Pharmaceutical Jurisprudence Drugs and Cosmetics Act and Rules-II 2 2 ee Se ad ee 2.1.1. Introduction Previously there were Schedule C and CC, drugs, and drugs other than those specified in these schedules. At the present time, there are: 1) Drugs not specified in Schedule C, C,, and X, 2) Schedule C and C, drugs, excluding Schedule X drugs, and 3) Schedule X drugs. Schedules M and Y were established in 1988. In relation to Jammu and Kashmir, the chapter related to import of drugs and cosmetics should take effect from the date after the commencement of the Drugs and — Cosmetics (Amendment) Act, 1972, the Central Government may appoint in this behalf by notifying the Official Gazette 2.1.2. Schedule G Medicines listed as schedule G carry a caution — on the label. The caution states that “It is dangerous to take this preparation except under medical supervision”. The caution is clearly printed and surround ed by a line no other words within. It is required to make proper bill of sale of Schedule G drugs. Records of purchase and sale of these medicines should be regulated for 2 years. Aminopterin,L_ -Asparaginase, Bleomycin, Busulphan, Chlorambucil, Chlorthiazide, Glibenclamide, Hydantion, Hydroxyurea, Insulin, Metformin, etc. are the examples of some drugs under schedule G. 2.1.3. Schedule H This schedule contains the prescription drugs, i.e., drugs that should be sold by retail only when a prescription is formed by a RMP. The time and date mentioned on the prescription should be noted. The drug label should have the texts “Rx” and Schedule H drug written on it. The label should also bea r warning that “To be sold by retail on the prescription of a registered medical practitioner only”. Drugs under Schedule H if comes under Narcotic Drugs and Psychotropic Substances Act, 1985 are labelled with the symbol “NRx” and Schedule H drug warning. Schedule H is alistof 536 drugs. Some examples are Abxicimab, Acylovir, Diclofenac, Baclofen, Carbidopa, Terazosin, Verapamil hydrochloride, Tretinoin,Drugs and Cosmetics Act and Rules-II (Chapter 2) 37 Schedule Hy This schedule was i ntroduced under the Drugs and Cosmetics (4 " Amendment) Rules 2013, by MOHFW on 30August, 2013 vide GSR 588(E) to control the sale of antibiotics. Ithasa separate regulation to check unauthorised sale of antibiotics, hence monitors the use and abuse of these antibiotics. The drugs under Schedule H are labelled with symbol “Rx” in red noticeably displayed on the left corner of the label with the — next words in box with red border. Some examples are Alprazolam, Gemifloxacin, Isoniazid, Cefixime, Levofloxacin, Cefpodoxime, Clofazimine, Zolpidem, etc. Warning 1) Itis dangerous to take this preparation except in accordance with the medical advice. 2) Itis not sold by retail without the prescription of a RMP. 2.1.4. Schedule M This schedule deals with Good Manufacturing Practices and Requirements of Pilot Equipment for Allopathic Drugs: 1) Location and Surrounding: The factory should be located in a place not adjacent to an open sewage, drain, public lavatory , ora factory producing offensive odour or fumes or huge a = mount of soot, dust or, smoke. The factory should be situated in a sanitary place, distant from dirty surrounds. 2) Buildings: The buildings used for the factory should be made at licence production under hygienic situations, and should meet the conditions given in the Factories Act, 1948. The part of the building used for manufacture should not be used as a sleeping place and no sleeping place should be present in its vicinity. The walls of the rooms in which manufacturing process es are done should be 6 feet high from the floor. The walls should — be smooth, wate r- proof, and easily cleanable. The floor should be smooth, even, washable, and should not allow dust accumulation. There should be no cracks or gaps in the walls or floor. 3) Water Supply: The water used in manufacturing process should be pure and drinkable. It should be free from pathogenic microorganisms. 4) Waste Disposal: Waste water and other residues from the laboratory may be harmful to the workers or the public health , thus should be disposed off after appropriate treatment to reduce them inoffensive. 5) Health, Clothing, and Sanitary Requirements of the Staff: All workers should be free from transmissible disease s. Their clothing should be clean and should have white or coloured uniform appropriate to the nature of work and the climate. 6) Medical Services: The manufacturer should provide the following faciliti i) Suitable facilities for first aid. ii) Medical inspection of the workers the time of employment, followed by periodic check-up at least once a year. iii) Services for vaccination and inoculation against enter ic or other epidemic group of diseases.38 7) Pharmaceutical Jurisprudence iv) Precautions for safeguarding the head of the workers, and alos suitable measures to avoid industrial accidents or diseases. Working Benches: These are used by the _ workers for carrying out filling, labelling, packi ng operations, etc. _ Arrangements, separated from the manufacturing operations, for the washing, cleaning and drying containers with suitable equipment for the purpose are provided. —_Sterilising facilities should also be provided wherever required. Requirements of Plant and Equipment 1) 2) The following equipment is required for manufacturing ointments, emulsions or lotions, and suspensions: i) Mixing tanks, ii) Kettle, steam, gas or electrically heated, iii) A suitable power driven mixer, iv) Storage tanks or pots, v) Acolloid mill or a suitable emulsifier, vi) A triple roller mill or an ointment mill, ii) Liquid filling equipment, and viii) Jar or tube filling equipment. An area of 30 square metres is required for the basic installations. The following equipment is required for manufacturing syrups, elixirs, and solutions: i) Mixing and storage tanks, ii) Portable mixer, iii) Filter press or other suitable filtering equipment, such a__s metafilter or sparkler filter, iv) Vacuum or gravity filter, and v) Water still or deioniser. An area of 30 square metres is required for the basic installations. Equipment for manufacturing pills and compressed tablets including hypodermic tablets are divided into the following sections: i) Granulation Section: a) Disintegrator, b) Powder mixer, c) Mass mixer, d) Granulator, and e) Ovens, thermostatically controlled. Tableting Section: a) Tablet machine, single punch or rotary, b) Pill machine, c) Punch and dies storage cabinet, and d) Tablet counter. iii) Coating Section: a) Jacketed kettle, steam, gas or electrically heated for preparing solution, b) Coating pan,Drugs and Cosmetics Act and Rules-Il (Chapter 2) 39 4) 5) 6) 7) 8) c) Polishing pan, and d) Heater and exhaust system. The following equipment is required for manufacturing powders: i) Disintegrator, ii) Mixer, iii) Sifter, iv) Stainless steel vessels and scoops of suitable material, and v) Filling equipment. An area of 30 square metres is required to allow for the basic operation. The following equipment is required for filling of hard gelatin capsules: i) Mixing and blending equipment, ii) Capsule filling units, and iii) Capsule counters. An area of 20 square meters is required for the basic installations for capsules filling. The room shall be air conditioned and also dehumidified. The following equipment is required for manufacturing surgical dressings: i) Rolling machine, ii) Trimming machine, iii) Cutting equipment, iv) Folding and pressing machine for gauze, v) Mixing tanks for processing medicated dressings, vi) Hot air drying ovens, and vii) Steam steriliser or dry heat sterilizer. An area of 30 square metres is required for the basic installations. The following equipment is required for manufacturing other preparations for external use under aseptic conditions: i) Hot air oven electrically heated with thermostatic control, ii) Kettle, gas or electrically heated with suitable mixing arrangement, iii) Colloid mill or ointment mill, iv) Tube filling equipment, v) Mixing and storage tanks of stainless steel or of other suitable materials, vi) Sintered glass funnel, seitz filter or filter candle, vii) Liquid filling equipment, and viii) Autoclaves. An area of 25 square meters is required for the basic installations. The manufacture and filling should be carried out in an air -conditioned room which should also be dehumidified if antibiotic-containing preparations are being manufactured. The following equipment is required for manufacturing pessaries and suppositories: i) Mixing and pouring equipment, and ii) Moulding equipment. An area of 20 square metres is required for the basic installations.40 Pharmaceutical Jurisprudence 9) The following equipment is required for manufacturing inhalers and vitrallae: i) Mixing equipment, ii) Graduated delivery equipment for measurement of the medicament, and iii) Sealing equipment. An area of 20 square metres is required for the basic installations. 10) The following equipment is required for repacking installations of drugs and pharmaceutical chemicals: i) Sifter, ii) Stainless steel scoops and vessels, iii) Weighing and measuring equipment, and iv) Filling equipment. An area of 30 square metres is required for basic packing operations. 11) The manufacturing process of parenteral preparations _ is divided as. follows: i) Preparation of containers including cutting, washing, drying and sterilisation of ampoules or vials prior to filling, ii) Preparation of solution including preparation and filtration of solution, iii) Sterilisation, and iv) Testing. The following equipment is recommended: i) Manufacturing Area a) Storage equipment for ampoules and vials, b) Ampoule washing and drying equipment, c) Dust proof storage cabinets, d) Water still, e) Mixing and prepar ation tanks or other containers —_ made of either glass or such material as will not react with the liquids, f) Filtering equipments such as filter press or sintered glass funnel, g) Autoclave, and h) Hot air steriliser. Filling and Sealing Room a) Benches for filling and sealing, b) Filling and sealing unit. iii) Aseptic Filling and Sealing Rooms a) Bacteriological filters such as seitz filter, candles or sintered glass filters, b) Filling and sealing unit. iv) General Room a) Inspection table, b) Leak testing equipment, and c) Storage equipment including cold storage and refrigerators, if necessary.Drugs and Cosmetics Act and Rules-II (Chapter 2) 4 2.1.5. Schedule N This schedule includes the List of Minimum Equipment for the Efficient Running of a Pharmacy. These requirements are: 1) Entrance: The front of a pharmacy should have an inscription “Pharmacy”. 