Stability Regulations

This segment is a growing collection of laws, guidances and requirements pertaining to the stability function from various nations and recognized global and regional organizations. While some are legal requirements, others are guidances that can be fulfilled with justified alternative measures, but all are expectations of duly authorized regulatory bodies.

Document
Link
ANNEX V ASEAN GUIDELINES ON STABILITY STUDY AND SHELF-LIFE OF TRADITIONAL MEDICINEShttp://asean.org/storage/2017/09/ASEAN-Guidelines-on-Stability-and-Shelf-Life-TM-V1.0-with-disclaimer.pdf
ANVISA RDC N° 318/2019 Criteria for conducting Stability Studies for APIs and Drug Products, except for biological, and provides other arrangements' (6 November 2019)http://abracro.org.br/pdfs/RDC-318-06Nov2019-estudos-estabilidade_EN.pdf
ASTM F-1980-16 Std Guide Accelerated Aging of Sterile Barrier Systems for Med Deviceshttps://www.astm.org/Standards/F1980.htm
ASTM D-4332-14 Practice for Conditioning Containers, Packages, or Packaging Components for Testinghttps://www.astm.org/Standards/D4332.htm
ASTM-F-2097-16 Guide for Design and Evaluation of Primary Packaging for Medical Productshttps://www.astm.org/Standards/F2097.htm
CHPA Guideline for the Stability Testing of Nonprescription (OTC) Drug Products Not Regulated by an NDA/ANDAhttps://www.chpa.org/public-policy-regulatory/voluntary-codes-guidelines/guideline-stability-testing-nonprescription-otc
China (NMPA) Stability Studies of Pharmaceutical Packaging Materials in Chinahttps://www.westpharma.com/en/blog/2019/May/stability-studies-of-pharmaceutical-packaging-materials-in-china#
Development of the Chinese Pharmacopoeia 2020 Edition General Chapters: A Reviewhttps://www.sciencedirect.com/science/article/pii/S2095177921000496
EMA Guideline: Stability Testing of Existing Active Substances and Related Finished Products 2007http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003466.pdf
EMA Guideline on stability testing for applications for variations to a marketing authorisationhttp://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/04/WC500164972.pdf
EMA Note for Guidance on In-Use Stability Testing of Human Medicinal Products March 1 2001https://www.ema.europa.eu/documents/scientific-guideline/note-guidance-use-stability-testing-human-medicinal-products_en.pdf
EMA ‘Guideline on declaration of storage conditions: A: in the product information of medicinal products B: for active substances CPMP/QWP/609/96/Rev 2 (2007):https://www.ema.europa.eu/en/declaration-storage-conditions-medicinal-products-particulars-active-substances-annex
EMA ‘Quality of medicines questions and answers: Part 2’https://www.ema.europa.eu/en/human-regulatory/research-development/scientific-guidelines/qa-quality/quality-medicines-questions-answers-part-2
EMA Note on EU implementation of ICH Q12 (guideline on technical and regulatory considerations for pharmaceutical product lifecycle management)https://www.ema.europa.eu/en/ich-q12-technical-regulatory-considerations-pharmaceutical-product-lifecycle-management
EP 25-A Evaluation of Stability of In-Vitro Diagnostic Reagents-Approved Guidance (Sample)https://clsi.org/media/1424/ep25a_sample.pdf
EU Regulation EudraLex The Rules Governing Medicinal Products in the European Union Volume 4 EU Guidelines for Good Manufacturing https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2014-11_vol4_chapter_6.pdf
EU Regulation Practice for Medicinal Products for Human and Veterinary Use Part 1 Chapter 6: Quality Control Sections 6.26-6.36https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2014-11_vol4_chapter_6.pdf
EU Regulation Annex 1 2020 Rev 2 for comment Manufacture of Sterile Productshttps://ec.europa.eu/health/medicinal_products/consultations/2020_sterile_medicinal_products_en
EU Regulation Annex 19 Reference and Retention Samples 2005https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/pdfs-en/2005_12_14_annex19_en.pdf
