EMA updates Guidance for Post-Authorization Activities

Recommendation

17/18 September 2024

Drug Master File Procedures in the EU, the US and Japan - Live Online Training
With updates on the CEP 2.0!

The European Medicines Agency (EMA) recently posted its improved guidance for post-authorization activities. The announcement regarding the updated best practice guidelines including type II variations, post-authorization safety studies and quality variations has been published on July 14, 2017. Additionally, improved support documents for marketing authorization holders (MAHs) are provided.

EMA says that "the main aim is to improve the quality of post-authorization applications by better assisting applicants in complying with the legal and regulatory requirements and avoiding frequent mistakes. This will result in a more efficient validation process. The guidance documents are part of EMA's commitment to operational excellence."

According to EMA the specific revisions are:

• a new pre-submission checklist for type II variation applications to help applicants verify that they have completed all the necessary requirements before submitting the application;
• an updated questions-and-answers guide for post-authorization safety studies (PASS) including 15 new questions and answers (Q&As) to provide marketing-authorization holders with detailed information on the submission requirements, assessment and implementation of outcomes for protocols, protocol amendments and final study reports of non-interventional studies (non-interventional imposed PASS). Amongst others, a definition of non-interventional imposed PASS is provided and the question "What if the results of a non-interventional imposed PASS make a variation necessary?" is addressed;
• an update of the 'Classification of post-authorization changes - Quality aspects' with eight new questions and answers to help MAHs on the classification of changes to the marketing authorization post-authorization and certain variation classification categories.

In the type II variation pre-submission checklist, EMA lists about 100 items MAHs should have checked before submitting a type II variation application to ensure the submission is complete. The document also lists elements (in bold italics) that could prevent the start of the procedure until they are addressed satisfactorily. EMA says that the elements that are not emphasized can help with validation or assessment, but can be communicated during validation and will not delay the procedure. The Agency strongly recommends that this checklist is used in advance of submission of type II variation applications. However, the checklist should not be included in the submission.

Concerning the changes related to quality aspects, changes, such as the introduction of a new manufacturing site for the finished product or for an active substance (new) are discussed (What changes can I submit under a single type II scope?). Furthermore, Q&As on submitting information about a new working cell bank or reference standard for a biological medicine, are provided.

Interestingly, two Q&As deal with the topic: What changes in manufacturing sites, buildings and rooms, and in equipment used in the manufacturing process are covered by the company Quality Assurance System (GMP)?
Answer: Provided that module 3 is not impacted, with the exception of section 3.2.A.1 (for biotech medicinal products), the changes listed below (not an exhaustive list) are covered under the company’s quality management system and do not require a variation to the Marketing Authorization:

• Transfer of a manufacturing activity from one building to another in the same authorized site;
• Transfer of a manufacturing activity from one room to another in the same authorized building;
• Transfer of QC activity from one building to another in the same authorized site;
• New filling line identical to an already approved one in an authorized room, building, manufacturing site;
• New isolator in an authorized building;
• New media or buffer preparation room in an authorized building;
• Changes in the layout of an authorized manufacturing site;
• New equipment, provided that it is equivalent to the one currently used, and operates in the approved range of process parameters.

This is also in-line with contents of the proposed new ICH Q12 guideline on Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management which is expected to provide guidance on a framework to facilitate the management of post-approval changes in a more predictable and efficient manner across the product lifecycle.

For more information on the updated documents and checklists please go to the EMA News and press releases website.