

are handled

• The concept of QA should be fully discussed during training to facilitate proper

understanding to ensure its implementation

STEP 6: Key points (5 minutes)

• Personnel general requirements: Adequate number of personnel, All personnel should be

aware of GMP, personnel must receive training and have appropriate qualification

• Key personnel include: Authorized person , head of production and head of quality

control

STEP 7: Evaluation (5 minutes)

• What are general Personnel Requirements in GMP?

• Who are the key personnel as in accordance to GMP?

• What are general principles related to personnel in GMP?

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

Signore, A. A., & Jacobs, T. (2017). Good design practices for GMP pharmaceutical

facilities. Boca Raton, Fl.: CRC Press.

Lund, W. (2009). The pharmaceutical codex: Principles and practice of pharmaceutics. New

Delhi: CBS.

Aulton, M. E., & Taylor, K. (2018). Aulton s pharmaceutics: The design and manufacture of

medicines. Edinburgh: Elsevier.

Rawlins E.A, Editor: (1977) Bentley’s Textbook of Pharmaceutics, 8th Ed. Baillie're Tindall.

London

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 4: GMP Requirements on Raw Materials

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Define pharmaceutical raw material

• Mention types of raw materials used in pharmaceutical manufacturing

• Explain GMP requirements for pharmaceutical raw materials

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

15 minutes Presentation Definition of Pharmaceutical Raw Material

50 minutes Types of Pharmaceutical Raw Materials Used

Presentation

3 in Pharmaceutical Manufacturing

discussion

30 minutes GMP Requirements for Pharmaceutical Raw

4 Presentation Materials

10 minutes Presentation

5 Key Points

6 10 minutes Presentation Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Definition of Pharmaceutical Raw Materials (15 minutes).

Pharmaceutical raw materials generally are substrates or elements which are used for

manufacturing different types of drugs, and basically categorized into three major types

which are:

Raw Material of API: Any substance or mixture of substances intended to be used in the

manufacture of a pharmaceutical dosage form and that, when so used, becomes an active

ingredient of that pharmaceutical dosage form. Such substances are intended to furnish

pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or

prevention of disease or to affect the structure and function of the body. Main thing is that

Accuracy and Precision are must for the raw materials which is used for making the API.

Raw Material of Expedients: is a substance formulated alongside the active ingredient of a

medication, included for the purpose of long-term stabilization, bulking up solid formulations

that contain potent active ingredients in small amounts (thus often referred to as "bulking

agents", "fillers", or "diluents"), or to confer a therapeutic enhancement on the active

ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or

enhancing solubility. Excipients can also be useful in the manufacturing process, to aid in the

handling of the active substance concerned such as by facilitating powder flowability or non-

stick properties, in addition to aiding in vitro stability such as prevention of denaturation or

aggregation over the expected shelf life. The selection of appropriate excipients also depends

upon the route of administration and the dosage form, as well as the active ingredient and

other factors

Raw Material of Packaging: Raw material which is used in making most of the packaging

involve plastic & polymers, glass, paper, aluminum foil and paper boards

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

STEP3:Types of Raw Materials Used in Pharmaceutical Manufacturing (50

minutes)

Activity: Small Group Discussion ( 10 minutes)

DIVIDE students into manageable groups

ASK students to discuss in groups on the following questions

• What are major types of raw materials used in pharmaceutical manufacturing?

ALLOW students to discuss for 5 minutes

ALLOW groups to present for 5 minutes

CLARIFY and SUMMARIZE by using the contents below

The major types of raw materials used in pharmaceutical manufacturing are

• Active pharmaceutical ingredient-(API),

• excipients and

• Packaging materials as shown in step two of this lecture. The following are some of

pharmaceutical excipients commonly used in pharmaceutical manufacturing of solid

dosage forms.

TABLE ONE (1) EXCIPIENTS used in solid dosage forms.

Excipient Function in Working principle Examples

category formulation

Diluents Fillers Make up the bulk of solid Lactose, Directly

unit dosage forms when drug compressible

itself is inadequate to Starches, Dextrose,

produce the bulk Sorbitol,

Microcrystalline

cellulose, Dibasic

Calcium phosphate

Dehydrate

Binders and Impart cohesive Improves free flow Acacia, Gelatin, Starch

Adhesives qualities to powdered qualities by formulation of paste, Polyvinyl

material. granules to desired pyrrolidone, Glucose,

hardness and size Carboxymethyl

cellulose, Povidone

Lubricants Reduce inter-particular Interpose a film of low shear Talc, Stearic acid,

friction, prevent strength that interface Magnesium

adhesion of tablet between the tableting mass stearate, Calcium

material to the surface and die wall stearate, Polyethylene

of dies and punches glycol, Surfactants,

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

facilitate easy ejection vegetable oil

of tablet from die

cavity and improve the

rate of flow tablet

granulation

Glidants Improve flow Added in dry state prior Colloidal Silicone

characteristics of compression, it reduces dioxide

powder mixture friction between particles. (Carbosil), Asbestos free

starch, Corn starch

Disintergrants Facilitate breakup or Function by drawing water Starches, Clays,

disintegration into the tablet, swelling it Cellulose, Cross

after administration and causing the tablet to Linked polymers,

burst apart Modified starches such

as Primogel and

Explotab, Veegum HV.

Crosscarmalose, Cross

Povidone, Sodium starch

glycolate

Coloring Impart aesthetic FD and C, D and C dyes

agents ( these appearance to and lakes

must be dosage form, disguising

approved and off color drugs, product

certified ) identification

Flavors Limited to chewable Mask unpleasant taste Spray dried and other

tablets/ tablets flavors, syrups etc

Intended to dissolve in

mouth.

Sweeteners Impart sweet taste to Mannitol, Saccharin.etc

the formulation; use is

limited to chewable

tablets

Sorbents Moisture proofing Limits the fluid sorbing, Silica gel, activated

taking up of liquid or gas carbon, clay etc

either by adsorption or

absorption in dry state

Coating Protect tablet Hydroxypropylmethyl

materials ingredients from cellulose (HPMC),

deterioration by Synthetic polymers,

moisture, help Shellac, Corn protein

swallowing unpleasant Zein, Polysaccharides,

tasting tablets Capslues coated by

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Gelatin, Povidone, Ethyl

cellulose

Plasticizers For soft gelatin capsule Produce elasticity and Castor oil, Diacetylated

preparation, gelatin flexibility to the coating Monoglycerides,

based materials in case of tablets, Polyethylene glycol,

suppositories, film determine hardness of Polypropylene glycol,

coated capsule shell in Triacetin

tablets etc case of soft gelatin capsule

and impart softness and

resilience to suppositories

TABLE TWO (2) EXCIPIENTS USED IN LIQUID DOSAGE FORMS:

EXCIPIENT FUNCTION IN WORKING EXAMPLE

CATEGORY FORMULATION PRINCIPLE

Solvents. Dissolving Breaking of bonds Water, alcohol, acetic acid,

solute/Active and reducing acetone, ethyl

pharmaceutical effective charge acetates, syrups, etc

Ingredient. on ions thus

increasing Solute-

Co solvents Increase the solubility Solvent forces of

of solute in solvents attraction which

are eventually

greater than

Solute-Solute and

Solvent-Solvent

forces of attraction

Co-solvent system

works by reducing Ethanol, Sorbitol, Glycerin,

the interfacial Propylene glycol

tension between

predominantly

aqueous solutions

and hydrophobic

solutes

Buffers Maintain pH of the Act by binding Phosphate buffers, Acetate

Formulation hydrogen ions in buffers, Citric

acids and donating acid Phosphate buffers

hydrogen ions in

bases

Antimicrobial Prevent microbial Bacteriostatic Benzyl alcohol, Butyl

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Preservatives. growth in action paraben, Phenol,

formulations Thiomersal etc

Antioxidants. Control oxidation Act by getting Ascorbic acid, Sodium

preferentially bisulphate, Thiourea,

oxidized or by Butyl Hydroxy Toluene

blocking an (BHT),

oxidative chain Tocopherols.etc

reaction.

Wetting agents Aid wetting and Act by reducing Sodium Lauryl Sulphate

dispersion of interfacial tension (SLS), Tween 80, Spans,

hydrophobic active between solids Lecithins etc

pharmaceutical and liquids in

ingredients. suspensions

Antifoaming Discourage formation Lowers surface Simethicone, Organic

agents of stable foam. tension and phosphates, Alcohols,

cohesive binding Paraffin oils, Sterates and

of liquid phase glycols

Thickening Prevent Work by Methyl cellulose,

agents. settling/sedimentation, entrapment of Hydroxyethyl cellulose,

Modify viscosity. solid particles Microcrystallince cellulose

etc.

Humectants Retard evaporation of They are Propylene glycols, Glycerol,

aqueous vehicles from hygroscopic in Polyethylene glycol

dosage forms nature which helps

in preventing

evaporation of

solvent

Chelating agents Protect drug from Chelating agents Disodium EDTA, Dihydroxy

catalysts that form complexes ethyl glycine, Citric acid and

accelerate the with Tartaric acid

oxidative reaction metal ions

inactivating their

catalytic activity

in oxidation of

medicaments

Emulsifying Prevent coalescence Forms barriers at Sodium Lauryl Sulphate,

agents of the dispersed interface, and Cetrimide,

Globules. reduces interfacial Macrogol esters, Sorbitan

tension esters etc

Flocculating Prevent caking Addition of an Starch, Sodium alginate,

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

agents. electrolyte reduces Carbomer.etc

the magnitude of

zeta potential of

dispersed

particles.

Sweetening Impart sweetness Sucrose, Sorbitol, Saccharin,

agents Aspartame, Sucralase

Colors. Impart color Amaranth, Erythrosin, Eosin,

Tartarazine etc

Flavors Impart flavor Aromatic waters.

Excipient used in Developing pressure Trichloromonofluoromethane,

Aerosol in container which Dichlorodifluoromethane

Propellant expels the product

TABLE Three (3) EXCIPIENTS USED IN SEMI SOLID DOSAGE FORMS:

EXCIPIENT CATEGORY FX IN FORMULATION EXAMPLE

Structure forming Form gel like structure Cetosterly alcohol, sorbiton

excipients and other hydrophilic

surfactants , fluid

hydrocarbons like mineral

oils etc

Preservatives For preserving the Benzyl alcohol, proply

formulation paraben, methyl paraben,

chlorocresol, imidazolidinyl

urea, sodium benzoate

etc

Antioxidants Prevent oxidation Butyl hydroxy toulne , butyl

hydroxy anisole, ascorbic

acid etc

Solubilizers. Enhance solubility of the Lanolin, cholesterol or

active ingredient in ointments cholesterol esters

Gelling agents Form gels Carbomer934, pemulen®,

carboxy methyl cellulose,

hydroxy propyl cellulose,

xanthan gum etc

Emollients Modify vehicle/skin Glycerin, mineral oil,

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

characteristics to assist petrolatum, isopropyl

penetration of active palmitate etc

ingredient through skin

suppository bases Used to form base for Cocoa butter, glycerin,

dissolving coconut oil, gelatin,

active ingredient hydrogenated vegetable oil,

polyethylene glycol etc

STEP 4: GMP Requirements for Pharmaceutical Raw Materials (30

minutes)

General principle:

The main objective of a pharmaceutical plant is to produce finished products for patients‟ use

from a combination of materials (starting and packaging). Materials include starting

materials, packaging materials, gases, solvents, process aids, reagents and labeling materials.

Therefore the following should be taken into consideration, and that:

• No materials used for operations such as cleaning, lubrication of equipment and pest

control, should come into direct contact with the product. Where possible, such materials

should be of a suitable grade (e.g. food grade) to minimize health risks.

• All incoming materials and finished products should be quarantined immediately after

receipt or processing and inspection, until they are released for use or distribution.

• All materials and products should be stored under the appropriate conditions established

by the manufacturer and in an orderly manner to permit batch segregation and stock

rotation by First Expiry First Out and/or First In First Out rule.

• Appropriate stock management system and procedures should be established with the use

of bin cards and stock cards or any fully validated electronic record system.

