Regulations, Guidelines & Other Documents
A select list of recently released regulations, guidelines and other documents compiled by the ISPE Regulatory Quality Harmonization Committee (RQHC)’s Europe-Middle East-Africa Regional Focus Group
November 2022
- EC / NCA
- EU health programme for 2023 5 topics:
- Crisis preparedness
- Health promotion & disease prevention
- Cancer
- Health systems and Health Care Workforce
- Digital
- Other actions.
- Annex to the European Commission guideline on 'Excipients in the labelling and package leaflet of medicinal products for human use' (updated)
- EU health programme for 2023 5 topics:
- EMA
- Concept paper Annex 11 released for public consultation. Comments due to PIC/S EMA
- EMA has established a Quality Innovation Expert Group (QIG) to support innovative approaches for the development, manufacture, and quality control of medicines for the benefit of patients in the European Union (EU).
- The EMA has published a revised 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 . The document was updated as follows:
- Update of Q&A 10 to add nitroso-duloxetine
- Introduction of Q&A 21 on approach to control presence of nitrosamine while the AI is being established.
- MHRA
- Innovation, Quality & Transparency – a Compliance Team 1 Perspective - MHRA Inspectorate (blog.gov.uk)
- Return to International GMP Inspections - MHRA Inspectorate (blog.gov.uk)
- MHRA Process for approving Manufacturing Authorisations or API Registrations in relation to unlicensed Cannabis-Based Products for Medicinal Use - MHRA Inspectorate (blog.gov.uk)
- WHO
- the Report of the 75th meeting of the WHO Expert Committee on Biological Standardization (ECBS) was published: https://www.who.int/groups/expert-committee-on-biological-standardization and included
- Annex 2: WHO manual for the preparation of reference materials for use as secondary standards in antibody testing
- Annex 3 - Guidelines on evaluation of biosimilars (who.int);
- Annex 4 - Guidelines for the production and quality control of monoclonal antibodies and related products intended for medicinal us
- the Report of the 75th meeting of the WHO Expert Committee on Biological Standardization (ECBS) was published: https://www.who.int/groups/expert-committee-on-biological-standardization and included
- OTHERS
- FDA
- FDA has issued a final guidance: Comparability Protocols for Postapproval Changes to the Chemistry, Manufacturing, and Controls Information in an NDA, ANDA, or BLA
- Updating of guidance for industry Planning for the Effects of High Absenteeism to Ensure Availability of MedicallyNecessary Drug Products
- Updated final guidance (2007) "Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) - Small Entity Compliance Guide.“
- FDA has announced initiation of the CMC Development and Readiness pilot that features increased communication between FDA and sponsors and explores the use of science- and risk-based regulatory approaches.
- FDA published a new Manual of Policies and Procedures (MAPP), MAPP 5015.13 Quality Assessment for Products in Expedited Programs. This MAPP provides information on OPQ’s use of regulatory flexibilities to help overcome CMC readiness challenges.
- FDA recently revised two compliance programs that are implemented as of October 17, 2022:
- CP7346.832—Preapproval Inspections which provides preapproval inspection (PAI) coverage for new drug applications (NDAs) and abbreviated new drug applications (ANDAs); and
- CP7356.002—Drug Manufacturing Inspections which provides current good manufacturing practice surveillance inspection coverage for drug manufacturing establishments.
- ICH
- 2022
- October 2022
- EMA
- EMA has issued a Concept paper on the Establishment of a Guideline on the Development and Manufacture of Synthetic Oligonucleotides
- The EMA has published the Terms of reference of the HMA/EMA task force on availability of authorised medicines for human and veterinary use, as well as their Work programme.
- EC has released Cyber Resilience Act European Cyber Resilience(european-cyber-resilience-act.com)
- EMA
- August 25th 2022 Official publication of the updated Annex 1
- This document is applicable with implementation period 1 year and 2 years for the clause 8.123
- In some countries it will be considered as a guidance recommendation up to the translation in the local language.
- MHRA
- Others
- PIC/S has now published the revised GMP Annex 1 GMP Annex 1 on the manufacture of sterile products, as final. on the manufacture of sterile products, as final. The deadlines for implementation are aligned with the EU, that is 25 August 2023, except for point 8.123 on lyo (one year later).
- The TGA has published UDI Consultation 3 - Detailed considerations for implementing the proposed Australian medical device UDI regulatory framework
- ANVISA published the RDC # 750/22 that establishes a temporary optimized analysis procedure, which uses the evaluation carried out by an Equivalent Foreign Regulatory Authority (EFRA) for the verified analysis of the registration and post-registration applications of small molecules products, biological products and their active substances.
- EMEA Regulatory Update - ICH
- Q5A(R2) reached step 2b on 29 September 2022 review and is open for consultation
- EMA
- April 2022
- Reg awareness
- Multistakeholder workshop on EMA’s extended mandate | European Medicines Agency (europa.eu)
- EMA’s extended mandate role for drug shortages prevention
- Emergency Task Force
- Coordinating-expert-panels-high-risk-medical-devices-vitro-diagnostics
- Opening statements from stakeholders - Adrian van den Hoven (Medicines for Europe Director General) (europa.eu)
- Multistakeholder Workshop on EMA’s extended mandate – YouTube
- Monitoring and mitigating shortages of medicines and devices (europa.eu)
- Multistakeholder Workshop on EMA’s extended mandate session 1 - YouTube
- Addressing public health emergencies through the ETF (europa.eu)
- Multistakeholder Workshop on EMA’s extended mandate session 2 - YouTube
- Coordinating expert panels on high-risk medical devices and in vitro diagnostics (europa.eu)
- Multistakeholder Workshop on EMA’s extended mandate session 3 - YouTube
- The European Health Union (europa.eu)
- Regulation on EMA’s extended mandate becomes applicable | European Medicines Agency (europa.eu)
- Crisis preparedness and management | European Medicines Agency (europa.eu)
- Multistakeholder workshop on EMA’s extended mandate | European Medicines Agency (europa.eu)
- RQHC EMEA SC Copenhagen
- Topics Identification for next IWG-EMA/IP with EFPIA.
