pharmacovigilance in INDIA,US,EUROPEAN UNION

1. Department of Pharmaceutical Sciences,
Maharshi Dayanand University
Presented By…
Garima Saini
M.Pharm. D.R.A (SEM-II)
Guided By…
Ms. Poonam Yadav

2. PHARMACOVIGILANCE,
ADDITIONAL REQUIREMENTS
In INDIA,US and EUROPEAN UNION

3. 3
Pharmacovigilance Division (Human vaccine) is a part of Biological Division and
monitors all post licensure activities of vaccine related AEFI, PSUR and any other data
on adverse reactions.
PHARMACOVIGILANCE
INDIA

4. Pharmacovigilance Methods
Depend on the product, the indication, the population being treated and the issue to be addressed.
The method chosen can also depend on whether an identified risk, potential risk or missing
information is the issue and whether signal detection, evaluation or safety demonstration is the
main objective of further study.
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The MAH will develop a comprehensive pharmacovigilance plan as outlined below.

5. key methods used in pharmacovigilance
After obtaining either manufacturing license or import license from the office of DCG (I) at
CDSCO (HQ), the vaccine products are placed in the market and simultaneously initiate
collection and monitoring of all major and minor AEFI cases across the country by choosing
an appropriate method of vigilance activities as follows::
A) Passive Surveillance
• Spontaneous Reports
B) Stimulated Reporting
C) Active Surveillance
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 Individual Case Safety Report

6. A) Passive
Surveillance
• Describes one or more adverse drug
reactions in a patient who was given one or
more biological products and that does not
derive from a study or any organized data
collection scheme.
• Identification of safety signals once a drug is
marketed.
• Provide important information on at-risk
groups, risk factors, and clinical features of
known serious adverse drug reactions.
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Spontaneous Reports

7. B) Stimulated Reporting
• Stimulated adverse event reporting in the early post-marketing phase can lead
MAH to notify healthcare professionals of new therapies and provide safety
information early in use by the general population.
• This should be regarded as a form of spontaneous event reporting, and thus data
obtained from stimulated reporting cannot be used to generate accurate
incidence rates, but reporting rates can be estimated.
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8. • seeks to ascertain the number of
adverse events via a continuous pre-
organized process.
In general; it is more feasible to get
comprehensive data on individual
adverse event reports through an active
surveillance system than through a
passive reporting system.
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9. key methods used in pharmacovigilance
Present the world-wide safety experience of a medicinal product/vaccines at defined times post-authorization,
in order to report all the relevant new safety information from appropriate sources.
As per the Drugs and Cosmetics Rules, the applicants shall furnish Periodic Safety Update Reports (PSURs) in
order to-
(a) Report all the relevant new information from appropriate sources;
(b) Relate these data to patient exposure;
(c) Summarize the market authorization status in different countries and any significant variations related to
safety;
(d) Indicate whether changes should be made to product information in order to optimize the use of the
product.
However, all cases involving serious unexpected adverse reactions must be reported to the Licensing Authority
within 15 days of initial receipt of the information by the applicant.
New studies specifically planned or conducted to examine a safety issue should be described in the PSURs.9
 Periodic Safety Update Report

10. key methods used in pharmacovigilance
• Post Marketing trials are studies (other than routine surveillance) performed after drug
approval and related to the approved indication(s).
• These trials go beyond the prior demonstration of the drug’s safety, efficacy and dose
definition.
• These trials may not be considered necessary at the time of new drug approval but may be
required by the Licensing Authority for optimizing the new drug’s (vaccine’s) use.
• Phase IV trials include additional drug-drug interaction(s), dose-response or safety studies
and trials designed to support use under the approved indication(s), e.g.
mortality/morbidity studies, epidemiological studies etc.
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Post marketing trials (Phase-IV)

