EU | Revised EMA Guidance for Imposed PASS
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Real World Evidence (RWE) 101 – PASS Approval Requirements
Post-authorisation safety studies (PASS) are studies conducted after a medicine has been authorized (licensed) with the goal of acquiring more data about the medicine’s safety, or to measure the effectiveness of risk-management measures. These studies play a vital role in understanding the safety and effectiveness of a drug in a real-world context.
While specific requirements can vary by country, they often include:
[1] Ethics Committee Approval: Any study involving human subjects generally needs to be approved by an Ethics Committee (EC) or Institutional Review Board (IRB). This body ensures that the study is designed and implemented in a manner that respects the rights, safety, and well-being of the participants (i.e., compliance with the Declaration of Helsinki).
[2] Regulatory Approval: Depending on the country and type of PASS (e.g., Category 1, 2, 3, or voluntary PASS) additional regulatory approval may be needed. For instance, in the European Union, any category 1 or 2 PASS protocol of a medicine authorised through the Centralised Procedure has to be approved by the European Medicines Agency (EMA).
[3] Data Protection Laws Compliance: Studies must comply with all relevant data protection laws (e.g., GDPR). This includes regulations on the use and sharing of personal data, as well as provisions for protecting the privacy of participants.
[4] Study Registration: Most categories of PASS must be registered in a public database (i.e., EU PAS Register). This increases transparency and allows for the tracking and sharing of results.
[5] Adherence to Good Pharmacovigilance Practices (GVP): This is especially pertinent in the EU, where PASS must adhere to Module VIII of the GVP.
[6] Provision of Adequate Information to Participants: There’s usually a requirement that all participants must be given adequate information about the study, and that informed consent must be obtained.
[7] Reporting Requirements: There will be requirements to report adverse events, progress, and the final results to the respective regulatory bodies (i.e., ethics committees and national competent authorities).
However, these requirements can be subject to change over time and may vary in specifics from one country to another. Therefore, it’s crucial to consult with the appropriate regulatory body or a regulatory affairs professional familiar with these regulations when planning a post-authorisation safety study.
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Real World Evidence (RWE) 101 – Categories of PASS
Real-world evidence (RWE) is the clinical evidence about the usage and potential benefits or risks of a product derived from the analysis of real-world data (RWD). RWD and RWE are playing an increasingly important role in healthcare decisions.
In the context of pharmacovigilance, post-authorization safety studies (PASS) are studies performed after a medicine has been approved and is available on the market. The purpose of these studies is to obtain further information on a medicine’s safety, or to measure the effectiveness of risk-management measures.
Post-authorization safety studies (PASS) can be interventional (clinical trials) or non-interventional. As per EMA’s GVP Module V, there are 3 categories of PASS:
Category 1 PASS (Imposed PASS) – These are studies required by a regulatory authority as a condition of a (normal) marketing authorization. These studies are often required to clarify the safety profile of the drug, or to assess risks that were identified in pre-approval stages, but could not be fully characterized due to limitations like sample size of clinical trials or underrepresentation of certain populations. These studies are listed in Section II.C of the risk management plan (RMP) Summary.
Category 2 PASS (Specific Obligations) – These are studies that are specific obligations imposed when a medicine has received a conditional marketing authorisation. This applies to medicines that target conditions with an unmet medical need – for which no treatment option exists, or where they can offer a major therapeutic advantage over existing treatments. These studies are often required because the medicines approval has been accelerated to ensure timely access by patients, limiting the amount of safety data available at the time of approval. These studies are listed as “Specific Obligations” in Section II.C of the EPAR RMP Summary
Category 3 PASS (Other PASS) – These are studies might be required (as opposed to being imposed) by the EMA or a national competent authority in the RMP to investigate a safety concern or to evaluate the effectiveness of risk minimisation activities. These studies are listed as “Other Studies” in Section II.C of the RMP Summary.
Category 1 and 2 PASS are supervised under Articles 107m, 107n-q of Directive 2001/83/EC, meaning the protocol and study report must comply with Annex III of Regulation 520/2012/EU and EMA’s GVP Module VIII. The protocol must be approved (endorsed) by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) (medicines approved through the Centralised Procedure).
Category 3 PASS are supervised under Article 107m of Directive 2001/83/EC, which requires, for example, that studies are not promotional, healthcare professional renumeration is equivalent to fair market value, and final study reports should be send to the national competent authorities where the study is conducted.
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Real World Evidence (RWE) 101 – Postmarket Requirements (PMR) vs Post-Authorisation Safety Studies (PASS)
In the context of real-world evidence (RWE) and regulatory frameworks, postmarket requirements (PMRs) and post-authorization safety studies (PASS) are two distinct concepts that focus on monitoring and assessing the safety and effectiveness of medical products after they have been approved or authorized for use. Here’s an explanation of each:
Postmarket Requirements (USA): Postmarket requirements refer to the obligations imposed by the US FDA on manufacturers or sponsors of medical products (such as drugs and biologics) after they have been approved for marketing. These requirements are intended to gather additional data and monitor the product’s safety and effectiveness in real-world settings and INCLUDE observational studies that sponsors are required to conduct.
Compliance with these requirements ensures ongoing evaluation and surveillance of the product’s safety and effectiveness throughout its lifecycle.
Post-Authorization Safety Studies (EU): Post-authorization safety studies (PASS) are specific studies conducted to further assess the safety profile of a medical product in real-world settings after it has been authorized for use. PASS is a type of post-marketing study designed to gather additional safety data that may not have been captured during pre-market clinical trials due to the limited sample size, restricted patient population, or duration of the trials.
Key aspects of post-authorization safety studies include:
Study design: PASS typically involves observational study designs, such as cohort studies or case-control studies, to evaluate the safety outcomes associated with the product’s use in a larger patient population.
Sample size: PASS often involves a larger number of participants than pre-market clinical trials to increase the likelihood of detecting rare or long-term safety events.
Data collection: Data for non-interventional PASS is collected from real-world sources, such as electronic health records, claims databases, registries, or other healthcare databases.
Safety outcomes: The primary focus of PASS is to assess and monitor the occurrence of safety events, adverse drug reactions, or any potential safety concerns associated with the product’s use.
Post-authorization safety studies are typically conducted as a regulatory requirement, based on the authorization conditions set by the EMA (i.e., Category 1 and 2 PASS). The findings from these studies contribute to ongoing risk-benefit assessments of the product and inform regulatory decision-making, labelling updates, or risk management strategies.
Overall, postmarket requirements encompass a broader set of obligations imposed on manufacturers after a product’s approval, while post-authorization safety studies specifically focus on conducting additional studies to assess the safety profile of authorized medical products in real-world settings.
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stuart.mccully2023-08-07T22:02:40+00:00August 7, 2023|2023, RWE 101|
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stuart.mccully2023-08-07T21:50:20+00:00August 7, 2023|2023, RWE 101|
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