Post-Authorization Safety Studies (NI-PASS)

There are two different studies that a Health authority may request an MAH (Marketing Authorisation Holder) to conduct after authorisation. One with the key objective of safety and another for efficacy, although it's always that we will get both outputs, and safety and efficacy go hand in hand.

So the post-authorisation efficacy study and post-authorisation safety studies (PASS). Both these studies can be interventional or non-interventional, and each MAH has its own processes to define and implement these regulations.

PASS falls under the realm of pharmacovigilance; therefore, we will discuss it further in this blog. 

PASS includes the following when non-interventional. Non-interventional studies wherein the product is prescribed and administered to patients as a part of routine clinical practice. 

PASS when interventional, they are our clinical trials. 

•  HCP surveys conducted for the effectiveness of any risk minimization measures implemented by MAH ( e.g., providing patient alert cards to each patient and explaining to them the risk it outlines
• Public registries that MAH has to enroll patients of approved therapeutic indications and characterise the known risk, or establish the safety profile
• Consortia (one or more MAH form the group to conduct a particular registry to gather data)
• Market surveys to characterise and analyse the product safety.

Post-authorization safety studies (PASSs) can be mandatory or voluntary.

• Mandatory PASSs are required by Health Authorities. For example, they may be needed when a medicine has been approved under exceptional circumstances or when the Pharmacovigilance Risk Assessment Committee (PRAC) asks the MAH to conduct PASS to confirm the safety profile, characterize the risk or measure the effectiveness of risk minimization measures.

• Voluntary PASSs are started by MAH themselves. These can include studies that the company chooses to do, or studies that are part of a risk management plan but not formally required by any Health authority.

Starting January 2025, all marketing authorization holders will need to use the IRIS platform to manage their post-authorization safety studies (PASSs) after the initial submission in the EU, as per EMA. PASS studies are also registered in the EU PAS register/now called as catalogue of real-world data studies, which is a European Union register electronically for post-authorization studies on the European network of centers for pharmacoepidemiology and pharmacovigilance (https://catalogues.ema.europa.eu/). A EU CT number is mandatory for all PASS registered by MAH. 

Table on the category of PASS:

Category	PASS	PAES
Category 1	Imposed (GVP Module V)	Imposed
Category 2	Imposed (Commitment in MA, exceptional approval)	Imposed
Category 3	Voluntary, Part of RMP commitment	Required/voluntary
Other		Voluntary

Every PASS study submitted as imposed PASS to EMA will require a Study protocol, major amendments to the protocol after the PRAC comments are received/ for nationally required PASS- assessment will be done by that national health authority. MAH will then need to submit interim study reports, final study reports to EMA, and also provide the summary and details of PASS in PV documents like PSUR, RMP in the respective sections. Any change in the safety profile of the product due to ongoing PASS based on interim results will then be submitted as part of an update to RMP, smpc, or based on the frequency and timing of PV documents. The timelines and requirements of PASS progress to EMA are specified in the study protocol approval and will be part of study planning.

EMA publishes the outcome of PASS in the EPAR (European public assessment report ) and on EU PAS register platform.

Key takeaway:

As PV  professional, you will be involved in PASS depending on your role in the organisation, but having a basic understanding helps. To know the definition of PASS, how they become part of RMPs, and PSURs. Knowing the concepts helps to review or take strategic decisions from PV for protocols and outcomes of studies and their impact on the safety of the product.

Written by:

Dr.Shraddha Bhange.

Connect with me Via comments below. (I do not respond to Facebook messages)

Support the cause of better rural education with me: ThinkSharp Foundation http://thinksharpfoundation.org/#home 

References:

1. Non-interventional imposed PASS are set in Articles 107n-q of Directive 2001/83/EC.

2.https://www.ema.europa.eu/en/human-regulatory-overview/post-authorisation/pharmacovigilance-post-authorisation/post-authorisation-safety-studies-pass#non-interventional-imposed-pass-questions-and-answers-6931

3. https://www.ema.europa.eu/en/documents/other/guidance-format-and-content-protocol-non-interventional-post-authorisation-safety-studies_en.pdf

4. guideline-good-pharmacovigilance-practices-gvp-module-viii-post-authorisation-safety-studies-rev-3_en.pdf

5. GVP V module and EMA website