• Materials should not be kept directly in contact with floors, nearer to walls and ceilings in

order to allow appropriate space for cleaning and inspection.

• Water used in the manufacture of pharmaceutical products should be suitable for its

intended use.

STARTING MATERIAS.

• The purchase of starting materials is an important operation that should involve staff who

has a particular and thorough knowledge of the products and suppliers.

• Starting materials should be purchased only from approved suppliers and, where possible,

directly from the producer. It is also recommended that the specifications established by

the manufacturer for the starting materials be discussed with the suppliers. It is of benefit

that all critical aspects of the production and control of the starting material in question,

including handling, labeling and packaging requirements as well as complaints and

rejection procedures, are contractually agreed between the manufacturer and the supplier.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• For each consignment, the containers should be checked for at least integrity of package

and seal and for correspondence between the order, the delivery note, and the supplier‟s

labels.

• All incoming materials should be checked to ensure that the consignment corresponds to

the order. Containers should be cleaned where necessary and labeled, if required, with the

prescribed information. Where additional labels are attached to containers, the original

information should not be lost.

• Damage to containers and any other problem that might adversely affect the quality of a

material should be recorded and reported to the quality control department and

investigated.

• If one delivery of material is made up of different batches, each batch must be considered

as separate for sampling, testing and release.

PACKAGING MATERIALS

• The purchase, handling and control of primary and printed packaging materials should be

as for starting materials.

• Particular attention should be paid to printed packaging materials. They should be stored

in secure conditions so as to exclude the possibility of unauthorized access. Roll feed

labels should be used wherever possible. Cut labels and other loose printed materials

should be stored and transported in separate closed containers so as to avoid mix-ups.

Packaging materials should be issued for use only by designated personnel following an

approved and documented procedure.

• Each delivery or batch of printed or primary packaging material should be given a

specific reference number or identification mark.

• Out-dated or obsolete primary packaging material or printed packaging material should

be destroyed and its disposal recorded.

• All products and packaging materials to be used should be checked on delivery to the

packaging department for quantity, identity and conformity with the packaging

instructions

FINISHED PRODUCTS

• Finished products should be held in quarantine until their final release, after which they

should be stored as usable stock under conditions established by the manufacturer.

• The evaluation of finished products and the documentation necessary for release of

product for sale are described under “Good practices in quality control”.

WASTE MATERIALS

• Provision should be made for the proper and safe storage of waste materials awaiting

disposal. Toxic substances and flammable materials should be stored in suitably designed,

separate and enclosed cupboards.

• Waste material should not be allowed to accumulate. It should be collected in suitable

receptacles for removal to collection points outside the buildings and disposed of safely

and in a sanitary manner at regular and frequent intervals.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

MISCELLANEOUS

• Rodenticides, insecticides, fumigating agents and sanitizing materials should not be

permitted to contaminate equipment, starting materials, packaging materials, in process

materials or finished products.

STEP 5: Key points (10 minutes)

• The major types of raw materials used in pharmaceutical manufacturing are API,

excipients and packaging materials.

• Pharmaceutical raw materials generally are substrates or elements which are used for

manufacturing different types of drugs.

• Excipients categories include; preservatives, anti-oxidants, gelling agents, humectants,

wetting agents etc

• API: Any substance or mixture of substances intended to be used in the manufacture of a

pharmaceutical dosage form and such substances are intended to furnish pharmacological

activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of

disease or to affect the structure and function of the body.

STEP 6: Evaluation (10 minutes)

• Define API?

• What are major types of raw materials used in pharmaceutical manufacturing?

• What are examples of various excipients used in pharmaceutical manufacturing?

• What are pharmaceutical raw materials?

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

Signore, A. A., & Jacobs, T. (2017). Good design practices for GMP pharmaceutical

facilities. Boca Raton, Fl.: CRC Press.

Lund, W. (2009). The pharmaceutical codex: Principles and practice of pharmaceutics. New

Delhi: CBS.

Aulton, M. E., & Taylor, K. (2018). Aulton s pharmaceutics: The design and manufacture of

medicines. Edinburgh: Elsevier.

Rawlins E.A, Editor: 1977 Bentley’s Textbook of Pharmaceutics, 8th Ed. Baillie're Tindall.

London

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 5: GMP Documentations Requirements

Total Session Time: 120 minutes

Prerequisites

None

Learning Tasks

By the end of this session students are expected to be able to:

• Define documentation terms

• List good documentation practices

• Explain importance of Good Documentation

• Explain what constitutes Good Documentation

• Explain GMP documentation requirements

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• Pointer

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

2 15 minutes Presentation Definition of Documentation Terms

25 minutes Presentation

3 Good Documentation Practices

Buzzing

4 15 minutes Presentation Importance of Good Documentation

5 15 minutes Presentation Constituents of Good Documentation

35 minutes GMP Documentation Requirements

6 Presentation

7 05 minutes Presentation Key points

8 05 minutes Presentation Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning objectives and clarify

ASK students if they have any questions before continuing.

STEP 2: Definition of Documentation Terms (15minutes)

Batch (or lot): A defined quantity of starting material, packaging material, or product

processed in a single process or series of processes so that it is expected to be homogeneous.

It may sometimes be necessary to divide a batch into a number of sub-batches, which are

later brought together to form a final homogeneous batch. In the case

of terminal sterilization, the batch size is determined by the capacity of the autoclave. In

continuous manufacture, the batch must correspond to a defined fraction of the production,

characterized by its intended homogeneity. The batch size can be defined either as a fixed

quantity or as the amount produced in a fixed time interval.

“Manufacturing” includes all operations of receipt of materials, production, packaging,

repackaging, labelling, relabeling, quality control, release, storage and distribution of APIs

and the related controls

Master Formula: A document or set of documents specifying the starting materials with

their quantities and the packaging materials, together with a description of the procedures and

precautions required to produce a specified quantity of a finished product as well as the

processing instructions, including the in-process controls.

Master Record: A document or set of documents that serve as a basis for the batch

documentation (blank batch record).

ALCOA+ A commonly used acronym for „Attributable, Legible, Contemporaneous, Original

and Accurate‟ which puts additional emphasis on the attributes being „Complete, Consistent,

Enduring and Available‟– qualities which are implicit in the basic ALCOA principles.

Backup: A backup means a copy of one or more electronic files created as an alternative in

case the original data or system are lost or become unusable.

Computerized System: A computerized system can create, modify, maintain, archive,

retrieve or transmit electronic records. A computerized system consists of hardware, software

and network components which together fulfill certain functionalities. They can also be

defined as a logical entity, partially or entirely controlled by computer but may also include

some equipment, utilities, sensors and actuators along with the governing procedures.

Examples of such a system are Building Management System (BMS), Automated

Manufacturing/Laboratory System, Document Management System,

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Criterion Meaning

Attributable Attributable‟ means information is captured in the record such that it is

uniquely identified as executed by the originator of the data (e.g., a

person and/or a computer system).

Legible The terms „legible‟, „traceable‟ and „permanent‟ refer to the requirements

that data are readable, understandable and allow a clear picture of the

sequencing of steps or events in the record

Contemporaneous is the process of documentation (on paper or electronically)

at the time of the occurrence of an activity

Original Original‟ data includes the first capture or capture at source of data or

information and all subsequent data required to fully reconstruct the

conduct of the GxP activity

Accurate Accurate‟ means that data are correct, truthful, valid and reliable.

complete „Complete‟ means that all data from analysis, including any data

generated before a problem is observed, data generated after repeating

part or all of the work, or re-analysis performed on the sample are

contained in the data record

Consistent „ means that all elements of the analysis, such as the sequence of

events, follow on and data files are date-stamped (all processes) and time

stamped (when using a hybrid or electronic system) in the expected order

and such data are contained in the record.

Enduring Enduring‟ means that all data have been recorded on authorized media

which can be preserved for a period of time, e.g., laboratory notebooks,

numbered worksheets, for which there is accountability, or electronic

media. Data recorded on scrap paper or any other media which can be

discarded later, e.g., backs of envelopes, laboratory coat sleeves or

Post‑It notes, etc. are not considered enduring.

Available Available‟ means that the complete collection of records can be accessed

or retrieved for review and audit or inspection over the lifetime of the

record

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

STEP 3: Good Documentation Practices (GDocP) (25 minutes)

Activity: Buzzing (5minutes)

ASK students to pair up and buzz on the following questions for 5 minutes

• What is a good documentation practice?

ALLOW few pairs to respond and let other pairs add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

The equipments used in facility based pharmaceutical preparation

Good documentation practice is an essential part of the quality assurance and such, related

to all aspects of GMP” this definition is based on WHO.

Principle

Good documentation constitutes an essential part of the quality assurance system. Clearly

Written documentation prevents errors from spoken communication and permits tracing of

Batch history. Specifications, Manufacturing Formulae and instructions, procedures, and

Records must be free from errors and available in writing. The legibility of documents is of

Paramount importance. Instructions must be in the imperative – Go, Do, Stop Mix, Blend,

Wash, etc…… Look for short sentences. Long sentences do not allow the reader time to grasp

messages. A florid, roseate style over endowed with polysyllabic phraseology confuses the

reader.

Good documentation practices include the following;

• Records should be completed at time of activity or when any action is taken

• Superseded documents should be retained for a specific period of time

• Records should be retained for at least one year after the expiry date of the finished product

• Concise, legible, accurate and traceable

• Picture is worth a thousand words

• Clear examples

• Don‟t assume knowledge.

Purpose of Documentations

• Defines specifications and procedures for all materials and methods of manufacture and

control

• Ensures all personnel know what to do and when to do it

• Ensure that authorized persons have all information necessary for release of product

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• Ensures documented evidence, traceability, provide records and audit trail for

investigation

• Ensures availability of data for validation, review and statistical analysis.

STEP 4: Importance of Good Documentation (15 minutes)

Good documentation is an essential part of GMP because:

• An essential part of the quality assurance system and should exist for all aspects of GMP

(reference: WHO GMP,Volume 2)

• Correct, complete, current, and consistent information effectively meet customer and

stakeholder' requirements

• Helps to reduce observations raised on inadequate documentation practices

• Simplify Communication.

• minimizes Costs and losses

• Audit trail. In incase for easy retrieval of any matter arise

STEP 5: Constituents of Good Documentation (15minutes)

Good documentation constitutes the following:

• Approve, review and update documents

• Changes & current revision status of documents identified

• Relevant versions of applicable documents available at points of use

• Documents remain legible and readily identifiable

• Documents of external origin identified and their distribution controlled

• Prevent unintended use of obsolete documents, and archiving

STEP 6: GMP Documentation Requirements (35 minutes)

The general requirements of GDocP as in accordance to GMP of Pharmaceutical

manufacturing are explained below as follows;

• Documents should be designed, prepared, reviewed and distributed with care. They

should comply with the relevant parts of the manufacturing and marketing authorizations.

• Documents should be approved, signed and dated by the appropriate responsible persons.

No document should be changed without authorization and approval.

• Documents should have unambiguous contents: the title, nature and purpose should be

clearly stated. They should be laid out in an orderly fashion and be easy to check.

Reproduced documents should be clear and legible. The reproduction of working

documents from master documents must not allow any error to be introduced through the

reproduction process.

• Documents should be regularly reviewed and kept up to date. When a document has been

revised, a system should exist to prevent inadvertent use of the superseded version.

Superseded documents should be retained for a specific period of time.

• Where documents require the entry of data, these entries should be clear, legible and

indelible. Sufficient space should be provided for such entries.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• Any alteration made to a document should be signed and dated; the alteration should

permit the reading of the original information. Where appropriate, the reason for the

alteration should be recorded.

• Records should be made or completed when any action is taken and in such a way that all

significant activities concerning the manufacture of pharmaceutical products are

traceable. Records should be retained for at least one year after the expiry date of the

finished product.

• Specifications describe in detail the requirements with which the products or materials

used or obtained during manufacture have to conform. They serve as a basis for quality

evaluation.

• Manufacturing Formulae, Processing and Packaging Instructions state all the starting

materials used and lay down all processing and packaging operations.

