Guidelines

• USFDA: Drug Master Files: Guidelines
• USFDA: Drug Master File (DMF) Templates
• USFDA: Drug Master Files Guidance for Industry: DRAFT GUIDANCE
• USFDA: M4: The CTD — Quality Guidance
• USFDA: Review of Drug Master Files in Advance of Certain ANDA Submissions
• EMA (Europe): Active substance master file procedure – Scientific guideline
• EMA: Chemistry of active substances (chemistry of new active substances) – Scientific guideline
• EDQM: Guidance for Electronic submissions for Certificates of Suitability (CEP) applications
• EDQM / CEP: Certification Policy Documents & Guidelines (CEP: Certification of Suitability to the monographs of the European Pharmacopoeia)
• ICH M4 : The Common Technical Document Guidance
• WHO: Guidelines on active pharmaceutical ingredient master file procedure (2008)
• EDQM / CEP:  Content of the dossier for sterile substances, (Draft Guidance – PA/PH/CEP (23) 54, draft 4, May 2024)

• WHO TRS 1025 – Annex 4: WHO Good Chromatography Practices
• EC (European Council) Directive 96/23/EC: Concerning the performance of analytical methods and the interpretation of results
• USP <621> Chromatography FAQs

• USFDA Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice – Guidance
• Europe: Annexure 1, Manufacture of Sterile Medicinal Products (EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines)
• WHO Good Manufacturing Practices For Sterile Pharmaceutical Products
• WHO TRS 1010 – Annex 8: Guidelines on heating, ventilation and air-conditioning systems for non-sterile pharmaceutical products
• WHO TRS 1019 – Annex 2: WHO good manufacturing practices for heating, ventilation and air-conditioning systems for non-sterile pharmaceutical products (part 2): interpretation of guidelines
• WHO PQT Q&A: Heating, Ventilation and Air-conditioning Systems
• PICS: Revised Annex 1 : Manufacture of Sterile Medicinal Products (Guide to Good Manufacturing Practice for Medicinal Products)
• ISO 14644-1:2015 – Cleanrooms and associated controlled environments
• ISPE: Understanding Cleanliness Classifications for Life Science Facilities
• PDA: Understanding ISO 14644-1/2:2015 and Becoming Compliant; Eric Gottlieb; Particle Measuring Systems
• VDI 2083: Part 19: Cleanroom technology – Tightness of containments – Classification, planning, and testing

• APIC (Active Pharmaceutical Ingredients Committee): Guidance On Aspects Of Cleaning Validation In Active Pharmaceutical Ingredient Plants
• European Medicines Agency (EMA): Guideline on setting health based exposure limits; Questions and answers on Guideline on setting health-based exposure limits
• EMA: Questions and answers on implementation of risk-based prevention of cross-contamination in production and ‘Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities’ (EMA/CHMP/CVMP/SWP/169430/2012)
• USFDA Guide To Inspections : Validation Of Cleaning Processes
• PIC/S: Guideline On Setting Health Based Exposure Limits For Use In Risk Identification In The Manufacture Of Different Medicinal Products In Shared Facilities (PI 046-1 Annex 1 July 2018)
• PICS::Questions and Answers on Implementation of Risk-Based Prevention of crosscontamination in Production and ‘Guideline on setting Health-Based Exposure Limits for use in risk identification in the manufacture of different medicinal products in shared facilities
• PICS::AIDE-MEMOIRE Inspection of Health Based Exposure limit (HBEL) assessments and use in Quality Risk Management
• TGA: Cleaning Validation – A regulatory perspective (Presentation) 
• WHO TRS 1033 – Annex 2: Points to consider when including Health-Based Exposure Limits (HBELs) in cleaning validation
• Useful Info: Agency Expectations on PDE Determination and PDE Reports; GMP Verlag: LOGFILE Feature 14/2024

• USFDA Guidance for Industry Part 11, Electronic Records; Electronic Signatures — Scope and Application
• USFDA PART 11 – Electronic Records; Electronic Signatures; ECFR – 21 Part 11
• USFDA: Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers – Guidance for Industry
• USFDA: General Principles of Software Validation; Final Guidance for Industry and FDA Staff
• EC EudraLex (Europe): Annex 11: Computerised Systems – Guidance
• EDQM – OMCL – Validation of computerised systems – Core document:
  • Annexure 1 (Validation of Excel spread sheets);
  • Annexure 2 (Validation of complex computerised systems).
• PIC/S : Good practices for computerised Systems in regulated “GxP” environments (PIC/S Guidance)

• USFDA Controlled Correspondence Related to Generic Drug Development
• USFDA Guidance Document – Controlled Correspondence Related to Generic Drug Development.
• Cover Letter Attachments for Controlled Correspondences and ANDA Submissions – Guidance
• WHO Prequalification – Technical Advice; Advice to Manufacturers
• EMA – Scientific advice and protocol assistance

• USFDA Data Integrity and Compliance with Drug CGMP Questions and Answers – USFDA Guidance for Industry
• EMA (European Medicines Agency) Data Integrity Aug 2016 (European Medicines Agency)
• MHRA (Medicines & Healthcare products Regulatory Agency) ‘GXP’ Data Integrity Guidance and Definitions
• WHO TRS 1033 – Annex 4: WHO Guideline on Data Integrity
• PIC/S Guidance on Data Integrity; Good Practices For Data Management And Integrity In Regulated Gmp/Gdp Environments
• Comparison of EMA and FDA Guidance on Data Management and Data Integrity; Barbara W. Unger; Redica Systems
• Data Integrity checklist by Agilent (Useful checklist).

