F

(See rule 78) 1[Part I to Part XII-A]– Omitted _______ 2[PART XII B REQUIREMENTS FOR THE FUNCTIONING AND OPERATION OF A BLOOD BANK AND / OR FOR PREPARATION OF BLOOD COMPONENTS. I. BLOOD BANKS / BLOOD COMPONENTS A. GENERAL 1. Location and Surroundings : The blood bank shall be located at a place which shall be away from open sewage, drain, public lavatory or similar unhygienic surroundings. 2. Building : The building (s) used for operation of a blood bank and/or preparation of blood components shall be constructed in such a manner so as to permit the operation of the blood bank and preparation of blood components under hygienic conditions and shall avoid the entry of insects, rodents and flies. It shall be well lighted, ventilated and screened (mesh), wherever necessary. The walls and floors of the rooms, where collection of blood or preparation of blood components or blood products is carried out shall be smooth, washable and capable of being kept clean. Drains shall be of adequate size and where connected directly to a sewer, shall be equipped with traps to prevent back siphonage. 3. Health, clothing and sanitation of staff: The employees shall be free from contagious or infectious diseases. They shall be provided with clean overalls, head-gears, foot-wears and gloves, wherever required. There shall be adequate, clean and convenient hand washing and toilet facilities. B. ACCOMMODATION FOR A BLOOD BANK. A blood bank shall have an area of 100 square meters for its operations and an additional area of 50 square meters for preparation of blood components. It shall be consisting of a room each for – (1) registration and medical examination with adequate furniture and facilities for registration and selection of donors; (2) blood collection (air-conditioned); _________________________________________________ 1. Schedule ‘F’ subs. by G.S.R. 245(E), dt. 5.4.1999 and corrected vide corrigendum G.S.R. 27(E), dated 22.1.1993. 2. Parts XII-A XIIC subs. by G.S.R. 245(E), dt. 5.4.1999. Drugs and Cosmetics Rules, 1945 269 (3) blood component preparation. (This shall be air-conditioned to maintain temperature between 20 degree centigrade to 25 degree centigrade); (4) laboratory for blood group serology (air-conditioned); (5) laboratory for blood transmissible diseases like Hepatitis, Syphilis, Malaria, HIV-antibodies (air-conditioned); (6) sterilization-cum-washing; (7) refreshment-cum-rest room (air-conditioned); (8) store-cum-records. NOTES : (1) The above requirements as to accommodation and area may be relaxed, in respect of testing laboratories and sterilization-cum-washing room, for reasons to be recorded in writing by the Licensing Authority and/or the Central Licence Approving Authority, in respect of blood banks operating in hospitals, provided the hospital concerned has a pathological laboratory and a sterilization-cum-washing room common with other departments in the said hospital. (2) Refreshments to the donor after phlebotomy shall be served so that he is kept under observation in the blood bank. C PERSONNEL Every blood bank shall have following categories of whole time competent technical staff:- (a) Medical Officer, possessing the qualifications specified in condition (i) of rule 122-G. (b) Blood Bank Technician(s) possessing – (i) Degree in Medical Laboratory Technology (M.L.T) with six months’ experience in the testing of blood and/or its components; or (ii) Diploma in Medical Laboratory Technology (M.L.T) with one year’s experience in the testing of blood and / or its components, the degree or diploma being from a University / Institution recognized by the Central Government or State Government. (c) Registered Nurse(s); (d) Technical supervisor (where blood components are manufactured), possessing- (i) Degree in Medical Laboratory Technology (M.L.T) with six months’ experience in the preparation of blood components; or (ii) Diploma in Medical Laboratory Technology (M.L.T) with one year’s experience in the preparation of blood components, the degree or diploma being from a University / Institution recognized by the Central Government or State Government. Drugs and Cosmetics Rules, 1945 270 NOTES : (1) The requirements of qualification and experience in respect of Technical Supervisor and Blood Bank Technician shall apply in the cases of persons who are approved by the Licensing Authority and/or Central Licence Approving Authority after the commencement of the Drugs and Cosmetics (Amendment) Rules, 1999. (2) As regards, the number of whole time competent technical personnel, the blood bank shall comply with the requirements laid down in the Directorate General of Health Services Manual. (3) It shall be the responsibility of the licensee to ensure through maintenance of records and other latest techniques used in blood banking system that the personnel involved in blood banking activities for collection, storage, testing and distribution are adequately trained in the current Good Manufacturing Practices/Standard Operating Procedures for the tasks undertaken by each personnel. The personnel shall be made aware of the principles of Good Manufacturing Practices / Standard Operating Procedures that affect them and receive initial and continuing training relevant to their needs. D. MAINTENANCE The premises shall be maintained in a clean and proper manner to ensure adequate cleaning and maintenance of proper operations. The facilities shall include:- (1) Privacy and thorough examination of individuals to determine their suitability as donors. (2) Collection of blood from donors with minimal risk of contamination of exposure to activities and equipment unrelated to blood collection. (3) Storage of blood or blood components pending completion of tests. (4) Provision for quarantine, storage of blood and blood components in a designated location, pending repetition of those tests that initially give questionable serological results. (5) Provision for quarantine, storage, handling and disposal of products and reagents not suitable for use. (6) Storage of finished products prior to distribution or issue. (7) Proper collection, processing, compatibility testing, storage and distribution of blood and blood components to prevent contamination. (8) Adequate and proper performance of all procedures relating to plasmapheresis, plateletpheresis and leucapheresis. (9) Proper conduct of all packaging, labelling and other finishing operations. (10) Provision for safe and sanitary disposal of – (i) Blood and/or blood components not suitable for use, distribution or sale. (ii) Trash and items used during the collection, processing and compatibility testing of blood and / or blood components. Drugs and Cosmetics Rules, 1945 271 E. EQUIPMENT Equipment used in the collection, processing, testing, storage and sale/distribution of blood and its components shall be maintained in a clean and proper manner and so placed as to facilitate cleaning and maintenance. The equipment shall be observed, standardized and calibrated on a regularly scheduled basis as described in the Standard Operating Procedures Manual and shall operate in the manner for which it was designed so as to ensure compliance with the official requirements (the equipments) as stated below for blood and its components. Equipment that shall be observed, standardized and calibrated with at least the following frequencies: 1. Temperature Recorder Compare against thermometer Daily As often as necessary 2 Refrigerated centrifuge Observe speed and temperature Each day of use As often as necessary Hematocrit centrifuge – – Standardise before initial use, after repair or adjustments and annually. 4, General lab. Centrifuge – – Tachometer, every 6 months. 