Generic drugs are vital for improving healthcare affordability in India, addressing significant income disparities. However, maintaining their quality and efficacy remains a critical challenge.

• When a new drug is developed, it is protected by a 20-year patent.
• This allows the innovator company to recover its research and development (R&D) costs through exclusive sales during the patent period.
• Generic drugs are bioequivalent to branded or innovator drugs, meaning they have the same active ingredients, dosage form, strength, and route of administration as the original.
• Generics are sold under their chemical name rather than a brand name.

Differences Between Generics and Branded Drugs

• Generic drugs may use different binders (to hold ingredients together) and fillers (to add bulk or improve stability).
• Generic manufacturers do not bear the high expenses associated with new drug development or extensive clinical trials, making generics significantly cheaper.

Impact of Generic Drugs

• The lower cost of generics makes them more accessible, ensuring affordable healthcare for patients.                          
• 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.                  
• By offering cost-effective alternatives, generics play a crucial role in improving treatment adherence and reducing healthcare expenditure.                  
• With out-of-pocket healthcare expenditure at 39.4% of total health expenditure in 2021-22, generics reduce financial burdens and improve treatment adherence. 

Challenges Associated with Generic Medicines  

• Quality Control Lapses: Although generics are meant to be bioequivalent to branded drugs, there are instances where the quality doesn’t meet the expected standards, leading to concerns about their safety and efficacy.
• A study by doctors from PGIMER, Chandigarh, highlighted this issue. 
• When treating chronic pulmonary aspergillosis with the antifungal drug itraconazole, the innovator (branded) drug achieved therapeutic drug levels in 73% of patients within two weeks. 
• In contrast, generics reached the same therapeutic levels in only 29% of patients, often requiring longer treatment durations or higher doses to achieve similar outcomes. 

Reasons for Generic Drug Variability

• Differences in Excipients: Variations in excipients—such as binders, fillers, disintegrants, and coatings—can significantly alter a drug’s dissolution rate, stability, and delivery mechanism.
• Variations in Manufacturing Processes: Differences in 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, porosity can affect the drug’s disintegration and absorption in the bloodstream. 

• In some cases, while innovator drugs are designed to release the active pharmaceutical ingredient (API) slowly to provide a sustained therapeutic effect, generics may release the API more rapidly, which could lead to fluctuations in drug levels.
• Bioequivalence Threshold Limitations: Regulatory standards often allow pharmacokinetic parameters to fall within an 80%-125% range of the innovator drug’s performance. 
• These thresholds may not be sufficient for drugs with a narrow therapeutic index. 
• Even minor deviations in drug release or bioavailability can result in subtherapeutic effects or adverse reactions.
• Issues with Testing and Drug Formulation : Inconsistent stability testing and variations in drug formulation can undermine the shelf life and reliability of generic drugs, further contributing to variability in their performance and effectiveness.

Key Issues in India’s Drug Regulation System

• Decentralised Drug Regulation: India’s decentralised regulatory system grants significant authority to State Drug Regulatory Authorities (SDRAs), leading to:
• Inconsistent enforcement: Variability in quality standards.
• Regulatory arbitrage: Manufacturers exploit weaker oversight in certain states.
• Inadequate Stability Testing: Stability testing ensures that drugs maintain their quality under diverse climatic conditions. 
• Mandated by the Central Drugs Standard Control Organisation (CDSCO) in 2018, inconsistent implementation and lack of retrospective applicability to pre-2018 generics perpetuate the presence of substandard drugs.
• Permissive Drug Impurity Standards: India’s pharmacopoeia permits higher impurity levels compared to U.S. and EU standards. 
• The rejection of stricter ICH guidelines as “too expensive” compromises the overall quality of generic drugs.

Road ahead

• Centralisation of Drug Regulation:
• States should relinquish control over drug regulation, transferring this responsibility to the CDSCO for uniform enforcement of quality standards across the country.
• The Bhatia (1954), Hathi (1975), and Mashelkar (2003) committees have long advocated for centralisation, and their recommendations must be implemented without delay.
• Strengthening the CDSCO:
• Increase personnel, funding, and infrastructure to improve regulatory oversight.
• Establish more centralised drug-testing laboratories to ensure consistent and reliable quality checks for all generics across the country.
• Enhanced Stability Testing:
• Mandate periodic reassessment of all approved generics, including those cleared before 2018, to ensure they meet modern stability testing standards.
• Enforce uniform stability testing protocols across states to prevent quality issues and ensure the drugs remain effective throughout their shelf life.
• Stricter Impurity Standards:
• Align India’s impurity limits with international standards by adopting stricter ICH (International Council for Harmonisation) guidelines.
• This would help improve the safety and efficacy of generics, ensuring they meet global quality expectations.
• Overhaul Regulatory Thresholds:
• Revise bioequivalence thresholds for drugs with a narrow therapeutic index (NTI) to ensure stricter control.
• This would ensure tighter parameters for critical medications, preventing minor deviations from affecting therapeutic outcomes or causing adverse reactions.

Generic medicines are indispensable for equitable access to healthcare in India. However, their effectiveness must match affordability to sustain public trust.