2) Premises: The pharmacy premises should be separated from rooms for private purposes. The premises should be well-built, dry, properly lit, ventilated, and of suf ficient dimensions to allow the goods in stock (mainly medicaments and poisons) to be kept in a clearly visible locker. The areas of the section used as dispensing department should not be less than 6 m* for a pharmacist working there and additional 2m? for each additional pharmacist. The premises should have a minimum height of 2.5m>. The pharmacy floor should be smooth and washable. The walls should be plastered or tiled or oil painted so that the surface is smooth, durable , washable, and has no holes, cracks, and gaps. Water of good quality should be supplied to the pharmacy in sufficient amount. The dispensing department should be separated through a barrier to inhibit the entrance of public. 3) Furniture and Apparatus: The fumiture and apparatus of a pharm acy should be designed as per their uses and should correspond to the size and need of the establishment. Drugs, chemicals, and medicaments should be kept in a room in special containers to inhibit the deterioration of contents within or those in the vicinity. Droppers, glasses. , and other containers used for storing the medicaments should be of proper size and tightly closed to inhibit the entry of dust. Each container should have a label of proper size, readable, and having names of medicaments as given in the Pharmacopoeias. ‘A pharmacy should have a dispensing bench, which should be covered with a washable and impermeable material _(such as stainless steel, laminated plastic, etc.) from the top. A pharmacy should have a cupboard with lock and key for storing poisons. This cupboard should be marked with the word “POISON” in red letters on a white background. Containers of all concentrated solutions should have a different label marked with the words ‘To be diluted’. Any container taken from the poison cupb oard should be replaced immediately after use and the cupboard should be locked properly. The keys should be in the personal custody of the responsible person. A pharmacy should have the following apparatus and books required for making official preparations and prescriptions: Apparatus i) Balance, dispensing, sensitivity 30mg, ii) Balance, counter, capacity 3 kgm, sensitivity 1g, iii) Beakers, lipped, assorted sizes, iv) Bottles, prescription, ungraduated assorted sizes, v) Corks assorted sizes and tapers,42 Pharmaceutical Jurisprudence vi) Cork extractor, vii) Evaporating dishes, porcelain, viii) Filter paper, ix) Funnels, glass, x) Litmus paper, blue and red, xi) Measure glasses, cylindrical 10ml, 25ml, 100ml, and 500ml, xii) Mortars and pestles, glass, xiii) Mortars and pestles, wedgewood, xiv)Ointment pots with bakelite or suitable caps, xv) Ointment slab, porcelain, xvi)Pipettes, graduated 2ml, Sml, and 10ml, xvii) Ring, stand (retort) iron, complete with rings, xviii) Rubber stamps and pad, xix)Scissors, xx) Spatulas, rubber or vulcanite, xxi)Spatulas, stainless steel, xxii) Spirit lamp, xxiii) Glass stirring rods, xxiv) Thermometer, 0°to 200°C, xxv) Tripod stand, xxvi) Watch glasses, xxvii)Water bath, xxviii) Water distillation still in case eye drops and eye lotions are prepared xxix) Weights, Metric, Img. to 100g, and xxx) Wire Gauze: a) Pill finisher, boxwood, b) Pill machine, c) Pill Boxes. Books i) The Indian Pharmacopoeia (current edition), ii) National formulary of India (current edition), iii) The Drugs and Cosmetics Act, 1940, iv) The Drugs and Cosmetics Rules, 1945, v) The Pharmacy Act, 1948, and vi) The Narcotic Drugs and Psychotropic Substances Act. 4) General Provisions: A ph armacy should be under the continuous supervision of a registered pharmacist whose name should be displayed noticeably in the premises. The pharmacist should always put on clean overalls. The premises and fittings of the pharmacy should be in good order and clean. All records and registers should be regulated in agreement with the laws in force. 2.1.6. Schedule P This schedule deals with the Life Period of Drugs and the storage conditions of drugs. The period should be in months between date of manufacture and d ate of expiry. The schedule comprises of antibiotics, vitamins, insulin preparation, normal human plasma, sera toxins, toxoids, other toxins, anti-toxins, etc.Drugs and Cosmetics Act and Rules-II (Chapter 2) 43 Drugs Life Period (Months) Storage ‘Adramycin 30 Ina cool place Ampicillin 36 Ina cool place Ampicillin Sodium 36 Ina cool place Ampicillin wihydrate 30 In a cool place Schedule P, This schedule specifies the Pack Size of Drugs. It provides the names of drugs, along with the dosage form and the pack size. No other pack size than the one listed under this schedule should be marked. Drugs Dosage Forms Pack Sizes Aspirin (Low Dose) | Tablets 14 tabs Cholecalciferol Granules gm sachet Famotidine Tablets 14 tabs Glyceryl Trinitrate | Capsules 25 cap 2.1.7. Schedule T This schedule deal s with Good Manufacturing Practices for Ayurvedic, Siddha, and Unani Medicines. 1) Factory Premises: The manufacturing plant should have adequate space for: i) Receiving and storing raw material, ii) Manufacturing process areas, iii) Quality control section, iv) Finished goods store, v) Office, and vi) Rejected goods/drugs store. 2) Location and Surroundings: For the manufacturing of Ayurveda, Siddha , and Unani medicines, the factory building should be situated and constructed to avoid contamination from open sewerage, drain, public] avatory for any factory forming loathsome odour or fumes or extreme soot, dust and smoke. 3) Buildings: The factory buildings should facilitate drug production under hygienic conditions free from cobwebs and insects/rodents. The buildings should have proper facility of light and ventilation. The floor and the walls should not be damp or moist. The buildings used for manufacturing, processing, packaging , and labelling should be in conformity with the provisions of the Factory Act. 4) Water Supply: Pure and potabl e water should be used in manufacturing . Sufficient provisions of water should be available for washing the premises. 5) Disposable of Waste: — The waste water and the residues f rom the manufacturing section and laboratories should be disposed off properly as i t may be harmful to the workers and public health. 6) Container’s Cleaning: The factory areas where containers like glass bottles, vials and jars are used should have enough arrangements separated from the44 Pharmaceutical Jurisprudence manufacturing operations for washing, cleaning and dr ying of such containers. 7) Stores: These areas should have appropriate ventilation and should be free from dampness. The stores should have ample of space for storing different types of material s, like raw materials, packaging material s, and finished products. 8) Raw Materials: For manufacturing the raw materials should be stored in the raw materials store. Every container for raw material storage — should be appropriately labelled specifying the name of the raw material, its source of supply, and also the status like UNDER TEST — or APPROVED or REJECTED. 9) Packaging Materials: Bottles, jars, capsules etc. should be suitably stored. All containers and closure s should be sufficiently cleaned and dried before packing the products. 10) Finished Goods Stores: After proper pack aging, the _ finished goods transferred from the production area should be stored in the finished goods stores in quarantine area. After the accuracy of finished goods quality (its packaging and labelling) is checked by _ the quality control laboratory, they should be moved to ‘Approved Finished Goods Stock’ area. 11) Working Space: = Manufacturing area should have enough space (manufacture and quality control) for proper arrangement of equipment and materials used in any operations to ease the safe working, to reduce or remove the risk of mix -up between different drugs, raw materials , and to inhibit the chances of cross contamination of one drug with another drug manufactured, stored, or handled in the same sites. 12) Health Clothing, Sanitation, and Hygiene of Workers: The workers should not have any contagious diseases. The ir clothing should have proper and clean uniform appropriate to the nature of work and climate. The uniform should have cloth or synthetic covering for hands, feet , and head . Facilities for personal cleanliness like clean towels, soap and scrubbing brushes should be available. Separate provision should be made for lavatories to be used by men and women, and these _ lavatories should be situated at places away from the proces sing rooms. Facilities for changing clothes and to keep personal belongings should also be provided to the workers. 13) Medical Services: The manufacturer should provide services for first aid, medical examination of the workers at the time ofemployment, and periodical check-up (once a y ear) by a physician to make sure the workers have no infections. Records for such details should be maintained 14) Machinery and Equipments: — Manufacturing should be done using appropriate equipment (either manually operated or semi-automatic or fully automatic) based onthe operation size andthe — nature of manufactured product. These equipments should be correctly installed and kept clean. 15) Batch Manufacturing Records: — The licensee should — maintain batch manufacturing record of each batch of Ayurvedic, Siddha and Unani drugsDrugs and Cosmetics Act and Rules-Il (Chapter 2) 4s manufactured. These records give an account of the list of raw materials and their quantities obtained from the store, tests conducted during the different phases of manufacture such as taste, colour, physical features and chemical tests. 16) Distribution Records: Records of sale and distribution of each batch of Ayurveda, Siddha and Unani drugs should be maintained for the quick recall of the batch, whenever required. 17) Record of Market Complaints: A register to record all the reports of market complaints related to the products sold in the market should be maintained. The manufacturer should submit the record of such complaints to the licensing authority once in every six months. 18) Quality Control: Every licensee should provide a quality control section in his premises or by Government approved testing laboratory. The test s in this section shouldbe conducted as perthe Ayurveda, Siddha and Unani Pharmacopoeial standard. 