• Excipient Risk Assessment (Europe): Guidelines of 19 March 2015 on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use ( EC 2015/C 95/02)
• PIC/S Document: Guidelines On The Formalised Risk Assessment For Ascertaining The Appropriate Good Manufacturing Practice For Excipients Of Medicinal Products For Human Use

• IPEC Europe (International Pharmaceutical Excipients Council Europe)- How to do document on European Commission Guidelines on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use
• IPEC-PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients (version 5, 2022). IPEC Guidelines
• IPEC Europe (International Pharmaceutical Excipients Council Europe) – Resources (on Pharmaceutical Excipients)
• IPEC Americas (International Pharmaceutical Excipients Council Europe) –Document Depot (For several resources on Excipients (Standards, Test Methods, Discussion papers).
• IPEC Americas – S. Drug Master File Guide For Pharmaceutical Excipients (Download from Document Depot)
• USFDA Using the Inactive Ingredient Database (IID) Guidance for Industry; FDA Guidance; Search the IID

• USFDA Field Alert Reports;
• USFDA Field Alert Report Submission: Questions and Answers Guidance for Industry; Guidance
• USFDA Field Alert Report Form: Questions and Answers
• USFDA Field Alert Report (FAR) regulations: NDA: 21 CFR 314.81(b)(1); ANDAs: 21 CFR 314.98
• Europe: Informing National Competent Authority (NCA), Dealing with Quality Defects and Rapid Alerts Rapid Alerts; Presentation by David Cockburn, Head of Manufacturing and Quality Compliance European Medicines Agency
• Europe Quality Defects and Recall (EMA): Reporting of Product quality defect, including a suspected defect, of a centrally authorised medicine which could result in a recall or abnormal restriction on supply to the European Medicines Agency (EMA)
• Reporting a quality defect to EMA (Europe)
• PIC/S Procedure For Handling Rapid Alerts And Recalls Arising From Quality Defects (Europe)
• CDSCO (India): Guidelines On Recall And Rapid Alert System For Drugs

• USFDA 21CFR PART 210—Current Good Manufacturing Practice in Manufacturing, Processing, Packing, Or Holding Of Drugs; General
• USFDA 21 CFR PART 211—Current Good Manufacturing Practice For Finished Pharmaceuticals
• USFDA: Q&A on CGMP Requirements
• USFDA Q&A: Questions and Answers on Current Good Manufacturing Practice Requirements – Control of Components and Drug Product Containers and Closures
• WHO TRS 986 – Annex 2: WHO Good Manufacturing Practices for Pharmaceutical Products: Main Principles
• WHO TRS 957 – Annex 2: WHO Good Manufacturing Practices fFor Active Pharmaceutical Ingredients (APIs – Bulk Drug Substances)
• WHO TRS 957 – Annex 3: WHO good manufacturing practices for pharmaceutical products containing hazardous substances
• WHO: Quality assurance of pharmaceuticals: A compendium of guidelines and related materials; Tenth Edition : Volume 2 Good manufacturing practices and inspection
• Europe: EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines
  • EudraLex Introduction
  • EudraLex – Part I – Basic Requirements for Medicinal Products
  • EudraLex – Part II – Basic Requirements for Active Substances used as Starting Materials
  • EudraLex – Part III – GMP related documents
  • EudraLex – Annexes
  • EudraLex – Guidance On Good Manufacturing Practice and Good Distribution Practice: Questions And Answers
  • EudraLex: Other documents related to GMP and GDP
• PIC/S: Guide To Good Manufacturing Practice for Medicinal Products
  • PIC/S GMP Guide (Part I: Basic Requirements for Medicinal Products)
  • PIC/S GMP Guide (Part II: Basic Requirements for Active Pharmaceutical Ingredients)
  • PIC/S GMP Guide To Good Manufacturing Practice for Medicinal  Products ANNEXES
• ICH Q7A: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
• ICH Q7A – Q&A (ICH) & Q&A presentation
• APIC – GMPs for APIs – How to do – Interpretation of ICH Q7 Guide
• MHRA (UK): Volume 4 of the rules governing medicinal products in the EU
• TGA (Australia): PE009, the PIC/S guide to GMP for medicinal products; TGA interpretation and expectations for demonstrating compliance
• Health Canada: Good manufacturing practices guide for drug products (GUI-0001)
• South Africa- SA Guide To Good Manufacturing Practice for Medicines (SAHPRA); SAPHRA Guidelines Page