• Procedures give directions for performing certain operations e.g. cleaning, clothing,

environmental control, sampling, testing, and equipment operations.

• Data may be recorded by electronic data processing systems, photographic or other

reliable means, but detailed procedures relating to the system in use should be available

and the accuracy of the records should be checked. If documentation is handled by

electronic data processing methods, only authorized persons should be able to enter or

modify data in the computer and there should be a record of changes and deletions; access

should be restricted by passwords or other means and the result of entry of critical data

should be independently checked. Batch records electronically stored should be protected

by back-up transfer on magnetic tape, microfilm, paper or other means. It is particularly

important that the data are readily available throughout the period of retention.

STEP 7: Key Points (5 minutes)

• Master Record: A document or set of documents that serve as a basis for the batch

documentation (blank batch record).

• Master Formula: A document or set of documents specifying the starting materials with

their quantities and the packaging materials, together with a description of the procedures

and precautions required to produce a specified quantity of a finished product as well as

the processing instructions, including the in-process controls.

• Labels are required for all containers, equipment and premises.

STEP 8: Evaluation (5 minutes)

• What is GDocP?

• What is difference between master formula and master record?

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

Signore, A. A., & Jacobs, T. (2017). Good design practices for GMP pharmaceutical

facilities. Boca Raton, Fl.: CRC Press.

Lund, W. (2009). The pharmaceutical codex: Principles and practice of pharmaceutics. New

Delhi: CBS.

Aulton, M. E., & Taylor, K. (2018). Aulton s pharmaceutics: The design and manufacture of

medicines. Edinburgh: Elsevier.

Gad, S. C. (2008). Pharmaceutical manufacturing handbook production and processes.

Hoboken, NJ: Wiley-Interscience.

Rawlins E.A, Editor: 1977 Bentley’s Textbook of Pharmaceutics, 8th Ed. Baillie're Tindall.

London

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 6: GMP Equipments Requirements

Total Session Time: 120 minutes

Pre-requisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Explain the GMP requirements for equipment used in pharmaceutical manufacturing

• Explain the construction features of GMP compliant equipment

• Outline the basic equipment used in pharmaceutical production

• Explain the calibration of equipment used in pharmaceutical production

• Explain the cleaning of equipment used in pharmaceutical production

• Explain the preventive maintenance of equipment used in pharmaceutical production

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

10 minutes Buzzing

2 General Features of Manufacturing Equipment

Presentation

Small group

3 35 minutes discussion GMP Requirements for Equipments

Presentation

4 20 Minutes Presentation Construction of Equipment

20 minutes Basic Equipment in Pharmaceutical

5 Presentation

Manufacturing

20 Minutes Calibration, Cleaning and Maintenance of

6 Presentation

Equipment

7 05 minutes Presentation Key Points

8 05 minutes Presentation Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: General Features of Manufacturing Equipment (10 minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What are the features of pharmaceutical manufacturing equipment?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Equipment used in the manufacture, processing, packing or holding of a drug product must

be of appropriate design, adequate size, and suitably located to facilitate operations for its

intended use and for its cleaning and maintenance

• Effectiveness of equipment starts at the design stage

• Pharmaceutical manufacturing companies contribute indirectly in the design of equipment

by providing information on requirements and feedback on existing equipment

• Equipment must be located, designed, constructed, adapted and maintained to suit the

operations to be carried out

STEP 3: GMP Requirements for Equipments (35 minutes)

Activity: Small Group Discussion (10 minutes)

DIVIDE students into small manageable groups

ASK students to discuss on the following question

• What are the GMP requirements for equipment used in pharmaceutical production?

ALLOW students to discuss for 10 minutes

ALLOW few groups to present and the rest to add points not mentioned

CLARIFY and SUMMARIZE by using the contents below

• Pharmaceutical manufacturing equipment should meet the following requirements;

o Operating criteria

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

 Should be adequate to meet process, size, speed and effectiveness requirements

o Spare parts

 Availability of spares and servicing

 This can result in using different makes of an equipment in different parts of the

world

o Maintenance

 Frequency and ease of maintenance significantly impact on productivity and even

quality

 Equipment break down during process could adversely affect quality

 Cleanability of the equipment

 Accessibility to the parts of equipment needed to be cleaned

 Easy of disassembling and re-assembling the equipment

o Environmental issues

 Dust dissemination

 Potential for contamination of other products and requiring operators to wear

additional protective clothing and frequent cleaning of facility

 Noise and energy use

o Equipment design, size and space required for its location

o Construction materials of the equipment

o Process controls on the equipment

 Automatic weight adjustment on tablet presses

 Temperature recorders on ovens

o Cost of the equipment

 Base price of the equipment

 Additional costs related to installation, etc.

o Design and maintenance manuals

 Manuals are important for validation/qualification of the equipment and

maintenance programs

STEP 4: Construction of Equipment (20 minutes)

• Equipment layout and design must aim to minimize risks of error and permit effective

cleaning and maintenance

o This will avoid cross-contamination, dust and dirt-build up and any adverse effect on

the quality of the product

• Equipment must be installed to minimize risks of error and contamination

• The construction of the equipment must meet the following features;

o Surfaces

 Surfaces that contact components, in-process materials or drug product should be

smooth, nonreactive or absorptive

 These surfaces should not alter the safety, identity, strength, quality or purity of

the drug product beyond the official or other established requirements

o Fixed pipework (for transfer of materials through pipelines)

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

 All pipes used must be of right standard and specification for the material and

pipeline to prevent any wrong connections and mix-ups

 All pipes must be clearly labelled

 Labels in all pipes should indicate contents and direction of flow

 Servicing pipings and devices must be adequately marked

 The use of adaptors is not recommended

 Piping system should allow monitoring and testing of materials delivered in them

at regular intervals

o Substances required for operation of equipment

 Coolants, lubricants and other substances required for operation of the equipment

should not come into contact with components, drug product, containers,

closures, in-process materials or drug product

 Lubrication needs to be of good grade, controlled and monitored

o Potential sources of contamination

 Construction of equipment should be in a such a way that motors, drive belts,

gears and other potential sources of lubricant contamination are located away

from vessels or package openings that could result in product contamination

STEP 5: Basic Equipment in Pharmaceutical Manufacturing (20 minutes)

• Balances and measuring equipment

o Must be of appropriate range and precision

 All balances and measuring equipment must be capable of weighing or measuring

the materials over the desired range required for production and testing

 Appropriate weighing and measuring equipment must available in the relevant

areas i.e. production area and quality control laboratories

o Must be calibrated on scheduled basis

 Calibration must be done on regular intervals

 Check weighing must be done on daily basis

 Proper records of calibration must be maintained

o There are should be SOPs for use, calibration, cleaning and maintenance of weighing

and measuring equipment

• Production equipment

o Must Production equipment must be suitably designed for the intended uses

o not be hazardous to the product

o Some production equipment include mixers, granulators, tablet presses, capsule filling

machine, liquid filling machine, packing machine etc

o Defective equipment must be removed or labelled to prevent use

o Must be designed to allow easy cleaning even if it is dedicated to one product

o Relevant SOPs (use, cleaning, maintenance) must be available and in use

• Control laboratory equipment

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o Equipment and instruments in quality control laboratories must be suitable for the

tests to be performed

o Defective equipment must be removed or labelled to prevent their use

• Washing, cleaning and drying equipment

o Equipment used for washing and drying should be designed to promote easy cleaning

 Cleaning on scheduled basis

 Procedures (SOPS) should be followed and records kept

STEP 6: Calibration, Cleaning and Maintenance of Equipment (20

minutes)

• Equipment and utensils must be cleaned, maintained and sanitized at appropriate intervals

to prevent malfunctions or contamination

o Contamination alters safety, identity, strength, quality or purity of the drug product

beyond the official or other established requirements

• Calibration of equipment

o Control, weighing, measuring, monitoring and test equipment must calibrated

according to written SOP and an established schedule

o Performed using standards traceable to certified standards

o Calibration records maintained

o Current calibration status known and verifiable

o Out of calibration instruments should not be used, and deviations investigated to

determine if these could have had an impact on the quality of the intermediate(s) or

API(s) manufactured using this equipment since the last successful calibration

• Cleaning and Preventive Maintenance

o There should be SOPs and schedules to be followed for cleaning and preventive

maintenance of equipment

o SOPs for cleaning of equipment and its subsequent release for use

o Detailed cleaning SOPs to enable operators to clean each type of equipment in a

reproducible and effective manner.

o The SOPs should include;

• Assignment of responsibility for cleaning and maintaining equipment

• Maintenance and cleaning schedules

• Descriptions of methods, equipment and materials used in cleaning and maintenance

operations

 Methods for disassembling and reassembling equipment to ensure proper cleaning

and maintenance

• Removal or obliteration of previous batch identification

• Instruction for the protection of clean equipment from contamination prior to use

• Inspection of equipment for cleanliness immediately before use, if practical

• Establishing the maximum time that may elapse between the completion of processing and

equipment cleaning, when appropriate

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• Documentation

o Records of calibration, cleaning and preventive maintenance of all equipment must

be kept properly

STEP 6: Key Points (5 minutes)

• Equipment used in the manufacture, processing, packing or holding of a drug product must

be of appropriate design, adequate size, and suitably located to facilitate operations for its

intended use and for its cleaning and maintenance

• Equipment in pharmaceutical manufacturing must meet GMP requirements

• Basic equipment in pharmaceutical production include weighing and measuring equipment,

production equipment, quality laboratory equipment and equipment for washing, cleaning

and drying

STEP 7: Evaluation (5 minutes)

• What are the features of pharmaceutical manufacturing equipment?

• What are the GMP requirements for pharmaceutical equipment?

• What are the GMP requirements for equipment used in pharmaceutical production?

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

Signore, A. A., & Jacobs, T. (2017). Good design practices for GMP pharmaceutical

facilities. Boca Raton, Fl.: CRC Press.

Lund, W. (2009). The pharmaceutical codex: Principles and practice of pharmaceutics. New

Delhi: CBS.

Aulton, M. E., & Taylor, K. (2018). Aulton s pharmaceutics: The design and manufacture of

medicines. Edinburgh: Elsevier.

Gad, S. C. (2008). Pharmaceutical manufacturing handbook production and processes.

Hoboken, NJ: Wiley-Interscience.

Rawlins E.A, Editor: 1977 Bentley’s Textbook of Pharmaceutics, 8th Ed. Baillie're Tindall.

London

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 7: Quality Control and Assurance in Relation to

Preparation of Pharmaceutical Products

Total Session Time: 120 minutes

Prerequisites

Learning Tasks

By the end of this session students are expected to be able to:

• Define quality

• Outline the importance of quality in relation to preparation of pharmaceutical products

• Define quality assurance

• Define quality Control

• QC/QA comparisons

• List functions of quality control laboratory in relation to preparation of pharmaceutical

products

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

15 minutes Presentation

2 Definition of Quality

Buzzing

10 Minutes Presentation

3 Importance of Quality

4 10 minutes Presentation Definition of Quality Control

15 minutes Presentation

5 Definition of Quality Assurance

20 minutes Presentation

6 QC/QA Comparisons

Brain storming

Functions of Quality Control Laboratory in

Presentation Relation to Preparation of Pharmaceutical

35 minutes Products

8 05 minutes Presentation Key Points

9 05 minutes Presentation Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Definition of Quality (15 minutes)

Activity: Buzzing (5minutes)

ASK students to pair up and buzz on the following questions for 5 minutes

• What is quality?

ALLOW few pairs to respond and let other pairs add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

The equipments used in facility based pharmaceutical preparation unit include the following

• Quality is a set of inherent properties of a product, system or process fulfills requirements.

(Customer satisfaction). The ability of a product or service to satisfy the specific customer

needs. Achieved by conforming to established requirements and standards. Or alternatively

quality can be defined as; Is the attribute or collection of attributes appropriate for intended

use. Is the attribute or collection of attributes desirable for intended use?

Quality = E2+C,

EFFECTIVENESS – Meeting Customer Needs

EFFICIENCY – Quantity of Resources used to meet needs

COMPLIANCE – Meeting Regulatory Requirements.

