India decides whether a drug is new by its own record, not by the drug’s history elsewhere. The test is in rule 2(w) of the New Drugs and Clinical Trials Rules, 2019. Its first limb covers
“a drug, including active pharmaceutical ingredient or phytopharmaceutical drug, which has not been used in the country to any significant extent, except in accordance with the provisions of the Act and the rules made thereunder, as per conditions specified in the labelling thereof and has not been approved as safe and efficacious by the Central Licencing Authority with respect to its claims”
The other limbs extend the definition to an approved drug proposed with new claims, a new route of administration, dosage or dosage form; to a new fixed dose combination or a changed ratio; to a modified or sustained release form or a novel delivery system; and to vaccines, r-DNA derived products, living modified organisms, monoclonal antibodies, stem cell derived products, gene therapy products and xenografts.
The four-year line
“The drugs, other than drugs referred to in sub-clauses (iv) and (v), shall continue to be new drugs for a period of four years from the date of their permission granted by the Central Licencing Authority and the drugs referred to in sub-clauses (iv) and (v) shall always be deemed to be new drugs”
During those four years, another company that wants to import the same drug also follows the new drug route. Its application in Form CT‑18 carries the data listed in Table 2 of the Second Schedule (rule 75(3)).
Permission before licence
“No person shall import or manufacture for sale or for distribution any new drug in the form of active pharmaceutical ingredient or pharmaceutical formulation, as the case may be, except in accordance with the provisions of the Act and these rules.”
The Central Licencing Authority grants permission in Form CT‑19 for an active pharmaceutical ingredient or Form CT‑20 for a formulation, or rejects the application with reasons, within 90 working days (rule 76). Only then does the import licence follow:
“After obtaining permission under Rule 76, the person intending to import new drug for sale shall make an application to the Central Licencing Authority as per provisions of the Drugs and Cosmetics Rules, 1945 to obtain a licence for import of new drug for sale or for distribution.”
When a local trial may be waived
For an unapproved new molecule, the application carries the results of a local clinical trial (rule 75(2)). Rule 75(7) allows the trial to be left out, among other conditions, if
“the new drug is approved and marketed in countries specified by the Central Licencing Authority under rule 101 and if no major unexpected serious adverse events have been reported”
The countries are named by order of the Central Licencing Authority, with the approval of the Central Government (rule 101). The waiver further requires that nothing known suggests a difference in the Indian population affecting the drug’s pharmacokinetics, pharmacodynamics, safety or efficacy, and an undertaking in writing to conduct a Phase IV clinical trial.
Conditions that come with the permission
Rule 77 attaches conditions to the permission: the specifications approved by the Authority; labelling under the Drugs Rules; a warning on the label and the outer pack, in a red box, that the drug is to be sold by retail on prescription only; Periodic Safety Update Reports; reporting of adverse reactions; no claims beyond those approved; approval of the carton, labels and package insert before marketing; and a test or analysis report with each imported consignment.