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Top 20 observation series # 4 : 21 CFR 211.67

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- 2014 inspectional observations
- List of Top observations in 2014
- Sec. 21 CFR 211.67
- 483 observations
- Warning Letters
- Other Guidance
- How to avoid observations

Published in: Healthcare

Top 20 observation series # 4 : 21 CFR 211.67

  1. 1. 21 CFR 211.67 pharmauptoday@gmail.comConsult Yourself.... “Know Regulation - No Observation”
  2. 2. - 2014 inspectional observations - List of Top observations in 2014 - Sec. 21 CFR 211.67 - 483 observations - Warning Letters - Other Guidance - How to avoid observations pharmauptoday@gmail.com Contents
  3. 3. Total Inspectional Observations Center Name 483s Issued Foods 2476 Devices 972 Drugs 645 Veterinary Medicine 337 Bioresearch Monitoring 297 Biologics 146 Human Tissue for Transplantation 115 Parts 1240 and 1250 70 Radiological Health 16 Sum Product Area 483s from System* 5074 Actual Total in System 483s** 4943 Number of 483s Issued from the System* Inspections ending between 10/1/2013 12:00:00 AM and 9/30/2014 12:00:00 AM
  4. 4. Inspectional Observations - Drugs Summary Count (Number) Total 483’s issued for Drugs center in 2014 645 Total number of observations issued for Drugs center in 2014 2997 Total number of observations related to cGMP (21 CFR part 211) violations 2835 Total number of top 10 CFR part 211 violation 1653 (58%) Total number of top 15 CFR part 211 violation 2110 (74%) Total number of top 20 CFR part 211 violation 2398 (85%) Number of CFR part 211 parts violated 54
  5. 5. S.No. CFR Frequency % S.No. CFR Frequency % S.No. CFR Frequency % 1 21 CFR 211.160 235 8.3 19 21 CFR 211.186 48 1.7 37 21 CFR 211.204 10 0.4 2 21 CFR 211.22 218 7.7 20 21 CFR 211.63 41 1.4 38 21 CFR 211.101 9 0.3 3 21 CFR 211.192 209 7.4 21 21 CFR 211.80 41 1.4 39 21 CFR 211.105 6 0.2 4 21 CFR 211.67 184 6.5 22 21 CFR 211.142 32 1.1 40 21 CFR 211.115 6 0.2 5 21 CFR 211.100 167 5.9 23 21 CFR 211.167 32 1.1 41 21 CFR 211.134 6 0.2 6 21 CFR 211.165 143 5.0 24 21 CFR 211.170 31 1.1 42 21 CFR 211.82 6 0.2 7 21 CFR 211.42 143 5.0 25 21 CFR 211.125 29 1.0 43 21 CFR 211.196 5 0.2 8 21 CFR 211.113 128 4.5 26 21 CFR 211.56 28 1.0 44 21 CFR 211.44 5 0.2 9 21 CFR 211.166 115 4.1 27 21 CFR 211.150 23 0.8 45 21 CFR 211.48 4 0.1 10 21 CFR 211.25 111 3.9 28 21 CFR 211.46 20 0.7 46 21 CFR 211.52 4 0.1 11 21 CFR 211.68 99 3.5 29 21 CFR 211.122 19 0.7 47 21 CFR 211.184 3 0.1 12 21 CFR 211.198 95 3.4 30 21 CFR 211.130 19 0.7 48 21 CFR 211.86 3 0.1 13 21 CFR 211.84 91 3.2 31 21 CFR 211.58 18 0.6 49 21 CFR 211.87 3 0.1 14 21 CFR 211.110 89 3.1 32 21 CFR 211.182 17 0.6 50 21 CFR 211.34 2 0.1 15 21 CFR 211.194 83 2.9 33 21 CFR 211.103 14 0.5 51 21 CFR 211.65 2 0.1 16 21 CFR 211.188 74 2.6 34 21 CFR 211.137 13 0.5 52 21 CFR 211.89 2 0.1 17 21 CFR 211.180 72 2.5 35 21 CFR 211.111 12 0.4 53 21 CFR 211.176 1 0.0 18 21 CFR 211.28 53 1.9 36 21 CFR 211.94 11 0.4 54 21 CFR 211.208 1 0.0 21 CFR 211 Observations - Drugs