• USFDA: Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications – Guidance
• USFDA: Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities Guidance for Industry (Sep 2023)
• USFDA: Conducting Remote Regulatory Assessments – Questions and Answers (January 2024)
• USFDA – Inspection Guides
• USFDA: Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device Inspection (June 2024)
• USFDA: Compliance Program (7356.002): Drug Manufacturing Inspections (Chapter 56: Drug Quality Assurance)
• USFDA: Compliance Program (7346.832): Preapproval Inspections (Chapter 46—NEW DRUG EVALUATION)
• USFDA: Post-Warning Letter Meetings Under GDUFA (Sep 2023)
• EMA & EC (Europe): Conduct of Inspections of Pharmaceutical Manufacturers or Importers
• EMA: Guidance for applicants/MAHs involved in GMP, GCP and GVP inspections coordinated by EMA
• EMA: Inspections: verifying compliance
• EDQM: The Inspection Programme
• WHO: Inspection Services – Medicines
• WHO: Guideline To The Inspection Of Hormone Product Manufacturing Facilities (Working document QAS/08.256 February 2008 RESTRICTED) & ISPE Comments
• PIC/S Inspection Aide Memoire:
  • PIC/S Inspection of Active Pharmaceutical Ingredients
  • PIC/S Inspection of Health Based Exposure Limit (HBEL) Assessments and use in Quality Risk Management
  • PIC/S Inspection of Pharmaceutical Quality Control Laboratories
  • PIC/S Inspection of Utilities
  • PIC/S Inspection Of Biotechnology Manufactures
  • PIC/S:Inspection of Good Distribution Practice (GDP) for Medicinal Products in the Supply Chain

• USFDA – Expiration Dates – Questions and Answers
• USFDA Inspection Technical Guides: Expiration Dating and Stability Testing for Human Drug Products
• European Medicines Agency (EMA): Start of shelf-life of the finished dosage form (Annex to the note for guidance on the manufacture of the finished dosage form) – Scientific guideline.
• EMA Note for Guidance on Start of Shelflife of the Finished Dosage Form
• EMA – How should Expiry dates be calculated and expressed (EMA Quality of medicines questions and answers: Part 2)
• WHO – Points to consider for setting the remaining shelf-life of medical products upon delivery (TRS 1044-Annexure 8 (WHO Technical Report Series)
• WHO – DRAFT WORKING DOCUMENT FOR COMMENTS: Guidance on setting remaining shelf life for the supply and procurement of Emergency Health Kits

• ICH Q2(R2): Validation of Analytical Procedures; Final Version; Adopted on 1 November 2023
• ICH Q(14): Analytical Procedure Development; Final Version; Adopted on 1 November 2023
• ICH Q2(R2)/Q14 EWG Working group presentation; Analytical Procedure Development and Revision of Q2(R1) Analytical Validation
• VICH: Validation of Analytical Procedures: Definition and Terminology [CVM GFI #63 (VICH GL1)]
• VICH: Validation of Analytical Procedures: Methodology [CVM GFI #64 (VICH GL2)]
• USFDA Analytical Procedures and Methods Validation for Drugs and Biologics Guidance for Industry
• USP 1225: VALIDATION OF COMPENDIAL PROCEDURES (Please access USP to read)
• Validation of Analytical Methods (IPC/GD/04) – Indian Pharmacopeia convention
• EDQM: Comparability of alternative analytical procedures (5.27) (Refer Ph Eur)

• USFDA: Guidance for Industry: Control of Nitrosamine Impurities in Human Drugs;
• USFDA Updates on possible mitigation strategies to reduce the risk of nitrosamine drug substance-related impurities in drug products
• USFDA: Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (Aug 2023) – Guidance Document
• USP General Chapter <1469> Nitrosamine Impurities – Presentation; (Also Refer USP General Chapter)
• EMA (European Medicines Agency) Nitrosamine impurities
• EMA Questions and answers for marketing authorisation holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products
• EMA Guidance for marketing authorisation holders
• EMA Active substance-derived nitrosamines
• CMDh Information On Nitrosamines For Marketing Authorisation Holders
• EMA (Adopted by CHMP) Assessment report Nitrosamine impurities in human medicinal products
• European Pharmacopeia General Monographs : Substances for pharmaceutical use (2034) and Pharmaceutical preparations (2619) for Ph. Eur. approach to N-nitrosamine impurities (Access through Ph Eur (EP)
• OMCL/EDQM: Methods for determination of nitrosamines and NDSRIs
• APIC (CEFIC) Additional guidance on the assessment on the risk assessment for presence of N-nitrosamines in APIs
• APIC (CEFIC) Template for Nitrosamine Risk evaluation of APIs
• IPEC Europe: Questionnaire for Excipient Nitrosamines Risk Evaluation
• IPEC Americas: Federation Announces Updated Nitrosamines Questionnaire
• WHO Information Note Nitrosamine impurities
• Health Canada Nitrosamine impurities in medications: Guidance

• USFDA: Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production – Level 2 revision
• MHRA: Out-of-specification investigations

