1. Dr. R.K. Srivastava, DGHS Chairman Nirman Bhawan, New Delhi. 2. Prof. S.D. Seth, Member Chair in Clinical Pharmacology, ICMR, New Delhi

Transcription

1 1 MINUTES OF THE 57 th MEETING OF DRUGS TECHNICAL ADVISORY BOARD HELD ON 23 RD FEBRUARY 2009 IN THE COMMITTEE ROOM, FDA BHAVAN, KOTLA ROAD, NEW DELHI PRESENT 1. Dr. R.K. Srivastava, DGHS Chairman Nirman Bhawan, New Delhi. 2. Prof. S.D. Seth, Member Chair in Clinical Pharmacology, ICMR, New Delhi Shri R. Ranga Rao, Member Director, Drugs Control Administration, Drugs Control Bhawan, Vengal Rao Nagar, Hyderabad Dr. P.K. Guha, Member Director, Central Drugs Laboratory, 3, Kyd. Street, Kolkata Dr. K.R. Mani, Member Director, Central Research Institute, Kasauli (Himachal Pradesh), Pin Code Dr. Rishendra Verma, Member Head, Division of Biological Standardization, IVRI, Izatnagar Smt. Sudha Swamy, Member Research Chemist & govt. Analyst, Drugs Testing Lab, Bangalore, Karnataka. 8. Dr. Dharam Prakash, Member Hony. Secretary General, Indian Medical Association, New Delhi. 9. Dr. Surinder Singh, Member Drugs Controller General (India) Secretary FDA Bhavan, Kotla Road, New Delhi. Invitee 1. Shri Sudhir Kumar Under Secretary (Drugs) Ministry of Health and Family Welfare, New Delhi.

2 2 Dr. T.K. Chakraborty, Director, CDRI, Lucknow; Dr. Keshav Kuttinayaran, President, Medical Council of India, New Delhi, Prof. B.Suresh, President Pharmacy Council of India, Shri Subodh Priolkar, President IPA, Dr. Satish Reddy, M.D., Dr. Reddy Labs., Hyderabad, Prof. B.K.Gupta, Kolkata, Dr. V.P. Singh, Patna and Dr. B.N. Patel, Food and Drug Laboratory, Vadodara could not attend the meeting because of their pre-occupation. S/Sh. N.C. Dawan, DDG, M. Mitra ADC(I), A.K. Pradhan, ADC(I), Janak Raj ADC(I, Lalit Kishore, WHO Consultant, R. K. Rishi, Pharmacologist and A.K. Khanna, (TO) from Headquarter also attended the meeting. Dr. Surinder Singh, Drugs Controller General (India) and Member Secretary DTAB welcomed the Chairman and members of the Board and requested the Chairman to initiate the proceedings. Dr. R.K. Srivastava, DGHS and Chairman of the Board after ensuring that the quorum is complete as per bye-laws initiated the proceedings of the committee. He stressed the importance of this empowered committee and desired that there should be more participation of the members to have quality discussions and conscious decisions. The Board then agreed to allow Dr. Dharamprakash, Hony. Secretary General, Indian Medical Association, who had come as representative of IMA in place of notified member, to attend the meeting without having a voting right on any issue which is put to vote. DCG (I), Member Secretary, informed the members that this is the first meeting of DTAB being held in the FDA, Bhawan, Hqrs. of CDSCO. The office of DCG(I) has also been strengthened with the efforts of the Ministry of Health and assistance of WHO in view of the importance of quality control of drugs marketed and introduced in the country. The FDA Bhawan has provided the long desired environment for systematic functioning of the origination. With the assistance of Health Canada, under the aegis of WHO systems of dossier review of vaccines to be permitted to be marketed in the country has been put in place. A detailed Guidance document, Common Technical Dossiers (CTD) format, having 180 pages has been prepared and put on website for information of industry on submission of clinical trial applications for evaluating safety and efficacy. The USFDA has also shown keen interest in the clinical research in the country and has conducted training programmes in India in respect of clinical trial oversight in the country. The members appreciated the efforts made by the office of DCG (I) in upgrading the regulatory infrastructure at the centre and desired that copy of the Guidance document may be circulated to the members for their information. The member Secretary agreed to circulate the document to the members. The Chairman then requested the Member Secretary to initiate the agenda items for discussion and desired that the decisions taken in the meeting should be based on sound logic having clear interpretations.

