New EU Requirements for Qualification & Validation
48 likes10,791 views
This document presents an overview of the updated Annex 15 of the EU GMP Guide concerning qualification and validation in the pharmaceutical industry, highlighting significant changes that will take effect from October 1, 2015. Key points include the replacement of 'validation' with 'qualification and validation,' the elimination of retrospective validation, and the emphasis on quality risk management. It also discusses good documentation practices and the lifecycle approach to validation activities, ensuring robust product quality and compliance with current GMP standards.
New EU Requirements for Qualification & Validation
- 1. This presentation is prepared 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. 4/3/2015 1
- 2. This presentation is compiled from freely available resources like the website of EU, specifically “EU GMP Guide-Annex 15 Qualification & Validation” “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. 4/3/2015 2 Drug Regulations : Online Resource for Latest Information
- 3. Updated version of Annex 15 ◦ Qualification and Validation Draft released in February 2014 Final version released on the 30th of March , 2015 Will be effective on 01 October 2015 4/3/2015 3
- 4. May be used as supplementary optional guidance for active substances without introduction of additional requirements to EudraLex, Volume 4, Part II. Retrospective validation is no longer an acceptable approach The term “validation” has been replaced with “qualification and validation” to reflect the true intent of the Annex 15 in several instances 4/3/2015 4
- 5. An “equivalent document” to a VMP may be used for qualification and validation planning VMP no longer needs to include ◦ Protocol and report templates, ◦ scheduling and planning information ◦ Confirmation of materials and suppliers used 4/3/2015 5
- 6. For large and complex projects separate validation plans may be used The importance of Quality Risk Management is evident Risk assessment to be repeated if further knowledge and understanding is gained from any changes during the project phase or during commercial production, 4/3/2015 6
- 7. Data integrity is also mentioned were “appropriate checks” needs to be built into qualification and validation tasks “to ensure the integrity of all data obtained”. 4/3/2015 7
- 8. Current version of Annex 15 of the EU Guide to GMP ◦ Originally published in September 2001 ◦ Significant changes in the GMP environment ◦ Advancements in manufacturing technology and continuous manufacture processes. 4/3/2015 8
- 9. ◦ Many changes to other Chapters and Annexes which have an impact on Annex 15 ◦ Current version of the US FDA Guide on Process Validation, ◦ Approaches in ASTM E2500-07 “Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment “ All the above has justified the change 4/3/2015 9
- 10. This revision to Annex 15 takes into account ◦ Changes to Other sections of the EudraLex, Volume 4, Part I ◦ Relationship to Part II ◦ Annex 11 ◦ ICH Q8, Q9, Q10 and Q11 ◦ QWP guidance on process validation ◦ Changes in manufacturing technology 4/3/2015 10
- 11. Annex describes Principles of Qualification and Validation Applicable to ◦ Facilities ◦ Equipment ◦ Utilities and processes ◦ Manufacture of medicinal products May also be used as supplementary optional guidance for active substances without introduction of additional requirements to EudraLex, Volume 4, Part II 4/3/2015 11
- 12. Qualification & Validation ◦ GMP requirement ◦ Control critical aspects of particular operations ◦ Applicable over the life cycle of product and process ◦ Document any planned changes to the facilities, equipment, utilities and processes, which may affect the quality of the product, and the impact on the validated status or control strategy assessed. 4/3/2015 12
- 13. Qualification & Validation ◦ Validate computerised systems :Annex 11. ◦ Use concepts and guidance of ICH Q8, Q9, Q10 and Q11 4/3/2015 13
- 14. Qualification & Validation ◦ Apply quality risk management approach throughout the lifecycle ◦ Determine scope and extent of qualification and validation on risk assessment of the facilities, equipment, utilities and processes. ◦ Document the risk assessment ◦ Retrospective validation is no longer considered an acceptable approach. 4/3/2015 14
- 15. Qualification & Validation ◦ Data obtained from sources outside of the manufacturers own programmes May be used Justify this approach Adequate assurance that controls were in place throughout the acquisition of such data. 4/3/2015 15
- 16. Qualification & Validation ◦ Plan all activities ◦ Implement the life cycle approach ◦ Consider Facilities Equipment Utilities Process Product 4/3/2015 16
- 17. Qualification & Validation ◦ Performed by suitably trained personnel ◦ Follow approved procedures ◦ Qualification/validation personnel should report as defined in the pharmaceutical quality system ◦ Not essential to be a quality management or a quality assurance function. ◦ Appropriate quality oversight over the whole validation life cycle is essential 4/3/2015 17