• USFDA Guidance for Industry: E2E Pharmacovigilance Planning
• USFDA: Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment
• USFDA Presentation: An Overview of Pharmacovigilance in the Center for Drug Evaluation and Research (PDF – 2MB)
• Europe (EMA): Pharmacovigilance system: Questions and Answers
• European Medicines Agency: Good pharmacovigilance practices
• Europe (EMA): Guideline on good pharmacovigilance practices (GVP) Module II – Pharmacovigilance system master file (Rev 2)
• Europe (EMA): Guideline on good pharmacovigilance practices (GVP) Module I – Pharmacovigilance systems and their quality systems
• ICH Pharmacovigilance (E2A-E2F); ICH E2E Pharmacovigilance planning (Pvp) – Scientific guideline
• Pharmacovigilance Programme of India (PvPI); ADR Reporting Form
• MHRA: Guidance on qualified person responsible for pharmacovigilance (QPPV) including pharmacovigilance system master files (PSMF)
• MHRA: Exceptions and modifications to the EU guidance on good pharmacovigilance practices that apply to UK MAHs and the MHRA
• MHRA: Guidance updates on to how to notify the MHRA of changes to the PV System

• USFDA: Process Validation: General Principles and Practices – Guidance for Industry
• European Medicines Agency (EMA) : Process validation for finished products – information and data to be provided in regulatory submissions – Scientific guideline
• EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use Annex 15: Qualification and Validatio
• WHO TRS 1019 – Annex 3: Good manufacturing practices: Guidelines on validation
• PICS: Validation Master Plan, Installation And Operational Qualification, Non-Sterile Process Validation, Cleaning Validation
• PIC/S: Guide to Good Manufacturing Practice for Medicinal Products Annexes; Annex 15 Qualification and Validation)

• Annex 16: Certification by a Qualified Person and Batch Release (EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines Annexes)
• Guidance for the template for the qualified person’s declaration concerning GMP compliance of active substance manufacture “The QP declaration template”
• Template for the qualified person’s (QP) declaration concerning good manufacturing practice compliance of active substance manufacture “The QP declaration template” – Scientific guideline & Template

• ICH Q8(R2): Pharmaceutical Development (For dosage forms)
  • ICH Q8, Q9 and Q10: Questions & Answers (R4)
  • ICH Training presentations: Training Programme for Q8/Q9/Q10
• ICH Q11: Development And Manufacture Of Drug Substances (Chemical Entities (APIs) And Biotechnological/Biological Entities)
  • ICH Q11:Questions and Answers
  • ICH Training presentations: Q11 Training Materials
• EMA (European Medicines Agency): Quality: Quality by Design (QbD) (EMA references and links to ICH Q8, Q9, Q10 for QbD)
• USFDA: Q8(R2) Pharmaceutical Development (Same as ICH Q8(R2))
• Implementation of Quality by Design (QbD) Principles in Regulatory Dossiers of Medicinal Products in the European Union (EU) Between 2014 and 2019 (Journal Article Judith P. ter Horst, Sada L. Turimella, Frans Metsers & Alex Zwiers; Therapeutic Innovation & Regulatory Science volume 55, pages583–590 (2021)

• ICH: Quality Risk Management – Q9(R1) – Final version – Adopted on 18 January 2023
• ICH: Q9(R1) Step 4 Presentation
• ICH: Training Programme for Q8/Q9/Q10 – Presentations
• PIC/S: Aide-Memoire For Assessment Of Quality Risk Management Implementation
• WHO TRS 981 – Annex 2: WHO Guidelines on Quality Risk Management

• USFDA on Recall: Initiation of Voluntary Recalls Under 21 CFR Part 7, Subpart C : Guidance document
• USFDA: Product Recalls, Including Removals and Corrections (March 2020) – Guidance document
• USFDA 21CFR Part 7 Subpart C Recalls (Including Product Corrections) – Guidance on Policy, Procedures, and Industry Responsibilities (21 CFR 7.40 – 7.59).
• USFDA: Public Warning and Notification of Recalls Under 21 CFR Part 7, Subpart C: Guidance for Industry and FDA Staff
• Europe Quality Defects and Recall (EMA): Reporting of Product quality defect, including a suspected defect, of a centrally authorised medicine which could result in a recall or abnormal restriction on supply to European Medicines Agency (EMA)
• Reporting a quality defect to EMA (Europe)
• Europe: Informing National Competent Authority (NCA), Dealing with Quality Defects and Rapid Alerts Rapid Alerts; Presentation by David Cockburn, Head of Manufacturing and Quality Compliance European Medicines Agency
• TGA Australia About Australian recall actions
• CDSCO India Guidelines On Recall And Rapid Alert System For Drugs (Including Biologicals & Vaccines)

• Refer USP General Notices:
  • USP General Notices: Significant Figures and Tolerances
  • USP General Notices & Requirements 7.20 Rounding Rules
  • USP 1010 Analytical Data – Interpretation & Treatment
• FDA ORA Lab Manual Vol. III Section 4 – Basic Statistics and Data Presentation (III04)

• USFDA: 211.170 Reserve samples.
• USFDA – Retention of Bioavailability and Bioequivalence Testing Samples
• USFDA: Handling and Retention of Bioavailability BA and Bioequivalence BE Testing Samples
• EU GMP Annex 19: Reference and Retention Samples

• EMA – EU Site Master File (EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines; Part III – GMP related documents)
• WHO: TRS 961 – Annex 14: WHO guidelines for drafting a site master file; Guideline
• PIC/S: Explanatory Notes For Pharmaceutical Manufacturers On The Preparation Of a Site Master File
• SAHPRA (South Africa): Guidelines For Preparation Of Site Master File
• TGA (Australia): TGA uses the PIC/S harmonised template for an SMF.