  6. 6. 21 CFR 211 Observations - Drugs 0 50 100 150 200 250 21CFR211.22 21CFR211.25 21CFR211.28 21CFR211.34 21CFR211.42 21CFR211.44 21CFR211.46 21CFR211.48 21CFR211.52 21CFR211.56 21CFR211.58 21CFR211.63 21CFR211.65 21CFR211.67 21CFR211.68 21CFR211.80 21CFR211.82 21CFR211.84 21CFR211.86 21CFR211.87 21CFR211.89 21CFR211.94 21CFR211.100 21CFR211.101 21CFR211.103 21CFR211.105 21CFR211.110 21CFR211.111 21CFR211.113 21CFR211.115 21CFR211.122 21CFR211.125 21CFR211.130 21CFR211.134 21CFR211.137 21CFR211.142 21CFR211.150 21CFR211.160 21CFR211.165 21CFR211.166 21CFR211.167 21CFR211.170 21CFR211.176 21CFR211.180 21CFR211.182 21CFR211.184 21CFR211.186 21CFR211.188 21CFR211.192 21CFR211.194 21CFR211.196 21CFR211.198 21CFR211.204 21CFR211.208
  7. 7. List of “Top 20 – CFR parts to know” S.No. CFR Frequency % 1 21 CFR 211.160 235 8.3 2 21 CFR 211.22 218 7.7 3 21 CFR 211.192 209 7.4 4 21 CFR 211.67 184 6.5 5 21 CFR 211.100 167 5.9 6 21 CFR 211.165 143 5.0 7 21 CFR 211.42 143 5.0 8 21 CFR 211.113 128 4.5 9 21 CFR 211.166 115 4.1 10 21 CFR 211.25 111 3.9 11 21 CFR 211.68 99 3.5 12 21 CFR 211.198 95 3.4 13 21 CFR 211.84 91 3.2 14 21 CFR 211.110 89 3.1 15 21 CFR 211.194 83 2.9 16 21 CFR 211.188 74 2.6 17 21 CFR 211.180 72 2.5 18 21 CFR 211.28 53 1.9 19 21 CFR 211.186 48 1.7 20 21 CFR 211.63 41 1.4 Total 2398 85 • The top 10 cGMP violations (21 CFR part 211 observations) comprises a huge percentage (58% i.e. 1653 number of observations). • The top 20 cGMP violations (21 CFR part 211 observations) comprises a high percentage (85% i.e. 2398 number of observations). • If the top 20 violations are eliminated, 85 % of the observations can be reduced.
  8. 8. Subpart I--Laboratory Controls Sec. 211.160 General requirements. 21 CFR 211.160 (a) 21 CFR 211.160 (b) 21 CFR 211.160 can be accessed from the link: http://www.slideshare.net/skvemula/top-20-observation- series-1-21-cfr-211160 pharmauptoday@gmail.com 21 CFR 211.160
  9. 9. Subpart B--Organization and Personnel Sec. 211.22 Responsibilities of quality control unit. 21 CFR 211.22 (a) 21 CFR 211.22 (b) 21 CFR 211.22 (c) 21 CFR 211.22 (d) can be accessed from the link: http://www.slideshare.net/skvemula/top-20-observation- series-2-21-cfr-21122 pharmauptoday@gmail.com 21 CFR 211.22
  10. 10. Subpart J--Records and Reports Sec. 211.192 Production record review. 21 CFR 211.192 can be accessed from the link: http://www.slideshare.net/skvemula/top-20-observation- series-3-21-cfr-211192 pharmauptoday@gmail.com 21 CFR 211.192
  11. 11. Subpart D--Equipment Sec. 211.67 Equipment cleaning and maintenance. 21 CFR 211.67(a) 21 CFR 211.67(b) 21 CFR 211.67(c) pharmauptoday@gmail.com 21 CFR 211.67
  12. 12. 483 citations related to 21 CFR 211.67 Year Number 2006 137 2007 142 2008 111 2009 143 2010 171 2011 190 2012 175 2013 192 2014 184 0 50 100 150 200 250 2006 2007 2008 2009 2010 2011 2012 2013 2014 483 Observations
  13. 13. pharmauptoday@gmail.com Regulation
  14. 14. CFR part 211 Regulation - 21 CFR 211.67(a) Subpart D--Equipment Sec. 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.
