Comparision of US & Indian GMP's

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In the month of February 2014 US Food and Drug Administration Commissioner Margaret Hamburg visited India to discuss issues of drug quality with her counterparts in the Indian Government. The FDA has imposed a rash of regulatory sanctions on Indian generic makers in the last year, triggering concerns about the quality of the medicines supplied by the $14 billion industry to countries including the United States, the biggest market. India is second only to Canada as a drug exporter to the United States, where it supplies about 40 percent of generic and over-the-counter drugs.There were comments made about the US and Indian GMP Standards. Drug Regulations has now compared the GMP standards of US and India. The comparison is given in the presentation here.

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  • It is excellent presentation to learn..Thanks.
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  • I appreciate the effort for making this type of comparison. However, it is not proper to treat US GMP' s as a benchmark and compare them with Schedule-M. Schedule-M has its own merits in Indian context. I do not agree with you on many of your slides that Schedule-M do not have equivalent provisions with US GMP. Schedule-M has to be read with the corresponding provisions in the Act and Rules. However, there is a need for Harmonization of the GMP's in the interest of all.
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  • Excellent compilation - rather long as a presentation - what could have been done is split it into various categories like Design, Process, Documentation etc.
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Comparision of US & Indian GMP's

  1. 1. This presentation is compiled by ― Drug Regulations‖ a non profit organization which provides free online resource to the Pharmaceutical Professional. Visit http://www.drugregulations.org for latest information from the world of Pharmaceuticals. 3/13/2014 1
  2. 2.  This presentation is compiled from freely available resources like the websites of FDA, EMA, WHO.  ―Drug Regulations‖ is a non profit organization which provides free online resource to the Pharmaceutical Professional.  Visit http://www.drugregulations.org for latest information from the world of Pharmaceuticals. 3/13/2014 2Drug Regulations : Online Resource for Latest Information
  3. 3. 3Drug Regulations : Online Resource for Latest Information
  4. 4. 4  The recent ban on Ranbaxy‘s 4th plant in India & the visit of US FDA commissioner created a debate about US & Indian GMP‘s standards.  This presentation compares & highlights the differences.  The GMP‘s in the Indian Act is specified under Schedule M I Part I for Drug products.  The number referred in the comparison for US GMP‘s are from 21 CFR part 210 and 211 ; those for the Indian GMP‘s are from Schedule M Part I Drug Regulations : Online Resource for Latest Information
  5. 5. 5  PART 210—CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL 1. Product is not classified as Adulterated if GMP‘s are not followed. ( 210.1 c ) 2. No separate license or GMP‘s for biological products (210.2 a ) 3. Investigational drug has not been defined ( 210.2 c ) 4. There are no specific requirements for Investigational drugs. ( 210.2 c ) 5. Experimental drugs are completely exempted from GMP‘s Drug Regulations : Online Resource for Latest Information
  6. 6. 6 6. Following terms are not defined ( 210.3 b ) ◦ Component ◦ Non fiber ◦ Fiber ◦ In process material ◦ Manufacture, processing , Holding Packing ◦ Medical Feed , Medical premix ◦ Quality Control Unit ◦ Strength ◦ Theoretical Yield , Actual Yield ,Percentage Theoretical Yield ◦ Acceptance Criteria ◦ Representative Sample ◦ Gang Printed Labeling Drug Regulations : Online Resource for Latest Information
  7. 7. 7  Subpart A—General Provisions 1. No separate classification for OTC drugs ( 211.1 c) 2. Drugs marketed as OTC drugs follow all requirements of Drugs ( 211. 1 c)  Subpart B—ORGANIZATION AND PERSONNEL 1. Requirement that the authority of QC to review production records other than manufacturing records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated is not specified. ( 211.22 a) 2. Requirement that the responsibility of the quality control unit for approving or rejecting all procedures impacting on the identity, strength, quality, and purity of the drug product not specified. ( 211.22 c). Specified only for specifications and manufacturing records. 3. Requirement of training in GMP‘s is not specified. ( 211.25 a).
  8. 8. 8 4. Use of protective apparel, such as head, face, hand, and arm coverings, shall be worn as necessary to protect drug products from contamination is not specified. ( 211.28 a) 5. Requirement that only personnel authorized by supervisory personnel shall enter those areas of the buildings and facilities designated as limited-access areas is not specified. ( 211.28 c ) 6. Requirement that consultants advising on the manufacture, processing, packing, or holding of drug products shall have sufficient education, training, and experience, or any combination thereof, to advise on the subject for which they are retained; Records shall be maintained stating the name, address, and qualifications of any consultants and the type of service they provide has not been specified ( 211.34) Drug Regulations : Online Resource for Latest Information
  9. 9. 9  Subpart C—BUILDINGS AND FACILITIES 1. Requirement that equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature shall be provided when appropriate for the manufacture, processing, packing, or holding of a drug product is not specified. ( 211.44 b) 2. Requirement that if air is recirculated to production areas, measures shall be taken to control recirculation of dust from production is not specified. ( 211.46 c) 3. Requirement that potable water to be supplied under continuous positive pressure is not specified. ( 211. 48 a) 4. Requirement that written procedures for use of suitable rodenticides, insecticides, fungicides, fumigating agents is not specified. Specified for cleaning & sanitizing agents and for warehouse only. ( 211. 56 c). Drug Regulations : Online Resource for Latest Information
  10. 10. 10  Subpart C—BUILDINGS AND FACILITIES  Requirement that such written procedures (see 4 above) shall be designed to prevent the contamination of equipment, components, drug product containers, closures, packaging, labeling materials, or drug products and shall be followed is not specified . (211. 56 c )  Requirement that rodenticides, insecticides, and fungicides shall not be used unless registered and used in accordance with the Federal Insecticide, Fungicide, and Rodenticide Act (corresponding Indian Act) is not specified. ( 211.56 c) 5. Requirement that sanitation procedures shall apply to work performed by contractors or temporary employees as well as work performed by full- time employees during the ordinary course of operations is not specified. ( 211.56 d) Drug Regulations : Online Resource for Latest Information
  11. 11. 11  Subpart D—Equipment 1. Requirement that equipment and utensils shall be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements is not specified. ( 211.67 (a) )  Mentioned in a confused way at different place under Blood bank , Equipment, Batch Packing & Processing Records and under different dosage forms. Drug Regulations : Online Resource for Latest Information
  12. 12. 12  Subpart D—Equipment 2. Requirement that written procedures shall be established and followed for cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing, or holding of a drug product is specified in a very confusing way under Part I General requirements and under Part 1 F for API‘s . ( 211.67 (b) ) 3. Requirement that records shall be kept of maintenance, cleaning, sanitizing, and inspection as specified in §§211.180 and 211.182 is not clearly specified. ( 211.67 (c) ) 4. Requirement that automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product is not specified for automatic & Electronic equipment. ( 211.68 (a) ). Drug Regulations : Online Resource for Latest Information
  13. 13. 13  Subpart D—Equipment  Requirement that if such equipment is so used, it shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance is not specified for automatic & electronic equipment.. ( 211.68 (a) ).  Requirement that written records of those calibration checks and inspections shall be maintained is not specified for automatic & electronic equipment. ( 211.68 (a) ) Drug Regulations : Online Resource for Latest Information
  14. 14. 14  Subpart D—Equipment 5. Requirement that input to and output from the computer or related system of formulas or other records or data shall be checked for accuracy is not specified. ( 211.68 (b) )  Requirement that the degree and frequency of input/output verification shall be based on the complexity and reliability of the computer or related system is not specified. ( 211.68 (b) ) Drug Regulations : Online Resource for Latest Information
  15. 15. 15  Subpart D—Equipment  Requirement that a backup file of data entered into the computer or related system shall be maintained except where certain data, such as calculations performed in connection with laboratory analysis, are eliminated by computerization or other automated processes is not specified except for batch records. (211.68 (b) )  Requirement that in such instances a written record of the program shall be maintained along with appropriate validation data is not specified. (211.68 (b) )  Requirement that hard copy or alternative systems, such as duplicates, tapes, or microfilm, designed to assure that backup data are exact and complete and that it is secure from alteration, inadvertent erasures, or loss shall be maintained is not specified. (211.68 (b) ) Drug Regulations : Online Resource for Latest Information
  16. 16. 16  Subpart D—Equipment 6. Requirement that fiber-releasing filters may be used when it is not possible to manufacture such products without the use of these filters is not specified. ( 211.72)  Requirement that if use of a fiber-releasing filter is necessary, an additional nonfiber-releasing filter having a maximum nominal pore size rating of 0.2 micron (0.45 micron if the manufacturing conditions so dictate) shall subsequently be used to reduce the content of particles in the injectable drug product is not specified. ( 211.72)  Prohibition of asbestos containing filter is not specified. ( 211.72) Drug Regulations : Online Resource for Latest Information
  17. 17. 17  Subpart E—Control of Components and Drug Product Containers and Closures 1. Handling of components and drug product containers and closures to prevent cross contamination is not specified. ( 211.80 (b) ) 2. Coding of grouping of containers is not permitted. ( 211.80 (d) ) Drug Regulations : Online Resource for Latest Information
  18. 18. 18  Subpart E—Control of Components and Drug Product Containers and Closures 3. Requirement of checking appropriate labeling as to contents and contaminations as well checking of grouping of containers is not specified. Checking is specified for the integrity of the package and seal only and that too for individual containers only. (211.82 ( a) 4. The finished product shelf life can not exceed the shelf life of the starting or input materials ( Both Active & Inactive) is specified. ( 211.84 (a) ) Drug Regulations : Online Resource for Latest Information
