Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Assessment of the Quality Part of a Finished Product Dossier of old products - Typical gaps, possible root causes, consequences of gaps ***

Kathrin Sugg (Abschlußjahr: 2020)

Summary
Language: English
The cost of development of drugs is huge. Not every company has the resources to do a full preclinical and clinical development of drug products. One option to circumvent the costs of preclinical/clinical studies, is to undergo a general overhaul with a medicinal product developed in the past. Possibly some changes are performed in order to make the product more attractive for the current market. This requires an update of the pharmaceutical documentation to today’s regulatory requirements.
There is not much information available on typical gaps of old product dossiers and how to remediate them. The thesis discusses CMC dossier updates for products, which already have a marketing authorisation (or had a marketing authorisation in the past)

• For old dossiers that shall be reactivated but the product has not been on the market for some time
• For old dossiers that shall be reactivated but the marketing authorisation has been withdrawn due to economic reasons for some time.
• For old dossiers that have not been in the focus of maintenance but shall be updated
• For products from a 3rd party that shall be in-licenced  

The focus is on the changes in the regulatory framework of the European Union within the last 20 years (2000- mid 2020). Typical gaps will be explained as well as their consequences for the pharmaceutical dossiers to be updated.
Changes in the regulatory framework have been investigated for each submodule of the quality part of the pharmaceutical documentation ("pharmaceutical dossier", "dossier") for human medicinal products. Advanced therapy medicinal products, biotechnical/biological products, herbals and radiopharmaceuticals are excluded from the scope. In favour of the volume of the thesis, the active substance part of module 3 (3.2.S) has also not been discussed.
Mostly current and previous regulations, directives and guidelines were compared.
The changes on the regulatory provisions done for the modules 3.2.P.2, 3.2.P.4, 3.2.P.5 and 3.2.P.8 have the highest potential for the necessity of resource- intensive new studies. They may be needed in order to generate data for the dossier update and fill existing gaps. Among them, gaps in the development part (3.2.P.2) are most critical, because the development part lays the foundation for the rest of the module 3 dossier. Those gaps bear the risk that results of new studies cannot confirm the assumptions and concepts established during development or afterwards.
Recommendations for the update of the dossier were given.
Pages: 131, Annexes 04, Pages 58