Expanding Master Files for human medicinal products in the EU/EEA

Joint position from EFPIA, CEPI and Vaccines Europe

Executive Summary

Sponsors for Marketing Authorisation Applications of biological medicinal products (e.g. recombinant proteins, advanced therapy medicinal products, vaccines) frequently rely on collaboration with third party manufacturers to source components required to produce new, innovative medicines. These materials often have intellectual property held by the third-party suppliers, however, the current European regulatory framework has little capacity to protect proprietary confidential information between collaborating parties for biologicals, whereas small, synthetic molecule products have tools such as Active Substance Master Files with ‘open’ and ‘closed’ parts to protect IP. Other Master File tools currently exist in the EU, for vaccines with the Vaccine Antigen Master File (VAMF), the recent veterinary vaccine Platform Technology Master File (vPTMF), and for plasma-derived products with the Plasma Master File (PMF).

Similarly, the absence of a Master File mechanism for biological medicinal products in the EU/EEA results in the reuse of the same information being structured, submitted and re-reviewed by agencies when common components and manufacturing process steps are being described in the Marketing Authorisation Applications for different products that use platform manufacture, formulations, primary container closure systems etc. This is further exemplified by the resubmission and rereview of information when prior knowledge across different products has been described and previously approved in other applications. Indeed, EFPIA proposed in 2017 at the BWP/QWP Prior knowledge workshop “to consider the Use of a ‘Master File’ (DMF-type approach) as a way to gather prior knowledge information, where the relevant information can be reviewed and approved once by a competent authority and then cross-referenced in subsequent submissions. As the information needs to be kept current, use of a DMF would also facilitate lifecycle management through ongoing data maintenance and exchange with regulators.” [1]

This position paper proposes a modular, flexible Master File type approach, similar to the Drug Master File procedure of the FDA, by extending the scope of already implemented EU approaches:

  • Expansion of the existing Active Substance Master File approach to apply to biological active substances and ATMPs, and to include raw materials, excipients, adjuvants, drug product and product intermediates etc, as a Pharmaceutical Master File (PhMF);
  • Expansion of the veterinary vaccine Platform Technology Master File approach as a general Platform Technology Master File that may be applied to innovative technologies, platform manufacturing capabilities and prior knowledge data across different molecules, as applicable for all types of human medicinal products;
  • Allowance for clinical trial applications to make reference to approved, commercial product Master Files, and implementation of investigational master files following the concepts outlined above, however relying on abbreviated procedures and appropriate quality requirements for investigational medicinal products.
  • Case studies outlining how a more flexible EU/EEA legal framework extended to modular Master Files could facilitate a more streamlined Marketing Authorisation and Clinical Trial Application submission and review procedure are provided in Annex 1 in addition to protecting intellectual property.