Masterstudiengang "Drug Regulatory Affairs"


Addition of a manufacturing site for a sterile medicinal product (lyophilisate) - Points to consider for transfer of manufacturing process to a contract manufacturer and impact of changes with regard to the registration dossier in the light of the current variation procedure ***

Dr. Christina Veiel-Fietzek (Abschlußjahr: 2009)

Language: English

Nowadays, pharmaceutical companies are faced with the need to outsource the manufacture of their products for a variety of reasons and outsourcing the production of pharmaceutical products is today an important aspect of the manufacturing strategy. Thus strategic outsourcing allows pharmaceutical companies for instance to access needed technologies, reduce costs and improve flexibility. When outsourcing products it is important to select the most suitable contract manufacturer (CMO) based on a rationale decision analysis with preset and weighted selection criteria.

Deciding to implement a second source for product manufacture, the effective management of the CMO/sponsor relationship is critical not only in satisfying regulatory requirements with strict requests concerning quality control and manufacture, but also in meeting the overall commercial aim of the project and the given timelines.

This is especially true for sterile drug products where special requirements apply for this critical drug product, usually manufactured by complex manufacturing processes. The technology transfer of a sterile drug product will therefore play a crucial role for the success of the project and the long-term partnership between sponsor and CMO. Key deciding factors have to be elaborated and listed prior to transferring a technology process to a contract manufacturer. In particular for sterile drug products certain essential prerequisites have to be met and should be controlled and qualified by the pharmaceutical company in advance. Control of aseptic filtration and clean areas, simulation of the manufacturing process and validation of the sterilisation processes are only a few aspects that should be qualified with special care in the view of contract manufacturing. Consideration of legal and regulatory aspects at any time during the cooperation is mandatory and GMP requirements as well as validated processes and methods should be implemented and established.

The addition of a new manufacturer for the finished drug product always implies the change of the Marketing Authorisation and will result in a variation submission to the competent authority. Different sections of the registration dossier might be affected by the change in manufacturer and will be subject of an update of the documentation in order to support the change and variation application with adequate documentation. For updating and revising the registered chemical-pharmaceutical documentation, the current regulation and regulatory guidelines will have to be followed for processing a variation procedure. To date and depending on the nature of the Marketing Authorisation (national or European) the variation procedure may differ within the several European member states since there is - until now - no harmonised variation system in place. Yet, the regulatory agencies and the industry are currently facing a revision in the variation system and the major regulation has already been revised with the new “Variation Regulation” CR (EC) No. 1234/2008 applying from January 1st, 2010.

In summary it can be stated, that although the addition of an alternative manufacturer seems to be uncomplicated, since the technology process is supposed to be already well-known and validated, such a transfer must be seen from a different angle and with more detailed care in terms of sterile drug products. Sterile drug products are assessed as critical products with regard to their manufacture and all critical transfer steps require a risk-based examination by the pharmaceutical company. Hence, such a change has an extensive impact on the technology transfer management but also on the related variation of the Marketing Authorisation that should always be considered in advance by the pharmaceutical company and involved in-house departments when planning such a change. Last but not least, the current regulations are constantly under revision by the competent commissions and organisations and should therefore be in the focus of the project leader at any time.

Pages: 102,
Annexes: 3, pages: 13