KMR ADVICE

B.Pharm Exam Strategy & Important Questions Guide

Mr. K. Mallikarjuna Reddy

Associate Professor, M. Pharma (Pharmacology)

Vasantidevi Patil Institute of Pharmacy, Kodali, Maharashtra

EXAM STRATEGY & IMPORTANT QUESTIONS GUIDE

8.3 BP805ET · PHARMACOVIGILANCE (THEORY · ELECTIVE)

Complete PCI B.Pharm Semester VIII syllabus coverage · 22 questions · past-paper-driven + syllabus-completeness selection
+ 🎯 Career Guidance & 🧠 Knowledge Self-Checker

📖 HOW TO USE THIS GUIDE

⭐ Stars reflect past-paper repeat frequency across major Indian universities (2019-2023).

🔴 High Priority · 🟡 Medium Priority · 🔵 Low / Syllabus-Completeness Priority.

📚 Each question has detailed answer + 🪝 Hook line + 📊 Comparison tables + 🔄 Flowcharts + ⚡ At-a-Glance Summary.

🎯 At the end: Career Guidance Tab + 🧠 Knowledge & Interest Self-Checker.

📋 PCI B.Pharm Semester VIII · BP805ET Pharmacovigilance — Syllabus Coverage Checklist

Unit	Hours	PCI Topics	This Guide Q-Map
I	10h	Introduction — definition, history (Thalidomide), aims, scope · ADR — definition, classifications (Rawlins-Thompson A-F, WHO), severity (Hartwig), seriousness, predictability · drug-related problems · medication errors.	Q1, Q2, Q3, Q4
II	10h	Pharmacovigilance methods — passive (spontaneous reporting), active (cohort event monitoring, sentinel sites), prescription event monitoring (PEM), targeted spontaneous, registries · global PV systems (WHO-UMC, FDA FAERS, EudraVigilance, MHRA Yellow Card).	Q5, Q6, Q7, Q8
III	8h	Causality assessment — WHO-UMC scale, Naranjo, Hartwig severity, Schumock-Thornton preventability · drug dictionaries — WHO-DD, MedDRA hierarchy.	Q9, Q10, Q11, Q12
IV	10h	ICSR — components, E2B(R3) format · expedited reporting (15-day SUSAR rule, 7-day fatal/life-threatening) · PSUR / PBRER (ICH-E2C) · DSUR (E2F) · Risk Management Plan (RMP, ICH E2E) · signal detection methods (PRR, ROR, BCPNN, MGPS).	Q13, Q14, Q15, Q16, Q17
V	7h	Indian PV system — PvPI, IPC Ghaziabad, AMC network, NDCT Rules 2019 · vaccine pharmacovigilance — AEFI, SAFE-VAC · pharmacist's role · PV in herbal & biologic products.	Q18, Q19, Q20, Q21, Q22

✅ All five PCI units fully mapped · ⏱️ Total syllabus = 45 hours theory.

📊 Past-Paper Frequency Analysis (2019-2023) — Verified Citations Only

Topic	Hits	Priority	Verified Source-University
Definition + history (Thalidomide) + aims of PV	4	⭐⭐⭐⭐⭐	RGUHS 2019, AKTU 2021, JNTU-K 2022, KUHS 2023
ADR — definition + classification (A-F) + severity	4	⭐⭐⭐⭐⭐	RGUHS 2020, AKTU 2021, JNTU-K 2022, KUHS 2023
Causality assessment (WHO-UMC, Naranjo)	3	⭐⭐⭐⭐	RGUHS 2021, AKTU 2022, JNTU-K 2023
PvPI / IPC Ghaziabad / AMC structure	3	⭐⭐⭐⭐	RGUHS 2020, AKTU 2022, JNTU-K 2022
ICSR — Suspected ADR form components	3	⭐⭐⭐⭐	JNTU-K 2020, RGUHS 2022, AKTU 2023
PV methods — passive + active monitoring	2	⭐⭐⭐	AKTU 2021, RGUHS 2023
Signal detection (PRR, ROR)	2	⭐⭐⭐	JNTU-K 2022, AKTU 2023
WHO-UMC + VigiBase	2	⭐⭐⭐	RGUHS 2021, JNTU-K 2023
PSUR / PBRER (ICH-E2C)	2	⭐⭐⭐	JNTU-K 2021, AKTU 2022
MedDRA / WHO Drug Dictionary	2	⭐⭐⭐	RGUHS 2022, JNTU-K 2023
AEFI vaccine surveillance	1	⭐⭐	AKTU 2023
Risk Management Plan (RMP)	1	⭐⭐	JNTU-K 2023
Pharmacist's role in PV	1	⭐⭐	RGUHS 2023
PV in herbal/biologic products (sparse)	0-1	📘 Syllabus-completeness	Combined with Q22
NDCT Rules 2019 (sparse)	0-1	📘 Syllabus-completeness	Combined with PvPI

Sources audited: AKTU, JNTU-K, RGUHS, PARU, KUHS, Anna University.

🎯 Priority Reading Guide

🔴 HIGH PRIORITY — 5★ & 4★ (~70% of marks)

Definition + history (Thalidomide) + aims of PV (Q1, Q2).
ADR — classification A-F (Rawlins-Thompson) + Hartwig severity (Q3).
Causality assessment (Q9) — WHO-UMC scale, Naranjo, Hartwig.
PvPI / IPC Ghaziabad / AMC structure (Q18).
ICSR — Suspected ADR form components (Q13).

🟡 MEDIUM PRIORITY — 3★ (~22% of marks)

PV methods (Q5) — passive vs active vs cohort event monitoring.
Signal detection (Q17) — PRR, ROR, BCPNN.
WHO-UMC + VigiBase (Q7).
PSUR / PBRER (ICH-E2C) (Q15).
MedDRA + WHO Drug Dictionary (Q11, Q12).

🔵 LOW / SYLLABUS-COMPLETENESS — 1-2★ (~8% of marks)

AEFI vaccine surveillance + SAFE-VAC (Q19).
Risk Management Plan (RMP, ICH E2E) (Q16).
Pharmacist's role in PV (Q20).
PV in herbal & biologic products (Q21).
NDCT Rules 2019 + medication errors (Q22, Q4).

📘 UNIT I — Introduction to Pharmacovigilance

Q1Define Pharmacovigilance (PV). Discuss its history, aims, scope and importance.⭐⭐⭐⭐⭐

10 marksRGUHS 2019AKTU 2021JNTU-K 2022KUHS 2023

🪝 Hook: "Pharmacovigilance = the watchdog of drug safety, born from the Thalidomide tragedy."

1. Definition (WHO 2002)

"Science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem." Etymology: Greek pharmakon (drug) + Latin vigilare (to watch). Term coined by French pharmacologist Begaud (1973); formal WHO programme launched 1968.

2. Historical Milestones

Year	Event
1937	Sulphanilamide elixir disaster (USA) — diethylene glycol solvent killed 107, mostly children → led to FD&C Act 1938
1961	Thalidomide tragedy — phocomelia (limb deformities) in > 10,000 babies in 46 countries (W. McBride, Lancet)
1962	Kefauver-Harris Amendment (USA) — proof of efficacy + safety mandatory
1968	WHO Pilot International Drug Monitoring Programme — Geneva
1978	WHO Collaborating Centre at Uppsala (UMC), Sweden — global ADR database (now VigiBase)
1986	India joins WHO programme
1996	Rofecoxib (Vioxx) withdrawal — cardiovascular events
2002	WHO formal definition of pharmacovigilance
2010	India launches PvPI — IPC Ghaziabad as NCC
2019	India NDCT Rules 2019 — mandatory reporting timelines

3. Aims of Pharmacovigilance

1. Detect previously unrecognised ADRs (signals).
2. Assess risk-benefit ratio of medicines in marketed phase.
3. Understand mechanism, severity, frequency.
4. Prevent harm — label updates, restrictions, withdrawal, education.
5. Promote rational, safe, effective drug use.
6. Improve public health & clinical practice.
7. Educate healthcare professionals + patients.

4. Scope

ADRs · medication errors · drug interactions · poor-quality / counterfeit / sub-standard drugs · drug abuse / misuse · drug-induced disease · therapeutic failure · effects on pregnancy / lactation · vaccine adverse events (AEFI) · medical-device safety · phytomedicines / herbal products · biologics / biosimilars · gene + cell therapy.

5. Importance

• Pre-marketing trials are limited (small n, short duration, restricted population) — rare or delayed ADRs only emerge post-marketing.
• Public-health protection, patient safety, regulatory trust.
• Economic — prevents costly drug-related morbidity (~$76 billion/yr USA).
• Drug-development feedback for next-generation molecules.

⚡ AT-A-GLANCE — Q1 Pharmacovigilance Overview
Definition (WHO 2002): science of detection, assessment, understanding & prevention of ADRs/drug-related problems. Etymology: pharmakon + vigilare; Begaud 1973. History: 1937 sulphanilamide-elixir → 1961 Thalidomide → 1962 Kefauver-Harris → 1968 WHO programme → 1978 UMC Uppsala → 1986 India joins → 2010 PvPI → 2019 NDCT Rules. Aims: detect, assess, understand, prevent, promote rational use, educate. Scope: ADRs, medication errors, interactions, counterfeit, abuse, AEFI, herbal, biologics. Importance: pre-marketing limits + post-marketing reality + economic burden.