2.1.8. Schedule U This schedule deals with Particulars to be shown in Manufacturing Records: 1) Substances Other than Parenteral Preparations in General i) Serial number, ) Name of the product, Reference of Master Formula Records, iv) Lot/Batch size, y) Lot/Batch number, vi) Date of beginning and completing the manufacture and assigned date of expiry, vii) Name of all ingredients and their quantities, viii) Control numbers of raw materials used in the formulation, ix) Date, time, and duration of mixing, x) Details of environmental controls like room temperature, relative humidity, xi) Date of granulation, wherever applicable, xii) Theoretical weight and actual weight of granules/powder blend, xiii) Records of in-processes controls: a) Uniform of mixing. b) Moisture content of granules/powder in case of tablet/capsules. c) pH of solution in case of liquid. d) Weight variation. e) Disintegration time. f) Hardness. g) Friability test. h) Leak test in case of strip packing. i) Filled volume of liquids. j) Quantity of tablets/ capsules in the final container. k) Content of ointment in the filled containers. xiv) Date of compression of tablets or date of filling of capsules,2 Pharmaceutical Jurisprudence xv) Date of sealing, coating, or polishing of capsules and tablets., xvi)Reference to analytical report number indicating the result of analysis, xvii) Separate records of the disposal of rejected batches and of the batches withdrawn from the market, Theoretical yield an d actual production yield and packing particulars indicating the size and quantity of finished packings, xix) Specimen of label , carton with batch coding information like batch number, manufacture and expiry date, retail price and inserts used in the finished packings, xx) Date and signature of the skilled technical staff, xxi) Counter-signature of the head of the testing units or other approved person-in-charge of testing who has _ verified the batch records and released the batch for sale and distribution, The release date and quantity released of finished packings for sale and distribution, ii) The quantity of finished packings transferred to warehouse, and xxiv) Records should be maintained for hypodermic tablets and ophthalmic preparations manufa ctured under aseptic conditionst 0 indicate the precautions taken during the ir manufacturing to confirm that aseptic conditions were maintained. xxii Parenteral Preparations: (i) to (x) points are same as_ that of Substances Other than Parenteral Preparations in General: i) pH of the solution, ii) Date and method of filtration, iii) Sterility test, reference on bulk batch wherever applicable, iv) Record of check on volume filled, v) Date of filling, vi) Records of tests employed: a) Toensure that sealed ampoules are leak proof, b)_ To check the presence of foreign particles, c) Pyrogen test, wherever applicable, and d) Toxicity test, wherever applicable. vii) Records of checking of instruments and apparatus of sterilisation, viii) Records of cleaning and sterilisation of containers and closures, ix) Records of heat sterilisation of parenteral preparations comprising of the time, temperature, and pressure used. These records should be marked to relate to the sterilisation of the batch, x) Number and size of containers filled and quantity rejected, xi) Reference to analytical report numbers stating whether or not of standard quality, xii) Records should be maintained to indicate the precautions taken during the manufacturing to confirm that aseptic conditions were maintained, xiii) Points (xvii) to (xxi) are of Substances Other than Parenteral Preparations in General, and xiv)Records of reprocessing and particulars of reprocessing.Drugs and Cosmetics Act and Rules-II (Chapter 2) 47 Records of Raw Materials Records related to each raw material should be maintained properly _ to indicate the receipt date, invoice number, name and address of the manufacturer/supplier, batch number, quantity received, pack size, manufacture and expiry date, date of analysis (if any), release/rejection by quality control, analytical report number (if any), quality issued, date of issue , and details of the name and batch numbers of products, and proper disposal of the stocks. Particulars to be shown in the Analytical Records 1) Tablets and Capsules: i) Analytical report number, ii) Name of the sample, iii) Date of receipt of sample, iv) Batch/Lot number, v) Protocols of tests applied: a) Description, b) Identification, c) Uniformity of weight, d) Uniformity of diameter (if applicable), e) Disintegration test (time in minutes), f) Any other tests, and g) Results of assay. vi) Signature of the analyst, and vii) Opinion and signature of the approved analyst. 2) Parenteral Preparations: (i) to (iv) po ints are same as that of Tablets and Capsules: i) Number of containers filled, ii) Number of containers received, iii) Protocols of tests applied, a) Clarity, b) pH wherever applicable, c) Identification, d) Volume in container, e) Sterility: e Bulk sample wherever applicable, ¢ Container sample. f) Pyrogen test, wherever applicable, g) Toxicity test, wherever applicable, h) Any other tests, and i) Results of Assay. iv) Points (vi) and (vii) are of Tablets and Capsules. 3) For Other Drugs : (i) to (iv) points are same as that of Tablets and Capsules: i) Protocol of tests applied: a) Description, b) Identification,48 Pharmaceutical Jurisprudence c) Any other tests, and d) Results of as ii) Points (vi) and ( 4) Raw Materials i) Serial number, ii) Name of the materials, iii) Name of the manufacturer/supplier, iv) Quantity received, y) Invoice/Challan number and date, and vi) Protocols of tests applied. are of Tablets and Capsules. 5) Container Packing Materials, etc. : (i) to (vi) points are same as that of Raw Materials: i) Remarks, ii) Signature of the examiner. 2.1.9. Schedule V This schedule deals with Standards for Patent or Proprietary Medicines. Subject to the provisions of these rules, patent or proprietary medicines should fulfil the following standards: 1) Patent or proprietary medicines should fulfil the following needs: i) Tablets: Medicines should fulfil the needs for tablets as given in the IP. The nature of coating and the permitted colours should be added on the label. Nature of tablets (uncoated, sugar coated, or film coated) should be given on the label. Capsules: Medicines should fulfil the requirements for capsules as given inthe I.P. The capsules should be free from distortion , discolouration, and other physical defects suchas leakage of powder from joints, pinholes or cracks. iii) Liquid Oral Dosage Forms: On shaking, e mulsions and suspensions should disperse. Homogeneous solutions should have no sediments. Net content of the product in the container should not be less than the volume mentioned on the label . The ethanol content of pharmaceutical products should be between 90-110% of the labelled contents. Injections: Medicines should fulfil the needs for injections as given in the LP. Ointments: Medicines should fulfil the needs for ointments as given in the LP. 2) The content of active ingredients, other than vitamins, enzymes » and antibiotics, should be between 90 -110% of the labelled content. In dry formulations of antibiotics, the limit should be 90 -130% of the labelled contents. In liquid antibiotics, the limit should be 90-140% of the labelled contents. iv, Vv 3) Alll patent or proprietary medicines having aspirin should undergo free salicylic acid test, the limit of which should be 0.75%.Drugs and Cosmetics Act and Rules-II (Chapter 2) 49 4) Patent or proprietary medicines to be tested under the provisions of rule 121- A for pyrogen should be tested by injecting into rabbits in doses not below to that for the humans depending on the body weight of a 60kg human. 5) In injectable patent or proprietary medicines __, the test for freedom from toxicity should be conducted as given in the IP. 2.1.10. Schedule X This schedule deals with the List of Narcotic Drugs and Psychotropic Substances. Amobarbital, ampheta _ mine, barbital, cyclobarbital, dexamphetamine, ethchlorvynol glutethimide, meprobamate, methaqualone, methylphenobarbital, pentobarbital, phencyclidine, phenmetrazine, phenobarbital, secobarbital are the examples of drugs comes under schedule X. Any stereoisometric form of the substance specified in this Schedule, any salt of the substance and preparation containing such substances are also covered by this Schedule. Preparations containing the above substances are also covered by this Schedule. 2.1.11. Schedule Y This schedule deals with the Requirements and Guidelines for Permission to Import and/or Manufacture of New Drugs for Sale or to Undertake Clinical Trials. 1) Application for Permission: Application for approval to import or manufacture new drugs for sale or to undertake clinical trials should be made in Form 44 along with the following data: i) Chemical and pharmaceutical information, ii) Animal pharmacology data: a) Certain pharmacological actions and _therapeutic potential for humans should be defined as per the ani mal models and species used, b) General pharmacological actions, and c) Pharmacokinetic data of the test substance. iii) Animal toxicology data, Human clinical pharmacology data: a) Clinical trials for new drug substances discovered in India are carried out from Phase I and related data should be submitted. b) The data needed will be based on the purpose of the new drug application. The number of study subjects and sites to be involved in the clinical trial will be based on the study nature and objective. c) Application for permission to start a phase of clinical trial should also have the investigator,,s brochure, proposed protocol, case record form, study subject,.s informed consent document(s), investigator,,s undertaking, and ethics committee clearance. d) The study report shou Id be certified by the p rincipal investigator, otherwise by each investigator involved in the study.2) Pharmaceutical Jurisprudence vy) Regulatory status in other countries having information on limits enforced, on the use of drug s in other countries (such as dosage limits, exclusion ofs pecific age groups, waming related to adverse drug reactions, etc.). vi The prescribing information should be submitted as part of the new drug application for marketing. This —_ information (package insert) should include generic nam e, composition, dosage form indications, dose, administration method, use in special populations (like pregnant women, lactating women, paediatric __s, geriatric s,_etc.), contraindications, warnings, precautions, drug interactions, side effects, overdose, pharmacodynamic and pharmacok inetic properties, incompatibilities, shelf-life, packaging information, storage and handling instructions. vii) As a part of new drug application for marketing, the testing protocol for quality control