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Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
Advanced gm ps  for 21st century from regulatory perspectives
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Advanced gm ps for 21st century from regulatory perspectives

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Continuous changes of Regulations and GMP Guidelines

Continuous changes of Regulations and GMP Guidelines

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  • 1. ADVANCED GMPs for 21st Century Regulatory PerspectiveMr.J.RamniwasFounder and CEOSAI PHARMA SOLUTIONS INC. VADODARA
  • 2. Outline Changing Paradigm for GMPs 21st Century Initiatives Concept of Modern Quality Systems Basis of Advanced GMPs Quality System Approach What’s new to meet challenges GMP Improvements Global Registration Requirements Expectations Summary J.Ramniwas 2
  • 3. Changing Paradigm for GMPsProduct Process Systems -1970 1980 - 1990 21st [QC] [QA] Century [QS] J.Ramniwas 3
  • 4. Background of FDA’s 21st Century InitiativesLimited resources and increased volume of work August 2002 – FDA announced the Pharmaceutical cGMPs for the 21st Century – A Risk Based Approach Focus on the greatest potential risk to the public FDA’s intent to integrate quality systems and risk management approaches - to modernize FDA’s regulations Encourage industry to adopt modern and innovative manufacturing technologies as well as modern quality system approaches Necessary to harmonize the cGMPs with other non- U.S. pharmaceutical regulatory systems Need to harmonize with FDA’s own medical device quality systems regulations J.Ramniwas 4
  • 5. Background of FDA’s 21st Century Initiatives contd...Encourage Risk-Based approaches which focus on critical elements Ensure FDA’s Review, Compliance and Inspection Policies –based on state-of-art pharmaceutical science! Risk-Based Approach to Manufacturing and Regulation•#Pharmaceutical Inspectorate– Experienced Field Investigators•#Process Analytical Technology (PAT) Guidance– Real-time measurements•#Process Validation Guidance– Life Cycle Approach - Built-in Quality, not tested into product•#21 CFR 11 Electronic Records Guidance•#Quality Systems Guidance - September 2006 – FDA issued the finalversion of the “,-./0123#456#71/-896:#51#;-0<.9:#=:893>8#?@@6502A#95Pharmaceutical cGMP Regulations”•#Systems-Based Inspection•#6 systems J.Ramniwas 5
  • 6. Philosophy of cGMP andModern Quality SystemsQuality should be built intothe product, and testingalone cannot be reliedon to ensure productquality. J.Ramniwas 6
  • 7. IA5-FA#,GH#.8#0#<3F0<#01/#63F-<0956:#EA5-FA#,GH#.8#0#<3F0<#01/#63F-<0956:#requirementK#.98#630<#.>@5690123#.8#.1#requirementJ#.98#630<#.>@5690123#.8#.1#protecting the health and ensuring theconfidence of those who use theproducts we maL3 maM3 J.Ramniwas 7
  • 8. A. Management Responsibilities Contd.. j Structure the organization to ensure the assigned authorities and responsibilities l k Organizational structure is documented n m Support the total quality model p o Quality Systems departments have equal standing with other departments within an organization r q The Quality Manager has the authority to detect problems, implement solutions, and provide prompt feedback on quality issues to the organization. organization. J.Ramniwas
  • 9. A. Management Responsibilities Contd.. Play a key role in the design, implementation, and management of a robust quality systems. t s Align quality plans with company’s visions and mission v u Actively participate in Management Review meetings – to ensure continuing suitability, adequacy and effectiveness x w Articulate their vision of and commitment to quality to all levels of the organization. z y Advocate continuous improvement of the operation of Quality System •#Strong •#Strong and visible support for the quality system •#Internal •#Internal communication on quality issues at all levels € • Commit necessary resources J.Ramniwas