3 3 AGENDA No.1. ACTION TAKEN ON MATTERS ARISING OUT OF THE 56 TH MEETING OF DTAB HELD ON 16 TH JANUARY 2008 AT NEW DELHI. The Member Secretary briefed the members about the action taken on the recommendations of 56 th meeting of DTAB held on 16 th January, Certain agenda items which required further consideration by the Board were again placed before DTAB for its deliberations. Copies of the notifications referred to in the ATR were circulated to the members for their information. The Board approved the ATR report. AGENDA NO.2 CONSIDERATION OF PROPOSAL TO AMEND RULE 43 A OF THE DRUGS AND COSMETICS RULES TO INCLUDE INLAND CONTAINER DEPOTS AT TUGLAKABAD AND PATPARGANJ, DELHI AND TUTICORIN IN TAMILNADU AS PORT OF ENTRY FOR DRUGS The member Secretary briefed the members that with the growing trade in the Pharma sector requests for opening more and more port of entries for drugs were being received in the office of DCG (I) as well as Ministry of Health. The proposal to include Inland Container Depots (ICDs) at Patparganj and Tuglakabad at Delhi and Tuticorin port in Tamil Nadu under rule 43 A of the Drugs and Cosmetics Rules was placed before the Board for its consideration. It was further informed that requests for opening up of Bangalore Airport and Goa Port as port of entry are under examination in the office of DCG (I). He further stated that in order to ensure that port of entries are notified in time to address the difficulties of the industry, it was proposed to amend rule 43 A to enable the Government of India to specify port of entries through a Gazette notification. The present process of amendment of the rule for inclusion of each entry takes around six months to one year after the approval of DTAB. The Board after deliberations agreed to the inclusion of ICDs at Patparganj and Tuglakabad at Delhi and Tuticorin port in Tamil Nadu under rule 43 A of the Drugs and Cosmetics Rules. The Board further recommended that for the purpose of amendment of rule 43 A empowering the Government to specify port of entry through a notification, the Government should prepare a Guidance document specifying bench marks for declaring a port of entry. The member Secretary may form a sub-committee to prepare the guidelines which then should be duly approved by DTAB before the proposed amendment is considered. This will ensure that there is a system in place for declaring a place as port of entry for drugs by the Government.

4 4 AGENDA NO.3 CONSIDERATION OF THE PROPOSAL FOR CREATION OF A NEW SCHEDULE H(1) FOR SPECIAL DRUG PRODUCTS WHICE ARE REQUIRED TO BE SOLD UNDER SPECIFIED CONDITIONS The member Secretary stated that DTAB in its 55 th meeting held on 6 th July, 2007 had set up a sub-committee to suggest the modalities for creation of Schedule H 1 to regulate the sale of drugs which are required to be restricted in their use. In the absence of any provision under the Drugs and Cosmetics Act, a notification under Essential Commodities Act was then issued to restrict the sale of Oseltamivir (Tamiflu) for avian flu to avoid the drug becoming resistant because of excessive preventive use. The sub-committee examined the issue and in its report recommended creation of Schedule H 1 specifying extent and conditions of restrictions for each drug to be included in the Schedule. In the meanwhile, the Drugs and Cosmetics (Amendment) Act, 2008 has been passed by the Parliament under which a new section 26B has been inserted to regulate or restrict the manufacture, sale or distribution of any drug for which the Government is satisfied that it is essential to do so in public interest. Board may consider as to whether the creation of a new Schedule is required in the present circumstances. The DTAB after deliberations agreed that in view of the amendment of the Act, it may not be necessary to create a new Schedule H1. The Government of India could issue notification under section 26B specifying extent and conditions of restrictions through a notification in the official gazette. This provision would also be useful to regulated the sale of drugs which are required for select use or drugs in short supply or highly toxic drugs or drugs for neglected diseases. AGENDA NO.4 CONSIDERATION OF THE PROPOSAL TO AMEND DRUGS AND COSMETICS RULES TO MAKE PROVISION FOR REGISTRATION OF ORGANIZATIONS/INDIVIDUALS FOR CONDUCTING CLINICAL TRIALS AND INTRODUCTION OF SCHEDULE Y 1 GIVING REQUIREMENTS AND GUIDELINES FOR THE PURPOSE The member Secretary stated that India has become an important destination for clinical research. Many clinical research organization (CROs) are at present functioning in the country conducting clinical trials However, there is no system of their registration or the bench marks to which these organizations should comply. In order to ensure that clinical research in the country conforms to global norms of scientific and ethical conduct of clinical trials, it is proposed to amend the Drugs and Cosmetics Rules to make it mandatory for registration of organization conducting clinical trials. An elaborate requirement for the purpose is being specified under Schedule Y 1. The DTAB after deliberations found that certain modifications are required in the proposed amendment before these could be considered to be made mandatory. The modified draft may be put on web site of CDSCO for the sensitization of the public and Pharma industry in particular.