- Chapter 4 Annex 11 still under development
- Holistic approach for Digitisation, AI, ML, Data management
- List of possible deep dives
- After Annex 1 release
- Training on ICH Q9 examples
- Drug shortages prevention
- Extended mandate of EMA by regulator.
- WHO hot topics
- 2023 regulatory summit or panel sessions in our conferences
- Topics Identification for next IWG-EMA/IP with EFPIA.
- Reg awareness
- March 2022
- EMEA Regulatory Update - EMA
- PRIME: 5 years' experience report
- Release of Annex 21 Imports and exports
- vol4_annex21_en.pdf (europa.eu) Deadline for coming into operation: 21 August 2022 (6 months after publication]
- This Annex summarizes the GMP requirements applicable to a Manufacturing Import Authorisation (MIA) holder, when importing medicinal products (human, investigational and veterinary) from outside the EU/EEA. The guidance in the main chapters and other annexes of the Guide to Good Manufacturing Practice for Medicinal Products ("the EU GMP Guide") also apply, as appropriate, for other GMP activities carried out and should be consulted for supplementary guidance. Medicinal products that enter the EU/EEA with the intention of export only and that are not processed in any form nor released for placing on the EU/EEA market, are not covered by this Annex.
- vol4_annex21_en.pdf (europa.eu) Deadline for coming into operation: 21 August 2022 (6 months after publication]
- EMEA Regulatory Update - MHRA
- MHRA Good Practice Symposia Week (7 to 11 March 2022) - MHRA Inspectorate (blog.gov.uk)
- Compliance Monitor process (Part 1) – An introduction - MHRA Inspec
- The MHRA’s delivery plan for 2021 to 2023 committed to the use of innovative interventions to ensure the UK continues to provide high quality medicines. We are preparing to pilot a new Compliance Monitor (CM) supervision process for appropriate GMP (Good Manufacturing Practices) and GDP (Good Distribution Practices) Inspection Action Group (IAG) cases.torate (blog.gov.uk)
- EMEA Regulatory Update - WHO
- WHO Meeting in end of April
- New GMP documents.
- WHO Meeting in end of April
- EMEA Regulatory Update - OTHERS
- Japanese Regulators Issue New Guidelines Covering Medical Device Cybersecurity
- Health Canada Guide to the exceptional importation and sale of drugs in response to drug shortages (GUI-0148) is effective 02-Mar-2022.
- EMEA Regulatory Update - FDA
- FDA - Guidance on Pre-Launch Activities Importation Requests (PLAIR): FDA is announcing the availability of a final guidance for industry
- FDA Proposes Amendments to Medical Device Quality System Regulation, mainly to include ISO
- FDA Guidance on Verification Systems under the drug Supply chain Security Act for certain Prescription drug
- Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs | FDA
- Comments due by May 9th 2022
- EMEA Regulatory Update - EMA
- February 2022
- EMA
- Regulation on EMA Extended Mandate Published - A Regulation strengthening the role of the EMA in crisis preparedness and management has been published in the EU Official Journal.The new regulation will apply from 1 March 2022 (with the exception of the provisions on shortages of critical medical devices, which will apply from 2 February 2023).
- Reflection paper on the use of interactive response technologies (interactive voice/web response systems) in clinical trials, with particular emphasis on the handling of expiry dates. This reflection paper seeks to provide the current thinking of the inspectors working groups on the use of interactive response technology systems, with particular mention of the removal of expiry dates from investigational medicinal product, for clinical trials conducted under the Clinical Trial Directive (2001/20/EC).
- EC
- Removal of TiO2 in Food industry
- EMA made a statement such implementation for pharma industry will require more than 10 years. In the attachment of EMA we have an EFPIA survey and EMA report.
- EFSA decision: Titanium dioxide: E171 no longer considered safe when used as a food additive | EFSA (europa.eu)
- EMA report: 2021-09-08-Report on pharmaceutical aspects on impact of removal of TiO2 on medicines + Executive summary - Final (word version) (europa.eu)
- EC Q&A: Re-evaluation (europa.eu)
- MHRA
- Interesting document with regulators feed back on clinical trials review dusring the pandemic period.
- Blog on lessons learned on clinical trials Regulator’s experience of clinical trials during the Covid-19 pandemic (Part 2) – what we have learned - MHRA Inspectorate (blog.gov.uk)
- Others
- China Released the Draft of Good Manufacturing Practice - Annex of Drugs for Clinical Trials
On Jan 18, NMPA released draft of the Good Manufacturing Practice - Annex of Drugs for Clinical Trials seeking comments before Feb 17th. Chinese version - Turkey - Guidelines on Variations for Registered Medicinal Products for Human Use
The Turkish Medicines and Medical Devices Agency (TITCK) has finalized and published new guidelines on variations for registered Medicinal Products for Human Use in the Official Gazette (Turkish language) numbered 31693 of 18 December 2021. - UK, USA and Canadian regulators identify 10 guiding principles to be addressed when medical devices use AI or machine learning software
These principles are intended to lay the foundation for developing good machine learning practices (GMLP) and will help guide future growth in this rapidly progressing field.
- China Released the Draft of Good Manufacturing Practice - Annex of Drugs for Clinical Trials
- US FDA
- Guidance Agenda: Guidance Documents CBER is Planning to Publish During Calendar Year 2022 (fda.gov) - The list includes topics that currently have no guidance associated with them, topics where updated guidance may be helpful, and topics for which CBER has already issued Level 1 draft guidances that may be finalized following review of public comments
- FDA’s recently published CDER 2022 guidance agenda. FDA is planning to publish 98 guidances (GL) separated in 17 categories.