  19. 19. 19  Subpart E—Control of Components and Drug Product Containers and Closures 6. Requirement that the number of containers to be sampled, and the amount of material to be taken from each container, shall be based upon appropriate criteria such as statistical criteria for component variability, confidence levels, and degree of precision desired, the past quality history of the supplier, and the quantity needed for analysis and reserve where required is not specified. ( 211.84 ( b) ). 7. Requirement that samples shall be collected in accordance with the following procedures is not specified: ( 211.84 ( c) ) ◦ (1) The containers of components selected shall be cleaned when necessary in a manner to prevent introduction of contaminants into the component is not specified. Drug Regulations : Online Resource for Latest Information
  20. 20. 20  Subpart E—Control of Components and Drug Product Containers and Closures 7. (c) Samples shall be collected in accordance with the following procedures is not specified: ( 211.84 ( c) ) ◦ (2) The containers shall be opened, sampled, and resealed in a manner designed to prevent contamination of their contents and contamination of other components, drug product containers, or closures is not specifed. ◦ (3) If it is necessary to sample a component from the top, middle, and bottom of its container, such sample subdivisions shall not be composited for testing is not specified. Drug Regulations : Online Resource for Latest Information
  21. 21. 21  Subpart E—Control of Components and Drug Product Containers and Closures 7. (c) Samples shall be collected in accordance with the following procedures is not specified: ◦ (4) Sample containers shall be identified so that the following information can be determined: name of the material sampled, the lot number, the container from which the sample was taken, the date on which the sample was taken, and the name of the person who collected the sample is not specified. Drug Regulations : Online Resource for Latest Information
  22. 22. 22  Subpart E—Control of Components and Drug Product Containers and Closures 8. In lieu of testing of components by the manufacturer, a report of analysis may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer, and provided that the manufacturer establishes the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals is not specified. ( 211.84 (d) (2)) 9. In lieu of such testing by the manufacturer, a certificate of testing may be accepted from the supplier, provided that at least a visual identification is conducted on such containers/closures by the manufacturer and provided that the manufacturer establishes the reliability of the supplier's test results through appropriate validation of the supplier's test results at appropriate intervals is not specified. ( 211.84 (d) (3))
  23. 23. 23  Subpart E—Control of Components and Drug Product Containers and Closures 10. When appropriate, components shall be microscopically examined is not specified ( 211.84 (d) (4)) 11. Each lot of a component, drug product container, or closure that is liable to contamination with filth, insect infestation, or other extraneous adulterant shall be examined against established specifications for such contamination is not specified. ( 211.84 (d) (5))
  24. 24. 24  Subpart E—Control of Components and Drug Product Containers and Closures 12. Retesting or re examination of components, drug product containers, and closures as appropriate, for identity, strength, quality, and purity and approved or rejected by the quality control unit in accordance with §211.84 as necessary, e.g., after storage for long periods or after exposure to air, heat or other conditions that might adversely affect the component, drug product container, or closure is not specified.(211.87)
  25. 25. 25  Subpart E—Control of Components and Drug Product Containers and Closures 13. Rejected components, drug product containers, and closures shall be identified and controlled under a quarantine system designed to prevent their use in manufacturing or processing operations for which they are unsuitable is not specified though a separate rejected area has been specified. (211.89) 14. Drug product containers and closures shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug beyond the official or established requirements is specified only for Sterile products & API‘s and for no other products. ( 211.94 ( a) )
  26. 26. 26  Subpart E—Control of Components and Drug Product Containers and Closures 15. Requirement that container closure systems shall provide adequate protection against foreseeable external factors in storage and use that can cause deterioration or contamination of the drug product is not specified.( 211.94 (b) )
  27. 27. 27  Subpart F—Production and Process Controls 1. Requirement that there shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess is not specified. ( 211.100 (a) )  Requirement that these written procedures, including any changes, shall be drafted, reviewed, and approved by the appropriate organizational units and reviewed and approved by the quality control unit is not specified.
  28. 28. 28  Subpart F—Production and Process Controls 2. Requirement that written production and process control procedures shall be followed in the execution of the various production and process control functions and shall be documented at the time of performance and any deviation from the written procedures shall be recorded and justified is not specified. ( 211.100 (b) ). 3. Requirement that the batch shall be formulated with the intent to provide not less than 100 percent of the labelled or established amount of active ingredient is not specified.( 211.101 (a) )
  29. 29. 29  Subpart F—Production and Process Controls 4. Requirement that the components for drug product manufacturing shall be weighed, measured, or subdivided as appropriate and that if a component is removed from the original container to another, the new container shall be identified with the following information is not specified: ( 211.101 (b) ) (1) Component name or item code; (2) Receiving or control number; (3) Weight or measure in new container; (4) Batch for which component was dispensed, including its product name, strength, and lot number.
  30. 30. 30  Subpart F—Production and Process Controls 5. Requirement that weighing, measuring, or subdividing operations for components shall be adequately supervised and that each container of component dispensed to manufacturing shall be examined by a second person to assure following is not specified for followig . (211.101 (c ) ):  (1) The component was released by the quality control unit;  (2) The weight or measure is correct as stated in the batch production records;  (3) The containers are properly identified. If the weighing, measuring, or subdividing operations are performed by automated equipment under §211.68, only one person is needed to assure paragraphs (c)(1), (c)(2), and (c)(3) of this section.
  31. 31. 31  Subpart F—Production and Process Controls 6. Requirement that such calculations shall either be performed by one person and independently verified by a second person, or, if the yield is calculated by automated equipment under §211.68, be independently verified by one person is not specified (211.103) 7. Requirement of proper identification of processing lines is not specified. ( 211.105 (a)). 8. Requirement of major equipment to be identified by a distinctive identification number or code that shall be recorded in the batch production record to show the specific equipment used in the manufacture of each batch of a drug product; and in cases where only one of a particular type of equipment exists in a manufacturing facility, the name of the equipment may be used in lieu of a distinctive identification number or code is not specified. ( 211.105 (b) )
  32. 32. 32  Subpart F—Production and Process Controls 9. Requirement of demonstrating adequacy of mixing to assure uniformity and homogeneity is not specified unambiguously but mentioned indirectly under requirement of batch records. ( 211.110 (a) (3) ) 10. Requirement of bioburden testing as an in-process test is not specified. ( 211.110 (a) (5) )
  33. 33. 33  Subpart F—Production and Process Controls 11. Requirement of valid in-process specifications for such characteristics to be consistent with drug product final specifications and shall be derived from previous acceptable process average and process variability estimates where possible and determined by the application of suitable statistical procedures where appropriate is not specified. ( 211.110 (b)) 12. Requirement of rejected in-process materials to be identified and controlled under a quarantine system designed to prevent their use in manufacturing or processing operations for which they are unsuitable is not specified except for tablets.
  34. 34. 34  Subpart F—Production and Process Controls 13. Requirement of time limits, when appropriate , for the completion of each phase of production shall be established to assure the quality of the drug products is not specified except for sterile & Liquid orals. ( 211.111)  Requirement of justifying & documenting deviations from established time limits may be acceptable if such deviation does not compromise the quality of the drug product is not specified.
  35. 35. 35  Subpart F—Production and Process Controls 14. Requirement to establish & follow appropriate written procedures, designed to prevent objectionable microorganisms in drug products not required to be sterile is not specified. ( 211.113 (a) )
  36. 36. 36  Subpart G—Packaging and Labeling Control 1. Requirement of destroying obsolete and outdated labels, labeling, and other packaging materials is not specified. ( 211.122 ( e ).
  37. 37. 37  Subpart G—Packaging and Labeling Control 2. Prohibition of gang-printed labeling for different drug products, or different strengths or net contents of the same drug product unless the labeling from gang-printed sheets is adequately differentiated by size, shape, or color is not specified. ( 211.122 (f) ). 3. Requirement of special control procedures for packaging and labeling operations if cut labeling is used for immediate container labels, individual unit cartons, or multiunit cartons containing immediate containers that are not packaged in individual unit cartons is not specified. ( 211.122 (g) ) ◦ (1) Requirement of dedication of labeling and packaging lines to each different strength of each different drug product is not specified;
  38. 38. 38  Subpart G—Packaging and Labeling Control ◦ (2) Use of appropriate electronic or electromechanical equipment to conduct a 100-percent examination for correct labeling during or after completion of finishing operations is not specified; or ◦ (3) Use of visual inspection to conduct a 100-percent examination for correct labeling during or after completion of finishing operations for hand-applied labeling and that such examination shall be performed by one person and independently verified by a second person is not specified. ◦ (4) Use of any automated technique, including differentiation by labeling size and shape, that physically prevents incorrect labeling from being processed by labeling and packaging equipment is not specified.
