Masterstudiengang "Drug Regulatory Affairs"
Master-Thesis
Plasma Master File - A Concept for Plasma-derived Medicinal Products
Josefine Bauer (Abschlußjahr: 2005)
Plasma Master File to the majority of people involved in Drug Regulatory Affairs this is most likely an unfamiliar term. However, for manufacturers of plasma-derived medicinal products the Plasma Master File (PMF) concept as stipulated by Commission Directive 2003/63/EC stands for a current requirement. In view of that, the presented thesis aims to enlighten the narrow field of the special features of plasma-derived medicinal products focusing on the PMF concept and its impact on manufacturers.
Plasma-derived medicinal products are defined according to Directive 2003/63/EC as biological medicinal products containing plasma as their starting material. Being a biological substance plasma always bears the risk of a possible contamination with infectious agents. To manufacture plasma-derived medicinal products a large amount of donations is pooled. The risk for a single infected donation to contaminate the batch and possibly transmit a disease to the recipients of the medicinal product is well recognised. Considering this, the quality and safety of plasma-derived medicinal products relies on the one hand on the careful donor selection and screening of the source material and on the other hand on the choice and control of the manufacturing processes for inactivation and/or removal of infectious agents.
In todays medical practice the therapeutic value of plasma-derived medicinal products such as immunoglobulins, albumins or coagulation factors used for a variety of indications is unquestioned. These products are manufactured on an industrial scale from identical plasma pools. Consequently, for several medicinal products a substantial part of the documentation necessary to apply for a marketing authorisation is identical.
The PMF concept was introduced into the European pharmaceutical legislation by Directive 2003/63/EC. It aims to provide marketing authorisation applicants and holders with the option to replace the dossier part on Information related to the starting and raw materials for all affected medicinal products with a PMF. In view of this, the objectives of the PMF concept are to reduce workload for manufacturers and competent authorities and to simplify the procedures throughout the lifecycle of plasma-derived medicinal products regarding the information related to the starting material. Furthermore, the PMF concept intends to ensure consistency throughout the EU without impairing public health.
A PMF compiled according to Directive 2003/63/EC covers the current state of scientific and technical knowledge with respect to the special quality and safety demands determined by the biological nature of the starting material. The stipulated ´two step´ assessment of the PMF certification system commences on Community level (EMEA) resulting in a certificate of compliance with Community legislation valid throughout the EU (first step). Subsequently, the certificate is recognised by the competent authorities on the level of national marketing authorisations (second step).
Considering the experience so far, the PMF concept provides several positive aspects to manufacturers. The single review approach is one of the main positive aspects also with respect to the fees due. Another noteworthy benefit is the possibility to refer to several PMFs, which is however connected to some constraints.
Nevertheless, certain issues of the PMF concept need to be reviewed. Main points to be reconsidered are the overall duration of the ´two step´ assessment as well as contract manufacturing and the mutual recognition of inspections and test kits.
Since the PMF concept only became part of the European Pharmaceutical legislation in the year 2003 first experience with respect to initial evaluation, variations and annual re-certification is currently in progress. Considering this, the upcoming years will show in how far the proposed objectives of the PMF concept will be translated into action.
Since the PMF concept only became part of the European Pharmaceutical legislation in the year 2003 first experience with respect to initial evaluation, variations and annual re-certification is currently in progress. Considering this, the upcoming years will show in how far the proposed objectives of the PMF concept will be translated into action.