Regulatory News & Updates

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

September - October 2024

EU Commission

A new version of the questions and answers related to Clinical Trials Regulation (EU) No 536/2014 has recently been published. The revisions include greater transparency on CTIS rules, reference to paediatric clinical trial results and deletion of SmPC requirements for authorised auxiliary medicinal products. A copy of the full document can be found using the following link.

EMA

The EMA has updated its scientific guideline on Environmental risk assessment of medicinal products for human use. It replaces the prior version dated 2016. The purpose of this guideline is to describe the assessment of the potential environmental risks and hazards of HMP. It outlines general considerations and the recommended stepwise procedure of assessment. An ERA is required for all new MAAs for a medicinal product submitted through a centralised, mutual recognition, decentralised or national procedure, and for type II variations if there is an anticipated increase in the environmental exposure. All pharmacologically active substances in the product need to undergo an ERA. The revised guideline applies as from 1 September 2024. In addition, the EMA has updated their Questions and answers on theguideline on the environmental risk assessment of medicinal products for human use.
Ongoing EMA updates: Appendix 1: Acceptable intakes established for N-nitrosamines to Questions and answers for marketing authorization 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 EMA has published a new Q&A document on co-processed excipients (CoPEs) for comments. The document highlights the benefits and risks associated with CoPEs, emphasizing the need for a risk-based approach to their evaluation. The document categorizes CoPEs into three risk levels (high, medium, and low) and outlines the regulatory dossier requirements for each category. It also provides guidance on the necessary quality control measures, including the description of manufacturing processes, specifications, and risk assessments.
The EMA has issued a specific Template for letter frommarketing-authorisation holder (MAH) permitting the Agency to send certificates elsewhere than to MAH address, for immediate use, such as for registration in a non-EU country.
The EMA posted a new Reflection Paper on the Use of AI in the Medicinal Product Lifecycle. This reflection paper reflects on principles relevant to the application of AI and machine learning (ML) at any step of a medicines' lifecycle, from drug discovery to the post-authorization setting. This reflection paper should be used in conjunction with legal requirements and overarching EU principles and legislation on AI, data protection, cyber security, and medicines regulation.
As already announced, the EMA has completely revised its Compilation of Union procedures oninspections and exchange of information. This is a tool for facilitating co-operation between the GMP and GDP inspectorates of the EU Member States and a means of achieving harmonisation. The procedures within it provide the basis for national procedures that form part of the national GMP inspectorates’ quality systems. The Compilation has two parts: procedures within the Part I and other documents (e.g. interpretation documents and forms used by regulators) within the Part II. Furthermore, the EMA has now published an Introduction to the Compilation, which provides additional background and helpful clarification on the inspectors' expectations, eg for importation.
European Pharmacopoeia bids adieu to rabbit pyrogen test in its monographs. Pyrogen detection is essential for ensuring the safety of parenteral medicines. For decades, the rabbit pyrogen test (RPT) has been the traditional method… In June 2024, as the outcome of a broad exercise aiming at the complete removal of the RPT from the Ph.Eur., the commission adopted 57 revised texts from which the RPT has been deleted, together with a new general chapter on Pyrogenicity (5.1.13), marking the end of the RPT era in the Ph. Eur. A list of these texts.
This is a major achievement for animal welfare and for the advancement of modern in vitro approaches for pyrogenicity testing. As a result, the use of the RPT will no longer be required in any text of the Ph. Eur. and it will be the responsibility of medicine developers to select a suitable in vitro test (e.g. the monocyte-activation test) to control the pyrogenicity of their product, based on a risk assessment as described in the new general chapter. The revised texts omitting the RPT and Pyrogenicity (5.1.13) will be published in Supplement 11.8 of the Ph. Eur., with an implementation date of 1 July 2025.
The EMA has updated its guidance to prospective applicants to the PRIME scheme, which aims to expedite the development of medicines addressing unmet medical needs: European Medicines Agency Guidance for applicants seeking access to PRIME scheme
PRIME – Paving the way for promising medicines for patients - Factsheet
QRD statements for metered dose inhalers containing fluorinated greenhouse gases has been published and can be found using this document. Additionally Section 3.6 of the EMA's Questions and answers on data requirements when transitioning to low global warming potential (LGWP) propellants in oral pressurised metered dose inhalers has been updated to include reference to the Questions and answers on labelling requirements for centrally authorised metered dose inhalers containing fluorinated greenhouse gases.