- PIC/S
- PIC/S News, February 2022 - The Pharmaceutical Inspection Co-operation Scheme "GMP Guide to Good Manufacturing Practice for Medicinal Products" has been revised to include a revised annex 13 on the manufacture of investigational medicinal products; and a new annex 16 on the certification by the authorized person and batch release. The revised GMP guide entered into force on Feb. 1. GMP Guide PE 009-16 - Publications (picscheme.org)
- EMA
- October 2022
- 2021
- November
- EU Commission
- EMA
- Final Programming Document 2021-2023 (europa.eu)
- European Medicines Agency mid-year report 2021 (europa.eu)
- 7.1 EMA’s Extended mandate progress update - H Boone (europa.eu)
- EU-Updated EMA/CMDh Nitrosamine Impurities Q&As - updates to Question 8 on confirmatory testing and Question 12
- EU-Electronic submission of investigational medicinal product data
- MHRA
- FDA
- ICMRA
- ‘Pre-Requisites for Regulatory Flexibility in Pharmaceutical Manufacturing Change Management’ and related report. published on the ICMRA website
- October
- EC Consultation - Dec 21st 2021 pharmaceutical legislation
- HERA- Health Emergency preparedness and Response Authority
- Improving the use and availability of Antimicrobials in Europe.
- 01_DRAFT Summary Record_82th meeting of the Pharmaceutical Committee - Cttee Members version (europa.eu)
- EMA - HMA report on real world metadata
- EMA - Big Data HMA-EMA Steering Group
- ICMRA – EMA
- EMA - GMP
- EMA - Nitrosamines
- WHO - Moving towards digital documentation of COVID-19 status (who.int)
- FDA - Flexibility for changes on integrity closure
- June
- EU – Medical Device Regulation applicable from 26th May
- EU – Modification of the Medical Devices ordinance (Switzerland)
- EU – Combination products in Switzerland
- 17th May – launch of Unique Device Identifier Helpdesk
- EU – Draft common standard for electronic product information for human medicines
- EU – Clinical Trial Information System (CTIS)
- Publication of several guides etc on this new system ahead of its planned launch
- EU – New Reflection Paper on forecasting demand for medicines (from EU Steering Group on Shortages)
- EU – Artificial Intelligence in Medicines Regulation (report from April Workshop)
- EU / Brazil – Working arrangement between EMA and ANVISA for the exchange of non-public information
- UK – MHRA establishes own GMDP database
- May
- EU – new Q&A on GMPs for ATMPs
- EU – allows importation site to be different to release site
- EU and Canada – recognition of extra-jurisdictional GMP inspection outcomes
- WHO – Transfer of technology in pharmaceutical manufacturing
- Report of the WHO Committee of Biological Standardisation
- Expert Committee on Biological Standardization (who.int)
- WHO IFPMA paper on Traceability of medical products
- Revision of PIC/S GMP Guide
- April
- EU Digital Health Agency
- To provide comprehensive support to the Digital Health and Care Innovation initiative.
- The project’s approach involves a number of actions that will boost innovation and advance the Digital Single Market priorities for the digital transformation of health and care (DTHC), as outlined in the European Commission’s 2018 Communication on the topic.
- The priorities concern:
- citizens’ secure access to and sharing of health data across borders
- better data to advance research, disease prevention and personalised health and care
- digital tools for citizen empowerment and person-centred care.
- To achieve these three priorities, the project work plan offers two forms of support. Together, they will form a common vision of EU coordination and support for DTHC beyond 2020.
- Support to large scale deployment of digital solutions for person-centred integrated care
- DigitalHealthEurope’s main objective the deployment of digital solutions for person-centred integrated care.
- The selected initiatives will have the opportunity to pursue replication and scaling-up. This will be done with the aid of instruments such as matchmaking and a twinning support scheme. A deployment support service will include guidelines, checklists and documented successful approaches. They will help define the “building blocks” for the scaling-up of innovative practices.
- DigitalHealthEurope will also facilitate the creation of a shared platform for multi-stakeholder communities. With the help of associated experts and contributors, they will provide key DHE outcomes such as white papers, guidelines and policy recommendations.
- DigitalHealthEurope will ensure mutual flow of information … into a roadmap, advice and recommended actions.
- EMA – Practical Guidance on Type 1A / 1B Variations
- EU – Mandate of Compliance Group in Joint Audit Programme
- MHRA – Return to ON SITE Inspections (in UK) from 29th March
- WHO
- Technical Reports (1033)
- Annex 1 – Specifications for Pharmaceutical Preparations
- Annex 2 – Health-based exposure limits in cleaning validation
- Annex 3 – Water for pharmaceutical use
- Annex 4 – Data integrity
- Annexes 5, 6 and 7 – Related to condom testing, storage and shipping and post-market surveillance
- Annex 8 – Biowaiver list
- Annex 9 – Certification scheme on quality of products
- Annex 10 – Good Reliance Practices
- Annex 11 – Good Regulatory Practices
- WHO Guidance on setting remaining shelf-life for the supply / procurement of emergency health kits (draft)
- FDA - Remote Interactive Evaluation Guidance from FDA
- EU Digital Health Agency
- February
- EU – ‘Toolbox’ guidance on scientific and regulatory approaches to support CMC development for PRIME programs
- Template to provide comments on the first page of the guidance
- Parallel application EU / Out of EU
- PIC/S inspector aide memoires
- Utilities; biotech; packaging; assessment of QRM implementation
- QM-System (picscheme.org)
- Aide memoire - GMP inspection focused on packaging/labelling/mix-up prevention (picscheme.org)
- 24 June 2002 Page 1 of 9 PI 009-1 (picscheme.org)
- 3820 (picscheme.org)
- EAEU pharmacopoeia effective from 1st March
- Armenia, Belarus, Kazakstan, Krygyzstan, Russia
- pharmacopoeia (eurasiancommission.org)
- Russia and Jordan apply to PIC/S
- Saudi Arabia – Draft guideline for Child resistant packaging Connecting Pharmaceutical Knowledge
- US FDA – CBER and CDER guidance agendas for 2021
- EU – ‘Toolbox’ guidance on scientific and regulatory approaches to support CMC development for PRIME programs
- January
- EU – EUDAMED database for Medical Devices
- WHO – Regulatory Considerations for RNA Vaccines
- WHO – Transfer of Technology in Manufacturing
- ICMRA – Recommendations on Interoperability of Track and Trace systems
- ANVISA accepted as member of PIC/S
- November
- 2020
- December
Pharmaceutical Legislation to be revised
- A pharmaceutical strategy for Europe
- Create a future proof regulatory framework and support industry in promoting research and technologies that reach patients and fulfil therapeutic needs while addressing market failures. Take into account the weaknesses exposed by the coronavirus pandemic and factor-in actions to strengthen the system.
