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
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:
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
- 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
- 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.
On behalf of the European Compliance Academy (ECA)