- 18. Qualification & Validation ◦ Define key elements of the site qualification and validation ◦ Document in a validation master plan (VMP) or equivalent document. 4/3/2015 18
- 19. Qualification & Validation ◦ VMP or equivalent document ◦ Define qualification/validation system ◦ Include or reference information on at least the following: 4/3/2015 19
- 20. Qualification & Validation Include or reference information on at least the following: ◦ Qualification and Validation policy ◦ Organisational structure ◦ Roles and responsibilities for qualification and validation activities 4/3/2015 20
- 21. Qualification & Validation Include or reference information on at least the following: ◦ Summary of the facilities, equipment, systems, processes on site ◦ Qualification and validation status ◦ Change control and deviation management for qualification and validation ◦ Guidance on developing acceptance criteria ◦ References to existing documents ◦ Strategy, including requalification, where applicable 4/3/2015 21
- 22. Qualification & Validation ◦ For large and complex projects, ◦ Added importance to planning ◦ Separate validation plans may enhance clarity 4/3/2015 22
- 23. Qualification & Validation ◦ Use quality risk management approach ◦ Repeat Risk assessment with increased knowledge & Changes Project Phase Commercial Phase ◦ Document the way in which risk assessments are used 4/3/2015 23
- 24. Qualification & Validation ◦ Incorporate appropriate checks ◦ Ensure the integrity of all data obtained 4/3/2015 24
- 25. Good Documentation Practices Important to support knowledge management Implement throughout the product lifecycle All documents should be approved and authorised by appropriate personnel as defined in the pharmaceutical quality system. Define the inter-relationship between documents in complex validation projects Prepare validation protocols which defines the critical systems, attributes and parameters and the associated acceptance criteria. 4/3/2015 25
- 26. Good Documentation Practices Documents may be combined together, where appropriate e.g. installation qualification (IQ) and operational qualification (OQ). 4/3/2015 26
- 27. Good Documentation Practices Any significant changes to the approved protocol during execution Acceptance criteria Operating parameters Document as a deviation Justify scientifically 4/3/2015 27
- 28. Good Documentation Practices Record results not meeting pre-defined acceptance criteria as a deviation Investigate all devotions Discuss any implications for the validation in the report 4/3/2015 28
- 29. Good Documentation Practices Each stage should have a formal release before proceeding to next stage Release should be authorised by relevant responsible personnel Release may be a part of validation report or as a separate summary document Conditional approval to proceed to the next qualification stage possible when Certain acceptance criteria or deviations have not been fully addressed There is a documented assessment that there is no significant impact on the next activity. 4/3/2015 29
- 30. Qualification activities Consider all stages Initial development of the user requirements specification through to End of use of the equipment, facility, utility or system. 4/3/2015 30
- 31. The main stages and some suggested criteria which could be included in each stage are indicated in subsequent slides: although this depends on individual project circumstances and may be different 4/3/2015 31
- 32. User requirements specification (URS) Define specification in a URS and/or a functional specification for Equipment Facilities Utilities or systems The essential elements of quality need to be built in at this stage GMP risks if any should be mitigated to an acceptable level. URS should be a point of reference throughout the validation life cycle. 4/3/2015 32
- 33. Design qualification (DQ) The next element in the qualification of equipment, facilities, utilities, or systems Demonstrate compliance of the design with GMP Document compliance Verify requirements of the user requirements specification during the design qualification. 4/3/2015 33
- 34. Factory acceptance testing (FAT) /Site acceptance testing (SAT) Equipment may be evaluated at the vendor prior to delivery. Confirm compliance with URS/functional specification prior to installation at the vendor site 4/3/2015 34
- 35. Factory acceptance testing (FAT) /Site acceptance testing (SAT) Documentation review & some tests could be performed at the FAT or other stages These tests need not be repeated on site at IQ/OQ if functionality is not affected by transport and installation. 4/3/2015 35
- 36. Factory acceptance testing (FAT) /Site acceptance testing (SAT) FAT may be supplemented by the execution of a SAT following the receipt of equipment at the manufacturing site. 4/3/2015 36
- 37. Installation qualification (IQ) Perform IQ on Equipment Facilities Utilities Systems. 4/3/2015 37
- 38. Installation qualification (IQ) IQ should include, but is not limited to the following: Verification of the correct installation of components, instrumentation, equipment, pipe work and services against the engineering drawings and specifications; Verification of the correct installation against pre-defined criteria; Collection and collation of supplier operating and working instructions and maintenance requirements; Calibration of instrumentation Verification of the materials of construction. 4/3/2015 38