5. Automated Blood typing Observe controls for correct results Each day of use – 6. Haemoglobinometer Standardize against cyanamethemoglob ulin standard −ditto− – 7. Refractiometer or Urinometer Standardize against distilled water − ditto − – 8. Blood container weighing device Standardize against container of known weight. − ditto – As often as necessary 9 Water Bath Observe temperature − ditto − −ditto− Rh view box (wherever necessary) –ditto– − ditto − − ditto− _______________________________________________________________ EQUIPMENT PERFORMANCE FREQUENCY FREQUENCY OF CALIBRATION _______________________________________________________________________________________________ Drugs and Cosmetics Rules, 1945 272 Autoclave Observe temperature Each day of use As often as necessary Serologic rotators Observe controls for correct results -- ditto-- Speed as often as necessary. 13 Laboratory thermometers – – Before initial use 14 Electronic thermometers – Monthly – 15 Blood agitator Observe weight of the first container of blood filled for correct results Each day of use Standardize with container of known mass or value before initial use, and after repairs or adjustments. F. SUPPLIES AND REAGENTS: All supplies and reagents used in the collection, processing, compatibility, testing, storage and distribution of blood and blood components shall be stored at proper temperature in a safe and hygienic place, in a proper manner and in particular:– (a) all supplies coming in contact with blood and blood components intended for transfusion shall be sterile, pyrogen-free, and shall not interact with the product in such a manner as to have an adverse effect upon the safety, purity, potency or effectiveness of the product. (b) supplies and reagents that do not bear an expiry date shall be stored in a manner that the oldest is used first. (c) supplies and reagents shall be used in a manner consistent with instructions provided by the manufacturer. (d) all final containers and closures for blood and blood components not intended for transfusion shall be clean and free of surface solids and other contaminants. (e) each blood collecting container and its satellite container(s), if any, shall be examined visually for damage or evidence of contamination prior to its use and immediately after filling. Such examination shall include inspection for breakage of seals, when indicated, and abnormal discoloration. Where any defect is observed, the container shall not be used or, if detected after filling, shall be properly discarded. (f) representative samples of each lot of the following reagents and/or solutions shall be tested regularly on a scheduled basis by methods described in the Standard Operating Procedures Manual to determine their capacity to perform as required, Drugs and Cosmetics Rules, 1945 273 Anti-human serum Blood grouping serums Each day of use Each day of use Lectin Each day of use Antibody screening and reverse grouping cells Each day of use Hepatitis test reagents Each run Syphilis serology reagents Each run Enzymes Each day of use HIV I and II reagents Each run Normal saline (LISS and PBS) Each day of use Bovine Albumin Each day of use. Reagents and solutions Frequency of testing alongwith controls G. GOOD MANUFACTURING PRACTICES (GMPs) /STANDARD OPERATING PROCEDURES (SOPs): Written Standard Operating Procedures shall be maintained and shall include all steps to be followed in the collection, processing, compatibility testing, storage and sale or distribution of blood and/or preparation of blood components for homologous transfusion, autologous transfusion and further manufacturing purposes. Such procedures shall be available to the personnel for use in the concerned areas. The Standard Operating Procedures shall inter alia include: 1. (a) criteria used to determine donor suitability. (d) method of accurately relating the product (s) to the donor; (e) blood collection procedure, including in-process precautions taken to measure accurately the quality of blood drawn from the donor; (f) methods of component preparation, including any time restrictions for specific steps in processing; (g) all tests and repeat tests performed on blood and blood components during processing; (h) pre-transfusion testing, wherever applicable, including precautions to be taken to identify accurately the recipient blood components during processing; (b) (c) methods of performing donor qualifying tests and measurements including minimum and maximum values for a test or procedure, when a factor in determining acceptability; solutions and methods used to prepare the site of phlebotomy so as to give maximum assurance of a sterile container of blood; Drugs and Cosmetics Rules, 1945 274 (n) quality control procedures for supplies and reagents employed in blood collection, processing and re-transfusion testing; (o) schedules and procedures for equipment maintenance and calibration; (p) labelling procedures to safeguard its mix-ups, receipt, issue, rejected and in-hand; (q) procedures of plasmapheresis, plateletphersis and leucapheresis if performed, including precautions to be taken to ensure re-infusion of donor’s own cells; (r) procedures for preparing recovered (salvaged) plasma if performed, including details of separation, pooling, labelling, storage and distribution; (s) all records pertinent to the lot or unit maintained pursuant to these regulations shall be reviewed before the release or distribution of a lot or unit of final product. The review or portions of the review may be performed at appropriate periods during or after blood collection, processing, testing and storage. A thorough investigation, including the conclusions and follow-up, of any unexplained discrepancy or the failure of a lot or unit to meet any of its specification shall be made and recorded. (2) A licensee may utilise current Standard Operating Procedures, such as the Manuals of the following organizations, so long as such specific procedures are consistent with, and at least as stringent as, the requirements contained in this Part, namely :- (i) Directorate General of Health Services Manual. (ii) Other Organisations or individual blood bank’s manuals, subject to the approval of State Licensing Authority and Central Licence Approving Authority. H. CRITERIA FOR BLOOD DONATION: Conditions for donation of blood: (1) General – No person shall donate blood and no blood bank shall draw blood from a person, more than once in three months. The donor shall be in good health, mentally alert and physically fit and shall not be inmates of jail, persons having multiple sex partners and drug-addicts. The donors shall fulfil the following requirements, namely: - (i) procedures of managing adverse reactions in donor and recipient reactions: (j) storage temperatures and methods of controlling storage temperatures for blood and its components and reagents; (k) length of expiry dates, if any assigned for all final products; (l) criteria for determining whether returned blood is suitable for re-issue; (m) procedures used for relating a unit of blood or blood component from the donor to its final disposal; Drugs and Cosmetics Rules, 1945 275 (a) the donor shall be in the age group of 18 to 60 years; (b) the donor shall not be less than 45 kilograms; ( c) temperature and pulse of the donor shall be normal; (d ) the systolic and diastolic blood pressure are within normal limits without medication; (e) haemoglobin which shall not be less than 12.5 grams; (f) the donor shall be free from acute respiratory diseases; (g) the donor shall be free from any skin diseases at the site of phlebotomy; (h) the donor shall be free from any