It will be based on 4 specific pillars, which include legislative and non-legislative action:
- Ensuring access to affordable medicines for patients, and addressing unmet medical needs (e.g. in the areas of antimicrobial resistance, rare diseases);
- Supporting competitiveness, innovation and sustainability of the EU’s pharmaceutical industry and the development of high quality, safe, effective and greener medicines;
- Enhancing crisis preparedness and response mechanisms, diversified and secure supply chains, address medicines shortages;
- Ensuring a strong EU voice in the world, by promoting a high level of quality, efficacy and safety standards.
- November
- EU – Agency of Health Security
- EU – Reflection Paper on Pharmaceutical Development of Products for Older Populations
- EU – File Type 1 Variations by end of November
- EU – Labelling and packaging flexibilities for COVID vaccines
- To support rapid deployment (eg use of English packs etc)
- EU Vaccine Strategy - Regulatory flexibility – Labelling and packaging flexibilities
- PIC/S webinar on Quality Risk Management
- WHO – GMPs for Investigational Products
- WHO – Access to COVID 19 tools – vaccines Q&As
- October
- EU – Medicines Regulatory Network Business Continuity plan
- WHO – Considerations for Evaluation of COVID-19 vaccines – points to consider for manufacturers
- EU – EMA Management Board meeting
- Covers COVID 19 activities; nitrosamines; IT systems for Clinical Trial Regulation; review of EMA Working Parties
- ICH – Issue of Step 2 draft of Q3D (elemental impurity) revised guideline
- Section giving PDEs for topical products
- Updates to PDEs for Au, Ag and Ni
- July/Aug/Sept
- EU – Updated Guidance on FMD Safety features
- EU – Revised Guidance on Water Quality
- EU – New Aides Memoire for Inspectors
- EU – Q&As on Clinical Trial Regulation
- EU – Pilot on Shortage Notification POSTPONED
- EU – Joint Audit Programme Update
- EU – EMA / FDA Collaboration on Medicines
- EU – EU / Canada Mutual Recognition Agreement Updated
- EU – EMA Annual Report
- WHO – Water Pharmaceutical Use (revision draft)
- WHO – Evaluating and designating regulatory authorities as WHO Listed Authorities (draft)
- WHO – Revision – Guidelines for Data Integrity
- WHO – Good Reliance Practices
- New Eurasian Economic Union Pharmacopoeia
- 157 general Articles – implement from 1/3/21 ; comply by 1/1/26
- https://docs.eaeunion.org/docs/ru-ru/01426917/err_13082020_100
- New Eurasian Economic Union GMP
- Inspectable expectations from 1/1/26
- Azerbaijan applies to PIC/S
- Saudi Arabia – Draft guideline for Variations
- ICH – Athens ICH meeting will be VIRTUAL
- ICH – M7 Q&As published for comment – mutagenic impurities (but not nitrosamines …)
- ICH – Training materials for ICH M7 Q&A
N-Nitrosamines
- EU – Nitrosamines – CHMP Article 5(3) Opinion
- EU – Q&A for MAHs based on Article 5(3) Nitrosamines
- Revised reporting dates – March and June 2021. All biological products now in scope.
- Q&A for marketing authorisation holders/applicants on the CHMP Opinion for the Article5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products
- EU – Publication of ‘sartans LL’ – nitrosamines
- EDQM – from 1/10/20 CEPs must include a nitrosamine risk assessment
- US – FDA have also issued nitrosamines guidance for immediate implementation
- June
- Covid-19 International Regulatory Alignment
- US – FDA Guidance – Developing drugs and biological products for treatment / prevention
- EC – Roadmap – Pharmaceutical Strategy for Europe
- EU – Commission eases rules for renewing Notified Body designations
- WHO – Good reliance practices in regulatory decision making
- PIC/S – Cross-contamination in Shared Facilities
- Q&A and aide memoire in support of the 2018 guideline
- April/May
- EU – MDR delay official – industry calls to push back IVDR
- EU – MDCG offers new MDR implementation plan and significant change guidance
- EU – Medical Device Coordination Group issues more details on clinical evidence and performance evaluation and Class 1 translational provision
- EU – Draft GMP annex on Importation
- EU – Update to EMA publication on Nitrosamine expectations
- EU – Publishes on ICH Q12 product lifecycle management
- EU – Guidance for accelerated procedures for Covid-19 treatments and vaccines
- EU – Update on management of clinical trials during Covid -19
- EU – Covid19 Q&A - reg expectations for med. products during pandemic (‘regulatory flexibilities’)
- EU – Update on actions to support medicine availability during COVID crisis
- EU – Devices – new guidance on Notified Body Audits during the pandemic
- EU – EMA to issue electronic certificates for medicines
- WHO – FAQs on manufacturing, trials and testing during Covid-19
- There are MANY other Covid crisis management publications, from MHRA and others
- ICH – Q3C solvents guideline updates
- ICH – Implementation of ICH guidelines
- ICH – Q1 stability training module
- WHO – Technical Reports
- Annex 1 – procedure for development of monographs for inclusion in Int. Pharm.