Q2Discuss the Thalidomide tragedy and its impact on drug regulation worldwide.⭐⭐⭐

8 marksPCI Syllabus

🪝 Hook: "One sleeping pill, 10,000 deformed babies, and the birth of modern pharmacovigilance."

1. Background

Thalidomide = sedative/hypnotic + anti-emetic developed by Chemie Grünenthal, Germany (1957) under brand Contergan. Marketed as "safer than barbiturates" + "non-toxic in animals". Used widely for pregnancy nausea (morning sickness) without prior teratogenicity testing.

2. The Tragedy (1961)

Dr William McBride (Australia) and Dr Widukind Lenz (Germany) independently reported in The Lancet Dec 1961 that thalidomide caused phocomelia (seal-limb) and other birth defects in babies whose mothers took it during the first trimester (sensitive period: days 20-36 post-conception). ~10,000 affected children in 46 countries; ~5000 survived to adulthood.

3. Lucky USA

Frances Kelsey, FDA reviewer, refused to approve thalidomide in the USA citing inadequate safety data → very few US cases (only "investigational" exposures). Earned Presidential Award (Kennedy 1962).

4. Regulatory Impact

1. Kefauver-Harris Amendment 1962 (USA) — drugs must prove BOTH safety AND efficacy before approval; informed consent mandatory in trials.
2. 1963 — Committee on Safety of Drugs in UK (now Commission on Human Medicines).
3. Yellow Card scheme (UK 1964) — first national spontaneous-reporting system.
4. WHO Pilot International Drug Monitoring Programme 1968 — eventually became WHO-UMC.
5. India's Drug Controller (now CDSCO) strengthened drug-licensing process.
6. Pregnancy-category labelling (FDA categories A/B/C/D/X) introduced.
7. Pre-clinical teratogenicity testing made mandatory.

5. Modern Use

Thalidomide is now used for multiple myeloma, leprosy ENL (erythema nodosum leprosum) with strict STEPS / iPledge risk-management programmes including pregnancy-test mandate, dual contraception, restricted prescribers.

⚡ AT-A-GLANCE — Q2 Thalidomide Tragedy
Thalidomide (Chemie Grünenthal 1957, brand Contergan) — sedative/anti-emetic for morning sickness. 1961: McBride + Lenz reported phocomelia in 10,000 babies (46 countries). USA spared by FDA reviewer Frances Kelsey. Regulatory impact: Kefauver-Harris 1962 (efficacy + safety + IC) · UK Committee on Safety of Drugs 1963 · Yellow Card 1964 · WHO programme 1968 · pregnancy-category labelling · mandatory teratogenicity testing. Modern use: myeloma + ENL leprosy under STEPS / iPledge programmes.

Q3Define ADR. Discuss classification (Rawlins-Thompson Type A-F + WHO type) and severity grading (Hartwig).⭐⭐⭐⭐⭐

10 marksRGUHS 2020AKTU 2021JNTU-K 2022KUHS 2023

🪝 Hook: "A — Augmented (predictable) · B — Bizarre (allergic) · C — Chronic · D — Delayed · E — End-of-use · F — Failure."

1. Definition (WHO 1972)

"Any noxious, unintended & undesired effect of a drug that occurs at doses used in humans for prophylaxis, diagnosis or therapy." Excludes overdose & therapeutic failure.
Edwards-Aronson 2000 revised definition: "An appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration."

2. Classification — Rawlins-Thompson (1977, expanded to A-F)

Type	Mnemonic	Mechanism	Predictable?	Example
A	Augmented	Pharmacological, dose-dependent	Yes	Bleeding with warfarin · hypoglycaemia with insulin · sedation with diazepam
B	Bizarre	Idiosyncratic / allergic; non-dose-related	No	Anaphylaxis with penicillin · SJS with carbamazepine · halothane hepatitis · aplastic anaemia with chloramphenicol
C	Chronic	Long-term use, time-related	Yes	Steroid-induced osteoporosis · neuroleptic tardive dyskinesia · analgesic nephropathy
D	Delayed	Appears years after exposure	Sometimes	Carcinogenicity (alkylating agents) · teratogenicity (thalidomide) · vaginal Ca with DES
E	End-of-use / withdrawal	On stopping the drug	Yes	Opioid withdrawal · clonidine rebound HTN · steroid adrenal insufficiency · benzo seizures
F	Failure	Therapeutic failure	Yes	Inadequate dose · drug-resistance · contraceptive failure · interaction

3. WHO ADR Classification (parallel)

Type 1 (Toxic) · Type 2 (Allergic / Hypersensitivity) · Type 3 (Idiosyncratic) · Type 4 (Drug interactions).

4. Severity Grading — Hartwig & Siegel (1992)

Level	Description
Mild (1)	No antidote / treatment / prolonged hospitalisation
Mild (2)	ADR requires change in treatment, but no extension of hospital stay
Moderate (3)	Requires change in treatment + hospital stay extended ≤ 1 day
Moderate (4)	Stay extended > 1 day OR specialist consultation required
Severe (5)	Requires intensive care
Severe (6)	Permanent disability / harm to patient
Severe (7)	Death directly / contributed by the ADR

5. Seriousness Criteria (ICH-E2A)

SAE = Serious Adverse Event = ADR that:
1. Results in death.
2. Is life-threatening.
3. Requires inpatient hospitalisation or prolongs existing.
4. Causes persistent / significant disability or incapacity.
5. Causes congenital anomaly or birth defect.
6. Important medical event — judged serious by clinician.
+ Unexpected if not consistent with current product information → SUSAR (Suspected Unexpected Serious Adverse Reaction) — must be reported within 15 days (or 7 days for fatal/life-threatening) per ICH-E2A.

⚡ AT-A-GLANCE — Q3 ADR Classification
WHO 1972 ADR def: noxious unintended effect at therapeutic dose (excludes OD & failure). 6 types Rawlins-Thompson: A-Augmented (dose-dependent: warfarin bleeding) · B-Bizarre (allergic/idiosyncratic: penicillin anaphylaxis) · C-Chronic (steroid osteoporosis) · D-Delayed (thalidomide teratogen) · E-End-of-use (opioid withdrawal) · F-Failure. Hartwig severity: 7 levels mild → moderate → severe (death). Seriousness (ICH-E2A): death · life-threatening · hospitalisation · disability · congenital · important medical event. SUSAR = expedited 15-day (7d if fatal).

Q4Discuss Medication Errors and Drug-Related Problems (DRPs) — types, prevention, role in PV.⭐⭐

6 marksPCI Syllabus

🪝 Hook: "To err is human · to systematise is divine — most medication errors are system failures, not individual ones."

1. Definitions

Medication Error (NCCMERP): "any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient or consumer." DRP (Hepler-Strand): any undesirable event experienced by a patient that involves or is suspected to involve drug therapy and that interferes with desired health outcomes.

2. Classification of Medication Errors

Stage	Examples
Prescribing	Wrong drug, dose, route, frequency, duration, drug interaction, patient allergy, illegible writing
Transcribing	Misreading; miscopying onto chart
Dispensing	Wrong drug from look-alike/sound-alike (LASA) — Adderall vs Inderal; mix-up between strengths
Administration	Wrong patient/wrong route/wrong time; missed dose
Monitoring	Failure to monitor INR, drug levels, lab parameters

3. NCCMERP Severity Index (A-I)

A = Capacity to cause error; B = Error did not reach patient; C = Reached but no harm; D = Required monitoring; E = Temporary harm; F = Hospitalisation/prolong; G = Permanent harm; H = Required intervention to sustain life; I = Death.

4. Drug-Related Problems (DRP) — Hepler-Strand 8 categories

1. Untreated indication.
2. Improper drug selection.
3. Sub-therapeutic dose.
4. Failure to receive drug (compliance).
5. Over-dose.
6. ADR.
7. Drug interaction.
8. Drug use without indication.

5. Prevention Strategies

• e-Prescribing with CDSS (Clinical Decision Support System).
• Bar-code medication administration (BCMA).
• "Five Rs" of medication: right patient, drug, dose, route, time.
• Look-Alike Sound-Alike (LASA) tall-man lettering (e.g., DOPamine vs DOBUTamine).
• Medication reconciliation at admission/discharge/transfer.
• Pharmacist-led medication review.
• Read-back / repeat-back for verbal orders.
• Independent double-checks for high-alert drugs (heparin, insulin, opioids, KCl).
• Reporting culture — no-blame "just culture" model.

⚡ AT-A-GLANCE — Q4 Medication Errors & DRPs
Medication error (NCCMERP) = preventable inappropriate medication use. Stages: prescribing · transcribing · dispensing (LASA) · administration · monitoring. NCCMERP severity A-I: A capacity → C reached no harm → E temporary → F hospitalisation → G permanent → I death. DRP (Hepler-Strand 8): untreated indication · improper drug · sub-therapeutic dose · non-compliance · OD · ADR · interaction · use without indication. Prevention: e-prescribing + CDSS, BCMA, 5 Rs, LASA tall-man, medication reconciliation, double-check, no-blame culture.

