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Facility & Equipment Quality System Outline

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Facility & Equipment sub-system of the Quality System approach - a very brief introduction

Facility & Equipment Quality System Outline

  1. 1. Joseph T. Busfield Pharmaceutical Technical Services [email_address] www.PTSGMP.com A very brief outline of the Facility & Equipment System component of the GMP Quality System Seminar offered by PTS Note: This presentation has been distilled from the complete session and is less than 25% of the material Materials System Laboratory Control System Production System Quality System Facilities & Equipment System Packaging and Labeling System
  2. 2. <ul><li>The Quality System Inspection </li></ul><ul><li>approach consists of </li></ul><ul><li>Six Inspection Areas: </li></ul><ul><li>Quality System </li></ul><ul><li>Materials System </li></ul><ul><li>Facilities and Equipment System </li></ul><ul><li>Production System </li></ul><ul><li>Packaging and Labeling System </li></ul><ul><li>Laboratory Control System </li></ul>
  3. 3. <ul><li>Points to consider: </li></ul><ul><li>Not new requirements </li></ul><ul><li>New Inspection Technique </li></ul><ul><li>Designed to maximize limited Agency resources </li></ul><ul><li>Failure of a system means failure of firm </li></ul><ul><li>System oriented </li></ul><ul><li>At least two systems to be inspected (four for full inspection) </li></ul><ul><li>One system is always the Quality System </li></ul>
  4. 4. <ul><li>Facility & Equipment System Parts </li></ul><ul><li>Construction and maintenance of buildings and facilities </li></ul><ul><li>Equipment qualifications, calibrations, maintenance, cleaning and validation of cleaning processes </li></ul><ul><li>Evaluation of HVAC, compressed gases, steam and water systems, etc. </li></ul>
  5. 5. <ul><li>Facility Specific </li></ul><ul><li>Cleaning and Maintenance </li></ul><ul><li>Layout and air handling to prevent cross contamination (esp. Penicillin, cytotoxics, etc.) </li></ul><ul><li>Areas design to prevent contamination and mix ups </li></ul><ul><li>General air handling </li></ul><ul><li>Change Control </li></ul><ul><li>Lighting, potable water, sanitary facilities, etc. </li></ul><ul><li>Sanitization, pest control, etc </li></ul>
  6. 6. <ul><li>Equipment Specific </li></ul><ul><li>IQ and OQ </li></ul><ul><li>Design, Size, and Location </li></ul><ul><li>Surfaces </li></ul><ul><li>Product contact substances </li></ul><ul><li>Cleaning procedures and validation </li></ul><ul><li>Control for cross contamination </li></ul><ul><li>Calibration and Maintenance </li></ul><ul><li>Equipment Identification </li></ul><ul><li>Discrepancy investigation </li></ul>
  7. 7. <ul><li>This Approach </li></ul><ul><li>Will emphasize major areas (systems) </li></ul><ul><li>Will use the Engineering Life Cycle model as a guide </li></ul>
  8. 8. <ul><li>Components of the life cycle </li></ul><ul><li>Project Engineering </li></ul><ul><li>URS </li></ul><ul><li>Preliminary Design </li></ul><ul><li>Detailed Design </li></ul><ul><li>Procurement </li></ul><ul><li>FAT </li></ul><ul><li>SAT/Commissioning/Start-up </li></ul><ul><li>IQ/OQ </li></ul><ul><li>PV </li></ul><ul><li>Operation </li></ul><ul><li>Cleaning/Maintenance/Calibration </li></ul><ul><li>Etc. </li></ul>--------Change Control-----------
  9. 9. The Three Legged Compliance Stool <ul><li>Procedures </li></ul><ul><li>Practices </li></ul><ul><li>Paperwork </li></ul>Compliance programs MUST have all three legs of the stool! Procedures Practices Paperwork Compliance Compliance