- 39. Operational qualification (OQ) OQ normally follows IQ May be performed as a combined Installation/Operation Qualification (IOQ). Depends on the complexity of the equipment 4/3/2015 39
- 40. Operational qualification (OQ) OQ should include but is not limited to the following: Tests that have been developed from the knowledge of processes, systems and equipment to ensure the system is operating as designed; Tests to confirm upper and lower operating limits, and /or “worst case” conditions. 4/3/2015 40
- 41. Performance qualification (PQ) PQ should normally follow the successful completion of IQ and OQ. Could also be performed in conjunction with OQ or Process Validation. 4/3/2015 41
- 42. Performance qualification (PQ) PQ should include, but is not limited to the following: Tests using Production materials, Qualified substitutes or Simulated product proven to have equivalent behaviour Normal operating conditions Worst case batch sizes. Justify the frequency of sampling used to confirm process control 4/3/2015 42
- 43. Performance qualification (PQ) PQ should include, but is not limited to the following: Tests should cover the operating range of the intended process No need for this if documented evidence from the development phases confirming the operational ranges is available. 4/3/2015 43
- 44. RE-QUALIFICATION Evaluate at an appropriate frequency to confirm that following remain in a state of control Equipment Facilities Utilities Systems 4/3/2015 44
- 45. RE-QUALIFICATION Justify requalification period Define criteria for reevaluation Assess the possibility of small changes over time 4/3/2015 45
- 46. General Principles Applicable to the manufacture of all pharmaceutical dosage forms. Initial validation of new processes Subsequent validation of modified processes Site transfers and ongoing process verification 4/3/2015 46
- 47. General Principles Robust product development process required to enable successful process validation This guidance should be used in conjunction with the current EMA guideline on Process Validation for Finished Products. 4/3/2015 47
- 48. General Principles Guideline on Process Validation for Finished Products (LINK) Guidance on information and data to be provided in the regulatory submission only. However GMP requirements for process validation continue throughout the lifecycle of the process Apply this approach to link product and process development. 4/3/2015 48
- 49. General Principles Manufacturing processes may be developed using a Traditional approach Continuous verification approach 4/3/2015 49
- 50. General Principles Before any product is released to the market & irrespective of the approach used Processes must be shown to be robust Ensure consistent product quality 4/3/2015 50
- 51. General Principles Traditional approach Only prospective validation programme prior to certification of the product. Retrospective validation is no longer an acceptable approach. 4/3/2015 51
- 52. General Principles New products Cover all intended marketed strengths Cover all sites of manufacture Bracketing could be used. Justify based on Extensive process knowledge from the development stage An appropriate ongoing verification programme 4/3/2015 52
- 53. General Principles Site Transfer Transferred from one site to another Within the same site, 4/3/2015 53
- 54. General Principles Site Transfer Number of validation batches could be reduced by the use of a bracketing approach. Justify based on Existing product knowledge, Content of the previous validation Use bracketing for Different strengths Batch sizes Pack sizes Container types 4/3/2015 54
- 55. General Principles Site Transfer of Legacy products Manufacturing process and controls must comply with the marketing authorisation Meet current standards for marketing authorisation for that product type. If necessary, variations to the marketing authorisation should be submitted. 4/3/2015 55
- 56. General Principles Attributes and parameters Important for ensuring the validated state and acceptable product quality Process validation should establish whether these can be consistently met by the process Document the basis for identifying criticality of parameters & attributes 4/3/2015 56
- 57. General Principles Process validation batches Same size as the intended commercial scale batches Justify use of any other batch sizes 4/3/2015 57
- 58. General Principles Development studies & Process knowledge Basis of all validation activities For all products Irrespective of validation Should be accessible to the manufacturing site, Other wise justify 4/3/2015 58
- 59. General Principles Process validation batches Production personnel Development personnel Other site transfer personnel Use only trained personnel Manufacture in accordance with GMP Use approved documentation Production personnel should facilitate product understanding 4/3/2015 59