  39. 39. 39  Subpart G—Packaging and Labeling Control 4. Printing devices on, or associated with, manufacturing lines used to imprint labeling upon the drug product unit label or case shall be monitored to assure that all imprinting conforms to the print specified in the batch production record is not specified. ( 211.122 (h)) 5. Requirement of strict control to be exercised over labeling issued for use in drug product labeling operations is not specified. ( 211.125 (a) )
  40. 40. 40  Subpart G—Packaging and Labeling Control 6. Careful examination of labeling materials issued for a batch for identity and conformity to the labeling specified in the master or batch production records is not specified. ( 211.125 (b) ) 7. Waving of labeling reconciliation for cut or roll labeling if a 100-percent examination for correct labeling is performed is not specified. ( 211.125 ( c ) )
  41. 41. 41  Subpart G—Packaging and Labeling Control 8. Requirement of destroying all excess labeling bearing lot or control numbers is not specified. ( 211.125 (d)). 9. Requirement of written procedures describing in sufficient detail the control procedures employed for the issuance of labeling and the requirement to follow such written procedures is not specified. ( 211.125 ( f ) ).
  42. 42. 42  Subpart G—Packaging and Labeling Control 10. Requirement of written procedures with features given below designed to assure that correct labels, labeling, and packaging materials are used for drug products and that such written procedures shall be followed is not specified. ( 211.130) • Requirement to Prevent mixups and cross-contamination by physical or spatial separation from operations on other drug products is not specified . ( 211.130 (a) )
  43. 43. 43  Subpart G—Packaging and Labeling Control • Requirement of identification and handling of filled drug product containers that are set aside and held in unlabeled condition for future labeling operations to preclude mislabelling of individual containers, lots, or portions of lots is not specified. ( 211.130 (b) ). 11. The Indian Act , Rules or the GMP‘s do not have separate classification for OTC drugs. ( 211.132 (a)) 12. Requirement of an OTC drug product (except a dermatological, dentifrice, insulin, or lozenge product) for retail sale that is not packaged in a tamper-resistant package or that is not properly labelled under this section is adulterated is not specified. ( 211.132 (a) )
  44. 44. 44  Subpart G—Packaging and Labeling Control 13. Features of Tamper Evident packing are not specified. ( 211.132 (b) ) 14. Special labeling to make consumers aware of tamper evident packing is not specified. ( 211.132 (c ) ). 15. Requirements of exemption from tamper evident packing and labeling have not been specified. ( 211.132 ( d ) )
  45. 45. 45  Subpart G—Packaging and Labeling Control 16. Requirement of examining packaged and labelled products during finishing operations to provide assurance that containers and packages in the lot have the correct labels is not specified . ( 211.134 (a) ) 17. Requirement of visually examining a representative sample of units at the completion of finishing operations for correct labeling is not specified. (211.134 (b) ) 18. Requirement of documenting results of these examinations in the batch production or control records is not specified. ( 211.134 (c ) )
  46. 46. 46  Subpart G—Packaging and Labeling Control 19.Requirement that if the drug product is to be reconstituted at the time of dispensing, its labeling shall bear expiration information for both the reconstituted and unreconstituted drug products is not specified. ( 211.137 (c ) ).
  47. 47. 47  Subpart G—Packaging and Labeling Control 20. Requirement that New drug products for investigational use are exempt from the requirements of Packaging & Labeling Controls , provided that they meet appropriate standards or specifications as demonstrated by stability studies during their use in clinical investigations is not specified. ( 211.137 (g) )  Requirement that where new drug products for investigational use are to be reconstituted at the time of dispensing, their labeling shall bear expiration information for the reconstituted drug product is not specified.
  48. 48. 48  Subpart H—Holding and Distribution 1. Requirement of storage of drug products under appropriate conditions of temperature, humidity, and light so that the identity, strength, quality, and purity of the drug products are not affected is not specified clearly & directly. ( 211.142 (b) )
  49. 49. 49  Subpart I—Laboratory Controls 1. Requirement of investigating any deviation from the written specification , standards, sampling plans, test procedures, or other laboratory control mechanism is not specified ( 211.160 (a) ). 2. Requirement of determination of conformance to written specifications and a description of sampling and testing procedures for in-process materials and that such samples shall be representative and properly identified is not specified. ( 211.160 (b) (2) )
  50. 50. 50  Subpart I—Laboratory Controls 3. Requirement of determination of conformance to written descriptions of sampling procedures and appropriate specifications for drug products and that such samples shall be representative and properly identified is not specified. (211.160 (b) ( 3)) 4. Requirement of having provisions for remedial action in the event accuracy and/or precision limits are not met during calibration and the requirement of not using instruments, apparatus, gauges, and recording devices not meeting established specifications is not specified. (211.160 (b) (4) )
  51. 51. 51  Subpart I—Laboratory Controls 5. Where sterility and/or pyrogen testing are conducted on specific batches of shortlived radiopharmaceuticals, such batches may be released prior to completion of sterility and/or pyrogen testing, provided such testing is completed as soon as possible is not specified. ( 211.165 (a) ) 6. Requirement of acceptance criteria for the sampling and testing conducted by the quality control unit to be adequate to assure that batches of drug products meet each appropriate specification and appropriate statistical quality control criteria as a condition for their approval and release is not specified.( 211.165 (d) )
  52. 52. 52  Subpart I—Laboratory Controls 7. Requirement of establishing and documenting the accuracy, sensitivity, specificity, and reproducibility of test methods employed by the firm is not specified. ( 211.165 ( e ) ). 8. Requirement of Sample size and test intervals based on statistical criteria for each attribute examined to assure valid estimates of stability is not specified. ( 211.166 (a) (1) )
  53. 53. 53  Subpart I—Laboratory Controls 9. Requirement of a written testing program designed to assess the stability characteristics of drug products is specified only for New Drugs under Schedule Y to the Act. Similarly the requirement that results of such stability testing shall be used in determining appropriate storage conditions and expiration dates and that the written program shall be followed and shall include requirements given below is specified for New Drugs Only.: ( 211.166 (a) (1) to (5) )
  54. 54. 54  Subpart I—Laboratory Controls • Sample size and test intervals based on statistical criteria for each attribute examined to assure valid estimates of stability is not specified at all. ( 211.166 (a) (1) ) • Storage conditions for samples retained for testing is specified for New products only; ( 211.166 (a) (2) ) • Reliable, meaningful, and specific test methods is specified for new products only. ( 211.166 (a) (3) ) • Testing of the drug product in the same container-closure system as that in which the drug product is marketed is specified for new products only; ( 211.166 (a) (4) ) • Testing of drug products for reconstitution at the time of dispensing (as directed in the labeling) as well as after they are reconstituted is specified for new products only. ( 211.166 (a) (5))
  55. 55. 55  Subpart I—Laboratory Controls 10. Requirement of adequate number of batches of each drug product shall be tested to determine an appropriate expiration date and a record of such data shall be maintained is not specified.( 211.166 (b) ) ◦ Requirement of accelerated studies, combined with basic stability information on the components, drug products, and container-closure system, may be used to support tentative expiration dates provided full shelf life studies are not available and are being conducted is not specified. ( 211.166 (b) )
  56. 56. 56  Subpart I—Laboratory Controls ◦ Requirement that where data from accelerated studies are used to project a tentative expiration date that is beyond a date supported by actual shelf life studies, there must be stability studies conducted, including drug product testing at appropriate intervals, until the tentative expiration date is verified or the appropriate expiration date determined is not specified ( 211.166 (b) )
  57. 57. 57  Subpart I—Laboratory Controls 11. Requirement that for each batch of controlled-release dosage form, there shall be appropriate laboratory testing to determine conformance to the specifications for the rate of release of each active ingredient and that the test procedures shall be in writing and shall be followed is not specified. ( 211.167 ( C ) ) 12. Requirement that for an active ingredient in a radioactive drug product, except for nonradioactive reagent kits, the reserve sample shall be retained for: ◦ (i) Three months after the expiration date of the last lot of the drug product containing the active ingredient if the expiration dating period of the drug product is 30 days or less; or ◦ (ii) Six months after the expiration date of the last lot of the drug product containing the active ingredient if the expiration dating period of the drug product is more than 30 days is not specified ( 211.170 ( a) (2) )
  58. 58. 58  Subpart I—Laboratory Controls 13. Requirement of storing the reserve sample under conditions consistent with product labeling is not specified. ( 211.170 (b) ) 14. Except for those for drug products described in paragraph (b)(2) of this section, reserve samples from representative sample lots or batches selected by acceptable statistical procedures shall be examined visually at least once a year for evidence of deterioration unless visual examination would affect the integrity of the reserve sample is not specified. (211.170 (b) )
  59. 59. 59  Subpart I—Laboratory Controls 15. Requirement of performing investigations on evidence of reserve sample deterioration is not specified. ( 211.170 (b) ) 16. Requirement that if a reasonable possibility exists that a non-penicillin drug product has been exposed to cross-contamination with penicillin, the non-penicillin drug product shall be tested for the presence of penicillin is not specified. ( 211.176 ) ◦ Further such drug product shall not be marketed if detectable levels are found when tested according to procedures specified in ‗Procedures for Detecting and Measuring Penicillin Contamination in Drugs,‘ which is incorporated by reference is not specified..
  60. 60. 60  Subpart J—Records and Reports 1. Requirement that all records required under this part, or copies of such records, shall be readily available for authorized inspection during the retention period at the establishment where the activities described in such records occurred is not specified. ( 211.180 (c ) )  Requirement that these records or copies thereof shall be subject to photocopying or other means of reproduction as part of such inspection is not specified  Requirement that records that can be immediately retrieved from another location by computer or other electronic means shall be considered as meeting the requirements of this paragraph is not specified.
