A new FDA Draft Guidance for Industry with the title The Use of Mechanical Calibration of Dissolution Apparatus 1 and 2 - Current Good Manufacturing Practice (cGMP) of October 2007 is directed at manufacturers of medicinal products and related contract laboratories. The guideline was created at the Center for Drug Evaluation and Research (CDER) within the FDA.

It is the aim of this guidance to support manufacturers of medicinal products in replacing the use of "calibration tablets" with "mechanical calibration" when calibrating apparatuses used for dissolution testing.

Since 1978, chemical calibration has been the predominating calibration procedure, among other reasons because it is required by USP General Chapter <711>. Usually, every six months a chemical calibration is conducted in addition to the mechanical calibration.

The FDA Guidance describes in detail the history of the different standard tablets.

What is remarkable is the FDA statement that the use of USP calibration tablets can lead to variability in the dissolution measurement system. The USP 10-mg prednisone tablet in use today is not as stable as its predecessors. Over time, lower dissolution results are obtained with the paddle method and higher ones, with the basket method.

The text lists a whole range of other difficulties encountered when using USP calibrator tablets.

The conclusion of the FDA guidance is really interesting: Since the variability of the USP tablets makes it difficult for the chemical calibration to assess the calibration of apparatuses for dissolution testing, the FDA wants to give supporting advice on the use of mechanical calibration as an alternate approach.

The FDA concretely suggests an alternative procedure, which can be found on the FDA website, and even permits firms to use other methods - instead of the calibrator tablets!

Finally, the FDA expressly emphasises that an "appropriately rigorous mechanical calibration method properly executed will satisfy the CGMP requirement for dissolution apparatus calibration under § 211.160(b)(4)".

It is really astonishing that, in this matter, the FDA openly contradicts the USP with this document. This FDA document is still only a draft. However, the FDA's proposal will certainly meet with broad approval among the industry!

The complete document can be found here:
http://www.fda.gov/cder/guidance/7232dft.pdf

And the document Mechanical Qualification of Dissolution Apparatus 1 and 2 by the FDA Division of Pharmaceutical Analysis is available here:
http://www.fda.gov/cder/Offices/OTR/dissolution.pdf


Author:
Dr Günter Brendelberger
On behalf of the European Compliance Academy