Testo Expert Knowledge The GxP Dictionary 1st edition Definitions relating to GxP and Quality Assurance 1 Note: Some of the information contained in this GxP Dictionary does not apply equally to all countries. Depending on the respective local legislation, other definitions may apply to certain terms and topics. The sections affected are not separately identified. 2 Foreword Efficacy, identity and purity are qual- This GxP Dictionary explains the ity attributes, which are required of majority of terms relating to GxP, products from the GMP-regulated qualification, validation and quality environment. The term “Good Manu- assurance. facturing Practice” sums up the quality assurance requirements from national It is intended as a compact reference and international regulations and laws. guide and aid for all those involved Other GxP forms have now been de- in GMP, and does not purport to be veloped, whose scope also expands complete. to adjacent sectors such as medical devices and life sciences. Testo SE & Co. KGaA The complex requirements of the “GMP compliance” generate a variety of specific concepts and abbrevia- tions. 3 GxP Dictionary Contents Contents 10 Terms and Definitions C 15 Calibration 0-9 15 CAPA 10 21 CFR 210/211 15 Capacity Test 10 483 15 CEP (Certificate of Suitability of Monographs of the European A Pharmacopoeia) 11 Action Limits 15 CFR 11 Active Pharmaceutical Ingredient 15 CFU (Colony-Forming Unit) (API) 16 cGMP 11 ADI (Acceptable Daily Intake) 16 Challenge Test 11 Airlock Concept 16 Change Control 11 Annex 16 Clean Corridor Principle 12 Annual Product Review (APR) 16 Cleaning Validation 12 API 17 Cleanroom 12 APR 17 Cleanroom Classes 12 Audit 18 Cleanroom Principle 12 Audit Trail 18 Compliance 12 Authorization 18 Computer System/ Software Validation (CSV) B 18 Computer Validation 13 Batch 18 Concurrent Validation 13 Batch Documentation 19 Conformity 13 Batch Record Review 19 Containment 14 Biological Safety Cabinet (BSC) 19 Contamination 14 Bulk Ware 19 Continued Process Verification (CPV) 4 E 19 Continuous Validation 23 EC Directive 19 Continuous Validation/ 23 EC Regulation Verification 23 EDMF 20 Corrective Action/ 24 eDMS Preventive Action (CAPA) 24 EMA Guideline 20 Corrective and Preventive 24 EMA/EMEA Actions 24 EP 20 CPV 24 ETA 20 CSV 24 EU GMP Guidelines 25 European Pharmacopoeia D 25 Event Tree Analysis 21 Data Review 21 Design Qualification (DQ) F 22 Deviation 26 Factory Acceptance Test (FAT) 22 Deviation Management 26 Fault Tree Analysis 22 Disaster Recovery 26 FDA 22 DMS 27 FDA Guidance for Industry – 22 Document Management System Process Validation (DMS) 27 Fishbone Diagram/Method 22 DQ 28 FMEA (Failure Mode and Effects Analysis) 29 FMECA (Failure Mode, Effects and Criticality Analysis) 29 Formulation 29 FTA 29 Functional Specification 5 GxP Dictionary Contents G L 30 GAMP 36 Life-Cycle Approach 30 GCP 36 Life-Cycle Model 30 GDP 36 Logbook 30 GEP 30 GLP M 30 GMP 37 Major Change 30 GMP-Compliant Plant Design 37 Material Flow 30 GSP 37 Matrixing 30 GxP 37 Method Validation (analytical) 38 Metrological Traceability H 38 Minor Change 31 Head of Production 38 Monitoring 31 Head of Quality Control N I 39 NOAEL 32 ICH 39 NOEL 32 Information Officer 33 In-Process Controls O 33 Installation Qualification (IQ) 39 Official Calibration 33 IPC 39 OOS 33 IQ 39 OOT 33 Ishikawa Diagram/Method 40 Operational Qualification (OQ) 33 ISO 13485 40 OQ 34 ISO 14644 40 Out-of-Specification (OOS) 35 ISPE 40 Out-of-Trend (OOT) 6 P Q 41 Parenterals 46 QA 41 Particle Monitoring 46 QbD 41 Performance Qualification (PQ) 46 QP 42 Personnel Flow 46 Qualification 42 Pharmaceutical Excipient 46 Qualification Master Plan 42 Pharmacology 47 Qualification Plan 42 PIC/S 47 Qualification Report 43 Postal Audit 48 Qualified Person (QP) 43 PPQ 48 Qualified Person for 43 PQ Pharmacovigilance 43 PQR 49 Quality Assurance (QA) 43 Primary Packaging 49 Quality by Design (QbD) 43 Process 49 Quality Management Manual 44 Process Capability 50 Quality Risk Management (QRM) 44 Process Capability Study 44 Process Performance Qualification (PPQ) 44 Process Validation (PV) 45 Product Quality Review (PQR) 45 Product Specification 45 Prospective Qualification 45 Prospective Validation 45 PV (Process Validation) 7 GxP Dictionary Contents R S 51 RABS 55 Secondary Packaging 51 Reproducibility 55 Secondary Contamination 51 Requalification 55 Self-Inspection 51 Requirement Specification 56 Site Acceptance Test (SAT) 52 Reserve Sample 56 Site Master File (SMF) 52 Responsibility Delimitation 56 SOP (Standard Operating Agreement Procedure) 52 Restricted Access Barrier 56 Specification System (RABS) 57 Sterility 52 Retrospective Qualification 57 Sterilization 53 Returns 57 Stress Test 53 Revalidation 57 Supplier Audit 53 Risk Analysis (RA) 53 Risk Assessment T 53 Risk-Based Qualification 57 Test Plan Systems 57 Third-Party Audits 54 Risk Communication 58 