  15. 15. pharmauptoday@gmail.com Previous observations
  16. 16. 483 citations related to 21 CFR 211.67(a) Cite Id Reference Number Short Description Long Description Frequency 2014 2013 1213 21 CFR 211.67(a) Cleaning / Sanitizing / Maintenance Equipment and utensils are not [cleaned] [maintained] [sanitized] at appropriate intervals to prevent [malfunctions] [contamination] that would alter the safety, identity, strength, quality or purity of the drug product. Specifically, *** 63 71
  17. 17. pharmauptoday@gmail.com Regulation
  18. 18. CFR part 211 Regulation - 21 CFR 211.67(b) Subpart D--Equipment Sec. 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; (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; (6) Inspection of equipment for cleanliness immediately before use.
  19. 19. pharmauptoday@gmail.com Previous observations
  20. 20. 483 citations related to 21 CFR 211.67(b) Cite Id Reference Number Short Description Long Description Frequency 2014 2013 1215 21 CFR 211.67(b) Written procedures not established/followed Written procedures are not [established] [followed] for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product. Specifically, *** 72 77 4303 21 CFR 211.67 b) Written procedures fail to include Written procedures for cleaning and maintenance fail to include [assignment of responsibility] [maintenance and cleaning schedules] [description in sufficient detail of methods, equipment and materials used] [description in sufficient detail of the methods of disassembling and reassembling equipment as necessary to assure proper cleaning and maintenance] [instructions for removal or obliteration of previous batch identification] [instructions for protection of clean equipment from contamination prior to use] [parameters relevant to the operation]. Specifically, *** 23 26 1219 21 CFR 211.67(b)(2) Cleaning SOPs/schedules Procedures for the cleaning and maintenance of equipment are deficient regarding maintenance and cleaning schedules, including, where appropriate, sanitizing schedules. Specifically, *** 1 1 1220 21 CFR 211.67(b)(3) Cleaning SOPs/instructions Procedures for the cleaning and maintenance of equipment are deficient regarding sufficient detail of the methods, equipment, and materials used in the cleaning and maintenance operation, and the methods of disassembly and reassembling equipment as necessary to assure proper cleaning and maintenance. Specifically, *** 3 1 1222 21 CFR 211.67(b)(4) Cleaning SOPs/equipment identification Procedures for the cleaning and maintenance of equipment are deficient regarding the removal or obliteration of the previous batch identification. Specifically, *** 1 1 1223 21 CFR 211.67(b)(5) Cleaning SOPs/equipment protection Procedures for the cleaning and maintenance of equipment are deficient regarding the protection of clean equipment from contamination prior to use. Specifically, *** 2 0 1224 21 CFR 211.67(b)(6) Cleaning SOP/inspection Procedures for the cleaning and maintenance of equipment are deficient regarding inspection of the equipment for cleanliness immediately before use. Specifically, *** 1 1
  21. 21. 483 citations related to 21 CFR 211.67(b) Ref: 483 of Andrx Pharmaceuticals Inc (04/2006)
  22. 22. 483 citations related to 21 CFR 211.67(b) Ref: 483 of Andrx Pharmaceuticals Inc (04/2006)
  23. 23. 483 citations related to 21 CFR 211.67(b) Ref: 483 of Andrx Pharmaceuticals Inc (04/2006)
  24. 24. 483 citations related to 21 CFR 211.67(b) Ref: 483 of Andrx Pharmaceuticals Inc (04/2006)
  25. 25. 483 citations related to 21 CFR 211.67(b) Ref: 483 of Teva Parenteral Medicines Inc (07/2009)
  26. 26. 483 citations related to 21 CFR 211.67(b) Ref: 483 of Teva Parenteral Medicines Inc (07/2009)
  27. 27. 483 citations related to 21 CFR 211.67 Ref: 483 of Hospira Inc (02/2013)
  28. 28. Warning letter observations -2014 - 21 CFR 211.67(b) Failure to adequately complete and follow written procedures for cleaning equipment and its release for use in API manufacture, and to maintain adequate records of major equipment usage. • Your firm failed to ensure that employees adequately cleaned (b)(4) after use. Your (b)(4) equipment cleaning standard operating procedures (SOP-HE 063-02 - instruction 4.2.2.1, SOP-HE 064-02 – instruction 4.3.4.3, and SOP-HE 055-02 – instruction 4.2.1.1), require that employees visually inspect equipment after the cleaning process. Our inspection found (b)(4) in the manufacturing workshop for (b)(4) with various levels of contamination and foreign objects inside, including what looked like the remains of a pen in one of the (b)(4). Your employees had labeled this equipment as clean. These (b)(4) are used for the manufacture of multiple APIs. • In addition, your firm’s production system did not maintain equipment logs or other documents that adequately record manufacturing operations performed on individual pieces of equipment. • We note that your production operation supervisors and Quality Unit (QU) failed to detect and correct these deficient cleaning practices. Ref: WL: Tianjin Zhongan Pharmaceutical Co., Ltd. 6/10/14 (320-14-09)
  29. 29. Warning letter observations -2013 - 21 CFR 211.67(b) Ref: WL: Ameriderm Laboratories, Ltd. 12/2/13 (14-NWJ-02) Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)). For example, the cleaning procedures described in Chapter 2-SOP-5 Cleaning of Batching Vessels lack detailed instructions for the cleaning and sanitization of non- dedicated equipment, including mixing kettles and tanks, used to manufacture your OTC drug products. There is no assurance that the cleaning and sanitization methods described in your cleaning validation documents are adequate. In addition, your firm does not maintain individual equipment logs for non-dedicated equipment, including mixing kettles and tanks, in order to document equipment cleaning, maintenance, and use.
