Company : Sol Infotech Pvt. Ltd. Website : www.courtkutchehry.com Drugs And Cosmetics (Eighth Amendment) Rules, 2015 [30 November 2015] CONTENTS 1. Rule 1 2. Rule 2 3. Rule 3 4. Rule 4 5. Rule 5 6. Rule 6 Drugs And Cosmetics (Eighth Amendment) Rules, 2015 [30 November 2015] G.S.R. 918(E).-Whereas a draft of the rules further to amend the Drugs and Cosmetics Rules, 1945, was published, as required by section 12 and section 33 of the Drugs and Cosmetics Act, 1940 (23 of 1940), vide notification of the Government of India in the Ministry of Health and Family Welfare (Department of Health and Family Welfare), number G.S.R. 702(E), dated the 24th October, 2013, in the Gazette of India, Extraordinary, Part II, Section 3, Sub-section (i), dated the 24th October, 2013, inviting objections and suggestions from all persons likely to be affected thereby before the expiry of a period of forty-five days from the date on which the copies of the Official Gazette of the said notification were made available to the public; A nd whereas copies of the Gazette were made available to the public on the 29th October, 2013; And whereas, the objections and suggestions received from the public on the said draft rules have been considered by the Central Government. Now, therefore, in exercise of the powers conferred by section 12 and section 33 of the Drugs and Cosmetics Act, 1940 (23 of 1940), the Central Government, after consultation with the Drugs Technical Advisory Board, hereby makes the following rules further to amend the Drugs and Cosmetics Rules, 1945, namely:- 1. Rule 1 :- (1) These rules may be called the Drugs and Cosmetics (Eighth Amendment) Rules, 2015. (2) They shall come into force on the date of their publication in the Official Gazette. 2. Rule 2 :- In rule 2 of the Drugs and Cosmetics Rules, 1945 (hereinafter referred to as the said rules), after clause (ea) the following clause shall be inserted, namely:- ( e b ) . "Phytopharmaceutical drug" includes purified and standardised fraction with defined minimum four bio-active or phyto-chemical compounds (qualitatively and quantitatively assessed) of an extract of a medicinal plant or its part, for internal or external use of human beings or animals for diagnosis, treatment, mitigation or prevention of any disease or disorder but does not include administration by parenteral route.. 3. Rule 3 :- In rule 122-A of the said rules,- (i) in sub-rule (1), in clause (b), in the second proviso, for the words, figures and letter "Appendix I or Appendix IA", the words, figures and letters, "Appendix I or Appendix IA or Appendix IB", shall be substituted; (ii) in sub-rule (2), for the words, figures and letter "Appendix I or Appendix IA", the words, figures and letters, "Appendix I or Appendix IA or Appendix IB", shall be substituted. 4. Rule 4 :- In rule 122-B of the said rules,- (i) in sub-rule (1), in clause (b), in the second proviso, for the words, figures and letter "Appendix I or Appendix I A", the words, figures and letters, "Appendix I or Appendix IA or Appendix I B", shall be substituted; (ii) in sub-rule (2), for the words, figures and letter "Appendix I or Appendix IA", the words, figures and letters, "Appendix I or Appendix IA or Appendix IB", shall be substituted. 5. Rule 5 :- In rule 122-E of the said rules, in clause (a), after the words "bulk drugs substance," the words "or phytopharmaceutical drug" shall be inserted. 6. Rule 6 :- In Schedule Y of the said rules, after APPENDIX IA, the following Appendix shall be inserted, namely:- "APPENDIX I B DATA TO BE SUBMITTED ALONG WITH APPLICATION TO CONDUCT CLINICAL TRIAL OR IMPORT OR MANUFACTURE OF A PHYTOPHARMACEUTICAL DRUG IN THE COUNTRY PART - I 1. Data to be submitted by the applicant: 1.1. A brief description or summary of the phytopharmaceutical drug giving the botanical name of the plant (including vernacular or scriptural name, wherever applicable), formulation and route of administration, dosages, therapeutic class for which it is indicated and the claims to be made for the phytopharmaceutical product. 1.2. Published literature including information on plant or product or phytopharmaceutical drug, as a traditional medicine or as an ethno medicine and provide reference to books and other documents, regarding composition, process prescribed, dose or method of usage, proportion of the active ingredients in such traditional preparations per dose or per days consumption and uses. 1.3. Information on any contraindications, side effects mentioned in traditional medicine or ethno medicine literature or reports on current usage of the formulation. 