disease transmissible by blood transfusion, insofar as can be determined by history and examination indicated above; (i) the arms and forearms of the donor shall be free from skin punctures or scars indicative of professional blood donors or addiction of self injected narcotics. (2) Additional qualifications of donor – No person shall donate blood, and no blood bank shall draw blood from a donor, in the conditions mentioned in column (1) of the Table given below before the expiry of the period of deferment mentioned in the column (2) of the said Table. Table: Deferment of blood donation ___________________________________________________________________________ CONDITIONS PERIOD OF DEFERMENT ___________________________________________________________________________ _____________________(1)___________________________(2)______________________ (a) Abortions 6 months (b) History of Blood transfusion 6 months (c) Surgery 12 months (d) Typhoid 12 months after recovery (e) History of Malaria and duly treated 2 months (endemic) 3 years (non endemic area) (f) Tattoo 6 months (h) Breast feeding 12 months after delivery (i) Immunization (Cholera, Typhoid, Diphtheria, Tetanus, Plague, Gammaglobulin) 15 days (j) Rabies vaccination 1 year after vaccination (k) History of Hepatitis in family or close contact 12 months (l) Immunoglobulin 12 months (3) No person shall donate blood and no blood bank shall draw blood from a person, suffering from any of the diseases mentioned below, namely:– (a) Cancer (b) Heart disease Drugs and Cosmetics Rules, 1945 276 (c) Unexplained weight loss (d) Diabetes-controlled on insulin 1[(f) Hepatitis infection] (g) Chronic nephritis (h) Signs and symptoms, suggestive of AIDS (i ) Liver diseases (j) Tuberculosis (k) Polycythemia Vera. (l) Asthma (m) Epilepsy (n) Leprosy (o) Schizophrenia (p) Endocrine disorders I. GENERAL EQUIPMENTS AND INSTRUMENTS. 1. For blood collection room: (i) Donor beds, chairs and tables: These shall be suitably and comfortably cushioned and shall be of appropriate size. (ii) Bedside table (iii) Sphygmomanometer and stethoscope (iv) Recovery beds for donors. (v) Refrigerators, for storing separately tested and untested blood, maintaining temperature between 2 to 6 degree centigrade with digital dial thermometer, recording thermograph and alarm device, with provision for continuous power supply. (vi) Weighing devices for donor and blood containers. (i) Copper sulphate solution (specific gravity 1.053) (ii) Sterile lancet and impregnated alcohol swabs. (iii) Capillary tube (1.3 x 1.4 x 96 mm for Pasteur pipettes) (iv) Rubber bulbs for capillary tubings. (v) Sahli’s haemoglobinometer / Colorimetric method. (i) Clinical thermometers (ii) Watch (fitted with a second-hand) and a stop-watch. (i) Citrate Phosphate Dextrose Adenine solution (CPDA) or Citrate Phosphate Dextrose Adenine – 1 (CPDA-1) – 14 ml solution shall be required for 2. For haemoglobin determination: 3. For temperature and pulse determination. 4. For blood containers: (a) Only disposable PVC blood bags shall be used (closed system) as per specifications of IP/USP/BP. (b) Anti-coagulants: The anti-coagulant solution shall be sterile, pyrogen-free and of the following composition that will ensure satisfactory safety and efficacy of the whole blood and/or for all the separate blood components. 1 . Subs. by G.S.R. No. 40(E), dt. 29.1.2001. Drugs and Cosmetics Rules, 1945 277 100 ml of blood. Note 1.- (i) In case of single/double/triple/quadruple blood collection bags used for blood component preparations, CPDA blood collection bags may be used. (ii) Acid Citrate Dextrose solution (A.C.D. with Formula-A) I.P. – 15 ml solution shall be required for 100 ml of blood, (iii) Additive solutions such as SAGM, ADSOL, NUTRICEL may be used for storing and retaining Red Blood Corpuscles up to 42 days. Note 2.- The licensee shall ensure that the anti-coagulant solutions are of a licensed manufacturer and the blood bags in which the said solutions are contained have a certificate of analysis of the said manufacturer. 5. Emergency equipments/items: (i) Oxygen cylinder with mask, gauge and pressure regulator. (ii) 5 per cent Glucose or Normal Saline. (iii) Disposable sterile syringes and needles of various sizes. (iv) Disposable sterile I.V. infusion sets. (v) Ampoules of Adrenaline, Noradrenaline, Mephentin, Betamethasone or Dexamethasone, Metoclorpropamide injections. (vi) Aspirin. 6. Accessories: (i) Such as blankets, emesis basins, haemostats, set clamps, sponge forceps, gauze, dressing jars, solution jars, waste cans. (ii) Medium cotton balls, 1.25 cm adhesive tapes. (iii) Denatured spirit, Tincture Iodine, green soap or liquid soap. (iv) Paper napkins or towels. (v) Autoclave with temperature and pressure indicator. (vi) Incinerator (vii) Stand-by generator 7. Laboratory equipment: (i) Refrigerators, for storing diagnostic kits and reagents, maintaining a temperature between 4 to 6 degree centigrade (plus/minus 2 degrees centigrade) with digital dial thermometer having provision for continuous power supply. (ii) Compound Microscope with low and high power objectives. (iii) Centrifuge Table Model. (iv) Water bath: having range between 37 degree centigrade to 56 degree centigrade. (v) Rh viewing box in case of slide technique. (vi) Incubator with thermostatic control. (vii) Mechanical shakers for serological tests for Syphilis. (viii) Hand-lens for observing tests conducted in tubes. (ix) Serological graduated pipettes of various sizes. (x) Pipettes (Pasteur). (xi) Glass slides. Drugs and Cosmetics Rules, 1945 278 (xii) Test tubes of various sizes / micrometer plates (U or V type). (xiii) Precipitating tubes 6mm x 50mm of different sizes and glass beakers of different sizes. (xiv) Test tube racks of different specifications. (xv) Interval timer electric or spring wound. (xvi) Equipment and materials for cleaning glass wares adequately. (xvii) Insulated containers for transporting blood, between 2 degree centigrade to 10 degree centigrade temperatures, to wards and hospitals. (xviii) Wash bottles. (xix) Filter papers. (xx) Dielectric tube sealer. (xxi) Plain and EDTA vials. (xxii) Chemical balance (wherever necessary). (xxiii) ELISA reader with printer, washer and micropipettes. J. SPECIAL REAGENTS : (1) Standard blood grouping sera Anti A, Anti B and Anti C with known controls. Rh typing sera shall be in double quantity and each of different brand or if from the same supplier each supply shall be of different lot numbers. (2) Reagents for serological tests for syphilis and positive sera for controls. (3) Anti Human Globulin Serum (Coomb’s serum). (4) Bovine Albumin 22 percent Enzyme reagents for incomplete antibodies. (5) ELISA or RPHA test kits for Hepatitis and HIV I & II. (6) Detergent and other agents for cleaning laboratory glass wares. K. TESTING OF WHOLE BLOOD : (1) It shall be responsibility of the licensee to ensure that the whole blood collected, processed and supplied conforms to the standards laid down in the Indian Pharmacopoeia and other tests published, if any, by the Government. (2) Freedom from HIV antibodies (AIDS) Tests. – Every licensee shall get samples of every blood unit tested, before use, for freedom from HIV 1 and HIV II antibodies either from laboratories specified for the purpose by the Central Government or in his own laboratory. The results of such testing shall be recorded on the label of the container. (3) Each blood unit shall also be tested for freedom from 1[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] VDRL and malarial parasite and results of such testing shall be recorded on the label of the container. NOTES (a) Blood samples of donors