SCHEDULE T(GMP of Indian system of medicines)

Schedule T (GMP for ISM )
The manufacturing practices about the Indian system of medicine mainly focused on ASU drugs (Ayurveda,Siddha,Unani)

1. Schedule -T (gmp of Indian SYSTEM OF MEDICINES ) GUIDED BY- Z ubala Mirza Ma’am Dept of pharmacognosy and phytochemistry, GCOP Amravati PRESENTED BY- Mohammad Ahfaz Zaid  M.pharm 1st year Dept of pharmacognosy and phytochemistry, GCOP Amravati GOVERNMENT COLLEGE OF PHARMACY AMRAVATI GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI

2. CONTENT GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Sr. No. Content 1 Introduction 2 Objectives/Principles of GMP 3 Components of GMP 4 Quality assurance in ISM 5 Challenges in Safety Monitoring of Herbal Medicines 6 References

3. Introduction  

4. Schedule T: (Schedule T describes the Good Manufacturing Practice for Ayurvedic, Siddha and Unani Medicines.) The Good Manufacturing Practices (GMP) are prescribed as follows:> Raw materials used in the manufacture of drugs are authentic, of prescribed quality and are free from contamination. The manufacturing process is as has been prescribed to maintain the standards. Adequate quality control measures are adopted.The manufactured drug which is released for sale is of acceptable quality. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 1

5. In India GMP was introduced under schedule-M as an amendment to Drugs and Cosmetics rules 1945 . Then after this Schedule was further elaborated in 23 june 2000 which specific the GMP features to be followed for ISM (Indian System of Medicine) drugs. Units registered prior to 23 June 2000 are given two years time to comply with individual Vaidya's/Siddhas/Hakim's exempted. Request for GMP certificate will be made on plain paper. After proper inspection, GMP certificate will be issued within three months GMP certificate will be given in form EL(under Rule 157-B) for a period of three years. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 2

6. Objectives/Principles of GMP Implementation of GMP ensures total quality assurance covering all the spheres in a manufacturing system. These are highlighted below Raw material and Finished products - Their authenticity, quality, freedom from foreign matter and contaminant. Manufacturing process confirms to prescribed quality standards. Adoption adequate quality control measures. Documentation- Methodologies and procedure. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 3

7. Components of GMP Different components of GMP are given below in order of appearance in Schedule-T Personal Location in surroundings Buildings Water supply containers cleaning Disposal of waste GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 4

8. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 5 Store Working space Machinery and equipments Health and hygiene. Packaging. Documentation and records

9. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 6 Personn e l   Qualification and practical experience. The manufacturer should have an adequate number of personnel with the necessary qualifications and practical experience.  Authorities and responsibilities. The responsibilities placed on any one individual should not be so extensive so as to present any risk to quality. The personnel must be given adequate authority to perform his work.

10. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 7 2. Location and surroundings. The factory building for manufacture of ASU(Ayurveda, Siddha and Unani) medicines shall be so situated and shall have such construction as to avoid contamination from open sewerage, drain, public lavatory for any factory which produces disagreeable or obnoxious odour or fumes or excessive soot, dust and smoke.

11. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 8 3. Buildings (Factory premises) The buildings used for factory shall be such as to permit production of-:• Drugs under hygienic conditions and should be free from cobwebs and insects/rodents.• It should have adequate provision of light and ventilation.• The floor and the walls should not be damp or moist.

12. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 9 4. Water supply Water used in manufacturing should be pure and of potable quality. Adequate provision for washing of premises should be made. Potable water should conform to prescribed standards (ICMR standards) Ion-exchange treatment and distillation plants may be installed for the availability of purified water and water for injection respectively.

13. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 10 5. Container cleaning. There there should be provision for independent area for cleaning of containers Adequate arrangement of washing, cleaning and drying of containers,(bottles, jars etc Use for packaging of various doses form should be made

14. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 10 6 .Disposal of waste From the manufacturing section and laboratories the waste water and the residues which, might be prejudicial to the workers or public health shall be disposed off.

15. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 11 7.Store Raw material stores :• For the storage of raw material appropriates containers as per materials (physical and chemical properties) may be used to prevent from dampness, microbiological contamination, rodent and insects infection. In ISM manufacturing unit raw material may be categorised as follows for their appropriate storage:-

16. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 12 In ISM manufacturing unit raw material may be categorised as follows for their appropriate storage:- Fresh herbs eg.Mint,Basil Dry herbs eg. Parsley, Rosemary Plant extracts and exudates/resins etc. Volatile oils/perfumes and flavours e.g. Peppermint, Clove, Caraway Animal origin eg. Honey, Royal jelly, Beeswax.

17. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 13 Mineral origin E g. Clays,Bentonite, Aggregates, Kaolin Excipients eg.colorants, sweeteners, binders, diluents.

18. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 14 Each container should be properly labeled and informative in following format: Name of raw material Source of supply Status- Under test/ Approved/ Rejected Batch/Lot no. Date of receipt.

19. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 15 * Working space: Manufacturing area should be have adequate space and arrangement to prevent cross contamination. 8.Working space

20. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 16 Space requirement for manufacturing of Ayurveda and siddha medicine: Category of medicine. Mini. Space required. 1 . Anjana/ pisti 100 sq.ft 2. Churna / manjun / Lepa / Nasya 200 sq. ft 3. Pills/ Vatti / Gutika 100 sq.ft 4. Tablets 100 sq.ft 5. Bhasma / Lavana / Satva / Sindura 100 sq.ft 6. kajal 150 sq.ft 7. Capsule 100 sq.ft 8. Asava / Arishtha 150 sq.ft 9. Sura 200 sq.ft 10. Ark Tinir 100 sq. ft

21. Category of medicine. Mini. Space required. 1 . Majoon / laooq / Itrifla Tiryao 100 sq.ft 2. Arq 100 sq. ft 3. Habb (Pills) 100 sq.ft 4. Sufoof (power) 100 sq.ft 5. Raughan (oils) 100 sq.ft 6. Marham,Zimad (ointment) 100 sq.ft 7. Qurs (tablets) 100 sq.ft 8. Qutoor Chasm & Marham (eye drop &eye ointment ) 100 sq.ft 9. Sharbat & jushanda 100 sq.ft 10. Murabba 100 sq. ft GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 17 Space requirement for manufacturing of Unani medicine :

22. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 18 9. Machinery and Equipments Machinery and equipments should be according to the size of operation and nature of product. Manufacturing process could be manual, semi-automatic or automatic. These equipments have to be properly installed and maintained with proper cleaning. There should be adequate space between machines to facilitate the cleaning and maintenance operation. Proper Standard Operational Procedures (SOPs) for cleaning, maintaining and performance of every machine should be laid down.

23. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 19 Space requirement for manufacturing of Ayurveda and siddha medicine: Category of medicine. Machinery and equipment required. Ajana / pisti Kharel - machanized / Motorized , ball-mill, sieves/shifters, 2. Churna / manjun / Lepa / Nasya Grinder, disintegrator, powder mixer, pulverize,sieves /shifter 3. Pills/ Vatti / Gutika Ball mill,mass mixer,vati cutting machine, stateless steel trays/containers for storage 4. Tablets Ball mill, mass mixer/powder mixer, granulator, dryer, compressing machine and sugar coating machine 5. Bhasma / Lavana / Satva / Sindura Bhatti, Karahi/stainless steel vessels/ Patila flask,/plaster of Paris, copper rod,furnace

24. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 19 Space requirement for manufacturing of Ayurveda and siddha medicine: Category of medicine. Machinery and equipment required. 6. Capsule Air conditioner, de-humidifier , hygrometer, thermometer, capsule feeling machine 7. Ointment/ marham pasa Tube feeling machine, crimping machine/ointments mixer, end runner / mill 8.Asava / Arishtha Tincture press, exhaust fan fitted and fly proof, bhatti section, bottle washing machine, liquid feeling machine, fermentation tank, containers,

25. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 21 All the workers should be free from contagious disease. Their uniforms should be suitable to nature of work climate. Clean towel, soap, scrubbing brushes etc. should be provided to them. Their hand should be cover with cloth or synthetic covering. Stress should be on personal cleaness . 10. Health and hygiene

26. 11. Packaging BY GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 22 • Packaging important for avoiding contamination.  •   requirements for pharmaceutical product labelling, ensure accurate, clear, and legible labels. •  Include essential information like product name, strength, dosage form, lot number, expiration date, and manufacturer details .

27. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 23 Manufacturing records are required to provide an account of the list of raw materials and their quantities obtained from the store, tests conducted during the various stages of manufacture like taste, colour, physical characteristics and chemical tests as may be necessary or indicated in the approved books of Ayurveda, Siddha and Unani mentioned in the First Schedule of the Drugs and Cosmetics Act, 1940 (23 of 1940. 12. Documents & Records 1.Batch Manufacturing Records

28. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 24 Manufacturing shall maintain the following records Each batch manufacturing record of every machine. List of raw material used ,quality obtained from the store for production of medicine. Quality control tests such as color ,physical characteristics etc

29. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI 23 Records of sale and distribution of each batch of Ayurveda, Siddha and Unani Drugs shall be maintained in order to facilitate complete recall of the batch , if necessary. 2. Distribution Records 3. Records of market complaints All reports of market complaints received regarding the products sold in the market.• Manufacturer shall enter all data received on such market complaints, investigations carried out by the manufacturers regarding the complaint as well as any corrective action initiated to prevent recurrence of such market complaints shall also be recorded.

30. QUALITY CONTROL/ASSURANCE FOR ASU DRUG INDUSTRY GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Quality Control/Assurance is the department, which controls all activities at various level of manufacturing as National & International standard. Quality Control is a part of quality management focused on full filling quality requirement. Quality Assurance providing confidence that quality requirement will be fulfilled. There are various issues & challenges related to drug quality for ASU&H Pharmaceutical Industries in India. This needs proper attention of policy makers and regulator & academia. Complete Implementation of GMP (schedule T) norm/guidelines and quality control/assurance procedure and activities is a big challenge for ensuring good quality of drug; hence we first need to understand what is quality.

31. What is Quality? GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Word "Quality" derived from Latin word 'quails" means kind. Reasons for quality becoming a cardinal priority for most organizations as Competition - Today's market demand high quality products at low cost. Having "high quality reputation is not enough! Internal cost of maintaining the reputation should be less Changing customer - The new customer is not only commanding priority based on volume but is more demanding about the "quality system." Product complexity - As systems have become more complex/integral, the reliability requirements for suppliers of ingredients have become more stringent. Higher levels of customer satisfaction - Higher customer's expectations are getting spawned by increasing competition.

32. What is Quality Control ? GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Control on entire production process with the set-norm/Standards is carried out by the Quality Control/Assurance Quality Control: QC is a part of quality management focused on full filling quality requirement. Quality Assurance: QA providing confidence that quality requirement will be fulfilled. QC is defect detection & product oriented however QA is defect prevention & Process oriented. QC is actually testing process and QA is its verification.

33. Methodology of Q.C./QA GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Methodology of Testing of Crude Drugs The quality assessment shall be done by Quality control and Quality assurance Department through proper sampling as per sampling plan and Sample should be taken before production .

34. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Macroscopic examination : Visual examination as Size, Colour , Surface, Characteristics, Texture and Other examination as Odour, Taste. Macroscopic examination : Preparation of sample, Inspection by microscopy, Inspection by colour filter of ground glass, Histo -chemical detection, Section study (T.S./LS.). Chemical identification TLC/HPTLC FP profile Purity-Physico-Chemical profile (as above as applicable as per dosage form). Strength-Active marker/Assay (wherever required) Safety Heavy metal profile (Lead, Mercury, Arsenic, Cadmium) Microbiological limit testing (Total Aerobic Bacterial count, Total yeast/ mould count and Presence of pathogens (Salmonella, P. aeruginosa, E.coli, S. aureus 1) Aflatoxins (B1, B2, G1, G2) Pesticide residue

35. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Methodology of Testing of Compound Drugs The quality assessment shall be done by Quality control and Quality assurance Department through proper sampling as per sampling plan. Sample should be taken from In-process stage and finished product from Quarantine area. QC/QA Technical person should also ensure about compliance of other regulators requirement such as Label claim under rule 161 of drug & cosmetic act. As drug name, formulation & composition, Drug mfg Ref, main therapeutic indication/uses, dose, vehicle, direction of use (if any), self life, caution/warning (if any), storage condition elc .

36. GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Testing Protocol of drugs (as per API/UPI Monograph/testing protocol) Determination of foreign matter Determination of Ash value (at 500-8000C) Determination of extractable matter Determination of water & volatile matter  Determination of Moisture content (L.O.D. at 1100C) Determination of bitterness value Determination of Tannins Determination of swelling index Determination of foaming index Determination of pesticide residue Determination of arsenic & Heavy Metal Determination of Bulk density Determination of Radio-active contamination Comparative TLC/HPLC/HPTLC/GC-MS

37. Challenges in Safety Monitoring of Herbal Medicines GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Introduction Safety is a fundamental principle in the provision of herbal medicines and herbal products for health care, and a critical component of quality control. These guidelines provide practical technical guidance for monitoring the safety of herbal medicines within pharmacovigilance systems.