5 5 AGENDA NO.5 CONSIDERATION OF THE PROPOSAL TO AMEND CONDITION NO.5 OF FORM - 45 AND FORM 46 TO REMOVE THE DISCREPANCY WITH REGARD TO POST MARKETING SURVEILLANCE OF A NEW DRUG The member Secretary briefed the members that under para 4 of Schedule Y relating to Post Marketing Surveillance, the applicant is required to furnish Periodic Safety Update Reports (PSURs) every six months for the first two years of a new drug and then annually for subsequent two years. However, the condition no.5 of permissions in Form 45 and Form 46 require the PMS study to be conducted during the initial period of two years of marketing of the new drug formulations. The above condition was proposed to be amended so that it is in line with the requirements of Schedule Y. The DTAB after deliberations agreed to the amendment of condition no.5 of Form 45 and Form 46 in the following manner. (5) As Post Marketing Surveillance, the applicant shall submit Periodic Safety Update Reports (PSUR) every six months for the first two years. For subsequent two years the PSURs need to be submitted annually. AGENDA NO.6 CONSIDERATION OF THE PROPOSAL TO PROHIBIT RIMONABANT AN ANTI OBESITY DRUG UNDER SECTION 26 A OF THE DRUGS AND COSMETICS ACT DCG (I) briefed the members that the drug Rimonabant, an anti obesity drug, was approved for marketing in the country in May, The drug was permitted in many European countries since A press release of EMEA dated 23 rd October 2008 recommended suspension of marketing authorization of the drug from Sanofi Aventis as the benefits no longer outweigh the risks. Psychiatric side effects were identified as majors safety issue. In view of this the matter was examined in consultation with an expert committee constituted for the purpose. The committee after detailed deliberations recommended the suspension of the import/manufacture, sale and distribution of Rimonabant in the country. It also recommended for stopping ongoing clinical trials on the drug in the country. It was further recommended that the matter may placed before DTAB for consideration of prohibition of manufacture and sale of the drug in the country under section 26 A. The permission to manufacture the drug granted to the applicants in the country was withdrawn on 20 th November The State Drugs Controllers were also requested to suspend the manufacture for sale and distribution of the drug with immediate effect. DTAB after deliberations agreed for the withdrawal of the drug from the country as recommended by the Expert Committee. In order to ensure that the drug is prohibited for use in the country, it recommended that the drug may be prohibited under Section 26A for manufacture and sale in the country and under section 10A for import and sale in the country.