in pilot tube and the blood samples of the Recipient shall be preserved for 7 days after issue. (b) The blood intended for transfusion shall not be frozen at any stage. (c) Blood containers shall not come directly in contact with ice at any stage. L RECORDS : Drugs and Cosmetics Rules, 1945 279 The records which the licensee is required to maintain shall include inter alia the following particulars, namely: (2) Master records for blood and its components: It shall indicate bag serial number, date of collection, date of expiry, quantity in ml. ABO/Rh Group, results for testing of HIV I and HIV II antibodies, Malaria, V.D.R.L. 1[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] and irregular antibodies (if any), name and address of the donor with particulars, utilization issue number, components prepared or discarded and signature of the Medical Officer in charge. (3) Issue Register: It shall indicate serial number, date and time of issue bag serial number, ABO/RH Group, total quantity in ml, name and address of the recipient, group of recipient, unit/institution, details of cros-matching report, indication for transfusion. (4 ) Records of components supplied: Quantity supplied; compatibility report, details of recipient and signature of issuing person. (5) Records of ACD/CPD/CPD-A/SAGM bags giving details of manufacturer, batch number, date of supply, and results of testing. (6) Register for diagnostic kits and reagents used: name of the kits/reagents, details of batch number, date of expiry and date of use. (7) Blood bank must issue the cross matching report of the blood to the patient together with the blood unit. (8) Transfusion adverse reaction records. (9) Records of purchase, use and stock in hand of disposable needles, syringes, blood bags, shall be maintained. NOTE : The above records shall be kept by the licensee for a period of five years. M. LABELS : The labels on every bag containing blood and/or component shall contain the following particulars, namely; (1) The proper name of the product in a prominent place and in bold letters on the bag. (2) Name and address of the blood bank (3) Licence number 1 Subs. by G.S.R. 40(E), dt. 29.1.2001 (w.e.f. 1.6.2001). (1) Blood donor record: It shall indicate serial number, date of bleeding, name, address and signature of donor with other particulars of age, weight, haemoglobin, blood grouping, blood pressure, medical examination, bag number and patient’s detail for whom donated in case of replacement donation, category of donation (voluntary / replacement) and deferral records and signature of Medical Officer In-charge. Drugs and Cosmetics Rules, 1945 280 (4) Serial number (5) The date on which the blood is drawn and the date of expiry as prescribed under Schedule P to these rules. (6) A colored label shall be put on every bag containing blood. The following color scheme for the said labels shall be used for different groups of blood: _______________________________________________ Blood Group Colour of the label O Blue A Yellow B Pink AB White (7) The results of the tests for 1[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] syphilis, freedom from HIV I and HIV II antibodies and malarial parasite. (8) The Rh. Group. (9) Total volume of blood, the preparation of blood, nature and percentage of anti- coagulant. (10) Keep continuously temperature at 2 degree centigrade to 6 degree centigrade for whole human blood and/or components as contained under III of Part XII B. (11) Disposable transfusion sets with filter shall be used in administration equipment. (12) Appropriate compatible cross-matched blood without atypical antibody in recipient shall be used. (13) The contents of the bag shall not be used if there is any visible evidence of deterioration like haemolysis, clotting or discoloration. (14) The label shall indicate the appropriate donor classification like “Voluntary Donor” or “Replacement Donor” in no less prominence than the proper name. NOTES : 1. In the case of blood components, particulars of the blood from which such components have been prepared shall be given against item numbers (5), (7), (8), (9) and (14). 2. The blood and/or its components shall be distributed on the prescription of a Registered Medical Practitioner. II. BLOOD DONATION CAMPS. A blood donation camp may be organized by – 1. Subs. by G.S.R 40(E), dt. 29.1.2001. Drugs and Cosmetics Rules, 1945 281 (a) a licensed designated Regional Blood Transfusion Centre ; or (b) a licensed Government blood bank; or 1[(c) the Indian Red Cross society; or (d) a licensed blood bank run by registered voluntary or charitable organizations recognized by State or Union Territory Blood Transfusion Council.)] NOTES: (i) “ Designated Regional Blood Transfusion Centre” shall be a center approved and designated by a Blood Transfusion Council constituted by a State Government to collect, process and distribute blood and its components to cater to the needs of the region and that center has also been licensed and approved by the Licensing Authority and Central Licence Approving Authority for the purpose. (ii) The designated Regional Blood Transfusion Centre, Government blood bank and Indian Red Cross Society shall intimate within a period of seven days, the venue where the blood camp was held and details of group wise blood units collected in the said camp to the Licensing Authority and Central Licence Approving Authority. For holding a blood donation camp, the following requirements shall be fulfilled/complied with, namely: - (A) Premises, personnel etc. (a) Premises under the blood donation camp shall have sufficient area and the location shall be hygienic so as to allow proper operation, maintenance and cleaning. (b) All information regarding the personnel working, equipment used and facilities available at such a Camp shall be well documented and made available for inspection, if required, and ensuring - (i) Continuous and uninterrupted electrical supply for equipment used in the Camp; (ii) Adequate lighting for all the required activities; (iii) Hand-washing facilities for staff; (iv) Reliable communication system to the central office of the Controller/ Organizer of the Camp; (v) Furniture and equipment arranged within the available space; (vi) Refreshment facilities for donors and staff; (vii) Facilities for medical examination of the donors; (viii) Proper disposal of waste. (B) Personnel for Out-door Blood Donation Camp: To collect blood from 50 to 70 donors in about 3 hours or from 100 to 200 donors in 5 hours, the following requirements shall be fulfilled / complied with: 1 Subs. by G.S.R. No.218(E), dt. 28-03-2001 Drugs and Cosmetics Rules, 1945 282 (i) one Medical Officer and two nurses or phlebotomists for managing 6-8 donor tables; (ii) two medico social workers; (iii) three blood bank technicians; (iv) two attendants; (v) vehicle having a capacity to seat 8-10 persons, with provision for carriage of donation goods including facilities to conduct a blood donation camp; (C) Equipments : 1. BP apparatus. 2. Stethoscope. 3. Blood bags (single, double, triple, quadruple). 4. Donor questionnaire. 5. Weighing device for donors. 6. Weighing device for blood bags. 7. Artery forceps, scissors. 8. Stripper for blood tubing. 9. Bed sheets, blankets/mattress. 10. Lancets, swab stick/tooth picks. 11. Glass slides. 12. Portable Hb meter/copper sulphate. 13. Test tube (big) and 12x100mm (small). 14. Test tube stand. 15. Anti-A, Anti-B and Anti-AB, Antisera and Anti-D. 16. Test tube sealer film. 17. Medicated adhesive tape. 18. Plastic waste basket. 19. Donor cards and refreshment for donors. 