The typical dictionary deﬁnition of quality refers to the „„degree or grade of excellence‟‟;

in this sense, quality is a relative measure of goodness. Deﬁning quality as goodness is so

General that it offers no operational content. How do we build an operational deﬁnition?

The answer is, „„Adopt a customer focus.‟‟ Operationally, a quality product or service

is one that meets or exceeds customer expectations? In effect, quality is customer satisfaction.

ut what is meant by „„customer expectations‟‟? Customer expectations can be

Described by quality attributes or by what are often referred to as „„dimensions of quality.

‟Thus, a quality product or service is one that meets or exceeds customer expectations on the

following eight dimensions:

1. Performance

2. Aesthetics

3. Serviceability

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

4. Features

5. Reliability

6. Durability

7. Quality of conformance

8. Fitness for use

The ﬁrst four dimensions describe important quality attributes but are difficult to measure.

Performance: refers to how consistently and how well a product functions. For services, the

inseparability principle means that the service is performed in the presence of the customer.

Thus, the performance dimension for services can be further deﬁned by the attributes of

responsiveness, assurance, and empathy. Responsiveness is simply the willingness to help

customers and provide prompt, consistent service. Assurance refers to the knowledge and

courtesy of employees and their ability to convey trust and conﬁdence. Empathy means

providing caring, individualized attention to customers.

Aesthetics: is concerned with the appearance of tangible products (for example, style and

beauty) as well as the appearance of the facilities, equipment, personnel, and communication

materials associated with services.

Serviceability: measures the ease of maintaining and/or repairing the product. Features

(quality of design) refer to characteristics of a product that differentiate between functionally

similar products. For example, the function of automobiles is to provide transportation. Yet,

one auto may have a four-cylinder engine, a manual transmission, vinyl seats, room to seat

four passengers comfortably, and front disk brakes; another may have a six-cylinder engine,

an automatic transmission, leather seats, room to seat six passengers comfortably, and

antilock brakes. Similarly, ﬁrst class air travel and economy air travel reﬂect different design

qualities. First-class air travel, for example, offers more leg room and more luxurious seats.

Obviously, in both cases, the product features are different. Higher design quality is usually

reﬂected in higher manufacturing costs and in higher selling prices. Quality of design helps a

company determine its market. A market exists for the four-cylinder and the six-cylinder cars

as well as economy air travel and ﬁrst-class air travel.

Reliability: is the probability that the product or service will perform its intended function

for a speciﬁed length of time.

Durability: is deﬁned as the length of time a product functions.

Quality of conformance: is a measure of how a product meets its speciﬁcations. For

example, the speciﬁcations for a machined part may be a drilled hole that is three inches in

diameter, plus or minus /8 inch. Parts falling within this range are deﬁned as conforming

parts.

Fitness of use: is the suitability of the product for carrying out its advertised functions. If

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

there is a fundamental design ﬂaw, the product may fail in the ﬁeld even if it conforms to its

speciﬁcations. Product recalls are frequently the result of ﬁtness-of-use failures.

Improving quality, then, means improving one or more of the eight quality dimensions

while maintaining performance on the remaining dimensions. Providing a higher-quality

product than a competitor means outperforming the competitor on at least one dimension

while matching performance on the remaining dimensions. Although all eight dimensions are

important and can affect customer satisfaction, the quality attributes that are measurable tend

to receive more emphasis. Conformance, in particular, is strongly emphasized. In fact, many

quality experts believe that „„quality is conformance‟‟ is the best operational deﬁnition. There

is some logic to this position. Product speciﬁcations should explicitly consider such things as

reliability, durability, ﬁtness for use, and performance. Implicitly, a conforming product is

reliable, durable, ﬁt for use, and performs well. The product should be produced as the design

speciﬁes it; speciﬁcations should be met. Conformance is the basis for deﬁning what is meant

by a nonconforming, or defective, product.

A defective product is one that does not conform to speciﬁcations. Zero defects means

that all products conform to speciﬁcations. ut what is meant by „„conforming to

speciﬁcations‟‟? The traditional view of conformance assumes that there is an acceptable

range of values for each speciﬁcation or quality characteristic. A target value is deﬁned, and

upper and lower limits are set that describe acceptable product variation for a given quality

characteristic. Any unit that falls within the limits is deemed non defective. For example,

losing or gaining zero minutes per month may be the target value for a watch, and any watch

that keeps time correctly within a range of plus or minus two minutes per month is judged

acceptable. On the other hand, the robust quality view of conformance emphasizes ﬁtness of

use. Robustness means hitting the target value every time. There is no range in which

variation is acceptable. A non-defective watch in the robust setting would be one that does

not gain or lose any minutes during the month. Since evidence exists that product variation

can be costly, the robust quality deﬁnition of conformance is superior to the traditional

deﬁnition.

STEP 3: Importance of Quality (10 minutes)

The following are importance of quality

• Helps in describing attributes of a product hence facilitating contractual or legal

agreements. product identity

• Helps in defining the superiority of a product over other similar products. product beauty

• Helps in designing new or advanced product attributes. Product novelty. Therefore, when

the quality of a product is defined as “the degree to which a set of inherent properties of a

product, system or process fulfills requirements”, the requirements are those attributes

that reflect the identity, beauty and novelty of the product

STEP 4: Definition of Quality Control (10 minutes)

QC is defined as that part of Good Manufacturing Practice which is concerned with sampling,

specifications and testing, and with the organization, documentation and release procedures

which ensure that the necessary and relevant tests are actually carried out and that materials

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

are not released for use, nor products released for sale or supply, until their quality has been

judged to be satisfactory. The GMP requirement is:

• Adequate facilities, trained personnel and approved procedures are available for

sampling, inspecting and testing starting materials, packaging materials, intermediate,

bulk, and finished products, and where appropriate for monitoring environmental

conditions for GMP purposes

• Samples of starting materials, packaging materials, intermediate products, bulk products

and finished products are taken by personnel and by methods approved by Quality

Control;

• Test methods are validated;

• Records are made, manually and/or by recording instruments, which demonstrate that all

the required sampling, inspecting and testing procedures were actually carried out. Any

deviations are fully recorded and investigated;

• The finished products contain active ingredients complying with the qualitative and

quantitative composition of the marketing authorization, are of the purity required, and

are enclosed within their proper containers and correctly labeled;

• Records are made of the results of inspection and that testing of materials, intermediate,

bulk, and finished products is formally assessed against specification. Product assessment

includes a review and evaluation of relevant production documentation and an assessment

of deviations from specified procedures

• No batch of product is released for sale or supply prior to certification by an authorized

person that it is in accordance with the requirements of the relevant authorizations;

• Sufficient reference samples of starting materials and products are retained to permit

future examination of the product if necessary and that the product is retained in its final

pack unless exceptionally large packs are produced

STEP 5: Definition of Quality Assurance (15 minutes)

• QA is defined as wide-ranging concept, which covers all matters, which individually or

collectively influence the quality of a product.

• It is the sum total of the organized arrangements made with the objective of ensuring that

medicinal products are of the quality required for their intended use.

• Quality Assurance therefore incorporates Good Manufacturing Practice plus other factors

like product design and development.

• The system of Quality Assurance appropriate for the manufacture of medicinal products

should ensure that:

o Medicinal products are designed and developed in a way that takes account of the

requirements of Good Manufacturing Practice;

o Production and control operations are clearly specified and Good Manufacturing

Practice adopted;

o Managerial responsibilities are clearly specified;

o Arrangements are made for the manufacture, supply and use of the correct starting

and packaging materials;

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o All necessary controls on intermediate products, and any other in process controls and

validations are carried out;

o The finished product is correctly processed and checked, according to the defined

procedures;

o Medicinal products are not sold or supplied before an authorized person has certified

that each production batch has been produced and controlled in accordance with the

o Requirements of the marketing authorization and any other regulations relevant to the

production, control and release of medicinal products;

o Satisfactory arrangements exist to ensure, as far as possible, that the medicinal

products are stored, distributed and subsequently handled so that quality is maintained

throughout their shelf life;

o There is a procedure for self-inspection and/or quality audit, which regularly appraises

the effectiveness and applicability of the quality assurance system.

o Deviations are reported, investigated and recorded;

o There is a system for approving changes that may have an impact on product quality;

o Regular evaluations of the quality of pharmaceutical products should be conducted

with the objective of verifying the consistency of the process and

o Ensuring its continuous improvement.

o pharmaceutical products are designed and developed in a way that takes account of

the requirements of GMP and other associated codes such as those of good laboratory

practice (GLP)1 and good clinical practice (GCP);

• The manufacturer must assume responsibility for the quality of the pharmaceutical

products to ensure that they are fit for their intended use, comply with the requirements of

the marketing authorization and do not place patients at risk due to inadequate safety,

quality or efficacy. The attainment of this quality objective is the responsibility of senior

management and requires the participation and commitment of staff in many different

departments and at all levels within the company, the company‟s suppliers, and the

distributors. To achieve the quality objective reliably there must be a comprehensively

designed and correctly implemented system of quality assurance incorporating GMP and

quality control. It should be fully documented and its effectiveness monitored. All parts

of the quality assurance system should be adequately staffed with competent personnel,

and should have suitable and sufficient premises, equipment, and facilities.

STEP 6: QA/QC Comparisons (20minutes)

Activity: Brainstorming (5minutes)

ASK student to brainstorm on the following question for 5 minutes

• What is the difference between QA and QC?

ALLOW students to brainstorm for 5 minutes

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

WRITE their responses to the flip chart/ board

CLARIFY and SUMMARIZE by using the content below

Quality Assurance and Quality Control can be compared as follows:

QUALITY ASSURANCE QUALITY CONTROL

QA is the sum total of organized QC is that part of GMP which is concerned

arrangements made with the object of with sampling, specifications, testing and

ensuring that product will be of the Quality within the organization, documentation, and

required by their intended use release procedures which ensure that the

necessary and relevant tests are carried out

All those planned or systematic actions Operational laboratory techniques and

necessary to provide adequate confidence activities used to fulfill the requirement of

that a product will satisfy the requirements Quality

for quality

QA is company based QC is lab based

STEP 7: Functions of Quality Control Laboratory in Relation to

Preparation of Pharmaceutical Products. (35 minutes)

Good Laboratory Practice (GLP) is a quality system concerned with the organizational

process and the conditions under which tests are planned, performed, monitored, recorded,

archived and reported.

• Normally, Quality Control laboratories should be separated from production areas.

• This is particularly important for laboratories for the control of biological, microbiological

and radioisotopes, which should also be separated from each other.

• Control laboratories should be designed to suit the operations to be carried out in them.

• Sufficient space should be given to avoid mix-ups and cross contamination.

• There should be adequate suitable storage space for samples and records.

• Separate rooms may be necessary to protect sensitive instruments from vibration, electrical

interference, humidity, etc.

• Special requirements are needed in laboratories handling particular substances, such as

biological or radioactive samples.

Laboratory must have the following managerial and technical personnel:

• Head of laboratory (supervisor)

• Head of central registry

• Analysts

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• Technical staff

• Head of central store

• Quality Manager

• Reference material coordinator

Quality control Laboratory is divided into the following sections.

• Instrumentation

• Wet Chemistry

• Microbiology room

• Stability studies

Instrumentation

• Gas Chromatography

• Dissolution Instruments

• HPLC

• UV/VIS visible spectrophotometer

• Viscometer

• Melting point apparatus

• FTIR machine

• PH meter

• Hardness tester

• Conductivity meter

• Friability Tester

Wet Chemistry

The unit for preparation of reagent and volumetric solution standardization.

• Dissolution tester

• Friability Tester

• Refractometer

• Muffle furnace

• Density tester

• Leak Test Apparatus

• Disintegration tester

• Log books

• Reference standard and working standard are to be stored at 2-8ºC and in a locked

cabinet.

• Working standards stock card.

• Equipment usage log

• Eye shower and hood chamber

• Flammable and corrosive reagents and solvents to be provided with separate storage

cabinet installed with exhaust system.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Microbiology room

• The microbiology laboratory is responsible for microbial limit test and sterility test. It is

divided into instrument room, media preparation room, incubation room and analysis

room.

