Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Optimisation of Master File Procedures for Biologics: Comparison of Master File Procedures - EU and USA ***

Nadine Herzog (Abschlußjahr: 2008)

Language: English

In the EU as well as in the USA four different types of Master Files are in force at present, which have been developed in different ways in both regions.

In this master thesis the similarities and differences of both regions regarding the Master File procedures will be compiled and compared and the possible development for biological substances will be discussed.

In the USA several materials used in the manufacturing of drug products could be filed as DMF (Drug Master File), such as drug substances, drug substance intermediates and materials used in their preparation, drug products, packaging materials, excipients, colourants, flavours, essences or materials used in their preparation and also for FDA accepted reference information. Whereas in the EU the Master File concept is strictly limited to well defined materials such as active substances, substances included in the Ph. Eur., plasma and vaccine antigens.

The USA has completely transferred the principle of protection of know-how of the manufacturer in the DMF system. The complete information of the DMF is not disclosed to the Applicant, so only the authorities have access to the information included in the DMF and only they can assess the impact on the drug product. The Applicant is completely dependent on the DMF holder, especially regarding the up-to-dateness of the content.

In the EU for the ASMF (Active Substance Master File) a system with open part (Applicants Part, AP) and closed part (Restricted Part, RP) exists. The AP is available for the Applicant/MAH and the RP is only for the authorities prepared. For the PMF (Plasma Master File) and VAMF (Vaccine Antigen Master File) the main focus lies on the reduced paper- and workflow for authorities as well as for industries, since one plasma or vaccine antigen is used for several plasma-derived medicinal products or vaccines from different marketing authorisations (national, MRP, DCP and CP).

For both regions the reduced paper- and workflow regarding new submissions and the maintenance of existing Master Files for authorities as well as for industries is a big advantage. With the Master File system it is also easier to keep the contents of the different applications harmonised.

In the EU there is also a certification procedure available for substances described in a general and/or specific monograph of the European Pharmacopoeia. Manufactures can apply for such a CEP at the EDQM without connection to a MAA/MAV and without disclosure of any information of the DMF to a third party. With this CEP companies can enter also markets outside of the EU/EEA.

Especially innovative packaging materials as well as novel excipients are more and more developed from specialised companies and not only from the companies, which act as Applicant. Therefore it is also necessary to improve the European Master File system for example through extension of the scope of the ASMF procedure or through implementation of a more US-like concept.

The second issue, which should be solved in the EU, is to open up a possibility of a Master File principle for biological substances and to develop the existing Master File principles for biological substances. This should also be an ICH topic for the future, since more and more medicinal products are of biological source and the special know-how for this is often located in small companies, which cannot act as Applicant/MAH, because of their resources.

Pages: 114,
Annexes 16