Home India Ministry of Health and Family Welfare Public notice regarding Consideration of orders of High Cour...
Date: 2019-02-13 Category: Not Applicable State: Union Government Country: India

Public notice regarding Consideration of orders of High Court of Karnataka dated 14.08.2013 &24.07.2017 to examine the issue of safety and efficacy of Fixed dose combination of Flupenthixol +Melitracin for human use in light of notifications G.S.R. 377(E) dated 18.06.2013 & G.S.R. 498(E) dated 11.07.2014 and to provide hearing to the petitioners/manufacturers

Issued by Ministry of Health and Family Welfare · Central Drugs Standard Control Organization

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Executive Summary & Key Takeaways

**Executive Summary:** This public notice concerns the review of the safety and efficacy of the Fixed Dose Combination (FDC) of Flupenthixol Melitracen for human use, following orders from the High Court of Karnataka and notifications G.S.R. 377E and G.S.R. 498E. A Sub-Committee of the Drugs Technical Advisory Board (DTAB) has been formed to examine the issue, and the notice requests petitioner-manufacturers to submit information in a prescribed format by March 15, 2019, to comply with the court's directions. **Key Points / Main Content:** * **Context:** Review of Flupenthixol Melitracen FDC due to High Court of Karnataka orders and notifications G.S.R. 377E and G.S.R. 498E. * **DTAB Sub-Committee:** * A Sub-Committee has been constituted to examine the safety and efficacy of the FDC. * The Sub-Committee is chaired by Dr. Nilima Kshirsagar. * **Information Submission:** * Petitioner-manufacturers must submit information in the format outlined in Annexure A. * Submissions must be in hard copy and soft copy (CD form). * Deadline for submission: March 15, 2019, by 5:00 PM. * **Information Required in Annexure A:** * Product Composition * Brand names * Applicant details (Manufacturer, Marketer, Petitioner/appellant) * Approving Authority Details * Drug Particulars (Dosage form, Composition, Pharmacological classification) * Indications * Copy of Package Insert (Schedule Y) * FDC Approval Category (Appendix V1) * Therapeutic justification rationale for each ingredient * Therapeutic value claimed * Pharmacokinetic pharmacodynamics rationality * Published safety and efficacy data * Original safety efficacy data * Regulatory status in other countries * Specimen labels and cartons * PPT presentation (7 slides max) **Impact Analysis** * **Petitioner-Manufacturers:** * *Impact:* Required to compile and submit detailed information on the Flupenthixol Melitracen FDC as per Annexure A. * *Action Required:* Prepare and submit the required information in both hard and soft copy by March 15, 2019. * **Indian Drugs Manufacturing Associations, OPPI, IDMA, FOPECI, IIPA:** * *Impact:* Expected to disseminate this notice to their members. * *Action Required:* Communicate the notice to their members and publicize it widely. * **CDSCO (Central Drugs Standard Control Organization):** * *Impact:* Responsible for making information available to stakeholders. * *Action Required:* Post the notice on the CDSCO website for information and necessary action by petitioners and stakeholders. * **All Stakeholders:** * *Impact:* Need to be aware of the review process and potential outcomes. * *Action Required:* Stay informed about the process and comply with any further requests for information or action.