11. PHARMACOVIGILANCE
US
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12. Types of post marketing safety reports
submitted to the FDA
Must be reported to the FDA as soon as possible, but in no case later than 15 calendar days
of initial receipt of the information by the applicant.
This information should include, an identifiable patient, an identifiable reporter, a suspect
product, and a serious, unexpected adverse experience
FDA encourages applicants to include relevant hospital discharge summaries and autopsy
reports/death certificates.
Applicants should also include in their report a list of other relevant documents (e.g., medical
records, relevant laboratory data, electrocardiograms, and other concise critical clinical data.
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A. 15-Day Reports of Serious, Unexpected Adverse Experiences

13. Post marketing periodic reports are required to be submitted to the FDA for each approved NDA,
ANDA, and BLA and are due quarterly for the first 3 years after U.S. approval of the application
and annually thereafter.
Periodic reports due quarterly must be submitted within 30 calendar days of the last day of the
reporting quarter.
The regulations require a post marketing periodic report to contain:
• A narrative summary and analysis of the information in the report and an analysis of the
15-day Alert reports submitted during the reporting interval
• An FDA Form 3500A for each spontaneously reported adverse experience occurring in the
United States that was not reported in a 15-day Alert report
• A history of actions taken since the last report because of adverse experiences.
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B. Periodic Reports

14. An applicant must submit at periodic intervals
two copies of a report containing information
about the quantity of the product distributed
domestically (including distributors) under the
BLA.
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D. Distribution Reports for
Biological Products
Including Vaccines

15. Post marketing, Clinical Trial, or
Surveillance Studies
• Adverse experiences incidental to other types of studies not involving monitoring adverse
experiences of products should be treated as spontaneous reports
• Serious, unexpected adverse experiences that occur during a study must be submitted as
15-day reports.
• Adverse experiences occurring with marketed drug or biological products during IND trials
must also be submitted, to the FDA new drug review division in the Center for Drug
Evaluation and Research or the product review office in the Center for Biologics Evaluation
and Research that has responsibility for oversight of the IND.
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16. Individual case safety reports of adverse experiences that occur domestically for vaccines, must be
submitted a VAERS form must be used for vaccines.
Foreign adverse experiences associated with the use of vaccines can be submitted on either a
VAERS form or, if preferred, a CIOMS I form.
Vaccine Adverse Event Reporting System (VAERS)
Council for International Organizations of Medical Sciences (CIOMS)
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17. PHARMACOVIGILANCE
EUROPEAN UNION

18. Pharmacovigilance Plan
There are special considerations for both routine and additional pharmacovigilance
activities for vaccines such as the need to investigate serious but rare adverse
reactions (even if the sole aim is to provide reassurance on safety), batch-related
adverse reactions, if appropriate, safety of concomitant vaccination and evaluation
of the impact of different immunization schedules.
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19. An important source for the detection of safety issues in the post- authorization phase, in
particular with regard to rare, serious adverse reactions with a low background event rate.
Different types of adverse reactions should be considered:
• Those that are perceived as adverse reactions, but may be visible signs of the immune response
of the host (interleukin response, e.g. fever);
• Those reflecting the clinical picture of the disease for which immunization has been given (e.g.
measles-like rash following vaccination); and
• Those that are unexpected and for which a causal relationship remains to be elucidated.
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20. Vaccines are intended to have powerful effects on the immune system. It is understandable
therefore that Healthcare Professionals and the public may perceive adverse events occurring in
temporal association with vaccination as causally related, even if no causal link exists.
AEFIs might be reported to either regulatory authorities as well as Marketing Authorization Holders
as spontaneous reports. In the EU, legal definitions and reporting requirements are laid down for
adverse reactions but not for AEFIs.
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An Adverse event following immunization (AEFI) is any untoward medical
occurrence which follows immunization and which does not necessarily have a
causal relationship with the usage of the vaccine.