• Microbial limit testing (MLT) must be conducted for every finished products, water and

raw materials including environmental monitoring in the critical areas.

• The laboratory should have separate entry/exit for samples and personnel with air lock

door (self-closing)

• Microbiology labs should contain incubators used separately for Fungal, bacterial growth

and E. Coli monitoring including microbial limit test.

• Deep Freezer 2 – 8ºC dedicated for storage of media and agar,

• Laminar Air Flow (LAF) cabinet

• Steam sterilizer Autoclave for media preparation

• All equipment to be qualified/calibrated and affixed with status labels.

• The sample preparation room is to be kept under positive pressure relative to the

surrounding to control ingress of contaminants

• Stability studies

Essential for shelf -life determination. The Stability chambers to be set at different

conditions

• 25±2°C/60±5%RH

• 30C5/65%5 RH

• 30C5 & 75%5 RH

• Accelerated: 40C5 & 75%5 RH

• Adequate space for placement of samples.

General and specific safety instructions in quality control laboratories must be

• Available to each staff member and

• Supplemented regularly as appropriate (e.g. written material, poster displays, audio-visual

material, and occasional seminars).

• General rules for safe working in accordance with the national regulation and SOPs

include normally

• Availability of safety data sheets to staff prior to testing being carried out

• Prohibition of smoking, eating, and drinking in the laboratory

• Familiarity with the use of fire-fighting equipment, including fire extinguishers, fire

blankets, and gas masks

• The use of laboratory coats or other protective clothing including eye protection

• Special handling as required for example for highly potent, infectious, or volatile

substances

• Full labeling of all containers of chemicals, including prominent warnings (e.g. "Poison",

"Flammable", "Radiation", etc.) whenever appropriate

• Adequate insulation and spark-proofing of electrical wiring and equipment, including

refrigerators

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• Observation of safety rules in handling cylinders of compressed gases and familiarity

with their color identification codes

• Awareness of avoiding solitary work in the laboratory

• Provision of first-aid materials and instruction in first-aid techniques, emergency care,

and use of antidotes

STEP 8: Key points (5 minutes)

• QA is the sum total of organized arrangements made with the object of ensuring that

product will be of the Quality required by their intended use

• QC is that part of GMP which is concerned with sampling, specifications, testing and

within the organization, documentation, and release procedures which ensure that the

necessary and relevant tests are carried out

STEP 9: Evaluation (5 minutes)

• What is quality?

• What is the importance of quality in relation to preparation of pharmaceutical product?

• What is quality assurance?

• What is quality Control?

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

Gravells, A. (2016). Principles and practices of quality assurance – a guide for internal and

ex. Sage Publications.

Quality assurance of pharmaceuticals: A compendium of guidelines and related materials.

(2007). Geneva: World Health Organization.

Donabedian, A. (1990). The Process of quality assurance.

Lund, W. (2009). The pharmaceutical codex: Principles and practice of pharmaceutics. New

Delhi: CBS.

Aulton, M. E., & Taylor, K. (2018). Aulton s pharmaceutics: The design and manufacture of

medicines. Edinburgh: Elsevier.

Signore, A. A., & Jacobs, T. (2017). Good design practices for GMP pharmaceutical

facilities. Boca Raton, Fl.: CRC Press.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 8: The Operating Principles of Equipments and

Machines

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• List equipment used in facility based pharmaceutical preparation unit (Reverse Osmosis

Machine, Distiller, Autoclave, De-ionizer etc.)

• Explain the operating principles of an Autoclave

• Explain the operating principles of a Reverse Osmosis Machine

• Explain the operating principles of a De-ionizer

• Explain the operating principles of a Distiller

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• LCD Projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

10 minutes Presentation Equipment Used in Facility Based

Buzzing Pharmaceutical Preparation Unit

25 Minutes Presentation Operating Principles of an Autoclave

30minutes Operating Principles of a Reverse Osmosis

4 Presentation

Machine

20 minutes Presentation

5 Operating Principles of a De-ionizer

20 minutes Presentation

6 Operating Principles of a Distiller

7 05 minutes Presentation Key points

8 05 minutes Presentation Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning objectives and clarify

ASK students if they have any questions before continuing.

STEP 2: Equipment Used in Facility Based Pharmaceutical Preparation

Unit(10 minutes)

Activity: Buzzing (5minutes)

ASK students to pair up and buzz on the following questions for 5 minutes

• What are equipments used in facility based pharmaceutical preparation unit?

ALLOW few pairs to respond and let other pairs add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

The equipment used in facility based pharmaceutical preparation unit include the following:

• Reverse Osmosis Machine,

• Distiller,

• Autoclave,

• De-ionizer

STEP 3: Operating Principles of an Autoclave (25 minutes)

• The autoclave involves sterilization of materials using steam and pressure is a

dependable procedure for the destruction of all forms of microbial life.

• However, the autoclave must be properly used and understood to be effective.

• Do not assume that merely pushing the button on an autoclave will result in the proper

sterilization of your materials.

• There are some established guidelines for the effective use of steam sterilizers

(autoclaves) for the decontamination of cultures and other materials, for preparing

sterile supplies, and for the safe operation of the autoclave.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Figure 8:1 Autoclave machine

Source: KSP IV Production Mannual

• The theory of operation

o The basics: Why is an autoclave such an effective sterilizer? An autoclave is a large

pressure cooker; it operates by using steam under pressure as the sterilizing agent.

 High pressures enable steam to reach high temperatures, thus increasing its heat

content and killing power.

 Most of the heating power of steam comes from its latent heat of vaporization.

This is the amount of heat required to convert boiling water to steam.

 This amount of heat is large compared to that required to make water hot. For

example, it takes 80 calories to make 1 liter of water boil, but 540 calories to

convert that boiling water to steam.

 Therefore, steam at 100º C has almost seven times more heat than boiling water.

Steam is able to penetrate objects with cooler temperatures.

o How does killing occur? Moist heat is thought to kill microorganisms by causing

coagulation of essential proteins.

 Another way to explain this is that when heat is used as a sterilizing agent, the

vibratory motion of every molecule of a microorganism is increased to levels that

induce the cleavage of intra-molecular hydrogen bonds between proteins.

 Death is therefore caused by an accumulation of irreversible damage to all

metabolic functions of the organism.

 Death rate is directly proportional to the concentration of microorganisms at any

given time. The time required to kill a known population of microorganisms in a

specific suspension at a particular temperature is referred to as thermal death time

(TDT).

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

 All autoclaves operate on a time/temperature relationship; increasing the

temperature decreases TDT, and lowering the temperature increases TDT.

o What is the standard temperature and pressure of an autoclave? Processes conducted

at high temperatures for short time periods are preferred over lower temperatures for

longer times. Some standard temperatures/pressures employed are 115 °C/10 p.s.i.,

121°C/ 15 p.s.i., and 132 °C/27 p.s.i. (psi=pounds per square inch).

 Please note that after loading and starting the autoclave, the processing time is

measured after the autoclave reaches normal operating conditions of 121°C

(250°F) and 15 psi pressure, NOT simply from the time you push on the bottom.

o Time is critical. As the cycle time will vary with the composition of the load, it is

important to determine the appropriate time requirement. Some (ignorant) people

assuming that a time of 30 minutes is sufficient, however this often proves to be a

very costly mistake.

o Volume. Obviously, the higher the volume, the more time is needed for sterilization

(see general guidelines below). Generally, the volume of liquid per container is a

more important consideration than the total volume. A 2-liter flask containing 1-liter

of liquid takes longer to sterilize than four 500 mL flasks each containing 250-mL

of liquid.

o Microbial load. Contaminated items take longer to sterilize than clean items.

Consequently, water sterilizes faster than yeast-extract containing media (which

contains lots of microbes), or media left at room temperature for a while before

autoclaving (which allows the concentration of microbes to increase). Also, some

types of microbes are more resistant to autoclaving than others.

o Some general guidelines. Here are some recommended times for autoclaving liquids

of the following volume per container:

 75–200 ml 20 minutes

 200–500 ml 25 minutes

 500–1000 ml 30 minutes

 1000–1500 ml 35 minutes

 1500–2000 ml 40 minutes

 Remember to modify these times as needed!!!!! For example, more time is

required if the flasks in a plastic tray (which is the standard method); if many

bottles are close to each other in the tray; if the chamber is full of several trays; if

the liquid contains microbes; if you are using plastic instead of glass containers;

etc. Therefore, you probably need to go longer than the times indicated above

STEP 4: Operating Principles of a Reverse Osmosis Machine

(30minutes)

• Reverse Osmosis is a technology that is used to remove a large majority of contaminants

from water by pushing the water under pressure through a semi-permeable membrane.

• Reverse Osmosis is a process whereby involve demineralising or deionising water by

pushing it under pressure through a semi permeable reverse osmosis membrane.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• Osmosis is a process where a weaker saline solution will tend to migrate to a strong saline

solution.

• A solution that is less concentrated will have a natural tendency to migrate to a solution

with a higher concentration.

• A semi-permeable membrane is a membrane that will allow some atoms or molecules to

pass but not others.

• Reverse Osmosis is the process of Osmosis in reverse.

• Whereas Osmosis occurs naturally without energy, to reverse the process of osmosis you

need to apply energy to the more saline solution.

• In Reverse Osmosis, membrane is a semi-permeable membrane that allows the passage of

water molecules but not the majority of dissolved salts, organics, bacteria and pyrogens.

• However, you need to „push‟ the water through the reverse osmosis membrane by

applying pressure that is greater than the naturally occurring osmotic pressure in order to

desalinate (demineralise or deionise) water in the process, allowing pure water to pass

through while holding back a majority of contaminants.

• When pressure is applied to the concentrated solution, the water molecules are forced

through the semi-permeable membrane and the contaminants are not allowed to pass

through.

Figure 8: 2 Reverse Osmosis Machine

Source: KSP IV Production Manual

• How does Reverse Osmosis machine work?

o Reverse osmosis machine works by using a high pressure pump to increase the

pressure on the salt side of the reverse osmosis and force the water across the semi-

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

permeable reverse osmosis membrane, leaving almost all (around 95% to 99%) of

dissolved salts behind in the reject stream.

o The amount of pressure required depends on the salt concentration of the feed

water.

o The more concentrated the feed water, the more pressure is required to overcome

the osmotic pressure.

o In very simple terms, feed water is pumped into a Reverse Osmosis system and you

end up with two types of water coming out of the reverse osmosis system: namely

good water and bad water.

o The good water that comes out of a reverse osmosis system has the majority of

contaminants removed and is called permeate water.

o Another term for permeate water is product water.

o Permeate is the water that was pushed through the RO membrane and contains very

little contaminants

o The bad water is the one that contains all of the contaminants that were unable to

pass through the reverse osmosis membrane and is known as the concentrate,

reject, or brine water. (all the three terms are used interchangeable and mean the

same thing)

As the feed water enters the reverse osmosis membrane under pressure the water

molecules pass through the semi permeable membrane and the salts and other

contaminants are not allowed to pass and are discharged through the concentrate stream,

which goes to drain or can be fed back into the feed water supply in some

circumstances to be recycled through the reverse osmosis system to save water.

o It is important to understand that reverse osmosis system employs cross filtration

rather than standard filtration where the contaminants are collected within the filter

media. With cross filtration, the solution passes through the filter, or crosses the filter,

with two outlets: under cross filtration, the filtered water goes one way and the

contaminated water goes a different route.

o To avoid build up of contaminants, cross flow filtration allows water to sweep away

contaminant build up and also allow enough turbulence to keep the membrane surface

clean.