  30. 30. Warning letter observations -2013 - 21 CFR 211.67(b) Ref: WL: P.A. Benjamin Manufacturing Co., Ltd. 1/29/13 (WL: 320-13-07) Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)). For example, your firm failed to validate a cleaning method used for the multi- product manufacturing equipment and utensils. Your firm has no assurance that your current, manual cleaning methods are effective in removing residues of drug products and detergents from the manufacturing equipment and utensils. Additionally, your firm failed to validate the “(b)(4)” device used to detect (b)(4) traces on the equipment surfaces after cleaning. Finally, your firm failed to implement procedures on the proper use of the device.
  31. 31. Warning letter observations -2013 - 21 CFR 211.67(b) Ref: WL: CMI Cosmetic Manufacturers Inc. 4/25/13 (WL: 320-13-13) Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)). For example, your firm has failed to evaluate the effectiveness of your cleaning procedures. You do not have data to show that your equipment cleaning procedure is adequate to prevent cross-contamination. Specifically, your firm has not conducted cleaning validation, cleaning verification, or swab recovery studies for multi-use equipment used in the production of your OTC drug products.
  32. 32. pharmauptoday@gmail.com Regulation
  33. 33. CFR part 211 Regulation - 21 CFR 211.67(c) Subpart D--Equipment Sec. 211.67 Equipment cleaning and maintenance. (c) Records shall be kept of maintenance, cleaning, sanitizing, and inspection as specified in 211.180 and 211.182.
  34. 34. pharmauptoday@gmail.com Previous observations
  35. 35. 483 citations related to 21 CFR 211.67(c) Cite Id Reference Number Short Description Long Description Frequency 2014 2013 1227 21 CFR 211.67(c) Cleaning/maintenance records not kept Records are not kept for the [maintenance] [cleaning] [sanitizing] [inspection] of equipment. Specifically, *** 18 12
  36. 36. 483 citations related to 21 CFR 211.67(c) Ref: 483 of Amylin Pharmaceutical Inc (12/2009)
  37. 37. Warning letter observations -2014 - 21 CFR 211.67 Failure to document manufacturing operations at the time they are performed. • When reviewing the entries in your (b)(4) use, cleaning, and maintenance logbook for the days immediately prior to the inspection, our investigator found missing entries. Your operators stated that lines were left blank to later add information about cleaning events that may have occurred during a previous shift. • During the inspection, our investigator found other similar instances of missing data or belated data entry in your manufacturing records. These practices are not consistent with CGMP. Operators acknowledged that there is no system in place to report these lapses in the documentation system; documentation errors of this type did not require deviation investigations or notification to the Quality Unit. Ref: WL: Zhejiang Jiuzhou Pharmaceutical Co., Ltd. 7/9/14 (320-14-12)
  38. 38. Summary of Observations • Inadequate equipment cleaning and validation protocols • Cleaning methods for common equipment not validated • Inadequate sampling and testing of equipment surfaces • No record to document alarms with the cleaning equipment • CIP record sheets that document the CIP of the manufacturing equipment are not reviewed by Production or Quality Assurance Staff. • Residue limits for potential contaminants not established • Specificity and sensitivity of analytical methods not established • No testing for residues of solvents used in API production • The CIP validation didn’t include studies to determine or evaluate what are the most difficult (“Hot Spot”) locations to clean.