  • 10. A. Management Responsibilities Contd.. ‚ • Management controls are always reviewed by FDA •#CAPA •#CAPA •#People •#People qualifications •#Change •#Change control •#Validation •#Validation J.Ramniwas
  • 11. B. RESOURCES. Œ ‹ General Arrangements Personnel Development – Communicative Facilities and Equipment Control Outsourced Operations J.Ramniwas
  • 12. B. RESOURCES Contd...• Appropriate allocation of resources intended purpose – collection, storage, examination of in-process, stability, and reserve samples in- Personnel knowledge -solving and communicative culture – Education, training and experience – GMP J.Ramniwas
  • 13. C. MANUFACTURING! Design, develop and document Product and Processes •#$%&()* •#-./012)3)4.2 •#7(4)4/38#&(./***;: Examine Inputs <#=3)(438* >#=3)(438*@? Perform and Monitor A&(3)4.2* B&(3)4.2* •#$2)4(#D(.E0/)#F4G#7H/8 •#7(4)4/38#D(./***#– N3(43M484)H •#7(4)4/38#D(./***# – L3(43M484)H •#P)3)4*)4/38#D(./**#7.2)(.8#QPD7R •#DUV#– •#DUV#– Monitor & reduce QC testingYX Address Nonconformities J.Ramniwas
  • 14. C. MANUFACTURING Contd... • Ž Address Nonconformities •#Investigations, •#Investigations, conclusion and follow -up must follow- be documented. •# •#CAPA •#CAPA J.Ramniwas 2
  • 15. D. EVALUATION ACTVITIES– Analyze Data for Trends Conduct Internal Audits sustainability of Quality Systems – FDA is to refrain from both reviewing and copying reports or records that result from internal audits J.Ramniwas 2
  • 16. D. EVALUATION ACTVITIES Contd... Quality Risk Management •#Understanding •#Understanding of quality issues Effective decision- making decision- •#Risk •#Risk assessment and the severity of harm •#Engage •#Engage appropriate parties in risk assessment, e.g. regulatory affairs, customers, appropriate manufacturing personnel, development scientist, other stakeholders •#Risk •#Risk management – as a tool in the development of product specifications and critical process parameters •#Repeat •#Repeat risk assessment – to improve processes •#Proactive •#Proactive approach to quality Mitigate risk J.Ramniwas 22
  • 17. D. EVALUATION ACTVITIES Contd... Corrective Action significant problems do not recur Preventive Actions – Identify potential problems and root causes – Assess possible consequences – Consider appropriate actions CAPA level of detail of the evaluation process J.Ramniwas 23
  • 18. D. EVALUATION ACTVITIES Contd... £ Sources of recurring problems ¤ – Non-conformance reports and re Non- – Product Returns – Complaints – Internal and External audits – Trending data and risk assessment – Management review decisions •#Effectiveness •#Effectiveness of CAPA J.Ramniwas 24
  • 19. D. EVALUATION ACTVITIES Contd...  Promote Improvement •#´44329.µ31388#01/#344.2.312:#54#0#¶-0<.9:#8:893> •#=31.56#G010F3>319#– •#=31.56#G010F3>319#– involve in the evaluation of improvement process •#½33@#0¾63089#54#2A01F38#.1#82.319.4.2#/3µ3<5@>3198##### and regulatory requirements J.Ramniwas 25
  • 20. System Based cGMP Inspection 1. Quality System 2. Facility 6. Packaging Full Inspection the five systems Abbreviated Inspection system and one of the five systems J.Ramniwas 26
  • 21. State of Control Á À FD are developed, manufactured and held in a state of control, i.e. contribute to SISPQ Identity, Strength, Purity, Quality à  Detailed inspection of a system so that the findings reflect the state of control in that system for every product Å Ä If one of the six systems is out of control, the company is considered out-of-control out-of- J.Ramniwas 27
