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NTA Level 5 • Semester 2 • PST05207 Standard Operating Procedures for Equipments and Machines Quality Assurance of Pharmaceutical Products • Source Session/Topic 9 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 3 Brainstorming, 60 minutes Presentation Importance of SOPs in the Production of Pharmaceuticals 4 5 05 minutes Presentation Key Points 6 05 minutes Presentation Evaluation 67 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) 68 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. 69 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? 70 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

NTA Level 5 • Semester 2 • PST05207 The Operating Principles of Equipments and Machines Quality Assurance of Pharmaceutical Products • Source Session/Topic 8 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 2 Buzzing Pharmaceutical Preparation Unit 25 Minutes Presentation Operating Principles of an Autoclave 3 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 56 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. 57 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). 58 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

NTA Level 5 • Semester 2 • PST05207 Quality Control and Assurance in Relation to Preparation of Pharmaceutical Products Quality Assurance of Pharmaceutical Products • Source Session/Topic 7 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 7 35 minutes Products 8 05 minutes Presentation Key Points 9 05 minutes Presentation Evaluation 45 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 46 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 47 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

NTA Level 5 • Semester 2 • PST05207 GMP Equipments Requirements Quality Assurance of Pharmaceutical Products • Source Session/Topic 6 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 38 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 39 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) 40 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

NTA Level 5 • Semester 2 • PST05207 GMP Documentations Requirements Quality Assurance of Pharmaceutical Products • Source Session/Topic 5 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 31 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, 32 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 33 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.

NTA Level 5 • Semester 2 • PST05207 GMP Requirements on Raw Materials Quality Assurance of Pharmaceutical Products • Source Session/Topic 4 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 2 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 20 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 21 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, 22 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 23 PST 05207 Quality Assurance of Pharmaceutical Products NTA Level 5

NTA Level 5 • Semester 2 • PST05207 GMP -Personnel requirements Quality Assurance of Pharmaceutical Products • Source Session/Topic 3 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 2 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 13 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. 14 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

NTA Level 5 • Semester 2 • PST05207 Components of GMP Total Session Time: 120 minutes Quality Assurance of Pharmaceutical Products • Source Session/Topic 2 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 7 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 8 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. 9 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

NTA Level 5 • Semester 2 • PST05207 Introduction to Good Manufacturing Practices Quality Assurance of Pharmaceutical Products • Source Session/Topic 1 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 6 05 minutes Presentation 7 Evaluation 1 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) 2 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 3 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. 4 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