Pharmaceutical Sciences Notes

NTA Level 6 • Semester 2 • PST06211 Documentation of Pharmacovigillance Data Monitoring and Evaluation of Medicine Use • Source Session/Topic 10 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 10: Documentation of Pharmacovigillance Data Total Session Time: 120 minutes Prerequisites • None Learning Tasks By the end of this session students are expected to be able to: • Explain pharmacovigillance tools • Explain handling pharmacovigillance data • List characteristic of good documentation practices in pharmacovigillance Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • Computer and LCD Projector SESSION OVERVIEW Activity/ Step Time Content Method 1 05 minutes Presentation Introduction, Learning Tasks Presentation 2 10 minutes Pharmacovigillance Tools Brainstorming 50 minutes Handling Pharmacovigillance Data 3 Presentation 45 minutes Presentation Characteristic of Good Documentation 4 Buzzing practices in Pharmacovigillance 5 05 minutes Presentation Key Points 6 05 minutes Presentation Evaluation PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 78 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: Pharmacovigillance Tools (10 minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: • What are the Guidelines for Monitoring of Medicines safety? ALLOW few students to respond? WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below • Guidelines for Monitoring of Medicines safety o These are guidelines provided regulatory authority (TFDA) that facilitate the collection of pharmacovigillance information • Tanzania Pharmacovigillance Training Manual- manual for training stakeholders who are involve in documenting and reporting of pharmacovigillance information • Other tools include; o Yellow forms (ADR forms)  The Yellow card system for collecting information on suspected adverse drug reactions (ADRs) to medicines.  The system allows the safety of the medicines and vaccines that are on the market to be monitored.The system was founded in 1964 after the thalidomide disaster.  Yellow Cards are available from TFDA and a few are presented near the back of the BNF as tear-off pages. o Patient reporting forms –are used by patients to report any ADRs during the cause of treatment o Poor Quality Products reporting forms-they are used to report medicines that show poor efficacy or poor quality products o Patient alert cards-are carried by patient to identify them as patient with hypersensitive or allergic to particular kind of drug PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 79 STEP 3: Handling Pharmacovigillance Data (50 minutes) • Companies are required to take appropriate measures against unauthorised or unlawful processing of personal data and against accidental loss, destruction or damage. • Documentation containing Pharmacovigillancedata should not be left unattended and companies should adopt a clear desk policy for Pharmacovigillance documents. • Hard copies of documents, including those in workflow progress should be stored in a secure and robust area such as fire- retardant cupboards/archives. • Any database containing personal data used in PV should be fully validated or tested, as appropriate, to ensure changes to data can be identified and access to these systems should be restricted to named individuals. Companies may also consider configuring Pharmacovigillance databases to restrict access to sensitive personal data so only the country of collection has access, although this is not a requirement of the law. • Sensitive data should be encrypted to ensure the integrity of data transmissions. • Data and record management o All data, documents and records related to pharmacovigillance system are physically and electronically stored in designated folders and databases, and retained in accordance with the relevant legislation and requirements of the regulatory integrated quality management system on data and record management. o Acknowledgement on receipt of the Pharmacovigillance information o Entering the data into Vigi Flow  Done by trained officer  Manager review and audit the data before commitment  A web based data management tool used to manage ADR database.  All data are stored on a database server in Uppsala, Sweden. o Receipt of pharmacovigillance data and follow up  Companies collect data using a variety of tools and sources.  When an Adverse Effect is reported to a company it is important that some personal data is collected to meet the Pharmacovigillance requirements of having an identifiable patient and reporter.  Good Vigilance Practices requires that companies ensure individual case safety reports (ICSRs) contain a minimum set of information.  It also specifies that information relating to the patient is as complete as possible, in accordance with local privacy laws.  However, data subjects (persons who have experienced an Adverse Effect and if different, the persons making the Adverse Effect reports) must understand what personal data relating to them is being collected, by whom and for what purposes.  Data subjects should be allowed to give their consent.  Company follow-up request forms or Adverse Effect forms sent to a reporter for completion. PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 80  Data entered into safety databases must only be processed for Pharmacovigillance purposes and should not be processed for purposes not disclosed to the data subject. STEP 4: Characteristics of Good Documentation practices in Pharmacovigillance (55 minutes) Activity: Buzzing (10 minutes) ASK students to pair up and buzz on the following question • Which are characteristics of good pharmacovigillance practices in documentation? 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 • To ensure good pharmacovigillance practices, it is essential to have documentation with the following characteristics : • They must be designed, prepared, reviewed, and distributed on the basis of