  • 22. It is not the strongest species thatsurviveÇsurviveÆ nor the most intelligentÈ but intelligentÉthe ones most responsive tochange”Charles Ì06Í.1 Î06Í.1See today with the eyes oftomorrow and change before thechange comes. comes. J.Ramniwas 28
  • 23. A Unique Feature of Indians ………#………Ð……#……Ñ#71/.01# Pharmaceutical Ó#71/.01#HA06>023-9.20<# Ô#71/.01#HA06>023-9.20<# Community has got fantastic flexibility to accept any challenge Õ#0/0@9#95# Ö#0/0@9#95# accept any challenge ×#0/0@9#95# Ø#0/0@9#95# Change ………………#………………Ñ# J.Ramniwas 29
  • 24. The PlanÜ1/368901/#9A3#63F-<09.518Û1/368901/#9A3#63F-<09.518•#´µ0<-093#ÍA363#:5-#063#µ368-8#ÍA363#:5- need to be•#Ì3µ3<5@#0#@65F60>#54#63¶-.63/#029.µ.9.38•#Ì3936>.13#ÍA363#:5-#133/#3â93610<#8-@@569•#H65/-23#0#82A3/-<3•#Ì3936>.13#9A3#2589 J.Ramniwas 3
  • 25. AdvantagesQuality by designLogical movement of personnel and materialControl at every stage of manufactureReduced risk of cross-contaminationScience based approachRisk based approachConfidence building J.Ramniwas 3
  • 26. Number ICH Guidelines Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients Q8 Pharmaceutical Development Q9 Quality Risk Management Q10 Quality Management System Q11 Development and Manufacturing of Drug Substances FDA Process Validation Guidelines J.Ramniwas 32
  • 27. è.FA36#<3µ3<8#54#3â@32909.518#.1#9A3following areas é Quality function Road Maps êA565-FA#63µ.3Í#01/#96018@06312:#.1# exhibit batches Compliance and Audits ë60.1.1F##01/#344329.µ31388 J.Ramniwas 33
  • 28.  ì31/56#?-/.98#01/#2369.4.209.51 Environment controls and contamination control í3Í#25123@98#.1#80>@<.1FJ#9389.1FJ# contamination control and cleaning validation J.Ramniwas 34
  • 29.  Quality of Operation reflectedthrough SOPs. IQ, OQ, PQ and higher levels ofscientific skills in validations Plant upgradations to the latestin Pharma standards. J.Ramniwas 35
  • 30. Quality of Water and HVAC systemsStringent controls for sterile products manufacture and asceptic manufactured products J.Ramniwas 36
  • 31. Recent Changes to PICProduct Quality Review (new clause 1.î Commenced on 1 ï01-06:#ðññòÑ ó01-06:#ðññòÑõô Requires annual quality reviews of all products to verify the consistency of the existing process to highlight trends ö#95 ÷#95 identify the need for productø@652388#.>@65µ3>3198Ñ productù@652388#.>@65µ3>3198Ñûú Requires reviews ofü ofý•þ Starting ‚ pacƒing materials„ especially from new sources…• Critical in•process controls and finished product results… in•• All batches that failed to meet specifications…• All significant deviations…• All changes to processes and analytical methods…• Marƒeting Authorisation variations…• Stability monitoring and any trends…• Recalls„ complaints and returns…• Qualification status of equipment ‚ utilities…• †echnical agreements… J.Ramniwas 37
  • 32. Upcoming Changes to PICOn-On-going stability (new clauses 6.2 – 6. Expected to commence on 1 June 2006 or soon after. Requires monitoring of stability after marketing, against a written protocol. Stability program should be extended to the end of the shelf life of the product. One batch per year of each product strength primary packaging type. Maintain a written summary of the data generated. J.Ramniwas 38
  • 33. Upcoming Changes to PICReference Samples "#$%&%&()#*+,-.%/#0%1#2%3#4 !65 Expected to commence on 1 June 2006 or soon after.87 Purpose and definitions.:9 Duration of storage.<; Size of samples.>= Storage conditions.@ EB(&&%#+CB%%,%&/D? AB(&&%#+CB%%,%&/DG OI+&#&)#J)#(#&I%#%K%&#)L#&I%#M.)/NB%#)L#+#F HI+&#&)#J)#(#&I%#%K%&#)L#&I%#M.)/NB%#)L#+#manufacturer. J.Ramniwas 39