  61. 61. 61  Subpart J—Records and Reports 2. Requirement that records required under this part may be retained either as original records or as true copies such as photocopies, microfilm, microfiche, or other accurate reproductions of the original records is not specified. ( 211.180 (d) ).  Where reduction techniques, such as microfilming, are used, suitable reader and photocopying equipment shall be readily available is not specified. ( 211.180 (d) ).
  62. 62. 62  Subpart J—Records and Reports 3. Requirement that written records required by this part shall be maintained so that data therein can be used for evaluating, at least annually, the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures is not specified. ( 211.180 (e) )  Requirement of establishing written procedures which shall be followed for such evaluations and shall include following provisions is not specified.
  63. 63. 63  Subpart J—Records and Reports  Requirement that a review of a representative number of batches, whether approved or rejected, and, where applicable, records associated with the batch is not specified. ( 211.180 (e) (1 ) )  Requirement that a review of complaints, recalls, returned or salvaged drug products, and investigations conducted under §211.192 for each drug product is not specified. ( 211.180 (e) (1 ) )
  64. 64. 64  Subpart J—Records and Reports 4. Requirement that procedures shall be established to assure that the responsible officials of the firm, if they are not personally involved in or immediately aware of such actions, are notified in writing of any investigations conducted under §§211.198, 211.204, or 211.208 of these regulations, any recalls, reports of inspectional observations issued by the Food and Drug Administration, or any regulatory actions relating to good manufacturing practices brought by the Food and Drug Administration is not specified. (211.180 ( f ) )
  65. 65. 65  Subpart J—Records and Reports 5. Requirement that a written record of major equipment cleaning, maintenance (except routine maintenance such as lubrication and adjustments), and use shall be included in individual equipment logs that show the date, time, product, and lot number of each batch processed is not specified . ( 211.182)  Requirement that if equipment is dedicated to manufacture of one product, then individual equipment logs are not required, provided that lots or batches of such product follow in numerical order and are manufactured in numerical sequence. In cases where dedicated equipment is employed, the records of cleaning, maintenance, and use shall be part of the batch record is not specified.
  66. 66. 66  Subpart J—Records and Reports  Requirement that the persons performing and double-checking the cleaning and maintenance (or, if the cleaning and maintenance is performed using automated equipment under §211.68, just the person verifying the cleaning and maintenance done by the automated equipment) shall date and sign or initial the log indicating that the work was performed and entries in the log shall be in chronological order is not specified.
  67. 67. 67  Subpart J—Records and Reports 6. Requirement of permitting reasonable variations, however, in the amount of components necessary for the preparation in the dosage form, provided they are justified in the master production and control records is not specified ;( 211.186 (b) (4) ) 7. Requirement of a statement of theoretical yield, including the maximum and minimum percentages of theoretical yield beyond which investigation is required is not specified; ( 211.186 (b)
  68. 68. 68  Subpart J—Records and Reports 8. Requirement that if a significant step in the operation is performed by automated equipment under §211.68, the identification of the person checking the significant step performed by the automated equipment be recorded is not specified. ( 211.188 (b) (11) 9. Requirement of any investigation made be recorded is not specified. ( 211.188 (b) (12)
  69. 69. 69  Subpart J—Records and Reports 10. Requirement of thoroughly investigating any unexplained discrepancy (including a percentage of theoretical yield exceeding the maximum or minimum percentages established in master production and control records) or the failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed is not specified. ( 211.192)  Requirement that the investigation shall extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy and the requirement of making a written record of the investigation with the conclusions and follow-up is not specified. ( 211.192)
  70. 70. 70  Subpart J—Records and Reports 11. Requirement that the records shall indicate the location of data that establish that the methods used in the testing of the sample meet proper standards of accuracy and reliability as applied to the product tested is not specified. ( 211.194) 12. Requirement to keep complete records of any modification of an established method employed in testing; and the requirement that such records shall include the reason for the modification and data to verify that the modification produced results that are at least as accurate and reliable for the material being tested as the established method is not specified. ( 211.194 (b ) )
  71. 71. 71  Subpart J—Records and Reports 13. Requirement of maintaining complete records of any testing and standardization of laboratory reference standards, reagents, and standard solutions is not specified. (211.194 (c ) ) 14. Requirement of Complaint handling procedures to include provisions for review by the quality control unit, of any complaint involving the possible failure of a drug product to meet any of its specifications and, for such drug products, a determination as to the need for an investigation is not specified ( 211.198 (a) )  Requirement that such procedures include provisions for review to determine whether the complaint represents a serious and unexpected adverse drug experience which is required to be reported to the Food and Drug Administration is not specified.
  72. 72. 72  Subpart J—Records and Reports 15. Following requirement of complaint file is not specified. ( 211.198 (b)) ◦ A written record of each complaint shall be maintained in a file designated for drug product complaints. The file regarding such drug product complaints shall be maintained at the establishment where the drug product involved was manufactured, processed, or packed, or such file may be maintained at another facility if the written records in such files are readily available for inspection at that other facility.
  73. 73. 73  Subpart J—Records and Reports 15. Following requirement of complaint file is not specified. ( 211.198 (b)) ◦ Written records involving a drug product shall be maintained until at least 1 year after the expiration date of the drug product, or 1 year after the date that the complaint was received, whichever is longer. In the case of certain OTC drug products lacking expiration dating because they meet the criteria for exemption under §211.137, such written records shall be maintained for 3 years after distribution of the drug product.
  74. 74. 74  Subpart J—Records and Reports 15. Following requirement of complaint file is not specified. ( 211.198 (b)) ◦ ((1) The written record shall include the following information, where known: the name and strength of the drug product, lot number, name of complainant, nature of complaint, and reply to complainant. ◦ (2) Where an investigation under §211.192 is conducted, the written record shall include the findings of the investigation and followup. The record or copy of the record of the investigation shall be maintained at the establishment where the investigation occurred in accordance with §211.180(c). ◦ (3) Where an investigation under §211.192 is not conducted, the written record shall include the reason that an investigation was found not to be necessary and the name of the responsible person making such a determination.
  75. 75. 75  Subpart K—Returned and Salvaged Drug Products 15. Following requirements of returned products is not specified. ( 211.204 ) ◦ Returned drug products shall be identified as such and held. If the conditions under which returned drug products have been held, stored, or shipped before or during their return, or if the condition of the drug product, its container, carton, or labeling, as a result of storage or shipping, casts doubt on the safety, identity, strength, quality or purity of the drug product, the returned drug product shall be destroyed unless examination, testing, or other investigations prove the drug product meets appropriate standards of safety, identity, strength, quality, or purity.
  76. 76. 76  Subpart K—Returned and Salvaged Drug Products 15. Following requirements of returned products is not specified. ( 211.204 ) ◦ A drug product may be reprocessed provided the subsequent drug product meets appropriate standards, specifications, and characteristics. Records of returned drug products shall be maintained and shall include the name and label potency of the drug product dosage form, lot number (or control number or batch number), reason for the return, quantity returned, date of disposition, and ultimate disposition of the returned drug product. If the reason for a drug product being returned implicates associated batches, an appropriate investigation shall be conducted in accordance with the requirements of §211.192. Procedures for the holding, testing, and reprocessing of returned drug products shall be in writing and shall be followed.
  77. 77. 77  Subpart K—Returned and Salvaged Drug Products 15. Following requirements of returned products is not specified. ( 211.204 ) ◦ Drug products that have been subjected to improper storage conditions including extremes in temperature, humidity, smoke, fumes, pressure, age, or radiation due to natural disasters, fires, accidents, or equipment failures shall not be salvaged and returned to the marketplace. Whenever there is a question whether drug products have been subjected to such conditions, salvaging operations may be conducted only if there is (a) evidence from laboratory tests and assays (including animal feeding studies where applicable) that the drug products meet all applicable standards of identity, strength, quality, and purity and(b) evidence from inspection of the premises that the drug products and their associated packaging were not subjected to improper storage conditions as a result of the disaster or accident. Organoleptic examinations shall be acceptable only as supplemental evidence that the drug products meet appropriate standards of identity, strength, quality, and purity. Records including name, lot number, and disposition shall be maintained for drug products subject to this section.