The EMA has published a new guideline on Quality and equivalence oflocally applied, locally acting cutaneous products. It provides guidance on the quality requirements of cutaneous products containing new or known chemical active substances, throughout their life cycle. In addition, it gives a framework to establish protocols for demonstrating therapeutic equivalence, thus waiving the need for in vivo therapeutic equivalence studies, under certain conditions. The guideline will come into effect on 1 April 2025.
EMA and the Heads of Medicines Agencies (HMA) have published their draft joint EU network strategy to 2028 for an eight-week public consultation. Access document!

FDA

FDA revises nitrosamines guidance (FR Sept 5, 2024, Docket No. FDA–2020–D–1530] - This is the second revision of a guidance, “Control of Nitrosamine Impurities in Human Drugs,” that explains the agency’s thinking about how drug manufacturers and applicants can detect and prevent unacceptable levels of nitrosamine impurities in their products. This final guidance replaces the one of the same name issued on February 24, 2021. It includes information about nitrosamine drug substance related impurities (NDSRIs), potential root causes of NDSRIs, and mitigation strategies to prevent or reduce the presence of NDSRIs. With this revision, this guidance describes two general structural classes of nitrosamine impurities: small-molecule nitrosamine impurities (nitrosamine impurities that do not share structural similarity to the API and are found in many different drug products) and NDSRIs that share structural similarity to the API and are generally unique to each API. This guideline recommends implementation of new nitrosamine control strategies and provides an updated timeline for manufacturers and applicants to implement these recommendations. One of the key features of the updated guidance is an incorporated web page that will be updated, as appropriate, when new information becomes available. As per Pfizer SMEs, the updates to the FDA guidance do not include any new risks that we have not already considered.
Note: "FDA recommends conclusion of NDSRI confirmatory testing of drug products and submission of required changes in drug applications by August 1, 2025."
information collection revision entitled “Pharmaceutical Distribution Supply Chain; Drug Supply Chain Security.”
Federal Register notice Sept 6, 2024 - FDA is seeking comments on an information collection revision entitled “Pharmaceutical Distribution Supply Chain; Drug Supply Chain Security.” The collection helps support agency regulations that govern the pharmaceutical distribution supply chain. The agency says it has revised Form FDA 3911 (notification of illegitimate products) and the instructions for completing the form, to add a new field requesting information about the geographic location of the incident that is the subject of the notification.
FDA Recognizes Additional Sterilization Standards to help advance innovation in medical device sterilization processes:
- ISO 11737-3:2023 Sterilization of health care products - Microbiological methods - Part 3: Bacterial endotoxin testing
- ISO 11140-1:2014 Sterilization of health care products - Chemical indicators - Part 1: General requirements
- ISO 13004:2022 Sterilization of health care products - Radiation - Substantiation of selected sterilization dose: Method VDmaxSD.
  Citing FDA-recognized standards with a declaration of conformity generally reduces the amount of supporting documentation needed in a device submission. Learn more at the Division of Standards and Conformity Assessment’s.
AI Glossary: On Sept 26, 2024, the FDA published a digital health and artificial intelligence glossary as an educational resource to help support consistent use of digital health and artificial intelligence terminology by the FDA and interested parties (such as industry, digital health developers, academia, health care professionals, and patients). The FDA plans to update the glossary as appropriate.
FDA grants further Waivers and Exemptions Beyond the Stabilization Period | FDA. While much progress has been made, including establishing electronic system data connections, this exemption is intended to support continued implementation of DSCSA without disrupting patient access to their medications.
The duration of the exemption varies depending on the eligible trading partners:
- Manufacturers and Repackagers: May 27, 2025
- Wholesale Distributors: August 27, 2025
- Dispensers with 26 or more full-time employees: November 27, 2025
Trading partners who utilize these exemptions do not need to notify FDA.
FDA’s Office of Inspections and Investigations (OII) Is Official as the agency implements the reorganization of the former Office of Regulatory Affairs and human foods program Oct. 1
FDA corrected final rule on device GMP requirements under the Quality System regulation. In February 2024, FDA published a final rule that amended the device CGMPs requirements. The preamble indicated that the definition for “batch” or “lot” was set forth at 21 CFR 820.3, but the definition for “batch” or “lot” was inadvertently omitted. FDA is, therefore, correcting the codified for § 820.3 to include these definitions. See link for details.

International

Following the approval of ICH Q2(R2) and Q14 guidelines and on behalf of PhRMA’s representatives to the ICH Q2(R2)/Q14 Implementation Working Group on Analytical Method Validation and Development, the draft training materials are available for review, looking for any major concern/showstoppers by COB, October 3rd. The training materials are planned for finalization by March 2025.