  • 34. Upcoming Changes to PIC*#]^_Sterile Products (changes to Annex 1)QP Expected to commence on 1 June 2006 or soon after.SR Changes to some particle size limits for clean -room clean- classification purposes.UT Media fill limits specified for the validation of aseptic processing.W Pre-V Pre-sterilization bioburden assays required for aseptic processing and terminal sterilization.YX Grade A environment required forZ for[- Partially stoppered freeze drying vials.- Area where aluminium caps on aseptically filled vials arecrimped. J.Ramniwas 4
  • 35. Clean Room Environment Control Environment monitoring Scheduled programmes Establishment of limits and training. Sanitization, efficacy and monitoring methods. J.Ramniwas 4
  • 36. Activities for Advanced GMP Compliance Quality System Improvements– Calibration– Maintenance– Change Control– ZAP[#-43)4.2#1323]12)[#7UDU ^AP[#-43)4.2#1323]12)[#7UDU– Training– Complaints and recall procedures– Critical utility and environmental monitoring and sampling– Gowning, personnel monitoring– Material control– Cleaning , sterili_3)4.2#32E#*324)4_3)4.2 sterili`3)4.2#32E#*324)4_3)4.2 42
  • 37. Activities for Advanced GMP Compliance Documentation– Site Master File– Quality Manual– Master Batch Records– SOPs and associated forms– Trending Records– Log books– Approved critical drawings– Documentation to support CTD•#a%K%.)-,%&+.#-B)&)M)./#+J#B%-)B&/•#*&+d(.(&e#&%/&(C#-B)&)M)./#+J#B%-)B&/ J.Ramniwas 43
  • 38. Activities for Advanced GMP Compliance Upgrading Environments– layout of facility– Classification of environment– gh_2#L(.&%B#(&%CB(&e#&%/&(C ih_2#L(.&%B#(&%CB(&e#&%/&(C– Room pressure differentials– Air flows– Air velocity and volume– Monitoring and control– Access of materials and personnel J.Ramniwas 44
  • 39. Activities for Advanced GMP Compliance•#Upgrading l+&%B#*e/&%,/ m+&%B#*e/&%,/– Overall design– Instrumentation– Dead legs, Slopes– Valves– Backflow prevention– Materials, finishes– Spray balls, vent filters, sanitary heat exchangers– Sanitisation and operation– Recirculation, Flow rate– Monitoring and control J.Ramniwas 45
  • 40. Activities for Advanced GMP Compliance•#o-CB+J(C#p),-B%//%J#]+/#*e/&%,/– Moisture– reJB)M+Bd)s#t(.#uB%% veJB)M+Bd)s#t(.#uB%%– Particles– Filters– Materials– Monitoring J.Ramniwas 46
  • 41. Activities for Advanced GMP Compliance Upgrading Equipment•#– Equipment Capability – 6 sigma– Materials, Finishes– Local environment– Cleaning, sanitisation– Monitoring and control– “x+.(J+&+d(.(&e”#– 21 CFR Part 11 “x+.(J+&+d(.(&e”#– J.Ramniwas 47
  • 42. The Common Technical Document (CTD)•#|I%#p|a#(/#+#L)B,+&#+CB%%J#de#hos#o*2#+J### Japan for submitting applications for new products.•#•&#(/#)BC+(/%J#(#€#,)JN.%/D#^)JN.%#4#(/# unique to each region. Modules 2 to ‚#+B%# ƒ#+B%# common across all regions• Module 1 – Administrative Requirements•#^)JN.%#…#– ‰(CI#.%K%.#/N,,+B(%/#)L#ˆN+.(&es#•#^)JN.%#…#– ‡(CI#.%K%.#/N,,+B(%/#)L#ˆN+.(&es# Clinical and Non clinical J.Ramniwas 48
  • 43. The Common Technical Document (CTD)• Module Š#– Quality - Chemical, Pharmaceutical ‹#– and Biological Documentation•#^)JN.%#•#–•#^)JN.%#•#– Toxicological and Pharmacological (non clinical) study reports•#^)JN.%#€#–•#^)JN.%#€#– Clinical Study Reports J.Ramniwas 49
  • 44. The Common Technical Document (CTD)• Generally dossier must be in English or the language of the Reference Member State• eCTD format was obligatory. But now obligatory. mandatory• Mock up of packaging, specimen of packaging and leaflet also required in language of Reference Member State J.Ramniwas 5
  • 45. VALIDATION•#Usually a ma—)B#L+(.(C#L)B#,+e#,+NL+M&NB%B/ ma˜)B#L+(.(C#L)B#,+e#,+NL+M&NB%B/•#*&B+&%C(M#a)MN,%&+&()– Production of an overall Validation Master Plan and Validation Plans for specific areas.– Production of a validation schedule– Production of System Boundary drawings– System Impact Assessment J.Ramniwas 5