- 60. General Principles Qualify suppliers of critical starting and packaging materials prior to manufacture Otherwise Justify based on of quality risk management principles Document justification 4/3/2015 60
- 61. General Principles Design Space & Mathematical Models Could be used for Process control strategy Following should be available Underlying process knowledge Development of any mathematical models Justification 4/3/2015 61
- 62. General Principles Release of Validation batches to the Market Pre-define Manufacture should fully comply with GMP Validation acceptance criteria Continuous process verification criteria (if used) Marketing authorisation Clinical trial authorisation. 4/3/2015 62
- 63. General Principles Investigational medicinal products (IMP), Refer to Annex 13. 4/3/2015 63
- 64. Concurrent validation Routine production starts before completion of validation Concurrent validation can be used under exceptional circumstances A strong benefit-risk ratio for the patient required Justify decision to carry out concurrent validation Document the decision in the VMP for visibility Decision should be approved by authorised personnel 4/3/2015 64
- 65. Concurrent validation Have sufficient data to support a conclusion that Any given batch of product is uniform Meets the defined acceptance criteria. Document the results and conclusion formally Document should be available to the Qualified Person prior to certification of the batch 4/3/2015 65
- 66. Traditional process validation Number of batches of the finished product are manufactured under routine conditions to confirm reproducibility. 4/3/2015 66
- 67. Traditional process validation Number of batches manufactured & Number of samples taken Use Quality Risk Management principles Allow the normal range of variation and trends to be established Provide sufficient data for evaluation. 4/3/2015 67
- 68. Traditional process validation Number of batches manufactured & Number of samples taken Determine and justify the number of batches necessary to demonstrate a high level of assurance that the process is capable of consistently delivering quality product. 4/3/2015 68
- 69. Traditional process validation Generally acceptable Without prejudice to earlier requirement Minimum of three consecutive batches manufactured under routine conditions could constitute a validation of the process 4/3/2015 69
- 70. Traditional process validation Generally acceptable Alternative number of batches may be justified based on Whether standard methods of manufacture are used Whether similar products or processes are already used at the site. 4/3/2015 70
- 71. Traditional process validation Generally acceptable Supplement an initial validation exercise with three batches with further data obtained from subsequent batches as part of an on-going process verification exercise. 4/3/2015 71
- 72. Traditional process validation Process validation protocol should be prepared which defines Critical process parameters (CPP), Critical quality attributes (CQA) Associated acceptance criteria Base this on development data or documented process knowledge. 4/3/2015 72
- 73. Traditional process validation Process validation protocols should include, but are not limited to the following: 1. A short description of the process and a reference to the respective Master Batch Record; 2. Functions and responsibilities; 3. Summary of the CQAs to be investigated; 4. Summary of CPPs and their associated limits; 4/3/2015 73
- 74. Traditional process validation Process validation protocols should include, but are not limited to the following: 4. Summary of other (non-critical) attributes and parameters which will be investigated or monitored during the validation activity, and the reasons for their inclusion; 5. List of the equipment/facilities to be used (including measuring/monitoring/recording equipment) together with the calibration status; 6. List of analytical methods and method validation, as appropriate 4/3/2015 74
- 75. Traditional process validation Process validation protocols should include, but are not limited to the following: 7. Proposed in-process controls with acceptance criteria and the reason(s) why each in-process control is selected; 8. Additional testing to be carried out with acceptance criteria; 9. Sampling plan and the rationale behind it; 10. Methods for recording and evaluating results; 11. Process for release and certification of batches (if applicable) 4/3/2015 75
- 76. Continuous process verification Can be used as an alternate approach for traditional process validation for Products developed by a quality by design approach Scientifically established control strategy during development A strategy which provides a high degree of assurance of product quality 4/3/2015 76
- 77. Continuous process verification Define the method by which the process will be verified Put in place a science based control strategy for the required attributes to confirm product realisation for Incoming materials Critical quality attributes Critical process parameters 4/3/2015 77
