PHARMAQUEST DAY 3

1. Pharmacovigilance
Dr. Rovin C. Vincent

2. Overview
Introduction
ICSRs
Signal Management
Risk Minimisation Measures

3. Pharmaco
vigilance
Health care
Providers
Patients &
Care Givers
Academics
Regulatory
Authority
Biopharmac
eutical
Industry

4. Goal
Benefit for Patient
Risk for Patient

5. Classification
Beyond
ICSRs
ICSRs

6. Individual Case Safety Report(ICSR)
Format and Content for Submission of Individual reports of Suspected Adverse reactions
In relation to a medicinal Product
That occur in a single patient
At a specific point of time

7. Validity of ICSRs
1. Reporter
2. Patient
3. Suspected Adverse Reaction
4. Suspected Medicinal Product

8. Few Concepts in ICSRs
Adverse Event selection
Seriousness & Seriousness Criteria
Dechallenge & Rechallenge
Expectedness/Labeling
Causality

9. Adverse
Event
Selection

10. Case 1
A 45 year old female patient was on drug A from 2014 for Multiple Sclerosis. In 2020 he developed
Fever and Diarrhea. He was diagnosed with Bacterial Gastroenteritis and treated with antibiotics. The
patient recovered.

11. Answer
Verbatim/ Reported Reaction Term: Bacterial Gastroenteritis
(Symptoms Fever and Diarrhea subsumed under Diagnosis Bacterial Gastroenteritis)

12. MedDRA
Medical Dictionary for Regulatory Activities
Updated twice a year
Maintained by Maintenance and Support Services Organization (MSSO)

13. SOC: System Organ
Class
27
HLGT: High level group term
337
HLT: High level term 1737
PT: Preferred term 24289
LLT: Lowest level term 81812

14. 27 SOC
• Blood and lymphatic system disorders;
• Cardiac disorders;
• Congenital, familial and genetic disorders;
• Ear and labyrinth disorders;
• Endocrine disorders;
• Eye disorders;
• Gastrointestinal disorders;
• General disorders and administration site conditions;
• Hepatobiliary disorders;
• Immune system disorders;
• Infections and infestations;
• Injury, poisoning and procedural complications;
• Investigations;
• Metabolism and nutrition disorders;
• Musculoskeletal and connective tissue disorders;
• Neoplasms benign, malignant and unspecified (including cysts and polyps);
• Nervous system disorders;
• Pregnancy, puerperium, and perinatal conditions;
• Psychiatric disorders;
• Renal and urinary disorders;
• Reproductive system and breast disorders;
• Respiratory, thoracic and mediastinal disorders;
• Skin and subcutaneous tissue disorders;
• Social circumstances;
• Surgical and medical procedures;
• Vascular disorders;
• Product issues

15. SOC:
Infections and
infestations
HLGT: Infections -
pathogen
unspecified
HLT: Abdominal and
gastrointestinal infections
PT: Gastroenteritis
LLT: Gastroenteritis

16. SOC:
Gastrointestinal
disorders
HLGT:
Gastrointestinal
infections
HLT: Gastric and gastroenteric
infections
PT: Gastroenteritis
LLT: Gastroenteritis

17. Case 2
A 22 year old female patient with history of Ankylosing Spondylitis was started on Drug B
Infusion for Ankylosing Spondylitis. 20 min after starting the Infusion the patient had
Anaphylactic Reaction. The Infusion was stopped.
What is/are the event/s

18. Answer
Anaphylactic Reaction
Infusion Related Reaction

19. Case 3
A 30 year old male patient has a medical history of Psoriatic Arthritis and Uveitis. He was started
on Drug C for Psoriatic Arthritis. His joint pain has improved. He also noticed an improvement in
his uveitis.
Is there a need for a case
If Yes; What is/are the event/s

20. Answer
A case has to be created
Event: Unexpected Therapeutic Benefit

21. Seriousness
(and Seriousness Criteria)

22. Seriousness & Reporting Timelines
Assess Case and Events Serious or Non Serious
◦ Serious cases Reported within 15 Days
◦ Nonserious cases Reported within 30 Days
Assess Seriousness Criteria

23. Seriousness
Any untoward medical occurrence
◦results in death,
◦is life-threatening,
◦requires hospitalization
◦results in persistent or significant disability
◦or is a congenital anomaly/birth defect.
◦Cases can be made serious made on medical judgement.

