What does the FDA expect? What is the state of the art? In which direction does the FDA move? These and similar questions are asked time and again in the pharmaceutical industry. One of the answers is: The FDA expects the implementation of the GMP guidelines (21 CFR 210/211). Another answer can e. g. be found in the FDA guidances for industry. Even though they are not legally binding, they represent FDA's "current thinking". And where is the FDA headed? To answer this question, one can consult different sources. Among them are the documents called "white papers", which describe future developments, as well as FDA's reports.

Many know the Initiative "cGMPs for the 21st Century: A Risk-Based Approach". This report was published in 2004. Since then, one has not heard much about it from the FDA. Still, the FDA published an "Update Report" in 2007, which is not well known even among insiders.

You can find this report at: http://www.fda.gov/oc/cgmp/report0507.html.

The 2007 report describes the changes since the first report on the FDA initiative "cGMPs for the 21st Century" published in 2004. Besides, it is meant to show that the topic is still up to date and therefore being pursued. In principle, the FDA initiative concentrates on 5 points:

• Reinforced introduction of new technologies in the pharmaceutical industry
• Facilitated integration of modern quality management techniques into all areas of the pharmaceutical industry
• Implementation of risk-based approaches in order to concentrate on essential issues in the industry AND in the FDA
• Ensuring that regulatory activities (review, compliance, inspections) are conducted according to the pharmaceutical "state of the art"
• Improving consistency and co-ordination of the FDA "Drug Quality Regulatory Program"

The 8-page overview then addresses activities in connection with the FDA initiative. First it deals with the topic of communication. Here the text lists workshops held between 2005 and 2007, but also draft guidances. The paragraph on Quality Management Systems describes internal and external activities. It explains different systems that have been developed or implemented (e. g. CMC Review). A separate paragraph is dedicated to international co-operations, among others the participation in the ICH and potential PIC/S membership. Another section describes the FDA's PAT activities. Interestingly, the text expressly points out a PAT Committee founded recently by the ASTM. What is also mentioned is the establishment of a Pharmaceutical Inspectorate within ORA as well as the scientific collaboration with universities and the introduction of "standards" for the acceleration of procedures. A detailed statement is given on Quality by Design.

The remaining 14 pages encompass 20 appendices giving further insight, e. g. into the respective working groups.


A particularly interesting feature is Appendix 19 "Quality by Design Graphic".

This leads us back to the starting point of the question: "What is to be expected in the future?" One could express it in the catchy phrase: "Everything is Quality by Design." The FDA considers "Quality by Design" to be playing a pivotal role in drug manufacture. It results in the corresponding designs for the process and the product accompanied by a suitable control strategy with the objective to maintain process understanding and product knowledge. And all of this is intended to be continually improved. Here, we can see a direct reference to the methods coming from the field of six sigma. One possible method for controlling and understanding a process could e. g. be statistical process control (SPC).

The FDA will adhere to the adopted path, i. e. go in the direction of Quality by Design and Quality Risk Management. This is also shown by the current US discussions on the FDA Foreign Inspection Program. FDA Commissioner Andrew C. von Eschenbach stressed the fact that a reaction to the new complex structure of the pharma supply chain must be based on a risk-based inspection practice.

Author:
Sven Pommeranz
On behalf of the European Compliance Academy (ECA)