Strengthening of Quality Control System in the States/UTs for

Strengthening of Quality Control System in the States/UTs for Ayurvedic, Siddha, Unani and Homoeopathy (ASU&H) Drugs Dr D.C. Katoch Adviser (Ay.) & Head- Drug Control Ministry of AYUSH, Govt. of India

Functionaries dealing with ASU&H drugs Registered Practitioners 7,73,668* Total Teaching Institutions (ASU&H): (A-281, U-44, S-9, H- 197) 622 Postgraduate Institutions (ASU&H): (A-112, U-9, S-3, H-43) 201 9 Annual Intake in Degree courses: (A-15117, U-2131, S- 410, H-13658) 33,601 Annual Intake in PG courses: (A-3089, U-147, S-140, H-918) 4,876 Hospitals in Government Sector 3,943 Dispensaries in Government Sector 27, 698 Drug Manufacturing units (A-7439, U- 585, S-235, H-408) 9038 *Coverage: About 6 AYUSH practitioners per 10,000 population . 2

Integrated or Co-located AYUSH Functionaries AYUSH services available in506 out of 697 District Hospitals, 374 out of 2725 Sub-district Hospitals, 2871 out of 11225 Community Health Centres, 8995 out of 31849 Primary Health Centres 5716 other healthcare centres. 15649 AYUSH practitioners appointed for National Child Health Program and 12263 for imparting general health services.

Need for Regulatory Provisions & Quality Control System To prescribe and enforce standards for manufacturing, distribution, sale and dissemination of information of drugs. To ensure availability of standard drugs ( quality, safety, efficacy) to the people. To promote public protection hazards/harmful effects of drugs. from

Legal Provisions /Regulations for ASU &H drugs Drugs and Cosmetics Act, 1940 – Section 3(a) & (h), Chapter IVA from Section 33B to 33O and First Schedule pertain to ASU drugs. – Second Schedule (4A) provides for quality standards of Homoeopathic drugs. Drugs and Cosmetics Rules, 1945 – Rules 151 to 170, Schedules E(I) for poisonous substances, T for GMP and TA for consumption data of raw materials pertain to ASU drugs. – Rules 30AA, 67, 85 (A to I), 106-A, Schedule K, Schedule M-I pertain to Homoeopathic drugs. Drugs & Magic Remedies (Objectionable Advertisements) Act, 1954 and Rules Principal Act meant for prohibiting advertisement of all kinds of drugs for certain diseases/conditions and improper claims.

Types of Legal Provisions Enabling provisions Prohibitive provisions Penal provisions Empowering provisions for Government authorities and for taking specific actions Exemption provisions

ASU drugs related provisions of Chapter IVA ASUDTAB and ADUDCC- Advisory bodies to Central and State Governments. Misbranded, Spurious and Adulterated drugs Standards of ASU drugs Prohibition of manufacturing and sale of ASU drugs by State Government. Prohibition of manufacturing, sale etc of ASU drugs by Central Government. Appointment of Government Analysts, Inspectors Penalties Confiscation of the stock of ASU drugs Disclosure of ASU drug information to the Inspector Maintenance of records and furnishing of information by license holder Cognizance of offences Rules making power of the Central Government Powers of Central Government to amend First Schedule Powers of Central Government to give directions to State Governments

Nature of ASU Drugs Made from wholesome natural substances of plant, animal, mineral or marine origin. Formulation may be of single ingredient or multiple ingredients or combination of different formulations. Formulation could be herbal, herbo-mineral or any kind of mixture of two or more natural substances. Wholesome extract of medicinal plant (aqueous extract or hydro-alcoholic extract or any other extract) can be the ingredient of ASU formulations.

Broad Types of ASU Drugs Classical/Shastriye/Traditional: Ayurvedic, Siddha or Unani drug includes all medicines intended for internal or external use for or in the diagnosis, treatment, mitigation or prevention of disease or disorder in human beings or animals, and manufactured exclusively in accordance with the formulae described in the authoritative books of Ayurvedic, Siddha and Unani Tibb systems of medicine, specified in the Schedule I of the Act. i.e such formulations as are described in 103 authoritative books including pharmacopoeias and formularies.

Contd Patent or Proprietary: ASU formulations containing only such ingredients, which are mentioned in the formulae described in the authoritative books and do not include a medicine for parenteral administration and the formulation mentioned in any of the authoritative books. i.e. only ingredients/natural substances mentioned in the authoritative books can be used for manufacturing of patent/proprietary ASU medicines.

Phytopharmaceuticals are not ASU Drugs Phytocpharmaceutical drug means and includes purified and standardized fraction with defined minimum four bio-active or phytochemical 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.