FDA 1998 Withdrawn Guidance for Industry Stability Testing of Drug Substances and Drug Productshttp://academy.gmp-compliance.org/guidemgr/files/1-7-3.PDF
FDA Draft Guidance Quality Considerations for Continuous Manufacturing Productshttps://www.fda.gov/media/121314/download
FDA Guidance for Pharmaceutical Quality Control Labs (July 1993)https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-guides/pharmaceutical-quality-control-labs-793
FDA Guidances for Industry “ANDAs: Stability Testing of Drug Substances and Products” (June 2013)https://www.fda.gov/regulatory-information/search-fda-guidance-documents/andas-stability-testing-drug-substances-and-products
FDA Guidance for Industry ANDAs: Stability Testing of Drug Substances and Products Questions and Answershttps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM366082.pdf
FDA Guidance for CMC Information for Human Gene Therapy INDshttps://www.fda.gov/media/113760/download
FDA Guidance CMC Changes to an Approved Application: Certain Biological Productshttps://www.fda.gov/media/109615/download
FDA Guidance Immediate Release Solid Oral Scale-Up & Postapproval Changes CMC In-VitroDissolution & In-Vivo Bioequivalence Documentation
https://www.fda.gov/media/70949/download
FDA Guidance for Industry Expiration Dating of Unit-Dose Repackaged Solid Oral Dosage Form Drug Productshttps://www.fda.gov/media/70985/download
FDA Guidance In-Use Stability Studies and Associated Labeling Statements for Multiple-Dose Injectable Animal Drug Productshttps://www.fda.gov/media/102469/download
FDA Guidance for Industry and FDA Staff CGMP Requirements for Combination Productshttps://www.fda.gov/downloads/regulatoryinformation/guidances/ucm429304.pdf
FDA Guidance for Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Productshttps://www.fda.gov/regulatory-information/search-fda-guidance-documents/container-and-closure-system-integrity-testing-lieu-sterility-testing-component-stability-protocol
FDA Guidance Effects of COVID-19 on Meetings and User Fees Q&Ashttps://www.fda.gov/media/138358/download
FDA Guidance Expiration Dating and Stability Testing for Human Drug Productshttps://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/expiration-dating-and-stability-testing-human-drug-products
FDA Guidance Methods, Method Verification and Validation https://www.fda.gov/media/73920/download
Requirements for Combination Productshttps://www.fda.gov/combination-products/guidance-regulatory-information/combination-products-guidance-documents
Review and Update of Device Establishment Inspection Processes and Standardshttps://www.fda.gov/media/139466/download
Health Canada Guidance for Industry Stability Testing of Existing Drug Substances and Products. 2003 (superceded by 2017 Quality CMC)http://publications.gc.ca/collections/Collection/H49-183-2003E.pdf
Health Canada Guidance Document: Quality (Chemistry and Manufacturing): New Drug Submissions (NDSs) and Abbreviated New Drug Submissions (ANDAs) 2017https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/chemical-entity-products-quality/guidance-document-quality-chemistry-manufacturing-guidance-new-drug-submissions-ndss-abbreviated-new-drug-submissions.pdf
Health Canada Guidelines for environmental control of drugs during storage and transportation (GUI-0069)https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/good-manufacturing-practices/guidance-documents/guidelines-temperature-control-drug-products-storage-transportation-0069.html
ICH Q1A (R2) Stability Testing of New Drug Subtances and Products http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1A_R2/Step4/Q1A_R2__Guideline.pdf
ICH Annex 10 Stability testing of api's & fin pharma prod. (See WHO Annex 10)https://www.who.int/medicines/areas/quality_safety/quality_assurance/TRS1010annex10.pdf?ua=1
ICH Q1B Photostability Testing of Stability Testing of New Drug Subtances and Productshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1B/Step4/Q1B_Guideline.pdf
ICH Q1C Stability Testing of New Dosage Formshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1C/Step4/Q1C_Guideline.pdf
