On October 31, 2024, FDA issued its final version of the ICH M13A guidance for industry, titled “M13A Bioequivalence for Immediate-Release Solid Oral Dosage Forms”. This guideline provides recommendations for conducting bioequivalence (BE) studies during development and post-approval phases for orally administered immediate-release (IR) solid oral dosage forms designed to deliver drugs to the systemic circulation, such as tablets, capsules, and granules/powders for oral suspension. The pharmacokinetic (PK) principles of this guideline are generally applicable to other orally and non-orally administered drug products in which reliance on systemic exposure measures is suitable for establishing BE, e.g., certain rectal, inhalation, and nasal drug products. Furthermore, FDA’s guidance covers BE studies for both new and generic drug products.
Efficiency in Global Drug Development
This harmonized guideline, which has been adopted by participating global regulatory authorities, including the US FDA, allows for the consistent adoption of these consensus-based guidelines by regulators around the globe and has contributed to improvements in the quality and efficiency of global drug development and manufacturing. Although selection of comparator products in different jurisdictions is usually governed by local laws rather than scientific guidelines, M13A includes study designs containing multiple comparator products to reduce the associated burden without affecting local requirements.
Two additional guidelines in this series are proposed to address biowaiver considerations for additional strengths (M13B) and data analysis and BE considerations for highly variable drugs, narrow therapeutic index drugs, and complex BE study designs.
Changes to Requirements for BE Studies
The main considerations and design concepts for BE studies remain the same as in previous guidance documents. The most significant change is the removal of the general requirement for both fasting and fed BE study for all products. For a majority of the products considered low risk, a single fasting BE study is now considered sufficient. The M13A guideline continues to recommend both fasting and fed BE studies for products that are considered high-risk where the drug substance characteristics in combination with the complexity of the formulation design or manufacturing process may lead to different in vivo performance between fasted and fed conditions.
In conjunction with the publication of this guideline, the FDA also published 814 draft Product-Specific Guidances (PSGs) for a subset of immediate-release oral drug products. The revised PSGs recommend that applicants submitting an Abbreviated New Drug Application (ANDA) conduct one BE study for non-high-risk products under either fasting or fed conditions, as appropriate, rather than conducting two BE studies, one BE under fasting conditions and one BE study under fed conditions.
ProPharma: Your Global Regulatory Affairs Partner
ProPharma assists Sponsors with all facets of branded and generic drug development. Armed with a breadth of scientific knowledge, we are proactive in helping our clients move their drug through the development process.
Even when there is no product-specific guidance for a generic drug being developed by one of our clients, we can still help. Thanks to in-depth experience, our team can work with that client to hopefully get them a meeting with the FDA to discuss what the process of demonstrating bioequivalence ought to be for their specific drug.
Contact us today to learn how our team of expert regulatory affairs consultants can help with the development of your generic drug.