  10. 10. The Project Engineering Program Materials System Laboratory Control System Production System Quality System Facilities & Equipment System Packaging and Labeling System
  11. 11. <ul><li>Project Engineering Goals </li></ul><ul><li>Ensure a project that: </li></ul><ul><ul><li>Is cost effective </li></ul></ul><ul><ul><li>Meets operations needs </li></ul></ul><ul><ul><li>Compliant with business process </li></ul></ul><ul><ul><li>Compliant with Good Engineering Practices </li></ul></ul><ul><ul><li>Compliant with Regulations </li></ul></ul><ul><ul><li>Can be efficiently validated </li></ul></ul>
  12. 12. <ul><li>Bases (21 CFR 211) </li></ul><ul><li>§211.42 Design and construction features. </li></ul><ul><li>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. </li></ul><ul><li>§211.63 Equipment design, size, and location. </li></ul><ul><li>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. </li></ul>
  13. 13. <ul><li>Project Engineering </li></ul><ul><li>Basic Requirements </li></ul><ul><li>Definition of project complexity </li></ul><ul><ul><li>Used to determine the level of control </li></ul></ul><ul><li>Project Teams </li></ul><ul><ul><li>Members, Roles, Meetings, etc </li></ul></ul><ul><li>Process to initiate, review, and approve to be identified as project steps </li></ul>
  14. 14. <ul><li>Project Engineering First Steps of Life Cycle </li></ul>
  15. 15. <ul><li>Project Engineering </li></ul><ul><li>User Requirements </li></ul><ul><ul><li>What does the customer need? (not necessarily what the customer wants) </li></ul></ul><ul><ul><ul><li>Basis for developing a design scheme </li></ul></ul></ul><ul><ul><ul><li>The raison d’ ê tre for an engineering function </li></ul></ul></ul><ul><ul><ul><li>Includes operational requirements AND compliance requirements </li></ul></ul></ul><ul><ul><li>When? </li></ul></ul><ul><ul><ul><li>At the beginning!! </li></ul></ul></ul><ul><ul><li>Not infallible nor unchangeable (though controlled)! </li></ul></ul>
  16. 16. <ul><li>Project Engineering </li></ul><ul><li>Functional Requirements </li></ul><ul><ul><li>What does it take to meet the needs of the customer </li></ul></ul><ul><ul><ul><li>More Technical Requirements </li></ul></ul></ul><ul><ul><ul><li>Additional basis for developing a design scheme </li></ul></ul></ul><ul><ul><ul><li>Includes operational requirements AND compliance requirements </li></ul></ul></ul>
  17. 17. <ul><li>Project Engineering </li></ul><ul><li>Preliminary Design </li></ul><ul><ul><li>First Pass(es) </li></ul></ul><ul><li>Detailed Design and Specification Preparation </li></ul><ul><li>So far – fairly typical. What’s different in a regulated industry? </li></ul>
  18. 18. <ul><li>Project Engineering Reviews </li></ul><ul><li>Operations </li></ul><ul><li>Validation </li></ul><ul><li>Quality Unit </li></ul><ul><li>When Reviewed? </li></ul><ul><li>At each document/transition stage: </li></ul><ul><li>User and Functional Requirements </li></ul><ul><li>Preliminary Design </li></ul><ul><li>Detailed Design </li></ul><ul><li>Agency Review </li></ul>
  19. 19. <ul><li>Project Engineering </li></ul><ul><li>How to review? </li></ul><ul><li>Recommendation: </li></ul><ul><ul><li>Large projects – a dedicated team </li></ul></ul><ul><ul><li>Smaller projects – a standing team </li></ul></ul>
  20. 20. <ul><li>Project Engineering </li></ul><ul><li>involvement in </li></ul><ul><li>Next Steps </li></ul>