NTA Level 6 • Semester 2 • PST06211 Reporting Pharmacovigillance Data Monitoring and Evaluation of Medicine Use • Source Session/Topic 11 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 11: Reporting Pharmacovigillance Data Total Session Time: 120 minutes Prerequisites • None Learning Tasks By the end of this session students are expected to be able to: • Explain ways of reporting pharmacovigillance data • List expedited reporting requirements • List necessary information in pharmacovigillance Reports Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • Computer and LCD Projector SESSION OVERVIEW Activity/ Step Time Content Method 1 05 minutes Presentation Introduction, Learning Tasks 35 minutes Presentation 2 Ways of Reporting pharmacovigillance Data Buzzing 3 25 minutes Presentation Expedited Reporting Requirements 45 minutes Presentation Necessary Information in pharmacovigillance 4 Brainstorming Reports 5 05 minutes Presentation Key Points 6 05 minutes Presentation Evaluation PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 84 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: Ways of Reporting Pharmacovigilance Data (35 minutes) Activity: Buzzing (10 minutes) ASK students to pair up and buzz on the following question • What are ways of reporting pharmacovillance data? 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 following are ways of reporting pharmacovigillance data • Spontaneous reporting o Spontaneous reports are termed spontaneous as they take place during the clinician's normal diagnostic appraisal of a patient, when the clinician is drawing the conclusion that the drug may be implicated in the causality of the event. o Spontaneous reporting system relies on vigilant physicians and other healthcare professionals who not only generate a suspicion of an ADR, but also report it. o It is an important source of regulatory actions such as taking a drug off the market or a label change due to safety problems. o Spontaneous reporting is the core data-generating system of international pharmacovigillance, relying on healthcare professionals to identify and report any adverse events o One of the major weaknesses of spontaneous reporting is that of under-reporting. o Spontaneous reports are a crucial element in the worldwide enterprise of pharmacovigillance and form the core of the World Health Organization Database • Clinical trial reporting o Also known as SAE (serious adverse event) reporting from clinical trials, safety information from clinical studies is used to establish a drug's safety profile in humans PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 85 and is a key component that drug regulatory authorities consider in the decision-making as to whether to grant or deny market authorization (market approval) for a drug. o SAE reporting occurs as a result of study patients (subjects) who experience serious adverse events during the conducting of clinical trials. (Non-serious adverse events are also captured separately.) o SAE information, which may also include relevant information from the patient's medical background, are reviewed and assessed for causality by the study investigator. This information is forwarded to a sponsoring entity (typically a pharmaceutical company) that is responsible for the reporting of this information, as appropriate, to drug regulatory authorities. • Expedited reporting o This refers to ICSRs (individual case safety reports) that involve a serious and unlisted event (an event not described in the drug's labelling) that is considered related to the use of the drug. o Spontaneous reports are typically considered to have a positive causality, whereas a clinical trial case will typically be assessed for causality by the clinical trial investigator and or the license holder. • Periodic Safety Update Reporting o Periodic Safety Update Reports (PSURs) are important pharmacovigillance documents. o They provide an opportunity for Marketing Authorization Holders (MAHs) to review the safety profile of their products and ensure that the Summary of Product Characteristics (SPC) and Package Leaflets are up to date. o They also provide a valuable source of pharmacovigillance data. o MAHs should submit PSURs to regulatory outhority example TFDA. • PSURs should as a minimum contain the following information: o Information on the product (i.e. brand name, dosage form, strength, manufacturer and country of origin), o The scope of drug safety data and the surveillance period, o Collection of adverse drug reaction (ADR) information (i.e. local serious ADRs, local non-serious ADRs, foreign serious ADRs, foreign non-serious ADRs, case reports published on international or local literatures including academic conferences). • Patient reporting o A simplified reporting form (Annex 5 of TFDA) should be used by patients to report information on suspected adverse drug reactions. o Patients should be encouraged to report adverse events and seek medical attention through their health care providers. o Further information on the report can be sought from the health care provider for serious and/or unknown reaction reported directly from patients. PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 86 PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 87 STEP 3: Expedited reporting requirements(25 minutes) • All serious reactions must be reported on an expedited basis using the same ADR reporting form (Annex 1of TFDA). • Expedited reports should be submitted to TFDA immediately and not later than 15 calendar days from receipt of the minimum information required for an adverse reaction report by a health care provider or personnel of the manufacturer. • Serious suspected adverse reactions occurring in all post-marketing studies of which the manufacturer is aware should be reported to the TFDA on an expedited basis. • When additional medically relevant information is received for a previously reported case, the

