Pondicherry accounts for highest number of FDCs approved without prior permission from DCGI

Pondicherry, which has been recently in the news regarding violation of 122E Drug & Cosmetic Rules, was found to have approved the highest number of fixed dose combinations without the prior approval of the Drug Controller General of India (DCGI) in the past.

According to the information gathered by the Union Health Ministry, of the total 23 such cases of approvals to FDCs, Pondicherry has reported as many as 8 cases. The Centre had fixed October 1, 2012 as the cut-off date for implementing the rule to get prior permission by the state authorities from the DCGI for approving FDCs.

After Pondicherry, Uttarakhand was found to have sanctioned five FDCs while Maharashtra, Madhya Pradesh and Himachal Pradesh reported two each cases. Goa, Tamil Nadu, Haryana and Union Territory of Daman and Diu sanctioned one FDC each. Out of these, 11 were approved during 2011 and the rest during 2012, as per the information.

“As many as 23 cases of new FDCs , considered as new drugs, were also found to be licenced by State Licensing Authorities (SLAs) without approval of the DCGI . In all such cases, the office of DCG (I) took up the matter with respective SLAs for necessary action,” according to official sources.

“The State Drug Controllers have been requested in the Drugs Consultative Committee meeting to ensure that new drugs and FDCs are not permitted without approval from the office of DCG (I) and the drugs prohibited by the Central Government are withdrawn from the market with immediate effect. States have also been advised to strengthen their infrastructure for better enforcement and develop vigilance mechanism over the drugs moving in the market,” sources added.

On October 1, 2012, the Central Government issued statutory directions under Section 33 P of the Drugs and Cosmetics Act, 1940 to all State/UT Governments to instruct their respective drug licensing authorities to abide by the provisions prescribed under the Drugs and Cosmetics Rules for grant of manufacturing licenses for the drugs falling under the definition of the term “new drug” and not to grant licenses for manufacture for sale or for distribution or for export of such new drugs, except in accordance with the procedure laid down under the said rules without prior approval of the DCG (I).

Recently, the health secretary to the government of Pondicherry had issued show-cause notices to 20 pharmaceutical manufacturing companies operating in region for violation of provision of 122E of the Drugs & Cosmetics Rules following a probe by the Government on the alleged nexus between a former official and a section of the manufacturers.

Source: Pharmabiz

Fixed Dose Combination (FDC) issue - will there be an end to it ?

A lasting solution to the vexed Fixed Dose Combination (FDC) issue, which has been evading a solution for almost four years, does not appear to be on the cards as the expert panel, headed by DCGI, is adamant that the industry should come out with clinical trial details on each of the FDC products, even those products which were in the market for decades together.Industry sources said that the expert panel, which consisted of doctors from renowned hospitals, was not ready to even consider the drugs which were in the market for several years. Though the industry also took the help of several renowned doctors, that too specialists in each area, the panel simply refused to consider the pleas of these doctors and insisted on clinical trials for each of the FDC products, sources said.

After a long gap of more than one year, the expert panel on FDC held its meeting on April 19 and 20 this year to take a call on most of the remaining FDC drugs. In fact, the industry was optimistic on finding a lasting solution to the vexed issue during the two-day meeting, especially in the wake of DCGI Dr Surinder Singh's public announcement on January 7 this year in Mumbai that the long pending FDC issue would be resolved within one month. On that day, the DCGI was addressing the captains of Indian pharma industry on the occasion of the 49th annual day celebrations of the Indian Drug Manufacturers Association (IDMA) in Mumbai.But the insistence of the DCGI-headed expert panel on clinical trial for all the products has belied such a hope.Taking strong exception to the adamant attitude of the panel, industry sources said that if the DCGI wanted clinical trials for every product, the entire exercise of holding periodic meetings between the industry and the expert panel is a waste of time for one and all. “The industry has roped in several renowned doctors to present their case in the meetings. But, their views were not heeded by the panel,” the industry regretted. In fact, the industry is annoyed with the DCGI over his indifferent attitude in handling the entire FDC issue. There is resentment among the industry over the inordinate delay on the part of the DCGI in sending the list of FDCs, which have been accepted as 'good and rational' by the expert panel, to the State Licensing Authorities (SLAs) as the SLAs are directing the companies to approach DCGI office in Delhi for getting the license renewal of drugs which have been in the market for as long as 10 to 15 years. The expert panel on FDC had so far cleared more than 200 of the total 294 controversial combination drugs as 'good'. But, the DCGI is yet to officially communicate the same to the SLAs in writing, leaving the industry to approach the DCGI office for licenses.

DTAB recommendations to re-examine many FDCs likely to prolong issue further

Even as the sub-committee of the Drug Technical Advisory Board (DTAB) is meeting for two days from today, the vexed issue over Fixed Dose Combinations (FDC) is unlikely to be settled early, as being reiterated by the authorities.

The process of clearing the FDCs is going to be long-time affair as the sub-committee is scheduled to re-examine a number of FDCs already cleared by them earlier. Apart from this, the panel will also assess 64 FDCs, out of the remaining 80 FDCs to be covered, according to the agenda fixed for sessions spread on April 19 and 20.

The sub-committee will also examine six FDCs approved before 1988, as per the decision taken by it in the meeting held on October 1, 2008. They include dicyclomine+mefenamic acid+ paracetamol, dicyclomine + paracetamol + clinidium bromide, dicyclomine + paracetamol + clinidium bromide + chlordiazepoxide, mefenamic acid + dicyclomine, paracetamol + dicycloverine + mefenamic, and propranolol + Diazepam.