testing with complete impurity profile and release specifications for the product should be submitted. Clinical Trial: i) Human Pharmacology (Phase I): The aim of this phase is to estimate the safety and tolerability with the initial administration of an investigational new drug to human(s). Drugs with potential toxicity (such as cytotoxic drugs) are mainly studied. Phase I trials should be conducted by investigators skilled in clinical pharmacology who carefully observe and monitor the subjects, Following are the objectives of studies conducted in phase I trials: a) Maximum Tolerated Dose: It is done to regulate the tolerability of the dose range that may be required in future for clinical studies and to control the nature of expected adverse reactions. b) Pharmacokinetics: It is done to characterise a drug’s absorption, distribution, metabolism, and excretion. ¢) Pharmacodynamics: The pharmacodynamic data acquired from the subjects can lead the dosage and dose regimen to be used in later studies if there are suitable validated sign of activity and potential efficacy. d) Early Measurement of Drug Activity: Preliminary studies of activity or potential therapeutic benefits are conducted in later phases; however it is suitable when drug activity can be easily measured with a small duration of drug exposure in patients at this initial stage. Therapeutic Exploratory Trials (Phase II): The main objective of phase II trials is to assess the efficiency of a drug for a specific indication/s in patients with the situations under study. Another objective isto determine the common short -term side-effects and risks related to the drug. iii) Therapeutic Confirmatory Trials (Phase III): The main objective of phase III trials is to demonstrate the therapeutic benefits, to confirm theDrugs and Cosmetics Act and Rules-I (Chapter 2) 5 results of Phase II that a drug is safe and effective for a parti cular indication and recipient population. These studies should provide a suitable basis for marketing approval. iv) Post Marketing Trials (Phase IV): These studies are done after the approval of drug and related to the approved indication(s). These trials go beyond the previous demonstration of the drug,,s safety, efficacy, and dose. These trials cannot be considered necessary at the time of new drug approval, however can be needed by the Licensing Authority for optimising the drug’s use. Phase IV trials compr ise additional drug-drug interaction(s), dose response or safety studies, and trials intended to support use under the approved indication(s), such as mortality/morbidity studies, epidemiological studies, etc. 2.1.12. Schedule F - Part XII B This schedule deals with the Requirements for the Functioning and Operation of a Blood Bank and/or for Preparation of Blood Components. 1) 2) General Requirements: i) Location and Surroundings: The blood bank should be at a place away from open sewage, drain, public lavatory, or unhygienic surroundings. Buildings: The building s used for operation of a blood bank and/or preparation of blood components should be build such that all the operations and manufacturing are done under hygienic conditions. Also, the entry of insects, rodents , and flies should be avoided. The building should be adequately lighted, ventilated , and screened. The walls and floors of premises where collection of blood or preparation of blood components or blood products is done should be smooth, washable, and cleanable. iii) Health, Clothing and Sanitation of Staff: The employees should not have contagious or infectious diseases. They should wear clean overalls, head-gears, foot-wears, and gloves. The premises should have clean and convenient hand washing and toilet services. Accommodation for a Blood Bank: A blood bank should be of 100m? area to carry out the operations, and an extra 50 m* area for preparation of blood components. It should have room for: i) Registration and medical examination with enough furniture and services for registration and selection of donors, ii) Blood collection (air-conditioned), iii) Blood component preparation (air-conditioned to maintain temperature between 20-25°C), iv) Laboratory for blood group serology (air-conditioned), v) Laboratory for blood transmissib _ le diseases like hepatitis, syphilis, malaria, and HIV-antibodi \ir-conditioned), vi) Sterilisation-cum-washing, vii) Refreshment-cum-rest room (air-conditioned), and viii)Store-cum-records.52 Pharmaceutical Jurisprudence 3) Personnel: Each blood bank should have the following groups of full time competent technical staff: i) Medical officer with required qualifications, ii) Blood bank techi (s) with: a) Degree in Medical Laboratory Tec hnology (M.L.T) from a Central or State Government recognised university/institution and 6 months’ experience in the testing of blood and/or its components, or b) Diploma in Medical Laboratory Technology (M.L.T) from a Central or State Government recognised university/institution and a year’s experience in the testing of blood and/or its components. iii) Registered nurse(s), and iv) Technical supervisor with: a) Degree in Medical Laboratory Technology (M.L.T) and 6 months’ experience in the preparation of blood components, or b) Diploma in Medical Laboratory Technology (M.L.T) and a year’s experience in the preparation of blood components. 4) Maintenance: The premises should be clean and properly manage —d._ for accurate cleaning and operation maintenance. The following facilities should be included: i) Privacy and thorough examination of individuals shouldbe done for determining whether or not they are suitable donors, ii) Collection of blood from donors with negligible risk of contamination of exposure to actions and equipment unconnected to blood collection, iii) Storage of blood or blood components pending completion of tests. iv) Provision for quarantinand storage of blood and blood components pending repetition ofthe tests that initiall gave questionable serological results. vy) Provision for quarantine, storage, handling, and disposal of products and reagents not suitable for use. vi) Storage of finished products prior to distribution. vii) Proper collection, processing, compatibility testing, storage + and distribution of blood and blood components to prevent contamination. viii) Proper conduction of all plasmapheresis, plateletpheresis and leucapheresis procedures. ix) Proper conduction of all packaging, labelling, and finishing operations. x) Provisions for disposal of b lood and/or blood components not suitable for use, distribution , or sale. Also provisions for t rash and items used during the collection, processing and compatibility testing of blood and/or blood components are available. 5) Equipment: Collection, processing, testing, storage , and sale/distribution of blood require clean equipments, which should be observed, standardised, and calibrated regularly. General Equipments and Instruments i) For Blood Collection Room: a) Donor beds, chairs and tables of appropriate size should be suitably and comfortably cushioned. b) Beside table.Drugs and Cosmetics Act and Rules-II (Chapter 2) 53 iii) iv, ” vi) c) Sphygmomanometer and stethoscope. d) Recovery beds for donors. e) Refrigerators, for storing separately tested and untested blood, maintaining temperature between 2 -6°C__ with digital dial thermometer, recording thermograph and alarm device, with provision for continuous supply. f) Weighing devices for donor and blood containers. For Haemoglobin Determination: a) Copper sulphate solution, b) Sterile lancet and impregnated alcohol swabs, c) Capillary tube (1.3 x 1.4 x 96mm for Pasteur pipettes), d) Rubber bulbs for capillary tubings, and e) Sahli’s haemogolobinometer/Colorimetric method. For Temperature and Pulse Determination: a) Clinical thermometers, b) Watch (fitted with a second-hand) and a stop-watch. For Blood Containers: a) Only disposable PVC blood bags shall be used (closed system) as per specifications of IP/USP/BP. Anti-coagulant solution, which should be sterile, pyrogen -free, and of such composition that will ensure satisfactory safety and efficacy of the whole blood and/or for all the separate blood components. c) Citrate Phosphate Dextrose Adenine solution (CPDA) or Citrate Phosphate Dextrose Adenin-1 (CPDA-1) solution should be required for 100m! of blood. Emergency Equipments/Items a) Oxygen cylinder with mask, gauge and pressure regulator, b) 5 per cent Glucose or Normal Saline, c) Disposable sterile syringes and needles of various sizes, d) Disposable sterile I.V. infusion sets, e) Ampoules of adrenaline, noradrenaline, mephentin, betamethasone, dexamethasone, and metoclopramide injections, and f) Aspirin. Accessories a) Such as blankets, eme: ins, haemostats, set clamps, sponge forceps, gauze, dressing jars, solution jars, waste cans, b) Medium cotton balls, 1.25cm adhesive tapes, c) Denatured spirit, tincture iodine, green soap or liquid soap, d) Paper napkins or towels, e) Autoclave with temperature and pressure indicator, f) Incinerator, and g) Stand-by generator. b) vii) Laboratory Equipment a) Refrigerators, for storing diagnostic kits and regents, maintaining a temperature between 4 -6°C (42°C) with digital dial thermometer having provision for continuous power supply,S4 6) Pharmaceutical Jurisprudence b) Compound microscope with low and high power objectives, c) Centrifuge table model, d) Water bath between 37-56°C, e) Rh viewing box in case of slide technique, f) Incubator with thermostatic control, 2) Mechanical shakers for serological tests for syphilis, h) Hand-lens for observing tests conducted in tubes, i) Serological graduated pipettes of various sizes, j) Pipettes (Pasteur), k) Glass slides, 1) Test tubes of various sizes/micrometre plants (U or V type), m) Precipitating tubes 6mm x 50mm of different sizes and glass beakers of different sizes, n) Test tubes racks of different specifications, 0) Interval times electric or spring wound, p) Equipment and materials for cleaning glass wares adequately, q) Insulated containers for transporting blood, between 2 -10°C temperatures, to wards and hospitals, r) Wash bottles, s) Filter papers, t) Dielectric tube sealer, u) Plain and EDTA vials, v) Chemical balance (wherever necessary), and w) ELISA reader with printer, washer and micropipettes. Supplies and Reagents: All the supplies and reagents utilised in the collection, processing, c ompatibility testing, storage , and distribution of blood and blood components should be stored in a safe and hygienic area at a proper temperature: i) The supplies coming in contact with blood and blood components to be used for transfusion should be sterile, pyrogen -free,and should not interact with the product ina way to produce an adverse effe ct on the safety, purity, potency, or effectiveness of the product. ii) The supplies and reagents not having an expiry date should be stored in a way that the oldest one is used first. iii) The supplies and reagents should be used in a way consistent with instructions given by the manufacturer. iv) The final containers and closures for blood and blood components not to be used for transfusion should be clean and free of surface solids and other contaminants. v) The blood collecting containers and satellite containers (if any) should be visually examined for damage or contamination prior to use and also after filling. The examination should include inspection for breakage of seals and abnormal discoloration. Incase of any defect, the container should not be use d. If the def ect is detected after filling , the container should be discarded.Drugs and Cosmetics Act and Rules-I (Chapter 2) 55 7) vi) Representative samples of each lot of the following reagents and/or solutions should be tested periodically by methods given in the Standard Operating Procedures Manual for determining their performing ability. Special Reagents i) Standard blood grouping sera anti-A, anti-B and anti-D with known controls, Rh typing sera shall be in double quantity and each of different brands or if from the same supplier each supply shall be of different lot numbers. ii) Reagents for serological tests for syphilis and positive sera for controls. iii) Anti-human globulin serum (Coomb’s serum). iv) Bovine albumin 22% enzyme reagents for incomplete antibodies. v) ELISA or RPHA test kits for hepatitis and HIV I and IT. vi) Detergent and other agents for cleaning laboratory glass wares. Criteria for Blood Donation: i) ii No one should donate blood and no blood bank should draw blood from a person more than once in three months. The donor should be in good health, mentally alert , physically fit, and should not be jail prisoners, having multiple sex partners, and drug -addicts. The donors should comply with the following requirements: a) The donor should be in the age group of 18-65 years, b) The weight of the donor should not be less than 45kg, c) Temperature and pulse of the donor should be normal, d) The systolic and diastolic blood pressure of the donor should be normal without medication, e) Haemoglobin should not be less than 12.5gm, f) The donor should not have any acute respiratory diseases, g) Thedonorshou Id nothave any skindis eases at the site of phlebotomy, h) The donor should not have any disease that could be transmitted via blood transfusion, and i) The arms and forearms of the donor should not have any punctures or scars indicative of professional blood d onors or addiction of self - injected narcotics. Additional Qualifications of Donor: No one should donate blood and no blood bank should take blood from a donor under the conditions given in column (1) and before the expiry of the deferment period given in column (2) of the table 2.1: Table 2.1: Deferment of Blood Donation Conditions Deferment Period —_| Abortions 6 months | History of blood transfusion 6 months | Surgery 12 months | Typhoid 12 months after recovery _| History of malaria and duly treated 2 months (endemic) and 3 years (non-endemic area)8) 9) Pharmaceutical Jurisprudence Tattoo 6 months Breast feeding 12 months after delivery Immunisation (Cholera, Typhoid, Diphtheria, | 15 days Tetanus, Plague, Gammaglobulin) Rabies vaccination 1 year after vaccination History of Hepatitis in family orclose | 12 months contact Immunoglobulin 12 months iii) No one should donate blood and no blood bank should take blood from an individual suffering from cancer, heart disease, abnormal bleeding tendencies, unexplained weightloss , diabetes-controlled on insulin hepatitis, chronic nephritis, signs and symptoms of AIDS, liver diseases, tuberculosis, polycythemia, asthma, epilepsy, leprosy, schizophrenia, and endocrine disorders. Testing of Whole Blood: i) The licensee should confirm that the whole blood collected, treated, and supplied obeys the standards given in the LP. and other tests published by the Government. ii) The licensee should get blood samples tested (prior to use) for freedom from HIV | and HIV II antibodies either from the Central Government laboratories or from his own laboratory. The results of such tests should be mentioned on the container label. iii) The blood units should also be tested to be free from Hepatitis B surface antigen and Hepatitis C Virus antibody and malarial parasite. The results of such tests should be mentioned on the container label. Records: The licensee should maintain records including the following particulars: i) Blood Donor Record: It shows serial number, date of bleeding, name, address, signature, age, weight, haemoglobin, blood group, blood pressure, and medical examination of the donor, bag number, and details of the patient for whom blood was donated in case of replacement donation, donation category (voluntary/ replacement), deferral records, and signature of the medical officer in-charge. Master Records for Blood and its Components: It shows the bag serial number, date of collection, date of expiry, and quantity in ml. iii) Issue Register: It shows serial number, date and time of issue bag serial number, ABO/RH Group, tot al quantity in ml, name and address of the recipient, group of recipient, unit/institution, details of | cross-matching report, and indication for transfusion. iv) Records of Components Supplied : It shows the quantity supplied, compatibility report, details of recipient, and signature of issuing person. Records of ACD/CPD/CPD -A/SAGM bags showthe details of manufacturer, batch number, date of supply, and results of testing. Register for Diagnostic Kits and Reagents Used: [t shows name of the kits/reagents, details of batch number, date of expiry, and date of use. ii Vv. viDrugs and Cosmetics Act and Rules-II (Chapter 2) 37 vii) Blood bank should issue the cross -matching report of the blood to the patient together of the blood unit. viii) Transfusion adverse reaction records. ix) Records of purchase, use and stock in hand of disposabl eneedles, syringes, blood bags should be maintained. 10) Labels: The labels on bags containing blood and/or blood components should bear the following particulars: i) The product name in a prominent place and in bold letters on the bag. ii) Name and address of the blood bank. iii) Licence and serial number. iv) The date on which blood was drawn and the date of expiry. v) Acoloured label should be placed on the blood-containing bags. The colour scheme in the table below for the said labels should be u_ sed for various blood groups: Blood Groups | Colour of the Label ° Blue A Yellow B Pink AB White vi) The test results forh epatitis B surface antigen and hepatitis C virus antibody, syphilis, freedom from HIV I and [I antibodies, and malarial parasite. vii) The Rh Group. viii) Total volume of blood, preparation of blood, and nature and percentage of anticoagulant. ix) The whole human blood and/or components should be kept at 2 -6°C temperature. x) Disposable transfusion sets with filter should be used in administration equipment. xi) Proper compatible cross -matched blood without atypical antibody in recipient should be used. xii) The bag contents should not be used in case of any sign of deterioration, such as haemolysis, clotting, or discoloration. xiii) The proper donor classification such as Voluntary Donor or Replacement Donor in no less prominence than the proper name. 2.1.13. DMR (OA) The Drugs and Magic Remedies (Objectionable Advertisements) Act, 1954 is passed for regulating the advertisements of some drugs, and the advertisements of remedies having qualities of magic. The objective of this Act is to maintain ethical standards when manufacturers advertise any drugs. Under the guidelines of this Act, advertisements offending38 Pharmaceutical Jurisprudence the decency or morality can be banned. Also, those claiming magical powers for certain drugs, €.g., enhancement of potency, cure for incurable diseases, etc. should be banned. Magical remedies include the use of talismans or charms such as “mantras”, “kavachas”, etc. 2.1.14. Sale of Drugs Sale is the process of passage of drugs from the manufactur ers to the consumers. The different kinds of licenses issuable for wholesale and retail of drugs are in figure 2.1: Wholesal From Shops From Motor Vehicles License for wholesale License for drugs other — License for C License for drugs other Schedule of Cand C1 than Schedule C and C1 and C1 drugs than C and Cl Retail From Shops Vendors Pharmacy Chemists Drug Store Only specified drugs in and Druggist specified areas Separate license forC Separate license Separate license and C1 drugs for X drugs for other drugs Figure 2.1: Licenses for Wholesale and Retail Sale of Drugs The process of passing drugs from manufactur ers to consumers is termed as sale. In India, selling of drugs was an open trade til 1 1940; hence, anyone can sell, compound, or dispense drugs without any restriction. But, after the implementation of the Drugs and Cosmetics Act 1940, selling of drugs became a restricted practice, and only the licenced individuals (by the Licensing Authorities of the States) can involve in wholesale, retail, compounding, or dispensing of drugs. Licences are required for the wholesale or distribution from a motor vehicle or retail sale of drugs, and a separate licence is needed for each premise where drugs are sold. 2.1.14.1. Wholesale of Drugs A wholesaler with a valid trade licence can approach the drug manufacturer for supplying medicine for selling to the retailers. Following are the conditions of granting the licences for wholesale of drugs: 1) Adequate infrastructural facilities, 2) Records, 3) Sale only to licenced retailers, and 4) Inspection.Drugs and Cosmetics Act and Rules-II (Chapter 2) 59 Wholesale from Fixed Premises Wholesale of drugs can be done from fixed premises or by motor vehicles. Separate licences are needed for wholesale of drugs under Schedules C andC and other than those in Schedules C and C, Wholesale of Schedule C and C, Drugs Licences for wholesale of SchedulesC andC —, drugs can be granted on the following conditions: 1) The licensee must have adequate premises not be less than 10 square meters in area, equipped with adequate facilities for storage of drugs in order to preserve their potency. 