Masterstudiengang "Drug Regulatory Affairs"
Master-Thesis
ICH Q8: Pharmaceutical Development. Regulatory Requirements Directed by the New Note for Guidance (EMEA/CHMP/167068/2004) in Comparison to the Previous Guideline (CPMP/QWP/155/96). A Critical View from the Generic Pharmaceutical Industry. ***
Dr. Joachim Ahlert (Abschlußjahr: 2007)
Language: English
In November 2005 the new guideline ICH Q8 Pharmaceutical Development was finalised and came into operation in the tripartite regions, e.g. in Europe as a Note for Guidance, EMEA/CHMP/167068/2004 in May 2006.
On the first glance this guideline is the current successor of the already existing European guideline Development Pharmaceutics, CPMP/QWP/155/96 from January 1998. But since no indication can be found that the new guideline eventually replaces the previous one, it must therefore be regarded that both guideline are in operation and applicable in Europe.
ICH Q8 is the reflection of an increased knowledge in pharmaceutical science in all ICH regions. The applicant is invited to give better insight into his developmental studies, which result in the formulation and production process as intended for the market. Therefore, ICH Q8 provides the opportunity to combine the pharmaceutical development studies with quality risk management tools and quality systems as outlined in ICH Q9 and Q10.
The comparison of both guidelines makes evident that many analogue requirements exist. On the other side the new guideline is less focused on detailed guidance, e.g. by requirements for specific dosage forms. These are now no longer regarded in detail in the current guideline.
The main innovation of the new guideline is the opportunity of the design space. This is defined as the multidimensional combination of input variables and process parameters, which shall demonstrate the assurance of quality. The basis for the design space is the gained knowledge from pharmaceutical development studies and manufacturing experience provided by the applicant and approved in each case by the authorities. This information shall demonstrate that a product and manufacturing process of appropriate quality have been developed with regard to the intended performance of the product.
Beyond a baseline expectation of information ICH Q8 leaves more responsibility to the applicant to acquire and compile critical input and process attributes of the product and the adequate control of these. Different quality aspects like drug substance, excipients, manufacturing process improvement or different container closure systems can be included. The more knowledge can be gained, the more this will provide the desired flexibility of a design space, which can result in the opportunity to reduce the need of post-approval variations.
The question comes up why the previous guideline remains in operation. Is the new guideline with the provision of the design space not sufficient? A clear answer has not been provided by the EMEA, but it is no disadvantage for industry and regulators to have both guidelines in operation. Even more, the positive response to ICH Q8 on both sides is encouraging further expansion, and an ICH working group is developing annexes e.g. on special dosage forms in the future. This implies that the whole subject of ICH Q8 has not been finished yet but is rather an ongoing process. Once these annexes come into operation, the ICH Q8 complex might eventually replace the previous guideline.
The generic pharmaceutical industry faces different challenges than the originator, also during the pharmaceutical development. The new guideline does not distinguish between both. However, the generic focus is more directed to the selection of the drug components, i.e. the active substance sources and different excipients. Besides the formulation development especially the manufacturing process development is of major focus for the generic applicant. Due to economic competition, the availability and replacement of any component sources of the drug product as well as the manufacturing process improvement and optimisation are the main challenges during the life cycle management of any generic product. An increased scientific knowledge gained by development studies e.g. on different used API and excipient sources or grades or packaging materials, can provide a good opportunity to broaden the design space. These studies make most sense during the development phase but less after market entry since any additional data (e.g. to provide or extend the design space) will result in a post-approval variation, usually a type II.
For the time being, the experience on the amount of necessary developmental studies, the application and evaluation of the design space is still low on both sides, authorities and industry. The near future will show how both parties can maintain this desirable approach. Nevertheless, the regulatory framework for this purpose has now already been provided by ICH Q8 and this is a chance also for the generic industry.
Pages: 51