As the present system in India for granting manufacturing license for dosage forms by the state drug control authorities does not require a quality test of the product, the licensing officers are completely unaware whether the final product is actually fit for patient use or not. It is just an assumption that the manufacturers would maintain the standards like bioequivalence, required quantity and the accepted practices of formulation process while issuing the license. By granting the permission on such assumption, the licensing officer is actually leaving millions of patients across the country at high risk.
The bioequivalence of the product, the most critical factor for a drug formulation, is not required to be proved by the manufacturer before it launches the product in the market. Similarly, the actual quantity of the API, which determines the price of the product and the formulation process including the quality of excipients, solvents and the method of release etc are also not required to have any specified standards as the bioequivalence test is not mandatory.
Says a senior official in a state drug control department, "The state authority is designated to issue manufacturing license, so they are not supposed to bother about the implication of marketing the product." Currently in India, once the Drug Controller General of India (DCGI) grants the marketing approval for a drug, any manufacturer can apply to the concerned state authority for license to manufacture various dosage forms of the drug with the permission from the DCGI in case of a new drug and without the central permission for existing drugs.
"At present, there is no mandatory requirement as per the Drugs & Cosmetics Act to verify the analytical details of the dosage form what is going be launched by the manufacturer while issuing manufacturing license by the state licensing officer. In case of manufacturing license application, the manufacturer only provides the name of the drug, dosages and also brand name if it is decided already. The licensing authority while clearing the application, verifies only whether the drug is approved in the country and also the details of the manufacturing facility. "The rest is all just assumptions that the manufacturer would keep the drug standards specified for various dosage forms as per pharmacopoeia," says another official in a state Food and Drug Control Administration.
Shockingly, there are alarming number of cases reported today like dosage forms of approved drugs in the market with serious functional inadequacies as the samples are not tested for bioequivalence before the drug authorities grant the manufacturing licenses in India. As a result, the therapeutic effect of drug formulations of same drug with same strength by different companies varies. And there is no provision to ensure the required bioavailability of the drugs from the dosage forms in the absence of a relevant rule. Therefore getting a right dosage form is always left to the fate of the patient on the assumption of the doctor.
Although there were deliberations in the Drug Technical Advisory Board (DTAB) by several drug experts in the past on the need to make bioequivalence test mandatory, no serious attempt was ever made in this direction by the government as there is stiff resistance from the industry. The industry is not in favour of the same as conducting bioequivalence test of each dosage forms while seeking the manufacturing and marketing license would increase the cost.
At the same time, the drug companies which export the formulations to regulated markets and also to other foreign markets invariably do the bioequivalence tests irrespective of the costs incurred as it is mandatory in the regulated as well as unregulated markets. The defective products are often go unnoticed in India as there is no strict ADR monitoring in the country.
Drug experts and practicing doctors say that as there is no effective system for ADR monitoring unlike the developed countries, the defective products make a success in marketing despite many dosage forms sold in the country show wide variations in bioequivalence. "As there is no mandatory bioequivalence test adopted in the country for approving drug products, the licensing authorities can not even ask the manufacturers to produce certificates to prove the efficacy of his formulation," he added.
There are several new launches even from major pharmaceutical companies, which were duly approved by the state and central drug control offices for manufacturing and marketing in the country show poor efficacy as the dosage form does not have the therapeutic effect as it is expected.
Another senior drug control official admits that since the analytical chemistry often differs from therapeutical chemistry, a bioequivalence test is always required to evaluate the actual efficacy of the product. All dosage forms should always be bioequivalent and identical and if it varies, obviously the same therapeutic effect cannot be expected from all the products. "Though ensuring the bioavailability and identical nature of the dosage forms is essential, it is unfortunate that in India it is still not mandatory," he said.