Key Entities Referenced

Flupenthixol Melitracen: Fixed Dose Combination (FDC) drug, the safety and efficacy of which is under examination. High Court of Karnataka: The court that issued orders dated 14.08.2013 and 24.07.2017 regarding the examination of Flupenthixol Melitracen. G.S.R. 377E dated 18.6.2013: Government notification related to drugs and cosmetics. G.S.R. 498E dated 11.07.2014: Government notification related to drugs and cosmetics. Drugs Technical Advisory Board DTAB: Advisory board that deliberated on the directions of the High Court of Karnataka regarding Flupenthixol Melitracen. Directorate General of Health Services: Organization under whose chairmanship the DTAB meeting was held. Dr. Nilima Kshirsagar: Chairperson of the Sub-Committee constituted to examine the safety and efficacy of Flupenthixol Melitracen. Indian Council of Medical Research ICMR, Mumbai, Maharashtra: Organization to which Dr. Nilima Kshirsagar is affiliated and where the clinical pharmacology chair is located.
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File No. 04-01/2011-DC (Pt. Deanxit) Govt. of India Directorate General of Health Services Central Drugs Standard Control Organization (FDC Division) FDA Bhawan, Kotla Road New Delhi-110002 Dated: PUBLIC NOTICE it 3 FEB 2019 Subject: Consideration of the orders of High Court of Karnataka dated14.08.2013 & 24.07.2017 to examine the issue of safety and efficacy of Fixed Dose Combination of Flupenthixol + Melitracen for human use in light of notifications G.S.R. 377(E) dated 18.6.2013 & G.S.R. 498(E) dated 11.07.2014 and to provide hearing to the petitioners/manufacturers -regarding. In the 81 meeting of the Drugs Technical Advisory Board(DTAB) held on 29.11.2018 under the Chairmanship of the Director General of Health Services, the DTAB deliberated the directions/orders of the of Hon'ble High Court of Karnataka dated14.08.2013 & 24.07.2017. Accordingly, a Sub-Committee has been constituted under the Chairmanship of Dr. Nilima Kshirsagar, The Chair in Clinical Pharmacology, Indian Council of Medical Research (ICMR), Mumbai to examine the issue of safety and efficacy of Fixed Dose Combination of Flupenthixol + Melitracen for human use in light of notifications G.S.R. 377(E) dated 18.6.2013 & G.S.R. 498(E) dated 11.07.2014 and orders of High Court of Karnataka dated14.08.2013 & 24.07.2017. In this regard, a meeting of the Sub-Committee of DTAB took place on 06" Feb, 2019. The Committee has desired and requested that the Petitioner/Manufactures may submit the information in the prescribed format as per Annexure ‘A’ which is enclosed herewith for further action in compliance to the directions of the Hon’ble High Court of Karnataka. Accordingly all the petitioners/manufacturers are requested to submit the information in the prescribed format in hard copy as well as in soft copy (i.e. in C.D. form) to this office latest by the 15.03.2019 till 05:00pm to fulfil the DTAB Sub-Committee proceedings as per Hon’ble High Court of Karnataka. This is for the information of all stakeholders. (Sanjeev mar) Convener, Sub-Committee of DTAB Encl: Annexure A Copy to: 1. Dr. Nilima Kshirsagar, The Chair in Clinical Pharmacology, Indian Council of Medical Research (ICMR), Mumbai, (Chairperson) 2. Indian Drugs Manufacturing Associations OPPI/IDMA/FOPE/CIPI/IPA- with the request to communicate it to your members and publicize it widely so that all concerned can avail this opportunity. 3. Website of CDSCO for information and necessary action of all petitioners and stakeholders for complying the hearing and subsequent report submission process.Annexure A Format for submission of information by appellant/petitioner/manufacturer/marketing company on FDC to DTAB Sub-Committee (Submit information as hard copy as well as soft copy) s. | Item Response No (a) Composition of Product: (Details of all | strengths/dosage forms) (b ) Brand ‘name/s, if any: (c) Name of the Applicant, specify if i. Manufacturer: | ii. Marketer : ili, Petitioner/appellant '(d) Approving authority with Name of the Authority Year of Approval year of approval Signature of the Authorized representative: E Name: _ Designation: _ Date: Place: Communication (Address, Telephone, Email) Details: Company Seal:Item Response No. \ 2. Particulars of the drug: Dosage form, composition of the formulation (including allactiveingredients, ; pharmacological classification) 3 Indication(s) 4 Provide a copy of Package insert as per Schedule Y of Drugs & Cosmetics Rules. ee 3 State the category (as per Appendix V1) under which FDC approval is claimed oe hie and quantity in the FDC al 6. a) Therapeutic justification / rationale for each ingredient b) Therapeutio value claimed or purported to be claimed of the FDC (Postulated advantage/ value of FDC) (Submit a one-page summary with highest level of evidence, supporting the claim of postulated advantage/rationale. The evidence should be enclosed in the form of maximum of five relevant full text articles in peer-reviewed journals/ relevant pages from textbooks) [Tick (V) approptiate option(s)] i. Increased efficacy ii. Reduced incidence and/or severity of adverse effects ili, Dose reduction iv. Reduced cost v._ Booster for another drug vi. Improved patient adherence/ Convenience vii, Minimization of abuse of other actives viii. Simpler logistics of procurement and/ or distribution ix. Reduced development of microbial resistance x. Any other (please specify)Response S. : Item 7. Pharmacokinetic/ pharmacodynamics rationality with half-life details of individual ingredients, dosage schedule of individual drugs (Submit a one-page summary with highest level of evidence, supporting the claim of postulated | advantage/rationale. The evidence should be enclosed in | the form of maximum of five relevant full text articles in | peer-reviewed journals/ relevant pages from textbooks) | 8. Published data regarding safety and efficacy of FDC (Submit a one-page summary with highest level of evidence, supporting the claim of postulated advantage/rationale. The evidence should be enclosed in the form of maximum of five relevant full text articles in peer-reviewed journals/ relevant pages from textbooks) | 9. Original Safety & Efficacy data if any, regarding the | FDC, generated by the applicant (Submit a one-page summary.Also submit the article based on these data, if publishedorone-page abstract of each study if unpublished with CTRI number, if ___| available) 10. | Regulatory status of the FDC in other countries 10.1 | Countries where the drug is: (a) Marketed (b) Approved _(c) Approved as IND (d) withdrawn, if any, with reasons 10.2 | Restrictionson use, if any, in countries where _marketed/approved 1 Specimen of labels and cartons 12 “Any other relevant information 13. | Submit PPT of presentation in hard copy (Maximum 7 | slides) which the company will present to the committee {oo} (Note: Individual Form shall be submitted for each FDC and all above information shall be provided for each strength/ dosage form for an FDC in the same form or separate form if required )

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