Sub-Types of Proprietary ASU Formulations Medicinal Formulation Nutritive Formulation (Balya, Poshak) Aqueous or Hydro alcoholic Extract based Formulation Cosmaceutical Formulation (Saundaryaprasadak) Other Extract-based Formulation

Essentials for Manufacturing of ASU &H drugs 1. License for the manufacturing unit and regulatory approval of intended formulations 2. GMP Compliance 3. 4. Compliance to prescribed Standards, Norms, Guidelines and quality assurance Adequate infrastructural facility, staff, equipment, reference books , reference standards record keeping etc.

License requirements for Classical/Shastriye Formulations 1. Shastriye ASU formulation with Safety study not required dosage form and indications as per Evidence of effectiveness authoritative text authoritative source required. from with Safety study not required Evidence of effectiveness from published literature required. 2. Shastriye ASU formulation change in dosage form 3. Shastriye ASU formulation with new Safety study not required indication Evidence from published literature and/or proof of effectiveness required.

License Requirements for Proprietary Formulations 1. Proprietary formulation with Safety study not required ingredients not from Schedule E(I) and Evidence of effectiveness of based on textual rationale from ingredients from published literature authoritative books. required. Proof of effectiveness from a pilot study required. 2. Proprietary formulation with any of the Safety study required ingredients from Schedule E(I) and based Evidence of effectiveness from on textual rationale from authoritative published literature and proof from books. pilot study required.

License Requirements for Extract-based Formulations References from the authoritative texts required 1. Aqueous extract as per text 2. Aqueous extract as per text Safety study not required but with new indication Proof of effectiveness required 3. Hydro-alcoholic extract as per text 4. Specific Hydro-alcoholic extract Safety study required with New Indication Evidence and proof of effectiveness required 5. Other extracts made from various solvents. Evidence of effectiveness may be required on case to case basis. Acute and Chronic Toxicity, Mutagenicity and Teratogenicity data required. Evidence of effectiveness from published literature and proof from clinical study required.

Regulatory Framework Central Govt. State Govt. Statutory bodies Makes and amends regulatory provisions. Responsible to enforce the legal provisions for ASU&H drugs and related matters. ASUDCC to advise Central & State Governments for uniform implementation of the Act. Has the powers direction to the respect of objectives of the Cosmetics Act. to give States in achieving Drugs & Pharmacopoeia Commission of Indian Medicine & Homoeopathy and Pharmacopoeia Committees. Central Laboratories – PLIM and HPL with Govt. Analysts. Appointment of Licensing Authority/Drug Controller, Drug Inspectors Drug Testing Laboratory ASUDTAB to advise Central & State Governments for technical/policy matters of ASU drugs Appointment Analyst. Sub-committee of Homoeopathy and DTAB. of Govt.

Requirements for making License Application Reference of the formulation/ingredients from the authoritative books listed in the Drugs & Cosmetics Act, 1940. Manufacturing unit should be compliant with the GMP guidelines as prescribed in Schedule ‘T’ of the Drugs & Cosmetics Rules, 1945. Proof of safety and effectiveness as prescribed in Rule 158-B for various categories of ASU medicines.

Contd . Standards of identity, purity and strength and permissible limits of heavy metals, aflatoxins, microbial load and pesticide residue of medicinal plant materials prescribed in the respective Pharmacopeias. Standardized classical formulations prescribed in National Formularies. Label of the drug must contain true list of ingredients (with plant part and form), manufacturing and expiry dates and caution in case of presence of any of Schedule E(I) ingredients in the formulation. Test report/Certificate of Analysis of not more than 12% v/v self generated alcohol in Asavas & Arishtas. In-house standards and testing protocols for proprietary medicines.

Standards of Identity – Purity-Strength of ASU& H Drugs Ayurvedic Pharmacopoeia Unani Pharmacopoeia Siddha Pharmacopoeia 645 (9) 298 monographs 139 monographs monographs of Single Drugs 202 (4) monographs of compound formulations of Single Drugs 150 monographs of compound formulations of Single Drugs Homoeopathic Pharmacopoeia– 1117 monographs

Standard ASU Formulations Ayurvedic Formulary of India National Formulary of Unani Medicine Siddha Formulary of India 985 (3 volumes) including 280 mineral-based formulations 1229 (6 volumes) 399 (2 volumes)

Quality Certification Systems GMP certification must. Free Sale Certificate and Non-conviction Certificate on demand. WHO-GMP/COPP certification for export-oriented ASU herbal drugs. Voluntary certification of quality of AYUSH products through Quality Council of India (QCI) scheme. – Ayush Standard Mark: based on compliance to the standards more than the domestic regulatory requirements. – Ayush Premium Mark: broadly based on compliance to WHO-GMP/USFDA criteria or GMP prescribed by importing country or fulfillment of quality requirements as per international norms.