📘 UNIT II — Pharmacovigilance Methods & Global Systems

Q5Discuss methods of Pharmacovigilance — passive vs active monitoring, with examples.⭐⭐⭐

8 marksAKTU 2021RGUHS 2023

🪝 Hook: "Passive PV waits for reports · Active PV goes hunting for them."

1. Two Broad Approaches

Approach	Description	Pros	Cons
Passive	Wait for spontaneous reports from healthcare workers / patients	Cheap, ongoing, covers all marketed drugs, all populations	Under-reporting (~5% true ADR rate); biased; no denominator
Active	Pre-organised, prospective tracking of pre-defined patients/events	Quantifies incidence, robust signal-detection	Expensive, time-limited, restricted population

2. Passive Methods

Method	Description	Example
Spontaneous Reporting	HCP/patient voluntarily fills ADR form (Yellow card / Suspected ADR / VAERS)	UK Yellow Card, India PvPI, USA FAERS
Stimulated reporting	Active solicitation in defined period (e.g., post-launch newsletter)	Post-launch awareness drives
Case reports / case series	Published in journals (Lancet, NEJM)	Hypothesis generation

3. Active Methods

Method	Description	Example
Cohort Event Monitoring (CEM)	WHO methodology: enroll all patients prescribed a new drug → monitor all events ≥ 6 mo	India CEM for new anti-malarials, anti-TB drugs
Prescription Event Monitoring (PEM)	UK Drug Safety Research Unit (DSRU) — monitors first 10,000 Rxs of new drugs via post-Rx green-form questionnaire to GPs	UK PEM; Australia adopted similar
Targeted spontaneous reporting	Spontaneous reporting in defined patient group (e.g., HIV cohort)	HIV cohort surveillance
Sentinel sites	Selected hospitals/clinics actively detect & report ADRs	FDA Sentinel Initiative (USA); India hospital-based ADR monitoring
Drug-event Monitoring / Registries	Pregnancy registries (e.g., Antiretroviral Pregnancy Registry, MotherToBaby)	Vaccines: V-safe (CDC, smartphone-based)
Database studies (EHR / Claims)	Mining electronic health records / insurance claims for safety signals	FDA Sentinel · Aetion · OHDSI · UK CPRD
Cohort & Case-Control Studies	Pharmacoepidemiology hypothesis-testing	Vioxx / rofecoxib CV-event studies

4. Comparison — Passive vs Active

Passive: cheap, ongoing, broad — but biased & under-reported. Active: precise incidence, but resource-intensive. Modern PV uses BOTH — passive for breadth + active for depth.

⚡ AT-A-GLANCE — Q5 PV Methods
Passive: spontaneous reporting (UK Yellow Card, India PvPI, FAERS, VigiBase), stimulated, case reports — cheap but under-reported (~5%). Active: CEM (WHO methodology, ≥6 mo follow-up), PEM (UK DSRU, first 10k Rxs), targeted spontaneous, Sentinel sites (FDA Sentinel), pregnancy registries (V-safe, MotherToBaby), database studies (EHR, claims, OHDSI, UK CPRD), cohort/case-control. Modern PV combines BOTH.

Q6Discuss Spontaneous Reporting Systems — types of cards, who reports, advantages, limitations.⭐⭐⭐

8 marksPCI Syllabus

🪝 Hook: "Yellow card to e-form — every reported ADR is a brick in the wall of drug safety."

1. Concept

Spontaneous Reporting = voluntary submission of suspected ADRs by HCPs (doctors, pharmacists, nurses, dentists), patients, and consumers. The cornerstone of pharmacovigilance globally.

2. National Spontaneous-Reporting Systems

Country	Programme / Card	Year started
United Kingdom	Yellow Card Scheme (MHRA + CHM)	1964 (oldest national)
India	Suspected ADR Reporting Form / VigiFlow (PvPI)	2010
USA	MedWatch (Form 3500A) → FAERS	1993
EU	EudraVigilance (national systems feed in)	2001
WHO Global	VigiBase (Uppsala UMC)	1968
Australia	Blue Card
Canada	Canada Vigilance Programme
South Africa	SAHPRA Pink Forms

3. Who Can Report

Any HCP — doctor, pharmacist, dentist, nurse, midwife. Patients/caregivers (since 2010 in many countries). Industry (Marketing Authorisation Holders) — mandatory. NGOs & consumer organisations — encouraged.

4. Advantages

• Continuous, ongoing surveillance.
• Covers ALL marketed drugs + all patient populations.
• Cheap to run.
• Detects rare & delayed ADRs.
• Generates signals for further study.

5. Limitations

• Under-reporting — only ~5-10% of true ADRs reported.
• Biased reporting (recent / severe / well-known drugs over-reported).
• No denominator → cannot calculate true incidence.
• Variable data quality (incomplete forms).
• Selection / reporting bias (Weber effect — peak in year 2 after launch then decline).
• Influenced by media (e.g., Vioxx).
• Confounding (multiple drugs).
• Causality inference requires expert evaluation.

⚡ AT-A-GLANCE — Q6 Spontaneous Reporting Systems
Voluntary submission of suspected ADRs by HCPs/patients. National schemes: UK Yellow Card 1964 (oldest) · India PvPI 2010 (Suspected ADR form, VigiFlow) · USA MedWatch (Form 3500A) → FAERS · EU EudraVigilance · WHO VigiBase Uppsala UMC. Reporters: any HCP, patient, MAH (mandatory), NGO. Advantages: continuous, broad, cheap, detects rare ADRs, signal generation. Limitations: under-reporting (5-10%), biased, no denominator, Weber effect, media-driven, confounding, causality requires expert.

Q7Discuss the WHO International Drug Monitoring Programme, UMC Uppsala, and VigiBase.⭐⭐⭐

8 marksRGUHS 2021JNTU-K 2023

🪝 Hook: "From a 10-country pilot in 1968 to 170+ countries today — UMC Uppsala is the world's drug-safety brain."

1. WHO Programme for International Drug Monitoring (PIDM)

Started 1968 as a 10-country pilot at WHO HQ Geneva, after Thalidomide. Initial members: USA, UK, Germany, Netherlands, Sweden, Denmark, Australia, NZ, Canada, Czechoslovakia.
Now: 170+ full member countries + 24 associate. India joined 1986. Ireland, Japan, China later.

2. WHO Collaborating Centre — Uppsala Monitoring Centre (UMC)

Established 1978 in Uppsala, Sweden. Independent, non-profit foundation under Swedish Medical Products Agency. Manages WHO PIDM operationally.

3. UMC Activities

1. VigiBase — world's largest ICSR database (35+ million reports, 170+ countries).
2. WHO Drug Dictionary (WHO-DD) + Anatomical Therapeutic Chemical (ATC) classification.
3. WHO Adverse Reaction Terminology (WHO-ART).
4. VigiFlow — web-based ICSR-management tool used by AMCs in PvPI India + 60+ other countries.
5. VigiLyze — analytics & signal-detection platform.
6. Causality assessment — WHO-UMC scale.
7. Training programmes — Uppsala Reports, Uppsala University Master in PV.
8. WHO-UMC Caring Heart Award for PV champions.

4. VigiBase Specifics

• Database of suspected ADRs reported globally since 1968.
• 35+ million ICSRs (2024).
• Updated with 1.5+ million new ICSRs/year.
• Coded with WHO-DD + WHO-ART (transitioning to MedDRA).
• Searchable by health authorities; restricted access for research.
• Signal-detection tool: BCPNN (Bayesian Confidence Propagation Neural Network) — pioneered by UMC.

5. India's Role in WHO PIDM

India joined 1986 — initial NCC at AIIMS Delhi → CDSCO → finally IPC Ghaziabad (2010 onwards). Today, India contributes ~1 million ICSRs/year to VigiBase — 4th largest contributor after USA, UK, Germany.

⚡ AT-A-GLANCE — Q7 WHO Programme + UMC + VigiBase
WHO PIDM 1968 (post-Thalidomide); started 10-country pilot, now 170+ members. India joined 1986. UMC Uppsala 1978 — independent foundation, manages PIDM operationally. UMC products: VigiBase (35M+ ICSRs from 170+ countries) · WHO-DD + ATC · WHO-ART → MedDRA · VigiFlow (PvPI India + 60+ countries) · VigiLyze analytics · WHO-UMC causality scale · BCPNN signal-detection. India NCC = IPC Ghaziabad (2010-) → ~1M ICSRs/yr → 4th largest VigiBase contributor.

Q8Compare FDA FAERS, EU EudraVigilance, MHRA Yellow Card systems.⭐⭐

6 marksPCI Syllabus

🪝 Hook: "Three regulators · three databases · one mission — global drug safety."

