Generic medicines are more widely welcomed in India, as they are cheaper and make healthcare more affordable. The generic drugs contain the same active ingredient(s), in the same strength and dosage form, and are intended to be administered through the same route as the corresponding branded medicine. They are expected to possess comparable quality, performance characteristics, and therapeutic efficacy.
On the other hand, pioneer drugs or branded medicines cost substantially more than generic medicines because pharmaceutical companies invest billions of dollars in R&D, pre-clinical studies, clinical trials, and numerous unsuccessful attempts before successfully bringing a drug to the market. To recoup these investments, the pioneer drug manufacturer secures patent protection, enjoys the monopoly conferred by patent law, and prices its product at a level higher than the cost incurred for its production. After exercising the monopoly for the duration of the patent term, typically 20 years, generic medicines enter the market.
Before entering the market, an innovator or new drug is subjected to a stringent regulatory framework involving pre-clinical studies and clinical trials designed to establish its safety, efficacy, dosage, and tolerability, followed by regulatory review and approval by the Central Drugs Standard Control Organisation (CDSCO) or the corresponding regulatory authority in the relevant jurisdiction.
On the other hand, the regulatory pathway for generic medicines is comparatively simpler. Regulatory frameworks across various jurisdictions generally require generic medicines to establish therapeutic equivalence through bioequivalence studies, which have become the principal regulatory tool for assessing whether a generic product can be substituted for its reference counterpart. Bioequivalence refers to the similarity in the rate and extent of absorption of the active pharmaceutical ingredient from the generic formulation and the reference formulation when administered under similar conditions and at the same molar dose.
Speaking in the context of India, bioequivalence studies are not mandated for all drugs across the board; rather, they are required for new drugs as defined under Rule 2(w) of the New Drugs and Clinical Trials Rules, 2019, and for drugs with low solubility.
However, all pharmaceutical manufacturers, including generic medicine manufacturers, are required to comply with Good Manufacturing Practices (GMP) prescribed under Schedule M of the Drugs and Cosmetics Rules, 1945, framed under the Drugs and Cosmetics Act, 1940. The present article intends to highlight the importance of incorporating product-specific GMP standards for complex generics.
Complex Generics: A distinct category
Neither the Drugs and Cosmetics Act, 1940, nor the CDSCO defines a “complex generic.” However, the United States Food and Drug Administration (FDA) has attempted to define complex generics by classifying them as products involving complex active ingredients, complex formulations, complex routes of delivery, complex dosage forms, drug-device combination products, and other products whose complexity creates uncertainty regarding the appropriate approval pathway.
There is an emerging consensus across various jurisdictions and among academic scholars that conventional bioequivalence (BE)/pharmacokinetic (PK) studies may be insufficient, by themselves, to establish equivalence for complex generics, as they may not adequately capture product characteristics that influence therapeutic performance[1]. The US FDA (here) has similarly observed that demonstrating bioequivalence is not always straightforward or efficient, particularly for complex drug products. It was observed by the US FDA that
“However, demonstrating bioequivalence is not always straightforward and efficient, particularly for drug products that are complex. Complex drugs include those that are intended to deliver medication to local sites of action, such as the lung (e.g., an inhaled medication for asthma) or the skin (such as a cream or ointment for eczema), where measuring how much drug is present at different times—known as the rate of absorption—can be difficult.”
The need for Product - Specific GMP
As discussed earlier, the two major regulatory requirements to be satisfied by drug manufacturers across various jurisdictions are adherence to Good Manufacturing Practices (GMP) and, in the case of generic medicines, establishing bioequivalence.
Focusing on GMP, these standards are drafted at a high level of generality so that they can be applied uniformly across a broad spectrum of pharmaceutical products. They are directed towards preventing contamination and mix-ups, prescribing sanitary conditions, maintaining adequate documentation, validating manufacturing processes, controlling materials, and promoting consistency in production.
In the case of complex generics, it can be said that the process is the product, and the performance of the drug is influenced by factors such as complex excipients, multiple active molecular components, and drug-device interactions. These, in turn, depend on formulation characteristics, particle size distribution, encapsulation efficiency, release kinetics, excipient characteristics, device functionality, device interfaces, and polymer characteristics, which are product-specific attributes controlled through the manufacturing process[2].