- Annex 2 – GMP for radiopharmaceuticals
- Annex 3 – Production of WFI by means other than distillation
- Annex 4 – good chromatography practices
- Annex 5 – Quality management systems requirements (national inspectorates)
- Annex 6 – PtC for environmental aspects of manufacturing practices for prevention of antimicrobial resistance
- Annex 7 – Good storage and distribution practices
- Annex 8 – PtC setting remaining shelf-life of products
- Annex 12 – Biowaiver list
- Annex 13 – Implementation of QMS for national regulatory authorities
- March
- EU – New GMP Annex 1 – targeted consultation
- EU – Falsified Medicines – Q&A version 17 on Safety Features
- EU – European Commission issues new guidance on EUDAMED Medical Device database nomenclature
- UK – MHRA releases updated guidance on clinical device investigations
- US – Shortage Report
- Africa – South African Development Community BIOSIMILAR Guidances
- WHO – Revision of GMP for Sterile Products
- PIC/S – Saudi Arabia applies for PIC/S membership (February)
- February
- EU – Draft Reflection Paper on GMP for MAHs
- EU – Pilot of simultaneous National Scientific Advice
- EU – Electronic Product Information
- EU – New guidance for Medical Devices and IVD Cybersecurity Under MDR and IVDR
- ICH – Recommended Adoption of ICH Guidelines in CHINA
- ICH Q8; Q8,9,10 Q&A; Q10; Q11; Q11 Q&A recommended for adoption
- Coming into force January 2020 – Q2; Q3AA, Q3B, Q3C, Q3D; Q5A, Q5B, Q5C, Q5E; Q6A; M7
- PIC/S Meetings in Toyama
- PIC/S Pilot on Inspection of Manufacturers of Steriles
- January
- EMA – Midyear Report 2019
- EU – Nitrosamine Impurity Q&As UPDATED
- EU – Rolling overview link on Nitrosamines
- EU – Commissioner for Health states Medical Device Regulation deadline on May 26th 2020 will not change
- EU – Updated Guideline on Package Leaflet information for ETHANOL
- EU – Falsified Medicines Directive – Aide Memoire for GDP inspection
- EU – Genetically-Modified Organism requirements for in vivo gene therapy products
- ICH – Q12 CMC Product Lifecycle guideline completed
- WHO – Evaluating and designating regulatory authorities as WHO LISTED Authorities
- WHO- signs memo of understanding with IGBM (generic and biosimilar association) to promote access
- PIC/S – New recommendation on how to gauge the effectiveness of a PQS with risk-based change management
- ASTM – Ballot on draft standards
- on Microbial Ingress testing for Single-Use systems
- on Stability of Early Phase Protein Products
- on Removal of Retrovirus by filtration
- December
- 2019
- November
- EU – Nitrosamine Impurity Assessment Templates
- EU – Benefit Risk assessment for Phthalates in Medical devices
- EU – Process for Requesting EMA Certificates (Nov to Jan 2020 interim process)
- EU – Q&A on Implementation of MDR and IVDR
- EU – New guidance for manufacture of implantable devices
- EU – Commission announces (2y) delay for Eudamed Device database
- EU- China Dialogue on Medicines Regulation
- ICH Q3C Correction – PDE for ethylene glycol reinstated to previous value …
- WHO – Guidelines on Data Integrity
- October
- EU – Proposed document on requirements for Regulatory Authority recognition of conformity assessment bodies conducting Medical Device regulatory reviews
- EU – Commission explains new MDR, IVDR rules on Expert Device Panels
- EU – Revised guidance on FMD Safety Features
- MHRA – Update on strategy for pharmacopoeial public quality standards for biological medicines
- EU – Requirements on N-nitrosamines in APIs / Products
- Two documents released –
- Information on Nitrosamines for MAHs - Request to evaluate the risk of the presence on nitrosamine impurities in human medicinal products containing chemically synthesised active pharmaceutical ingredients (EMA/189634/2019)
- 6M period (from publication date) to assess all synthetic APIs/derived medicinal products
- 3y (2y in Canada) to verify with analytical testing
- At present, biological products stated to be out of scope
- Questions and Answers on ‘ Information for MAHs’ (EMA/428592/2019)
- Information on Nitrosamines for MAHs - Request to evaluate the risk of the presence on nitrosamine impurities in human medicinal products containing chemically synthesised active pharmaceutical ingredients (EMA/189634/2019)
- Call to clarify these publications 29th October
- EMA meeting on Sartans Learnings (TA invitees, HCPs, patient reps) in Amsterdam, 4th November
- Webex on topic by end year
- August/September
- EU – US – Mutual Recognition Agreement fully in place (24th July)
- EU – Information on batch testing in context of Brexit
- EU – Limits for nitrosamines
- EU – Quality of peptone used in API manufacture
- EC – Additional guidance clarifying medical device vigilance requirements
- France – Draft Medical Device Cybersecurity Recommendations
- EU – 2 new guidelines on DP shortage notification
- EMA submits comments to FDA on Biosimilars draft guidance
- EU – Ombudsman report on EMA pre-submission assessment activities
- EU-US – Meeting report from Workshop on Quality / CMC acceleration for early access approaches (Breakthrough and PRIME)
- EU – Guidance on Categorisation of Extension Applications and Variation applications
- EC – New guidances on Medical Device and In Vitro Diagnostic Regulations
- EU – Q&A on use of Out of Specification batches of Advanced Therapy products
- EU – updated Q&A on FMD Safety Features
- WHO – Guideline (rev1) on Good Storage and Distribution Practices
- WHO – Guideline (rev1) on Production of WFI by means other than distillation
- WHO – Policy (rev1) on Remaining Shelflife of medicinal products
- WHO – Guideline on Good Chromatography Practices
- July
- EU – Uptick in EMA Activities
- EU – US Mutual Recognition
- Germany now recognised
- Only Slovakia remains
- Germany now recognised
- EU – 2 new guidelines on DP Shortage Notification and Communication
- “a shortage occurs when supply does not meet demand at a national level”
- Guidance on detection and notification of shortages of medicinal products for Marketing Authorisation Holders (MAHs) in the Union (EEA)
- Good practice guidance for communication to the public on medicines’ availability issues
- And from French Health Ministry (Buzyn) – New Roadmap to Fight Against Product Shortages
- EU – Update of the EMA Q&A Guidance on GMP
- Create a new section on GMP for ATMPs AND
- EU – Q&A on Use of OOS batches of advanced therapy products
- TGA – guidance for sponsors seeking to obtain GMP clearance for an overseas manufacturing site of a medicine or API intended for supply in Australia.