20 Emergency medical kit. 21 Insulated blood bag containers with provisions for storing between 2 degree centigrade to 10 degree centigrade. 22. Dielectric sealer or portable tube sealer. 23. Needle destroyer (wherever necessary). III. PROCESSING OF BLOOD COMPONENTS FROM WHOLE BLOOD BY A BLOOD BANK The Blood components shall be prepared by blood banks as a part of the Blood Bank services. The conditions for grant or renewal of licence to prepare blood components shall be as follows: - A. ACCOMMODATION: (1) Rooms with adequate area and other specification, for preparing blood components depending on quantum of workload shall be as specified in item B under the heading “1. BLOOD BANKS/BLOOD COMPONENTS’ of this Part. Drugs and Cosmetics Rules, 1945 283 (2) Preparation of Blood components shall be carried out only under closed system using single double, triple or quadruple plastic bags except for preparation of Red Blood Cells Concentrates, where single bags may be used with transfer bags. B. EQUIPMENT : (i) Air Conditioner; (ii) Laminar air flow bench; (iii) Suitable refrigerated centrifuge; (iv) Plasma expresser; (v) Clipper and clips and/or dielectric sealer; (vi) Weighing device; (vii) Dry rubber balancing material; (viii) Artery forceps, scissors; (ix) Refrigerator maintaining a temperature between 2 degree centigrade to 6 degree centigrade, a digital dial thermometer with recording thermograph and alarm device, with provision for continuous power supply; (x) Platelet agitator with incubator (wherever necessary); (xi) Deep freezers maintaining a temperature between minus 30 degree centigrade to minus 40 degree centigrade and minus 75 degree centigrade to minus 80 degree centigrade; (xii) Refrigerated Water bath for Plasma Thawing; (xiii) Insulated blood bag containers with provisions for storing at appropriate temperature for transport purposes; C. PERSONNEL: The whole time competent technical staff meant for processing of Blood Components (that is Medical Officer, Technical Supervisor, Blood Bank Technicians and Registered Nurse) shall be as specified in item C, under the heading “ 1. BLOOD BANKS/BLOOD COMPONENTS” of this Part. D. TESTING FACILITIES: General: Facilities for A, B, AB and O groups and Rh(D) grouping. 1[(Hepatitis B surface antigen and Hepatitis C Virus antibody)], VDRL, HIV I and HIV II antibodies and malarial parasites shall be mandatory for every blood unit before it is used for the preparation of blood components. The results of such testing shall be indicated on the label. E. CATEGORIES OF BLOOD COMPONENTS: (1) CONCENTRATED HUMAN RED BLOOD CORPUSCLES: The product shall be known as “Packed Red Blood Cells” that is Packed Red Blood Cells remaining after separating plasma from human blood. General Requirements: (a) Storage: Immediately after processing, the Packed Red Blood Cells shall be kept at a temperature maintained between 2 degree centigrade to 6 degree centigrade. (b) Inspection: The component shall be inspected immediately after separation of the Drugs and Cosmetics Rules, 1945 284 plasma, during storage and again at the time of issue. The product shall not be issued if there is any abnormality in color or physical appearance or any indication of microbial contamination. (c) Suitability of Donor: The source of blood for Packed Red Blood Cells shall be obtained from a donor who meets the criteria for Blood Donation as specified in item H under the heading “I. BLOOD BANKS/BLOOD COMPONENTS” of this Part. (d) Testing of Whole Blood: Blood from which Packed Red Blood Cells are prepared shall be tested as specified in item K relating to Testing Of Whole Blood under the heading “I. BLOOD BANKS/BLOOD COMPONENTS” of this Part. (e) Pilot samples: Pilot samples collected in integral tubing or in separate pilot tubes shall meet the following specifications: ___________________________________________________________ (i) One or more pilot samples of either the original blood or the Packed Red Blood Cells being processed shall be preserved with each unit of Packed Red Blood Cells which is issued. (ii) Before they are filled, all pilot sample tubes shall be marked or identified so as to relate them to the donor of that unit or Packed Red Blood Cells. (iii) Before the final container is filled or at the time the final product is prepared, the pilot samples tubes accompanying a unit of Packed Red Blood Cells, shall be attached in a tamper-proof manner that shall conspicuously identify removal and re-attachment. (iv) All pilot sample tubes, accompanying a unit of packed red blood cells, shall be filled immediately after the blood is collected or at the time the final product is prepared, in each case, by the person who performs the collection of preparation. 1. Subs. by G.S.R. 40(E), dt. 29.1.2001. F. Processing: (i) Separation: Packed Red Blood Cells shall be separated from the whole blood, -- (a) if the whole blood is stored in ACD solution within 21 days, and (b) if the whole blood is stored in CPDA-1 solution, within 35 days, from the date of collection. Packed Red Blood Cells may be prepared either by centrifugation done in a manner that shall not tend to increase the temperature of the blood or by normal undisturbed sedimentation method. A portion of the plasma, sufficient to ensure optimal cell preservation, shall be left with the packed Red Blood Cells. Drugs and Cosmetics Rules, 1945 285 (ii) Packed Red Blood Cells Frozen: Cryophylactic substance may be added to the Packed Red Blood Cells for extended manufacturer’s storage not warmer than minus 65 degree centigrade provided the manufacturer submits data to the satisfaction of the Licensing Authority and Central Licence Approving Authority, as adequately demonstrating through in-vivo cells survival and other appropriate tests that the addition of the substance, the material used and the processing methods results in a final product meets the required standards of safety, purity and potency for Packed Red Blood Cells, and that the frozen product shall maintain those properties for the specified expiry period. (iii) Testing: Packed Red Blood Cells shall conform to the standards as laid down in the Indian Pharmacopoeia. (2) PLATELETS CONCENTRATES: The product shall be known as “Platelets Concentrates” that is platelets collected from one unit of blood and re-suspended in an appropriate volume of original plasma. General Requirements: (i) Source: The source material for platelets shall be platelet rich plasma or buffy coat which may be obtained from the whole blood or by plateletpheresis. (ii) Processing : (a) Separation of buffy-coat or platelet-rich plasma and platelets and re- suspension of the platelets shall be in a closed system by centrifugal method with appropriate speed, force and time. (b) Immediately after collection, the whole blood or plasma shall be held in storage between 20 degree centigrade to 24 degree centigrade. When it is to be transported from the venue of blood collection to the processing laboratory, during such transport action, the temperature as close as possible to a range between 20 degree centigrade to 24 degree centigrade shall be ensured. The platelet concentrates shall be separated within 6 hours after the time of collection of the unit of whole blood or plasma. (c) The time and speed of centrifugation shall be demonstrated to produce an unclamped product, without visible haemolysis, that yields a count of not less than 3.5 x 10 (3.5 x 10 raised to the power of 10) and 4.5 x 10 (4.5 x 10 raised to the power ten) i.e. platelets per unit from a unit of 350 ml and 450 ml blood respectively. One percent of total platelets prepared shall be tested of which 75 per cent of the units shall conform to the above said platelet count. (d) The