  39. 39. pharmauptoday@gmail.com Other Guidance …
  40. 40. Validation of Cleaning Processes (7/93)
  41. 41. Questions and Answers on Current Good Manufacturing Practices, Good Guidance Practices, Level 2 Guidance - Laboratory Controls
  42. 42. USP General Chapter <1072> DISINFECTANTS AND ANTISEPTICS
  43. 43. USP General Chapter <1072> DISINFECTANTS AND ANTISEPTICS
  44. 44. Comparison between US and EC GMP
  45. 45. EC GMP Guide
  46. 46. EMA Guide
  47. 47. EU Non-Compliance Reports Firm Name Nature of non-compliance Wockhardt Limited, Aurangabad; Jan 2015 A major deficiency was cited with regards to equipment and facility, maintenance, design and qualification. Examples included, inappropriate pressure differentials that were not in line with the original design but had not been changed using change control, cleaning validation that was not sufficiently robust to confirm cleaning practices and maintenance issues, such as the failure to spark test glass lined reactor vessels for integrity especially following maintenance. MANUEL RIESGO S.A., Spain; Nov 2014 Utensils are not cleaned and stored to prevent contamination. Taishan City Chemical Pharmaceutical Co. Ltd., China; Nov 2014 Multiple risks of contamination identified in the production areas of Ciclosporin (e.g. no protection of clean equipment outlets, equipment under status “to be used for production” stored dirty for several months, open parts of the final steps exposed in dirty surroundings); VETPROM AD, Bulgaria; Aug 2014 The procedure for cleaning validation is ineffective and does not include all medicines (human and animal medicinal use);
  48. 48. Health Canada – GMP
  49. 49. Health Canada – GMP • Examples of observations from frequently cited sections of the Food and Drug Regulations - Good Manufacturing Practices Inspections
  50. 50. ICH
  51. 51. ICH
  52. 52. ICH
  53. 53. PDA
  54. 54. WHO
  55. 55. APIC
  56. 56. pharmauptoday@gmail.comHow to avoid 21 CFR 211.67 observations ?
  57. 57. Basics Clean(liness) (adj.) • visually clean - absence of materials which would adulterate a product when inspected with the eyes • detectably clean - absence of materials which would adulterate a product down to the level of detection • chemically clean - absence of all chemicals which would adulterate a product. Cleaning validation • Documented evidence to establish that cleaning procedures are removing residues to predetermined levels of acceptability, taking into consideration factors such as batch size, dosing, toxicology and equipment size.
  58. 58. Cleaning Documentation • The cleaning validation must document the efficiency of a cleaning procedure • The cleaning procedure must be reliable with regard to removal of contamination (e.g. products, cleaning agents, microorganisms) to a predetermined acceptable level • Procedures for cleaning of areas in product contact must be validated (with consideration to areas out of product contact). • The intervals between use and cleaning of equipment as well as between cleaning and reuse must be validated.
  59. 59. Recordings • Preceding product • ”Batch to batch” cleaning or ”product to product” cleaning • The cleaning documentation for equipment which is considered to be critical for the product • Sampling of equipment which is considered critical for the product • Applied cleaning agents and concentrations (batch no.) • Time of cleaning – date of performance and signature • Observations during inspection of equipment prior to production
  60. 60. Equipment Cleaning • Preparation and storage of cleaning solutions, maintenance of cleaning equipment, such as mops, buck, etc., and procedures used for cleaning. • review the regulatory requirements for establishing a cleaning program. • Discuss personnel qualifications, written procedures, selection of cleaning agents, and recordkeeping. • Determine if the procedures are being followed, and if they specify the cleaning agents and the preparation of those cleaning agents. • Ensure that the cleaning agents, their concentration, and the procedure for use are consistent with those that have been used in the cleaning validation. • Review the written procedures for equipment cleaning. Ensure that the purpose of the cleaning is consistent with the agent chosen for use. For example, if the objective of the cleaning is to sanitize a piece of equipment, ensure that the cleaning agent chosen is designed to accomplish the desired sanitization by reviewing the technical literature available from the supplier.