  78. 78. 78
  79. 79. 79 FDA GMP‘s Indian GMP‘s • §210.1 Status of current good manufacturing practice regulations. • (a) The regulations set forth in this part and in parts 211, 225, and 226 of this chapter contain the minimum current good manufacturing practice for methods to be used in, and the facilities or controls to be used for, the manufacture, processing, packing, or holding of a drug to assure that such drug meets the requirements of the act as to safety, and has the identity and strength and meets the quality and purity characteristics that it purports or is represented to possess. • Schedule M does not specify the requirement of following GMP‘s . However this is specified in the ― The Drugs & Cosmetics Rules‖ under the requirement of ― Conditions of Licence as ―The factory premises shall comply with the conditions prescribed in Schedule M.‖ Drug Regulations : Online Resource for Latest Information
  80. 80. 80 FDA GMP‘s Indian GMP‘s • §210.1 Status of current good manufacturing practice regulations. • (b) The failure to comply with any regulation set forth in this part and in parts 211, 225, and 226 of this chapter in the manufacture, processing, packing, or holding of a drug shall render such drug to be adulterated under section 501(a)(2)(B) of the act and such drug, as well as the person who is responsible for the failure to comply, shall be subject to regulatory action. • Not following GMP;s does not render the product to be classified as ― Adulterated‖. • However rule 85 specifies that if conditions of licence are not followed the manufacturing license can be cancelled. Drug Regulations : Online Resource for Latest Information
  81. 81. 81 FDA GMP‘s Indian GMP‘s • §210.1 Status of current good manufacturing practice regulations. • (c) Owners and operators of establishments engaged in the recovery, donor screening, testing (including donor testing), processing, storage, labeling, packaging, or distribution of human cells, tissues, and cellular and tissue-based products (HCT/Ps), as defined in §1271.3(d) of this chapter, that are drugs (subject to review under an application submitted under section 505 of the act or under a biological product license application under section 351 of the Public Health Service Act), are subject to the donor- eligibility and applicable current good tissue practice procedures set forth in part 1271 subparts C and D of this chapter, in addition to the regulations in this part and in parts 211, 225, and 226 of this chapter • Biological products do not have a separate licence. • Nothing is specified for human cells, tissues, and cellular and tissue-based products in schedule M. • Schedule F specifies requirements for Blood banks and blood components; requirements for manufacture of blood products, requirements for umbilical cord blood and derived stem cells. • Schedule F 1 specifies requirements for vaccines. Drug Regulations : Online Resource for Latest Information
  82. 82. 82 FDA GMP‘s Indian GMP‘s • §210.1 Status of current good manufacturing practice regulations. • (c) Failure to comply with any applicable regulation set forth in this part, in parts 211, 225, and 226 of this chapter, in part 1271 subpart C of this chapter, or in part 1271 subpart D of this chapter with respect to the manufacture, processing, packing or holding of a drug, renders an HCT/P adulterated under section 501(a)(2)(B) of the act. Such HCT/P, as well as the person who is responsible for the failure to comply, is subject to regulatory action. • [43 FR 45076, Sept. 29, 1978, as amended at 69 FR 29828, May 25, 2004; 74 FR 65431, Dec. 10, 2009] • Not following GMP;s does not render the product to be classified as ― Adulterated‖. • However the rule 85 specifies that if conditions of licence are not followed the manufacturing license can be cancelled. Drug Regulations : Online Resource for Latest Information
  83. 83. 83 FDA GMP‘s Indian GMP‘s • §210.2 Applicability of current good manufacturing practice regulations. • (a) The regulations in this part and in parts 211, 225, and 226 of this chapter as they may pertain to a drug; in parts 600 through 680 of this chapter as they may pertain to a biological product for human use; and in part 1271 of this chapter as they are applicable to a human cell, tissue, or cellular or tissue-based product (HCT/P) that is a drug (subject to review under an application submitted under section 505 of the act or under a biological product license application under section 351 of the Public Health Service Act); shall be considered to supplement, not supersede, each other, unless the regulations explicitly provide otherwise. In the event of a conflict between applicable regulations in this part and in other parts of this chapter, the regulation specifically applicable to the drug product in question shall supersede the more general. • Applicability of GMP requirements is specified in rules for conditions of grant of a manufacturing licence. • Biological products do not have a separate licence nor separate GMP requirements. Drug Regulations : Online Resource for Latest Information
  84. 84. 84 FDA GMP‘s Indian GMP‘s • §210.2 Applicability of current good manufacturing practice regulations. • (b) If a person engages in only some operations subject to the regulations in this part, in parts 211, 225, and 226 of this chapter, in parts 600 through 680 of this chapter, and in part 1271 of this chapter, and not in others, that person need only comply with those regulations applicable to the operations in which he or she is engaged. • Biological products do not have a separate licence nor separate GMP requirements. Drug Regulations : Online Resource for Latest Information
  85. 85. 85 FDA GMP‘s Indian GMP‘s • §210.2 Applicability of current good manufacturing practice regulations. • (c) An investigational drug for use in a phase 1 study, as described in §312.21(a) of this chapter, is subject to the statutory requirements set forth in 21 U.S.C. 351(a)(2)(B). The production of such drug is exempt from compliance with the regulations in part 211 of this chapter. However, this exemption does not apply to an investigational drug for use in a phase 1 study once the investigational drug has been made available for use by or for the sponsor in a phase 2 or phase 3 study, as described in §312.21(b) and (c) of this chapter, or the drug has been lawfully marketed. If the investigational drug has been made available in a phase 2 or phase 3 study or the drug has been lawfully marketed, the drug for use in the phase 1 study must comply with part 211. • [69 FR 29828, May 25, 2004, as amended at 73 FR 40462, July 15, 2008; 74 FR 65431, Dec. 10, 2009] • Investigational drug has not been defined and there are no specific requirements for Investigational drugs. • Rules 86 to 93 define requirements for manufacture of products for experimental purposes. These rules define the labeling and storage of such material and the procedure to apply for a test licence. • Rule 86 defines that the exemption for such products from the requirements of Section 18 of the Drugs and Cosmetics Act. Section 18 specifies the Quality standards for products. Therefore most of the requirements of the act , rules and schedules do not apply to such materials.
  86. 86. 86 FDA GMP‘s Indian GMP‘s • §210.3 Definitions. • (a) The definitions and interpretations contained in section 201 of the act shall be applicable to such terms when used in this part and in parts 211, 225, and 226 of this chapter. • (b) The following definitions of terms apply to this part and to parts 211, 225, and 226 of this chapter. • (1) Act means the Federal Food, Drug, and Cosmetic Act, as amended (21 U.S.C. 301 et seq.). • (2) Batch means a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture. • (3) Component means any ingredient intended for use in the manufacture of a drug product, including those that may not appear in such drug product. • Defined in the Act : Section 3 • Not defined. However explanation given in rules under labeling and packing provisions as to how a batch number is to be given for different products like parenteral products , crams liquids etc. Slide 157 , Slide 158 • Though the term ― Component‖ has been used several times in the Act , Rules and GMP‘s several times it has not been defined. Drug Regulations : Online Resource for Latest Information
  87. 87. 87 FDA GMP‘s Indian GMP‘s • §210.3 Definitions. • (6) Nonfiber releasing filter means any filter, which after appropriate pretreatment such as washing or flushing, will not release fibers into the component or drug product that is being filtered. • (7) Active ingredient means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect. • (8) Inactive ingredient means any component other than an active ingredient. • Not defined • Though the term ― Active Ingredient‖ has been used several times in the Act , Rules and GMP‘s it has not been defined. • The definition of ― Drug‖ in the Act includes amongst several other things active ingredient. • Though the term ―In active Ingredient‖ has been used several times in the Act , Rules and GMP‘s it has not been defined. • The definition of ― Drug‖ in the Act includes amongst several other things inactive ingredient. Drug Regulations : Online Resource for Latest Information
  88. 88. 88 FDA GMP‘s Indian GMP‘s • §210.3 Definitions. • (9) In-process material means any material fabricated, compounded, blended, or derived by chemical reaction that is produced for, and used in, the preparation of the drug product. • (10) Lot means a batch, or a specific identified portion of a batch, having uniform character and quality within specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified amount produced in a unit of time or quantity in a manner that assures its having uniform character and quality within specified limits. • (11) Lot number, control number, or batch number means any distinctive combination of letters, numbers, or symbols, or any combination of them, from which the complete history of the manufacture, processing, packing, holding, and distribution of a batch or lot of drug product or other material can be determined. • Though the term ― In process material ‖ has been used a few times in the Act , Rules and GMP‘s , it has not been defined. • The term lot has been used several times in the Act , the rules and the GMP‘s .However the term has not been defined. • The term lot number has been used several times in the Act , the rules and the GMP‘s .However the term has not been defined.
