FDA has launched a pilot program for inspection systems in routine GMP inspections. It focuses to an increased extent on the function of the Quality Unit as the key element of the company-internal compliance status. FDA is sending a clear signal here to the pharmaceutical industry that it expects a functioning Quality Unit (QU) which has all the necessary regulating mechanisms and which is also strong enough to prevent products of inferior quality from entering the market.

Why is FDA focusing so much on the QU?

Two trends were decisive for this. On the one hand FDA's experience that due to staff reductions and personnel fluctuation in the Quality Units knowledge about specific products and processes have been lost with the result that proper troubleshooting is no longer possible. On the other hand there is the knowledge that increasing defects in the detection of problems by Quality Units have actually occurred.

Whereas in the past the companies largely initiated their recalls themselves, this has changed during the past two years. Over 60% of the recalls took place only after an FDA inspection. The head of the Manufacturing and Product Quality department of the Office of Compliance, Joseph Famulare, urges that companies improve their quality assurance systems. For this reason FDA will in future perform targeted inspections of the Quality Units. Famulare recommended that the companies assure themselves by means of self-inspection that their Quality Units are functioning adequately.

In a guide for inspectors FDA describes the background, the implementation and the focal areas of inspection of the new system.

Whereas in the past inspections were product-oriented, the focus has now shifted to a general inspection. It is FDA's goal to reduce by means of this “new program” the extent and the depth of pre-approval inspections - depending on the experiences with the individual companies. FDA's evaluation of the companies is computer-assisted.

How are these new “system-related inspections” to be conducted?

They will take place according to a two-stage model. In Stage 1 the inspector evaluates whether the QU fulfills its responsibilities as regards the review procedures. In Stage 2 the documentation is evaluated in order to detect quality problems.

In this second stage the inspection will cover with respect to material systems in particular the handling of starting materials and finished products, container closure and every water and gas quality which enters the product or comes into contact with it. Other focal areas are the stocktaking and storekeeping and the distribution of medicinal products.

In the production area the focus will be on process validation. In the laboratory area FDA will concentrate on analytical tests and the development of stability programs. With respect to buildings and equipment the focus will be on maintenance, calibration, IQ and OQ. In the area of packaging/labeling the main focus will be on preventing intermixing and the handling of labels and on validation.

Stefanie Gray, former head of the Office of Compliance at FDA, has said of the new inspection system that it will enable the authority to react much more rapidly after the inspection and, since it gives a general view of the company as a whole, will also have a greater influence on marketing authorizations. As an example S. Gray mentioned a company that received its warning letter already one (!) week after the FDA inspection according to the new inspection system.

Would you like more practical information about the new FDA inspection system?

Richard M. Bonner, head of QA/QC at Eli Lilly, GB-Liverpool, will report at the Auditor Education Course on October 16/17, 2001 in Copenhagen  about his experiences with several inspections according to this new inspection system.

Are you looking for information about the defects most frequently complained about by FDA? The GOLD SHEET reports that the most frequent complaints in warning letters concern process validation and out-of-specification results (OOS).

Literature: The Gold Sheet, Vol. 35, No 4, April 2001

PS. For more information about Quality Units in comparison with quality assurance and quality control we highly recommend the article by Rudolf H. Völler, Pharm. Ind. 59, No. 3 , pp. 243 ff. (1997).