After the Office of New Drug Quality Assessment (ONDQA) within the Center for Drug Evaluation and Research (CDER) of FDA had published a very interesting document as early as February 2007, but had withdrawn it soon afterwards (MAPP - Manual of Policies and Procedures 5310.7; see our GMP News of 9 May 2007), the document now came into force again on 3 November 2007!

This document is of great interest to all those in the pharmaceutical industry who are involved in regulatory affairs or the inspection of incoming goods.

The back story was that, when applying for a marketing authorisation in the US, it is not unusual for registrants to suggest monographs of the British Pharmacopoeia (BP), the European Pharmacopoeia (EP) or the Japanese Pharmacopoeia (JP) as quality standards (monographs) for active pharmaceutical ingredients or excipients. However, since the US Pharmacopoeia (USP/NF) represents the official compendium in the US, the FDA reviewers had been very reluctant to recognise BP, EP or JP standards and methods as part of the application, even if a monograph from these pharmacopoeias was equivalent or superior to a USP/NF monograph. And in the past, FDA reviewers also gave different advice on this topic.

The now published FDA document MAPP (Manual of Policies and Procedures) 5310.7 of 3 November 2007 says among others:

It is reasonable to accept an applicant’s proposal to use a quality standard from the BP, EP, or JP as part of the specifications for an excipient, drug substance, or drug product in the drug application, if the standard in the BP, EP, or JP is equivalent to or better than the corresponding standard in the USP/NF.

Equivalent standards have the same acceptance criteria and make use of analytical procedures based on similar principles (e.g., chromatographic, spectroscopic, titration) and performance characteristics (e.g., specificity, accuracy, precision). A standard can be considered better than a corresponding standard for a number of reasons, including narrower ranges for acceptance criteria or superior performance of the analytical procedure (e.g, improved specificity, greater accuracy).

These regulations concern the CMC evaluation of applications for marketing authorisations of medicinal products conducted by CDER/OPS/Office of New Drug Quality Assessment.

The FDA writes that it does not intend to establish BP, EP and/or JP as official compendia in addition to or as a replacement for the USP.

This new flexibility of the American registration and supervisory authority represents a surprising and independent step towards harmonisation and will be greatly welcomed by the pharmaceutical industry.

The complete text of the FDA document MASPP 5310.7 can be found here:
http://www.fda.gov/cder/mapp/5310.7R.pdf

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