volume of original plasma used for re-suspension of the platelets shall be determined by the maintenance of the pH of not less than 6 during the storage period. The pH shall be measured on a sample of Drugs and Cosmetics Rules, 1945 286 platelets which has been stored for the permissible maximum expiry period at 20 degree centigrade to 24 degree centigrade. (e) Final containers used for platelets shall be colorless and transparent to permit visual inspection of the contents. The caps selected shall maintain a hermetic seal to prevent contamination of the contents. The container material shall not interact with the contents, under the normal conditions of the storage and use, in such a manner as to have an adverse effect upon the safety, purity, potency, or efficacy of the product. At the time of filling, the final container shall be marked or identified by number so as to relate it to the donor. (iii) Storage: Immediately after re-suspension, platelets shall be placed in storage not exceeding for a period of 5 days, between 20 degree centigrade to 24 degree centigrade, with continuous gentle agitation of the platelet concentrates maintained throughout such storage (iv) Testing: The units prepared from different donors shall be tested at the end of the storage period for – (a) Platelet count; (b) pH of not less than 6 measured at the storage temperature of the unit; (c) measurement of actual plasma volume; (d) one percent of the total platelets prepared shall be tested for sterility; (e) the tests of functional viability of the platelets shall be done by swirling movement before issue. (f) if the results of the testing indicate that the product does not meet the specified requirements, immediate corrective action shall be taken and records maintained; (v) Compatibility Test: Compatible transfusion for the purpose of variable number of Red Blood Cells, A, B, AB and O grouping shall be done if the platelets concentrate is contaminated with red blood cells. (3) GRANULOCYTE CONCENTRATES: (i) Storage: It shall be kept between 20 degree centigrade to 24 degree centigrade for a maximum period of 24 hours; (ii) Unit of granulocytes shall not be less than 1 x 10 (i.e. 1 x 10 raised to the power of 10) when prepared on cell separator; (iii) Group specific tests/HLA test wherever required shall be carried out. (4) FRESH FROZEN PLASMA: Plasma frozen within 6 hours after blood collection and stored at a temperature not warmer than minus 30 degree centigrade, shall be preserved for a period of not more than one year. (5) CRYOPRECIPITATE: Concentrate of anti-hemophiliac factor shall be prepared by thawing of the fresh plasma frozen stored at minus 30 degree centigrade. Drugs and Cosmetics Rules, 1945 287 (a) Storage: Cryoprecipitate shall be preserved at a temperature not higher than minus 30 degree centigrade and may be preserved for a period of not more than one year from the date of collection. (b) Activity: Anti-hemophiliac factor activity in the final product shall be not less than 80 units per bag. One percent of the total cryoprecipitate prepared shall be tested of which seventy five percent of the unit shall conform to the said specification. F PLASMAPHERESIS, PLATELETPHERESIS, LEUCAPHERESIS, USING A CELL SEPARATOR. An area of 10 square meters shall be provided for apheresis in the blood bank. The blood banks specifically permitted to undertake the said apheresis on the donor shall observe the criteria as specified in item H relating to Criteria for blood donation “1 Blood Banks/Blood Components” of this Part. The written consent of the donor shall be taken and the donor must be explained, the hazards of apheresis. The Medical Officer shall certify that the donor is fit for apheresis and it shall be carried out by a trained person under supervision of the Medical Officer. (A) PLASMAPHERESIS, PLATELETPHERESIS AND LEUCAPHERESIS: The donors subjected to plasmapheresis, plateletpheresis and leucapheresis shall, in addition to the criteria specified in item H relating to the CRITERIA FOR BLOOD DONATION, under the heading “I. BLOOD BANKS/BLOOD COMPONENTS” of this Part being observed, be also subjected to protein estimation on post-pheresis/first sitting whose results shall be taken as reference for subsequent/sitting. It shall also be necessary that the total plasma obtained from such donor and periodicity of Plasmapheresis shall be according to the standards described under validt. Standard Operating Procedures. NOTE : (i) At least 48 hours must elapse between successive apheresis and not more than twice in a week. (ii) Extracoporeal blood volume shall not exceed 15% of donor’s estimated blood volume. (iii) Platelet pheresis shall not be carried out on donors who have taken medication containing Asprin within 3 days prior to donation. (iv) If during plateletpheresis or leucapheresis, RBCs cannot be re-transfused then at least 12 weeks shall elapse before a second cytapheresis procedure is conducted. (B) MONITORING FOR APHERESIS: Before starting apheresis procedure, hemoglobin or haematocrit shall be done. Platelet count, WBC counts, differential count may be carried out. In repeated plasmapheresis, the serum protein shall be 6 gm./ml. Drugs and Cosmetics Rules, 1945 288 (C) COLLECTION OF PLASMA: The quantity of plasma separated from the blood of donor shall not exceed 500 ml. per sitting and once in a fortnight or shall not exceed 1000 ml per month. PART XII C I. REQUIREMENTS FOR MANUFACTURE OF BLOOD PRODUCTS The blood products shall be manufactured in a separate premises other than that meant for blood bank. The requirements that are essential for grant or renewal of licence to manufacture blood products such as Albumin, Plasma Protein Fraction, Immunoglobins and Coagulation Factor Concentrates, shall be as follows, namely: - A. GENERAL REQUIREMENTS: 1. Location and surroundings, buildings and water supply: The requirements as regards location and surrounding, buildings and water supply as contained in paragraphs 1.1.1, 1.1.2, 1.1.3 of Part 1 of Schedule M shall apply mutatis mutandis to the manufacture of blood products. 2. Disposal of waste and infectious materials: (i) The requirements as regards disposal of waste and infectious materials as contained in paragraph 1.1.4 of Part 1 of Schedule M shall apply mutatis mutandis to the manufacture of blood products. (ii) Proper facility shall also be provided for potentially infectious materials, particularly HIV I & HIV II 1[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] through autoclaving, incineration or any other suitable validt. methods. 3. Health, clothing and sanitation personnel: (i) The requirement as contained in paragraph 3 of Part of Schedule M shall be complied with. (ii) The personnel working in the manufacturing areas shall be vaccinated against Hepatitis B virus and other infectious transmitting diseases. 