24. Dechallenge
&
Rechallenge

25. Dechallenge
A 22 year old female patient had severe rashes after
starting with Drug D initiated for Pneumonia. The drug
was stopped, antihistamines were prescribed and the
patient recovered.
What is the Dechallenge
Options
1. Positive
2. Negative
3. Unknown
4. Not Applicable

26. Answer
Dechallenge: Not Applicable
Treatment was given: Dechallenge cannot be assessed: Not Applicable

27. Rechallenge
A 22 year old female patient had dyspnea about 30 min after
starting infusion with Drug E initiated for Multiple Myeloma.
Infusion was stopped for 15 min and the patient recovered.
30 min later the infusion was restarted. The infusion was
completed without further issues and patient went home
after being in observation for some time.
What is the Rechallenge
Options
1. Positive
2. Negative
3. Unknown
4. Not
Applicable

28. Answer
Rechallenge: Negative
Patient did not have dyspnoea after restarting the drug

29. Expectedness
/Labelling

30. Expectedness
Whether the event is known to occur with the drug or not
Assessed by using Reference Safety Information
◦ SMPC
◦ CCDS
◦ USPI
◦ IB

31. Causality

32. Causality
A 22 year old female patient had nausea and vomiting about 30
min after starting infusion with Drug E initiated for Rheumatoid
arthritis. Infusion was stopped and the patient recovered.
Infusion was restarted after 15 min. The patient completed the
infusion without any further issues and was discharged.
What is the Causality
Options
1. Related
2. Not Related
3. Not Assessable

33. TRENDS criteria
Temporal Association
Rechallenge
Exclusion
Novelty
Dechallenge
Scientific Plausibility

34. TRENDS criteria
Temporal Association: Compatible: 30 min
Rechallenge: No
Exclusion: Unknown
Novelty: ?
Dechallenge: Yes
Scientific Plausibility: Yes

35. Answer
Causality: Related
Based on the temporal association, positive dechallenge and scientific plausibility of the drug to
cause the events, causality is considered related.

36. Few Concepts
in Signal
Management

37. Safety
Observation
Signal Safety Issue

38. Safety Observation
Information that is different from Expectation
◦ Quantitatively
◦ Qualitatively
Has the Potential to affect the safety Profile

39. Safety Observation
Quantitatively Safety Observations
◦ Signals of Disproportionate Reporting
Qualitative Safety Observations
◦ ICSR: DME, SUSARs, Watchlist events
◦ Patterns in Special Population, Off label use,
◦ RMP Topics

40. DME
Designated Medical Events.
Events with high attributable risk.

42. SUSARs
Serious [Seriousness]
Unexpected [Expectedness/Labeling]
Suspected [Causality]
Adverse
Reaction

43. Signal
A new potentially causal Association Or
A new aspect of a known Association
Between an Intervention & Event/Set of related Events
Either Adverse/Beneficial
That justify a Verificatory Action

44. Signals
Signals Include
◦ ICSRs: Safety Observations that meet SNIP criteria
◦ Any SDR (Medical Judgement)
◦ Aggregate Reports

45. SNIP Criteria
Strength of the Association
Newness of the event
Clinical Importance
Potential for Preventive Action

46. Safety Issue
A confirmed Signal is a Safety Issue
It may require a mitigatory Action

47. Risk
Minimisation
Measures

48. Risk Minimisation Measures
Communication
◦ Inform HCPs
◦ Inform Patients
Amendments to Product Information (SmPC, CCDS, IB, Package Leaflets)
Can add
◦ Side Effects
◦ Precautions
◦ Contraindications

49. Risk Minimisation Measures
Performing a test before the start of treatment
Monitoring of laboratory parameters during treatment
Monitoring for specific signs and symptoms
Adjusting the dose or stopping the treatment when adverse events are observed
Providing contraception recommendations
Prohibiting the use of other medicines while taking the product

50. Risk Minimisation Measures
Restriction of a Drug
◦ Drugs to be given only in Hospital Environment
◦ Prescription only Drugs
◦ Special Medical Prescription
Withdrawal

52. References and Further Reading
Good Pharmacovigilance Practices by European Medicines Agency [GVP Modules 1 to 10, 15 &
16]
https://www.ema.europa.eu/en/human-regulatory/post-authorisation/pharmacovigilance/good-
pharmacovigilance-practices
Uppsala Monitoring Centre Training Materials
https://www.who-umc.org/education-training/online-courses/
MedDRA
https://www.meddra.org/