The meeting will re-examine a set of 22 FDCs for rationality, as per the recommendation of the meeting of DTAB. They fall in the categories of nutritionals, orthopaedics, and antihistamines. They have been already cleared by the expert panel, but the 57th meeting of the DTAB has directed re-examination of the same.

Likewise, another set of 16 FDCs will also be re-examined by the panel for rationality, as per the direction of the last DTAB meeting. These combinations are of antimicrobial with lactic acid bacillus and had been discussed by the sub-committee at its meeting on January 23 and 24.

Thus in total, the two-day meeting of the sub-committee has to clear 107 FDCs after examining the rationality. The recommendation by the DTAB for re-examination would further prolong the process of putting a final solution to the vexed issue of FDCs, though DCGI had recently claimed that the matter would be solved within one month.

DTAB sub-committee on FDC to meet on April 19, 20 after long gap

After a long gap of more than one year, the sub-committee of the Drug Technical Advisory Board (DTAB) on the issue of long pending Fixed Dose Combination (FDC) issue will hold a two-day meeting on April 19 and 20 and take a call on most of the remaining FDC drugs.

The much-awaited meeting of the panel, headed by the Drug Controller General of India (DCGI) and having representatives of major pharma associations along with the experts in the field, will examine as many as 64 FDCs during the sessions spread across two days, though as many as 80 odd FDCs, out of the controversial 294 FDCs, were still remaining to be assessed.

The panel will examine the feasibility and decide on the fate of FDCs belonging to dermatological, nutritionals, CNS, anti-microbial, anti-diabetic, orthopaedics, cough and cold categories, according to the list of FDCs shortlisted for deliberations at the meeting, sources said.

“The next meeting of sub-committee is scheduled to be held on April 19, from 11 am to 5.30 pm and on April 20, from 2 pm to 5.30 pm for examining the issues relating to the list of 294 FDCs,” said the letter from DCGI.

The expert panel on the FDC held its last meeting on February 24, 2010 and analysed 18 FDC products falling under the category of cardiovascular and diabetes therapeutic areas. The industry associations have been pressing for the next meeting for long now, with the hope that the FDC issue could finally be solved. The DCGI himself had announced in January that the issue would be cleared shortly.

The FDC issue became controversial when the then DCGI Dr M Venkateswarlu in June 2007 asked the state drug licensing authorities to withdraw licenses of the 294 FDC drugs for irrational combinations and the issue became a bone of contention between the industry and the DCGI. The industry then moved court and got stay order against the DCGI order from Madras High Court, which is yet to be vacated.

DCGI to introduce 'Preliminary Scrutiny' for approval of FDCs from Jan 1

Aiming to streamline the submission of application for approval of Fixed Dose Combination (FDC) drugs and their review by the drug authorities, the Drug Controller General of India (DCGI) has introduced a system of 'preliminary scrutiny' of such applications while receiving them to determine the acceptability for review by the DCGI office.

This will come into effect from January 1, 2011.The new system is intended to avoid unnecessary delays in approvals of FDC applications. So far, the applicants have used many different approaches in organizing the information and the differences in organization of data in each application has made reviewing more difficult and can also lead to omission of critical data or analyses which could result in unnecessary delays in approvals.

The preliminary scrutiny of the applications will be done by CDSCO officers based on checklists prepared for each of the several categories of FDC. During the preliminary examination, the CDSCO officers will scrutinize the applications to ensure that it contains all the required administrative as well as technical information in proper manner as per the checklist. If application submitted is not in accordance with the format and the checklist, it will not be accepted by CDSCO.Once an application is accepted, the adequacy of the data will be reviewed by CDSCO as per the specified requirements and guidelines. In case the data submitted is not adequate or satisfactory, applicant will be requested to generate/submit adequate data for consideration and approval of the FDC.The proposed fixed dose combination should be based on therapeutic rationale.

The applicant is required to justify the combination based on the rationale. While submitting the rationale for a FDC, the applicant must address the issues like drug-drug interaction between the ingredients, food effects and dosage schedule of individual active ingredients vis-a-vis that of the FDC. Further, the indication/claim for the FDC should be such that the individual active ingredients makes a contribution to the claimed effect and the product should be formulated so that the dose and proportion of each substance in the FDC is appropriate.Trial batches of new drugs for test and analysis/clinical trial/BE study purpose should be manufactured after obtaining Licence in Form 29 from the concerned State Licensing Authority and copy of the licence should be submitted along with the application. While submitting reply to a query, the applicant should always enclose with the reply, a copy of query letter issued by CDSCO.The applicant should submit stability data generated on 3 trial batches manufactured by them under Licence in Form 29 issued by State Licensing Authority (SLA). The stability data and the clinical trial protocol should be submitted as per the CDSCO format.

In case of clinical trial/ bioequivalence study NOC, the applicant should submit the adequate chemical and pharmaceutical information. The applicant should always submit certificate of analysis, dissolution data (in case of oral dosages form, as appropriate), stability study data etc. in respect of formulation, duly signed by the In-charge/Manager QC.Before preparing the application, the applicant must categorise their proposal and submit information as per the checklist for that category. Application in Form 44 should be complete in all respects and signed by the authorized person of the firm with name and designation. The TR challan receipt submitted by the applicant should mention the name of the FDC including correct head of the account, payable at, bank clearance, etc. The documents must be submitted with indexing and page number. Without indexing or page number, no application will be accepted. Clear and unequivocal information should be provided along with the application.