ICH Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Productshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1D/Step4/Q1D_Guideline.pdf
ICH Q1E Evaluation for Stability Datahttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1E/Step4/Q1E_Guideline.pdf
ICH Q1E Evaluation for Stability Data (Presentation)http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1E/Presentation/Q1E_Presentation.pdf
ICH Q1F Stability Data Package for Registration Applications in Climatic Zones III and IV (withdrawn)https://www.ich.org/page/quality-guidelines; https://database.ich.org/sites/default/files/Q1F_Explanatory_Note.pdf
ICH Q2 (R1) Validation of Analytical Procedures: Text and Methodologyhttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf
ICH Q3A (R2) Impurities in New Drug Substanceshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3A_R2/Step4/Q3A_R2__Guideline.pdf
ICH Q3B (R2) Impurities in New Drug Productshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3B_R2/Step4/Q3B_R2__Guideline.pdf
ICH Q3C (R6) Impurities: Guideline for Residual Solventshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3C/Q3C__R6___Step_4.pdf
ICH Q3C (R6) Impurities: Guideline for Residual Solventshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3C/Concept_papers/Q3C_Concept_Paper.pdf
ICH Q3C (R6) Impurities: Guideline for Residual Solventshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3C/ICH_Q3CR6_Step4_09Jan2017.pdf
ICH Q3C (R7) Impurities: Guideline for Residual Solvents (revision of R6 in progress for 3 new solvents)http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3C/Q3C-R7EWG_WorkPlan_2018_0221.pdf
ICH Q3D Guideline for Elemental Impuritieshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3D/Q3D_Step_4.pdf
ICH Q3D (R1) Guideline for Elemental Impuritieshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3D/Q3D-R1EWG_Document_CadmiumPDEGuideline_Step2_2018_0518.pdf
ICH Q3D (R2) Guideline for Elemental Impurities Final Concept Paper 2016http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3D/Q3D_R2__EWG_final_Concept_Paper_Cutaneous_and_Transdermal_1Sep2016.pdf
ICH Q3D Final Concept Paper Q3D: Elemental Impurities IWGhttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3D/Q3D_IWG_Final_Concept_Paper_October_21_2014.pdf
ICHQ3D Training; Implementation of Guideline for Elemental ImpuritiesSee previous line for preliminary link
ICH Q4-Q4B PharmacopoeiasSee http://www.ich.org/products/guidelines/quality/article/quality-guidelines.html for listing of multple links
ICH Q5C Stability Testing of Biotechnological/Biological Productshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q5C/Step4/Q5C_Guideline.pdf
ICH Q5E Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing Processhttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q5E/Step4/Q5E_Guideline.pdf
ICH Q6A Specifications: Test Procedures and Acceptance Criteria for New DS and DP Chemical Substanceshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q6A/Step4/Q6Astep4.pdf
Decision Trees for Q6Ahttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q6A/Step4/Decision_Trees.pdf
ICH Q6B Specifications: Test Procedures and Application Criteria for Biotechnical/Biological Productshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q6B/Step4/Q6B_Guideline.pdf
ICH Q7 Good Manufacturing Guide for Active Pharmaceutical Ingredientshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q7/Step4/Q7_Guideline.pdf
Q&A on ICH Q7 – Good Manufacturing Practice Questions and Answers Documenthttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q7/ICHQ7_Q_AStep4Presentation_2017_0821.pdf
ICH Q8 Pharmaceutical Developmenthttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_Guideline.pdf
Q8, Q9, Q10 Training Programhttp://www.ich.org/products/guidelines/quality/training-programme-for-q8q9q10/presentations.html
ICH Q9 Quality Risk Managementhttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q9/Step4/Q9_Guideline.pdf