Aspect	FDA FAERS (USA)	EU EudraVigilance	MHRA Yellow Card (UK)
Regulator	FDA	EMA (European Medicines Agency)	MHRA (Medicines + Healthcare products Regulatory Agency)
Form	MedWatch (Form 3500A) for HCPs/Industry; Form 3500B for consumers	E2B(R3) electronic only	Yellow Card (paper, online, app)
Year started	1993 (replaced spontaneous-reporting since 1969)	2001 (mandatory 2017 for all reports)	1964 (oldest national PV scheme)
Database size	22M+ ICSRs (2024)	23M+ ICSRs	~1.5M ICSRs cumulative
Publicly searchable	FAERS dashboard	EudraVigilance ADR website	Yellow Card iDAP, MHRA dashboard
SUSAR reporting	15-day expedited; 7-day fatal/life-threatening	Same (per ICH-E2A)	Same
Patient reporting	Yes (since 2008)	Yes (since 2012)	Yes (since 2005)
Signal detection	Empirica Signal (Oracle), MGPS algorithm	EudraVigilance signal management; PRR, ROR	MHRA signal-detection team

⚡ AT-A-GLANCE — Q8 FAERS / EudraVigilance / Yellow Card
FAERS (USA, 1993): FDA + MedWatch Form 3500A/B; 22M+ ICSRs; MGPS algorithm; patient-reporting since 2008. EudraVigilance (EU, 2001): EMA + E2B(R3) e-only; 23M+ ICSRs; signal-management; patient-reporting since 2012. Yellow Card (UK, 1964 — oldest): MHRA + paper/online/app; 1.5M cumulative; signal-detection team; patient-reporting since 2005. All follow ICH-E2A 15-day SUSAR rule (7-day fatal).

📘 UNIT III — Causality Assessment & Drug Dictionaries

Q9Discuss Causality Assessment tools — WHO-UMC scale, Naranjo algorithm, Hartwig severity, Schumock-Thornton preventability.⭐⭐⭐⭐

10 marksRGUHS 2021AKTU 2022JNTU-K 2023

🪝 Hook: "Did the drug really cause it? — Causality assessment turns clinical suspicion into structured judgment."

1. Need for Causality Assessment

A reported ADR is only a suspected association. Causality assessment uses standardised algorithms to estimate the likelihood that the drug caused the event — distinguishing from coincidence, disease progression, or other drugs.

2. WHO-UMC Causality Scale (Most-Used Globally)

Category	Criteria
Certain	Plausible time relationship · cannot be explained by disease/other drugs · positive de-challenge · positive re-challenge if needed (rare in practice)
Probable / Likely	Reasonable time · unlikely attributable to disease/other drugs · positive de-challenge · re-challenge not required
Possible	Reasonable time · could also be explained by disease/other drugs · de-challenge information lacking
Unlikely	Implausible temporal relationship · disease/drugs provide plausible explanations
Conditional / Unclassified	More data required for assessment
Unassessable / Unclassifiable	Cannot be judged due to insufficient or contradictory information; cannot be supplemented or verified

3. Naranjo Algorithm (Most-Used in Practice)

10-question structured questionnaire, each scored +2 / +1 / 0 / −1. Total score interprets as:

Score	Interpretation
≥ 9	Definite
5-8	Probable
1-4	Possible
≤ 0	Doubtful

Sample questions: previous reports? · onset after drug? · improvement with stopping? · re-appearance with re-exposure? · alternative cause? · placebo response? · drug detected in body fluids? · response dose-related? · previous similar reaction? · objective evidence?

4. Hartwig & Siegel Severity Scale (covered in Q3)

7 levels — Mild (1, 2) · Moderate (3, 4) · Severe (5, 6, 7).

5. Schumock-Thornton Preventability Scale (1992)

Category	Criteria
Definitely preventable	Yes to ≥1 of: (a) inappropriate dose / route / frequency for patient's age, weight, disease state; (b) drug not appropriate for clinical condition; (c) required therapeutic monitoring / blood levels not done; (d) history of allergy / previous reaction known but ignored; (e) drug interaction documented but ignored; (f) toxic serum level documented; (g) poor compliance.
Probably preventable	Yes to ≥1 of related but less explicit criteria.
Not preventable	None of the above.

6. Other Algorithms

• Karch & Lasagna algorithm.
• Kramer algorithm.
• Begaud French method.
• Liverpool ADR Causality Assessment Tool (paediatrics).
• Council for International Organizations of Medical Sciences (CIOMS) RUCAM (for hepatotoxicity).
• Roussel-Uclaf RUCAM for drug-induced liver injury.
• Drug-induced skin reactions — ALDEN.

⚡ AT-A-GLANCE — Q9 Causality Assessment
WHO-UMC scale: Certain · Probable · Possible · Unlikely · Conditional · Unassessable. Naranjo 10-Q score: ≥9 Definite · 5-8 Probable · 1-4 Possible · ≤0 Doubtful. Hartwig severity 7 levels Mild → Severe (death). Schumock-Thornton preventability: Definitely / Probably / Not preventable. Other: Karch-Lasagna, Kramer, Begaud, Liverpool (paeds), CIOMS RUCAM (DILI), ALDEN (skin).

Q10Apply Naranjo Algorithm step-by-step on a sample case (paracetamol-induced rash).⭐⭐

6 marksPCI Syllabus

🪝 Hook: "10 questions, one number — that's the Naranjo verdict."

1. Naranjo's 10 Questions + Scoring

#	Question	Yes	No
1	Are there previous conclusive reports on this reaction?	+1	0
2	Did the adverse event appear after the suspected drug was administered?	+2	−1
3	Did the adverse reaction improve when the drug was discontinued or a specific antagonist was administered?	+1	0
4	Did the adverse reaction reappear when the drug was readministered?	+2	−1
5	Are there alternative causes that could on their own have caused the reaction?	−1	+2
6	Did the reaction reappear when a placebo was given?	−1	+1
7	Was the drug detected in the blood or other fluids in concentrations known to be toxic?	+1	0
8	Was the reaction more severe when the dose was increased, or less severe when the dose was decreased?	+1	0
9	Did the patient have a similar reaction to the same or similar drugs in any previous exposure?	+1	0
10	Was the adverse event confirmed by any objective evidence?	+1	0

2. Sample Case

Case: A 28-yr-old male takes paracetamol 500 mg for fever. Within 2 h develops itchy maculopapular rash on chest. Discontinued; rash resolves in 48 h. Re-challenged inadvertently 3 weeks later — rash recurs. No other concomitant medication; no known food allergy.

Q	Answer	Score
1. Previous reports of paracetamol rash?	Yes (rare but reported)	+1
2. Onset after drug?	Yes (2 h after)	+2
3. Improved on stopping?	Yes (48 h)	+1
4. Reappeared on re-challenge?	Yes	+2
5. Alternative cause?	No (no other drug, no food allergy)	+2
6. Placebo response?	Don't know	0
7. Drug levels toxic?	Don't know	0
8. Dose-related?	Don't know	0
9. Previous similar reaction?	No (first time)	0
10. Objective evidence?	Yes (visible rash, photographed)	+1
TOTAL		+9 — DEFINITE ADR

3. Interpretation

Score 9 (≥ 9) → Definite ADR. Add to patient's allergy alert; warn against future paracetamol use; counsel on alternatives (avoid NSAIDs which may cross-react). Report to AMC under PvPI.

⚡ AT-A-GLANCE — Q10 Naranjo Worked Example
Naranjo = 10 questions × +2/+1/0/-1 scoring → ≥9 Definite · 5-8 Probable · 1-4 Possible · ≤0 Doubtful. Sample case (paracetamol rash with positive de-challenge + re-challenge + no alternatives + visible rash) → score +9 → DEFINITE. Action: allergy alert · counselling · ADR report to AMC.

Q11Discuss WHO Drug Dictionary (WHO-DD) & ATC classification.⭐⭐⭐

6 marksRGUHS 2022

🪝 Hook: "WHO-DD = the world's drug encyclopaedia · ATC = the universal address of every drug."

1. WHO Drug Dictionary (WHO-DD)

Maintained by Uppsala Monitoring Centre (UMC). Standardised drug nomenclature dictionary used to code drug names in ICSRs. Allows analysis across languages, formulations, brand-names. ~150,000+ medicinal products.

2. WHO-DD Enhanced (WHODrug Global)

Latest version provides:
• INN (International Non-proprietary Name) preferred name.
• Trade names worldwide.
• Active ingredients.
• ATC code.
• Form / strength.
• MAH information.
• 200+ countries' drugs covered.

3. ATC Classification (Anatomical Therapeutic Chemical)

Hierarchical 5-level system maintained by WHO Collaborating Centre for Drug Statistics Methodology, Oslo.

Level	Type	Example (Metformin)
1	Anatomical main group (1 letter)	A — Alimentary tract & metabolism
2	Therapeutic subgroup (2 digits)	A10 — Drugs used in diabetes
3	Pharmacological subgroup (1 letter)	A10B — Blood glucose lowering, excluding insulins
4	Chemical subgroup (1 letter)	A10BA — Biguanides
5	Chemical substance (2 digits)	A10BA02 — Metformin

4. Defined Daily Dose (DDD)

"The assumed average maintenance dose per day for a drug used for its main indication in adults." Used for drug-utilisation studies; allows comparison of consumption across countries / time. Example: Metformin DDD = 2 g.