• What will reverse Osmosis machine remove from water?

o Reverse Osmosis is capable of removing up to 99%+ of the dissolved salts (ions),

particles, colloids, organics, bacteria and pyrogens from the feed water (although an

RO system should not be relied upon to remove 100% of bacteria and viruses).

o A Reverse osmosis membrane rejects contaminants based on their size and charge.

o Any contaminant that has a molecular weight greater than 200 is likely to be

rejected by a properly running reverse osmosis system.

o Because an reverse osmosis system does not remove gases, the permeate water can

have a slightly lower than normal pH level depending on CO2 levels in the feed

water as the CO2 is converted to carbonic acid due to CO2 are not highly ionized

(charged) while in solution and have very low molecular weght.

o In order to accurately measure the performance of an RO system you need the

following operation parameters at a minimum:

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

 Feed pressure

 Permeate pressure

 Concentrate pressure

 Feed conductivity

 Permeate conductivity

 Feed flow

 Permeate flow

 Temperature

• Reverse osmosis Pre-treatment

o Proper pre-treatment using both mechanical and chemical treatments is critical for

an RO system to prevent fouling, scaling and costly premature reverse osmosis

membrane failure and frequent cleaning requirements.

o Fouling occurs when contaminants accumulate on the membrane surface effectively

plugging the membrane.

o Fouling can be caused by the following

 Particulate or colloidal matter e.g. Dirt, silt, clay etc.

 Organic compounds.

 Microorganism.

o Scaling. As certain dissolved (inorganic) compounds become more concentrated,

then scaling can occur if these compounds exceed their solubility limits and

precipitate on the membrane surface as scale. an example of common scale that

tends to form on reverse osmosis membrane is calcium carbonate .

o Mechanical Damage: If there is too much back pressure on the reverse osmosis

system then mechanical damage to the reverse osmosis membranes can also occur.

STEP 5: Operating Principles of a De-ionizer (20 minutes)

• Deionizers are important pieces of equipment that remove dissolved ionic salt and minerals

from a solution using an ion exchange process they are also known as ion exchangers or

demineralizers.

• Types of Deionizers. Deionizers may be categorized as "mixed bed", containing both cat

ion and anion resin in a single vessel, or "dual bed", where each resin type is in a separate

vessel. Mixed bed deionizers produce water containing the lowest ionic concentrations.

• Dual bed deionizers produce water of lesser quality, generally unacceptable for specialized

medical purposes such as hemodialysis.

Figure 8: 3 De – ionizer machine

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Source: KSP IV Production Mannual

• Principles of Operation.

o Deionizers remove both cat ions and anions, releasing hydrogen ions (H+) in

exchange for the former, and hydroxyl ions (OH-) for the latter.

o The hydrogen and hydroxyl ions subsequently combine to form pure water.

Figure 8:3:1 Schematic representation of ion Exchange showing exchange of sodium and

Chloride for hydrogen ion and hydroxyl ions. The latter combine to form water

Source: Google (2014).

• It should be noted that while deionizers produce water of high ionic quality, they do not

remove bacteria, endotoxins or pyrogens.

• In fact, deionizers often worsen quality in terms of bacteria and endotoxins, the resin bed

providing an environment which is conducive to bacterial proliferation.

• For this reason, it is prudent to follow deionization purification with equipment that

removes bacteria and/or endotoxins, such as ultra filtration, submicron filtration, steam

distillation or even ultraviolet irradiation.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

STEP 6: Operating Principles of a Distiller (20 minutes)

• Water distillers can remove most minerals, metals, organic chemicals and micro-

organisms from water. A clean, well-maintained distiller will remove over 95 per cent of

the minerals, including sodium, sulfate, nitrate and arsenic. Biological contaminants such

as bacteria, viruses and cysts are destroyed during distillation. Water distillers can be

simple, versatile drinking water treatment devices.

• Distillers are generally only used for producing small amount of water for drinking and

cooking which is due to the cost of operation and slow rate of treated water production.

• When large amount of treated water are required then reverse osmosis system is often

more suitable.

• Distillers may also fail to remove volatile organic compounds from water.

• Operation of distiller. Work on the principle of evaporation and condensation.

o An electric heating element (1,000 to 1,500 watts) boils water in a stainless steel tank.

o The resulting steam leaves the tank and enters a stainless steel cooling coil.

o In the cooling coil, the steam condenses to form distilled water.

o Some distillers use air to cool the steam.

o Others use incoming water for cooling.

When most of the water is boiled out of the distiller, a float switch turns off the power

to the heating element.

o The concentrated mineral solution left in the boiling tank is drained off, and the

boiling chamber is refilled manually or automatically. Some distillers are built as

portable countertop units. These are usually refilled manually and plugged into

normal 120 volt power outlets. Countertops units normally batch distill 3 to 4 litres of

water at a time.

Other distillers are permanently installed, usually in the house basement.

o They are plumbed into a water supply line, distilled water is collected in a storage

container, and then a small pump is used to pump water to treated water taps,

humidifiers, or fridges and icemakers.

o These units are normally continuous flow type distillers.

Figure 8: 4 distiller operation air cool type

Source 🙁 n.d).Retrieved from

https://www.gooogle.com/search (2018).

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

STEP 7: Key Points (5 minutes)

• The equipments used in facility based pharmaceutical preparation unit include: Reverse

Osmosis Machine, Distiller, Autoclave, De-ionizer etc.

• An autoclave is a large pressure cooker; operates by using steam under pressure as the

sterilizing agent.

• Reverse Osmosis is the process of Osmosis in reverse under pressure through a semi-

permeable membrane.

• Deionizers produce water of high ionic quality, they do not remove bacteria, endotoxin

or pyrogens.

• Water distillers can remove most minerals, metals, organic chemicals and micro-

organisms from water.

STEP 8: Evaluation (5 minutes)

• What are equipment used in facility based pharmaceutical preparation unit?

• What is Reverse Osmosis Machine?

• What are the operating principles of an Autoclave?

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

“Reverse Osmosis.” Egyptian Journal of Medical Human Genetics, Elsevier,

www.sciencedirect.com/topics/chemistry/reverse-osmosis.

Editorial Board. (2016). Egyptian Journal of Medical Human Genetics,17(4), Iii.

doi:10.1016/s1110-8630(16)30059-3

(n.d.). Retrieved from https://www.google.com/search?q=preventive maintenance procedures

for autoclave WHO&rlz=1C1CHBF_enTZ812TZ812&oq=preventive maintenance

procedures for autoclave

Pearce G., (2007),The case of UF/MF pretreatment to RO in seawater applications,

Desalination 203 , 286-295 Pilat B.,(2001), Practice of water desalination by

electrodialysis, Desalination 139 . 385-392

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 9: Standard Operating Procedures for

Equipments and Machines

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Define standard operating procedures

• Explain the components of an SOP

• Explain the importance of SOPs in the production of pharmaceuticals

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

15 minutes Definition of Standard Operating

Presentation

2 Procedures

Buzzing

30 minutes Presentation Components of an SOP

Brainstorming,

60 minutes Presentation Importance of SOPs in the Production of

Pharmaceuticals

5 05 minutes Presentation Key Points

6 05 minutes Presentation Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Definition of Standard Operating Procedures (15minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• What is Standard Operating Procedures?

ALLOW few pairs to respond and let other pairs to add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• Standard Operating Procedures (SOPs) is a set of written instructions that document a

routine or repetitive activity which is followed by employees in an organization. The

development and use of SOPs are an integral part of a successful quality system. It

provides information to perform a job properly, and consistently in order to achieve pre-

determined specification and quality end-result.

• SOPs must contain step by step instructions that employ must refer in daily work to

complete various tasks more reliably and consistently.

• SOPs detail the regularly recurring work processes that are to be conducted or followed

within an organization.

STEP 3: Components of an SOP (30minutes)

Activity: Brainstorming (5minutes)

ASK student to brainstorm on the following question

• What are the components of SOP?

ALLOW few students to respond

WRITE their responses to the flip chart/ board

CLARIFY and SUMMARIZE by using the content below

The following are components of standard operating procedures (SOP)

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• Scope-the activity which is to be covered by the SOP

• Objective-the purpose of following the procedure

• Responsibility-who will be carrying out the activity

• Procedure-instructions on what to be done

• Audit-to identify areas of improvement

STEP 4: Importance of SOPs in the Production of Pharmaceuticals

(60minutes)

The following are importance of SOPs in the production of pharmaceuticals:

• It provides people with all the safety, health, environmental and operational

information necessary to perform a job properly. Placing value only on production

while ignoring safety, health and environment is costly in the long run. It is better to train

employees in all aspects of doing a job than to face accidents, fines and litigation later.

• It ensures that production operations are performed consistently to maintain quality

control of processes and products. Consumers, from individuals to companies, want

products of consistent quality and specifications. SOPs specify job steps that help

standardize products and therefore quality.

• It ensures that processes continue uninterrupted and are completed on a prescribed

schedule. By following SOPs, you help ensure against process shut-downs caused by

equipment failure or other facility damage.

• It ensures that no failures occur in manufacturing and other processes that would

harm anyone in the surrounding community. Following health and environmental

steps in SOPs ensures against spills and emissions that threaten plant neighbors and create

community outrage.

• It serves as a training document for teaching users about the process for which the

SOP was written. Thorough SOPs can be used as the basis for providing standardized

training for employees who are new to a particular job and for those who need re-training

• It serves as a checklist for co-workers who observe job performance to reinforce

proper performance. The process of actively caring about fellow workers involves one

worker coaching another in all aspects of proper job performance. When the proper

procedures are outlined in a good SOP, any co-worker can coach another to help improve

work skills

• It serves as a checklist for auditors. Auditing job performance is a process similar to

observation mentioned in the previous item only it usually involves record keeping. SOPs

should serve as a strong basis when detailed audit checklists are developed.

STEP 5: Key Points ( 5 minutes)

• SOPs are a set of written instructions that document a routine or repetitive activity which

is to be followed.

• Components of SOP include scope, objectives, responsibility, procedures and audit.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

• SOPs serves as checklist for co-workers and auditors, training document, ensures no

failures occur during production and provides safety among people.

STEP 6: Evaluation (5 minutes)

• What is SOPs?

• What are the components of SOPs?

• What is the importance of SOP?

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

Saluja, Gp. “Chapter-01 Standard Operating Procedure for Preparing, Revising and Using

Standard Operating Procedures SOPs .” Standard Operating Procedures and

Regulatory Guidelines: Blood Banking, 2014.

Saluja, G. (2014). Chapter-01 Standard Operating Procedure for Preparing, Revising and

Using Standard Operating Procedures (SOPs). Standard Operating Procedures and

Regulatory Guidelines: Blood Banking.

Moriarty, D. (2015). Error management and standard operating procedures for

organizations. Practical Human Factors for Pilots.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 10: Preventive Maintenance Procedures for

Equipments and Machines

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Explain the importance of proper preventive maintenance of equipment and machines

• Describe general considerations in preventive maintenance of machines and equipment

• Describe preventive maintenance procedures for equipment and machines (Reverse

Osmosis Machine, Distiller, Autoclave, De-ionizer etc.)

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

45 minutes Presentation Importance of Proper Preventive

Buzzing Maintenance of Equipment and Machines

10 minutes General Considerations in Preventive

3 presentation

Maintenance of Machines and Equipment

50 minutes Presentation Preventive Maintenance Procedures for

Brainstorming Equipment and Machines

5 05 minutes Presentation Key Points

6 05 minutes Presentation Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Importance of Proper Preventive Maintenance of Equipment

and Machines (45minutes)

Activity: Buzzing (5minutes)

ASK students to pair up and buzz on the following questions for 5 minutes

• What is preventive maintenance?

