Regulatory Updates
Brexit
A list of select Brexit updates compiled by the ISPE Regulatory Quality Harmonization Committee (RQHC)’s Europe-Middle East-Africa Regional Focus Group.
February 2020 Update
- January 2020 Update
- 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 Update
- May 2019 Update
- January 2019 Update
- 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
- September 2018 Update
- 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 2018 Update
- May 2018 Update
- 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 2018 Update
- 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 2018 Update
- 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 2018 Update
- 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 2018 Update
- Post Brexit Licensing and Supply
- EU – Practical guidance for procedures related to BREXIT (centralised procedure)
- HPRA – Brexit Guidance for Stakeholders
Regulations, Guidelines & Other Documents
A select list of recently updated regulations, guidelines and other documents compiled by the ISPE Regulatory Quality Harmonization Committee (RQHC)’s Europe-Middle East-Africa Regional Focus Group
February 2020 Update
- 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 2020 Update
- 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
- November 2019 Updates
- 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 2019 Updates
- 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 2019 Updates
- 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 2019 Update
- 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 2019 Update
- 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 2019 Update
- 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 2019 Update
- 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 2019 Update
- 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 Update
- 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 2018 Update
- 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 2018 Update
- 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 2018 Update
- 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 2018 Update
- 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 2018 Update
- 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 2018 Update
- 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 2018 Update
- 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 2018 Update
- 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