The US Food and Drug Administration (FDA) has adopted and released a new guidance document intended to clarify the International Conference on Harmonisation's (ICH) Q4B guideline on the use of pharmacopoeial texts.
ICH is a regional harmonization group composed of the US, EU and Japan, as well as other countries which serve in a voluntary capacity.
The aim of the group is to allow the regulatory processes of each to better align with those of the others, thereby allowing greater efficiencies for industry. This is perhaps best exemplified by the common technical document, which permits a company to submit a pharmaceutical dossier to all three countries with only minimal changes to a single module of the submission format to account for minor regional differences.
That standardization process, however, goes far beyond just submission formats, extending as well to certain supporting texts, such as the regional pharmacopoeias of the ICH regions.
On 13 June 2014, FDA announced the release of an ICH document, Q4BEvaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on Harmonisation Regions; Annex 6: Uniformity of Dosage Units General Chapter (Q4B Annex 6).
Like other Annex documents in the Q4B series, the text is intended to clarify which pharmacopoeial texts on the uniformity of dosage units are equivalent between regions, and whether conditions apply to their use in certain regions.
As the document explains, ICH has deemed three texts mostly interchangeable:
- Europe: Ph. Eur. 2.9.40. Uniformity of Dosage Units
- Japan: JP 6.02 Uniformity of Dosage Units
- United Stated: USP General Chapter <905> Uniformity of Dosage Units
However, those texts are subject to some limitations:
- (2.1.1) Unless the 25 milligrams (mg)/25% threshold limit is met, the use of the Mass/Weight Variation test as an alternative test for Content Uniformity is not considered interchangeable in all ICH regions. (US)
- (2.1.2) For specific dosage forms that appear in local text in the pharmacopoeias by enclosing the text in black diamond symbols, application of the Uniformity of Dosage Units test is not considered interchangeable in all ICH regions.
- (2.1.3) If a correction factor is called for when different procedures are used for assay of the preparation and for the Content Uniformity Test, the correction factor should be specified and justified in the application dossier.
FDA explained that it may request that companies demonstrate "that the chosen method is acceptable and suitable for a specific material or products, irrespective of the origin of the method," and that it will not accept the first limitation (listed above) as suitable "for regulatory purposes."
Q4BEvaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on Harmonisation Regions; Annex 6: Uniformity of Dosage Units General Chapter (FR)