Making affordable generics more reliable

Generic drugs are crucial for addressing healthcare affordability in a population marked by significant income disparities. Bioequivalent to branded drugs, generics offer cost-effective alternatives. India leverages economies of scale and low production costs to supply affordable medication domestically and internationally.

With out-of-pocket healthcare expenditure at 39.4% of total health expenditure in 2021-22, generics reduce financial burdens and improve treatment adherence. By August 2024, generic medicines worth ₹5,600 crore sold through Pradhan Mantri Bhartiya Janaushadhi Pariyojana over a decade saved consumers an estimated ₹30,000 crore.

Ensuring the quality of generic medicines in India is vital to make them affordable and effective as innovator drugs. Despite being bioequivalent to brand-name drugs, quality control lapses have occasionally compromised their efficacy and safety.

A study by doctors of the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, published in Mycoses, investigated the efficacy of itraconazole in treating chronic pulmonary aspergillosis using the innovator drug and 22 generic formulations. The innovator itraconazole achieved therapeutic drug levels in 73% of patients within two weeks, compared to only 29% for generics, which often required 6–8 weeks, dose escalation, or switching to the innovator. Further, generic capsules had significant defects, including fewer and unevenly sized pellets, critical for optimal drug absorption and bioavailability.

But why do generic and innovator drugs differ in some cases despite being made from the same active ingredient? Generics can differ significantly in their excipients and manufacturing processes, leading to variability in therapeutic outcomes. First, differences in excipients — such as binders, fillers, disintegrants, and coatings — can alter a drug’s dissolution rate, stability, and delivery mechanism.

Second, manufacturing processes, including the type of punching machines, compression force, and granulation methods, can influence the drug’s physical and chemical properties. Variations in tablet hardness, particle size, and porosity can affect disintegration and absorption. In some cases, while an innovator drug is designed to release the API slowly to achieve a sustained therapeutic effect, generics may release the API more rapidly, potentially leading to fluctuations in drug levels.

Third, the limitations of bioequivalence thresholds contribute to the problem. Regulatory standards often allow pharmacokinetic parameters to fall within 80%–125% of the innovator drug’s range. These thresholds may be insufficient for medications with a narrow therapeutic index. Even minor deviations in drug release or bioavailability can lead to subtherapeutic effects or adverse reactions. Stability issues can also further undermine the drug’s shelf life and reliability.

The key issue lies in India’s decentralised drug regulation system, which grants significant authority to State Drug Regulatory Authorities (SDRAs), leading to inconsistent enforcement and quality standards. The Central Drugs Standard Control Organisation (CDSCO) can only recommend action, leaving States to act. Despite repeated calls for centralisation, crucial functions remain with States, enabling regulatory arbitrage as manufacturers exploit weaker oversight. India must centralise drug regulation, strengthen CDSCO with resources and personnel, and establish more central drug-testing labs to address this issue.

Another reason is the inadequate enforcement of stability testing to ensure drug efficacy under diverse climatic conditions. Stability testing, mandated by the CDSCO in 2018, requires manufacturers to demonstrate that drugs maintain their quality, strength, and identity under specified conditions. However, inconsistent implementation by State licensing authorities and the absence of clear, centralised guidelines undermine compliance. Moreover, the lack of retrospective applicability to generics approved before 2018 perpetuates the presence of substandard drugs in the market. India must enforce uniform stability testing protocols, ensure centralised regulatory oversight, and mandate periodic reassessment of all approved generics to build confidence in drug quality.

Thirdly, India’s Pharmacopoeia permits higher drug impurity levels than U.S. and EU standards. The Pharmacopoeia Commission (PC) and CDSCO rejected stricter ICH guidelines as “too expensive”. Thus, these standards should be made a bit more stringent. In that case, action needs to be taken at the level of PC, CDCSO, and Centre.

Centralising drug regulation will only be effective with a comprehensive overhaul of the CDSCO. It must be reorganised to deliver robust regulatory safeguards, protecting patients from the dangers of substandard and counterfeit medicines through stringent regulatory protocols and effective inspection and enforcement mechanisms.

We must champion generics — they are indispensable for ensuring equitable access to medicines. But, equity cannot come at the expense of quality. States must relinquish their fragmented control over drug regulation, which has long undermined public confidence in generics. It is time to act on the decades-old recommendations of the Bhatia (1954), Hathi (1975), and Mashelkar (2003) committees, all of which have called for centralised oversight.

Aditya Sinha is a public policy professional. Views are personal