• WHO TRS 929 – Annex 4: WHO Guidelines for Sampling of Pharmaceutical Products and Related Materials
• ISO 2859-2:2020 – Sampling procedures for inspection by attributes — Part 2: Sampling plans indexed by limiting quality (LQ) for isolated lot inspection
• IPA: Visual Inspection of Sterile Products – Best Practices Document
• Useful Info: Explaining Acceptance Quality Limit (AQL) for product inspection – Eurofins Document

• USFDA 21 CFR 211.42: Design and construction features.(Pencillins require dedicated facilities)
• USFDA Guidance: Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross Contamination (Draft Guidance: June 2022)
• ICH Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients: D. Containment (4.4)
• EMA: Setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities – Scientific guideline
• Europe (EC GMP Guide): Manufacture Of Veterinary Medicinal Products Other Than Immunological Veterinary Medicinal Products
• WHO TRS 957 – Annex 3: WHO good manufacturing practices for pharmaceutical products containing hazardous substances
• Also read: WHO Guideline To The Inspection Of Hormone Product Manufacturing Facilities (Working document QAS/08.256 February 2008 RESTRICTED) & ISPE Comments
• PICS: Guideline On Setting Health Based Exposure Limits For Use In Risk Identification In The Manufacture Of Different Medicinal Products In Shared Facilities
• PICS: Questions And Answers On Implementation Of Risk-Based Prevention Of CrossContamination In Production And ‘Guideline On Setting Health-Based Exposure Limits For Use In Risk Identification In The Manufacture Of Different Medicinal Products In Shared Facilities’
• PICS: Cross-Contamination In Shared Facilities
• Schedule M (Page 428): Drugs And Cosmetics Act And Rules, India
• ISPE Baseline® Guide: Volume 7 – Risk-Based Manufacture of Pharmaceutical Products (Second Edition)
• Useful Info; The requirements for manufacturing highly active or sensitising drugs comparing Good Manufacturing Practices (Petrelli F, Caraffa A, Scuri S, Grappasonni I, Magrini E, Cocchini A. Acta Biomed. 2019 May 23;
• Useful Info: Mitigating Cross-Contamination in Shared Production Facilities Using Risk-Based Cleaning Validation Methods: Considerations and Case Study (USP & USAID)
• Useful Info: Prevention of contamination and cross-contamination in medicinal manufacturing facilities; Pharmout White Paper; Novermber 2021.

• ICH Q6A: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances And New Drug Products: Chemical Substances
• ICH Q6A: Specifications: Decision Tree
• ICH Q6B: Specifications: Test procedures and Acceptance criteria for Biotechnological / Biological products
• ICH Q3A(R2): Impurities in new Drug substances
• ICH Q3B(R2): Impurities in new Drug products
• ICH Q3C(R8) Impurities: Guideline for Residual Solvents
• ICH Q3D(R2): Guideline for Elemental Impurities
• ICH M7(R2): Assessment and control of DNA reactive (Mutagenic) impurities in Pharmaceuticals to limit potential Carcinogenic risk
• ICH Addendum to M7(R2): Application of the principles of the ICH M7 Guideline to calculation of compound-specific Acceptable Intakes
• ICH M7(R2): 2nd Addendum Step 4 document.
• ICH M7(R2) Q&As: Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk; Questions and Answers
• VICH: GL39 Test procedures and acceptance criteria for new veterinary drug substances and new medicinal products: chemical substances – Scientific guideline (VICH: GL39)
• EMA (European Medicines Agency): Specifications and control tests on the finished product – Scientific guideline
• EMA (European Medicines Agency): Setting specifications for related impurities in antibiotics – Scientific guideline
• USP General chapters: General Tests & Assays – General requirements for tests and assays (Access from USP)
  • Chapter 1: Injections and Implanted Drug Products (Parenterals)—Product Quality Tests
  • Chapter 2: Oral Drug Products—Product Quality Tests
  • Chapter 3: Topical and Transdermal Drug Products—Product Quality Tests
  • Chapter 4: Mucosal Drug Products—Product Quality Tests
  • Chapter 5: Inhalation and Nasal Drug Products—General Information and Product Quality Tests
• USP<1111> Microbiological Attributes of Nonsterile Pharmaceutical products & USP <1111>: Microbiological examination of Nonsterile products: Acceptance criteria for Pharmaceutical preparations Substances for Pharmaceutical use (Access from USP)
• European Pharmacopeia (Access from EP or Ph.Eur):
  • Substances for Pharmaceutical Use (2034);
  • 10. Control of impurities in substances for Pharmaceutical use (51000)
  • 4. Residual Solvents
• USFDA : Policy on testing ethanol isopropyl alcohol for methanol
• USFDA: Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol

• USP Chapter 11: REFERENCE STANDARDS (Access USP)
• European Pharmacopoeia Chapter 5.12 – Reference Standards (Access Ph Eur)
• USFDA Guidance Analytical Procedures and Methods Validation for Drugs and Biologics Section V. REFERENCE STANDARDS AND MATERIALS
• Secondary Standards – Considerations in Traceability to Pharmacopoeial Standards (USP& EDQM Joint presentation October 2023)
• The Value of Pharmacopeial Reference Standards (Christian Zeine, Doug Podolsky, Jane Weitzel, Ravi Reddy, Steven L. Walfish, Pharmaceutical Technology-02-02-2021, Volume 45, Issue 2) – Useful Reference paper
• Reference-Standard Material Qualification; Pharmaceutical Technology, Pharmaceutical Technology-04-02-2009, Volume 33, Issue 4
• WHO TRS 943 – Annex 3: WHO general guidelines for the establishment, maintenance and distribution of chemical reference substances
• Reference Standard Characterization – Steve Lane, General Manager, NSF Reference Standards
• Other references: ICH Q7A, ICH Q6B

• USFDA : Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice – Guidance
• USFDA : Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products – Guidance
• USFDA : Sterilization Process Controls (Inspection)
• USFDA: Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products
• USP 1211: Sterilization And Sterility Assurance Of Compendial Articles (Access and read USP Chapter 1211))
• Europe: Annexure 1, Manufacture of Sterile Medicinal Products (EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines)
• EMA : Sterilisation of the medicinal product, active substance, excipient and primary container – Scientific guideline
• PICS: Revised Annex 1 (Manufacture of Sterile Medicinal Products) /Guide to Good Manufacturing Practice for Medicinal products
• PICS::Validation of Aseptic Processes (Jan 2011)
• WHO: TRS 1044 – Annex 2: WHO good manufacturing practices for sterile pharmaceutical products (WHO Technical Report Series, No. 1044, 2022)
• WHO: Good Manufacturing Practices For Sterile Pharmaceutical Products  (WHO Technical Report Series, No. 961, 2011)
• ISPE : Validation of Aseptic Processes Using Media Fill
• PDA Technical Report No. 22 (Revised 2011):  Process Simulation for Aseptically Filled Products
• PDA Technical Report No. 28 Revised, (TR 28) Process Simulation Testing for Sterile Bulk Pharmaceutical Chemicals (single user digital version)
• ISO 13408-1:2008 :  Aseptic processing of health care products (Access to the documented is a paid service)
• Useful Readings:
• Product Sterility Testing . . . To Test or Not to Test? That Is the Question (Elaine Daniell; Trabue Bryans; Kimbrell Darnell; Joyce Hansen; Victoria M. Hitchins; Manuel Saavedra; Biomed Instrum Technol (2016) 50 (s3): 35–43)

• ICH Q1A (R2): Stability Testing: Stability testing of new drug substances and drug products
• ICH Q1B: Stability Testing: Photostability testing of new active substances and medicinal products
• ICH Q1C Stability testing: Requirements for new dosage forms (Annex to the ICH Harmonised Tripartite Guideline on Stability Testing for New Drugs and Products)
• ICH Q1D: Bracketing and matrixing designs for stability testing of drug substances and drug products
• ICH Q1E: Evaluation of stability data; ICH Q1E presentation (Sumie Yoshioka)
• ICH Q1F Stability Guideline WHO 2018: Annexure 10: Stability testing of active pharmaceutical ingredients and finished pharmaceutical products (ICH withdrew original Q1F, to follow WHO Annexure 10).
• EMA: Stability testing for applications for variations to marketing authorisation – Scientific guideline
• EMA: Start of shelf-life of the finished dosage form (Annex to the note for guidance on the manufacture of the finished dosage form) – Note for guidance on start of shelf-life of the finished dosage form (annex to note for guidance on the manufacture of the finished dosage form)
• EMA: Maximum shelf-life for sterile products for human use after first opening or following reconstitution – Note for guidance on maximum shelf-life for sterile products for human use after first opening or following reconstitution
• EMA: Declaration of storage conditions for medicinal products particulars and active substances (Annex) – Scientific guideline
• EMA: In-use stability testing of human medicinal products – Note for guidance on in-use stability testing of human medicinal products
• EMA: Stability testing of existing active ingredients and related finished products – Scientific guideline
• WHO TRS 953 – Annex 2, Appendix 1: Stability Testing of Active Pharmaceutical Ingredients and Finished Pharmaceutical Products: Stability Conditions for WHO Member states by region
• WHO TRS 1010 – Annex 10: WHO Guidelines on Stability Testing of Active Pharmaceutical Ingredients and Finished Pharmaceutical Products
• USFDA: Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products – Guidance for Industry
• USFDA: ANDAs: Stability Testing of Drug Substances and Products, Questions and Answers – Guidance
• USFDA: ANDAs: Stability Testing of Drug Substances and Products – Guidance
• USFDA: CVM GFI #242 In-Use Stability Studies and Associated Labeling Statements for Multiple-Dose Injectable Animal Drug Products – Guidance
• USFDA: CVM GFI #5 Drug Stability Guidelines – Guidance
• TGA: Stability testing for prescription medicines (Addresses Temperature cycling studies) – Guidance
• ANVISA: Impact from the Recent Issuance of ANVISA Resolution RDC-53/2015 on Pharmaceutical Small Molecule Forced Degradation Study Requirements. American Pharmaceutical Review
• PDA: PDA Technical Report No. 39 Revised 2021 (TR 39) Guidance for Temperature-Controlled Medicinal Products – Maintaining the Quality of Temperature-Sensitive Medicinal Products through the Transportation Environment
• Stability Studies Needed to Define the Handling and Transport Conditions of Sensitive Pharmaceutical or Biotechnological Products; Claude Ammann, AAPS PharmSciTech, Vol. 12, No. 4, December 2011 (# 2011)

