Masterstudiengang "Drug Regulatory Affairs"


CMC - Variation in a Globally Operating Pharmaceutical Company ***

Veronika Etges (Abschlußjahr: 2003)

The paper starts with the Quality Assurance System, its legal background, the basic principles and describes a model of a Change Control Procedure as it could be operated in a multinational company. Besides the procedure the responsibilities of the participants in the procedure are detailed. Considerations of building up a suitable Change Control Team in the individual situation beyond the core members are explained. Differences in procedure when more than one site is affected by the change, for example in a Mother / Daughter Plant Change Control Procedure or in a production transfer situation, are depicted.

The second part of the paper deals with the regulatory procedures to follow in case of a change with impact on the regulatory status of a product.

It describes the basic principles of the systems and compares the regions / countries European Union, USA and Japan as well as the national systems in the member states of the European Union, the European Economic Area (EEA) and EFTA. An outline of the European variation system is given. Experiences with different handling of variation procedures in the mutual recognition procedure by the member states are reported. The specific issues of timing of variation applications and the relation to other regulatory procedures like registration renewals, start of second wave mutual recognition procedures for the same product and pending variations are discussed.

With the example of a multinational company it is shown that the national variation procedures still represent the majority of the variation procedures to be conducted. An overview on the national variation procedures in the European countries, its peculiarities and deviating requirements is given.

As among the member states of the European Union as far as the nationally approved products are concerned, also on the ICH level a common position of the three ICH regions / countries European Union, USA and Japan on how to deal with the follow up procedures does not exist.

The variation systems of the countries outside the ICH regions are briefly described, mainly on the basis of company experiences and data collections built up in the company as there is little officially published information in English available on the procedures in the developing countries.

In two case studies the conduct of a Change Control Procedure for a product is described with examples of a production transfer and the replacement of an excipient in an ointment.

The legal and practical issues of implementing a change when managing a variation affecting the markets worldwide are highlighted. The issue of the obligation to comply with the registration versus the wide range of timelines for approval of the variations worldwide is discussed.

Regarding the current situation characterized by a high degree of regulations of the change of products that differ from country to country or region the variation of existing products is a resource intensive, costly and time-consuming activity in a globally operating pharmaceutical company. As the attention in a big company is focused first of all on the development products, there is always a competition to be observed for the resources assigned to the new products and those spent on the maintenance of the existing ones. This is true even if the significance of the existing products for the commercial success of a company and the contribution of these products to the financial basis for research and development cannot be doubted. With the Clinical Trials Directive becoming effective in 2004 requiring a pharmaceutical- chemical dossier for approval of clinical trials in the member states of the European Union it is to be expected that variations to the chemical-pharmaceutical documentation will gain significance also for products under development.

Pages: 54