NTA Level 6 • Semester 2 • PST06211 Introduction to Adverse Drug Reactions (ADRs) Monitoring and Evaluation of Medicine Use • Source Session/Topic 12 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 12: Introduction to Adverse Drug Reactions (ADRs) Total Session Time: 120 minutes Prerequisites • None Learning Tasks By the end of this session students are expected to be able to: • Define ADRs • Explain the predisposing factors for ADRs • Classify ADRs • Explain each class of ADRs Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • Computer and LCD Projector SESSION OVERVIEW Activity/ Step Time Content Method 1 05 minutes Presentation Introduction to Learning Tasks 10 minutes Presentation 2 Definition of ADRS Buzzing 3 20 minutes Presentation Predisposing Factors for ADRs 20 minutes Presentation 4 Classification of ADRS Brainstorming 5 55minutes Presentation Explanations on each Class of ADRs 6 05 minutes Presentation Key Points 7 05 minutes Presentation Evaluation PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 91 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 ADRS (10 minutes) Activity: Buzzing (10 minutes) ASK students to pair up and buzz on the following question • What is Adverse drug reaction? 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 • Adverse drug reaction is a noxious and unintended reaction that occurs at a dose used for the treatment, diagnosis and prevention of disease, disorder or syndrome. • Side effects and ADRs are associated with drug use posing serious health consequences. Sometimes the word side effect and ADR are used alternatively but there is a clear difference between them. Side effect is often termed as type A ADR. • Sid effect is also an undesirable effect of drug and comes under ADR. STEP 3: Predisposing Factors for ADRs (20 minutes) • Age:The incidence of adverse drug reaction appears to be highest in the very young and very old people. In these two extreme periods of life, there is poorly developed and altered physiological function respectively. Therefore, metabolism and elimination of some drugs may be delayed. • Pathophysiological conditions:Diseases may alter the pharmacokinetic handling of a drug, its tissue sensitivity or the response to a drug. That is, diseases can alter drug absorption, metabolism, elimination and the body‘s response to drugs. • Amount of drug administered:An excessive response to drug or prolonged therapy may be a predisposing factor for ADRs. Over dosage is often relative rather than absolute because the individual response to a drug varies. PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 92 • Sex:several studies have shown that for some drugs women are more likely to suffer from ADRs than men. This is due to pharmacokinetic and or pharmacodynamic sex-related factors. • Previous history of allergy:Patients who have previously suffered an allergic drug reaction appear to be more susceptible than others to allergic ADRs in general. Heredity may make some people more susceptible to the toxic effects of certain drugs • Racial or Genetic Factors: There may be racial differences in the incidence of some type of ADRs or some individuals have a genetically determined response to development of ADRs. e. g. Ethno-pharmacological difference such as glucose 6-phosphate dehydrogenise deficiency, which predisposes to some drug induced haemolytic anaemia, is commoner amongst Africans. • Multiple Drug Therapy (Polypharmacy) The incidence of ADRs increases with the number of drugs given due to risk of interactions. Interaction between prescribed drugs is therefore an area, which is of concern to every health care professional. STEP 4: Classification of ADRS (20 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes • What are classes of adverse drug reactions? 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 • There are four basic systems used to classify ADRs o Alphabetical or ABCDE system – by Rawlins and Thompson o According to intensity o Underlying mechanism mode o ADR according to frequency STEP 5: Explanations on each class of ADRs (55 minutes) • ABCDE SYSTEM – classify ADRs into five types o Type A („augmented―)  These ADR are expected PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 93  They can be predicted on the base of pharmacodynamic properties of drug  They depend on drug dose, they appear at higher doses  Frequency is high > than 1%  Mortality is low  Therapy consists in dose adjustment  e.g.: cough after ACEI, bleeding from GIT after NSAIDs, aspirin, corticoids o Type B (bizard―)  Idiosyncratic reactions  These ADR are not expected  They can be hardly predicted  Doesn´t depend on dose  Occur in predisposed, intolerant patients – can be explained by rare genetic polymorphism, allergic reactions  Frequency is low < than 0,1%  Mortality is high o Type C continuous)  This type of ADR increases number of ―spontaneous― diseases  They occur usually after long-lasting administration  They are often serious and persistent  Mechanism of genesis is unclear  They are unexpected, not predictable  They can´t be verified experimentally  e.g.: oral contraceptives and increased occurrence of thromboembolia. o Type D (delayed)  Adverse effect may be presented years after a drug was used (years resp. generations)  Teratogenity  Carcinogenetic  Mutagenity  e.g.: cancer of vagina at daughters of

NTA Level 6 • Semester 2 • PST06211 Documentation of ADRs Monitoring and Evaluation of Medicine Use • Source Session/Topic 13 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 13: Documentation of ADRs Total Session Time: 120 minutes Prerequisites • None Learning Tasks By the end of this session students are expected to be able to: • List necessary information for documentation in ADRs • Explain types of ADR reporting forms • Explain handling of ADR data Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • Computer and LCD Projector SESSION OVERVIEW Activity/ Step Time Content Method 1 05 minutes Presentation Introduction, Learning Tasks 30 minutes Presentation Necessary Information for Documentation of 2 Brainstorming ADRs 30 minutes Presentation 3 Types of ADR Reporting Forms Buzzing 5 40 minutes Presentation Handling of ADR Data 6 10 minutes Presentation Key Points 7 05 minutes Presentation Evaluation PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 97 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: Necessary Information for Documentation of ADRs (30 minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: • What are the necessary information for documentation of ADRs? ALLOW few students to respond? WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below • Properly charting a patient‘s ADR can protect him/her from further harm and shield you and your facility from legal problems. • Because a significant part of the evaluation for any drug's long-term safety occurs after it's on the market, serious ADRs should be reported to TFDA. • Document the patient's clinical condition, your interventions, and the patient's response. • Fill out an incident report and internal ADR report, which should contain all the information that will be needed. • To properly document an ADR, first document the clinical facts in the patient's medical record. Then complete an incident report. • Your documentation in the patient's chart and incident report should include: o Patient information, such as date of birth, sex, race, and weight; pre-existing or coexisting medical conditions; other medications taken, allergies; and relevant diagnostic and lab results o The date of the event o Specific patient outcomes attributed to the ADR, such as prolonged hospitalization o A clear, factual, objective and chronologic description of the problem or event. o Document your assessment findings and interventions, all persons notified and their responses, the dates and times of these notifications, and the actions taken by those you've informed and the patient's response to interventions. PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 98 o The name of the drug, the manufacturer, the lot number and expiration date on the packaging (if available), dosage, frequency, duration, route, and times of administration. Returning any packaging or containers to the pharmacy or retaining them as evidence. o Your name, title, and credentials as a reporter. STEP 3: Types of ADR Reporting Forms (30 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question What are types of documents used to report ADRs? 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 following forms/tool are used to document and report ADRs; o Yellow form -for reporting ADRs to medicines or vaccines  The Yellow card system for collecting information on suspected adverse drug reactions (ADRs) to medicines.  The system allows the safety of the medicines and vaccines that are on the market to be monitored.The system was founded in 1964 after the thalidomide disaster.  Yellow Cards are available from TFDA and a few are presented near the back of the BNF as tear-off pages.  Blue form -for reporting poor quality products. This can be used to report substandard and counterfeit drugs o Pharmacovigillance Register – For recording details on filled forms o Green form -for reporting ADRs by patients themselves o Pink card -Patient ADR alert card. The criteria for issue of alert card to patient include  Patients who are hypersensitive/allergic/intolerance to particular drug  Patient who develop near fatal reaction to any particular drug  Patient who had a drug induce morbidity to any drug  Patient who had hospital admission due to an ADR to any drug • Apart from ADR reporting tools other documents may help obtaining information for patients such as • Personal Medication Record PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 99 o The personal medication record (PMR) is a comprehensive record of the patient‘s medications (prescription and non-prescription medications, herbal products, and other dietary supplements). o Pharmaceutical personnel in their carrier may use personal medication record to include category which will need the patient to report other medication-related problems (e.g., what medication caused the problem? What was the problem?) o This will help to trace signal STEP 5: Handling of ADR Data(40 minutes) • An acknowledgement letter or note will be sent to the reporter for every ADR report received with an additional reporting form. • The ADR reports shall be stored in a confidential database at TFDA and analysed report sent to the WHO database of International Programme on safety monitoring of drugs to which all case reports received by the National centres are sent. • The names of reporter and the patient will be removed before any details about a specific adverse drug reaction are used or communicated to others. • Publications will not disclose trade name of products unless regulatory actions have

NTA Level 6 • Semester 2 • PST06211 Reporting of ADRs Monitoring and Evaluation of Medicine Use • Source Session/Topic 14 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 14: Reporting of ADRs Total Session Time: 120 minutes Prerequisites • None Learning Tasks By the end of this session students are expected to be able to: • List objective of ADRs monitoring • Explain procedures for reporting ADRs • List centres for monitoring ADRs Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard marker • Computer and LCD Projector SESSION OVERVIEW Activity/ Step Time Content Method 1 05 minutes Presentation Introduction, Learning Tasks 15 minutes Presentation Objective of ADRs Monitoring 2 Buzzing 70 minutes presentation and Procedures for Reporting ADRs 3 group discussion 4 10 minutes presentation Centres for Monitoring ADRs 5 10 minutes Presentation Key Points 6 10 minutes Presentation Evaluation PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 103 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: Objectives of ADRs Monitoring (15 minutes) • The System of ADRs notification in Tanzania is a centralized reporting, whereby suspected case reports of ADR are reported by health care professionals and pharmaceutical manufacturers to TFDA. • ADR reporting covers all pharmaceutical products, biologicals, herbal drugs, cosmetics and medical devices circulating in the Tanzanian market • In addition, drug monitoring is important in detection of lack of efficacy, detection and prevention of counterfeit and substandard products in clinical practice. • It is essential that the ADR monitoring program for safety of medicinal product be supported by health care professionals • Objectives Of ADRs