2) No drug, to which this licence is applicable, should be sold unless precautions have been taken for its preservation when it was possessed by the licensee. The drugs should be sold to persons with licence to retail them. However, this condition is not applicable to the sale of drugs to hospitals, medical, educational or research institutions or manufacturers of hydroge nated vegetable oils, beverages, confectionery and other non —_-medical products where such drugs are used for processing products or to an officer or authority purchasing on behalf of the Government. Along with the supplies of drugs, a cash or credit memo wi th the supply date, name, address and the licence number of the licensee to whom sold, names, quantities and the batch numbers of drugs and names of the manufacturers should also be accompanied. 4) If the licensee desires to sell any other categories of drugs (not specified in his license), he should seek permission from the Licensing Authority. Records of all purchases and sales of Schedule C drugs by wholesale dealings should be maintained under the following headings: i) The dates of purchases and sales, ii) Names and addresses of the firms from whom purchased and of the firms to whom sold, iii) Names and quantities of the drugs and their batch numbers, and iv) Names of the manufacturers of drugs. 6) The records should be preserved from the date of sale to a period of at least three years. 7) Licence should be displayed in the premises so that it is open to the public. 2 3 Wholesale of Drugs other than those Specified in Schedules C and C, Licences for wholesale of drugs other than those specified in Schedules C and C, can be granted on the following conditions: 1) The drugs should not be sold to any person who does not possess a licence for the retail sale or distribution of drugs. However, this condition is not applicable to the sale of drugs to hospitals, medical, educational or research institutions and manufacturers of hydrogenated vegetable oils, beverages, confectionery and other non -medical products where such drugs are needed for processing of these products or to registered medical practitioners or officers authorised by the Government for the purchase of drugs.60 Pharmaceutical Jurisprudence 2) The licence should be displayed in such a part of the premises from where it is open to the public. 3) All other provisions of the Act and the Rules discussed above should be observed as far as applicable. Wholesale from Motor Vehicles At the present time, licences are being granted for drug distribution via motor vehicles. Separate licences are needed for wholesale of drugs under Schedules C and C, and other than those in Schedules C and C __,. The conditions for these licenses are same as the conditions for wholesale of drugs. Drugs should be bought from a licenced manufacturer or wholesaler and distributed to individuals having valid licences for retail sale of drugs. The drugs are distributed to an officer or authority purchasing on behalf of aGovern _ ment or to hospitals, educational or research institutions or to registered medical practitioner. They are also distributed to manufactur ers of beverages, confectionery, or othernon —- medical products which require these drugs for the manufacturing products. The licences should be displayed on the vehicle. In case any change is made in the ownership of the vehicle or constitution of the firm that was granted licence, the Licensing Authority should be informed within a week of the change made. 2.1.14.2. Retail Sale of Drugs Retailing of drugs is done through shops or by vendors. Certain important basics for retail selling of drugs are given below: Retail Sale from Shops Following are the rules for the retail sale from shops: 1) Facilities as per Schedule N 2) Purchase only from licenced wholesaler, 3) No sale of specified drugs (Schedule H and Schedule X without prescription), 4) Separate licences for Schedules C, C1 and X drugs, 5) Sale under qualified supervision, 6) Records, 7) Inspection, and 8) Sale of specified household drugs from drug stores (Condi tions (1) to (5) not applicable). Retail sale of drugs can be done from the following shops: 1) Chemists and Druggists Establishments: Chemists and Druggists establishments, functioning un der the supervision of a ,,registered pharmacist’ but do not compound drugs. 2) Pharmacies: Establishments, functioning under the su pervision of a “Registered Pharmacist’ and engaged in compounding of drugs.Drugs and Cosmetics Act and Rules-II (Chapter 2) 61 Chemists, Druggists and Pharmacists require separate licences for the sale of: 1) Schedules C and C1 drugs, 2) Schedule X drugs, and 3) Drugs other than those specified in Schedules C and C1, and Schedule X. After the fulfilment of the following conditions, licences for chemist’s and druggist’s shops and pharmacies are granted: 1) The licensee should have premises equipped with adequate facili _ties for proper drug storage and a registered pharmacist should supervise and control the sale and distribution of drugs. 2) Requirements specified in Schedule N for a ‘pharmacy’ should be fulfilled. 3) A person (with a licence to sell Schedule C and C1 drugs) should seek permission from the Licensing Authority if he wishes to sell categories of drugs not listed in his licence. 4) All registers and records maintained should be kept for a period of at least 2 years from the date of the last entry made. 5) Licensee should allow the inspection of the premises and _ the registers and records by an authorised Inspector to ascertain whether or not the provisions of the Act and Rules are being followed. 6) The Licensing Authority should be informed about any change in the qualified staff by the licensee within a month of such change. 7) Schedule C and CI drugs should not be sold without taking precautions for their storage during the period when they were possessed by the licensee. Retail Sale from Vendors Sometimes drugs are sold by vendors who do not have a fixed place of business but have been granted a licence by the Licensing Authority to conduct business in a particular area. Persons who distribute drugs in sparsely populated areas with no other agencies for drug distribution or to travelling agents of firms dealing in drugs are issued licences to sell drugs. The licences to sell drugs are issued only for drugs other than those specified in Schedules C and C,. 2.1.14.3, Restricted Licences For the restricted sale of drugs other than those specified in Schedule C, C, and X and those specified in Schedule C andC__, but not in Schedule X, licences are issued in Form 20A and 214A, respectively. Restricted licences can be given to: 1) Dealers or persons for drugs whose sale does not need to be supervised by a qualified person. 2) Itinerant vendors in exceptional cases, for bona fide travelling agents of firms dealing in drugs, or 3) Toa vendor who purchases drugs from a licenced dealer for distributing drugs in sparsely populated areas with no other agencies dealing with drug distribution. 4) Toatravelling agent of a firm for drug distribution to medical practitioners or dealers, for supply of biological and other special products specified in aa ‘esSo Pharmaceutical Jurisprudence Travelling agents of licenced manufacturers and agents of importers of drugs can distribute the free medicine samples to any member of medical profession, hospitals, dispensaries, and medical or research institutions without any licence. Conditions for Restricted Licence 1) 2) 6) 7) The licensee should have premises well-equipped with drug storage facilities; but this condition is not valid for the vendors. The licence should be displayed in the premises in such a place that it is easily visible to the public; while the vendors should keep the licence with them so they can present it on demand to an authorised Inspector or any other officer (appointed by the State Government). The licensee should fulfil the provisions of the Drugs and Cosmetics Act and Rules. The drugs should be bought only from a licenced dealer or manufacturer. The licensee can deal in those drugs that can be sold without the supervision ofa ‘qualified person’. In case the licensee is a vendor and has no fixed place of business, he should purchase the drugs from dealers as given in his licence. Drugs should be sold in their original container. The Licensing Authority should consider the occupation, trade, or business of the applicant and also the number of licences granted in a area in the last three years, before granting the restricted licence. 2.1.14.4. Procedure for the Sale, Purchase, and Storage of Drugs In different kinds of establishments for the sale of a drug. following important procedures should be followed: 1) Dispensing and Compounding of Drugs: Drugs compounded at the premises against the prescription of a Medi cal Practitioner should be compounded either by a Registered Pharmacist or under his supervision. All supplies of drugs on a prescription should be recorded in a register maintained with the following headings: i) Serial No. of the entry, ii) Date of supply, iii) Prescriber’s name and address, iv) Patient’s name or name and address of the owner of animal, if drug is for veterinary use, v) Names and quantities of the drugs, vi) Manufacturer's name, batch number and expiry date of Schedule C and H drugs, vii) Signature of the Registered Pharmacist under whose supervision the medicine was made up and supplied, viii) Drug supplied on a prescription should comply with its description in the prescription, manufacturer, etc. ix) The details of the drugs which are not compounded but supplied in or from original containers should be entered in a cash or credit memo book, serially numbered and properly maintained for this purpose. If theDrugs and Cosmetics Act and Rules-II (Chapter 2) 63 Licensing Authority feels that the entries of carbon copies of the cash/credit memo book are not understandable he shou Id maintain records in a register. 