⚡ AT-A-GLANCE — Q11 WHO-DD & ATC
WHO-DD: UMC-maintained drug-nomenclature dictionary; INN + trade names + actives + ATC + form/strength + MAH; 150k+ products in 200+ countries. ATC (WHO-CC Oslo): 5 levels — A (anatomy) → A10 (therapeutic) → A10B (pharmacological) → A10BA (chemical subgroup) → A10BA02 (substance: Metformin). DDD = assumed average daily maintenance dose for drug-utilisation comparison (Metformin DDD = 2 g).

Q12Discuss MedDRA — Medical Dictionary for Regulatory Activities — hierarchy, use in PV.⭐⭐⭐

8 marksJNTU-K 2023

🪝 Hook: "MedDRA = the universal medical thesaurus — turning 'tummy pain' into a globally-coded concept."

1. Background

MedDRA = Medical Dictionary for Regulatory Activities, developed by ICH (1998) — clinically validated international medical terminology used by regulatory authorities, pharmaceutical industry, CROs and academia. Maintained by MSSO (Maintenance and Support Services Organization); updated bi-annually (March + September). Current version: 27.0+ (2024).

2. MedDRA Hierarchy (5 Levels)

Level	Name	Code structure	Example (Headache)
1 (top)	System Organ Class (SOC)	27 SOCs	Nervous system disorders
2	High Level Group Term (HLGT)		Headaches
3	High Level Term (HLT)		Headaches NEC
4	Preferred Term (PT)	Used in coding ICSR	Headache
5 (bottom)	Lowest Level Term (LLT)	Used by reporters; mapped to PT	"Hammering headache" / "tummy pain" / "thunderclap"

3. Standardised MedDRA Queries (SMQs)

Pre-validated grouping of MedDRA terms relating to defined medical conditions or areas of interest. Used for systematic searches of safety databases. Examples: SMQ "Anaphylactic reaction", SMQ "Suicide/self-injury", SMQ "Severe cutaneous adverse reactions (SCAR)", SMQ "Drug-induced liver injury (DILI)".

4. Use in Pharmacovigilance

• Coding of suspected ADRs in ICSRs.
• Aggregate reporting (PSUR/PBRER) — adverse-event tabulations.
• Signal detection — searches by SOC / SMQ.
• Regulatory submission — required by FDA, EMA, PMDA.
• Replaces older WHO-ART (in transition).

5. Indian Adoption

PvPI uses MedDRA for ICSR coding (transitioned from WHO-ART). MedDRA training mandatory for AMC PV staff. Coding done in VigiFlow.

⚡ AT-A-GLANCE — Q12 MedDRA
MedDRA (ICH 1998, MSSO maintained, v27 in 2024) = international clinical terminology for regulatory PV. 5-level hierarchy: SOC (27 top classes) → HLGT → HLT → PT (used in ICSR coding) → LLT (reporter's wording). SMQs = pre-validated queries (Anaphylaxis, SCAR, DILI, Suicide/self-injury). Uses: ICSR coding, PSUR/PBRER, signal detection, regulatory submission. PvPI India uses MedDRA in VigiFlow.

📘 UNIT IV — ICSR · PSUR · RMP · Signal Detection

Q13Discuss the components of Suspected ADR Reporting Form (ICSR) as per CDSCO/PvPI & ICH-E2B(R3).⭐⭐⭐⭐

10 marksJNTU-K 2020RGUHS 2022AKTU 2023

🪝 Hook: "ICSR = the building block of pharmacovigilance — every report begins with these 4 minimum criteria."

1. ICSR — Definition

Individual Case Safety Report (ICSR) = format / content for the report of one or more suspected adverse reactions to a medicinal product that occur in a single patient at a specific point in time. ICH-E2B(R3) defines the electronic transmission standard.

2. Four Minimum Criteria for a Valid ICSR

1. Identifiable patient (initials, age, gender — at least one).
2. Identifiable reporter (name + contact / profession).
3. Suspected drug.
4. Suspected reaction.
Without all four, the report is invalid for global submission.

3. Sections of CDSCO Suspected ADR Reporting Form (PvPI)

Section	Contents
A — Patient information	Patient initials, age (or DOB), weight, sex, ethnicity
B — Suspected adverse reaction	Date of reaction onset; duration; description; treatment given; outcome (recovered, recovered-with-sequelae, fatal, recovering, unknown); seriousness criteria (death/life-threatening/hospitalisation/disability/congenital/important medical event)
C — Suspected medication(s)	Brand + generic name; manufacturer; batch + expiry; dose & route; frequency; therapy date (started/stopped); indication; de-challenge response; re-challenge response (if any)
D — Concomitant medical products + medical history	Other drugs (with dates); relevant past illness; allergies; pregnancy; alcohol; smoking
E — Reporter information	Name, address, profession, signature, date; institution; email; phone

4. ICH-E2B(R3) — Electronic Transmission

Modern ICSRs transmitted via XML format (E2B R3) using ICH M2 messaging standard. Bidirectional acknowledgement via ICH ICH-M2 ACK/NACK messages. Replaces older E2B(R2) which used HL7 v3.

5. Reporting Timelines (ICH-E2A)

Type	Timeline
SUSAR (fatal/life-threatening)	7 calendar days (initial) + 8 days (follow-up)
SUSAR (other serious)	15 calendar days
Non-serious unexpected	Periodic (PSUR / PBRER)
Pregnancy outcome	15 days (if abnormal)

⚡ AT-A-GLANCE — Q13 ICSR / Suspected ADR Form
4 minimum criteria: identifiable patient + reporter + suspected drug + suspected reaction. Sections (PvPI): A patient (initials, age, sex, weight) · B reaction (onset, description, outcome, seriousness) · C suspected drug (brand, batch, dose, route, dates, de/re-challenge) · D concomitant + history · E reporter (name, profession, signature). ICH-E2B(R3) XML transmission via ICH-M2. Timelines: 7-day fatal/life-threatening SUSAR · 15-day other serious · periodic non-serious.

Q14Discuss Periodic Safety Update Report (PSUR / PBRER) as per ICH-E2C(R2).⭐⭐⭐

8 marksJNTU-K 2021AKTU 2022

🪝 Hook: "PSUR = the cumulative safety chronicle of a marketed drug — a periodic risk-benefit health-check."

1. Definition

PSUR / PBRER = Periodic Safety Update Report (older EU term, ICH-E2C R1) / Periodic Benefit-Risk Evaluation Report (newer ICH-E2C R2 term) — comprehensive periodic review of the worldwide safety experience of a medicinal product, including a benefit-risk evaluation. Marketing Authorisation Holder (MAH) must submit to regulators.

2. ICH-E2C(R2) — PBRER Format (16 Sections)

1. Introduction.
2. Worldwide marketing-authorisation status.
3. Actions taken in the reporting interval for safety reasons.
4. Changes to reference safety information (RSI).
5. Estimated exposure & use patterns.
6. Data in summary tabulations (cumulative ICSR counts).
7. Summaries of significant findings from clinical trials.
8. Findings from non-interventional studies.
9. Information from other clinical trials & sources.
10. Non-clinical data.
11. Literature.
12. Other periodic reports.
13. Lack of efficacy in controlled clinical trials.
14. Late-breaking information.
15. Overview of signals (new, ongoing, closed).
16. Signal & risk evaluation + integrated benefit-risk analysis + conclusion.

3. Submission Frequency

Period from approval	Frequency
First 2 years	Every 6 months
Next 2 years	Annually
Thereafter	Every 3 years
Generic drugs	Per Risk Management Plan

4. India PSUR Requirements

Per NDCT Rules 2019, MAH must submit PSUR to CDSCO within 30 days of data lock-point: every 6 months for first 2 years; annually for next 2 years; every 3 years thereafter. Format aligned with ICH-E2C(R2).

5. Related Reports

• DSUR (ICH-E2F) — Development Safety Update Report — for investigational drugs (IND/CTA stage); annual.
• RMP (ICH-E2E) — Risk Management Plan; submitted with new drug application.
• PADER (FDA) — Periodic Adverse Drug Experience Report; quarterly first 3 yrs, annually thereafter.

⚡ AT-A-GLANCE — Q14 PSUR / PBRER
PSUR (E2C R1) → PBRER (E2C R2) — periodic worldwide safety + benefit-risk evaluation by MAH. 16 sections incl. exposure, summary tabulations, CT findings, non-interventional, literature, signal evaluation, integrated B-R analysis. Frequency: 6-monthly Y1-2 → annually Y3-4 → every 3 yrs thereafter. India NDCT Rules 2019: 30-day data-lock submission. Related: DSUR (E2F, investigational annual) · RMP (E2E) · PADER (FDA quarterly Y1-3, annual after).

Q15Discuss Risk Management Plan (RMP) as per ICH-E2E.⭐⭐

6-8 marksJNTU-K 2023

🪝 Hook: "RMP = the proactive safety blueprint — anticipating risks before they cause harm."

1. Definition

Risk Management Plan (RMP) = comprehensive, dynamic document describing the safety profile of a medicinal product, characterising risks and outlining how they will be detected, characterised, minimised, & communicated. Required by EMA for new MA applications since 2005; ICH-E2E framework (2004).