Monitoring o To detect the nature and frequency of ADRs including periodic re-evaluation of the benefit-risk ratio of medicinal products in order to assist the drug regulatory authority, public health programs, scientists and consumer society take appropriate action to minimize risks of ADRs to consumers. o To identify risk factors that may predispose, induce or influence the development, severity and incidence of adverse reactions in the population of Tanzania, examples;  Patient factors: genetics, racial differences, diets, diseases, prescribing practices, culture of drug use and traditions of the people e.g. high carbohydrate, fat diet etc  Drug interactions, drug distribution, storage and use including indications, dose, availability and other underlying condition PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 104 STEP 3: Procedures for Reporting ADRs (70 minutes) Activity: Small group discussion (30 minutes) ASK students to form small manageable groups and discuss following questions • What are procedures for reporting ADRS? ALLOW few groups to respond and let other groups to add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below The following are procedures for reporting ADRs as per TFDA guidelines • What to report o Any undesirable adverse event suspected to be associated with use of drug; biological (including blood products), herbal drugs, cosmetics or medical devices should be reported. They should include;  All ADRs as a result of prescription and non-prescription medicine  All suspected adverse drug reactions regardless of whether or not the product was used in accordance with the product information provided by the company marketing the product  Unexpected reaction, regardless of their nature or severity, whether not consistent with product information or labelling  An observed increase in frequency of a given reaction  A serious reaction, whether expected or not  All suspected ADRs associated with drug-drug, drug-food or drug-food supplements interactions  ADRs in special field of interest such as drug abuse and drug use in pregnancy and during lactation  ADRs occurring from overdose or medication error  Unusual lack of efficacy or when suspected pharmaceutical defects are observed o What information is required for ADRs case report?  The minimal standard information to be provided for proper assessment of the ADR case report are;  Patient information  Adverse reactions description (include laboratory results if available)  Information related to the suspected drug(s)  Information on management of the adverse reactions PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 105  Information about the reporter o Patient information  Patient identity: indicate initials or record number of the patient in hospital, medical institution, dispensary, clinic or pharmacy.  Birth dates or age: indicate date, month and year  Sex: Male or Female  Weight: should be in Kilograms • Adverse reaction(s) o Brief description of the ADR(s): indicate the adverse(s) reaction by marking X in the appropriate box. Preferably describe briefly the nature of the adverse reaction being reported but as clearly as possible, including the body site and severity. o Time/date of onset of the adverse reactions: State the time of onset or the occurrence of the adverse reaction in relation to the administration of the drug. Indicate the date of onset in the following order; day, month and year. For example, did the drug reaction appear immediately following drug administration or there was temporal or spatial correlation with administration. o Other relevant information: Patient medical history or laboratory data including dates if available, considered relevant to the case or the adverse reaction being reported should be entered.  Mention appropriate laboratory tests done to the patient and results to confirm the adverse reaction.  State this concisely but clearly • Suspected drug(s) o Name of the suspected drug (s): trade name should preferably be used, if trade name not available, generic name may be used. Strength of the drug (s) should be stated  Dosage, frequency and route of administration should be clearly notified. For example;  Dosage (specify

NTA Level 6 • Semester 2 • PST06211 Substandard and Counterfeit Medicines Monitoring and Evaluation of Medicine Use • Source Session/Topic 15 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 15: Substandard and Counterfeit Medicines Total Session Time: 120minutes Prerequisites • None Learning Tasks By the end of this session students are expected to be able to: • Explain substandard and counterfeit medicines • Distinguish between counterfeit and substandard medicines • Explain the effect of substandard and counterfeit medicines to the public health • List challenges in preventing counterfeit and substandard medicines Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • Computer and LCD Projector SESSION OVERVIEW Activity/ Step Time Content Method 1 05 minutes Presentation Introduction, Learning Tasks 20 minutes Presentation 2 Substandard and Counterfeit Medicines Buzzing 30 minutes Presentation Differences between Substandard and 3 Brainstorming Counterfeit Medicines 35 minutes Presentation Effect of Substandard and Counterfeit 4 Small Group Medicines to the Public Health Discussion 15 minutes Presentation Challenges in Preventing Counterfeit and 5 Substandard Medicines 6 10 minutes Presentation Key Points 7 05 minutes Presentation Evaluation PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 112 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: Substandard and CounterfeitMedicines (20 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes • What are the Substandard and Counterfeit Medicines? 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 • Counterfeit medicines are medicines that are deliberately and fraudulently mislabeled with respect to identity and /or source.