  21. 21. <ul><li>Change Control </li></ul><ul><li>Increasing rigor as one goes through the life cycle </li></ul><ul><li>Accomplished by the GMP reviews and – </li></ul><ul><li>Specific document reviews as per site procedure </li></ul><ul><ul><li>URS </li></ul></ul><ul><ul><li>Commissioning Plan </li></ul></ul><ul><ul><li>IQ/OQ </li></ul></ul><ul><ul><li>Etc. </li></ul></ul>
  22. 22. Joseph T. Busfield Pharmaceutical Technical Services [email_address] www.PTSGMP.com The Calibration & Maintenance Programs Materials System Laboratory Control System Production System Quality System Facilities & Equipment System Packaging and Labeling System
  23. 23. <ul><li>Why Maintenance & Calibration? </li></ul><ul><li>Second Law of Thermodynamics </li></ul><ul><li>It is possible to regard all natural processes from this point of view, and in all cases the result obtained is that there is a tendency on the part of nature to proceed toward a state of greater disorder . </li></ul><ul><li>Heat and Thermodynamics - Zemansky </li></ul>
  24. 24. Bases Maintenance (and Calibration) 21 CFR § 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: . . . (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; Procedures Compliance Compliance
  25. 25. <ul><li>Bases Maintenance </li></ul><ul><li>21 CFR § 211.67 Equipment cleaning and maintenance. </li></ul><ul><li>Equipment and utensils shall be cleaned, maintained, and sanitized 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. </li></ul><ul><li>(c) Records shall be kept of maintenance, cleaning, sanitizing, and inspection as specified in §211.180 and §211.182 . </li></ul>Practices Paperwork Compliance Compliance
  26. 26. <ul><li>CFR § 211.68 Automatic, mechanical, and electronic equipment . </li></ul><ul><li>(a) 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. If such equipment is so used, it shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained. </li></ul>Practices Procedures Paperwork Compliance Compliance
  27. 27. Procedures must be developed to cover areas of Maintenance for a Compliant Program, e.g.: <ul><li>Maintenance Overview </li></ul><ul><li>Addition, Deletions, Changes to PMs </li></ul><ul><li>PM System Operation </li></ul><ul><li>PM Out-of-Frequency Reporting </li></ul><ul><li>Corrective Work Orders and Recording </li></ul><ul><li>Corrective Maintenance and Change Control </li></ul><ul><li>Record Retention/Equipment Files </li></ul>
  28. 28. <ul><li>PM Procedures – Tasks and Frequencies – need to be: </li></ul><ul><ul><li>Related to manufacturer’s recommendations – though not identical </li></ul></ul><ul><ul><ul><li>Modified by the site’s use, application, environment, experience, etc. </li></ul></ul></ul><ul><ul><li>Documented and controlled </li></ul></ul><ul><ul><li>Reviewed and approved </li></ul></ul><ul><ul><li>Prepared before Validation is considered complete </li></ul></ul>Preventive Maintenance
  29. 29. <ul><li>If repairs beyond scope of PM are required, a Corrective WO must be generated. </li></ul><ul><li>Under no circumstances is any technician to make any modifications to GMP equipment other than restoring it to its original as-built, as-validated condition or under a Change Control procedure ! </li></ul><ul><li>(Commit this to memory and insure all technician are sufficiently indoctrinated) </li></ul>Preventive Maintenance
  30. 30. PM Out-of-Frequency Reporting <ul><li>Compliance Suggestion </li></ul><ul><li>If a PM cannot be done by due date someone has to notify management, usually the Maintenance Supervisor. </li></ul>Warning Surprising Plant Manager or QC department during an audit by having an investigator uncover missed/late PMs could be detrimental to a career!