2. Structure (EU GVP Module V)

Part I: Product overview.
Part II: Safety specification — Module SI to SVIII covering epidemiology, non-clinical, exposure, important identified risks, important potential risks, missing information, additional EU requirements.
Part III: Pharmacovigilance Plan — routine + additional PV activities (cohort, registry, PASS).
Part IV: Plans for post-authorisation efficacy studies.
Part V: Risk minimisation measures — routine (labelling) + additional (DHPC letter, education programme, restricted distribution, controlled-access programme, pregnancy prevention programme).
Part VI: Summary of activities for the RMP by product (lay summary).
Part VII: Annexes (templates, indicator tables).

3. Risk-Minimisation Activities

Type	Examples
Routine	SmPC labelling · package insert · pack size
Additional	DHPC (Direct Healthcare Professional Communication) letter · educational materials (e.g., Lariam booklet) · controlled-access (clozapine REMS-CPMS) · pregnancy-prevention programme (isotretinoin iPledge / Roaccutane) · prescriber registration · pharmacy stewardship

4. PASS (Post-Authorisation Safety Study)

Non-interventional study designed to identify, characterise or quantify a safety hazard, confirm safety profile, or measure effectiveness of risk-minimisation measures. Mandated within RMP. Reported via ENCePP (European Network of Centres for Pharmacoepidemiology and Pharmacovigilance).

⚡ AT-A-GLANCE — Q15 Risk Management Plan (RMP)
ICH-E2E framework (2004) + EU GVP Module V. 7 parts: I product · II safety specification (SI-SVIII) · III PV plan (routine + additional + cohort/PASS/registry) · IV efficacy studies · V risk-minimisation (routine SmPC + additional DHPC, education, REMS, pregnancy-prevention) · VI lay summary · VII annexes. Risk minimisation: Routine (labelling) + Additional (DHPC, education, controlled-access, iPledge, prescriber registration). PASS = mandated post-authorisation safety study via ENCePP.

Q16Discuss Signal Detection in pharmacovigilance — definition, methods (PRR, ROR, BCPNN, MGPS).⭐⭐⭐

10 marksJNTU-K 2022AKTU 2023

🪝 Hook: "Signal = a needle in the haystack of a safety database — find it before it becomes a tragedy."

1. Definition (CIOMS VIII)

"Information arising from one or multiple sources, including observations and experiments, which suggests a new potentially causal association, or a new aspect of a known association between an intervention and an event or set of related events, either adverse or beneficial, that is judged to be of sufficient likelihood to justify verificatory action."

2. Signal-Detection Methods

Method	Statistic	Database	Threshold
Proportional Reporting Ratio (PRR)	Frequentist disproportionality	FAERS, EudraVigilance, PvPI	PRR ≥ 2 + χ² ≥ 4 + N ≥ 3
Reporting Odds Ratio (ROR)	Frequentist (logistic)	EudraVigilance	Lower 95% CI > 1
Bayesian Confidence Propagation Neural Network (BCPNN)	Bayesian (information component IC)	WHO VigiBase (UMC)	IC025 (lower 95%) > 0
Multi-item Gamma Poisson Shrinker (MGPS)	Empirical Bayes (EB05/EBGM)	FAERS, Empirica Signal	EB05 ≥ 2

3. Disproportionality Calculation (2x2 Table)

	Event of interest	Other events
Drug of interest	a	b
Other drugs	c	d

PRR = (a / (a+b)) / (c / (c+d)); ROR = (a × d) / (b × c)

4. Signal Workflow

🔄 Signal Detection & Management Cycle

① Generate
(database disproportionality)

② Filter
(remove duplicates, noise)

③ Validate
(clinical review)

④ Confirm
(literature, additional cases)

⑤ Assess
(causality, frequency, mechanism)

⑥ Decide
(regulatory action)

⑦ Communicate
(label change, DHPC)

5. Famous Signals Detected

• Rofecoxib (Vioxx) → cardiovascular events (signal 2001 → withdrawal 2004).
• Cerivastatin (Baycol) → rhabdomyolysis (withdrawn 2001).
• Rosiglitazone (Avandia) → MI (restricted 2010).
• Bromfenac → hepatotoxicity (withdrawn 1998).
• Phenformin → lactic acidosis (banned 1976 in USA, India 2003).
• Sibutramine → CV events (withdrawn 2010).

⚡ AT-A-GLANCE — Q16 Signal Detection
CIOMS VIII signal def: causal hint requiring verification. Methods: PRR (frequentist, FAERS/PvPI; ≥2 + χ² ≥4 + N ≥3) · ROR (frequentist, EudraVigilance; LCI > 1) · BCPNN (Bayesian, WHO VigiBase; IC025 > 0) · MGPS (empirical Bayes, FAERS Empirica Signal; EB05 ≥ 2). 2×2 disproportionality: PRR = (a/a+b) / (c/c+d). Workflow: generate → filter → validate → confirm → assess → decide → communicate. Famous signals: rofecoxib (CV), cerivastatin (rhabdomyolysis), rosiglitazone, sibutramine.

Q17Discuss SUSAR, expedited reporting rules + 15-day vs 7-day timelines.⭐⭐

6 marksPCI Syllabus

🪝 Hook: "SUSAR = Suspected Unexpected Serious Adverse Reaction = highest-priority report on the regulator's desk."

1. Definitions

SAR (Suspected Adverse Reaction): any noxious response to a medicinal product for which a causal relationship between the product and event is at least a reasonable possibility.
SUSAR (Suspected Unexpected SAR): SAR that is BOTH unexpected (not consistent with current product information) AND serious.
SAE (Serious Adverse Event): any AE that meets ICH-E2A seriousness criteria (death, life-threatening, hospitalisation, disability, congenital anomaly, important medical event).
"Expedited" reporting = fast-track regulatory submission outside the routine PSUR cycle.

2. Expedited Reporting Timelines (ICH-E2A)

Type	Timeline (initial)	Follow-up
SUSAR — fatal or life-threatening	7 calendar days	+8 days for complete report
SUSAR — other serious unexpected	15 calendar days	Periodic update
Serious expected ADR	Per PSUR / PBRER	Aggregate
Non-serious unexpected	Per PSUR / PBRER	Aggregate

3. India NDCT Rules 2019 Specifics

CDSCO requires SAE reporting from clinical trials within 24 h by oral / written communication, followed by detailed report within 14 days. Compensation for clinical-trial injury / death determined by Sponsor + Investigator + IEC + DCGI committee.

4. Reporting Routes

• Sponsor / MAH → CDSCO + IEC + Investigator (in clinical trials).
• MAH → IPC PvPI (post-marketing).
• Hospital / Pharmacist / Patient → AMC → IPC PvPI.
• MAH → FDA FAERS (USA), EMA EudraVigilance (EU).
• MAH → WHO-UMC VigiBase (cross-listed).

⚡ AT-A-GLANCE — Q17 SUSAR & Expedited Reporting
SAR = suspected adverse reaction (causal possibility); SUSAR = SAR + Unexpected + Serious. Timelines (ICH-E2A): SUSAR fatal/life-threatening → 7 days initial + 8 days follow-up; other serious SUSAR → 15 days; serious-expected → PSUR; non-serious → PSUR. India NDCT Rules 2019: CT SAE within 24h oral + 14 days written. Routes: MAH → CDSCO + IPC PvPI · FDA FAERS · EMA EudraVigilance · WHO-UMC VigiBase.

📘 UNIT V — Indian PV System + AEFI + Pharmacist's Role

Q18Discuss the Pharmacovigilance Programme of India (PvPI) — structure, AMC network, achievements.⭐⭐⭐⭐

10 marksRGUHS 2020AKTU 2022JNTU-K 2022

🪝 Hook: "PvPI = India's national PV programme — from 0 ADRs in 2010 to 1+ million ICSRs/year in 2024."

1. Background

PvPI launched 14 July 2010 by CDSCO with initial 22 AMCs at Indian medical colleges. Coordinated by Indian Pharmacopoeia Commission (IPC), Ghaziabad as the National Coordination Centre (NCC) since 2011. Funded under National Health Mission (NHM).

2. Vision & Mission

Vision: safeguard the health of the Indian population by ensuring that the benefits of medicine use outweigh the risks.
Mission: generate evidence-based ADR reports to support regulatory decision-making by CDSCO.

3. PvPI Structure

🔄 PvPI Reporting Hierarchy

① Healthcare
professional /
patient

② Suspected ADR
Form / Mobile App
(ADR PvPI)

③ AMC
(ADR Monitoring
Centre)

④ NCC IPC
Ghaziabad

⑤ Steering Committee
+ CDSCO

⑥ WHO-UMC
VigiBase, Uppsala

4. AMC Network

As of 2024, ~330+ AMCs across India, plus 90+ associate AMCs. AMCs located in:
• Government & private medical colleges.
• Tertiary teaching hospitals.
• Specialty hospitals (oncology, cardiology, paediatrics, mental health).
• ESIC hospitals, Railway hospitals.
• AYUSH institutions (started 2017).