Traceability 54 Risk Control 58 Traceability Matrix 54 Risk Management 58 Track & Trace 54 Risk Monitoring 54 Risk Priority Number (RPN) U 55 Risk Reduction 59 URS (User Requirement 55 Robustness Specification) 8 V 59 Validation Master Plan (VMP) 60 Validation 60 Validation Matrix 60 Validation Plan 60 Validation Report 61 V Model W 62 Warning Letter 62 Warning Limit 63 WHO 63 Work Directive 63 Worst-Case Scenario Z 64 ZLG 66 GxP Regulations and Guidelines 9 GxP Dictionary Terms and Definitions Terms and Definitions 0-9 21 CFR 210/211 483 CFR: Code of Federal Regulations – The problem report is referred to as Federal Regulations of the USA Title 483, and it is issued by FDA inspectors 21: Food and Drugs – contains the (see FDA, p. 26) and documents the regulatory provisions for the food and complaints that arise during an inspec- drugs sector. tion. The name is derived from Form Part 210: current Good Manufacturing No. 483, which is used to prepare the Practice (see cGMP, p. 16) in Man- summary report. ufacturing, Processing, Packing, or A 483 is normally published, but with- Holding of Drugs; General out naming the company or product Part 211: current Good Manufacturing names concerned. Practice (see cGMP, p. 16) for Fin- Depending on the relevance of the ished Pharmaceuticals documented defects, a Warning Letter 21 CFR 210/211: contains very de- is created on the basis of the 483. See tailed GMP guidelines for the USA. Warning Letter, p. 62. Part 210 refers to the manufacturing and packaging process of drugs and food, while Part 211 primarily includes the rules for finished pharmaceuticals. 10 0-9 A A Action Limits Airlock Concept A limit value stipulated by laws, direc- Airlock Concepts consist of several tives or internal company provisions. If rooms, arranged one behind the other, this value is exceeded, then corrective which allow the transition of persons actions must be initiated without de- and material from a cleanroom area lay, accompanied by analysis of the to a cleanroom area with a higher or failure and removal of the cause. lower level of purity, without contami- nating one of the areas. Active Pharmaceutical Ingredient (API) Annex The medically (pharmacologically) Annexes are various appendices to active ingredient in a drug. the EU GMP Guidelines. Currently there’s Annex 1 to Annex 19, there is ADI (Acceptable Daily Intake) no longer an Annex 18. Annex 18 was The ADI specifies the amount of a published in 2005 as EU GMP Guide- certain substance, e.g. of an active lines Part II. pharmaceutical ingredient, that does not present any health risk, on the assumption that a person is exposed to it on a daily basis over a lifetime. 11 GxP Dictionary Terms and Definitions Annual Product Review (APR) of authorities other than the compe- A retrospective review of the history tent supervisory authority such as the of a drug, required by the FDA for FDA) and, in terms of how it is defined, products manufactured in or imported is separate from an inspection, which into the USA, undertaken on an annual may be carried out exclusively by the basis. competent supervisory authority, i.e. inspectors of the state authorities. API See Active Pharmaceutical Ingredient Audit Trail (API), p. 11. This is used to ensure the complete traceability of all activities, actions and APR system states by recording “traces”, See Annual Product Review (APR), which indicate when, by whom and/ p. 12. or what, a process was influenced. It usually consists of records of com- Audit puter and software systems and is Inspection or survey of a site (e.g. a required by 21 CFR Part 11 as well as company, a production site) for the Annex 11 (EU GMP). purpose of verifying compliance with the requirements it is supposed to Authorization fulfil (here: compliance with the GMP Authorization refers to the marketing regulations and their specifications). authorization for a medicinal product. An audit can be carried out by various In this regard, the product must always bodies (e.g. representatives of con- conform to the GMP. tracting authorities or representatives 12 B A Batch Batch Record Review B A homogeneous and defined quantity Batch Record Review is a system of starting material, medicinal prod- that collates all the information about ucts or packaging material produced the batch certification. For example, in a single operation or in a series of these include batch production and operations. test reports, as well as all records of deviations and OOS reports (see Batch Documentation Out-of-Specification (OOS), p. 40). The Batch Documentation includes This information is used by the QP instructions and protocols on manu- (Qualified Person) as the basis for facturing and packaging procedures, making decisions regarding the release as well as the test report. This enables of a batch (batch release). the entire history of a batch to be traced without any gaps.