  31. 31. <ul><li>The first person to read the closing notes is the Supervisor or Foreman. </li></ul><ul><li>The second person may be the FDA inspector ! </li></ul><ul><li>We do not want to risk our business, the well being of our customers and being out of compliance because someone did not prepare adequate “closing notes” on WOs! </li></ul>CLOSING NOTES! Corrective Work
  32. 32. <ul><li>Administrative SOP(s) </li></ul><ul><li>Classification (GMP Critical. GMP Non-critical, GMP Utility) </li></ul><ul><li>Directions for Setting Limits & Tolerances! (For OOTs) </li></ul><ul><li>Direction for Setting Intervals </li></ul><ul><li>Standard Operating Procedures for Device Calibration </li></ul><ul><li>Out-of-Tolerance Response </li></ul><ul><li>Scheduling Tool </li></ul><ul><li>Field Tagging </li></ul><ul><li>History Files </li></ul><ul><li>QA Review </li></ul><ul><li>Calibration Standards </li></ul><ul><li>Laboratory Instruments </li></ul><ul><li>Qualifications of technicians and contractors </li></ul><ul><li>Master Instrument List Control </li></ul>Components of a Compliant Calibration Program
  33. 33. Instrument Classification <ul><li>Critical </li></ul><ul><li>Non-critical </li></ul><ul><li>Diagnostic </li></ul><ul><li>Critical </li></ul><ul><li>Non-critical </li></ul><ul><ul><li>First Pass - GMP vs. Non-GMP </li></ul></ul><ul><li>Critical </li></ul><ul><li>Non-critical </li></ul><ul><li>Utility </li></ul><ul><ul><li>GMP Distinctions </li></ul></ul><ul><li>Potential GMP Scenarios </li></ul>
  34. 34. Example – WFI Multi-effect Still House Steam 1 st Effect 2nd Effect 3d Effect PI PI 2 PI PI 3 PI 1 Utility Non-critical Condenser AIT 1 Critical Conductivity
  35. 35. Understanding Calibration Parameters <ul><li>Limits, Tolerances and Parameters for: </li></ul><ul><ul><li>Accuracy Limits (Calibration requirements) </li></ul></ul><ul><ul><ul><li>Calibration Limits </li></ul></ul></ul><ul><ul><li>Tolerance Limits (Out-of-Tolerance response trigger) </li></ul></ul><ul><ul><ul><li>Process Calibration Tolerances </li></ul></ul></ul><ul><ul><li>Repeatability (Precision) </li></ul></ul><ul><ul><li>Frequency of calibration </li></ul></ul>
  36. 36. Process Tolerances Process Calibration Tolerances True Value The Importance of Relationships! Calibration Limits Manufacturer’s Stated Accuracy
  37. 37. Setting (and Reviewing) Calibration Intervals <ul><li>Three considerations for setting intervals </li></ul><ul><ul><li>Instrument Reliability (as stated) </li></ul></ul><ul><ul><li>Safety impact of measured/controlled parameter on product </li></ul></ul><ul><ul><li>Time from manufacture to use </li></ul></ul><ul><li>We are not making shoes! </li></ul>
  38. 38. Joseph T. Busfield Pharmaceutical Technical Services [email_address] www.PTSGMP.com Auxiliary Facility Programs Materials System Laboratory Control System Production System Quality System Facilities & Equipment System Packaging and Labeling System
  39. 39. <ul><li>Requirements for Auxiliary Systems </li></ul><ul><li>Systems to ensure validated state is achieved and maintained </li></ul><ul><li>Systems that may not be a large as Project Engineering, Maintenance, and Calibration, but can be of major impact (like a tooth ache!) </li></ul>
  40. 40. <ul><li>Systems to consider: </li></ul><ul><li>Pest Control </li></ul><ul><li>Cleaning (facility and equipment) </li></ul><ul><li>Drawing Control </li></ul><ul><li>Engineering Change Control </li></ul><ul><li>Spare Parts </li></ul><ul><ul><li>Lubricants </li></ul></ul><ul><li>Contractor Qualification </li></ul>
  41. 41. <ul><li>Pest Control </li></ul><ul><li>§211.56 Sanitation. </li></ul><ul><li>(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. </li></ul>
  42. 42. <ul><li>Pest Control </li></ul><ul><li>Pest control is: </li></ul><ul><li>Contacted by a licensed company </li></ul><ul><li>Physically performed by licensed individuals </li></ul><ul><li>The responsibility of the Company </li></ul><ul><li>Governed by a Procedure of the Company </li></ul>
  43. 43. <ul><li>Cleaning </li></ul><ul><li>Remember </li></ul><ul><li>§211.56 Sanitation. </li></ul><ul><li>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. </li></ul>
  44. 44. <ul><li>Cleaning </li></ul><ul><li>AND </li></ul><ul><li>§211.67 Equipment cleaning and maintenance. </li></ul><ul><li>Equipment and utensils shall be cleaned, maintained, and sanitized 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. </li></ul><ul><li>(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. . . . </li></ul>