ALLOW few pairs to respond and let other pairs add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• The goal of maintenance is to keep the production system in good working order at

minimal cost

• Maintenance –include all activities that maintain facilities and equipment in good

working order so that a system can perform as intended

• Goals of Maintenance-To keep production systems in good working order at minimal cost

• Reasons for maintenance

o To avoid production or service disruptions

o To not add production or service costs

o To maintain high quality

o To avoid missed delivery dates

• Preventive maintenance: goal is to reduce the incidence of breakdowns or failures in the

plant or equipment to avoid the associated costs

• Preventative Maintenance is a way to catch small issues with your machine before they

become big issues OR involves maintenance performed to extend the life of the device

and prevent failure

• Preventive maintenance is “that function of manufacturing management that is concerned

with day to day problem of keeping the physical plant in good operating condition”

• Preventive maintenance is periodic

o Result of planned inspections

o According to calendar

o After predetermined number of hours

• Five Components of a maintenance

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o Breakdown maintenance or corrective maintenance; Occurs when there is a work

stoppage due to machine breakdown

o Preventive maintenance; It is undertaken before the need arises and aims to minimize

the possibility of un -anticipated production interruption or major breakdowns

o Predictive maintenance; Conditions can be measured on a continuous basis and this

enables the maintenance people to plan for an overhaul.

o Routine maintenance; this includes activities such as periodic inspection, cleaning,

lubrication and repair of production equipments after their service life

o Planned maintenance; : it involves the inspection of all plant and equipments,

machinery, buildings according to a predetermined schedule in order to service

overhaul, lubricate or repair, before actual break down or deterioration in service

occurs

• Principle Objectives in Maintenance

o To achieve product quality and customer satisfaction through adjusted and serviced

equipment

o Maximize useful life of equipment

o Keep equipment safe and prevent safety hazards

o Minimize frequency and severity of interruptions

o Maximize production capacity – through high utilization of facility

• Advantages

o Reduces break down and thereby down time

o Lass odd-time repair and reduces over time of crews

o Greater safety of workers

o Lower maintenance and repair costs

o Less stand-by equipments and spare parts

o Better product quality and fewer reworks and scraps

o Increases plant life

o Increases chances to get production incentive bonus

• Importance of proper preventive maintenance of equipment and machines

o Dependability of service

o Assured quality

o Prevent equipment failure

o Cost control

o Huge investment in equipment

STEP 3: Considerations in Preventive Maintenance of Machines and

Equipment (10 minutes)

• Preventive Maintenance general considerations consists of

o Proper design and installation of equipment

o Documentation on Predictive Maintenance

o Periodic inspection of plant and other equipments if properly functioning

o Repetitive servicing and overhaul of malfunctioning equipment

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o Adequate lubrication, cleaning and painting

o Using of Personal Protective Equipments (PPE)

o Preventive maintenance Benefits and Control

STEP 4: Preventive Maintenance Procedures for Equipment and

Machines (Reverse Osmosis Machine, Distiller, Autoclave, (50 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

• What are PM procedures for RO machine?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Preventive maintenance procedures for reverse osmosis machine

o Design, Construction and Preventive maintenance of USP Purified Water Systems

o Reverse Osmosis (RO) is a well-established process

o For an RO system to work reliably and economically, the unit and associated

equipment must be routinely maintained

o Reverse osmosis is the most economical method of removing up to 99% of feed water

contaminants

o Requires pretreatment to avoid damaging the membrane;

o A Typical reverse osmosis preventive maintenance Checklist must be present in the

pharmaceutical preparation unit to avoid damaging of the membrane ,maintain

efficiency of the reverse osmosis machine and to ensure quality of the out coming

water:

• A Typical RO PM Checklist; indicating the following items to be routinely checked;

o Test RO feed water

o Chlorine and water hardness content

o Check and set pretreatment filter and water softener clocks

o Log RO pump pressure, flow rate and temperature

o Test RO product water and log flow rates

o Test RO reject water and log flow rates

o Log Recovery %

o Log Rejection %

o Log pressure gauge readings.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o Change RO pre-filters

o Check salt/ chemical tank levels and add as needed

o Repair any minor leaks.

o Update PM Logs

• Operational Checks for RO System

o Monitor the incoming and outgoing water pressures through the Multi-media Filters,

Activated Carbon Filters, UV Systems, Pre-filter to the RO Units to assure the there

is adequate pressure to operate each piece of equipment as designed.

o This includes monitoring the filter unit during the backwash mode and while the

other unit is on line to provide flow to the RO System.

o If necessary, adjust the separate source backwash pressure coming from the domestic

water side in order for the diaphragm valves located on the filters to work properly

During the backwash phase take off the tubing to the valves, one at a time to verify

that there is hydraulic pressure going to the valve in order for the valve to work

properly.

o Monitor each control device during operation to include the controllers located on the

Filters, the display panel on the UV units, the control panel on the RO unit, and the

control panel located on the Chorine Monitoring Skid.

o Make any necessary adjustments to the operation of the equipment if there are

changes to the incoming water that would include a change in water quality and

temperature that would affect the operation of the RO Units and the chlorine feed

system that chlorinates the product water going to the storage tanks.

o Make adjustments to the chemical feed system to assure that the compound is

receiving potable water with at least 0.2 to 0.4 mg/l of free chlorine.

o The onsite chlorine test will be taken with a hand held calibrated DPD test kit to

provide accurate analysis.

o Provide onsite water analysis of the incoming raw water, the reject water from the RO

unit, and the product water from the RO unit with a hand held calibrated instrument to

determine if the RO unit is performing in accordance with specifications.

o All services will be performed by a competent Stateside Licensed Water Treatment

Plant Operator

• Preventive maintenance procedures for Autoclave

o Autoclave operators should perform the following preventative maintenance on their

autoclave to maintain the autoclaves effectiveness:

o Remove the plug screen or drain strainer to make sure it is free of dirt, dust, or

sediment that may collect in it and it should be cleaned as necessary.

o Clean the interior surfaces of residues collected from the steam or materials being

sterilized as needed.

o Visually inspect the gaskets, doors, shelves and walls for residue build up or wear

regularly.

• Preventive maintenance procedures for distiller

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o The maintenance depends on the design and capacity of the distiller. The

maintenance of a distiller equipped with a stainless steel vapour generator tank with

immersion resistors and a condenser refrigerated through a ventilator impelling air

o Distiller operators should perform the following preventative maintenance on their

distiller to maintain the distiller effectiveness;

 Inspection and cleaning of the vapor generator tank- Clean accumulated deposits.

In general, the cleaning process requires a chemical product especially designed

for removing them.

 Change of the activated carbon filter-every three months, Install a new element

with the same characteristics as the original.

 Cleaning of the condenser –annually, remove the condenser. Aspirate dirt, and

dust

accumulated on the surface of the diffusing fins. Compressed air or a brush

dampened with soap and water can also be use

 Sterilization of the distilled water storage tank- Before operating a new water

distiller, it is recommended to insure that the distilled water storage tank is sterile

and clean. To carry out the sterilization, use a chemical process with domestic

bleach (chlorine based)

STEP 5: Key Points ( 5 minutes)

• The goal of preventive maintenance is to reduce the incidence of breakdowns or failures

in the plant or equipment to avoid the associated costs

• Preventive maintenance is “that function of manufacturing management that is concerned

with day to day problem of keeping the physical plant in good operating condition”

STEP 6: Evaluation (5minutes)

• What is preventive maintenance?

• What is the importance of proper PM of equipment and machines?

• What are the general considerations in PM of machines and equipment?

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

(n.d.). Retrieved from https://www.google.com/search?q=importance of proper preventive

maintenance of equipment and machines

Lund, W. (2009). The pharmaceutical codex: Principles and practice of pharmaceutics. New

Delhi: CBS.

amm, G., hler, . . Manual for decentralized infusion production: Infusion Unit

Project, Tanzania. Erscheinungsort nicht ermittelbar: Verlag nicht ermittelbar.

Aulton, M. E., & Taylor, K. (2018). Aulton s pharmaceutics: The design and manufacture of

medicines. Edinburgh: Elsevier.

Signore, A. A., & Jacobs, T. (2017). Good design practices for GMP pharmaceutical

facilities. Boca Raton, Fl.: CRC Press.

Gad, S. C. (2008). Pharmaceutical manufacturing handbook production and processes.

Hoboken, NJ: Wiley-Interscience.

Cooper, J. W., Gunn, C., & Carter, S. J. (1987). Dispensing for pharmaceutical students.

Edinburgh: Churchill Livingstone.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

Session 11: Procedures for Quality Testing of

Pharmaceutical Products

Total Session Time: 120 minutes

Prerequisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• List methods commonly used for quality testing of pharmaceutical products from

monographs

• Explain procedures for carrying out physical quality tests for solid pharmaceutical dosage

forms (Hardness, smell, colour, texture, thickness, diameter, friability, disintegration etc.)

• Explain procedures for carrying out physical quality tests for liquid pharmaceutical

dosage forms (pH, smell, colour, conductivity, osmolarity etc.)

• Explain procedures for carrying out microbiological quality tests for pharmaceutical

products (sterility tests, etc.)

• Explain procedures for carrying out chemical qualitative tests (volumetric analysis, colour

reaction, dissolution test etc.)

• Explain procedures for carrying out chromatographic quality tests (TLC, etc.)

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• LCD projector and computer

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION OVERVIEW

Activity/

Step Time Content

Method

1 05 minutes Presentation Introduction, Learning Tasks

15 minutes Methods Commonly Used for Quality

Presentation

2 Testing of Pharmaceutical Products from

Buzzing

Monographs

20 minutes Procedures for Carrying Out Physical

Presentation and

3 Quality Tests for Solid Pharmaceutical

Brainstorming

Dosage Forms

Procedures for Carrying Out Physical

4 20 minutes Presentation Quality Tests for Liquid Pharmaceutical

Dosage Forms

15 minutes Procedures for Carrying Out

5 Presentation Microbiological Quality Tests for

Pharmaceutical Products

15 minutes Presentation Procedures for Carrying Out Chemical

Qualitative Tests

20 minutes Presentation Procedures for Carrying Out

Chromatographic Quality Tests

8 05 minutes Presentation Key Points

9 05 minutes Presentation Evaluation

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning objectives and clarify

ASK students if they have any questions before continuing.

STEP 2: Methods Commonly Used for Quality Testing of

Pharmaceutical Products from Monographs (15 minutes)

Activity: Buzzing (5minutes)

ASK students to pair up and buzz on the following questions for 2 minutes

• What are various tests in quality testing of pharmaceutical products?

ALLOW few pairs to respond and let other pairs add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

• There are various tests involve in quality testing of pharmaceutical products, these

includes

• Physical quality tests for solid pharmaceutical dosage forms includes;

o Hardness,

o Smell,

o Colour,

o Texture,

o Thickness,

o Diameter,

o Friability test,

o Disintegration test

• Chromatographic quality tests includes

o Thin layer chromatography method-TLC

o High-performance liquid chromatography (HPLC

o Gas chromatography (GC)

o Paper chromatography

• Physical quality tests for liquid pharmaceutical dosage forms includes

o pH,

o Smell,

o Colour,

o Conductivity,

o Osmolarity

• Microbiological quality test include

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o Sterility tests for pharmaceutical products

o Chemical qualitative tests includes Volumetric analysis

o Colour reaction, Dissolution test

STEP 3: Procedures for Carrying out Physical Quality Tests for Solid

Pharmaceutical Dosage Forms (20 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

• What is disintegration?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

• Disintegration is the process where pharmaceutical solid dosage forms separate into

parts or lose intactness or solidness and break up into particle or constituent under

specified conditions

• Disintegration time is the time required for a dosage form to break up in to granules of

specified size (or smaller) under carefully specified conditions.

• Disintegration Test- This test determines whether dosage forms such as tablets,

capsules, pessaries and suppositories disintegrate within a prescribed time when placed in

a liquid medium under the prescribed experimental conditions.

For the purpose of this test, disintegration does not imply complete solution of the dosage

unit or even of its active constituent.

• Disintegration Apparatus consists of

o A basket-rack assembly,

o A 1-litre beaker,

o A thermostatic arrangement for heating the fluid

o Mechanical device for raising and lowering the basket in the immersion fluid at

a constant frequency rate

• Disintegration test procedures

o 6 tablets from each batch are taken and subjected to the disintegration test.

o One tablet is placed in the mesh screen at the bottom end of each of the 6 glass tubes,

o Tap water is used as disintegration medium. Simulated gastric fluid.

o The apparatus is maintained at a temperature of 37 ± 2°C.

o Glass tube maintains up and down movement in and out of the basket containing

1000mls distilled water. the basket move through a distance of 5-6cm at a frequency

of 28 to 32 cycles per minutes as specified by U.S.P

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o Disintegration time of the each tablet is noted by means of a stopwatch and recorded.

o Disintegration time does differ depending on the nature of the tablets e.g. uncoated,

coated. Uncoated USP tablets have disintegration time as low as 5 minutes but

majority have maximum disintegration time of 30 minutes. Disintegration test we start

with 6 tablets if one or two tablets failed to disintegrate completely test should be

repeated for additional 12 tablets the requirement met if not less than 16 of the total

18 are disintegrated.