  89. 89. 89 FDA GMP‘s Indian GMP‘s • §210.3 Definitions. • 12) Manufacture, processing, packing, or holding of a drug product includes packaging and labeling operations, testing, and quality control of drug products. • (13) The term medicated feed means any Type B or Type C medicated feed as defined in §558.3 of this chapter. The feed contains one or more drugs as defined in section 201(g) of the act. The manufacture of medicated feeds is subject to the requirements of part 225 of this chapter. • (14) The term medicated premix means a Type A medicated article as defined in §558.3 of this chapter. The article contains one or more drugs as defined in section 201(g) of the act. The manufacture of medicated premixes is subject to the requirements of part 226 of this chapter. • (15) Quality control unit means any person or organizational element designated by the firm to be responsible for the duties relating to quality control. • There is no definition in the Act , the rules or the GMP‘s • There is no definition in the Act , the rules or the GMP‘s • There is no definition in the Act , the rules or the GMP‘s • There is no definition in the Act , the rules or the GMP‘s
  90. 90. 90 FDA GMP‘s Indian GMP‘s • §210.3 Definitions. • (16) Strength means: • (i) The concentration of the drug substance (for example, weight/weight, weight/volume, or unit dose/volume basis), and/or • (ii) The potency, that is, the therapeutic activity of the drug product as indicated by appropriate laboratory tests or by adequately developed and controlled clinical data (expressed, for example, in terms of units by reference to a standard). • (17) Theoretical yield means the quantity that would be produced at any appropriate phase of manufacture, processing, or packing of a particular drug product, based upon the quantity of components to be used, in the absence of any loss or error in actual production. • (18) Actual yield means the quantity that is actually produced at any appropriate phase of manufacture, processing, or packing of a particular drug product. • There is no definition in the Act , the rules or the GMP‘s • There is no definition in the Act , the rules or the GMP‘s • There is no definition in the Act , the rules or the GMP‘s Drug Regulations : Online Resource for Latest Information
  91. 91. 91 FDA GMP‘s Indian GMP‘s • §210.3 Definitions. • (19) Percentage of theoretical yield means the ratio of the actual yield (at any appropriate phase of manufacture, processing, or packing of a particular drug product) to the theoretical yield (at the same phase), stated as a percentage. • (20) Acceptance criteria means the product specifications and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level, with an associated sampling plan, that are necessary for making a decision to accept or reject a lot or batch (or any other convenient subgroups of manufactured units). • There is no definition in the Act , the rules or the GMP‘s • There is no definition in the Act , the rules or the GMP‘s Drug Regulations : Online Resource for Latest Information
  92. 92. 92 FDA GMP‘s Indian GMP‘s • §210.3 Definitions. • (21) Representative sample means a sample that consists of a number of units that are drawn based on rational criteria such as random sampling and intended to assure that the sample accurately portrays the material being sampled. • (22) Gang-printed labeling means labeling derived from a sheet of material on which more than one item of labeling is printed. • [43 FR 45076, Sept. 29, 1978, as amended at 51 FR 7389, Mar. 3, 1986; 58 FR 41353, Aug. 3, 1993; 73 FR 51931, Sept. 8, 2008; 74 FR 65431, Dec. 10, 2009] • There is no definition in the Act , the rules or the GMP‘s • There is no definition in the Act , the rules or the GMP‘s Drug Regulations : Online Resource for Latest Information
  93. 93. 93 FDA GMP‘s Indian GMP‘s • Subpart A—General Provisions • §211.1 Scope. • (a) The regulations in this part contain the minimum current good manufacturing practice for preparation of drug products (excluding positron emission tomography drugs) for administration to humans or animals. • (b) The current good manufacturing practice regulations in this chapter as they pertain to drug products; in parts 600 through 680 of this chapter, as they pertain to drugs that are also biological products for human use; and in part 1271 of this chapter, as they are applicable to drugs that are also human cells, tissues, and cellular and tissue-based products (HCT/Ps) and that are drugs (subject to review under an application submitted under section 505 of the act or under a biological product license application under section 351 of the Public Health Service Act); • Requirement specified under rules for manufacturing licence: 69, 69A,70, 71, 71A, 74, 75, 75A,75B, 79. • GMP‘s for Drug products are specified in Schedule M • GMP‘s Biological Products are not specified. Assumed that Drug GMP‖s are applicable for Biological Products. Drug Regulations : Online Resource for Latest Information
  94. 94. 94 FDA GMP‘s Indian GMP‘s • Subpart A—General Provisions • §211.1 Scope. • ( b ) supplement and do not supersede the regulations in this part unless the regulations explicitly provide otherwise. In the event of a conflict between applicable regulations in this part and in other parts of this chapter, or in parts 600 through 680 of this chapter, or in part 1271 of this chapter, the regulation specifically applicable to the drug product in question shall supersede the more general. • (c) Pending consideration of a proposed exemption, published in the Federal Register of September 29, 1978, the requirements in this part shall not be enforced for OTC drug products if the products and all their ingredients are ordinarily marketed and consumed as human foods, and which products may also fall within the legal definition of drugs by virtue of their intended use. • GMP‘s for Drug products are specified in Schedule M • GMP‘s Biological Products are not specified. Assumed that Drug GMP‖s are applicable for Biological Products. • The Act does not have a separate classification for OTC products. • Therefore OTC products need to follow Drug GMP‖s Drug Regulations : Online Resource for Latest Information
  95. 95. 95 FDA GMP‘s Indian GMP‘s • Subpart A—General Provisions • §211.1 Scope. • ( c ) Therefore, until further notice, regulations under part 110 of this chapter, and where applicable, parts 113 to 129 of this chapter, shall be applied in determining whether these OTC drug products that are also foods are manufactured, processed, packed, or held under current good manufacturing practice. • [43 FR 45077, Sept. 29, 1978, as amended at 62 FR 66522, Dec. 19, 1997; 69 FR 29828, May 25, 2004; 74 FR 65431, Dec. 10, 2009] • The Act does not have a separate classification for OTC products. • Therefore OTC products need to follow Drug GMP‖s Drug Regulations : Online Resource for Latest Information
  96. 96. 96 FDA GMP‘s Indian GMP‘s • Subpart B—Organization and Personnel • §211.22 Responsibilities of quality control unit. • (a) There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in- process materials, packaging material, labeling, and drug products, • and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated. • The quality control unit shall be responsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company. • Part 1 . Clause : 16.0 : Quality control shall be concerned with sampling, specifications, testing, documentation, release procedures which ensure that the necessary and relevant tests are actually carried and that the materials are not released for use, nor products released for sale or supply until their quality has been judged to be satisfactory. • Not specified except for Manufacturing records. ( Schedule U ) 21. • Counter-signature of the head of the testing units or other approved person-in-charge of testing for having verified the batch records and for having released and batch for sale and distribution, the quantity released and date of release. • Specified
  97. 97. 97 FDA GMP‘s Indian GMP‘s • Subpart B—Organization and Personnel • §211.22 Responsibilities of quality control unit. • (b) Adequate laboratory facilities for the testing and approval (or rejection) of components, drug product containers, closures, packaging materials, in-process materials, and drug products shall be available to the quality control unit. • (c) The quality control unit shall have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product. • (d) The responsibilities and procedures applicable to the quality control unit shall be in writing; such written procedures shall be followed. • Facility Requirements specified in Part 1 ,clause 5 . • Slide 159 • Slide 160 • Not specified • Specified in Part 1, Clause 16.4 as Standard operating procedures shall be available for sampling, inspecting and testing of raw materials, intermediate bulk finished products and packing materials and, wherever necessary, for monitoring environmental conditions.
  98. 98. 98 FDA GMP‘s Indian GMP‘s • Subpart B—Organization and Personnel • §211.25 Personnel qualifications. • a) Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions. • Training shall be in the particular operations that the employee performs and in current good manufacturing practice (including the current good manufacturing practice regulations in this chapter and written procedures required by these regulations) as they relate to the employee's functions. • Training in current good manufacturing practice shall be conducted by qualified individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them. • Part 1, 6.1. The manufacture shall be conducted under the direct supervision of competent technical staff with prescribed qualifications and practical experience in the relevant dosage and / or active pharmaceutical products. • Necessity of GMP training not specified. • Part 1 ,6.6. The licensee shall ensure in accordance with a written instruction that all personnel in production area or into Quality Control Laboratories shall receive training appropriate to the duties and responsibility assigned to them. They shall be provided with regular in-service training. • Necessity of GMP training not specified.
  99. 99. 99 FDA GMP‘s Indian GMP‘s • Subpart B—Organization and Personnel • §211.25 Personnel qualifications. • (b) Each person responsible for supervising the manufacture, processing, packing, or holding of a drug product shall have the education, training, and experience, or any combination thereof, to perform assigned functions in such a manner as to provide assurance that the drug product has the safety, identity, strength, quality, and purity that it purports or is represented to possess. • (c) There shall be an adequate number of qualified personnel to perform and supervise the manufacture, processing, packing, or holding of each drug product. • Part 1, 6.6. The licensee shall ensure in accordance with a written instruction that all personnel in production area or into Quality Control Laboratories shall receive training appropriate to the duties and responsibility assigned to them. They shall be provided with regular in-service training. • Part 1, 6.5. Number of personnel employed shall be adequate and in direct proportion to the workload. Drug Regulations : Online Resource for Latest Information
  100. 100. 100 FDA GMP‘s Indian GMP‘s • Subpart B—Organization and Personnel • (§211.28 Personnel responsibilities • (a) Personnel engaged in the manufacture, processing, packing, or holding of a drug product shall wear clean clothing appropriate for the duties they perform. • Protective apparel, such as head, face, hand, and arm coverings, shall be worn as necessary to protect drug products from contamination. • (b) Personnel shall practice good sanitation and health habits. • Part 1, 7.7 All personnel shall wear clean body coverings appropriate to their duties • Not Specified. • Part 1, 7.3 All persons prior to and during employment shall be trained in practices which ensure personnel hygiene. A high level of personal hygiene shall be observed by all those engaged in the manufacturing processes. Instructions to this effect shall be displayed in change rooms and other strategic locations.
  101. 101. 101 FDA GMP‘s Indian GMP‘s • Subpart B—Organization and Personnel • (§211.28 Personnel responsibilities • (c) Only personnel authorized by supervisory personnel shall enter those areas of the buildings and facilities designated as limited-access areas. • Not specified.
  102. 102. 102 FDA GMP‘s Indian GMP‘s • Subpart B—Organization and Personnel • (§211.28 Personnel responsibilities • (d) Any person shown at any time (either by medical examination or supervisory observation) to have an apparent illness or open lesions that may adversely affect the safety or quality of drug products shall be excluded from direct contact with components, drug product containers, closures, in-process materials, and drug products until the condition is corrected or determined by competent medical personnel not to jeopardize the safety or quality of drug products. • All personnel shall be instructed to report to supervisory personnel any health conditions that may have an adverse effect on drug products. • Part 1, 7.4 No person showing, at any time, apparent illness or open lesions which may adversely affect the quality of products, shall be allowed to handle starting materials, packing materials, in-process materials, and drug products until his condition is no longer judged to be a risk. • Part 1, 7.5 All employees shall be instructed to report about their illness or abnormal health condition to their immediate supervisor so that appropriate action can be taken.
