The office of CDSCO has issued certain clarifications with respect to the requirements and guidelines for permission to import and/or manufacture of new drugs for sale or to undertake clinical trials. This is intended to have further clarity on the issue of new drug.

Drugs Controller General of India (DCGI) Dr Surinder Singh said that even though all requirements and guidelines for permission to import or manufacture of new drugs for sale or to undertake clinical trials are prescribed under Schedule Y of the Drugs &Cosmetics Rules 1945 and also his office had issued guidance for submission of applications with respect to FDC to further facilitate the industry for submitting the applications in a more organised manner with the required details, it is felt that certain issues need to be clarified to further facilitate the industry as well as all stakeholders for more clarity.

Clarifying the issue of Scale of Trial Batches, the DCGI notice said that it is “A batch of an API or FPP manufactured by a procedure fully representative of and simulating that to be applied to a full production-scale batch. For example, for solid oral dosage forms, a pilot scale is generally, at a minimum, one tenth that of a full production scale or 1,00, 000 tablets or capsules, whichever is the larger; unless otherwise adequately justified.

However, Batch size may be kept less than 1,00,000 tablets or capsules in case of drugs indicated in Life threatening, serious diseases or diseases of special relevance to the Indian health scenario when adequately justified. Further, it may be clarified that for oral liquid, topical preparations and sterile preparations, pilot scale is a minimum one-tenth that of a full production scale which must be manufactured by a procedure fully representative of and simulating that to be applied to a full production-scale batch.

On the issue of significant change criteria, the DCGI said that if significant change occurs at any time during 6 months testing under the accelerated storage condition, additional testing under an intermediate storage condition should be conducted and evaluated against significant change criteria. “Significant change” for an API is defined as failure to meet its specification.

Clarifying the issue of mentioning of address on Form 44, the DCGI has clarified that the applicant should mention the address of the actual manufacturing facility on Form 44 where simulated batches are to be manufactured. The DCGI has further clarified that if these batches are to be used for clinical trial including BA/BE study purpose and the same must be manufactured in GMP facility.

Clarifying on the issue of submission of data for New drug by an applicant desirous to manufacture the drug under loan License in a facility of other firm who has already obtained permission from  DCGI office to manufacture the same new drug in the same facility, the DCGI has clarified that Loan licensee shall establish and submit comparability data of minimum pilot scale batch with the marketed product of the original licensee manufactured in the same facility with the same equipment to obtain Form 46 on his license. However, if the applicant wants to manufacture new drug on P to P basis (contract agreement - manufactured by and marketed by principle), then SLA can grant such permissions.

On Co-Packaging products, it was clarified that co-packaged materials may fall into any of the categories as mentioned under Guidance document to Industry for FOG and therefore requirements for submission of documents will be same as listed under the various categories. However, it may be clarified that if the manufacturer already has a market authorization in respect of each component of co-packaged product then the quality information to support co-packaging of those pharmaceutical products will be limited to stability of the products in the co-packaging. However each pharmaceutical product should be identical in formulation and method of manufacturing to the products which have already Market Authorization. It may further be clarified if the packaging material of the proposed comb pack is same as that of already marketed product, stability studies of the products in co-packaging may also be relaxed provided that a commitment of post approval stability studies of three consecutive batches shall be made by the applicant.

Clarification with respect to submission of stability data, the DCGI notice said that as per schedule Y, an applicant is required to submit 12 months Long term stability studies and 6 months accelerated stability studies. However, if the applicant submits both accelerated as well as real time stability data for 6 months only, then an initial expiry of one year may only be considered which can be concurrently increased after submission of the adequate stability data and obtaining permission from this Directorate.