1 . 4 . Published scientific reports in respect of safety and pharmacological studies relevant for the phytopharmaceutical drug intended to be marketed,- (a) where the process and usages are similar or same to the product known in traditional medicine or ethno medicine; and (b) where process or usage is different from that known in traditional medicine or ethno medicine. 1.5. Information on any contraindications, side effects mentioned or reported in any of the studies, information on side effects and adverse reactions reported during current usage of the phytopharmaceutical in the last three years, wherever applicable. 1.6. Present usage of the phytopharmaceutical drug, - to establish history of usages, provide details of the product, manufacturer, quantum sold, extent of exposure on human population and number of years for which the product is being sold. 2. Human or clinical pharmacology information: 2.1. Published scientific reports in respect of pharmacological studies including human studies or clinical studies or epidemiological studies, relevant for the phytopharmaceutical drug intended to be marketed,- (a) where the process and usages are similar or same to the product known in traditional medicine or ethno medicine; and (b) where process or usage is different from that known in traditional medicine or ethno medicine. 2.2. Pharmacodynamic information (if available). 2.3. Monographs, if any, published on the plant or product or extract or phytopharmaceutical. (Copies of all publications, along with english translation to be attached.) PART - II Data generated by applicant 3 . Identification, authentication and source of plant used for extraction and fractionation: 3.1. Taxonomical identity of the plant used as a source of the phytopharmaceutical drug giving botanical name of genus, species and family, followed by the authority citation (taxonomists name who named the species), the variety or the cultivar (if any) needs to be mentioned. 3 . 2 Morphological and anatomical description giving diagnostic features and a photograph of the plant or plant part for further confirmation of identity and authenticity. (Furnish certificate of confirmation of botanical identity by a qualified taxonomist). 3.3 Natural habitat and geographical distribution of the plant and also mention whether the part of the plant used is renewable or destructive and the source whether cultivated or wild. 3.4 Season or time of collection. 3.5 Source of the plant including its geographical location and season or time of collection. 3.6 A statement indicating whether the species is any of the following, namely:- ( a ) determined to be endangered or threatened under the Endangered Species Act or the Convention on International Trade in Endangered species (CITES) of wild Fauna and Flora; (b) entitled to special protection under the Biological Diversity Act, 2002 (18 of 2003); (c) any known genotypic, chemotypic and ecotypic variability of species. 3.7. A list of grower or supplier (including names and addresses) and information on the following items for each grower or supplier, i f available or identified already, including information of primary processing, namely:- (a) harvest location; (b) growth conditions; (c) stage of plant growth at harvest; (d) harvesting time; (e) collection, washing, drying and storage conditions; (f) handling, garbling and transportation; (g) grinding, pulverising of the plant material; and (h) sieving for getting uniform particle size of powdered plant material. 3.8. Quality specifications, namely:- (a) foreign matter; (b) total ash; (c) acid insoluble ash; (d) pesticide residue; (e) heavy metal contamination; (f) microbial load; ( g ) chromatographic finger print profile with phytochemical reference marker; (h) assay for bio-active or phytochemical compounds; and (i) chromatographic fingerprint of a sample as per test method given under quality control of the phytopharmaceutical drug (photo documentation). 3.9 . An undertaking to supply specimen sample of plant duly labeled and photocopy of the certificate of identity confirmation issued by a qualified taxonomist along with drawings or photographs of the diagnostic morphological and histological features of the botanical raw material used for the confirmation of authenticity. 4. Process for extraction and subsequent fractionation and purification: 4.1. Quality specifications and test methods for starting material. 