The US Food and Drug Administration (FDA) has released a new guidance from the International Conference on Harmonization (ICH), an international pharmaceutical regulatory harmonization group, focused on testing products for the presence of bacterial endotoxins.
The ICH is a regional harmonization group composed of the US, EU and Japan, with other countries, such as Canada, participating 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 also extends to certain supporting texts, such as the regional pharmacopoeias of the ICH regions. One of ICH's related guidelines for pharmacopoeia standards harmonization, Q4B: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions, is actually a set of many guidelines, including the latest, Annex 14: Bacterial Endotoxins Test General Chapter.
The concept of the annexes is relatively straightforward: align pharmacopoeial texts among ICH's three main regions to make it easier for companies to adhere to standards across borders.
Annex 14: Bacterial Endotoxin Testing
For bacterial endotoxin testing, that means meeting the European Pharmacopoeia's (Ph. Eur.) 2.6.14 Bacterial Endotoxins, the Japanese Pharmacopoeia's (JP) 4.01 Bacterial Endotoxins Test, and the US Pharmacopoeia's (USP) General Chapter <85> Bacterial Endotoxins Test.
ICH's annex says that any of the three pharmacopoeial standards may be used interchangeably throughout the US, EU and Japan provided the following two conditions are met:
- Any of the three techniques can be used for the test. In the event of doubt or dispute, the gel-clot limit test should be used to make the final decision on compliance for the product being tested.
- In the section Photometric quantitative techniques, Preparatory testing, Test for interfering factors, the user should perform the test on solutions A, B, C, and D on at least two replicates using the optimal conditions as recommended by the lysate manufacturer.
Per FDA's new guidance, this means that manufacturers seeking to rely on endotoxin data for an application may submit testing that complies with any of the three standards. However, regulators cautioned that they "might request that a company demonstrate that the chosen method is acceptable and suitable for a specific material or products, irrespective of the origin of the method."
The final guidance was published on 11 October 2013.
Annex 14: Bacterial Endotoxins Test General Chapter