Bioequivalence requirements for generic medicine registration with Kenya PPB

Kenya's Pharmacy and Poisons Board requires bioequivalence data for generic medicines where the active substance is not considered high-solubility and high-permeability across the physiological pH range, or where the drug product is not a simple aqueous solution intended for intravenous administration. For oral solid dosage forms such as tablets and capsules, most generic applications require either a clinical bioequivalence study or a scientifically justified waiver.

The PPB follows the WHO guidance on bioequivalence studies and biowaivers, which aligns closely with the EMA and US FDA frameworks. Reference products must be the innovator product or, where the innovator is not available in Kenya, a product that can be demonstrated to be bioequivalent to it. The reference product used in the study must be the same as the proposed comparator identified in the dossier, and the batch used in the study must fall within its shelf life at the time of testing. Deviations from these requirements are among the most common grounds for rejection of bioequivalence data packages.

For combination products, specifically fixed-dose combinations, the bioequivalence strategy is more complex. The PPB generally requires that each component of the combination be evaluated, and where interaction between components affects absorption, the combination itself must be tested. Teams planning combination product registrations should seek regulatory scientific advice from the PPB before initiating studies, as the study design requirements may not be fully addressed by standard guidance documents.

The Biopharmaceutics Classification System provides a framework for waiving in vivo bioequivalence studies for orally administered solid dosage forms where the drug substance meets specific solubility and permeability criteria. The PPB accepts BCS-based biowaivers for Class I drugs, those with high solubility and high permeability, provided the drug product also dissolves rapidly (85% in 30 minutes) in all three compendial buffers and does not contain excipients that could affect gastrointestinal motility or absorption.

For Class III drugs, those with high solubility and low permeability, BCS-based biowaivers are also possible under WHO guidance, subject to additional conditions including that the formulation is very rapidly dissolving and qualitatively and quantitatively very similar to the reference product. This applies to a limited number of active substances and requires careful justification. The PPB expects this justification to include solubility data across the physiological pH range, validated dissolution data from the proposed product and the reference product in the same media, and a literature or experimental basis for the permeability classification.

What is frequently missing from biowaiver packages submitted to the PPB is the dissolution comparison data. Presenting only the solubility and permeability data without comparative dissolution profiles, or presenting profiles from a different formulation than the one being registered, is a guaranteed query trigger. The dissolution data must be from the proposed commercial formulation in final packaging, using the validated method described in the finished product specification.

Bioequivalence study reports are placed in CTD Module 5.3.1. The full study report must conform to the ICH E3 format and include the protocol, statistical analysis plan, data listings, individual subject pharmacokinetic parameters, and the bioequivalence conclusion. The 90% confidence intervals for Cmax and AUC must be stated explicitly and must fall within the 80.00–125.00% acceptance range unless a pre-approved wider range was negotiated.

The QOS section 2.7.1 must summarise the bioequivalence study design and results at a level of detail that allows the evaluator to confirm the conclusion without returning to the full study report. This includes the study design, reference product details, statistical method, results for both primary and secondary endpoints, and the bioequivalence conclusion. Discrepancies between the QOS summary and the full study report in Module 5, for example different reported confidence interval values or differing descriptions of the reference product, are a reliable source of queries.

For teams managing bioequivalence data across multiple markets, the challenge is often that the same study is submitted in slightly different formats, against different reference products, or with different statistical presentations to meet the requirements of different authorities. The PPB version of the submission must be fully internally consistent, regardless of how the same data appears in an EMA or ANVISA filing. This requires that the Module 5 study report, the Module 2.7 clinical overview, and the QOS are aligned to the same study version and the same reference product details for each authority submission.