- WHO – Guideline on Import Procedures for Medical Products
- WHO – Expert Committee on Biological Standardisation
- June
- EU – Draft Guideline on the Quality Requirements for Drug-Device combination products (integral and co-packaged)
- EU – Information in Clinical Trial (adult and paeds trials) database that will be made public
- EDQM – Inspection Report on Inspections and trends of deficiencies (2006-2018)
- UK – Consultation on the application of Analytical QbD principles to pharmacopoeial standards for medicines
- UK – MHRA Blogs on
- RSA – Released a set of guidances for comment
- eCTD; eSubmission; new registration validation templates (eCTD and esub)
- VARIATIONS addendum for orthodox medicines
- https://www.sahpra.org.za/Home/FullArticle/3bd90341-0e1a-417a-9676-d48513506e0a
- US – Development of Therapeutic Protein Biosimilars – DRAFT guidance on Comparative Analytical Assessment and other Quality-related considerations
- EU-US Mutual Recognition
- Netherlands and Luxembourg now recognised
- Only Germany and Slovakia remain
- Netherlands and Luxembourg now recognised
- EU – Recognise Korean-manufactured APIs as in line with EU standards
- Adding to Australia, Brazil, Israel, Japan and USA
- WHO – Guidelines for Implementation
- Guidances on
- Procedure for the development of WHO medicines quality assurance guidelines
- Heating, ventilation and air-conditioning systems fir non-sterile pharmaceutical products - HVAC
- GMPs on Validation – HVAC for non-sterile products; water systems; cleaning; analytical procedures; computerised systems; qualification; non-sterile process validation
- Procedure on conduct of equilibrium solubility determination for BCS classification
- Good practice for NRAs in implementing collaborative registration
- Example of a NRA reliance model
- Acknowledgement / approval of variations of products registered through the WHO collaborative procedure
- WHO – draft guidance on Quality Systems for Pharmaceutical inspectorates
- WHO – A framework for evaluating and designating WHO Listed Authorities
- Headline topics from most recent meeting of PIC/S Committee and Executive Bureau
- PICS Inspection Reliance Initiative – examples
- Updates on future revisions to PIC/S GMP Guide
- Steriles
- Biologicals and ATMPs
- IMP
- Certification and batch release
- Plan to develop an Aide-memoire on Tissue and Cell Therapy Product Inspections (excluding ATMPs)
- Completion of pre-accession of Saudi Arabia and application from Bangladesh
- Next Seminar on QA of Sterile Medicinal Products
- May
- EU - Variations Guidance Updates with CMC / GMP significance
- EU - EC launches portal to ease transition to new regulations on Medical Devices and In vitro Diagnostic Devices
- EU - Medical Device database to adopt Italy’s CND codes for Eudamed Device Database nomenclature
- EU - Draft corrigendum to Medical Devices Regulation
- EU - Medical Device Coordination Group Issues EUDAMED guidance
- FDA - confirms Bulgaria and Cyprus for Mutual Recognition
- Variations Guidance Updates with CMC / GMP significance: A series of updates to variation management approaches are issued by the EMA. These cover:
- Submission of changes to AUDIT DATES to verify GMP compliance for API manufacture
- Introduction of NEW MANUFACTURING SITE for DS or DP and what changes can be submitted under a single Type II Variation (changes to process, batch size, IPCs to adapt to new site settings - other changes should be submitted as a separate variations)
- Submission of change to Module 3.2.S or the update of an ASMF
- Submission of an updated CERTIFICATE OF SUITABILITY
- What is considered to be a 'non-significant IPC or specification parameter (does not include downgrade of CPP to non-CPP)
- What is considered to be within / outside range when applying for a NEW PACK SIZE
- Submission of NEW WORKING CELL BANK
- Submission of a new REFERENCE STANDARD FOR A BIOLOGICAL PRODUCT
- What changes in MANUFACTURING SITES, building, rooms and EQUIPMENT are covered by company quality system and GMP
- What is needed if there are changes to a MEDICAL DEVICE?
- How should one submit TRANSFER OF TEST METHODS for testing of BIOS products to a new or already authorised testing site; submission of editorial changes
- What is considered a NEW or MODIFIED THERAPEUTIC INDICATION.
- Feburary
- EU - GMP Annex 2 Updated
- EU - Draft Guideline on Quality and Equivalence of Topical Products
- EU - EDQM survey on Dissolution Test attribute in Ph.Eur.
- EU - Collated comments on ICH Q12
- EU - Q&A on safety features
- EU - Regulator’s Template for FMD Safety Features
- EU - Electronic product information for human medicines
- EU - EDQM guide for the elaboration and use of monographs on vaccines and immunosera
- January
- EU – Consultation on EMA Regulatory Science Plans to 2025
- EU – Mobile Scanning for Labelling and Product Leaflet
- EU – Draft revised BSE / TSE Guideline
- EU – Medicinal Products containing Genetically-Modified Organisms
- EU – Revision of Environmental Risk Assessment of Human Medicines
- EU –US Mutual Recognition Agreement
- PIC/S - DRAFT guidance on Good Practices for Data Integrity released
- ICH met in Charlotte NC, US in November
- Q12 – CMC Lifecycle management - EWG did not meet in Charlotte - public comment phase nearing completion. Comments now being collated. EWG will have an interim meet to consolidate comments in Japan in February
- M9 – BCS Based Biowaivers – EWG did not meet in Charlotte – public comment phase nearing completion. Comments now being collated.