Hold time studies:

• WHO TRS 992 – Annex 4: General guidance on hold-time studies
• EMA: Section 4.4. ‘Controls of Critical Steps and Intermediates’ – ‘Storage of intermediate and bulk products’ – Guideline on manufacture of the finished dosage form’
• EMA: Stability – Stability issues of pharmaceutical bulk products use in manufacture of the finished product; European Medicines Agency (EMA) Quality of Medicines Questions and Answers: Part 2

• Refer discussions under Questions and Answers on Current Good Manufacturing Practice Regulations | Production and Process Controls (USFDA)
• USFDA: Powder Blends and Finished Dosage Units — Stratified In-Process Dosage Unit Sampling and Assessment (October 2003) – Was withdrawn in August 2013 by FDA
• ISPE: Blend Uniformity and Content Uniformity (BUCU) Tools; Process Flow Diagram for Assessment of Blend and Content Uniformity for Process Design and Process Qualification Batches
• ISPE: Comparison of Two Relevant Statistical Approaches to Assess Content Uniformity; Also refer Presentation from James K. Drennen, III, Duquesne University, Centre for Pharmaceutical Technology
• ISPE: Blend Uniformity and Content Uniformity (BUCU) FAQs
• The use of Stratified Sampling of Blend and Dosage units to demonstrate adequacy of mix for Powder Blends (PQRI, December 2002)
• Refer Article Recommendations for the Assessment of Blend and Content Uniformity: Modifications to Withdrawn FDA Draft Stratified Sampling Guidance, J. Pharm. Innov. (2015) 10:76-83 (Paid Article)
• Refer Article: Assessment of Blend and Content Uniformity. Technical Discussion of Sampling Plans and Application of ASTM E2709/E2810”; J. Pharm. Innov. (2015) 10:84-97 (Paid content)
• ASTM E2810-19; Standard Practice for Demonstrating Capability to Comply with the Test for Uniformity of Dosage Units (Paid Article)
• ASTM E2709-19: Standard Practice for Demonstrating Capability to Comply with an Acceptance Procedure (Paid Article)

• WHO TRS 1025 – Annex 7: Good Storage and Distribution Practices for Medical Products (June 2020)
• WHO TRS 961 – Annex 9: Model Guidance for the Storage And Transport of Time and Temperature Sensitive Pharmaceutical Products (August 2011)
• WHO TRS 961 – Annex 9, Supplement 7: Qualification of Temperature-Controlled Storage Areas (October 2011)
• WHO TRS 961 – Annex 9, Supplement 14: Transport Route Profiling Qualification (October 2011)
• WHO TRS 961 – Annex 9, Supplement 15: Temperature and Humidity Monitoring Systems for Transport Operations (October 2011)
• WHO TRS 961 – Annex 9, Supplement 13: Qualification of Shipping Containers (October 2011)
• WHO TRS 961 – Annex 9, Supplement 11: Qualification of Refrigerated Road Vehicles (October 2011)
• WHO TRS 961 – Annex 9, Supplement 8: Temperature Mapping of Storage Areas (October 2011)
• TGA: Stability testing for prescription medicines (Addresses Temperature cycling studies) – Guidance
• Health Canada; Guidelines for environmental control of drugs during storage and transportation (GUI-0069)
• PDA: PDA Technical Report No. 39 Revised 2021 (TR 39) Guidance for Temperature-Controlled Medicinal Products – Maintaining the Quality of Temperature-Sensitive Medicinal Products through the Transportation Environment
• ANVISA: Impact from the Recent Issuance of ANVISA Resolution RDC-53/2015 on Pharmaceutical Small Molecule Forced Degradation Study Requirements. American Pharmaceutical Review
• Industry Perspective on Temperature Cycling Studies to Meet Regulatory Temperature Excursion Support Requirements: Survey Outcome and Recommendations; Claudia Arana et al., J Pharm Sci. 2023 Dec;112(12):2981-2990
• Stability Studies Needed to Define the Handling and Transport Conditions of Sensitive Pharmaceutical or Biotechnological Products; Claude Ammann, AAPS PharmSciTech, Vol. 12, No. 4, December 2011 (# 2011)
• USP<1079>: Good Storage and Shipping Practices (Refer USP)
• USP <1118>: Monitoring Devices-Time, Temperature, and Humidity (Refer USP)