4. Requirements for manufacturing area for Blood Products: (i) For the manufacture of blood products, separate enclosed areas specifically designated for the purpose shall be provided. These areas be provided with air locks for entry and shall be essentially dust free and ventilated with an air supply. Air supply for manufacturing area shall be filtered through bacteria retaining filters (HEPA Filters) and shall be at a pressure higher than in the adjacent areas. The filters shall be checked for performance on installation and periodically thereafter, and records thereof shall be maintained. (ii) Interior surfaces (walls, floors and ceilings) shall be smooth and free from cracks, they shall not shed matter and shall permit easy cleaning and disinfection. Drains shall be excluded from aseptic areas. Drugs and Cosmetics Rules, 1945 289 Routine microbial counts of the manufacturing area shall be carried out during manufacturing operations. The results of such counts shall be checked against well documented in-house standards and records maintained. Access to the manufacturing areas shall be restricted to a minimum number of authorized personnel. Special procedures for entering and leaving the manufacturing areas shall be prominently displayed. (iii) Sinks shall be excluded from aseptic areas. Any sink installed in other clean areas shall be of suitable material such as stainless steel, without an overflow, and be supplied with water of potable quality. Adequate precautions shall be taken to avoid contamination of the drainage system with dangerous effluents and airborne dissemination of pathogenic micro-organisms. ________________________________________________________________________ (iv) Lighting, air-conditioning, ventilation shall be designed to maintain a satisfactory temperature and relative humidity to minimize contamination and to take account of the comfort of personnel working with protective clothing. (v) Premises used for the manufacture of blood products shall be suitably designed and constructed to facilitate good sanitation. (vi) Premises shall be carefully maintained and it shall be ensured that repair and maintenance operations do not present any hazard to the quality of products. Premises shall be cleaned and, where applicable, disinfected according to detailed written validt. procedures. (vii) Adequate facilities and equipments shall be used for the manufacture of blood products derived from blood plasma. (viii) All containers of blood products, regardless of the stage of manufacture, shall be identified by securely attached labels. Cross contamination shall be prevented by adoption of the following measures, namely: – 1. Subs. by G.S.R. 40(E), dt. 29.1.2001. (a) processing and filling shall be in segregated areas; (b) manufacture of different products at the same time shall be avoided; (c) simultaneous filling of the different products shall be avoided; (d) ensure transfer, containers/materials by means of airlocks, air extraction, clothing change and careful washing and decontamination of equipment; (e) protecting containers/materials against the risk of contamination caused by re-circulation of untreated air or by accidental re-entry of extracted air; (f) using containers that are sterilized or are of documented low “bioburden”, (ix) Positive pressure area shall be dedicated to the processing area concerned; (x) Air-handling units shall be dedicated to the processing area concerned; (xi) Pipe work, valves and vent filters shall be properly designed to facilitate cleaning and sterilization. Valves on fractionation/reacting vessels shall be completely steam sterilisable. Air vent filters shall be hydrophobic and shall be validated for their designated use. Drugs and Cosmetics Rules, 1945 290 5. Ancillary Areas : (i) Rest and refreshment rooms shall be separated from other areas. (ii) Facilities for changing and storing clothes and for washing and toilet purposes shall be easily accessible and appropriate for the number of users. Toilets shall not be connected directly with production or storage areas. (iii) Maintenance workshops shall be separated from production areas. Wherever parts and tools are stored in the production area, they shall be kept in rooms or lockers reserved for that use. (iv) Animal houses shall be well isolated from other areas with separate entrance. B. COLLECTION AND STORAGE OF PLASMA FOR FRACTIONATION (a) Collection: (1) Plasma shall be collected from the licensed Blood Banks through a cold chain process and stored in frozen condition not warmer than minus twenty degree centigrade. (2) Individual plasma shall remain in quarantine till it is tested for 1[( Hepatitis B and Hepatitis C Virus antibody)], HIV I and HIV II. (3) A sample from pooled – lot plasma of about 10-12 units of different donors shall be tested for 1[(Hepatitis B and Heptitis C Virus antibody)] HIV I and HIV II and if the same sample found negative, only then it shall be taken up for fractionation. (b) Storage Area : (1) Storage areas shall be of sufficient space and capacity to allow orderly storage of the various categories of materials, intermediates, bulk and finished products, products in quarantine, released, rejected, returned, or recalled products. (2) Storage areas shall be designed or adopted to ensure good storage conditioning. In particular, they shall be clean, dry and maintained within temperature required for such storage and where special storage conditions are required (e.g. temperature, humidity), these shall be provided, checked and monitored. (3) Receiving and dispatch bays shall protect materials and products from the weather and shall be designed and equipped to allow containers of incoming materials to be cleaned, if necessary, before storage. (4) Where quarantine status is ensured by storage in separate areas, these areas shall be clearly marked and their access restricted only to authorized personnel. (5) There shall be separate sampling area for raw materials. If sampling is performed in the storage area, it shall be conducted in such a way so as to prevent contamination or cross-contamination. (6) Segregation shall be provided for the storage of rejected, recalled, or returned materials or products. (7) Adequate facility shall be provided for supply of ancillary material, such as ethanol, water, salts and polyethylene glycol. Separate facilities shall be provided for the recovery of organic solvents used in fractionation. Drugs and Cosmetics Rules, 1945 291 C. PERSONNEL : (1) Manufacture : The manufacture of blood products shall be conducted under the active 1. Subs. by G.S.R 40(E), dt. 29.1.2001 (w.e.f. 1.6.2001) direction and personal supervision of competent technical staff, consisting of at least one person who shall be a whole time employee, with one year practical experience in the manufacture of blood products / plasma fractionation and possesses –- (a) Post-graduate degree in Medicine–M.D. (Microbiology/Pathology/ Bacteriology/Immunology/Biochemistry); or (b) Post-graduate degree in Science (Microbiology); or (c) Post-graduate degree ib Pharmacy (Microbiology), from a recognized University or Institution. 2. Testing : The head of the testing unit shall be independent of the manufacturing unit and testing shall be conducted under the active direction and personal supervision of competent technical staff consisting at least one person who shall be a whole time employee. The Head of the testing unit shall have eighteen months practical experience in the testing of drugs, especially the blood products and possesses – (a) Post-graduate degree in Pharmacy or Science–(Chemistry/ Microbiology/ Bio-chemistry); or (b) Post-graduate degree in Medicine–M.D(Microbiology/Pathology/ Biochemistry), from a recognized University or Institution. D. PRODUCTION CONTROL : (1) The production area and the viral inactivation room shall be centrally air- conditioned and fitted with HEPA filters having Grade C (Class 10,000) environment as given in the Table below. (2) The filling and sealing shall be carried out under aseptic conditions in centrally air-conditioned areas fitted with HEPA Filters Grade A or, as the case may be, Grade B (Class 100) environment given in the said Table. TABLE AIR CLASSIFICATION SYSTEM FOR MANUFACTURE OF STERILE PRODUCTS. Maximum number of particles permitted per m Drugs and Cosmetics Rules, 1945 292 Grade Maximum number of particles permitted per m ______________________________ 0.5 – 5 micron Less than 5 micron