- M7 – Mutagenic Impurities – EWG reconvened to deliver clarification Q&As to the M7 guidance
- Q13 – Continuous Manufacturing – EWG met for first time (FDA rapporteur) – concept paper finalised and constituents now engaged in providing ‘outline’ content of desired guidance
- Q14 / Q2 – Analytical Development and Validation – early stages
- Quality Discussion Group – Re-established to determine next wave of potential Quality topics
- At present topics such as Extractables / leachables (proposed by PhRMA) are pre- any agreement to establish working group
- November
- 2018
- November
- EU – Workshop on Accelerating CMC for PRIME / Breakthrough programs
- EU – Reflection Paper on Impurity Qualification Approaches
- EU – Draft guideline on Quality of Water
- EU – Updates on Excipient Packaging and Labelling Expectations
- EU – Update on EU / US MRA
- EU – Overview of comments received for guideline on quality aspects included in the product information for Vaccines
- EU – Guideline on requirements for Quality documentation for biological investigational medicinal products
- EU – Guideline on equivalence studies for locally-acting products in the GI tract
- EU – Revised guideline on BSE
- EU – Workshop on Product Shortage
- EU – Reflection Paper on (animal) tests used for product quality
- EU – EMA Workshop on Advancing Regulatory Science
- EU – EC letter on FMD Safety features implementation
- EU – Consultations on medicines for children and rare diseases
- EU – EC new guidance documents on Unique Device Identification System
- UK – MHRA Update on health-based exposure limits
- Swiss – Guidance document on Variations and Extensions
- ICH – Update to Q3C residual solvents
- PIC/S – New guidance on classification of GMP deficiencies
- October
- EU – Dossier requirements for ancillary medicinal substances in a medical device
- EU – Updated Q&A on Safety Features – wholesaler and parallel importers / distributors
- EU – Concept paper for Neonate product development
- EU – New website for EMA
- EU – US Mutual Recognition – Portugal now recognised (15th country)
- Ireland – HPRA – Medicines Shortage Framework
- Russia – Draft Guideline on Data Integrity
- ICH – EWG presentation materials on ICH M9 BCS-based biowaivers
- WHO – Guidelines on Validation of Computerised Systems
- WHO – Appendix 6 Validation – Qualification
- WHO – Guideline on Analytical Validation
- PIC/S – Bulgaria applies for membership
- ISTM – Revision of E2891 Multi-variant data analysis standard
- FDA – Release of draft guidance on post-approval changes for drug substances
- September
- EU – Medicines Supply Task Force – Workplan and Workshop
- EU – Update on EDQM’s actions on valsartan impurity management
- EU – Quality of Herbal Medicinal Products
- EU – Draft guideline on Quality, Safety and Efficacy of Medicines containing Genetically-Modified Organisms
- EU - Outcome of consultation on Health-based exposure limits Q&As
- PIC/S – Bulgaria applies to PIC/S and Jordan applies for pre-accession
- WHO – Guidelines on Import Procedures for Medical Products
- Saudi Arabia – Difficulties with acceptance of German manufactured products into Saudi Arabia
- Various news reports. And also reports of EFPIA / PhRMA letter to Saudi Arabia on the topic.
- August
- EMA – Updated application form for certificate of medicinal product
- EU – Revised (final) GMP Annex 2 on Manufacture of Biologicals
- EU – Revised (final) Annex 17 on Real Time Release Testing and Parametric release
- EU – Final GMO requirements for Investigational Products
- EU – Final guideline on the Quality, Preclinical and Clinical aspects of Gene Therapy Products
- EU – Updated Q&A guidance on Safety Features
- EU – Update on impurity-driven recall (valsartan)
- EMA - Annual Report 2017
- EU – Annual Report of the Inspectors Working Group
- EU - EMA Action plan on Advanced Therapy Medicinal Products
- EU / US Mutual Recognition Update – Lithuania and Ireland added
- EU / Japan – Updated Mutual Recognition agreement
- EU / US - Reinforced collaboration on medicines
- EU – Commission meeting on Medicines shortages
- MHRA (UK) – Updates GDMP and preparation for inspection guide
- ICH – revision of ICH Q3D (elemental impurities) – updated PDE for cadmium (3ug/day from 2ug/day)
- ICH – Release of ICH M9 draft guidance on BCS-based biowaivers for public comment
- PIC/S – Revision of PIC/S GMP guide
- PIC/S – New guidance documents (essentially based on EU guidance on these topics)
- Cross-contamination in shared facilities
- Health-based limits
- Risk assessment for GMP for excipients
- Good Distribution Practices
- Inspection reliance
- WHO Q&As – Similar Biotherapeutic products
- WHO – Protocol for solubility measurements (draft)
- WHO – Drugs on essential medicines list eligible for biowaivers (draft)
- WHO – Proposal for revision of the WHO Certification Scheme
- WHO - Technical Report series 1010
- Including Annex 3 – final guideline on procedures and data requirements for changes to approved biotherapeutic products
- Annex 5 – Final guideline on testing of suspect falsified medicines
- Annex 8 – Final Guidance on HVAC systems for non-sterile pharmaceutical products
- Annex 9 – final guidance on good practice for desk assessment of compliance with GMPs
- Annex 10 – Stability Testing of APIs and FPs
- Annex 11 – National registration of pharmaceutical products and vaccines approved by stringent regulatory authorities
- Appendix 5 - Validation of Computerised systems (draft)
- May
- EMA – 2017 Annual Report
- EMA – Report on Prior Knowledge Workshop
- EMA – Final Q&As on Health-based exposure limits
- EMA – Requirements for Quality Documentation for Biological investigational products
- EMA – Revision of template for Serious GMP non-compliance
- EMA – Variation classifications
- EMA – Certificates of Medicinal Products issued by the EMA
- EC – Q&As on Clinical Trials regulation (largely administrative)
- MHRA – Updated Out-Of-Specification Guidance
- WHO – Proposed revision of the WHO Certification Scheme
- WHO – Guidelines on Import Procedures
- Australia – Consultation on adoption of EU guidelines
- EU GMP guide annexes: Supplementary requirements: Annex 16 (Updated May 2018)
- Can a site have more than one QP performing certification of batches?
- Can there be more than one QP involved in the certification of a given batch?
- In the context of handling unexpected deviations, what is included in the scope of registered specifications for medicinal products?
- What is an ‘unexpected’ deviation?
- Does Annex 16 permit QP certification of more than one batch affected by the same unexpected deviation?