Responsibilities of State Regulator/ Licensing Authority To ensure that manufacturing site has all required clearances and approvals and adequate manufacturing facilities. To ensure whether the manufacturing premises are complying with the GMP norms. To consider whether the documents submitted with license application are complete and the conditions laid down in Drugs & Cosmetics Rules, 1945 are fulfilled to grant or renew the license. To consider correctness of the contents on the label of medicines in accordance with labeling provisions. To undertake quality check of adequate number of ASU & H drug samples taken from manufacturing sites and market. To monitor advertisements of ASU&H drugs appearing in print and electronic media for misleading claims. To maintain the record of licensed manufacturers, approved medicinal products, raw materials consumption data and upload the details in the website. To take regulatory action against defaulters acting in contravention of the provisions of Drugs & Cosmetics Act and Drugs & Magic Remedies Act and rules thereunder.

Outcome Analysis of Quality Control of ASU&H drugs in last four years of NAM Implementation 28 State Drug Testing Laboratories and 32 State Pharmacies supported for improving their infrastructural and functional capacities. But the functional status is doubtful. Support provided to 31 states for testing of ASU&H drugs and strengthening of enforcement framework but lack of scientific manpower in the DTLs and weak regulatory mechanism continues Enforcement of legal provisions resulted in improved compliance to Good Manufacturing Practices (GMP) from 82.9% in 2014 to 85.8% in 2018, still licenses to manufacturing units are issued and renewed without GMP compliance. Efforts for effective control of misleading advertisements and Quality testing of drug samples need to be enhanced and action taken against the defaulters. 23 states reported to have appointed gazetted officers for monitoring of misleading advertisements of ASU&H drugs but their performance is not visible /reported. Grant funds are lying unutilized or not fully utilised and UCs not submitted /settled as per GFRs.

New initiatives for strengthening quality control of ASU&H drugs 1. Central AYUSH Vertical structure created in CDSCO in February, 2018 with 12 posts of Drug Inspectors, Assistant Drug Controllers and Deputy Drug Controllers. 2. Scheme of Pharmacovigilance for safety monitoring of ASU&H drugs and surveillance of misleading advertisements implemented since November, 2017. 3. e-aushadhi Portal for online Licensing/Certification etc. of ASU&H drugs has been developed and launched for trial and to get feedback from the states. 4. Rule 170 for prohibition of misleading advertisements of ASU drugs notified on 21st December, 2018 under Drugs & Cosmetics Rules, 1945. 5. Order for the Expert Committee in the State for examination of license applications of ASU formulations has been revised with specific ToRs and issued on 4h February, 2019.

Issues and concerns in the States about Quality Control of ASU&H drugs a) State Licensing Authority for ASU drugs must be a technical officer as per Rule 162-A of D&C Rules. b) One drug inspector per 30 manufacturing units may be appointed. Adequate number of Drug Inspectors required in following States: State Total no. of Existing number Additional Drug Manufacturing of Drug Inspectors inspectors units* required Andhra Pradesh Bihar D&N Haveli Daman & Diu 326 286 5 9 2 9 0 0 0 10 1 1

Sl. No State No. of Existing Manufacturing number of units* Drug Inspectors Additional drug inspectors required 5 Jharkhand 34 0 1 6 Karnataka 236 6 2 7 Kerala 753 8 17 8 Odisha 99 9 Puduchery 37 1 1 2 1 10 Rajasthan 317 4 7 11 4 Telangana 632 12 West 3 Bengal 316 * As on 1-4-2017(Source AYUSH in India 2017) 17 8

Contd . c) As per D&C Rules, 1945 GMP compliance is mandatory for manufacturing of ASU&H drugs. Following states are required to take urgent action for ensuring that licenses are not granted or renewed without GMP Compliance. S. No. State / UT Total Units* GMP Non-Compliant units* 1 Maharashtr a Uttar Pradesh Gujarat Bihar West Bengal Assam 834 391 1835 266 581 286 316 44 162 143 88 36 2 3 4 5 6

Contd. S.n o. 7 8 9 10 11 12 State / UT Total Units* Puducherry 37 Jharkhand 34 Odisha 99 Telangana 632 Rajasthan 317 Jammu & 22 Kashmir 13 Karnataka 236 * As on 1-4-2017 (Source AYUSH in India 2017) GMP NonCompliant units* 35 34 23 20 16 10 7

Contd . d) Actions may be taken to ensure that each State Drug Testing Laboratory (DTL) supported through NAM and erstwhile Centrally Sponsored Scheme i) is properly equipped with necessary infrastructure & technical manpower, made functional and is approved/licensed under Drugs & Cosmetics Rules, 1945 ( Rule 160 A to J). ii) Govt Analyst has been appointed and notified iii) Regular testing of sufficient number of ASU&H drug samples (taken from market, manufacturing units, Govt supplies, complaints is done and findings are reported to the State and Central Governments and action is initiated against the failed samples. iv) Financial support required for the DTL be clearly reflected in the State Annual Action Plan with necessary details and justification.