(WHO) o Their quality is unpredictable as they may count the wrong amount of active ingredients. o In all cases counterfeit medicines are manufactured secretly with no possibility of control. o Counterfeiting occurs both with branded and generic products. o It has been found that counterfeiters copy or imitate existing products but they also manufacture products that are completely invented o Counterfeit medicines represent an enormous public health challenge. o Anyone, anywhere in the world, can come across medicines seemingly packaged in the right way but which do not contain the correct ingredients and, in the worst – case- scenario may be filled with highly toxic substances. o In some countries, this is rare occurrence, but in others, it is an everyday reality. • Substandard medicine Any branded or generic drug that does not meet national or international standards for quality, purity, strength, or packaging. ―And the amount of active substance is lower or higher than as stated in standards for quality. • Substandard products could result from o Poor manufacturing practices,In some countries 10–20% of medicines fail laboratory tests for quality, substandard products could result from poor manufacturing practices, PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 113 unsuitable packaging, storage and distribution or when generic drugs are produced by unregistered manufacturers. Not only potency but also dissolution rates of tablets and capsules are a problem ,Unsuitable packaging, Storage and distribution o When generic drugs are produced by unregistered manufacturers. o Forms in which substandard and counterfeit occurs  Correct drug, correct ingredients not registered brand i.e. copies of original products  Wrong ingredients, but therapeutically active  No active ingredients  Toxic ingredients  Correct drug and quantities but fake packaging  Products with high level of impurities and contaminants  Incorrect quantities of Active Pharmaceutical Ingredient STEP 3: Differences between Substandard and Counterfeit Medicines (30mins) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: • What is the difference between substandard and counterfeit medicine? ALLOW few students to respond? WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below • Both counterfeit drugs and substandard drugs can be harmful, but it is important to understand that they are different. • By contrast, counterfeit medicines, defined by the World Health Organization (WHO) as ―spurious/falsely-labelled/falsified/counterfeit‖ medicines, are ―deliberately and fraudulently mislabelled with respect to identity and/or source‖ (World Health Organization 2010). • Although substandard and counterfeit medicines are similar in that both have serious public health implications, counterfeits are not produced by licensed manufacturers. • Although counterfeits tend to be substandard (in that they do not contain correct amounts of active ingredient), this is not inherent in the definition of counterfeits. • The difference in manufacturers means the problems with substandard and counterfeit medicines are distinct. PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 114 • Substandard medicines, for example, can be controlled through effective regulation and enforcement, because manufacturers are known and licensed. Counterfeits, however, can be produced in homes, small industries, and backyards, and are harder to regulate (International Medical Products Anti-Counterfeiting Taskforce 2008). • Substandard medicines are made by licensed manufacturers operating within the framework of national pharmaceutical regulatory standards. • Also referred to as ―out of specification‖ products, these include medicines sold past their expiration date, medicines that have been compromised in shipping or storage, and medicines that are missing active ingredients or contain the wrong ratio of active ingredients (World Health Organization n.d.c). • Substandard medicines may arise due to human error, negligence, or resource restrictions (World Health Organization 2003). They may result from both inadvertent and deliberate actions by a legitimate manufacturer. The differences exist between counterfeit and substandard medicine aresummarized in the table below; SUBSTANDARD MEDICINES COUNTERFEIT MEDICINES When substandard medicines are found, the With counterfeit drugs, the company that company that made them is known. manufactured them is unknown. Consequently, the authorities

NTA Level 6 • Semester 2 • PST06211 Detection of Substandard and Counterfeit Monitoring and Evaluation of Medicine Use • Source Session/Topic 16 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 16: Detection of Substandard and Counterfeit Medicines Total Session Time: 120 minutes Prerequisites • None Learning Tasks By the end of this session students are expected to be able to: • List methods for detecting substandard and counterfeit medicines • Explain methods for detecting substandard and counterfeit medicines • Explain how consumers can identify substandard and counterfeit Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • Computer and LCD Projector SESSION OVERVIEW Activity/ Step Time Content Method 1 05 minutes Presentation Introduction, Learning Tasks 30 minutes Presentation Methods for Detecting Substandard and 2 Buzzing Counterfeit Medicines 50 minutes Presentation and Explanation on Methods for Detecting 3 Small Group Substandard and Counterfeit Discussion 20 minutes Presentation and Identification of Substandard and Counterfeit 4 Brainstorming by Consumers 5 10 minutes Presentation Key Points 6 5 minutes Presentation Evaluation PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 121 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: Methods for Detecting Substandard and Counterfeit Medicines (30 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question in 2 minutes • What are the methods used to identify counterfeit and substandard medicines? 