Per the Concept Paper, the purpose of these training materials is to provide a training program that facilitates an aligned interpretation and harmonized implementation of ICH Q2(R2) and ICH Q14. The intent of this IWG is not to provide comprehensive training on all aspects of analytical development and validation but rather to illustrate the application of specific concepts or principles of Q2(R2) and Q14.

Expand All

2024
- August 2024
  Latin America Updates
  Brazil
  - ANVISA - New Regulation - Digital leaflet and exemption of printed leaflet
    RDC # 885/2024 provides for a pilot project for the implementation of the digital leaflet, allowing the optional exemption of printed leaflet on medication package for specific product types (the printed leaflet must be provided, if requested).
    The pilot seeks to take an initial step in building an electronical product information repository (ePIR), that could be accessed by reading the two-dimensional code (eg. QR code) placed on the medicine package.
    This ePIR will improve access to up-to-date electronic information for the product, including the leaflet, data on product recalls when available, access to Anvisa's adverse event notification channel and the possibility of including videos and other tools to make information available in a more simplified way to the user.
    The information collected and monitored during this pilot period will serve as input for future deﬁnitive regulation on the topic. This regulation will be in force as of 10-Sep-2024, and it will be valid until 31-Dec-2026.
  - ANVISA has revoked all current traceability regulations
    ANVISA has revoked all current traceability regulations in Brazil (RDC 157/2017, IN 19/2017, IN 100/2021) through the publication of through the publication of RDC 886/2024 (Portuguese) published on 10-July-2024
    In 2022, the Law 14 338 (May 11, 2022) has established that the distribution map is sufficient to maintain drug traceability in Brazil.
  - Anvisa - Optimized Procedure (Reliance) - GMP certificate for DP/API/ Cannabis products - Effective date: June, 03 rd, 2024
    Normative Instruction (IN) 292/2024 provides specific criteria and procedures for defining the Equivalent Foreign Regulatory Authorities (EFRA) for the GMP inspection process of manufacturers of API, Cannabis products for medicinal purposes, small molecules and biological products and establishes the optimized analysis procedure for the GMP certification purpose.
    The Health Authorities should be PIC/S and ICH member. A total of 42 EFRA recognized by ANVISA are described in this IN.
  - The following levels of regulatory confidence may be adopted to optimize the GMP certificate analysis procedure:
    1/ Partial: Complete review of the inspection report or other information from another EFRA (unilaterally adopted by Anvisa)
    2/ Full: Simplified review of the inspection report or the acceptance of part or all of the GMP certificate from another EFRA (unilaterally adopted by Anvisa)
    3/ Mutual Recognition: The decision from another EFRA entity is automatically adopted by Anvisa based on the GMP certificate or inspection report and must be adopted bilaterally between Anvisa and the EFRA.
  - * Regardless the confidence level, the GMP certificate will be issued by ANVISA. 
  - ANVISA Resolution RDC 876/2024 - Minor Revision of RDC 413/2020 (Biological Products PACs)
    This new RDC revises current ANVISA’s Resolution RDC 413/20 Article 22 to exclude the requirement to submit each quality change individually in cases of simultaneous quality changes for biological products that meet at least one of the criteria listed in the regulation. It is expected that this initiative will reduce the CMC Bio/Vac PAC queue in terms of number of submissions but not in terms of complexity/ requirements of the filings.
  - ANVISA Guide 72/2024: Guidelines for the Validation of Bioanalytical Methods and Analysis of Study Samples for Regulatory Submissions of Industrialized Medicinal Products for Human Use (version 1).
    This guide sets out the criteria for validating bioanalytical methods for quantifying synthetic and biological medicinal products and their metabolites and their application in the analysis of study samples for regulatory submissions of industrialized medicinal products for human use.
  - ANVISA Questions and Answers: Implementation of ICH M9 Guideline on Biopharmaceutics Classification System-Based Biowaivers
    This document is brought by ANVISA to explain the implementation of EMA/CHMP/ICH/493213/2018: ICH M9 Guideline on Biopharmaceutics Classification System-Based Biowaivers - Step 5 in the Brazilian regulation system. This guidance provides recommendations to support the biopharmaceutics classification of drug substances and the BCS-based biowaiver of bioequivalence studies for drug products. The BCS-based biowaiver principles may be applied to bioequivalence purposes not explicitly specified in the guideline, provided they can be supported by a thorough scientific rationale.
  Mexico
  - COFEPRIS Form Annex III: Variations to the Marketing Authorization Conditions and Justification of the Changes
    New template to be included in PAC Submissions.