• WHO TRS 1044 – Annex 4: WHO Guidelines on Technology Transfer in Pharmaceutical Manufacturing
• ISPE: Good Practice Guide: Technology Transfer (3rd Edition)
• PDA Technical Report No.65 Revised 2022 (TR 65) Technology Transfer
• IPA (India): Guidance for Technology Transfer

• USFDA: Changes to an Approved NDA or ANDA
• USFDA: Changes to an Approved NDA or ANDA: Questions and Answers Guidance for Industry
• USFDA: Changes to an Approved NDA or ANDA; Specifications – Use of Enforcement Discretion for Compendial Changes
• USFDA: SUPAC-IR: Immediate-Release Solid Oral Dosage Forms: Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation
• USFDA: SUPAC-IR – Questions and Answers about SUPAC-IR Guidance
• USFDA: SUPAC-MR: Modified Release Solid Oral Dosage Forms Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation
• USFDA: SUPAC-SS: Nonsterile Semisolid Dosage Forms; Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation
• USFDA: SUPAC: Manufacturing Equipment Addendum
• USFDA: Postapproval Changes to Drug Substances 
• USFDA: CVM GFI #126 BACPAC I-Intermediates in Drug Substance Synthesis Bulk Actives Postapproval Changes: Chemistry, Manufacturing, and Controls Documentation
• USFDA: CMC Postapproval Manufacturing Changes To Be Documented in Annual Reports
• USFDA: PAC-ATLS: Postapproval Changes – Analytical Testing Laboratory Sites
• USFDA: Postapproval Manufacturing Changes to Biosimilar and Interchangeable Biosimilar Products Questions and Answers
• EMA, EC ( European Commission) ‘Variations Guidelines’ 2013/C 223/01 (EC) No 1234/2008 of 24 November 2008)
• EMA: European Medicines Agency post-authorisation procedural advice for users of the centralised procedure
• Europe: CMDh Recommendation for classification of unforeseen variations according to Article 5 of Commission Regulation (EC) 1234/2008 (March 2023)
• EMA: Variations including extensions of marketing authorisationsCEP: Notifications, Revisions, Renewals and Sister Files
• CEP / EDQM: Notifications, Revisions, Renewals and Sister Files
• CEP / EDQM: Classification of changes; Submit changes; Sister files
• CEP / EDQM: Guideline on Requirements for Revision/Renewal of Certificates of Suitability to the European Pharmacopoeia Monographs (PA/PH/CEP (04) 2)
• CEP / EDQM: Management of applications for new Certificates of Suitability, Requests for Revision
• CEP / EDQM: Guidance on applications for «sister files» (PA/PH/CEP (09) 141)
• CEP / EDQM: Certification Policy Documents & Guidelines
• WHO: Amendments to APIMFs;
• WHO: Guidance on amendments to an active pharmaceutical ingredient master file (APIMF) submitted in support of a prequalified pharmaceutical product (FPP) or prequalified active pharmaceutical ingredient
• WHO: FAQ: Active pharmaceutical ingredient master file (APIMF) amendments
• WHO: Variations to FPPs (Finished Pharmaceutical Products); Multisource Generic FPPs: Classification of variations and assessment timelines
• WHO: FAQ: Variations to prequalified pharmaceutical products
• WHO: TRS 981:Annex 3, WHO guidelines on variations to a prequalified product

• USFDA: High Purity Water System; Guide To Inspections Of High Purity Water Systems
• ISPE: Baseline Guide Vol 4: Water & Steam Systems 3rd Edition (To be purchased)
• ISPE: Good Practice Guide: Commissioning & Qualification of Pharma Water & Steam Systems (Second Edition)
• EMA (European Medicines Agency):
  • Quality of water for pharmaceutical use – Scientific guideline (EMA)
  • Note for Guidance on Quality of Water for Pharmaceutical Use (EMA)
  • Questions and answers on production of water for injections by non-distillation methods – reverse osmosis and biofilms and control strategies (EMA)
• WHO
  • WHO TRS 1033 – Annex 3: Good Manufacturing Practices: Water for Pharmaceutical Use (Revision of WHO TRS, No. 970, Annex 2, 2011)
  • WHO TRS 1025 – Annex 3: Production Of Water for Injection by means other than Distillation
  • WHO Guidelines for drinking-water quality, 4th ed., incorporating the 1st addendum (chapters)
• Ph Eur. Monograph (European Pharmacopeia or EP) – Read (Water for Injections (0169); Water for preparation of extracts (2249); Purified Water (0008);
• USP 1231: Water for Pharmaceutical Purposes (Read)
• PIC/S: Inspection of Utilities