Contd e) State Pharmacies supported through NAM and earlier through the Centrally Sponsored Scheme should bei) properly equipped with required manpower; infrastructural facilities and ii) GMP compliant and licensed under Drugs & Cosmetics Rules, 1945; iii) Capable to manufacture and supply sufficient quantity of quality medicines to State Government dispensaries, hospitals and other health facilities; iv) Financial support required for strengthening may be reflected in SAAP with necessary details and justification in accordance with NAM guidelines.

Contd . f) Misleading advertisements with improper contents and exaggerated claims of ASU&H drugs in print and electronic media need to be controlled by enforcing the provisions of Drugs & Magic Remedies (Objectionable Advertisements) Act, 1954 and Rules thereunder and recently notified Rule 170 of the Drugs & Cosmetics Rules, 1945. i) Necessary legal action should be initiated immediately against the alleged advertisement on receiving information from the reporting officer/inspector of the State and the complaints escalated from Consumers, GAMA Portal of Department of Consumer Affairs, Advertising Standards Council of India (ASCI), Ministry of AYUSH and Pharmacovigilance Centres and through RTI Applications and Public Grievances. FIR can be filed with the Police in case details of the manufacturer or advertiser are not known and authority of concerned state can be approached.

Contd . ii) Regulatory officers in the states must undertake regular surveillance of misleading advertisements in the print and electronic media. iii) List of defaulters, faulty advertisements and action taken against them may be put in the website for protecting public from the use of such medicinal products and also reported to Central Government periodically and as & when asked for. iv) Misleading advertisements of ASU&H drugs manufactured in other state must be reported to the Licensing Authority of that state.

g) Settlement of long pending Utilization Certificates under the erstwhile Centrally Sponsored Scheme of Quality Control of ASU&H Drugs. Action required from following states: S. No. 1 2 3 4 5 6 State/UT Assam Bihar Himachal Pradesh Jharkhand Madhya Pradesh Maharashtra Amount of UC pending (Rs. in lakhs) and Since 25.72 (2003-04) 243.54 (2000-01) 86.80 (2002-03) 258.06 (2005-06) 100.00 (2011-12) 9.52 (2003-04)

S.No State/UT 7 8 9 Meghalaya Orissa Sikkim Amount of UC pending (Rs. in lakhs) and Since 25.85 (2003-04) 87.11 (2004-05) 134.89 (2006-07) ( Achievement cum Performance report, Register of Assets and Certificate of not availing any other grant for the same purpose are not provided with the recently submitted UCs) 10 11 12 13 14 Tamil Nadu Tripura Uttar Pradesh Uttarakhand Lakshadweep Total 136.00 (2007-08) 78.71 (2003-04) 226.18 (2000-01) 21.56 (2004-05) 16.00 (2007-08) 1449.94

Revised Funding Pattern of NAM for Drugs Quality Control Activities Intended Activity Existing Pattern Proposed revision Overall share for Drugs Quality Control No fixed norm 10% of the state envelop Pharmacy Maximum Rs 5.00 cr (70% i.e. Rs. 3.50 cr for building & equipment and 30% i.e Rs. 1.50 cr for recurring expenditure on manpower, raw materials etc. DTL Maximum Rs 4.00 cr (80% i.e. Rs. 3.20 cr for building & equipment and 20% i.e Rs. 1.20 cr for recurring expenditure on technical manpower, chemicals & Note: States/UTs may explore the possibility of establishing and maintaining pharmacy & DTL as joint asset by pooling resources and for effective management of supply and quality testing of medicines. Non Recurring: Rs. 3.50 cr for construction and Rs. 2.50 cr for equipment/instruments in two installments minus amount of grant already under NAM. Recurring: Rs 25 lakhs per year Non Recurring: Rs. 3.00 cr for construction and Rs. 2.00 cr for equipment/instruments in two installments minus amount of grant already under NAM. Recurring: Up to Rs 25 lakhs per year

Contd . Capacity building for enforcement of regulatory provisions & quality control Strengthening of Drugs Control framework ----- Upto Rs 50.00 lakh including Rs. 20.00 lakh as first installment and Rs. 30 .00 lakh in subsequent installments Upto Rs. 8.00 lakh per annum Documentation etc of quality control materials Testing of drugs Rs. 15.00 lakh per year for large states and Rs. 5.00 lakh per year for UTs & NE states except Assam. Up to Rs 25.00 lakh per year for quality control training workshop, computerization, data management, infrastructure strengthening etc of regulatory framework . -- -----

Thanks *For any regulatory/enforcement query, clarification or guidance, write [email protected] , [email protected] Drug Control Cell Ministry of AYUSH AYUSH Bhawan, ‘B’ Block, GPO Complex INA, New Delhi-110023.