4.2. Steps involved in processing. (a) details of solvent used, extractive values, solvent residue tests or limits, physico-chemical tests, microbial loads, heavy metal contaminants, chromatographic finger print profile with phytochemical reference markers, assay for active constituents or characteristic markers, if active constituents are not known; (b) characterisation of final purified fraction; (c) data on bio-active constituent of final purified fraction; ( d ) information on any excipients or diluents or stabiliser or preservative used, if any. 4.3. Details of packaging of the purified and characterised final product, storage conditions and labeling. 5. Formulation of phytopharmaceutical drug applied for: 5.1. Details of the composition, proportion of the final purified fraction with defined markers of phytopharmaceutical drug per unit dose, name and proportions of all excipients, stabilisers and any other agent used and packaging materials. 5.2. Test for identification for the phytopharmaceutical drug. 5.3. Quality specifications for active and inactive phytopharmaceutical chromatographic finger print profile with phytochemical reference marker and assay of active constituent or characteristic chemical marker. 6. Manufacturing process of formulation: 6.1. The outline of the method of manufacture of the dosage form, along with environmental controls, in-process quality control tests and limits for acceptance. 6.2. Details of all packaging materials used, packing steps and description of the final packs. 6.3. Finished products quality specifications, including tests specific for the dosage form, quality and chromatographic finger print profile with phytochemical reference marker and assay for active constituent or characteristic marker, if active constituents are not known. 7. Stability data: 7.1. Stability data of the phytopharmaceutical drug described at 4 above, stored at room temperature at 40 +/- 2 deg. C and humidity at 75%RH +/- 5%RH for 0, 1, 2, 3 and 6 months. 7.2 Stability data of the phytopharmaceutical drug in dosage form or formulation stored at room temperature at 40 +/- 2 deg. C and humidity at 75%RH +/- 5%RH for 0, 1, 2, 3 and 6 months, in the pack intended for marketing. 8. Safety and pharmacological information: 8.1. Data on safety and pharmacological studies to be provided. 8.2. Animal toxicity and safety data: (a) 28 to 90 days repeat dose oral toxicity on two species of animals; (b) In-vitro genotoxicity data (Ames test and Chromosomal aberration test as per Schedule Y); (c) dermal toxicity tests for topical use products; ( d ) teratogenicity study (only if phytopharmaceutical drug is intended for use during pregnancy). 9. Human studies: 9.1. Clinical trials for phytopharmaceutical drugs to be conducted as per applicable rules and guidelines for new drugs. 9.2. For all phytopharmaceutical drugs data from phase I (to determine maximum tolerated dose and associated toxicities) and the protocols shall be submitted prior to performing the studies. 9.3. Data of results of dose finding studies performed and the protocols shall be submitted prior to performing the studies: Provided that in the case of phytopharmaceutical drug already marketed for more than five years or where there is adequate published evidence regarding the safety of the phytopharmaceutical drug, the studies may be abbreviated, modified or relaxed. 10. Confirmatory clinical trials: 10.1. Submit protocols for approval for any specific or special safety and efficacy study proposed specific to the phytopharmaceutical drug. 10.2. Submit proposed protocol for approval for human clinical studies appropriate to generate or validate safety and efficacy data for the phytopharmaceutical dosage form or product as per applicable rules and guidelines. 10.3. Submit information on how the quality of the formulation would be maintained during the above studies. 11. Regulatory status: 11.1. Status of the phytopharmaceutical drug marketed in any country under any category like functional food or dietary supplement or as traditional medicine or as an approved drug. 12. Marketing information: 12.1. Details of package insert or patient information sheet of the phytopharmaceutical drug to be marketed. 12.2. Draft of the text for label and carton. 13. Post marketing surveillance (PMS): 13.1. The applicant shall furnish periodic safety update reports every six months for the first two years after approval the drug is granted. 13.2. For subsequent two years the periodic safety update reports need to be submitted annually. 14. Any other relevant information: Any other relevant information which the applicant considers that it will help in scientific evaluation of the application.".