Contents

Safety Data Generation.......................................................................................................................3

Post Approval Phase............................................................................................................................4
Regulatory Requirements...................................................................................................................5
Periodic safety update report..............................................................................................................6
Risk Management in Post Approval Phase........................................................................................7
Conclusion............................................................................................................................................9
Reference............................................................................................................................................10
 Safety Data Generation:
Clinical Phase

Introduction
The efficacy and safety of medicinal products should be demonstrated by clinical trials which
follow the guideline in good clinical practice consolidates guideline adopted by the ICH 1
may 1996.
Safety data generation refers to the process of collecting, analyzing and interpreting data
which is related to the safety profile of a product such as pharmaceutical product medical
devices or chemical compound.
This includes data on adverse events toxicity or other potential safety concern.
Safety data generation ensuring the continued safety and efficacy of products throughout their
lifecycle from pre-clinical development post-marketing surveillance. There are various
methodology involved .It include clinical and non-clinical studies, epidemiological research
and spontaneous case report.
Safety data generation typically involves several phases
Pre-clinical studies
Clinical studies
Post-marketing surveillance
Pre-clinical studies – Pre -clinical studies are conducted in laboratories using cells, tissues,
or animal models to assess the safety and efficacy of a potential drug or treatment before it's
tested in humans. These studies provide crucial data on the biological effects,
pharmacokinetics, and potential toxicity of the compound. They are essential for determining
whether a drug has the potential to move forward into clinical trials with humans.
Clinical Studies - Clinical studies, also known as clinical trials, are research studies conducted
to evaluate the safety and effectiveness of new medical treatments, drugs, or devices in
humans. They are crucial for advancing medical knowledge and improving patient care. Here
are some key details about clinical studies:
Purpose: Clinical studies aim to gather data on the safety, efficacy, and side effects of new
medical interventions.
Phases: Clinical trials are typically conducted in phases:
Phase 1: Initial testing on a small group of healthy volunteers to evaluate safety and dosage.
Phase 2: Testing on a larger group of patients to assess efficacy and further evaluate safety.
Phase 3: Large-scale testing on patients to confirm efficacy, monitor side effects, and
compare with standard treatments.
Phase 4: Post-marketing surveillance after the treatment is approved and available to the
public.

Post Approval Phase

The post-approval phase in pharmacovigilance is a crucial stage in the lifecycle of a drug

following its approval by regulatory agencies for marketing and distribution. This phase
involves ongoing monitoring and evaluation of the drug's safety profile in real-world clinical
practice, beyond the controlled settings of clinical trials.
Purpose and Significance:
 The primary goal of the post-approval phase is to ensure the continued assessment of
the safety and efficacy of a drug in diverse patient populations and clinical settings.
 It aims to detect and evaluate adverse drug reactions (ADRs) that may not have been
observed during pre-market clinical trials due to factors such as limited sample size,
restricted patient demographics, or short duration of exposure.
 The post-approval phase plays a critical role in identifying rare or long-term adverse
effects, assessing the impact of drug interactions, and evaluating the effectiveness of
risk minimization measures.
Regulatory Requirements: Regulatory agencies, such as the FDA in the United States or the
EMA in Europe, mandate PMS as part of the approval process for medical products. Post-
approval commitments, including the conduct of post-marketing studies and submission of
periodic safety reports, may be imposed by regulatory authorities to further evaluate the
safety and effectiveness of the drug.
Data Collection: PMS involves collecting and analysing data from various sources,
including adverse event reports, clinical studies, complaints, and quality control measures .
Risk Management: One of the primary goals of PMS is to identify and assess potential risks
associated with the use of medical products and take appropriate actions to mitigate those
risks.
Signal Detection: PMS helps to detect signals of potential safety issues or product failures
that may not have been evident during pre-market testing.
Compliance: Medical device and pharmaceutical companies are responsible for conducting
PMS activities and reporting any findings to regulatory authorities.
Continuous Improvement: Findings from PMS activities can inform product design
modifications, labelling, updates, or even product recalls to enhance patient safety and
product quality.