Q9 Briefing Packhttp://www.ich.org/products/guidelines/quality/q9-briefing-pack/briefing-pack.html
ICH Q10 Pharmaceutical Quality Systemhttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q10/Step4/Q10_Guideline.pdf
ICH Q10 - Pharmaceutical Quality System - Briefing Presentationhttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q10/Presentation/Q10_General_Presentation.pdf
ICH Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotech/Biological Entitieshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q11/Q11_Step_4.pdf
Questions and Answers for Q11 Development and Manufacture of Drug Substanceshttp://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q11/Q11IWG_Step4_QA_2017_0823.pdf
ICH Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Managementhttps://database.ich.org/sites/default/files/Q12_Guideline_Step4_2019_1119.pdf
ICH Q12 Annex for Tech and Regulatory Considerations for Pharmaceutical Product Life Cycle Managementhttps://database.ich.org/sites/default/files/Q12_Annexes_Step4_2019_1119.pdf
ICH Q13 Continuous Manufacturing of Drug Substances and Drug Products 11/2018https://database.ich.org/sites/default/files/Q13_EWG_Concept_Paper.pdf
ICH Q14 Analytical Procedure Dev & Rev Q2(R1) Analytical Validation 11/2018https://database.ich.org/sites/default/files/Q2R2-Q14_EWG_Concept_Paper.pdf
ISO 11607-1 Section 6.4 Stability Testinghttps://www.iso.org/obp/ui/#iso:std:iso:11607:-1:ed-1:v1:en
ISO 23640:2015 Evaluation of stability of in vitro diagnostic reagentshttps://shop.bsigroup.com/ProductDetail/?pid=000000000030326409
MHRA Inspectorate Blog Temperature Mapping-an introduction GDP Guide 3.2.1 https://mhrainspectorate.blog.gov.uk/2016/07/14/temperature-mapping-an-introduction/
PDA Tech Rpt 53:Guidance for Industry:Stability Testing to Support Distribution of New Drug Productshttps://store.pda.org/TableOfContents/TR53_TOC.pdf
PIC/S Draft Rec. Evaluate / Demo Effectiveness of Pharma Quality System in relation to Risk-based Change Management Nov 2019https://picscheme.org/en/news?itemid=62
PIC/S informationhttps://redica.com/pharma-pic-s-gmp-inspection-reliance-guidance-helps-global-agencies-during-pandemic/
US Regulation 21 CFR 211.166 Stability testinghttps://www.govinfo.gov/content/pkg/CFR-2011-title21-vol4/pdf/CFR-2011-title21-vol4-sec211-166.pdf
US Regulation 21 CFR 820 Medical Deviceshttps://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=820
US Regulation CGMP Compliance Considerations for Combination Product Manufacturing- Office of Manufacturing Quality, CDER/OChttps://www.fda.gov/media/102786/download
WHO Annex 2 to WHO Technical Report Series, No. 953 ‘Stability conditions for WHO Member States by Region (August 2018)https://www.who.int/medicines/areas/quality_safety/quality_assurance/StabilityConditionsTable2updatedAugust2018.pdf?ua=1
WHO Annex 4 General Guidance on Hold-time Studieshttps://www.who.int/medicines/areas/quality_safety/quality_assurance/Annex4-TRS992.pdf?ua=1
WHO Annex 8 ‘Points to consider for setting the remaining shelf-life of medical products upon deliveryhttps://www.who.int/docs/default-source/medicines/who-technical-report-series-who-expert-committee-on-specifications-for-pharmaceutical-preparations/trs1025-annex8.pdf?sfvrsn=dfb3eca3_2&download=true
WHO Annex 9 Guidance to storage & transport of time/temp sensitive pharma productshttps://www.who.int/medicines/areas/quality_safety/quality_assurance/ModelGuidanceForStorageTransportTRS961Annex9.pdf?ua=1
WHO Annex 10 - Stability testing of active pharmaceutical ingredients and finished pharmaceutical products (Final version 2018)https://www.who.int/medicines/areas/quality_safety/quality_assurance/TRS1010annex10.pdf?ua=1
WHO Establishing stability of in vitro diagnostic medical devices 2017http://www.who.int/biologicals/expert_committee/ECBS_2017_BS2304_In_vitro_diagnostic_medical_devices.pdf
Rpt on Consultation on regional guidelines/stability studies of medicines & biologicalshttp://apps.who.int/iris/bitstream/handle/10665/258560/WHO_EM_EDB_081_E_en.pdf?sequence=1&isAllowed=y