  - New president X COFEPRIS
    The new structure of COFEPRIS has not been informed yet but it is possible that some of the current COFEPRIS staff remain in the role.
  - El economista
    Sheinbaum analizará mantener actuales titulares del IMSS y Cofepris (eleconomista.com.mx)
    “Durante la conferencia de prensa matutina del pasado, 16 de julio, el presidente López Obrador comentó que era “probable” que Ruy López Ridaura, subsecretario de Prevención y Promoción de la Salud, Zoé Robledo, director general del Instituto Mexicano del Seguro Social y Alejandro Svarch Pérez, titular de la Comisión Federal para la Protección Contra Riesgos Sanitarios permanecieran en sus cargos en la próxima Administración”.
  EU Commission
  - The new variations regulation has been published on the EU Official Journal today, 17 June 2024:
    effective date is confirmed as 1 Jan 2025
  - In addition, we expect the variation guideline will follow about 3 months later:
    the new draft EU variation classification guideline is available: Variations guidelines: Proposed amendments to the European Commission guidelines on variations categories and procedures.
    It has been released for comments by 23 August 2024
    One essential highlight: PLCM is included
  - The EU Commission has updated their guidance on Phtalates for Medical devices:
    Update of the guidelines on the benefit-risk assessment of the presence of CMR/ED phthalates in certain medical devices. The main text describing the selection and evaluation procedure remains essentially the same as presented in the guidelines as published in 2019. The update mainly concerns the progress made in the last five years regarding the application, exposure and toxicology of alternatives for the phthalate plasticisers in medical devices which is presented in additional Annexes.
  - The EU Commission published in the Official Journal the final text of the Artificial Intelligence Act
    It establishes a legal framework to promote the uptake of "human-centric and trustworthy" AI for medical devices, in vitro diagnostic devices and other products
    The act also sets harmonized rules for placing products on the market, and is the world's first comprehensive AI law, according to the European Parliament.
    The requirements for high-risk devices will go into effect on 2 August 2026.
    The act aims to improve the functioning of the internal market, prohibits certain AI practices and adds specific requirements for high-risk AI systems.
  EMA
  - The EMA provides guidance to MAHs and other pharmaceutical industry actors on maintaining a continuous supply of their medicines on the EU single market and minimising the impact of any medicine shortages. To this aim, further to their earlier consultation, the EMA has published as final two new templates, respectively for Medicine shortage prevention plan (SPP) and Medicine shortage mitigation plan (SMP). The EMA's webpage Medicineshortages and availability issues: guidance for companies was therefore updated with a new section on 'Shortage prevention and mitigation plans’.
  - The EMA has organized a event on "European Shortages Monitoring Platform Essentials and Industry Reporting Requirements". This is the first event of a series to communicate broadly with industry (presentattion here). Another demonstration was done during the EMA's Quarterly System Demo – Q2 2024. The ESMP is expected to be open for industry for routine reporting in November, and the go-live for crisis and crisis preparedeness in February 2025.
  - The EMA has published key documents for the implementation of the upcoming European Shortages Monitoring Platform:
    Implementation guide for marketing authorisation holders
    Implementation guide for national competent authorities
    Stakeholder engagement plan
    Industry and network reporting requirements
    Marketing authorisation holder reporting templates
    Nationalcompetent authority reporting templates
    Frequently asked questions on the European Shortages Monitoring Platform (ESMP)
  - EMA published a list of questions for that biosimilar developers may have on the tailored scientific advice procedure, including:
    Whom to contact when considering submitting tailored biosimilar scientific advice request / Who can apply
    What should be included in briefing package / What should not be included in briefing package
    How will the procedure be handled/ Can a follow-up tailored scientific advice be submitted
    What will be the fees
  - CMDh agreed at their June meeting on a pragmatic approach for submitting variations for updates of CEPs for products containing hydrochlorothiazide (HCTZ), following the removal of the non-mutagenic impurity N-nitroso-hydrochlorothiazide. It outlines that for MAs with approved CEP revisions before the impurity's inclusion, only a single type IA variation is needed for the CEP revision where the impurity has been removed, skipping the version with the added impurity. For MAs with the approved revision of CEP with the included impurity, a type IA variation can be submitted instead of a type IB variation. The CMDh considered the workload for pharmaceutical companies and NCAs, emphasizing that this approach is specific to this case and cannot be generalized. MAHs are reminded to keep their dossiers up to date and not delay CEP update. Information on this agreement will be included in the June CMDh minutes.