2) Sale of Schedule X and Schedule H Drugs : Substances specified in Schedules H and X should be retailed only on a Registered Medical Practitioner's prescription. Dispensing of drugs prescribed in such prescription should not be done more than once. However, it may be repeated if it is specified in the prescription that it may be dispensed more than once at specified intervals. The dispenser should note the prescriber’s name, address and the date of dispensing above signature, at the time of dispensing. No substitution should be made in dispensing prescriptions with Schedule H and X drugs. The prescriptions should be in duplicate and retained for 2 years, in case of Schedule X drugs. Separate bound and paged registers with Separate sheets allotted for each drug should be maintained for supply. At the time of supply the following particulars should be entered: i) Date of supply and opening and closing stocks of drug on that day and relevant bill numbers, ii) Drug’s name, manufacturer’s name and batch no., iii) Purchaser’s name and address, iv) Date of prescription and RMP’s name and address, and v) Signature of Registered Pharmacist under whose supervi sion the supply is made. 3) Supply/Sale of Schedule C Drugs: At the time of supply, the supply of Schedule C drugs should be recorded in a register or cash or credit memo book maintained for this purpose. The recording should be done with the following headings: i) Serial no. of the entry, ii) Date of supply, iii) Purchaser’s name and address, iv) Name and quantity of the drugs supplied, v) Manufacturer’s name, vi) Batch No. as recorded on its label, vii) The expiry date as indicated on the label, and viii) Signature of the registered pharmacist under whose supervi sion the sale was affected. Schedule C drugs, with an expiry date ma__rked on the label, should not be sold after the expiry of such date. Schedule C and F drugs sold or supplied by wholesale dealings or on the prescriptions of medical practitioners are exempted from the provisions of the above rules. 4) Supply/Sale of Other Drugs: Following particulars should be included in the cash/credit memo in case of the supply of all the drugs other than those specified above: i) Name, address and licence number, ii) Name and quantity of drug supplied, and iii) Serial number of cash/credit memo.64 Pharmaceutical Jurisprudence 5) Records of Purchases of Drugs: —_ Records with the following headings should be maintained for all the drugs purchased, whether for selling by retail or wholesale: i) Purchase date, ii) Name and address of the licensee from whom drugs are purchased and no. of relevant licence held by him, iii) Drug’s name, quantity, and batch number, and iv) Manufacturer’s name. Purchase bills, including cash/credit memos should be kept as records. 6) Storage of Schedule X Drugs and Drugs with Expiry Dates: Schedule X drugs should be stored under lock and key, either in a drawer or a cupboard, for storing in the establishment in a part situated separately from the remainder of the premises with no access to the customers. Other drugs with an expiry date should be stored in a separate cupboard. 7) Storage of Veterinary Medi Drugs for veterinary use should be stored in a separate drawer or cupboard in a part of the premises where the entry of customers is prohibited. 8) Drug Stores:Licencesfor drug stores are granted on the followingonditions i) The licensee can only deal with drugs which are sold without the Registered Pharmacist’s supervision. ii) If the licensee is a vendor with no fixed place of busi ness, he should buy drugs only from dealers specified in his licence. iii) Licensee must take adequate precautions for preserving the properties of the drugs in his possession and drugs which have not been stored under prescribed conditions should not be sold. iv) The licence should be displayed in a part of the premises open to the public. If the licensee is a vendor with no fixed place of business, he should produce the licence on demand. v) Drugs should be sold in their original container. The Licensing Authority should consider the number of licences granted in a locality during the last one year andthe occ _upation, trade or business of the applicant, before granting the restricted licence. 2.1.14.5. Classes of Drugs whose Sale is Prohibited The drugs or classes of drugs whose sale is prohibited are: 1) Misbranded, spurious, adulterated, and non-standard quality drugs. 2) Patent and proprietary drugs with undisclosed formulae. 3) Drugs claiming by any statement, design, or device to cure any diseases specified in Schedule J. 4) Drugs manufactured or imported in violation of the provisions of the Act and the Rules. 5) Expired drugs; however, such drugs can be stocked in packages labelled “Not for sale” pending their withdrawal by manufacturers or disposal. 6) Drugs to be consumed by E.S.I.S., Central Government Health Scheme, Government Medical Depot, Armed Forces Medical Stores, or othe r Government institutions.Drugs and Cosmetics Act and Rules-II (Chapter 2) 65 7) Drugs to be distributed as a free sample to the members of the medical profession and bearing the words “Physician's Sample. Not to be sold” on the container. 8) Drugs not to be sold. Tt is a defence to prove that the person who s__ old the drug in violation of the Rules: 1) Acquired the same from a duly licenced manufacturer or dealer and the drug remained in the same state as when he obtained it and also it was stored adequately. 2) And he was not conscious and could not have with reasona ble diligence determined that the drug was in violation of the law. A person who needs to take benefit of the defence warranty given above should send a copy of the warranty to the prosecuting inspector within 7 days of the service of summons on him with the notice of his intention to take benefit of it. 2.1.14.6. Offences and Penalties The offence and penalties regarding the sale of drugs under this Act are enlisted in table 2.2: Table 2.2: Offences and Penalties with Respect to Sale of Drugs Offences Penalties 1) Sale, stocking, exhibition, or Imprisonment from 5 years to life and fine offer for sale of drugs which of not less than % 10,000. may cause death or serious hurt as per Section 320 of IPC. 2) Sale, stocking, exhibition, or Imprisonment of 1-3 years and fine of up to offer for sale of spurious drugs. | 5,000 rupees on first conviction; and imprisonment for2 -6 years and fine of 10,000 on subsequent convictions. 3) Sale, stocking, exhibition, or | Imprisonment for 3-5 years (less for offer for sale of spurious drugs. | adequate reasons) on first conviction; and imprisonment for2 -6 years and fine of 210,000 on subsequent offences. 4) Sale, stocking, exhibition, or Imprisonment from | to 2 years and fine offer for sale in contra vention of (less on adequate reasons) for subsequent any other provision. offence 2 to 4 years and/or % 5,000 fine. 5) Failure to keep records or Imprisonment for | year and/or fine of up disclose required information. to % 1,000. 6) False warranty to purchaser Imprisonment for | year and fine of up to 5,000 on first conviction; and imprisonment for up to 2 years or fine or both on subsequent conviction. 7) Use of reports of government Fine of up to = 500 on first conviction; and analysts or central drug imprisonment for up to 10 years or fine or laboratory for advertising. both on subsequent convictions.66, Pharmaceutical Jurisprudence 2.1.15. Labelling and Packing of Drugs The legal requirements for labelling of drugs are given as follows: 1) Identity of drug and its manufacturer is done by its official name, trade name, manufacturer’s name and address and licence number and batch number. Official names are used for Schedule W drugs. 2) Potence, standard, grade, dose, etc. are expressed in millilitres, grains, units, etc. 3) Net contents are expressed as volume or weight or number. 4) Manufacturing and expiry dates should be given for schedule P and C drugs only. 5) Precautions for handling, storage, sale/usage, should be given properly. 6) Special requirements for certain drugs such as physicians’ samples, veterinary drugs, drugs having certain materials like spirit, colour, etc. 7) There should be certain provisions for dispensed drugs or drugs for export. The only aim of pharmaceutical packaging is to confirm the safety of pharmaceutical preparations so they do not get contaminated, Packaging also prevents microbial growth, thus the product remains stable during the intended shelf-life. Packing is an important tool in pharmaceutical industries for product delivery and compliance associated with regulatory authorities. 2.1.15.1. General Labelling Requirements ‘The labelling requirements related to the name and use of drug, caution, etc. are enlisted in table 2.3: Table 2.3: Special Labelling Requirements for the Medicines of Different Schedules. Class and Nature of Medicines in Particulars which should Appear on Label which Contained ‘Schedule C, 1) The manufacture date Schedule C , drugsand their | 2) ‘The expiry date. preparations including 3) Import license number (if applicable) combinations with other drugs ‘Schedule F and F, The prescribed name ‘Schedule G The words “Caution. Itis dangerous to take this Medicines made up ready for | preparation except under medical supervision”, internal use in the treatment of | should be clearly printed and surrounded by a line human ailments. within which there should be no other words. ‘Schedule H 1) Symbol should be clearly displayed on the left Medicines for internal use of top comer of the label. human beings. 2) “Schedule H Drug — Warning: To be sold by retail on the prescription of a Registered Medical Practitioner only” ‘Schedule H 1) Symbol N should be clearly displayed on the Falling under Dangerous left top comer of the label Drugs Act, 1930. 2) “Schedule H Drug — Warning: To be sold by retail on the prescription of a Registered Medical Practitioner only”. ‘Schedule X 1) Symbol N should be clearly in red on left top Medicine for internal use of comer of the label. human beings. 2) “Schedule X Drugs — Warming: To be sold by retail on the prescription of a Registered Medical Practitioner only.”Drugs and Cosmetics Act and Rules-Il (Chapter 2) 67 In original form ‘Schedule X Symbol X given conspicuously in red. Bulk form ‘Schedule P 1) The manufacture date. Any drug 2) The expiry date. Schedule C 1) Proper name of the substance along with the name of any patent or proprietary. 2) License No. under which manufactured or imported. 3) Batch No. or Lot. No. 4) Statement of potency in units. 5) Name and address of the manufacturer of final product. 6) The manufacture date. 7) Ifatest for maximum toxicity is prescribed, a statement that the drug has passed the test. 8) The expiry date. 9) Nature and percentage of added antiseptic. 10) Precautions for preserving the drug properties. Single ingredient Schedule G 1) Proper name. Any Drug 2) Manufacturing or import license No. 3) Batch No. 4) Potency in units. 5) The expiry date. ‘Schedule W Proper name (no trade name). Preparations containing New Drug as Single Ingredient Generic name only, Patent and Proprietary 1) Quantities of the active ingredients. 