• Factors affecting the disintegration time

o Content-especially the quality and quantity of the Disintergrants and lubricant.

o Hardness .amount of binder, compression force.

o Design of granulation procedure which will affect the physical properties of the

granules

• Friability

o Friability is the tendency for a tablet to chip, crumble or break following compression.

o This tendency is normally confined to uncoated tablets and surfaces during handling or

subsequent storage.

o It can be caused by a number of factors including poor tablet design too sharp edges, low

moisture content, insufficient binder.

o For obvious reasons, tablets need to be hard enough such that they do not break up in the

bottle but friable enough that they disintegrate in the gastrointestinal tract

• Friability testing. Is a laboratory technique used by the pharmaceutical industry to test

the durability of tablets during transit. This testing involves repeatedly dropping a sample

of tablets over a fixed time, using a rotating wheel with a baffle. The result is inspected

for broken tablets, and the percentage of tablet mass lost through chipping

• Friability testing procedures

o 10 tablets from each batch are carefully de-dusted prior to testing.

o Accurately weighed and their weight recorded,

o placed in the drum of the friabilator and the drum rotated at 100 times in four

minutes,

o After 100 revolutions, tablets are removed,

o Loose dusts are removed from the tablets, and accurately weighed again.

o Note A maximum weight loss (obtained from a single test should be not more than

1.0%. If the tablet cracked, cleaved, or get broken after tumbling, the sample fails the

test

o Factors that affect the friability of tablets include tablet design such as too sharp

edges, moisture content, and binder being used.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

STEP 4: Procedures for Carrying Out Physical Quality Tests for Liquid

Pharmaceutical Dosage Forms (20 minutes)

• PH test

o PH of the oral liquid preparations must be Optimum as they are administered. The pH

value conventionally represents the acidity or alkalinity of an aqueous solution.

o In the pharmacopoeia, standards and limits of pH have been provided for those

pharmacopoeia substances in which pH as a measure of the hydrogen ion activity is

important from the standpoint of stability or physiological suitability.

o The determination is carried out at a temperature of 25±2°C, unless otherwise

specified in the individual monograph.

o The pH value of a solution is determined potentiometrically by means of a glass

electrode, a reference electrode and a PH meter either of digital or analogue.

• Conductivity test

o Conductivity may be measured by applying an alternating electrical current (I) to two

electrodes immersed in a solution and measuring the resulting voltage (V).

o During this process, the cations migrate to the negative electrode, the anions to the

positive electrode and the solution acts as an electrical conductor

STEP 5: Procedures for Carrying Out Microbiological Quality Tests for

Pharmaceutical Products (15 minutes)

• Microbiology testing services

o Are a crucial requirement across many industries worldwide where products,

processes and human health are at risk of being negatively affected by the presence

and breeding of micro-organisms such as specific pathogens, bacteria, yeast and

moulds.

• Sterility tests

o This test establishes the ability of new lots of medium to support growth when the

inoculums contain a small number of microorganisms.

o Sterility testing of pharmaceutical products is required during the sterilization

validation process as well as for routine release testing. USP requirements employ

sterility testing as an official test to determine suitability of a lot.

STEP 6: Procedures for Carrying Out Chemical Qualitative Tests

(15minutes)

Qualitative tests carried out include the following Volumetric analysis, Colour reaction, and

Dissolution test

• Dissolution test

o Is routinely used to provide critical in vitro drug release information for both quality

control purposes. It is used to assess batch-to-batch consistency of solid oral dosage

forms such as tablets, and drug development to predict in vivo drug release profiles

o Analytical data from drug dissolution testing are sufficient in many cases to

establish safety and efficacy of a drug product without in vivo tests, following minor

formulation and manufacturing changes

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o The general procedure for a dissolution involves a liquid known as Dissolution

Medium which is placed in the vessels of a dissolution unit

o The drug is placed within the medium in the vessels after it has reached sufficient

temperature and then the dissolution apparatus is operated

o Sample solutions collected from dissolution testing are commonly analyzed

by HPLC or Ultraviolet–visible spectroscopy

o For most dosage forms to be efficacious, the API(s) must be absorbed into the

systemic circulation so that it can be transported to its site of activity.

o This process contributes to the bioavailability of the drug substance and involves two

steps: namely dissolution and absorption (or permeability).

o Dissolution is the process of extracting the API out of the dosage form solid-state

matrix into solution within the gastrointestinal tract.

o Absorption is the process of transporting the drug substance from the gastrointestinal

lumen into the systemic circulation

• Procedures for preparing the sample solution

o Six tablets Weighed X mg are placed into each vessel of the dissolution apparatus

containing 900mls of 0.1M Hcl,

o Paddles are rotated at 75 revolutions per minute,

o iii. the apparatus is maintained at 37 degree centigrade

o After 30minutes a certain volume from each of the vessels is withdrawn and filtered

o then a certain volume of the filtrate from each tablet is poured into flask and made

up to volume using 0.1M NaoH

o Absorbance of all six tablets is obtained using UV-spectrophotometer and 0.1M

sodium hydroxide was used as blank.

o Absorptivity for each tablet is recorded

o The percentage absorbance of the tablet is obtained by taking percentage absorbance

of the test sample divide by that of reference standard

• Factors affecting dissolution

o Pka

o Stability

o Solubility as a function of pH/surfactant concentration

o Particle size

o The dosage unit, including dosage form type (tablet, capsule)

o Polymorphism

o Nature of excipients such as lubricants, Disintergrants.

o Moisture content, surface coating

STEP 7: Procedures for Carrying Out Chromatographic Quality Tests.

(20 minutes)

• Chromatography

o Is the collective term for a set of separation techniques that operate based on the

differential partitioning of mixture components between a mobile and a stationary PH

The mobile phase (a liquid or a gas) travels through the stationary phase (a liquid or a

solid) in a defined direction.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o The distribution of components between the two phases depends on adsorption, ionic

interactions, diffusion, and solubility or, in the case of affinity chromatography,

specific interactions.

o The following are examples of chromatographic techniques used in quality test of

pharmaceutical products

 Thin layer chromatography method-TLC

 High-performance liquid chromatography (HPLC

 Gas chromatography (GC)

 Paper chromatography

• Thin layer chromatography method-TLC-

o Is a chromatography technique used to separate non-volatile mixtures.

o Thin-layer chromatography is performed on a sheet of glass, plastic, or aluminium

foil, which is coated with a thin layer of adsorbent material, usually silica gel,

aluminium oxide (alumina), or cellulose

Figure; TLC-plate

Source: research gate (2012).

o After the sample has been applied on the plate, a solvent or solvent mixture (known as

the mobile phase) is drawn up the plate via capillary action.

o Because different analyte ascend the TLC plate at different rates, separation is

achieved

o For example, with silica gel which is a very polar substance, a non-polar mobile

phases such as heptanes are used

o After the experiment, the spots are visualized. Often this can be done simply by

projecting ultraviolet light onto the sheet

o The sheets are treated with a phosphor, and dark spots appear on the sheet where

compounds absorb the light impinging on a certain area.

o Also Chemical processes can also be used to visualize spots for example

anisaldehyde forms colored adducts with many compounds, and sulfuric acid will

char most organic compounds, leaving a dark spot on the sheet

o To quantify the results, the distance travelled by the substance being considered is

divided by the total distance travelled by the mobile phase.

o This ratio is called the retardation factor (R f )

o The mobile phase must not be allowed to reach the end of the stationary phase.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

o Thin-layer chromatography can be used to monitor the progress of a reaction, identify

compounds present in a given mixture, and determine the purity of a substance

o To run a thin layer chromatography plate, the following procedure is carried out

o A small spot of solution containing the sample is applied to a plate, about 1.5

centimetres from the bottom edge.

o The solvent is allowed to completely evaporate off to prevent it from interfering with

sample's interactions with the mobile phase in the next step starting point

o If a non-volatile solvent was used to apply the sample, the plate needs to be dried in a

vacuum chamber.

o This step is often repeated to ensure there is enough analyte at the starting spot on the

plate to obtain a visible result

o Different samples can be placed in a row of spots the same distance from the bottom

edge, each of which will move in its own adjacent lane from its own

o A small amount of an appropriate solvent is poured into a glass beaker or any other

suitable transparent container (separation chamber) to a depth of less than 1

centimetre.

o A strip of filter paper is put into the chamber so that its bottom touches the solvent

and the paper lies on the chamber wall and reaches almost to the top of the container

o The container is closed with a cover glass or any other lid and is left for a few minutes

to let the solvent vapours‟ ascend the filter paper and saturate the air in the chamber.

o Failure to saturate the chamber will result in poor separation and non-reproducible

results

o The TLC plate is then placed in the chamber so that the spot(s) of the sample do not

touch the surface of the eluent in the chamber, and the lid is closed.

o The solvent moves up the plate by capillary action, meets the sample mixture and

carries it up the plate (elutes the sample).

o The plate should be removed from the chamber before the solvent front reaches the

top of the stationary phase (continuation of the elution will give a misleading result)

and dried.

o Without delay, the solvent front, the furthest extent of solvent up the plate, is marked

o The plate is visualized.

 As some plates are pre-coated with a phosphor such as zinc sulphide, allowing

many compounds to be visualized by using ultraviolet light;

 Dark spots appear where the compounds block the UV light from striking the

plate.

o Uses of TLC

 Purity identification of any sample Identification of compounds Examination of

reactions

 Biochemical analysis One of the most important applications of TLC is in

separation of multi-component pharmaceutical formulations. For example In food

and cosmetic industry, TLC method is used for separation and identification of

colours e.g. preservatives, sweetening agent, and various cosmetic products.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

STEP 8: Key Points ( 5 minutes)

• Physical quality tests for solid dosage forms include; friability test, Disintegration test

• Friability is the tendency for a tablet to chip, crumble or break following compression.

• Chromatographic techniques include TLC, HPLC,GC

STEP 9: Evaluation (5 minutes)

• What is friability?

• What are examples of chromatographic techniques?

• What are the uses of TLC?

• What are factors affecting disintegration time?

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

References

Abdelelah, A. (2015, March 13). Disintegration and dissolution tests. Retrieved from

https://www.slideshare.net/ameraabdelelah/disintegration-and-dissolution-tests

Uddin, M., Mamun, A., Akter, N., Sarwar, M., Rashid, M., & Amran, M. (2016).

Pharmacopoeial Standards and Specifications for Pharmaceutical Oral Liquid

Preparations. Archives of Current Research International,

Formulation of pharmaceutical solid-dosage forms. (2018). Pharmaceutical, Cosmetic and

Personal Care Formulations,143-158. doi:10.1515/9783110587982-008

Djuris, J., Ibric, S., & Djuric, Z. (2013). Chemometric methods application in pharmaceutical

products and processes analysis and control. Computer-Aided Applications in

Pharmaceutical Technology,57-90. doi:10.1533/9781908818324.57

Pharmaceutical Sterility Testing. (n.d.). Retrieved from

https://www.contractpharma.com/issues/2008-03/view_features/pharmaceutical-

sterility-testing

The pharmaceutical codex: Incorporating the British pharmaceutical codex. (1979). London:

Royal Pharmaceutical Society of Great Britain.

Harrod, D. C., & Barnbrough, W. E. (1893). The British pharmacopoeia. London:

Spottiswoode &.

PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5 Semester 2

← View topic-by-topic index

PDF / OFFLINE NOTES

Unataka kutumiwa notes hizi kupitia WhatsApp?Kwa notes zilizopangiliwa vizuri kwa kusoma offline au PDF, bonyeza kitufe hapa chini. Ujumbe wenye Level, Semester, Module na Topic utaandaliwa moja kwa moja.TUMIWA NOTES WHATSAPP

WhatsApp: 255620339260