5. Software & Reporting Tools

• VigiFlow — web-based ICSR-management tool (UMC) used by AMCs.
• "ADR PvPI" mobile app — Android/iOS for HCP & consumer reporting (Hindi + English).
• Helpline 1800-180-3024 — toll-free PvPI ADR reporting.
• Email: pvpi.compat@gmail.com
• SAFE-VAC portal — Surveillance and Action for Events Following Vaccination.
• Materiovigilance Programme of India (MvPI, 2015) for medical-device adverse events.
• Hemovigilance Programme (HvPI) — blood/blood-product safety.

6. Achievements

• ICSR contribution: India ranked among top 5 global contributors to VigiBase (~1 million ICSRs/year).
• > 200 PvPI-driven label changes for marketed drugs.
• Established AMC capacity in 18 NIPER-affiliated colleges.
• Published ADR Quarterly newsletter "Medicines Safety Newsletter".
• PvPI Caring Pharmacist of the Year Award (2022).
• Launched National Centre for Coordination — Pharmacovigilance Programme of India for AYUSH (NCC-PvPI-AYUSH) at All India Institute of Ayurveda, Delhi (2018).

⚡ AT-A-GLANCE — Q18 PvPI
Launched 14 Jul 2010; coordinated by IPC Ghaziabad NCC; funded under NHM. Hierarchy: HCP/patient → ADR Form / app → AMC (~330+) → NCC IPC → Steering Committee + CDSCO → WHO-UMC VigiBase. Tools: VigiFlow, ADR PvPI mobile app, helpline 1800-180-3024, SAFE-VAC, MvPI (devices), HvPI (blood). Achievements: top-5 global VigiBase contributor (~1M ICSRs/yr), 200+ label changes, PvPI-AYUSH 2018.

Q19Discuss AEFI (Adverse Event Following Immunisation) — definition, classification, surveillance.⭐⭐

8 marksAKTU 2023

🪝 Hook: "AEFI = any untoward event after a shot — may or may not be caused by the vaccine, but every report counts."

1. Definition (WHO)

"Any untoward medical occurrence which follows immunisation and which does not necessarily have a causal relationship with the usage of the vaccine." Includes any unfavourable or unintended sign, abnormal lab finding, symptom or disease.

2. Classification of AEFI (WHO 2018)

Type	Description	Example
Vaccine product-related	Caused/precipitated by inherent properties of the vaccine	Vaccine-associated paralytic polio (VAPP) with OPV
Vaccine quality defect-related	Caused by defective vaccine (manufacturing)	Cold chain failure → loss of potency
Immunisation error-related	Caused by inappropriate vaccine handling, prescribing or administration	BCG abscess from over-dilution; reuse of needle → infection
Immunisation anxiety-related	Anxiety/stress reaction unrelated to vaccine itself	Vasovagal syncope; mass psychogenic illness
Coincidental	Unrelated to vaccine but happens around time of immunisation	SIDS occurring shortly after vaccination

3. Severity

Mild: local pain, low-grade fever, swelling. Moderate: high fever, persistent crying. Severe (SAE): anaphylaxis, Guillain-Barré syndrome, intussusception (rotavirus), thrombosis with thrombocytopenia syndrome (TTS, post-AstraZeneca/Janssen COVID), myocarditis (mRNA COVID), febrile seizures. Death.

4. Indian AEFI Surveillance — Structure

🔄 AEFI Reporting Hierarchy in India

① Vaccinator
(ANM/health-worker)

② Block /
District Health Officer

③ State AEFI
Committee

④ National AEFI
Committee

⑤ MoHFW / SAFE-VAC

⑥ WHO-UMC
VigiBase

5. SAFE-VAC Portal (India)

Surveillance and Action for Events following Vaccination — online portal for capturing AEFIs from UIP & COVID vaccination drives. Mandatory for serious AEFIs to be reported within 24 h.

6. CIOMS / Brighton Collaboration Standardised Case Definitions

Brighton Collaboration provides standardised case definitions for vaccine-related events (anaphylaxis, GBS, intussusception, TTS, myocarditis, etc.) to enable global comparability.

⚡ AT-A-GLANCE — Q19 AEFI
WHO def: untoward event after immunisation, not necessarily causal. 5 types: vaccine product-related (VAPP) · quality defect (cold-chain failure) · immunisation error (BCG abscess) · anxiety-related (vasovagal) · coincidental. Severe AEFI: anaphylaxis, GBS, TTS (AZ/J&J COVID), myocarditis (mRNA COVID), febrile seizures. India AEFI hierarchy: vaccinator → district AEFI officer → state AEFI committee → national AEFI committee → SAFE-VAC → WHO-UMC. Brighton Collaboration case definitions.

Q20Discuss the Pharmacist's Role in Pharmacovigilance — community, hospital, and industry settings.⭐⭐

6-8 marksRGUHS 2023

🪝 Hook: "Pharmacist = the most accessible PV reporter — serving both patients and the regulator."

1. Why Pharmacists Are Critical for PV

Pharmacists are present at every step of the medication-use cycle — procurement, dispensing, counselling, monitoring. India has 7+ lakh registered pharmacists; community pharmacists alone interact with 90% of the population. Yet only 6% of ADR reports in India come from pharmacists (vs ~20% globally) — significant capacity-building potential.

2. Roles in Different Settings

Setting	PV Activities
Community Pharmacy	Identify ADRs from walk-in customers · counsel on suspected ADR · refer serious cases to physician · fill suspected ADR form & submit to AMC · Schedule H1 / Schedule X register · counsel on warning signs
Hospital Pharmacy	ADR detection in IP/OP wards · participate in P&TC ADR reviews · operate AMC if institution is one · educate doctors & nurses · TDM advisory · medication-error reporting · pharmacovigilance audit
Clinical Pharmacy / ICU	Real-time ADR detection during medication-chart review & ward rounds · suggest dose adjustment in renal/hepatic impairment · TDM (vancomycin, digoxin, phenytoin) · contribute to mortality & morbidity reviews
Industry / MAH	Manage corporate PV system per ICH-E2A/E2B/E2C/E2D/E2E · author PSUR/PBRER · prepare RMP · ICSR processing in Argus/ARISg · MedDRA coding · signal-detection · regulatory inspection readiness
CRO / Outsourced PV	End-to-end PV service for multiple clients; case processing, narrative writing, expedited reporting, signal-detection
Academic / Research	Pharmacoepidemiology research · publish case reports · teach BP805ET · NIPER faculty · WHO-UMC fellowship
Regulatory / Government	CDSCO PV review · IPC PvPI staff · drug-safety panel member

3. WHO 7-Star Pharmacist + 8th (Researcher) — applied to PV

Caregiver (counsel) · Decision-maker (judge causality) · Communicator (educate) · Manager (PV system) · Lifelong Learner · Teacher (CME) · Leader · Researcher (publish, signal).

4. Capacity-Building Initiatives in India

• PvPI Caring Pharmacist of the Year Award.
• PvPI training programmes — National Pharmacovigilance Week (17-23 September annually).
• Diploma / Certificate in Pharmacovigilance from JLI Education, IGMPI, ASCI, JSS, NIPER, Henry Harvin (3-12 months).
• Online MOOCs — Coursera, FutureLearn.
• Master's in Pharmacovigilance from ICRI Delhi, Manipal etc.

⚡ AT-A-GLANCE — Q20 Pharmacist's Role in PV
Pharmacists at every medication-use step; only 6% PvPI reports from them (vs ~20% global) — big growth opportunity. Settings: Community (counsel + report) · Hospital (P&TC + AMC) · Clinical/ICU (real-time + TDM) · Industry/MAH (PSUR/RMP/Argus) · CRO (outsourced PV) · Academic · Regulatory (CDSCO/IPC). WHO 7-star + 8th (researcher) applied to PV. India training: PvPI awards · Pharmacovigilance Week (17-23 Sep) · Diplomas (JLI, IGMPI, NIPER) · MSc PV.

Q21Discuss Pharmacovigilance for Herbal Medicines, Biologics & Vaccines — special considerations.⭐⭐ (📘 Syllabus-completeness)

6-8 marksPCI Syllabus

🪝 Hook: "Beyond small molecules — biologics, herbals, vaccines need their own PV playbook."

1. Herbal & AYUSH Medicines

Challenges: ~60% of Indian population uses herbal / AYUSH; under-reporting of herbal ADRs; standardisation issues; herb-drug interactions (e.g., St John's wort + warfarin / digoxin / OCPs); contamination with heavy metals or steroids; concomitant use with conventional drugs.
India: NCC-PvPI-AYUSH at All India Institute of Ayurveda, Delhi (since 2018) — 35+ Peripheral Pharmacovigilance Centres; ADR form for AYUSH preparations; specific MedDRA AYUSH terminology in development.
WHO: WHO Traditional Medicine Strategy 2014-23 (extended to 2025); guideline on monitoring herbal-medicine safety.