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 following are ways of identifying counterfeit and substandard drugs o Chromatographic Techniques, Thin-layer chromatographic (TLC) method o HPLC, Gas Chromatography, Ion Chromatography, and Capillary Electrophoresis. o Visual inspection o Use of Cutting Edge Technologies ( example Truscan) o Test-tube colour reactions o Melting-point determination • A Fake drug is a drug product which is not what it purports to be. It is any drug product which is formulated or made to appear to be better than it really is. • The term can also refer to a drug which is deliberately and fraudulently mislabeled with respect to identity and/or source or with fake packaging • WHO basic tests represent one of the many screening procedures for verifying the identity of pharmaceutical dosage forms. • According to WHO, these tests were designed o To provide a simple and readily applicable method for verifying the identity of drug substances, using a limited range of easily available reagents, when the labeling and physical attributes give rise to doubt; PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 122 o To provide a practicable means of confirming the identity of a drug when a well- equipped laboratory facility is not available; o To indicate if gross degradation has occurred in certain substances that are known to decompose readily under adverse conditions. • Because these tests only confirm the identity of drug substances, or the presence of impurities, the tests are not in any way intended to replace the requirements of international pharmacopoeia or other pharmacopoeia monographs which give assurance of quality. • How Counterfeit Drug Enter Drug Distribution System o There can be one or more manufacturer or even repackager who handles the drug before it reaches the retailer. o Counterfeit drugs are associated with the practice of diversion. o Diversion is the sale of drugs outside the distribution channels for which they were originally intended o Diverted drugs can originate domestically-redirection of prescription drugs from other legitimate sources (free samples for doctors or lower priced drugs for non- profit clinics or Medicaid programs). o Diverted drugs can originate from the foreign market (prescription drugs are donated or a lower-priced product is diverted to a country where a higher price product is marketed. o Counterfeit drugs enter the distribution system, because they are purchased outside the normal distribution chain and without the usual regulatory safeguards. STEP 3: Explanation on Methods for Detecting Substandard and Counterfeit Medicines (50 minutes) Activity: Small Group Discussion ( 30 minutes) DIVIDE students into small manageable groups ASK students to discuss on the following question • What are Methods for Detecting Substandard and Counterfeit Medicines? ALLOW students to discuss for 15 minutes ALLOW few groups to present and the rest to add points not mentioned CLARIFY and SUMMARIZE by using the contents below • Thin-layer chromatographic (TLC) method o This method is used to identify and estimate the amount of the drug substance or the presence of impurities in a drug sample. TLC method for identifying drug substances is PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 123 based on selective affinity of test samples for the stationary or the mobile phase. TLC procedures have been found to be suitable for testing drug products with insufficient active ingredients and are chosen over WHO basic tests due to its specificity and selectivity. This method is also subject to less interference by excipients. o TLC is a planar chromatographic technique that is ideal for field drug testing o In TLC comparisons, authentic samples travel the same distance on a TLC plate and yield main spots of highly similar shapes, colours, intensities, and sizes as reference standards. o TLC is a qualitative and, when used with visual detection, semi-quantitative technique. o The distance the sample travels is associated with its identity; the intensity of the spot correlates with the amount of the drug present. o High concentrations of impurities may be visible on a TLC plate as well. o Many researchers use TLC to distinguish between authentic and falsified versions of several

NTA Level 6 • Semester 2 • PST06211 Controlling Substandard and Counterfeit Monitoring and Evaluation of Medicine Use • Source Session/Topic 17 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 17: Controlling Substandard and Counterfeit Medicines Total Session Time: 60 minutes Prerequisites • None Learning Tasks By the end of this session students are expected to be able to: • List and explain methods for controlling substandard and counterfeit medicines • Explain mechanisms for curbing spread of substandard and counterfeit medicines in Tanzania Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • Computer and LCD projector SESSION OVERVIEW Activity/ Step Time Content Method 1 05 minutes Presentation Introduction, Learning Tasks 25 minutes Presentation and Methods for Controlling Substandard and 2 Buzzing Counterfeit Medicines 20 minutes Curbing Spread of Substandard and Counterfeit Presentation and 3 Medicines in Tanzania Brainstorming 4 05 minutes Presentation Key Points 5 05 minutes Presentation Evaluation PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 131 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: Methods for Controlling Substandard and Counterfeit Medicines (25 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes • What measures can be taken to control substandard and counterfeit medicines? 