6 6 AGENDA NO.7 CONSIDERATON OF THE PROPOSAL TO AMEND PARA H OF THE SCHEDULE F OF THE DRUGS AND COSMETICS RULES TO ENHANCE THE AGE OF BLOOD DONOR FROM 60 TO 65 YEARS The member Secretary stated that Schedule F to the Drugs and Cosmetics Rules under Para H specify that for blood donation the donor shall be in the age group of 18 to 60 years. Representations have been received to increase the age limit to 65 years. National AIDS Control Organization (NACO) in their Standards for Blood Banks & Blood Transfusion Services specify that the donor should be betweeen age of 18 and 65 years. Many wester countries also permit blood donation upto the age of 65 years. It was therefore, proposed to increase the age limit under Schedule F from 60 to 65 years. DTAB after deliberations agreed to the proposed amendment. AGENDA NO.8 CONSIDERATION OF THE PROPOSAL TO AMEND RULE 49, 49A AND 50A TO BROAD BASE THE QUALIFICATIONS OF INSPECTORS, LICENSING AUTHORITY AND CONTROLLING AUTHORITY RESPECTIVELY UNDER THE DRUGS AND COSMETICS RULES. The member Secretary explained that a variety of highly specialized categories of drugs including vaccines, recombinant bio-technology products, stem cells derived products, cosmetics and medical devices are being regulated under the Drugs and Cosmetics Act in the country. In order to exercise effective regulatory control over these products, it is necessary that Drug Control Departments have professionally qualified staff in different fields of technologies. The Drugs and Cosmetics Rules prescribe qualifications of Drug Inspectors under Rule 49 while qualifications of licensing Authority and controlling authority are specified under Rule 49 A and 50 A. Under these rules qualifications are limited to a degree in pharmacy or pharmaceutical chemistry or in medicine with specialization in clinical pharmacology and microbiology. This limits the selection of candidates from the specified fields only. It was therefore, proposed to broad base the qualifications in the above rules so that variety of professional expertise is available to the Drug Control Departments. DTAB after deliberations agreed that it is necessary to broad base the qualifications prescribed under the rules and the persons with appropriate qualifications in chemistry, biochemistry, biotechnology, veterinary science, chemical engineering, bio-chemical and biomedical engineering and pharmacology may be considered for selection under the said rules. This would not only make wide choice available for the selection of capable persons but also make professionally qualified personnel available for wide variety of responsibilities.

7 7 AGENDA NO.9 CONSIDERATION OF THE PROPOSAL TO AMEND ENTRY NO.33 OF SCHEDULE K REGARDING NICOTINE GUM TO INCLUDE NICOTINE LOZENGES The member Secretary briefed the members that nicotine gum containing 2mg of nicotine is already exempted from sale licence under Schedule K and it was proposed to permit nicotine lozenges also under Schedule K as it is a similar type of formulations and would be used for the same purpose i.e cession of smoking. DTAB after deliberations agreed to amend entry no.33 of Schedule K to include nicotine lozenges also under its purview. AGENDA NO.10 CONSIDERATION OF THE REPORT OF THE EXPERT COMMITTEE TO REVEIW THE RATIONALITY AND SAFETY OF CERTAIN DRUG FORMULATIONS MARKETED IN THE COUNTRY The member Secretary briefed the members that the DTAB had set up an expert committee in its 55 th meeting held on to review the rationality and safety aspects of 294 Fixed Dose Combinations referred to it. The Committee had examined a large number of formulations and an interim report of the committee in respect of these products was placed before the Board for its consideration. The products examined by the sub-committee have been broadly divided into four categories as under: a. 43 products are either already banned under section 26A or are required to be discontinued because of lack of rationality b. 31 products are repeated products and need to be ignored c. 22 products have been approved by the office of DCG (I) d. 44 products are recommended as not irrational while for 5 FDCs additional data is required for further examination. Rest of the products are yet to be examined. The DTAB after deliberations accepted the interim report of the sub-committee. It however, recommended that the committee should expedite the process of examination of the formulations referred to it. It also recommended that 22 FDCs which were permitted by the office of DCG (I) on the basis of rationale furnished by the manufacturers should also be examined by the committee as they figure in the list of 294 drugs referred to it. In the list of 44 items under (d) above it recommended that the FDCs having lactobacillus or lactic acid bacillus should be re-examined by the sub- committee for their rationality.for other FDCs under (d), DTAB had no objection for their approval and continued marketing. In regard to the list of FDCs which the sub-committee considered are already prohibited or are required to be prohibited, the office of DCG (I) may take legal opinion in the