The post-approval phase in pharmacovigilance is essential for continuously monitoring the

safety and effectiveness of approved drugs in real-world clinical practice. By employing
various surveillance methods, risk management strategies, and regulatory mechanisms,
stakeholders can mitigate potential risks and ensure the optimal use of medicines for patient
benefit.

Regulatory Requirements

Regulatory requirements for the post-approval phase typically involve monitoring the drug's
safety and efficacy in real-world settings, reporting adverse events, conducting post-
marketing studies, and updating labeling as needed. These requirements vary by jurisdiction
and may include periodic safety update reports, risk evaluation and mitigation strategies
(REMS), and compliance with pharmacovigilance regulations.

In the post-approval phase, regulatory bodies often require pharmaceutical companies to

submit periodic safety reports, conduct post-marketing surveillance studies, monitor adverse
events, and update product labeling accordingly. These details help ensure ongoing
assessment of a drug's safety and effectiveness once it's on the market. Additionally,
companies may need to adhere to specific post-approval commitments outlined during the
regulatory approval process.
Post Marketing Safety Data Generation
1. Periodic safety update report.
2. PSUR process.
3. Intake of ADRs information.
4. Data retrieval.
5. PSURs should submitted every month for first 2 years.
Periodic safety update report

PSURs is a regulatory or pharmacovigilance document which provide an evaluation of the

safety profile of drug over a defined period PSURs required for marketing authorization
holders (MAHs) of medicinal products. The report includes data on adverse events, safety
concern, action taken to mitigate risk, essential tool for monitoring the ongoing safety of
medication.
Purpose: PSURs aim to monitor the safety of medicinal products after they have been
authorized for marketing. They provide a systematic and periodic review of safety data to
identify any new safety concerns, trends, or changes in the benefit-risk balance of the
product.
Contents: PSURs typically include information such as:
 Adverse drug reactions (ADRs) reported during the reporting period.
 Overall safety profile, including serious and non-serious adverse events.
 Exposure data, such as patient exposure and usage patterns.
 Benefit-risk assessment, evaluating the benefits of the product against its risks.
 Changes to the product's safety information, such as updates to the product label.

Regulatory Requirements: Regulatory agencies, such as the European Medicines Agency

(EMA) and the U.S. Food and Drug Administration (FDA), often require marketing
authorization holders to submit PSURs at predefined intervals for review and assessment.
Frequency: The frequency of PSUR submissions varies depending on factors such as the
product's approval status, the nature of the product, and regulatory requirements. Common
intervals include every six months, annually, or every three years.
Global Harmonization: Efforts have been made to harmonize PSUR requirements globally
to streamline the reporting process and ensure consistency in safety monitoring across
different regions.
Signal Detection: PSURs play a crucial role in signal detection, which involves identifying
potential safety concerns or new information about known risks associated with a medicinal
product.

PSURs process
1. Data collection : Gathering safety data from various sources,
2. Data analysis : Analyzing the collected data to identify new safety.
3. Risk assessment : Assessing the potential risk associates with drug based on
collecting data.
4. Preparation of PSURs : Compare all analyzed data assessment into a comprehensive
PSUR document.
5. Submission : Submitting the PSURs to regulatory authority.
6. Review and feedback : Regulatory authorities review the submitted PSURs and may
provide feedback or
7. Updates : Based on feedback and any new developments.