- ANSM – Guidelines of follow-up actions after an inspection
- April
- EU – Excipients in the labelling and package leaflet of medicinal products
- EU – Updated Q&A on Falsified Medicines Directive Safety Features
- MHRA – GXP data integrity
- WHO – Guideline on Validation
- WHO – Revised draft guidance on HVAC for Non-sterile products (part 2)
- WHO – Report on substandard and falsified medicines
- WHO – Production of Water for Injections
- Qatar – Guidelines for Variations
- March
- EU – Guidance on safety and efficacy follow-up for Advanced Therapy Medicinal Products
- EU – Certificate of Suitability – TSE Risk assessment
- EU – Q/A on Flu Vaccine Preparations
- EU – Quality Aspects in Product Information for Vaccines
- EU – Q/As on BSE and Vaccines
- EU – Vaccines testing and reduction of animal tests
- EU – EMA Workshop on Paediatric Regulatory Framework
- US – FDA Publication on the Quality Overall Summary
- February
- EU – In Use Shelf-life Studies – solid oral dosage forms
- EDQM – Revised guidance and application forms for electronic submissions of CEPs
- EU – Workplan for the Biosimilar Working Party
- EU – New monograph for Infliximab solution
- Australia – Implementation of PIC/S GMP guide
- ICH – New member and observer countries
- UAE – Registration of Innovative Medicines
- January
- EU – Issue of revision of Annex 1 – GMP for Sterile Manufacture
- EU – Working Parties – 2018 Workplans (Quality, Biologicals, Vaccines, Safety)
- EU – Annual Report of the GMP-GDP Inspectors Working group
- EU – Final revised guidance on Clinical Trial Products
- EU / ICH – Publication of Step 2 draft of ICH Q12 – CMC Lifecycle Management
- EU – Variations expectations
- EU – Recommendations on improvements to package leaflets
- WHO – Q&A on Biosimilars
- Ethiopia – Guidelines for registration of biotherapeutics, vaccines and similar biologic products
- November
Brexit
A list of select Brexit updates compiled by the ISPE Regulatory Quality Harmonization Committee (RQHC)’s Europe-Middle East-Africa Regional Focus Group.
- 2021
- April
EU – Reliance on GMP Inspections between EU and UK
- February
- MHRA
- UK-Canada Trade Continuity Agreement
- Will continue to recognise GMP certs and accept CoAs without import testing
- Common Statement Canada-United Kingdom (as of 1 January 2021) - GOV.UK (www.gov.uk)
- EMA
- April
- 2020
- November
EU / UK – Brexit Update – Northern Ireland extension related to health care expectations
- July/Aug
- February
- January
- After the December UK election, the UK Government (under Conservative Boris Johnson) now has a significant majority in the UK House of Commons
- The Government is now moving forwards with Brexit by 31st January
- November
- 2019
- November
- May
- January
- Brexit plan rejected by UK parliament 15th January
- Next steps not yet clear
- Could increase the chances of UK leaving on ‘no deal’ basis
- UK – MHRA Release response to consultation on No Deal
- EC – In event of No Deal – Implementing the Commission’s Contingency Action Plan
- Brexit plan rejected by UK parliament 15th January
- 2018
- September
- UK Government re. pharmaceutical company concern on no-deal BREXIT
- Whilst “good progress has been made in negotiations”, Government asking for a contingency planning approach
- Additional 6w supply of medicines – ensuring continuity of supply
- Continue to accept products that have been batch tested and release in accordance with EU rules (no further testing requirement)
- EU turns down support request to manage against staff loss
- EMA – simplified transfer approach for some MAAs affected by BREXIT
- UK Government re. pharmaceutical company concern on no-deal BREXIT
- August
- May
- Unclear if/how UK may secure associate membership of EMA
- EC warns MAHs not to ‘wait and see’ re preparing for Brexit
- EMA and member states complete redistribution of UKs portfolio of CP products
- Ireland’s HPRA surveys Irish medtech sector on impact of Brexit
- EMA - Issue guidance on MPs approved by MRP / DCP
- UK commit to EU clinical trial regulation post-Brexit
- UK government report encourages alignment of pharma industry to EU regulations
- April
- A 21 month transition period (March 29th to end of 2020) is agreed for BREXIT implementation.
- What level of MHRA participation in EMA will be agreed ?
- ‘limited’ ; ‘close alignment’ ?
- The EU have stated that the UK’s ‘red lines’ on leaving the single market and customs union would ‘inevitably’ limit the alignment
- ‘limited’ ; ‘close alignment’ ?
- Still more work to be done, including on activities of notified bodies (devices)
- What level of MHRA participation in EMA will be agreed ?
- EC posts minutes and presentations from technical expert seminar (8th March) on pharmaceutical matters following BREXIT
- 80 experts from 27 states. Meeting to inform experts about the ‘overall state of play’, the preparedness measures taken and collect expert perspectives on these measures and identify and discuss gaps / action plan.
- Comments on the ‘wait and see’ approach by MAHs… need to act swiftly “considering as a baseline for preparedness the withdrawal date of 30th march 2019” (not the transition period)
- Another technical seminar ‘may be convened’ Q2’18
- UK Health and Social Care Committee life science recommendations
- Main recommendation is that the UK and EU should aim to secure the ‘closest possible regulatory alignment’ – e.g. ‘close’ associate membership of the EMA
- A 21 month transition period (March 29th to end of 2020) is agreed for BREXIT implementation.
- March
- Industry stakeholder meeting on Brexit and operation of the Centralised procedure for human medicinal products
- EU - Position paper calls for Agency powers to apply to EU during BREXIT transition
- UK Parliamentary Health Committee warns pharma will step up contingency plans unless Brexit transition agreed soon
- February
- MHRA - Update to pharmaceutical companies on exit preparations (16th January)
- Some items seen as highlights here –
- EMA survey of pharma companies on BREXIT preparedness
- BREXIT talks restart
- Potential for a transitional period
- UK views on remaining part of EMA
- January
- Post Brexit Licensing and Supply
- EU – Practical guidance for procedures related to BREXIT (centralised procedure)
- HPRA – Brexit Guidance for Stakeholders
- September