  - The EMA has published a complete new version of its Compilation of Union procedures on inspections and exchange of information, which serves as a basis of reference documents (guidelines, templates) for GMP/GDP inspections and is used by EU/EEA inspectors (and therefore industry).
  - Revision to EMA guideline on the ‘Chemistry of active substances’ have been proposed. These include further recommendations on the prevention, risk mitigation and control of N-nitrosamines, other cohort of concern impurities and also other potent toxins.
  FDA
  - DSCSA Waivers and Exemptions Beyond the Stabilization Period
    FDA is issuing exemptions from certain requirements of section 582 of the Food, Drug and Cosmetic Act to small dispensers (pharmacies), and where applicable, their trading partners, until November 27, 2026. This provides small dispensers additional time to stabilize their operations to fully implement the enhanced drug distribution security requirements of DSCSA. 
    Additionally, FDA is reminding trading partners the Drug Supply Chain Security Act (DSCSA) one-year stabilization period ends on November 27, 2024. The agency is not extending the stabilization period beyond this date.
    Trading partners that do not qualify for the small dispenser exemptions and are unable to meet the enhanced drug distribution security requirements by November 27, 2024, may request a waiver or exemption from those requirements. The agency expects the trading partner to continue their efforts to meet the requirements until FDA has approved or denied the request.
    FDA also reopened a request for information to better understand the status of trading partners’ interoperable systems and processes for enhanced drug distribution security
    Updated FDA page: Drug Supply Chain Security Act (DSCSA)
  - FR 6/21/2024 - FDA published final guidance titled Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device Inspection. This guidance defines the types of behaviors (actions, inactions, and circumstances) that FDA considers to constitute delaying, denying, or limiting inspection, or refusing to permit entry or inspection for the purposes of section 501(j) of the Federal Food Drug & Cosmetic Act. The examples used in this guidance are not intended to serve as an exhaustive list; rather, they illustrate the most common situations that FDA has encountered in preparing for and conducting drug or device inspections as well as situations that FDA anticipates may occur. FDA does not interpret the four terms describing prohibited behavior (delay, deny, limit, refuse) necessarily to be mutually exclusive. Note - On July 9, 2012, the FDA Safety and Innovation Act (FDASIA) was signed into law. Section 707 of FDASIA added section 501(j) to the FD&C Act to deem adulterated a drug that “has been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection.”
  - The FDA 2023 Report on the State of Pharmaceutical Quality from the Office of Pharmaceutical Quality (OPQ) says there were 776 drug quality assurance inspections, over 40% more than the 548 in FY 2022. In addition, there were 187 mutual recognition agreement partner inspections, the highest number achieved to date.
    At the end of FY 2023, the CDER site catalog included 4,819 drug manufacturing sites, a 14% increase in the number of sites over the past five years.
    OPQ says the 93 drug quality-related import alert additions in FY 2023 were more than the 77 in FY 2021 and FY 2022 combined. Some 17% of recalled products were associated with ophthalmic drug products. The number of recalls was 26% less than in FY2022 but similar to the five-year average.
  - FDA says a final report on the Drug Supply Chain Security Act (DSCSA) pilot project program has been issued to mark the conclusion of the pilot. “All supply chain stakeholders can benefit from the information gathered and lessons learned,” an online post (includes a link to the final report) says. “This program was an opportunity to test technologies or methods for enhanced drug distribution security requirements outlined in the law.” FDA says it worked with the selected participants to explore and evaluate methods to enhance the safety and security of the drug supply chain.
  - FDA has issued as final guidance 'Container Closure System and Component Changes: Glass Vials and Stoppers’ . This guidance conveys recommendations to holders of NDAs, BLAs and ANDAs regarding the reporting and implementation of some common changes to container closure system (CCS) components consisting of glass vials and stoppers for approved sterile drug products, including biological products, administered parenterally. This guidance also discusses pathways available to application holders to obtain Agency feedback. Additionally, this guidance discusses risk-based tools available to facilitate the implementation of changes to CCSs consisting of glass vials and stoppers. It does not apply to CCS types other than glass vials and stoppers. Note : it supersedes the guidance issued March 2021 titled “COVID-19 Container Closure System and Component Changes: Glass Vials and Stoppers.”