  103. 103. 103 FDA GMP‘s Indian GMP‘s • Subpart B—Organization and Personnel • §211.34 Consultants. • Consultants advising on the manufacture, processing, packing, or holding of drug products shall have sufficient education, training, and experience, or any combination thereof, to advise on the subject for which they are retained. Records shall be maintained stating the name, address, and qualifications of any consultants and the type of service they provide. • Nothing mentioned or specified for consultants. Drug Regulations : Online Resource for Latest Information
  104. 104. 104 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.42 Design and construction features. • (a) Any building or buildings used in the manufacture, processing, packing, or holding of a drug product shall be of suitable size, construction and location to facilitate cleaning, maintenance, and proper operations. • (b) Any such building shall have adequate space for the orderly placement of equipment and materials to prevent mixups between different components, drug product containers, closures, labeling, in-process materials, or drug products, and to prevent contamination. • The flow of components, drug product containers, closures, labeling, in-process materials, and drug products through the building or buildings shall be designed to prevent contamination. • Part 1.2 Building and premises.- The building(s) used for the factory shall be designed, constructed, adapted and maintained to suit the manufacturing operations so as to permit production of drugs under hygienic conditions. • The premises used for manufacturing, processing, warehousing, packaging labeling and testing purposes shall be – (i) compatible with other drug manufacturing operations that may be carried out in the same or adjacent area / section; (ii) adequately provided with working space to allow orderly and logical placement of equipment, materials and movement of personnel so as to: (a) avoid the risk of mix-up between different categories of drugs or with raw materials, intermediates and in-process material; (b) avoid the possibilities of contamination and cross- contamination by providing suitable mechanism;
  105. 105. 105 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.42 Design and construction features. • (c) Operations shall be performed within specifically defined areas of adequate size. There shall be separate or defined areas or such other control systems for the firm's operations as are necessary to prevent contamination or mixups during the course of the following procedures: • (1) Receipt, identification, storage, and withholding from use of components, drug product containers, closures, and labeling, pending the appropriate sampling, testing, or examination by the quality control unit before release for manufacturing or packaging; • (2) Holding rejected components, drug product containers, closures, and labeling before disposition; • See last slide Last Slide • Part 2.1 Adequate areas shall be designed to allow sufficient and orderly warehousing of various categories of materials and products like starting and packaging materials, intermediates, bulk and finished products, products in quarantine, released, rejected, returned or recalled, machine and equipment spare parts and change items. • Part 2.5.Segregation shall be provided for the storage of rejected, recalled or returned materials or products. Such areas, materials or products shall be suitably marked and secured. Access to these areas and materials shall be restricted.
  106. 106. 106 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.42 Design and construction features. • (3) Storage of released components, drug product containers, closures, and labeling; • (4) Storage of in-process materials; • (5) Manufacturing and processing operations; • (6) Packaging and labeling operations; • (7) Quarantine storage before release of drug products; • (8) Storage of drug products after release; • (9) Control and laboratory operations; • Specified : see last slide • Specified : See last slide • Specified : See last slide • Specified : See last slide • Specified : See last slide • Specified : See last slide • Specified : See this slide Drug Regulations : Online Resource for Latest Information
  107. 107. 107 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.42 Design and construction features. • (10) Aseptic processing, which includes as appropriate: • (i) Floors, walls, and ceilings of smooth, hard surfaces that are easily cleanable; • (ii) Temperature and humidity controls; • (iii) An air supply filtered through high- efficiency particulate air filters under positive pressure, regardless of whether flow is laminar or nonlaminar; • (iv) A system for monitoring environmental conditions; • (v) A system for cleaning and disinfecting the room and equipment to produce aseptic conditions; • Specified under Part I A : Specific requirements for sterile products Drug Regulations : Online Resource for Latest Information
  108. 108. 108 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.42 Design and construction features. • (vi) A system for maintaining any equipment used to control the aseptic conditions. • (d) Operations relating to the manufacture, processing, and packing of penicillin shall be performed in facilities separate from those used for other drug products for human use. • [43 FR 45077, Sept. 29, 1978, as amended at 60 FR 4091, Jan. 20, 1995] • Specified under Part I A : Specific requirements for sterile products • Part 1, 3.2. In order to avoid the risk of cross- contamination, separate dedicated and self contained facilities shall be made available for the production of sensitive pharmaceutical products like penicillin or biological preparations with live micro-organisms. Separate dedicated facilities shall be provided for the manufacture of contamination causing and potent products such as Beta-Lactum, sex hormones and cytotoxic substances. Drug Regulations : Online Resource for Latest Information
  109. 109. 109 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.44 Lighting. • Adequate lighting shall be provided in all areas. • Part 1, 1.2 ( iv) The production and dispensing areas shall be well lighted…….. Also mentioned at several other places under different headings. • §211.46 Ventilation, air filtration, air heating and cooling. • Part 1, 1.2 (iv) air-conditioned, where prescribed for the operations and dosage forms under production. The production and dispensing areas shall be well lighted, effectively ventilated, with air control facilities and may have proper Air Handling Units (wherever applicable) to maintain conditions including temperature and, wherever necessary, humidity, as defined for the relevant product. These conditions shall be appropriate to the category of drugs and nature of the operation. These shall also be suitable to the comforts of the personnel working with protective clothing, products handled, operations undertaken within them in relation to the external environment. These areas shall be regularly monitored for compliance with required specifications;
  110. 110. 110 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.46 Ventilation, air filtration, air heating and cooling. • (a) Adequate ventilation shall be provided. • (b) Equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature shall be provided when appropriate for the manufacture, processing, packing, or holding of a drug product. • Specified : See last slide • Part 1, 8.2.1. The licensee shall prevent mix-up and cross-contamination of drug material and drug product (from environmental dust) by proper air- handling system, pressure differential, segregation, status labeling and cleaning. Proper records and Standard Operating Procedures thereof shall be maintained. • Nothing specified for adequate control over, microorganisms Drug Regulations : Online Resource for Latest Information
  111. 111. 111 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.46 Ventilation, air filtration, air heating and cooling. • (b) Equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature shall be provided when appropriate for the manufacture, processing, packing, or holding of a drug product. • Part 1 B : : Oral Solid Dosage Forms: • 1.5 : Where the facilities are designed to provide special environmental conditions of pressure differentials between rooms, these conditions shall be regularly monitored and any specification results brought to the immediate attention of the Production and quality Assurance Department which shall be immediately attended to. • Part I E Metered Dose Inhalers • 3.1. Where products or clean components are exposed, the area shall be supplied with filtered air of Grade C. • 3.3 There shall be a difference in room pressure between the manufacturing area and the support areas and the differential pressure shall be not less than 15 Pascals (0.06 inches or 1.5mm water gauge).
  112. 112. 112 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.46 Ventilation, air filtration, air heating and cooling. • (c) Air filtration systems, including prefilters and particulate matter air filters, shall be used when appropriate on air supplies to production areas. • If air is recirculated to production areas, measures shall be taken to control recirculation of dust from production. • In areas where air contamination occurs during production, there shall be adequate exhaust systems or other systems adequate to control contaminants. • Part 1, 8.2.1. The licensee shall prevent mix-up and cross-contamination of drug material and drug product (from environmental dust) by proper air- handling system, pressure differential, segregation, status labeling and cleaning. Proper records and Standard Operating Procedures thereof shall be maintained. • Not specified. • Specified
  113. 113. 113 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.46 Ventilation, air filtration, air heating and cooling. • (d) Air-handling systems for the manufacture, processing, and packing of penicillin shall be completely separate from those for other drug products for human use. • Part 1, 3.2. In order to avoid the risk of cross- contamination, separate dedicated and self- contained facilities shall be made available for the production of sensitive pharmaceutical products like penicillin or biological preparations with live micro-organisms. Separate dedicated facilities shall be provided for the manufacture of contamination causing and potent products such as Beta-Lactum, sex hormones and cytotoxic substances. • Part 1, 8.2.2 The licensee shall ensure processing of sensitive drugs like Beta-Lactum antibiotics, sex hormones and cytotoxic substances in segregated areas or isolated production areas within the building with independent air-handling unit and proper pressure differential. The effective segregation of these areas shall be demonstrated with adequate records of maintenance and services.
