ICH M9 Guideline on BCS-based Biowaivers

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

The International Council for Harmonization, ICH, published the draft of ICH M9 for comment. The multidisciplinary M9 Guideline is proposed to address Biopharmaceutics Classification System (BCS)-based biowaivers. This topic was endorsed by the ICH Management Committee in October 2016. The M9 draft Guideline is available for download on ICH´s Multidisciplinary Guidelines page. Stakeholders from ICH Regions are encouraged to submit their comments to their respective Regulatory Authorities (please see the M9 accordeon for each Regulatory region's commenting period).

According to the BCS drug substances are usually classified to four classes upon their solubility and permeability:

Class I - high permeability, high solubility
Class II - high permeability, low solubility
Class III - low permeability, high solubility
Class IV - low permeability, low solubility

BCS-based biowaivers may be applicable to BCS Class I and III drugs. However BCS-based biowaivers for these two classes are not recognized worldwide. This means that pharmaceutical companies have to follow different approaches in the different regions. The ICH M9 guideline will therefore provide recommendations to support the biopharmaceutics classification of medicinal products and will provide recommendations to support the waiver of bioequivalence studies. "This will result in the harmonization of current regional guidelines/guidance and support streamlined global drug development" ICH says.

In Addition, end of 2013 the European Medicines Agency, EMA, started to replace the general guidelines for conducting bioavailability/bioequivalence studies step by step through product or API specific guidelines. Further product specific information was published just recently.

Furthermore, the United States Pharmacopeia (USP) recently proposed additional changes to general chapter <1090> Assessment of Drug Product Performance—Bioavailability, Bioequivalence, and Dissolution. The current official USP chapter contains a compilation of resource documents available from the U.S. Food and Drug Administration (FDA) and the World Health Organization (WHO) along with the source information. The PF 42(4) proposal included incorporation of definitions, biowaiver approaches, and reference sources from the EMA. According to the comments received there are a number of issues within the revised chapter including concerns associated with two new FDA draft guidances issued in 2015:

• Dissolution Testing and Specification Criteria for Immediate-Release Solid Oral Dosage Forms Containing Biopharmaceutics Classification System Class 1 and 3 Drugs,
• Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System.

Therefore, the USP has decided to present a new proposal to <1090> once more in PF.