21. Spontaneously reported suspected adverse reactions remain an important source for the
detection of safety issues in the post- authorization phase, in particular with regard to rare,
serious adverse reactions with a low background event rate. Spontaneous reporting is also
useful to cover safety aspects in the diverse populations. Different types of adverse reactions
should be considered:
• Those that are perceived as adverse reactions, but may be visible signs of the immune
response of the host (interleukin response, e.g. fever);
• Those reflecting the clinical picture of the disease for which immunization has been given
(e.g. measles-like rash following vaccination); and
• Those that are unexpected and for which a causal relationship remains to be elucidated.
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Suspected Adverse Reactions

22. Most vaccines are not 100% effective.
Therefore cases of breakthrough infections are
expected.
Reporting of vaccine failures from effectiveness
studies at the level of the individual study
subject is normally not required.
Reporting procedures should be described in the
study protocol. The final study report should be
submitted to the national Competent
Authorities/EMEA
Vaccination failure should be addressed in the
RMP.
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Vaccine Failures

23. Inappropriate handling may lead to adverse events such as infection due to bacterial contamination
of the vaccine, transmission of blood-borne infection, abscess formation at the site of injection or
loss of efficacy. These issues apply particularly to multi-dose container vaccines without
preservatives.
For some vaccines, the method of administration may be associated with adverse reactions.
Marketing Authorization Holders should adequately follow-up the root cause of any errors and
address this appropriately through communication.
The potential for and risk minimization actions addressing such errors need to be described in the
RMP.
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Vaccination Errors

24. Periodic Safety Update Reports
(PSURs)
Special consideration should be given in PSURs for vaccines to any potential impact
on safety of changes in the manufacturing process. Issues related to batch(es), as
well as age-related adverse reactions should be evaluated. If relevant, the potential
for local and systemic adverse reactions should be analysed for different doses of
the vaccine and also across different vaccination schedules.
The following data should also be summarised and analysed in the PSUR:
• reports of vaccine failure, lack of efficacy/effectiveness;
• vaccination errors;
• vaccination anxiety-related reactions such as syncope;
• literature data with information relevant to other similar vaccines and vaccine
components such as stabilisers, preservatives and adjuvants.
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25. As rare but serious adverse reactions, reactions with delayed onset and reactions in subpopulations
are usually not detected prior to marketing authorisation post-authorisation evaluation of safety in
studies is critical for vaccines. Safety concerns arising during the post authorisation may relate to:
• the increased incidence of a natural disease;
• vaccine specific adverse reactions;
• a higher rate of expected adverse reactions compared to comparators or precursor vaccines.
If safety concerns, including concerns over missing data, arise, the conduct of post-authorisation
safety studies (PASS) may be necessary.
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26. It is of utmost importance that data are
managed in a form that allows data retrieval
and analysis by age groups (e.g. premature
infants, neonates, infants and the elderly),
number of doses, different vaccination
schedules, defined risk factors or underlying
diseases and adverse event/reaction types.
Clusters of reported adverse events/reactions
should be identified.
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Data Management

27. The objectives of pharmacovigilance for vaccines are to identify rare or new adverse events,
identify those that are causally related to the vaccine /vaccination and estimate their rate of
occurrence. In addition, any change in the frequency or severity of a known safety concern
requires prompt evaluation.
Errors in manufacturing, handling and administration should also be evaluated. Action to avoid
such errors should be explored.
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Risk Evaluation

28. The risk-benefit balance for vaccines depends largely on the incidence of the
infectious disease in the target population, the proportion of infected persons with
clinical disease, the severity of clinical disease as well as the risk of transmission,
identification of high risk groups and geographical and seasonal characteristics of
the infectious disease.
For vaccines already included into the extended vaccination programme, the impact
of the vaccine on the epidemiology of the vaccine-preventable condition should be
considered as well as the impact on individual protection.
Due to the success of vaccination programmes in their later stages, whether there
is herd immunity as well as individual protection, the risk-benefit balance might
change. Differences in morbidity and mortality of an infectious disease in different
countries have to be considered.
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Risk-Benefit Assessment

29. • https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf-
documents/biologicals/3GuidanceBioloGicalProducts.pdf
• https://www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarketing-
safety-reporting-human-drug-and-biological-products-including-vaccines
• https://www.ema.europa.eu/documents/regulatory-procedural-guideline/guideline-conduct-
pharmacovigilance-vaccines-pre-post-exposure-prophylaxis-against-infectious_en.pdf
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30. THANK YOU!