It is also the case that complex generics present manufacturing impediments that are fundamentally different from those encountered in conventional generics. As Complex generics are frequently characterised by heterogeneous structures and manufacturing-process-dependent variables, as discussed above. Their quality and performance may be influenced by highly product-specific variables including polymer composition, molecular-weight distribution, surface morphology, aerodynamic properties, and device-related characteristics. Even minor changes in manufacturing conditions may result in changes to drug release behaviour, deposition patterns, pharmacokinetic profiles, immunogenicity, or therapeutic performance. Additional manufacturing challenges include achieving batch-to-batch consistency, maintaining highly controlled and reproducible process parameters, and the inability of existing analytical methods to completely characterise all clinically relevant attributes of the product.
Henceforth, where the manufacturing process carries greater weight in determining drug stability, efficacy, and performance, and even to achieve batch -to- batch consistency, additionally where there is an emerging consensus that demonstrating bioequivalence may not, by itself, be sufficient or efficient to prove performance or determine efficacy for complex generics, the need for product-specific GMP standards assumes greater prominence. This is particularly relevant given the accepted difficulty of ensuring similarity with reference to the pioneer drug using conventional bioequivalence approaches across various jurisdictions.
The road ahead
The next question, therefore, is what may serve as a relevant source for developing product-specific manufacturing practices. One possible source is the regulatory dossier submitted by the pioneer drug manufacturer, which may contain significant information relating to stability data, critical process parameters, and other manufacturing considerations relevant to the product.
In addition to the regulatory dossier, disclosures contained in the patent specification may serve as an additional or supplementary source of information. This is particularly relevant in the Indian context, where Section 10(4) of the Patents Act, 1970 requires the applicant to disclose the best method of performing the invention known to the applicant.
Admittedly, pharmaceutical companies generally seek to protect their manufacturing know-how and commercially sensitive information as trade secrets.
Nevertheless, in the context of pharmaceutical inventions, a product cannot always be adequately described merely by reference to its composition or structural characteristics. This leads the applicants to rely on process patents or product-by-process claims to describe the product by reference to the manner in which it is manufactured. The decision of the Delhi High Court in Vifor (International) Ltd. v. MSN Laboratories Pvt. Ltd. is relevant in this regard. The Court observed that a product-by-process claim is an amalgamation of product and process claims and may be used where a novel product possesses unique attributes that are sought to be explained by reference to the process by which it is manufactured.
Further, the clarification of the scope of protection afforded by product-by-process claims in the judgment may encourage applicants to adopt such claims where the characteristics of a novel product are closely associated with its manufacturing process. The Court held that the scope of protection conferred by a product-by-process claim is not curtailed merely by the process limitations appearing in the claim; rather, the protection extends to the product itself, provided that the product is novel, inventive, and unknown in the prior art.
Henceforth, disclosures made in process patents and product-by-process patents may be particularly relevant in ascertaining and culling out information necessary for developing product-specific GMP standards.
While the introduction of generic medicines following patent expiry is essential for improving accessibility and affordability, an immediate and unqualified transition in the case of complex drugs may raise legitimate concerns. The assumption of inherent equivalence between innovator and generic products may not always hold true where manufacturing sensitivity plays a crucial role in determining the product's performance, particularly in light of the emerging consensus, discussed above, that conventional bioequivalence approaches may not be sufficient or efficient for complex drugs and may not adequately establish equivalence through traditional methods. Accordingly, there is a need for a more calibrated and drug-specific approach to GMP, particularly at the stage of generic entry, so as to ensure that increased access to complex medicines does not come at the cost of patient safety.
Sydney Stern and others, 'Research and Education Needs for Complex Generics' (2021) 38 Pharmaceutical Research 1991 https://doi.org/10.1007/s11095-021-03149-y accessed 30 August 2026. ↑
Amatha Sreedevi, Elstin Anbu Raj, D Sreedhar and Virendra S Ligade, 'Exploring the Challenges Faced by Generic Version of Complex Drugs: A Scoping Review' (2025) 14 Systematic Reviews 183 https://pmc.ncbi.nlm.nih.gov/articles/PMC12482112/ accessed 30 August 2026 ↑
Author is a Law student at Campus Law Centre, Delhi University. Views are personal.