  • 46. VALIDATION• Design Qualification– GMP review of Facility Design– DQ (protocols execution and reports) of ma•)B maž)B Direct Impact Systems and Equipment• Equipment Facilities and Utilities Qualification– IQ, OQ, PQ Protocols execution and reports for Direct Impact Systems including ¡x2ps Critical ¢x2ps Utilities, Process Equipment and Laboratory Equipment J.Ramniwas 52
  • 47. VALIDATION• Validation– Protocols execution and reports for Process Simulation (Media Fills), Cleaning Validation, Process Validation and Method Validation¤K%B(L(M+&() Validation£K%B(L(M+&() J.Ramniwas 53
  • 48. Environment Monitoring Sterile AreasMonitoring Methods : Surface Monitoring Active Air Monitoring Passive Air Monitoring Particulate Monitoring J.Ramniwas 54
  • 49. Some of the points cited in theRegulatory Inspections  Restricted access to computers and data handling.  Total traceability of Unit operation in BMR with respect to machine no., room no., time logs, operation logs and verification J.Ramniwas 55
  • 50. Some of the points cited in theRegulatory Inspections Contd…..  Risk assessment for critical facilities and equipments which can cause product quality to be altered e.g. air handling systems in sterile product manufacture  Air handling system with single pass with HEPA filters not re-circulation type. J.Ramniwas 56
  • 51. Some of the points cited in theRegulatory Inspections Contd…..  Validation Master Plan, detailed execution through protocols and executive summary on the study.  100% identification of Raw Materials in QC  TSE/BSE certification and SOP for incoming materials assessment through vendor approval system J.Ramniwas 57
  • 52. Some of the points cited in theRegulatory Inspections Contd…..  Pest control, procedure with schematic diagrams, effectiveness of chemicals and disposal of dead rodents.  Water systems with respect to plant design, system validation, chemical and microbial attributes and monitoring of pesticides and radioactive traces. J.Ramniwas 58
  • 53. Laboratory Reference standards, working standards, instrument logs, column register, calibration, stability monitoring and instrument audit trials. Annual Reports on each product is scrutinized. J.Ramniwas 59
  • 54. Laboratory Contd… Deviations and change control mechanism thoroughly investigated. Approved suppliers list and its tally with vendor approval system. OOS handling. J.Ramniwas 6
  • 55. Laboratory Contd…Technical agreements and its executions.Sterility assurance in bulk APIs and dosage forms.Media simulation trials and its applicability to production run. J.Ramniwas 6
  • 56. Some of the USFDA Inspectionsand Non-complianceDeficiency in validation work.Process validation as well as analytical validation.Process validation not done on worst case simulation. J.Ramniwas 62
  • 57.  In a multiple product manufacturing site, effectiveness of cleaning validation not demonstrated through worst case in a multiproduct matrix. Back-up system of stability chamber inadequate. Inadequate temperature mapping in warehouses. J.Ramniwas 63
  • 58.  Inadequate validation of vacuum transfer system for cleaning operations. Changes in production, QC and warehouse without change control. Complaint investigation lacking depth, tracebility and time frame commitment. J.Ramniwas 64
  • 59. ADVANCED GMPs CONCERNS Lab Controls  SOPs Records and Reports  Reprocessing / Process Controls Reworks Equipment Cleaning  Ingredients controls Process Validation  Buildings and Water Systems Facilities Stability Programs  Training  Investigations J.Ramniwas 65
  • 60. «¬Dp+&%C)B(%/#)L#$%CN.+&)Be#p)M%B1. API -#a)/+C%#^LC Pending corrective actions ¥2. Change of Site 6. Previous deviations®D##u+M(.(&e#1(&IJB+1# persist and not informed¯D##u(B,#)&#B%+Je#)# ¦D##A+B(C#§%&&%B inspection call°D##•+J%±N+&%# ¨D##*%(©NB% ²/N-%BL(M(+.³##### response ªD##•—NM&() 66 J.Ramniwas
