Rockville, MD (Feb. 26)—The US Food and Drug Administration has stated its considerations in regard to the three draft annexes to the International Conference on Harmonization’s Q4B document "Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions." The draft annexes were published in late 2008 and resulted from the Q4B processes for uniformity of dosage units, dissolution tests, and sterility tests.

The draft annexes state that the pharmacopoeial texts for each individual processes (i.e., dosage units, dissolution tests, and sterility tests) from the United States Pharmacopeia, Japanese Pharmacopoeia, and the European Pharmacopoeia can be considered interchangeable. FDA, however, “might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or product, irrespective of the origin of the method.”

In regard to uniformity of dosage units, FDA states in draft Q4B Annex 6 that it “finds unsuitable for regulatory purposes not more than (NMT) 2% relative standard deviation (RSD) exception to the 25 mg/25% threshold. Accordingly, for those items below the 25 mg/25% threshold, testing by content uniformity should be performed.”

FDA comments on Annex 7, addressing dissolution tests, state “An appropriately rigorous mechanical calibration method (such as ASTM International’s ASTM E2503-07, Standard Practice for Qualification of Basket and Paddle Dissolution Apparatus, or the procedures for Mechanical Qualification of Dissolution Apparatus 1 and 2, DPA-LOP.002, on the FDA website), when properly executed, will satisfy the current good manufacturing practice (CGMP) requirement for dissolution apparatus calibration under 211.160(b)(4) of Title 21 of the Code of Federal Regulations.”

The draft annexes can be downloaded here:

Annex 6: Uniformity of Dosage Units General Chapter. Comments are due April 20.

Annex 7: Dissolution Test General Chapter. Comments are due April 12.

Annex 8: Sterility Test General Chapter. Comments are due April 20.