Maximum number of Viable Micro-organism permitted per m A (Class 100) (Laminar - Airflow workstation) 3500 None Less than 1 B (Class 100) 3500 None Less than 5 C (Class 10,000) 3,50,000 2000 Less than 100 (3) The physical and chemical operations used for the manufacture of plasma fractionation shall maintain high yield of safe and effective protein. (4) The fractionation procedure used shall give a good yield of products meeting the in-house quality requirements as approved by the Licensing Authority and Central Licence Approving Authority reducing the risk of microbiological contamination and protein denaturation to the minimum. (5) The procedure adopted shall not affect the antibody activity and biological half- life or biological characteristics of the products. E. VIRAL INACTIVATION PROCESS : The procedure used by the licensee to inactivate the pathogenic organisms such as enveloped and non-enveloped virus, especially infectivity from HIV I & HIV II, 1[(Hepatitis B surface antigens and Hepatitis C Virus antibody)], the viral inactivation and validation methods adopted by the licensee, shall be submitted for approval to the Licensing Authority and Central Licence Approving Authority. NOTES: (1) No preservative (except stabilizer to prevent – protein denaturation such as glycine, sodium chloride or sodium caprylate) shall be added to Albumin, Plasma Protein Fraction, Intravenous Immunoglobulins or Coagulation Factor Concentrates without the prior approval of Licensing Authority and Central Licence Approving Authority. (2) The licensee shall ensure that the said stabilizers do not have deleterial effect on the final product in the quantity present so as not to cause any untoward or adverse reaction in human beings. F. QUALITY CONTROL: Separate facilities shall be provided for Quality Control such as Hematological, Bio- chemical, Physico-chemical, Microbiological, Pyrogens, Instrumental and Safety testing. The Quality Control Department shall have inter alia the following principal duties, namely :- (1) To prepare detailed instructions for carrying out test and analysis. (2) To approve or reject raw material, components, containers, closures, in-process materials, packaging material, labelling and finished products. (3) To release or reject batch of finished products which are ready for distribution. (4) To evaluate the adequacy of the conditions under which raw materials, semi- Drugs and Cosmetics Rules, 1945 293 finished products and finished products are stored. (5) To evaluate the quality and stability of finished products and when necessary of raw materials and semi-finished products. (6) To review production records to ensure that no errors have occurred or if errors have occurred that they have been fully investigated. (7) To approve or reject all procedures, or specifications impacting on the identity, strength, quality and purity of the product. (8) To establish shelf-life and storage requirements on the basis of stability tests related to storage conditions. ___________________________________________________________________ (9) To establish and when necessary revise, control procedures and specifications. (10) To review complaints, recalls, returned or salvaged products and investigations conducted there under for each product. (11) To review Master Formula Records/Cards periodically. 1. Subs. by G.S.R 40(E), dt. 29.1.2001 (w.e.f. 1.6.2001) G. TESTING OF BLOOD PRODUCTS: The products manufactured shall conform to the standards specified in the Indian Pharmacopoeia and where standards of any product is not specified in the Pharmacopoeia, the standard for such product shall conform to the standard specified in the United States Pharmacopoeia or the British Pharmacopoeia. The final products shall be tested for freedom from HIV I and HIV II antibodies 1[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] H. STORAGE OF FINISHED PRODUCT : (i) The final products shall be stored between two degree centigrade to eight degree centigrade, unless otherwise specified by the Central Licence Approving Authority. (ii) The shelf-life assigned to the products by the licensee shall be submitted for approval to the Licensing Authority and Central Licence Approving Authority. I. LABELLING : The products manufactured shall be labelled as specified in the Indian Pharmacopoeia, the British Pharmacopoeia or the United Stated Pharmacopoeia which shall be in addition to any other requirement stated under Part IX or Part X of these rules. The labels shall indicate the results of test for 1[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] freedom from HIV I and HIV II antibodies. J. RECORDS: The licensee shall maintain records as per Schedule U and also comply with Batch manufacturing records as specified in Paragraph 9 of Part -I of Schedule M and any other requirement as may be directed by Licensing Authority and Central Licence Approving Authority. K. MASTER FORMULA RECORDS: The licensee shall maintain Master Formula Records relating to all manufacturing and quality control procedures for each product, which shall be prepared and endorsed by the Drugs and Cosmetics Rules, 1945 294 Competent Technical Staff, i.e. Head of the manufacturing unit. The Master Formula Records shall contain: – (i) the patent or proprietary name of the product along with the generic name, if any, strength and the dosage form; (ii) a description or identification of the final containers, packaging materials, labels and closures to be used; (iii) the identity, quantity and quality of each raw material to be used irrespective of whether or not it appears in the finished product. The permissible overage that may be included in a formulated batch shall be indicated; (iv) a description of all vessels and equipments and the sizes used in the process; _____________________________________________________________________________________ (v) manufacturing and control instructions along with parameters for critical steps such as mixing, drying, blending, sieving and sterilizing the product; (vi) the theoretical yield to be expected from the formulation at different stages of manufacture and permissible yield limits; (vii) detailed instructions on precautions to be taken in the manufacture and storage of drugs and of semi finished products; and (viii) the requirements in-process quality control tests and analysis to be carried out during each stage of manufacture including the designation of persons or departments responsible for the execution of such tests and analysis. II. REQUIREMENTS FOR MANUFACTURE OF BLOOD PRODUCTS FROM BULK FINISHED PRODUCTS Where the blood products, such as Albumin, Plasma Protein Fraction, Immunoglobulins and Coagulation Factor Concentrates are manufactured through the manufacturing activities of filling and sealing the blood products from bulk powder or solution or both, the requirements as they apply to the manufacture of blood products from whole blood shall apply mutatis mutandis to such manufacture of blood products, unless other requirements have been approved by the Central Licence Approving Authority. 1[PART XIII GENERAL Indian Pharmacopoeia shall be deemed to be a method approved by the Licensing Authority. 2. The Licensing Authority shall publish in the Official Gazette from time to time particulars of any test or method of testing approved by him.] Drugs and Cosmetics Rules, 1945 295 ______________________________________________________________ Drugs and Cosmetics Rules, 1945 295 1. Subs. by G.S.R 40(E), dt. 29.1.2001(w.e.f. 1.6.2001) 1. For the purposes of this Schedule, any test or method of testing described in the 1. Renumbered by Notification No. F-18-1/46, dt. 18-6-48