  • 61. 10. Insufficient 1´D##p),-)%&#)B# development data intermediate controls11. Buildings ¹#L+M(.(&(%/ 1µD##a%K(+&()#LB),#a^u##### NDA ¶#2·a212. Inadequate change control procedure 16. Deviation from monograph1ºD##p)&+,(+&() 1¸D##hK(B),%&+.# controls 67
  • 62. 1ÂD##g).J(C##+J## 2»D##tBC+(©+&() distribution 2¼D##$%M)BJ/##B%-)B&/1ÃD##§+d#M)&B)./20. Master record non- 26. Reprocessing specific or deficient 2½D##*-%M(L(M+&()/21. Packaging and labeling controls 2¾D##*&+d(.(&e#-B)CB+,22. Production Ä##### 2¿D##*t_/#.+MÀ(C#)B#### process controls inadequate2ÅD##ˆ2#LNM&()/ Á¬D##|B+((C J.Ramniwas 68
  • 63. Ì4D##2_•#_B)M%//# ÆÇD##^%J(+#L(../ validation ȦD##*e/&%,#•ˆ##tˆÍ…D##p),-N&%B#K+.(J+&() ɨD##*M+.%-up validationΊD##h±N(-,%&#M.%+(C## failure validation Ê D##x+.(J+&()#-B)&)M).#Ï•D Equipment inadequate qualification ˬD#A+&%B#/e/&%,####ЀD##gx2p#K+.(J+&() validation J.Ramniwas 69
  • 64. GMP -ImprovementsRenovation of facilitiesÒÑ PlantÔ Ö+&%BÓ Õ+&%BØ Úx2p× Ùx2pÜÛ StorageÞÝ Disposalàß Training of personnelâá Upgrading equipmentäã Identifying critical stepsæ In-å In-process parametersèç Validationêé Self inspection J.Ramniwas 7
  • 65. Global Registration Requirements GMP •Basic prerequisite ˆ Semi•regulated countries also need GMP compliant Semi• facilities ˆ Many countries require pre•approved facilities pre• ˆ General GMP inspection of the facility ˆ Some countries inspect the product manufacturing line before granting marƒeting authorisation ˆ Product specific GMP inspection J.Ramniwas 7
  • 66. †he ExpectationsThe evaluation of the risk should ultimately link back to the potential risk to the patient. patient.The extent of the risk management process should be commensurate with the level of risk associated with the decision. decision.A more robust data set will lead to lower uncertainty. uncertainty.It is essential to have a clear delineation of the risk question. question.Risk management should be an iterative process. process. J.Ramniwas 72
  • 67. †he Expectations Contd……People who apply risƒ management should have the appropriate training„ sƒills and experience… experience…†he risƒ management process should be appropriately documented and verifiable… verifiable…Šefining specifically the risƒ management problem or question„ including the assumptions leading to the question… question…Assembling bacƒground information and data on the ha‹ard„ harm or human health impact relevant to the assessment… assessment… J.Ramniwas 73
  • 68. †he Expectations Contd……Identifying the necessary resources„ members of the team who have the appropriate expertise„ with the leader clearly identified… identified…Asƒing the right risƒ assessment questions… questions…Stating clearly the assumptions in the risƒ assessment… assessment…Assessing the quality and sufficiency of relevant data… data…Specifying and deliverables for the risƒ assessment… assessment… J.Ramniwas 74
  • 69. SummaryUse regular internal audits to identify those areas that require attention to comply with the GMP Guides. Guides. Utilise external consultant(s) if necessary. necessary.Prioritise implementation of corrective actions using a risk based approach. approach. Establish a budget to enable appropriate corrective actions to be implemented. implemented. ë%%- watch on Regulatory authority websites for ì%%- changes in GMPs coming up in the future. future. Establish industry networking system to monitor and report on inspection trends by GMP regulators. regulators. 75
  • 70. †hanƒ you for your attentionŒ Any Questions•Contact for consulting or technical advisory serviceseJ.RAMNIWASFounder & CEOSAI PfUg=U#PAFhViAjP#ij7kPhone No 76l0(#=.)).m#P)3()#).#G424*n[#(H)n42]#42#M)o2mk

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