  International
  - The Press Release of the ICH Assembly Meeting that took place on 5-6 June, 2024 in Fukuoka- Japan is available here. Some highlights:
    (i) ANMAT, Argentina and JFDA, Jordan as new ICH Members, bringing ICH to a total of 23 Members and 35 Observers;
    (ii) Elected Representatives to the ICH Management Committee for a 3-year term (2024-2027): ANVISA, Brazil; MFDS, Republic of Korea; NMPA, China; and SFDA, Saudi Arabia and Industry Members: BIO and IGBA;
    (iii) New topic for harmonisation: Addendum to the ICH M7 on “Assessment and Control of DNA Reactive (mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk” to address safety assessment and establishment of appropriate controls for nitrosamine impurities;
    (iv) Endorsement of ICH Reflection Paper on “Pursuing Opportunities for Harmonisation in Using Real-World Data to Generate Real-World Evidence, with a focus on Effectiveness of Medicines”.
  - The ICMRA PQKM pilot programs have completed their initial phase, aiming to enhance manufacturing capacity for high-priority medicines and facilitate collaborative quality assessments and inspections. The first pilot focused on collaborative assessment of post-approval changes, with five applications assessed and approvals issued within standard timelines. The second pilot aimed at improving global cooperation in inspections through a hybrid process, with three inspections completed. Feedback is being gathered, and summary reports are being prepared to support further progress towards regulatory convergence and reliance.
  - The ICH M13A Guideline and associated Q&As on “Bioequivalence for Immediate-Release Solid Oral Dosage Forms” reached Step 4 of the ICH Process on 23 July 2024.
  - ICH M13A Guideline and associated Q&As on “Bioequivalence for Immediate-Release Solid Oral Dosage Forms” reached Step 4 of the ICH Process on 23 July 2024. an Introductory Training presentation and further information can be found on the M13 page.
  - The U.S. FDA, Health Canada, and the UK MHRA jointly issued the Transparency for Machine Learning-Enabled Medical Devices: Guiding Principles.
  - The goal of the guiding principles is to foster international harmonization and underscore the importance of considering transparency throughout the life cycle of machine learning-enabled medical devices (MLMD's). The comprehensive integration of the principles of transparency across the entirety of the product life cycle works to ensure informational requirements are adequately addressed, thereby promoting the safe and effective use of MLMDs. Using human-centered design methods can provide an approach for developing MLMDs with a high degree of transparency, according to the FDA.
  - In 2021, Health Canada, the FDA and the MHRA jointly identified 10 guiding principles for good machine learning practice (GMLP). GMLP supports the development of safe, effective and high-quality artificial intelligence/machine learning technologies that can learn from real-world use and, in some cases, improve device performance. The FDA, Health Canada, and MHRA have further identified guiding principles for transparency for machine learning-enabled medical devices (MLMDs). These principles build upon the GMLP principles, especially:
    principle 7: Focus is placed on the performance of the human-AI team.
    principle 9: Users are provided clear, essential information.
  Regulatory Update - OTHERS
  Canada
  - On July 04, 2024, Health Canada updated the Annex 2 to the Good manufacturing practices guide – Manufacture of biologics (GUI-0027). This revised guide takes effect immediately, replacing the November 2010 version.The updated guidance aligns with the Pharmaceutical Inspection Cooperation Scheme (PIC/S) documents, specifically Annex 2B, which pertains to the manufacture of biological medicinal substances and products for human use, and Annex 14, which focuses on products derived from human blood or plasma.
  - Health Canada has announced plans to draft separate guidance for PIC/S Annex 2A, which will address the manufacture of advanced therapy medicinal products for human use, including gene, cell, and tissue therapies.
  Australia
  - The TGA adopted and published the PIC/sGuide to Good Manufacturing Practice (GMP): manufacturing principles for medicines, APIs and sunscreens (PE009-16). The guide is for Australian sponsors and manufacturers of medicines, active pharmaceutical ingredients and sunscreens made or supplied in Australia. It provides a summary of the changes in GMP requirements resulting from the recent update of the PIC/S guide (PE 009-16, Feb. 1, 2022). The most significant change is the inclusion of the updated Annex 16, which will apply to therapeutic goods manufactured starting Sept. 3. The transition period from 3 June to 2 September 2024 allows manufacturers to assess and plan for any changes needed to comply with Annex 16. TGA expectation is that by 3 September 2024 manufacturers will have:
    completed their assessment of the impact of the Annex 16 on their operations
    completed updating quality systems documentation and implementing revised practices
- July 2024
  Taiwan
  - Application for Drug Registration of Active Pharmaceutical Ingredients (API) According to Article 6 and Article 39 of the Pharmaceutical Affairs Act, the manufacturing and importation of the drugs which are used in preparing preparations shall be filed with the central competent health authority (Taiwan Food and Drug Administration, TFDA) for registration and market approval. No manufacturing or importation of such drugs shall be allowed until a drug permit license is approved and issued. According to Article 42 of the Regulations for Registration of Medicinal Products, the API submission shall be in accordance with its Appendix 8 and 9. To improve the quality of the submission and the review process efficiency, the refuse to file (RTF) action has been implemented since July 01, 2019. The following resources provide applicants with the information for registration of API.