8 8 matter in view of the stay granted by the Hon ble Court in the matter. The sub-committee, in the meanwhile, may provide the rationale for each category of drug recommended to be prohibited under section 26A of the Drugs and Cosmetics Act for the purpose of prohibiting them through the gazette notification. The committee also examined the entry no.55 in the list of banned drugs on Fixed Dose Combination of dextropropoxyphene referred to it for its expert opinion. The subcommittee examined the entry in depth and recommended that entry no.55 may be amended to read as under: 55. Fixed Dose Combination of dextropropoxyphene with any other drug other than one antispasmodic or one non-narcotic analgesic or one antiinflammatory drug The Board after deliberations agreed to the proposed amendment. AGENDA NO.11 CONSIDERATION OF THE PROPOSAL TO AMEND THE DRUGS AND COSMETICS RULES TO REGULATE IMPORT, MANUFACTURE AND SALE OF MEDICAL DEVICES IN THE COUNTRY The member Secretary briefed the members that it is proposed to regulate the quality of medical devices marketed in the country under the Drugs and Cosmetics Act. A core group set up by the Ministry of Health has prepared a guidance documents and the changes which are required to be made in the Drugs and Cosmetics Rules for regulating the quality of medical devices in the country. These requirements are harmonized with the requirements of Global Harmonization Task Force (GHTF) guidelines for medical devices. The matter was placed for consideration of DTAB. DTAB after deliberations agreed that even though the step is in right direction, but to regulate the quality of medical devices in the country, it is necessary to regulate them as medical devices with well defined parameters. It would require identification of notified bodies to certify the quality of medical devices, empowered committees to consider disputes and controversies, a dedicated regulatory infrastructure backed up by requisite legislative powers. It would also require enabling provisions under the Act to frame rules and regulations for the purpose. The Ministry of Health may expedite the process of introduction of enabling provisions in the Drugs and Cosmetics Act to regulate the import, manufacture, distribution and sale of medical devices in the country so that detailed provisions for regulating various categories of medical devices under the rules are incorporated..the Board further suggested that the proposed requirements for regulatory control over medical devices may be put on on the web site for the sensitisation of the public.

9 9 AGENDA NO.S-1 CONSIDERATION OF THE REPORT OF THE SUB-COMMITTEE OF DTAB TO EXAMINE THE ISSUES OF SAFETY, AVAILABILITY AND MISUSE OF DRUGS WHICH COULD BE PERMITTED TO BE SOLD FROM NON PHARMACY OUTLETS The member Secretary stated that a sub-committee was constituted by the DTAB in its 55 th meeting held on to examine the question of OTC drugs and look into the issue of safety, availability and misuse of drugs which could be permitted as OTC drugs. The sub-committee had submitted its report giving suggestions and the same was placed before DTAB for its consideration. The report of the sub-committee was examined by the DTAB and it made the following recommendations: 1. The drug products permitted to be sold without a sale licence under Schedule K may continue to be sold as such and any further entry to the Schedule should be examined by DTAB on case to case basis. 2. To increase of availability of certain household remedies in the country, the drugs considered safe to be sold without the supervision of a pharmacist could be permitted to be sold under licence in Form 20A and Form 21A for limited categories granted to the dealers desirous of selling drugs and having suitable storage conditions. 3. The list of drugs that could be permitted in the above premises should be examined by a committee of experts constituted by the DCG(I) and intimated to the State Licensing Authorities. AGENDA NO.S-2 IMPLEMENTATION OF THE DRUGS AND COSMETICS (AMENDMENT) ACT, 2008 PASSED BY THE PARLIAMENT ON 5 TH DECEMBER 2008 REGARDING ENHANCEMENT OF PENALTIES FOR OFFENCES RELATING TO SUB STANDARD AND SPURIOUS DRUGS. The member Secretary stated that the Drugs and Cosmetics (Amendment) Act 2008 was passed by the Parliament in December Under this Act punishments for manufacture of spurious and sub standard drugs and violations of provisions of the Act have been enhanced. The date of implementation of the Act is yet to be notified. The Drug Consultative Committee in its meeting held on 10 th December 2008 constituted a subcommittee for uniform of implementation of these provisions in view of the representation received from certain manufacturers associations. The date of implementation would be notified only after the guidelines are approved and circulated to the State Licensing Authorities. DTAB approved the proposal.