New Delhi: The Centre plans to require pharmaceutical companies to clearly distinguish biological medicines (biologics) from synthetic drugs when seeking licences and on packaging through changes to the Drugs Rules, 1945, according to two government officials close to the discussions and documents reviewed by Mint.
The proposed regulatory intervention aims to address ambiguity around drugs, such as semaglutide, that can be produced chemically as well as biologically.
The anti-diabetic and anti-obesity drug can be produced through either chemical synthesis or biological methods such as recombinant DNA (r-DNA) technology. The biological process involves combining DNA from different organisms and inserting it into a host such as yeast or bacteria, which then produces the target therapeutic protein.
But the existing framework lacks a statutory definition of biological products, allowing drugmakers to obtain licences under both categories for the same molecule.
To plug the loophole, the Indian government plans to define biological products and mandate manufacturers to declare whether an active ingredient is chemically synthesized or biologically derived from human, animal, or microbial sources.
“Form 28 governs licensing for synthetic products, while Form 28D is required for biological products under central oversight. Because the Drugs Rules, 1945, do not define a biological product due to its evolving nature, manufacturers are taking licences under different forms for the same product,” said one of the first officials cited above on the condition of anonymity.
Mint reported on 24 August that the Indian Pharmacopoeia Commission (IPC) was drafting a dedicated monograph for semaglutide, setting official standards for the drug’s identity, purity, potency and testing.
India’s biologics market is estimated at $13.3 billion, against an overall pharmaceutical market of about $60 billion. Demand for semaglutide alone is projected to reach $347.5 million in India by 2035, according to a CareEdge report.
Licensing confusion
This comes against the backdrop of the Central Drugs Standard Control Organisation (CDSCO) receiving multiple applications from manufacturers seeking permission to produce synthetic and r-DNA formulations at the same manufacturing facility.
While Schedule M of the Drugs Rules permits campaign-based manufacturing subject to cleaning validation and risk-mitigation measures, the substantive provisions do not define biological drugs. The rules also do not specifically address licensing overlaps in which a facility seeks approval under Form 28 for synthetic drugs and under Form 28D for biological products with central oversight, at the same site.
“Therefore, it is proposed that mandatory labelling provisions be introduced to indicate the origin of the drug as ‘synthetic origin’, ‘r-DNA-origin’, ‘human origin’, or ‘animal origin’, as applicable. Consequential amendments will also update Schedules C and C1 to cover biological-origin products across parenteral and non-parenteral dosage forms,” stated one of the documents.
Additionally, the government proposes to incorporate a definition of “biological products” into the Drugs Rules, 1945, and the New Drugs and Clinical Trials (NDCT) Rules, 2019, aligned with World Health Organization (WHO) standards. The definition would cover vaccines, recombinant therapeutic proteins, monoclonal antibodies, enzymes, hormones, and cell and gene therapy products.
Another document showed that the Drugs Technical Advisory Board (DTAB), India's highest statutory decision-making and advisory body on technical matters related to drugs and cosmetics, had agreed with the proposals.
“This regulatory move (is) about administrative and regulatory clarity. Semaglutide is perhaps the first molecule to be manufactured via two completely distinct routes—chemical synthesis and biological expression," said Viranchi Shah, national spokesperson of the Indian Drug Manufacturers’ Association (IDMA) representing 1,200 member companies.
Mint's queries emailed to the spokespersons of the Union ministry of health and family welfare, the Drugs Controller General of India (DCGI), Bharat Biotech, Biological E, Biocon, Cipla, Glenmark, Dr Reddy's Laboratories and Mankind remained unanswered.
Correct disclosures
It's about disclosure, keeping up with the realities of drug manufacturing. A drug produced by chemical synthesis and one made using r-DNA technology are not automatically interchangeable; they have different impurity profiles, immunogenicity risks, and quality-control procedures, added Hari Kiran Chereddi, founder, managing director and chief executive, pharmaceutical company HRV Global Life Sciences.
“In multi-origin molecules such as semaglutide, origin labelling does not give the patient a choice; rather, origin labelling provides vital traceability for post-market surveillance, adverse event investigations, and aligns India’s framework with US and EU standards,” he said.
It should be seen as a net benefit for the industry rather than simply a cost, he said.