2. Biologics & Biosimilars

Special concerns: Immunogenicity (anti-drug antibodies), batch-to-batch variability, cold-chain requirements, infusion reactions (rituximab, tocilizumab), sequence-specific traceability (lot/batch + brand) — critical because biosimilars have similar but not identical structures (e.g., adalimumab biosimilar Exemptia from Zydus).
EU EMA: mandates "automatic substitution" prohibited; brand + batch must be recorded in ICSR.
India: CDSCO Biosimilars Guidelines 2016 — PV plan mandatory; brand-name traceability.
WHO: WHO Similar Biotherapeutic Products (SBP) guidelines.

3. Vaccines (Vaccinovigilance — beyond AEFI)

• Larger denominators (population-level rollout) → small AE rates affect millions.
• Real-time surveillance (V-safe in USA, Yellow Card-Vaccines in UK).
• Brighton Collaboration case definitions for standardisation.
• Global Advisory Committee on Vaccine Safety (GACVS) at WHO.
• COVID-19 lessons: TTS with AstraZeneca/J&J, myocarditis with mRNA — detected via national VAERS/EMA EudraVigilance/CoWIN AEFI integration in days, not years.

⚡ AT-A-GLANCE — Q21 PV for Herbals / Biologics / Vaccines
Herbals/AYUSH: 60% Indians use; herb-drug interactions; contamination; NCC-PvPI-AYUSH 2018 at AIIA Delhi (35+ centres); WHO Traditional Medicine Strategy 2014-25. Biologics/biosimilars: immunogenicity, cold-chain, batch traceability mandatory; CDSCO Biosimilars Guidelines 2016; EMA prohibits auto-substitution. Vaccinovigilance: V-safe (USA), Brighton case definitions, GACVS-WHO; COVID lessons (TTS, myocarditis) detected rapidly via VAERS/EudraVigilance/CoWIN.

Q22Discuss NDCT Rules 2019 — Indian Pharmacovigilance Regulatory Framework.⭐⭐ (📘 Syllabus-completeness)

6 marksPCI Syllabus

🪝 Hook: "NDCT Rules 2019 = India's modern, ICH-aligned framework for clinical trials and pharmacovigilance."

1. Background

New Drugs and Clinical Trials Rules 2019 — published 19 March 2019 by MoHFW, replacing scattered provisions of D&C Act 1940 (Schedule Y). Aligns India with ICH-GCP, GVP, harmonises with global standards.

2. Key PV-Related Provisions

• Mandatory PSUR submission (within 30 days of data lock-point) for new drugs — every 6 months for first 2 years, annually for next 2 years, every 3 years thereafter (aligned with ICH-E2C(R2)).
• SAE reporting from clinical trials within 24 hours (oral) + 14 days written report.
• Compensation for clinical-trial injury / death determined by Sponsor + Investigator + IEC + DCGI committee.
• Sponsor's PV plan / Risk Management Plan required for new drug applications.
• Mandatory registration of all clinical trials in CTRI (Clinical Trials Registry-India) before recruitment.
• Approval timelines: 30 days for academic clinical trial; 90 days for industry-sponsored.
• Compensation for trial-related injury — within 30 days of SAE assessment.
• Conditional approval pathway (orphan drugs, rare diseases) — single Phase III trial possible.

3. Regulatory Authorities Involved

• DCGI (Drugs Controller General of India) — apex authority.
• CDSCO — secretariat.
• Subject Expert Committees (SEC) — therapeutic-area expert review.
• Apex Committee — policy decisions on new drugs.
• Technical Committee — appeals.
• Drugs Technical Advisory Board (DTAB) — under D&C Act, advises Centre.
• State Licensing Authority — state-level enforcement.

4. Other Indian PV-Related Acts & Rules

• Drugs & Cosmetics Act 1940 + Rules 1945 — Schedule Y (clinical trials), Schedule M (cGMP), Schedule H1 (antibiotics register), Schedule X (narcotic).
• Pharmacy Act 1948 — pharmacist registration via PCI.
• Drugs Price Control Order (DPCO 2013).
• Drugs & Magic Remedies (Objectionable Advertisements) Act 1954.
• Consumer Protection Act 2019 — patient redressal.

⚡ AT-A-GLANCE — Q22 NDCT Rules 2019
New Drugs & Clinical Trials Rules 2019 (19 Mar 2019) replaces Sch Y; aligns India with ICH-GCP/GVP. Key PV provisions: mandatory PSUR (30 days post data-lock; 6mo Y1-2 / annually Y3-4 / 3-yrly after) · CT SAE within 24h oral + 14d written · compensation for CT injury (30 days post-assessment) · RMP mandatory · CTRI registration mandatory · approval 30 days academic / 90 days industry · conditional approval for orphan/rare. Authorities: DCGI · CDSCO · SEC · Apex Committee · Technical Committee · DTAB · State Licensing. Related acts: D&C 1940 + Sch Y/M/H1/X · Pharmacy Act 1948 · DPCO 2013 · D&MR 1954 · CPA 2019.

📷 DIAGRAMS TO DRAW / INSERT — BP805ET

5 key diagrams essential for BP805ET exam answers — well-labelled diagrams fetch 30-50% of marks.

DIAG 1ADR Classification (Rawlins-Thompson A-F)

Mind-map of 6 types: A-Augmented (dose-dep), B-Bizarre (allergic), C-Chronic, D-Delayed, E-End-of-use, F-Failure. With examples for each.

ADR

DIAG 2PvPI Reporting Hierarchy

HCP/patient → Suspected ADR Form/app → AMC (330+) → NCC IPC Ghaziabad → Steering Committee + CDSCO → WHO-UMC VigiBase.

PV programme

DIAG 3MedDRA Hierarchy (5 Levels)

Pyramid: SOC (27 top) → HLGT → HLT → PT (used in ICSR) → LLT (reporter wording). Example: Headache from each level.

MedDRA

DIAG 4Signal Detection Workflow

Generate (database disproportionality) → Filter → Validate (clinical review) → Confirm (literature) → Assess (causality) → Decide (regulatory action) → Communicate.

Signal management

DIAG 5ICSR Form (CDSCO/PvPI Sections)

Suspected ADR Form: Section A (Patient) + B (ADR) + C (Suspected drug) + D (Concomitant) + E (Reporter). Mark fields.

ICSR

KMR ADVICE

EXAM STRATEGY & IMPORTANT QUESTIONS GUIDE

8.3 BP805ET · PHARMACOVIGILANCE (THEORY · ELECTIVE)

📖 HOW TO USE THIS GUIDE

📋 PCI B.Pharm Semester VIII · BP805ET Pharmacovigilance — Syllabus Coverage Checklist

📊 Past-Paper Frequency Analysis (2019-2023) — Verified Citations Only

🎯 Priority Reading Guide

🔴 HIGH PRIORITY — 5★ & 4★ (~70% of marks)

🟡 MEDIUM PRIORITY — 3★ (~22% of marks)

🔵 LOW / SYLLABUS-COMPLETENESS — 1-2★ (~8% of marks)

📘 UNIT I — Introduction to Pharmacovigilance

📘 UNIT II — Pharmacovigilance Methods & Global Systems

📘 UNIT III — Causality Assessment & Drug Dictionaries

📘 UNIT IV — ICSR · PSUR · RMP · Signal Detection

📘 UNIT V — Indian PV System + AEFI + Pharmacist's Role

📷 DIAGRAMS TO DRAW / INSERT — BP805ET

📚 BP805ET EXAM STRATEGY

🎯 CAREER GUIDANCE — Where Does BP805ET Take You?

🇮🇳 1. Drug Safety Associate / PV Officer (Entry-Level)

Role + Responsibilities

🇮🇳 2. Pharmacovigilance Scientist / Safety Physician Lead

Role + Responsibilities

🇮🇳 3. Aggregate Report Writer / PSUR Author

Role + Responsibilities

🇮🇳 4. Signal Detection & Risk Management Specialist

Role + Responsibilities

🇮🇳 5. EU-Qualified Person for Pharmacovigilance (EU-QPPV)

Role + Responsibilities

🇮🇳 6. Pharmacovigilance Auditor / Inspector Readiness

Role + Responsibilities

🇮🇳 7. PV Project Manager / Operations Lead

Role + Responsibilities

🇮🇳 8. Pharmacovigilance in CDSCO / IPC PvPI / NACO (Government)

Role + Responsibilities

🇮🇳 9. Pharmacovigilance Trainer / Educator

Role + Responsibilities

🇮🇳 10. Real-World Evidence (RWE) & Pharmacoepidemiology Analyst

Role + Responsibilities

🇮🇳 11. Industry — Brand-Level PV / Local Safety Officer (LSO)

Role + Responsibilities

🇮🇳 12. Academic Researcher / Faculty — Pharmacovigilance

Role + Responsibilities

🌍 INTERNATIONAL CAREER MARKETS — Pharmacovigilance

📜 STRATEGIC CERTIFICATIONS & SKILLS — 5-Year Action Plan

Year 1 (Final-year B.Pharm + first job)

Year 2-3 (Junior roles → consolidation)

Year 4-5 (Mid-career specialisation)

Software / Tools to Master

Languages & Communication

🧠 Knowledge & Interest Self-Checker — Pharmacovigilance Career

👨‍🏫 Author

🏛️ Institution

📧 Contact