- 78. Continuous process verification Put in place a science based control strategy for the required attributes to confirm product realisation Include regular evaluation of the control strategy. Process Analytical Technology and multivariate statistical process control may be used as tools. 4/3/2015 78
- 79. Continuous process verification Determine and justify the number of batches necessary to demonstrate a high level of assurance that the process is capable of consistently delivering quality product. The general principles presented earlier still apply. 4/3/2015 79
- 80. Hybrid approach A hybrid of the traditional approach and continuous process verification approach Could be used where there is Substantial amount of product and process knowledge Understanding which has been gained from manufacturing experience and historical batch data. 4/3/2015 80
- 81. Hybrid approach Could be used Even if the product was initially validated using a traditional approach For any validation activities after changes During ongoing process verification 4/3/2015 81
- 82. Ongoing Process Verification during Lifecycle Applicable to all three approaches to process validation mentioned earlier, i.e. Traditional, Continuous or Hybrid. 4/3/2015 82
- 83. Ongoing Process Verification during Lifecycle Monitor product quality Ensure that a state of control is maintained throughout the product lifecycle Evaluate relevant process trends 4/3/2015 83
- 84. Ongoing Process Verification during Lifecycle Periodically review extent and frequency of ongoing process verification. Any point during the life cycle appropriate to modify the requirements taking into account the current level of process understanding and process performance. 4/3/2015 84
- 85. Ongoing Process Verification during Lifecycle Conduct under an approved protocol or equivalent documents Prepare a corresponding report Document the results obtained Use Statistical tools to support any conclusions of variability and capability of a process Ensure a state of control 4/3/2015 85
- 86. Ongoing Process Verification during Lifecycle Use throughout the product lifecycle Support the validated status of the product as documented in the Product Quality Review. Consider Incremental changes over time Need for any additional actions, e.g. enhanced sampling, should be assessed. 4/3/2015 86
- 87. Applicable to Finished medicinal products Investigational medicinal products Bulk product Samples Above should be transported as defined in the Marketing authorisation the approved label product specification file As justified by the manufacturer 4/3/2015 87
- 88. Challenging due to the variable factors involved Define transportation routes clearly Consider seasonal and other variations during verification 4/3/2015 88
- 89. Perform a risk assessment Consider Impact of variables Transportation process Conditions which are continuously controlled or monitored, Delays during transportation Failure of monitoring devices Topping up liquid nitrogen Product susceptibility Any other relevant factors 4/3/2015 89
- 90. Variable conditions are expected during transportation Therefore perform continuous monitoring & recording of critical environmental conditions Justify if this is not done Document the justification 4/3/2015 90
- 91. Qualify primary and secondary packaging equipment for finished and bulk products Variation in equipment processing parameters These have significant impact on the integrity and correct functioning of the pack, Blister strips, sachets and sterile components, therefore 4/3/2015 91
- 92. Qualify primary packing equipment Qualify the minimum and maximum operating ranges defined for the critical process parameters Temperature Machine speed Sealing pressure Any other factors 4/3/2015 92
- 93. Perform qualification using the qualification steps described earlier following Seam Water Air Other gases 4/3/2015 93
- 94. Qualification Should reflect any seasonal variations Intended use of the utility 4/3/2015 94
- 95. Perform a risk assessment if there could be direct or indirect contact with the product, Heating, ventilation and air-conditioning (HVAC) systems Through heat exchangers Mitigate any risks of failure 4/3/2015 95
- 96. Validate all analytical test methods used in Qualification Validation Cleaning exercises Validate with an appropriate detection and quantification limit as defined in Chapter 6 of the EudraLex, Volume 4, Part I. 4/3/2015 96
- 97. Microbial testing of product Validate method to confirm that the product does not influence the recovery of microorganisms. 4/3/2015 97
- 98. Microbial testing of surfaces in clean rooms Perform validation to confirm that sanitising agents do not influence the recovery of microorganisms. 4/3/2015 98
- 99. Perform cleaning validation Confirm the effectiveness of all cleaning procedure for all product contact equipment. Simulating agents may be used with appropriate scientific justification. Similar types of equipment may be grouped together Provide a justification of the specific equipment selected for cleaning validation 4/3/2015 99
- 100. Visual check for cleanliness is an important part of the acceptance criteria Do not use this criterion alone Do not repeat cleaning and retesting until acceptable residue results are obtained not considered an acceptable approach 4/3/2015 10 0