    Please find more information at Rules and Regulations or visit the website Pharmaceutical Regulations in Taiwan
- June 2024
  Australia
  - The Therapeutic Goods Administration (TGA) is seeking public comment on potential reforms to Part 5 of the Therapeutic Goods Regulations 1990. The potential reforms are aimed at strengthening and modernizing the legislative framework for the examination, testing and analysis of therapeutic goods. All recent consultations can be found on TGA Consultation hub
- May 2024
  EMEA Regulatory Update – EC / NCA
  - European Pharmacopoeia has published the new general chapter 5.27. Comparability of alternative analytical procedures in Ph. Eur. 11.5. This general chapter, published for information, describes how the comparability of an alternative analytical procedure to a pharmacopoeial analytical procedure may be demonstrated.
  - The EU Commission has issued the 4 following factsheets, with the aim to communicate to the general public on these themes and showcasing inspiring practices :
    Factsheet - Steering innovation to address unmet medical needs
    Factsheet - Addressing shortages of medicines and ensuring security of supply
    Factsheet - Access to medicines in all Member States
    Factsheet - Incentives to steer innovation and achieve public health objectives
  - Nitrosamines update-Highlights from the 8th meeting of the Nitrosamine Implementation Oversight Group (NIOG): NIOG reviewed the scientific gaps on quality and safety/toxicological aspects and agreed on the need to also survey international authorities and industry interested parties.
  - On 10 April 2024 Members of the European Parliament adopted their position on the EU pharmaceutical legislation, which is one major step in the EU legislative process (next will be with the Council, and then trilogue between Commission, Parliament and Council).
  EC / NCA
  - The European Centre for Disease Prevention and Control (ECDC), the European Chemicals Agency (ECHA), the European Environment Agency (EEA), the European Food Safety Authority (EFSA), and the European Medicines Agency (EMA) published a joint framework for action to strengthen cooperation to support the implementation of the One Health agenda in the European Union (EU).
  EMA
  - The EMA has revised its guideline on Environmental risk assessment ofmedicinal products for human use.
  - The EMA has issued the Meeting Report of the second Listen and Learn Focus Group (LLFG) meeting of the Quality Innovation Group (QIG).
  - The EMA has published for consultation a 'Draft guideline on the pharmaceutical quality of inhalation and nasal medicinal products’.
  - The EMA has published the Annual report of the Good Manufacturing and Distribution Practice Inspectors Working Group 2023
  MHRA
  - MHRA launches AI Airlock to address challenges for regulating medical devices that use Artificial Intelligence
  FDA
  - The FDA has issued two final guidance documents ref ICH Q2 and Q14 on how to develop and validate analytical procedures for testing drugs.
    validation of analytical procedures
    analytical procedure development
  - HHS Releases White Paper Focused on Preventing Drug Shortages | HHS.gov - This paper describes policy concepts for consideration eg Manufacturer Resiliency Assessment Program (MRAP) and a Hospital Resilient Supply Program (HRSP)
  - The Office of Pharmaceutical Quality (OPQ) in CDER released its 2023 Annual Report. This report illustrates how OPQ uses its four strategic pillars of communication, engagement, collaboration, and innovation to assure quality drugs.
  - USP has a recently published a new general chapter <383> Cured Silicone Elastomers for Pharmaceutical Packaging and Manufacturing Components in USP-NF 2024 (issue 2)
  - Cured silicone components are used as elastomeric closures for pharmaceutical packaging and also as components in manufacturing operations for drug substances and drug products.
  - U.S. Food and Drug Administration (FDA) published its new paper “Artificial Intelligence and Medical Products: How CBER, CDER, CDRH, and OCP are Working Together”.
  ICH
  - The final version of the ICH Guidelines Q2(R2) Analytical Validation now available on the ICH website:
  - The ICH updated the ICH harmonized guideline "Impurities: Guideline for Residual Solvents Q3C(R9)" on 01/24/2024. As part of the maintenance process, the regulatory members of the ICH Assembly adopted a minor revision to section 3.4. including consideration of solvent volatility for analytical methods, (section 3.4., page 4) under Step 4. LINK for access to the full guideline.