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 Given the diverse and complex nature of the issues and challenges related to substandard and counterfeit medical products, a wide range of interventions are needed to effectively address them. • Member States should reaffirm their commitment to the fight against counterfeit medical products and engage in updating, developing, implementation and monitoring of national medicines policies. • Member States should establish NMRAs that have adequate legal mandate, independence and institutional capacity to ensure and strictly enforce compliance of medical products with standards of quality, safety and efficacy; and to effectively • Control the manufacture, export, import and distribution of substandard/spurious/falsely labeled/falsified/counterfeit medicines. • In order to address the problem of sufficient training and availability of qualified staff, Member States should develop and implement a sustainable human resource strategy for the pharmaceutical sector that ensures adequate human resource capacity including specialized training and retention of regulatory personnel • Continuing education and training programmes should be constituted into training curricula to enhance the knowledge and skills of health personnel to enable them to prevent, PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 132 recognize and appropriately deal with cases of substandard and counterfeit medical products. • Member States should put in place reliable supply systems and the requisite financial resources to ensure the availability of quality and affordable essential medical products in public health facilities. Comprehensive quality assurance systems for procurement and distribution should be strengthened for the public, private and other health care providers. • Necessary measures to ensure access to affordable medical products that meet quality and safety standards should be incorporated and given due emphasis in national health policies and strategic plans. Government authorities should monitor and regulate the prices of medical products to ensure their availability and affordability • Member States should establish effective systems to carry out specific studies and routine market surveillance to quantify the magnitude of the problem and to inform the development and implementation of appropriate policies and regulations • The strategy should involve all activities aimed at fighting illegal production, distribution and use of these medical products. • Based on the findings of the studies, Member States should develop information, education and communication strategies to increase awareness of policy makers, health workers and the general public about the dangers of using substandard/spurious/ falsely labeled/falsified/ counterfeit medical products • Member States should establish effective national, regional and interregional cooperation and collaboration mechanisms including reinforcing regulatory networks and exchange of information among public health, law enforcement, professional associations, NGOs and other relevant authorities to improve prevention, detection, investigation and prosecution of cases related to substandard/ spurious/falsely labeled/ falsified/counterfeit medical products. • WHO should o further develop tools and guidelines enabling Member States to adapt and implement policies and strategies; o Continue to assess and strengthen National Medicine Regulatory Aauthorities in order to ensure the quality, efficacy and safety of medical products o (Support Member States to mobilize more resources for developing human resource capacity for the pharmaceutical sector; o Continue to facilitate the exchange of objective and independent regulatory information among Member States o Intensify the promotion and implementation of good governance, accountability and transparency in Member States; o Strengthen the conduct and dissemination of operational research on substandard/spurious/falsely labeled/falsified/counterfeit medical products and encourage Member States to use evidence for policy actions; and o Strengthen monitoring and evaluation of programmes dedicated to combating the manufacture, distribution and use of substandard and counterfeit medicines. PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide 133 STEP 3: Curbing Spread of Substandard and Counterfeit Medicines in Tanzania (20 minutes) Activity:Brainstorming (5 minutes) Ask students to brainstorm on the following question: • What measures can be taken to control spread of substandard and counterfeit medicines in Tanzania? ALLOW few students to respond WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below • The following are measures to be taken to control spread of substandard and counterfeitmedicines in Tanzania o At the national levels, the government must:  Improve the availability and affordability of medicines;  Enact deterrent legislation prohibiting the manufacture, importation, exportation, distribution and sale of substandard and counterfeit medicines; 

NTA Level 6 • Semester 2 • PST06211 Distribution of Substandard and Counterfeit Medicines ………………………………….. 139 Monitoring and Evaluation of Medicine Use • Source Session/Topic 18 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 18: Distribution of Substandard and Counterfeit Medicines ………………………………….. 139 PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide ii 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 facilitator‘s guide and assessment plan was participatory approach which included a number of activities through various workshops such as PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide iii planning, and orientation of material development. After these preliminary workshops, experts developed materials individually and in-groups. Thereafter, developed 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 12 modules for NTA level 6 making 12 Facilitator guides and one Practicum guide. PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide iv 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. Gamuyafor 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.FadhiliLyimo Assistant Director Allied Health,MoHCDGEC Dr. Jacqueline Uriyo Acting Principal, CEDHA Dr.Sungwa N. Kabissi Project Manager – MAP, CSSC Ms. Diana H. Gamuya CEDHA Ms. Grace Mallange PC Mr.WensaaMuro KSP PST 06211 Monitoring and Evaluation of Medicines Use NTA Level 6 Semester 2 Facilitator Guide v Ms. Emily Mwakibolwa Pharmacy Council Mr.Samwel M. Zakayo Pharmacy Council Mr.SamweliMdallingwa NACTE Dr.ByeraShwekerela CEDHA Dr.MwanduJiyenze CEDHA Mr.StephanoKiberiti CEDHA Mr.Amani Phillip HKMU Mr.OmaryMejjah CUHAS Mr.Rajabu I. Amiri MUHAS Ms.Tumaini H. Lyombe MUHAS Ms.Dilisi J. Makawia KSP Mr.NemesUisso RAS-KLM Mr.GoodluckMdugi RuCU Mr.EvalistShileki DECOHAS Mr.EliabuMshashi KIUT Dr.Loishooki S. Laizer Director of Human Resources Development Ministry of Health, Community Development, Gender, Elderly and