- 101. Programme may take some time to complete Validation with verification after each batch may be required for some products, e.g. investigational medicinal products. Collect sufficient data from verification to support a conclusion that the equipment is clean and available for further use. 4/3/2015 101
- 102. Validation should consider Level of automation in the cleaning process. Automatic process Validate the specified normal operating range of the utilities and equipment 4/3/2015 102
- 103. Perform assessment of all cleaning processes Determine variable factors which influence cleaning effectiveness and performance Operators Level of detail in procedures such as rinsing times etc. Use worst case situations for cleaning validation studies identified 4/3/2015 103
- 104. Limits for the carryover of product residues should be based on a toxicological evaluation Document justification in a risk assessment Include all the supporting references. Establish limits for the removal of any cleaning agents used. Consider the potential cumulative effect of multiple items of equipment in the process equipment train to determine acceptance criteria. 4/3/2015 104
- 105. Limits for the carryover of product residues should be based on a toxicological evaluation Therapeutic macromolecules and peptides degrade and denature (when exposed to pH extremes and/or heat ) May become pharmacologically inactive. A toxicological evaluation may therefore not be applicable in these circumstances. 4/3/2015 105
- 106. Limits for the carryover of product residues should be based on a toxicological evaluation When testing for specific product residues is not feasible other representative parameters may be selected Total organic carbon (TOC) Conductivity 4/3/2015 106
- 107. Consider the risk presented by Microbial contamination Endotoxin contamination 4/3/2015 107
- 108. Consider Influence of the time between manufacture and cleaning between cleaning and use Based on this define for the cleaning process Dirty hold time Clean hold time 4/3/2015 108
- 109. For campaign manufacture consider Impact on the ease of cleaning at the end of the campaign Maximum length of a campaign (in time and/or number of batches) 4/3/2015 109
- 110. Worst case product approach Provide a scientific rationale for Selection of the worst case product Impact of new products to the site assessed Criteria for determining worst case Solubility Cleanability Toxicity Potency 4/3/2015 110
- 111. Cleaning validation protocols Specify or reference the locations to be sampled Rationale for the selection of these locations Define the acceptance criteria 4/3/2015 111
- 112. Sampling Swabbing Rinsing Other means depending on the production equipment. Sampling materials and method should not influence the result. Demonstrate recovery from all product contact materials sampled in the equipment with all the sampling methods used. 4/3/2015 112
- 113. Cleaning procedure Perform an appropriate number of times Base this on a risk assessment Meet the acceptance criteria in order to prove that the cleaning method is validated. 4/3/2015 113
- 114. Cleaning process Ineffective Not appropriate for some equipment Use Dedicated equipment Other appropriate measures for each product Refer chapters 3 and 5 of EudraLex, Volume 4, Part I. 4/3/2015 114
- 115. Manual cleaning of equipment Confirm effectiveness of the manual process at a justified frequency. 4/3/2015 115
- 116. Control of change Important part of knowledge management Handle within the pharmaceutical quality system 4/3/2015 116
- 117. Put written procedures in place & describe the actions to be taken if a planned change is proposed to Starting material Product component Process Equipment Premises Product range Method of production or testing Batch size Design space Any other change during the lifecycle that may affect product quality or reproducibility. 4/3/2015 117
- 118. When Design space is used Consider the impact on changes to the design space as registered in M A Assess need for any regulatory actions 4/3/2015 118
- 119. Use Quality Risk Management to evaluate planned changes to determine the potential impact on Product quality Pharmaceutical quality systems Documentation Validation Regulatory status Calibration Maintenance Any other system Avoid unintended consequences Plan for any necessary process validation, verification or requalification efforts. 4/3/2015 119
- 120. Changes Authorised Approved Responsible persons Relevant functional personnel Follow the pharmaceutical quality system. 4/3/2015 120
- 121. Review supporting data Confirm impact of change has been demonstrated prior to final approval. 4/3/2015 121
- 122. Perform an evaluation of the effectiveness of change Confirm that the change has been successful 4/3/2015 122
- 123. This presentation is compiled from freely available resources like the website of EU, specifically “EU GMP Guide-Annex 15 Qualification & Validation” “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. 4/3/2015 12 3 Drug Regulations : Online Resource for Latest Information