  114. 114. 114 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.48 Plumbing. • (a) Potable water shall be supplied under continuous positive pressure in a plumbing system free of defects that could contribute contamination to any drug product. Potable water shall meet the standards prescribed in the Environmental Protection Agency's Primary Drinking Water Regulations set forth in 40 CFR part 141. Water not meeting such standards shall not be permitted in the potable water system. • (b) Drains shall be of adequate size and, where connected directly to a sewer, shall be provided with an air break or other mechanical device to prevent back-siphonage. • [43 FR 45077, Sept. 29, 1978, as amended at 48 FR 11426, Mar. 18, 1983] • Potable water to be supplied under continuous positive pressure not specified. • Specified that potable water should meet Indian specifications. • Part 1, 1.2 , (v) Provided with drainage system, as specified for the various categories of products, which shall be of adequate size and so designed as to prevent back flow and/or prevent insets and rodents entering the premises. Open channels shall be avoided in manufacturing areas and, where provided, these shall be shallow to facilitate cleaning and disinfection;
  115. 115. 115 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.50 Sewage and refuse. • Sewage, trash, and other refuse in and from the building and immediate premises shall be disposed of in a safe and sanitary manner. • Part 1, 1.4 (i) The disposal of sewage and effluents (solid, liquid and gas) from the manufactory shall be in conformity with the requirements of Environment Pollution Control Board. • §211.52 Washing and toilet facilities. • Adequate washing facilities shall be provided, including hot and cold water, soap or detergent, air driers or single-service towels, and clean toilet facilities easily accessible to working areas. • Part 1, 4.2 Facilities for changing, storing clothes and for washing and toilet purposes shall be easily accessible and adequate for the number of users. Toilets, separate for males and females, shall not be directly connected with production or storage areas. There shall be written instructions for cleaning and disinfection of such areas. Drug Regulations : Online Resource for Latest Information
  116. 116. 116 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.56 Sanitation. • (a) Any building used in the manufacture, processing, packing, or holding of a drug product shall be maintained in a clean and sanitary condition. • Any such building shall be free of infestation by rodents, birds, insects, and other vermin (other than laboratory animals). • Trash and organic waste matter shall be held and disposed of in a timely and sanitary manner. • Part 1, 9.1 The manufacturing premises shall be cleaned and maintained in an orderly manner, so that it is free from accumulated waste, dust, debris and other similar material. A validated cleaning procedure shall be maintained. • Part 1, 1.2 (iii) designed / constructed / maintained to prevent entry of insects, pests, birds, vermins, and rodents. • Specified in Part 1, 1.4 : Disposal of waste. • (b) There shall be written procedures assigning responsibility for sanitation and describing in sufficient detail the cleaning schedules, methods, equipment, and materials to be used in cleaning the buildings and facilities; such written procedures shall be followed. • Specified. Drug Regulations : Online Resource for Latest Information
  117. 117. 117 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.56 Sanitation. • (c) There shall be written procedures for use of suitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents. • Such written procedures shall be designed to prevent the contamination of equipment, components, drug product containers, closures, packaging, labeling materials, or drug products and shall be followed. • Rodenticides, insecticides, and fungicides shall not be used unless registered and used in accordance with the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 135). • Written procedures for use of suitable rodenticides, insecticides, fungicides, fumigating agents is not specified except for warehoue. • Not specified. • Not Specified. Drug Regulations : Online Resource for Latest Information
  118. 118. 118 FDA GMP‘s Indian GMP‘s • Subpart C—Buildings and Facilities • §211.56 Sanitation. • (d) Sanitation procedures shall apply to work performed by contractors or temporary employees as well as work performed by full- time employees during the ordinary course of operations. • Not Specified. • §211.58 Maintenance. • Any building used in the manufacture, processing, packing, or holding of a drug product shall be maintained in a good state of repair. • Specified. Drug Regulations : Online Resource for Latest Information
  119. 119. 119 FDA GMP‘s Indian GMP‘s • Subpart D—Equipment • §211.63 Equipment design, size, and location. • Equipment used in the manufacture, processing, packing, or holding of a drug product shall be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance. • Part 1, 11.1 Equipment shall be located, designed, constructed, adapted and maintained to suit the operations to be carried out. The layout and design of the equipment shall aim to minimise the risk of errors and permit effective cleaning and maintenance in order to avoid cross contamination, build-up of dust or dirt and, in general any adverse effect on the quality of products. Each equipment shall be provided with a logbook, wherever necessary. • §211.65 Equipment construction. • a) Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements. • Part 1,11.3 The parts of the production equipment that come into contact with the product shall not be reactive, additive or adsorptive to an extent that would affect the quality of the product.
  120. 120. 120 FDA GMP‘s Indian GMP‘s • Subpart D—Equipment • §211.65 Equipment construction. • (b) Any substances required for operation, such as lubricants or coolants, shall not come into contact with components, drug product containers, closures, in-process materials, or drug products so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements. • Part 1, 11.4 To avoid accidental contamination, wherever possible, non-toxic/edible grade lubricants shall be used and the equipment shall be maintained in a way that lubricants do not contaminate the products being produced. Drug Regulations : Online Resource for Latest Information
  121. 121. 121 FDA GMP‘s Indian GMP‘s • Subpart D—Equipment • §211.67 Equipment cleaning and maintenance. • (a) Equipment and utensils shall be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements. • Mentioned in a confused way in different sections under Blood bank , Equipment, Batch Packing & Processing Records and under different dosage forms. • Blood Banks : Rules Part 12 B ( E ) :Equipment used in the collection, processing, testing, storage and sale/distribution of blood and is components shall be maintained in a clean and proper manner and so placed as to facilitate cleaning and maintenance. • Schedule M : Part 1, 11.1 Equipment shall be located, designed, constructed, adapted and maintained to suit the operations to be carried out. The layout and design of the equipment shall aim to minimise the risk of errors and permit effective cleaning and maintenance in order to avoid cross contamination, build-up of dust or dirt and, in general any adverse effect on the quality of products. Each equipment shall be provided with a logbook, wherever necessary.
  122. 122. 122 FDA GMP‘s Indian GMP‘s • Subpart D—Equipment • §211.67 Equipment cleaning and maintenance. • (a) Equipment and utensils shall be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements. • Part 1, 20.2 Before any packaging operation begins, check shall be made and recorded that the equipment and the work stations are clear of the previous products, documents or materials not required for the planned packaging operations, and that the equipment is clean and suitable for use. • Part 1, 21.2 Before any processing begins, check shall be performed and recorded to ensure that the equipment and work station are clear of previous products, documents or materials not required for the planned process are removed and the equipment is clean and suitable for use.
  123. 123. 123 FDA GMP‘s Indian GMP‘s • Subpart D—Equipment • §211.67 Equipment cleaning and maintenance. • (a) Equipment and utensils shall be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements. • Part I B : ( Oral Solid Dosage Forms) : • 1.6. Care shall be taken to guard against any material lodging and remaining undetected in any processing or packaging equipment. Particular care shall be taken to ensure that any vacuum, compressed air or air-extraction nozzles are kept clean and that there is no evidence lubricants leaking into the product from any part of the equipment. • 7.1. Care shall be taken when using automatic tablet and capsule counting, strip and blister packaging equipment to ensure that all ‗rogue‘ tablets, capsules or foils from packaging operation are removed before a new packaging operation is commenced.
  124. 124. 124 FDA GMP‘s Indian GMP‘s • Subpart D—Equipment • §211.67 Equipment cleaning and maintenance. • (a) Equipment and utensils shall be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements. • Part I D : ( Topical Dosage Forms) : • 4. The equipment used shall be designed and maintained to prevent the product from being accidentally contaminated with any foreign matter or lubricant. • Part 1 F ( API) • 4.2. If the equipment is used for different intermediates and active pharmaceutical ingredients, proper cleaning before switching from one product to another becomes particularly important. If cleaning of a specific type of equipment is difficult, the equipment may need to be dedicated to a particular intermediate or active pharmaceutical ingredient.
  125. 125. 125 FDA GMP‘s Indian GMP‘s • Subpart D—Equipment • §211.67 Equipment cleaning and maintenance. • (a) Equipment and utensils shall be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements. • Part 1 F ( API) • 4.4. Written procedures shall be established and followed for cleaning and maintenance of equipment, including utensils used in the manufacture, processing, packing or holding of active pharmaceutical ingredients. • 4.5. Equipment shall be cleaned between successive batches to prevent contamination and carry-over of degraded material or contaminants unless otherwise established by validation.
  126. 126. 126 FDA GMP‘s Indian GMP‘s • Subpart D—Equipment • §211.67 Equipment cleaning and maintenance. • (b) Written procedures shall be established and followed for cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing, or holding of a drug product. These procedures shall include, but are not necessarily limited to, the following: • (1) Assignment of responsibility for cleaning and maintaining equipment; • (2) Maintenance and cleaning schedules, including, where appropriate, sanitizing schedules; • Mentioned in a very confused way under different parts: under Part 1 General Requirements and under Part 1 F for API‘s as follows: • Part I : • 22.5.2 There shall be written standard operating procedures and the associated records of actions taken for: (c) maintenance, cleaning and sanitation; • Part 1 F : API • 4.4. Written procedures shall be established and followed for cleaning and maintenance of equipment, including utensils used in the manufacture, processing, packing or holding of active pharmaceutical ingredients. These procedures shall include but should not be limited to the following : • (a) assignment of responsibility for cleaning and maintaining equipment; • (b) maintenance and cleaning program schedules, including where appropriate
  127. 127. 127 FDA GMP‘s Indian GMP‘s • Subpart D—Equipment • §211.67 Equipment cleaning and maintenance. • (3) A description in sufficient detail of the methods, equipment, and materials used in cleaning and maintenance operations, and the methods of disassembling and reassembling equipment as necessary to assure proper cleaning and maintenance; • (4) Removal or obliteration of previous batch identification; • (5) Protection of clean equipment from contamination prior to use; Mentioned in a very confused way under different parts under Part 1 General Requirements and under Part 1 F for API‘s. See last slide . Drug Regulations : Online Resource for Latest Information
  128. 128. 128 FDA GMP‘s Indian GMP‘s • Subpart D—Equipment • §211.67 Equipment cleaning and maintenance. • (6) Inspection of equipment for cleanliness immediately before use. • (c) Records shall be kept of maintenance, cleaning, sanitizing, and inspection as specified in §§211.180 and 211.182. • [43 FR 45077, Sept. 29, 1978, as amended at 73 FR 51931, Sept. 8, 2008] • Specified. • Not Clearly specified for keeping records of maintenance, cleaning, sanitizing, and inspection Drug Regulations : Online Resource for Latest Information

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