38. OBJECTIVES GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Support member states, in the context of the WHO international drug monitoring program, to strengthen national pharmacovigilance capacity in order to carry out effective safety monitoring of herbal medicines Provide technical guidance on the principles of good pharmacovigilance and the inclusion of herbal medicines in existing national drug safety monitoring systems and where these systems are not in place, to facilitate the establishment of an inclusive national drug safety monitoring system Provide standard definitions of terms relating to pharmacovigilance, and safety. Monitoring of herbal medicines Promote and strengthen internationally coordinated information exchange on pharmacovigilance, and safety monitoring of herbal medicines among member states Promote the safe and proper use of herbal medicines. The regulation of herbal medicines and their place in national health-care systems differs from country to country, and these guidelines will therefore need to be adapted to meet the needs of the local situation.

39. 1. CHALLENGES IN MONITORING THE SAFETY OF HERBAL MEDICINES GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Regulation, quality assurance and control Regulation National regulation and registration of herbal medicines vary from country to country. Where herbal medicines are regulated, they may be categorized as either prescription or non-prescription medicines. Herbal products may also be categorized other than as medicines. Moreover, the regulatory status of a particular herbal product may differ in different countries. The national regulatory framework usually also includes involved qualified providers and distributors of respective substances. Regulatory status consequently determines the access to or distribution route of these products. National regulatory information on herbal medicines is not fully shared among national regulatory authorities, and is often not shared between national regulatory authorities and national safety monitoring/pharmacovigilance centres .

40. 2. QUALITY ASSURANCE AND CONTROL GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI Quality assurance and control measures, such as national quality specification and standards for herbal materials, good manufacturing practices (GMP) for herbal medicines, labelling, and licensing schemes for manufacturing, imports and marketing, should be in place in every country where herbal medicines are regulated. These measures are vital for ensuring the safety and efficacy of herbal 13 WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems medicines. Weak regulation and quality control may result in a high incidence of adverse reactions attributable to poor quality of herbal medicines, in particular resulting from adulteration with undeclared potent substances and/or contamination with potentially hazardous substances and residues. Requirements and methods for quality control of finished herbal products, particularly for mixture herbal products, are far more complex than for other pharmaceuticals. The quality of such products is influenced by the quality of the raw material used. Good agricultural and good collection practices (GACP) for medicinal plants, including plant selection and cultivation, are therefore important measures.

41. 3. NATIONAL/REGIONAL PHARMACOPOEIAS GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI National and regional pharmacopoeias define quality specifications and standards for herbal materials and some herbal preparations, such as essential oils and powdered herbal materials. Use and inclusion of herbal materials in such pharmacopoeias are based on local availability of these products. Availability is dependent on the original medicinal plants. Which have ecologically and environmentally specific habitats. Therefore, even if the same pharmacopeial monograph name is given to a herbal material, its listing in one pharmacopoeia may refer to a different original medicinal plant and/or processing method from that defined in another (see also section 4.3, Reporting of suspected adverse reactions, under Recording and coding the identity of herbal medicines). Action required: As with other medicines for human use, herbal medicines should be covered by a drug regulatory framework to ensure that they conform to required standards of safety, quality and efficacy

42. References https://pharmafranchisehelp.com/drug-cosmetic-act-rules-schedule-tgood- manufacturing-practice-ayurvedic-siddha unani / https://www.slideshare.net/manishagoyal29/gmp- 13558913?from action=save https://www.slideshare.net/bharathpharmacist/schedule-t- 39686357?from action=save Dr.Sufiyan Ahmad, "Schedule -T Good Manufacturing Practice of Indian systems of medicine Components of GMP (Schedule-T) and its objectives Infrastructural requirements. working space, storage area, machinery and equipments , standard operating procedures, health and hygiene. documentation and records. https://drsufiyan.blogspot.com/2020/02/schedule-t-good-manufacturing= practice.html?showComment =1586191843781 http://www.authorstream.com/Presentation/vipin99-3628800-herbal-drug= industry/9 April 2020 GOVERNMENT COLLEGE OF PHARMACY, AMRAVATI

43. Thank you