To the oft-used terms in the debate on medicine quality — good manufacturing practices (GMP) and Revised Schedule M — we must now add bioavailability and bioequivalence.
Bioavailability (BA) refers to the quantum of administered drug that reaches the bloodstream in a form that can produce a therapeutic effect. The formulation of a medicine determines how much of the active ingredient reaches blood circulation and how fast.
When two formulations of the same drug have a similar BA, they are considered bioequivalent (BE). A generic drug has bioequivalence with the innovator product if the BA matches.
BE is assessed through in vivo studies, where healthy volunteers receive both the innovator and generic formulations, and blood drug concentrations are compared over time. These studies mainly involve oral solid dosages, where formulation differences between manufacturers can affect bioavailability.
Under the internationally accepted Biopharmaceutics Classification System (BCS), immediate-release oral drugs fall into four classes based on solubility in gut fluids and permeability across gut wall. Many countries waive in vivo BE studies for high-solubility drugs, relying instead on laboratory dissolution tests. Low-solubility classes of drugs, however, generally require in vivo confirmation of BE in addition to routine quality testing.
Indian exports to well-regulated countries also comply with BE testing requirements. India historically did not mandate BE studies for drugs manufactured for domestic use. But on April 3, 2017, the government amended the law to mandate BE studies for low-solubility oral drugs, broadly aligning with global norms.
The mandate has not been enforced yet, but in September 2025 the Central Drugs Standard Control Organisation (CDSCO) signalled its intent to do so; this will substantially raise the cost of producing low-solubility oral drugs.
A BE study costs ₹20–80 lakh per product; failed formulations would need to be refined and put through repeat studies until BE is demonstrated. Given the large number of manufacturers, each producing multiple drugs, the testing burden will be massive.
It remains unclear whether BE requirements will apply to all products with existing marketing approval or only “new drugs”, as defined under current regulations. If mandated for all marketed products, then the consequences for pricing and availability could be severe. A large share of India’s essential oral formulations —including commonly used medicines like amoxicillin, rifampicin, hydrochlorothiazide, glimepiride, glipizide, and ibuprofen — is produced by micro, small and medium enterprises (MSMEs). They form the backbone of India’s identity as the ‘pharmacy of the developing world’. Many of them may find the mandatory BE testing unaffordable, leading to closures, consolidation, or significant transfer of cost burden to consumers — along with substantial job losses. Prices of widely used medicines could rise sharply. Also, testing capacity would need to be rapidly expanded, even as regulatory workload would increase greatly.
The challenge is multidimensional — technical, ethical, legal, economic, and political. Technological innovations may reduce BE costs, but not immediately. Limiting mandatory BE studies to new drugs could buy time, as could phased implementation until India has adequate testing infrastructure.
However, our goal must be parity in BA/BE compliance for exports and domestic products. The government could support BE studies, incentivising manufacturers who achieve BE on first attempt. This encourages drug quality without overwhelming MSMEs with compliance costs. Practical, balanced solutions are essential. Quality and affordability must go together.
[The writers are affiliated with Low Cost Standard Therapeutics (LOCOST), Vadodara. Views are personal]
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Published on December 29, 2025