Risk Management in Post Approval Phase

In the post-approval phase, risk management is crucial to ensure ongoing safety and
effectiveness of the approved product. This involves continuous monitoring for adverse
events, compliance with regulatory requirements, and addressing any emerging risks
promptly. Regular reviews of safety data, pharmacovigilance activities, and communication
with stakeholders are essential components of effective risk management during this phase.
Pharmacovigilance Activities: This includes monitoring and reporting of adverse events,
assessing their severity and frequency, and taking appropriate actions based on the findings.
Risk Evaluation and Mitigation Strategies (REMS): Implementing REMS programs to
manage known or potential risks associated with the product. These strategies may include
medication guides, communication plans, and restricted distribution programs.
Periodic Safety Update Reports (PSURs): Regularly submitting PSURs to regulatory
authorities, summarizing safety data and any new risks or concerns identified since approval.
Signal Detection and Management: Continuously monitoring for signals of potential safety
concerns through various sources such as spontaneous reporting systems, literature reviews,
and observational studies. If a signal is detected, it's investigated further and appropriate
actions are taken.
Labeling Updates: Ensuring product labeling reflects the latest safety information, including
any new risks or updated recommendations for safe use.
Communication with Healthcare Professionals and Patients: Providing timely and
accurate information to healthcare professionals and patients about the product's safety
profile, including any changes or updates.
Post-Marketing Studies: Conducting post-marketing studies to further evaluate the product's
safety and effectiveness in real-world settings, especially in patient populations or conditions
not adequately studied during clinical trials.
Risk Communication: Developing and implementing strategies for communicating risks to
healthcare professionals, patients, and the public in a clear and understandable manner.
Compliance Monitoring: Ensuring compliance with regulatory requirements and any
commitments made during the approval process, including post-approval commitments and
risk management plans.
Collaboration with Regulatory Authorities: Maintaining open communication and
collaboration with regulatory authorities to address any emerging safety concerns or
regulatory requirements
Recommendations are provided for post approval phases
1. Components and composition.
2. Manufacturing site.
3. Manufacturing process.
4. Specification.
5. Container closure system.
6. Labeling
7. Miscellaneous changes.
Labelling updates procedure for post approval phase
 In the post approval phase labelling updates typically follow a structured
procedure.
1. Identify need for update.
2. Gathering information.
3. Drafting.
4. Internal review.
5. Submission to regulatory authorities.
6. Approval process.
7. Implementation.
8. Communication.
9. Monitoring and feedback.
10. Documentation.
Conclusion

In pharmacovigilance, the post-approval phase stands as a critical pillar in safeguarding

public health. It serves as a rigorous monitoring process, essential for detecting, assessing,
and understanding adverse reactions to medications after they have been approved for use.
Through systematic evaluation of reported data, regulatory bodies and healthcare
professionals can identify potential safety concerns, update prescribing information, and
ultimately enhance patient care. The post-approval phase underscores the ongoing
commitment to drug safety, ensuring that the benefits of medications continue to outweigh
any associated risks in real-world settings.
The post-approval phase serves as the final checkpoint in ensuring that content meets all
necessary criteria before dissemination. It acts as a safeguard against misinformation,
offensive material, or content that may violate guidelines. By meticulously reviewing posts,
platforms can maintain credibility, uphold community standards, and foster a safe online
environment. This phase underscores the importance of responsible content moderation in
shaping a positive online experience for users.
Post approval studies are important to obtain additional safety and efficacy data after a drug
has been approved. Europe are particularly Spain is a convenient territory to execute these
types of studies,
The outcomes of such studies could be signals pharmaceutical epidemiological information,
need for controlled studies labelling changes with modified undesirable effects section
indication and closing schedules and regulatory action warning risk minimization action plan,

Reference

1. Gibbons R, Amatya A, Brown C, Bhaumik D. Post Approval Drug Safety

Surveillance. Doi-10.1146/annurev.publhealth.012809.103649
https://www.ncbi.nlm.nih.gov/pmc/artivles/PMC2841706
2. Article- Post Approval Studies Program.
https://www.fda.gov/medical-devices/postmarket-requirements-devices/post-
approval-studies-program
3. ICH guideline on Post Approval Safety Data: Definitions and Standards for
Management and Reporting of Individual Case Safety Reports.
4. Kara V, Garg A, Gofman K, Hauben M. Individual Case Safety Report Replication:
An Analysis of Case Reporting Transmission Networks. Doi- 10.1007/s40264-022-
01251-7
5. Pharmacovigilance by Dr. Snehalatha, Vaishnavi S. Nirali Prakashan, First Edition