  45. 45. <ul><li>Cleaning </li></ul><ul><li>Two areas of cleaning concern – Facilities and Equipment </li></ul><ul><li>Facilities cleaning usually performed by facilities staff </li></ul><ul><li>Equipment cleaning usually performed by operations folks </li></ul>
  46. 46. <ul><li>Cleaning </li></ul><ul><li>Both types of cleaning need approved SOPs and validation </li></ul>
  47. 47. <ul><li>Drawing control </li></ul><ul><li>Engineering drawings must reflect actual field conditions to maintain compliance. </li></ul><ul><li>Of particular interest to an inspector are: </li></ul><ul><li>People, product, material, waste flows to protect against contamination </li></ul><ul><li>Single line HVAC and balance drawings (Understandable by a non-engineer is preferable) </li></ul><ul><li>Single line or P&IDs of major utility system (Particularly Purified Water systems) </li></ul>
  48. 48. <ul><li>Engineering Change Control </li></ul><ul><li>Several systems can be incorporated in this system and its sub-systems: </li></ul><ul><ul><li>Drawing control </li></ul></ul><ul><ul><li>Preventive Maintenance Regimens </li></ul></ul><ul><ul><li>Calibration Parameter control </li></ul></ul><ul><ul><li>Functionally Equivalent Spare parts </li></ul></ul>
  49. 49. <ul><li>Engineering Change Control </li></ul><ul><li>These Routine changes do not impact regulatory submissions, should not impact validation or validation documents, and are best served by dedicated, knowledgeable reviewers </li></ul>
  50. 50. <ul><li>Engineering Change Control </li></ul><ul><li>However, each of these Routine changes should be reviewed by: </li></ul><ul><ul><li>Technical personnel </li></ul></ul><ul><ul><li>Operational personnel </li></ul></ul><ul><ul><li>Quality Personnel </li></ul></ul><ul><li>Thus there is change control even if not in the site Change Control program </li></ul>
  51. 51. <ul><li>Spare Parts </li></ul><ul><li>Note: NOT Change Parts – reused for different production runs, but replacement parts for equipment </li></ul><ul><li>There are several categories of spare parts: </li></ul><ul><ul><li>Consumable parts </li></ul></ul><ul><ul><li>Generic – cross referenced parts(belts, hoses, bearing, etc.) </li></ul></ul><ul><ul><li>OEM Parts (exact replacements) </li></ul></ul><ul><ul><li>Functionally Equivalent parts </li></ul></ul><ul><ul><li>Fabricated parts </li></ul></ul><ul><ul><li>Changed parts </li></ul></ul>
  52. 52. <ul><li>Spare Parts </li></ul><ul><li>Functionally Equivalent parts: </li></ul><ul><li>Parts that perform the same function and have the same specification as the original but are made by a different manufacturer should be evaluated and approved before use – not just a technician’s call. </li></ul>
  53. 53. <ul><li>Lubricants </li></ul><ul><li>Each manufacturer may recommend a particular brand or lube for their equipment </li></ul><ul><li>The result is redundant lubes with different logos, but the same functionality </li></ul>
  54. 54. <ul><li>Spare Parts - Lubricants </li></ul><ul><li>Develop a system to evaluate different brands of lubricants (much like the Functionally Equivalent Parts program) and maintain a controlled list of acceptable lubes. </li></ul>
  55. 55. Qualification & Training of Maintenance Technicians You must be able to demonstrate that the folks working on GMP equipment are qualified by training, education, and experience or some combination thereof to do the tasks assigned. In-house or out-house technicians. You do not dodge or fulfill your compliance responsibilities by signing a Purchase Order!
  56. 56. Qualification & Training of Maintenance Technicians <ul><li>PM Training </li></ul><ul><li>Sites may have thousands of PM procedures, making training on each PM impossible </li></ul><ul><li>However, PMs are made up of generic tasks – lube bearings, check alignment, check belts, etc. </li></ul><ul><li>If it can be demonstrated that the tech has had some basic training in the mechanical skills required, individual PM training may not be necessary. </li></ul><ul><li>Specialized equipment and functions require training. </li></ul>
  57. 57. Qualification of Outside Contractors Outside contractor organizations require qualification, the level of which depends on the level of support of field personnel. Example. A general tin-knocker company does not support field personnel technically and requires less rigor than a HEPA testing company providing test instruments and equipment and specialized training.

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