  61. 61. Approach The following considerations are proposed as part of a systematic approach to determine the most difficult-to- clean sampling locations in manufacturing equipment: • Equipment technical analysis. The type of surface, interfacial effects, and shadowed areas should be considered. Materials of construction (MOC) and geometrical configurations, type of processing (wet or dry), and problematic hard-to-clean areas of the equipment are noted. For example, stainless steel is generally harder to clean than glass or Teflon. Additionally, for a specific MOC, the smoothness of the surface can significantly affect its cleanability. • Observation of equipment after processing. The equipment is observed after processing typical pharmaceutical products. Areas of excessive process residue accumulation are noted. • Equipment disassembly review. The equipment is observed after disassembly. Product contact areas that are the most difficult to clean are noted. Equipment components that are disassembled for cleaning and subsequent evaluation pose a much lower risk than components that are part of the fixed equipment assembly and are cleaned in place. Accessibility of components on the fixed equipment assembly is noted. • Cleaning procedure review. The cleaning procedure for the equipment is reviewed. Ability to visually observe equipment and components is noted. Parts and equipment locations previously identified as difficult to clean may not be difficult to clean after equipment disassembly. • Operator interviews. Discussions with operators experienced with cleaning the equipment of interest are utilized to determine difficult-to-clean locations. Their recommendations of difficult-to-clean areas of the equipment based on actual experience are noted.
  62. 62. Considerations …. • Cleaning procedures should be sufficiently detailed to remove the possibility of any inconsistencies during the cleaning process. Following parameters are to be considered during cleaning procedures. A. Equipment Parameters to be evaluated • Identification of the equipment to be cleaned • 'Difficult to clean' areas • Property of materials • Ease of disassembly • Mobility B. Residues to be cleaned • Cleaning limits • Solubility of the residues • Length of campaigns C. Cleaning agent parameters to be evaluated • Preferable materials that are normally used in the process • Detergents available (as a general guide, minimal use of detergents recommended unless absolutely required) • Solubility properties • Environmental considerations • Health and safety considerations D. Cleaning techniques to be evaluated • Manual cleaning • CIP (Clean-in-place) • COP (Clean-out-of- place) • Semi automatic procedures • Automatic procedures • Time considerations • Number of cleaning cycles
  63. 63. Considerations …. • Automated Cleaning Vs Manual Cleaning • Clean-In-Place (CIP) Vs Clean-Out-of- Place (COP) Cleaning Program Criteria • Dedicated Vs Non- Dedicated Manufacturing Equipment • Dedicated Vs Non- Dedicated Cleaning Equipment • Non-Product Contact Vs Product Contact Surfaces • Non-Critical Site Vs Critical Site • Minor Equipment Vs Major Equipment Equipment Characteristics / Materials of Construction • Low Risk Vs High Risk Drugs • Highly Characterized Vs Poorly Characterized • Non-Sterile Vs Sterile Product Attributes • Solids Vs Liquids • Soluble (Active or Excipient) Vs Insoluble (Active or Excipient) Formulation Attributes • Single Product Facility Vs Multiple Product Facility • Campaign Production Vs Batch Production • Simple Equipment Train Vs Complex Equipment Train Operational Issues
  64. 64. Training Training practices will vary from one company to another but operator training may be enhanced by some of the following suggestions: - Clearly written, understandable and sufficiently detailed SOPs. - Use of checklists to determine that all operations are carried out in the proper sequence and are documented. - Periodic monitoring of cleaning processes to ensure proper training of operators and continued compliance with SOPs. - Dedicated or assigned cleaning personnel. - Feedback from operators to modify procedures. - Use of video to demonstrate proper cleaning operations and techniques. • Overall the operators should understand the process of cleaning and the operation of the equipment they are cleaning. In addition the operators should be aware of the cleaning process impact on the quality of the next product manufactured in the same equipment.
  65. 65. Major Sampling Techniques - Attributes
  66. 66. Typical Cleaning Validation Assay Methods
  67. 67. cGMPCleaningCompliance Source: 5 Tactics for Cleaning Validation Compliance (IVT Network)
  68. 68. pharmauptoday@gmail.com Thank You The module Consult Yourself.... “Know Regulation - No Observation” deals with most common (top 20) basic CFR regulations having frequent violations and previous observations for better understanding. The module will be continued with # 5 21 CFR 211.100 For “Pharma Uptoday” free daily newsletter write a mail to pharmauptoday@gmail.com for other Pharma Uptoday presentations & Monthly Magazines browse: http://www.slideshare.net/skvemula

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