2) Manufacturer’s name and address. Patent and Proprietary 1) “For Prophylactic use” containing Vitamins for or Prophylactic or Therapeuticuse | 2) “For Therapeutic use” ‘Non-Surgical Ligature and Suture ‘The words, “Non -sterile surgical ligature (suture) — not to be used for operations upon the human body unless effectively sterilised,” should be clearly printed with indelible red ink. Pharmacopocial and Other Drugs 1) Name or synonym as specified in the Pharmacopoeia followed by the letters ~ ‘LP.’, “BP.’, BPC’, ‘US.P.’, ‘NF’, etc., as the case may be or description of the substance (proper name being not less visible than trade name, if any) Net amount of the drug in terms of weight or measure in metric system or units of activity or in case of tablets, capsules, etc., the quantity in each. Amounts of active ingredients (content per single dose in oral preparations and in terms of volume in case of p arenteral preparations). For preparations of antibiotics, hormones, and other drugs for parenteral use whose dosage is expressed in units or by weight: total units or quantity in each container or number of units or weight per g orml (not necessary incase of pharmacopoeial preparations). Manufacturer’s name and address. Manufacturing License No. and Batch No. 3) 4)68 Pharmaceutical Jurisprudence Embrocation, liniment, lotion, ointment, antiseptic cream, Alcoholic Preparations Statement of the quantity of alcohol as average % of Any drug containing more than | absolute alcohol by volume. 3% viv alcohol. Preparations for External “For External Use Only" Application Medicines for the treatment of animals. liquid antiseptic, or other liquid medicine. Ophthalmic Ointments 1) Special storage instructions. 2) Warning: If irritation persists or discontinue the use and consult the physician, Medicines for Animals 1) The words, .Not for human use. For animal treatment only.” 2) Symbol depicting the head of a domestic animal. ‘Medicines Containing Methylated Spirit Medicines for the treatment of human ailments and containing industrial methylated spirit. *For External Use Only” Disinfectants 1) Product name and manufacturer's name and address. 2) Grade, type, and R.W. coefficient of the product. 3) Manufacture and expiry date. 4) Quantity in the container. 5) _ Indications and mode of use. “Mechanical Contraceptives 1) Particulars specified in Schedule R. 2) Manufacture and expiry date. 3) _ Storage conditions. Oral Contraceptives Manufacture date. Coloured Medicaments ‘Common name and % of colour. Replaced Containers Drugs supplied in containers other than those marketed by the manufacturer. Drug name and quantity, and the seller’s name and address. Drug Samples Drugs for free distribution to the medical profession, ‘The words, ‘Physician's Sample’, ‘Not to be sold’. 2.1.15. Specimen Labels for Drugs And Cosmetics Details mentioned on the container’s label should be properly visible on the innermost container having the drug is present and also on every following covering in which the container is packed. Any transparent covering or wrapper, or any other covering used for packing during transportation are not labelled with these details. The particulars should be either printed on the attached label, or are painted or permanently marked on the container (excluding the drug name which should not be so clear on only glass container except the ampoules).Drugs and Cosmetics Act and Rules-II (Chapter 2) 69 Red coloured letters are used for writing the drug name and followed by its trade name (if present). The trade name should not be written in red, and should be of the same size as proper name, except for veterinary, ear and eye drops, and sterile products. The containers of Schedules H and G drugs should be labelled in red letters against white background before being manufactured in dosage forms. Following are some examples of sample labels of the rules given above: 1) For 10ml vial of insulin 80units/c.c. (Schedule C and Schedule G drug.) 10c.c. Insulin 80 units/c.c. Caution: It is dangerous to take this preparation except under medical supervision Mfg. License No. 345, Batch No. 345 Date of Manufacture 1-1-98 NANDY and SEN Ltd. 20, Bow Bazar, Calcutta 2) For hair lotion containing 2% w/v Mercuric chloride RINSO HAIR LOTION Contains 2% wiv Mercuric Chloride For External Use Only Delhi Cooperative Chemists 32, The Fountain, Delhi 3) For 100 tablets of Phenobarbitone (Schedule X drug) 100 x 50mg. ‘Tablets of Phenobarbitone Schedule X drug. Warning: To be sold by retailers on the prescription of a Registered Medical Practitioner only. JOHN & JOHN Ltd. Chemists 75, Park Street, Calcutta70 Pharmaceutical Jurisprudence 4) For 10ml of Anti-pneumococcus Serum Type I 10m! Pneumocure (Anti-pneumococus Serum, Type 1) Natural Serum Containing 0.5% Phenol License No. 345 Batch No. 863, Date of manufacture 28-6-97 Date of expiry 28-6-99 Mehta & Co. Pharmaceutical Chemists 24th Road, Chembur, Bombay 2.1.15.3. List of Permitted Colours Following are the colours that can be added to the medicines. The common names and the percentage of colour added should be mentioned on the label of container. The medicines to which these colours are added shall not be deemed to be misbranded only due to the fact of adding of colours within: 1) Natural Colours: Annatto, carotene, cochineal, curcumin, chlo rophyll, red oxide of iron, yellow and black oxide of iron, and titanium dioxide. 2) Artificial Colours: Caramel. 3) Coal Tar Colours Table 2.4: Colours and their Chemical Names Common Names of | Colour ‘Chemical Names Colours Index Number Green Quinizarine Green] 61565 | 1, 4-Bis (p-tolyamino) anthraquinone. ss Alizarin Cyanine 61570 | Disodium salt of 1.4 -bis(__ o-sulfo-p-tulouino) Green F anthraquinone Fast Green FCF 42053 | Disodium salt of 4 -([4-(N-ethykp Sulfobenzylamino) ~ phenyl-]-(4-hydroxy2- sulfoniumphenyl)-methylene) [1 - (N-ethyl-N-p-sulfobenzyl]A 2, 5-cyclohexadienimine]. Green S 44090 Yellow Tartrazine 19140] Trisodium salt of 3 -carboxy-5- hydroxy-Ip-sulfophenyl- 4-p- Sulfophenyl azopyrazole. ‘Sunset YellowFCF | 15985 | Disodium salt of | -p-sulfophenyl azo -2- naphthol-6- sulfonic acid. Quinoline Yellow 47005 | Disodium salt of disulfonic acid of (2 - quinolyl)-1,3- ws indandione. Red ‘Amaranth 16185 | Trisodium salt of 1(4 -sulfo-Inaphthylazo) 2-naptho 1 -3, 6-disulfonic acid. Erythrosine 45430 | Disodium salt of 9 -o-carboxyphenyl 6 -hydroxy 2,4-5,7- tetriodo-3-isoxanthone.Drugs and Cosmetics Act and Rules-II (Chapter 2) 1 Eosin YS or BosinG | 45380 | Disodium salt of 2,4.5.7 -tetrabromo-9-p-carboxyphenyl- 6-hydroxy 3-isoxanthone. Toney Red or Sudan | 26100 _| 1-p-phenylazophenylazo-2-naphtho. it Ponceau 4R 16255 | Trisodiumsalt of 1 -(4-sulpho-I-I- Napthylazo)- 2 napthol-6 : 8-disulphonic acid. Carmoisine 147720 | Disodium salt of 2 -(4-sulpho-1-napthylazo)-1 napthol -4 sulphonic acid. Fast Red E 16005 | Disodium 2 ~hydroxy-1-(4-sulpho- | -naphthylazo) naphthalene -6-sulfonate acid. Blue Indigo Carmine 73015, Disodium salt of indigotin Brilliant Blue FCF 42090 | Disodium saltof4 _ -[{4(N-ethyl-psulfobenzylamino)-| phenyl }-](2- sulfonium phenyl)-methylene)-1-(N- ethyl- N-psulfobenzyl)- A 2, 5-cyclohexadienimine. Violet Alizurol Purple 60725 | Disodium saltof | phenylazo ~2-naphtho-6,8- disulphonic acid. Brown: Resorein Brown 20170 | Monosodium salt of 4 -p-sulfophenylazo-2(2.4- xylylazol )-3-resoreinol. Black Naphthol Blue 20470 Disodium salt of 8 -amino-7 5-nitrophenylazo-2- naphthol-3,6-disulfonic acid 2.1.15.4. Offences And Penalties The offences which can be committed medicinal products are: 1) Selling or supplying a product not in a container, 2) Issuing a false or misleading label with the medicinal product, 3) Packing a product in a container that does not fulfil the — requirements of the regulations, 4) Selling, supplying, or possessing for sale a product that is not of the colour or not marked requirements of the regulations, and 5) Selling products from an automatic machine not marked as per the requirements of the regulations. 2.1.16. Administration of the Act and Rules The Drugs and Cosmetics Act forms the agencies given in table 2.5, along with while packaging and labell ing of their functions: Table 2.5: Agencies and their Functions Agencies Functions 1) Advisory i) Drugs Technical Advises Central and State Governments on technical Advisory Board matters arising out of the operation of the Act. (DTAB) ii) Drugs Consultative Advises governments and DTAB on issues related to Committee uniform operation of the Act throughout country. 2) Analytical i) Central Drugs ‘Analyses and submits report on samples ofdmgso Laboratory cosmetics sent by custom collectors or courts.2 Pharmaceutical Jurisprudence ii) State Drug Control | Analyses and submits report on samples of drugs or Laboratory cosmetics sent by the drug inspec tor; analyses samples Of private agencies on prescribed payment. 3) Executive i) sing Authority | In-charge of drugs control: issues licenses and implementation of Act. ii) Drug Inspectors Inspects the licensed establishments and assists the licensing authorities in implementation of the Act iii) Customs Collectors | Aids in the implementation of the Act to a certain extent with respect to imported drugs or cosmetics. 2.1.16.1. Drugs Technical Advisory Board (DTAB) DTAB has the following members: 1) Ex-Officio Members i) Director-General of Health Services, who is also the Chairman, ii) Drugs Controller of India, iii) Director, Central Drugs Laboratory, Kolkata, iv) Director, Central Research Institute, Kasauli, v) Director, Indian Veterinary Research Institute, Izzatnagar, vi) President, Pharmacy Council of India, vii) President, Medical Council of India, and viii) Director, Central Drugs Research Institute, Lucknow. 2) Nominated Members i) One person from pharmaceutical industry nominated by the Central Government, ii) Two govemment analysts, appointed under the Act, nomi nated by the Central Government, and iii) Two persons from amongst the persons who are in-charge of the drug control agencies in the States, nominated by the Central Government. 3) Elected Members i) A teacher in pharmacy, pharmaceutical chemistry, or pharmacognosy on the staff of a university or affiliated college elected by the Executive Committee of Pharmacy Council of India, ii) A teacher in medicine or therapeutics on the staff of a university or affiliated college elected by the Executive Committee of the Medical Council of India, iii) One person elected by the Council of the Indian Pharma ceutical Association, iv) One person elected by the Council of the Indian Medical Association, and v) One pharmacologist elected by the Governing Body of the Indian Council of Medical Research. Functions 1) Itadvises the Central and the State Governments on technical matters of the administration of this Act. 2) Itmakes modifications and amendments in the Act by consulting the Board. 3) It carries out the other functions assigned by the Act.