  - The ICH Q12 Implementation Working Group has published the much-anticipated Module 8 training case studies.
  - M4Q(R1) revision: M4Q(R1) has been due for revision to further improve registration and lifecycle management efficiency, leverage digital technologies, and accelerate patient and consumer access to pharmaceuticals. Comments on the draft ICH M4Q(R2) guideline were due in April.
  WHO
  - Saudi Arabia regulatory system becomes third to reach WHO Maturity Level 4: In October 2023 the Saudi Food and Drug Authority (SFDA), National Regulatory Authority (NRA) of Saudi Arabia achieved WHO maturity level four (ML4) for medicines and vaccines regulation. This is the highest level in WHO’s classification of regulatory authorities
  - The WHO is asking for comments by 9 June for two Appendixes in its Guideline for Excipients used in pharmaceutical products (working draft available here), namely:
  - Appendix 1: Risk Management in the production and control of excipients used in pharmaceutical products. Appendix 2: List of examples of high-risk excipients
  - WHO has published WHO good manufacturing practices considerations for the prevention and control of nitrosamine contamination in pharmaceutical products for consultation.
  - 57th Expert Committee on Specifications for Pharmaceutical Preparations meeting report is published. The report is available electronically on this link WHO Technical Report Series 1052, 2024. The report is also now available on the WHO website under publications TRS 1052 - 57th report of the WHO Expert Committee on Specifications for Pharmaceutical Preparations.
  OTHERS
  - Health Canada (3/21/24) opened a consultation (GUI-0036) on the "ew Annex 13 to the Good manufacturing practices guide for drugs used in clinical trials (GUI-0036)," As an active participating member of PIC/S, HC will continue to update this guidance to align it with their standards.
  - Health Canada’s Guidance on nitrosamine impurities in medications has been updated. Several updates to General and Quality-related topics have been incorporated into the guidance document
  - Health Canada has revised the Guidance document on the Lot Release Program for Schedule D (biologic) drugs to capture proposed administrative, terminology and operational changes or updates.
  - Health Canada : Annex 1 to the Good manufacturing practices guide - Manufacture of sterile drugs (GUI-0119)
  New information regarding sustainability
  - Information sharing with sustainability COP. Brussels wants to move out micro pollutants specially from drug products. In April, the European Parliament made it compulsory to remove them from wastewater before returning them to the environment or reusing them. Waste water treatments in cities will have to consider this and make investment to comply for 150 000 citizens and in critical zones 10 000 citizens. The Eco contribution directive will be adopted in June, Object 2030 20% of waste water treatment for 150 000 citizens will treat micro pollutants. 2045 100%.
  - PFAS are still in examination ECHA has to review 6000 comments including several heavy word documents.
  - Cyclosiloxanes
- March 2024
  - European Commission
    The new variations delegated act was published on 11 March: Pharmaceuticals – changes to marketing authorisations (review of EU rules) (europa.eu)
    EDQM pre-publishes revised Propylene glycol monograph
    The revised monograph on Propylene glycol (0430) was adopted by the European Pharmacopoeia Commission (EPC) in response to the public health risk posed by the discovery of ethylene glycol (EG) and diethylene glycol (DEG) contamination in several medicinal products in African and Asian countries and Indonesia. EPC decided to revise the monograph to include a test for EG and DEG.
  - EMA
    The EMA has published new or updated workplans for several of its committees, including:
    Vaccine Working Party (VWP) work plan 2022-2024
    3-year work plan for the joint CHMP/CVMP Quality Working Party 2024-2026
    3-year work plan for the Quality Innovation Group 2024-2026
    3-year work plan for Biosimilar Medicinal Products Working Party (BMWP) 2024-2026
    3-year work plan for the Biologics Working Party (BWP) 2024-2026
    Each plan describes the strategic goals, the tactical goals (ie activities/projects to deliver the strategic goals) and some operational goals (ie medicinal product-specific activities) of the committee
    EMA has provided update to Acceptable intakes established for N-Nitrosamines: Appendix 1: Acceptable intakes established for N-nitrosamines (updated 02/15/2024)
    The EMA launched a consultation on the Preliminary QIG Considerations regarding Pharmaceutical Process Models. This Quality Innovation Group (QIG) document follows on from their 2 first events in 2023 on Continuous manufacturing and on Digital novel technologies, respectively. These highlighted the need for more specific regulatory guidance on process models, while recognising that regulatory expectations in this area are evolving. This document is to share QIG’s current thinking with stakeholders and seek their comments.
    The EMA has published the agenda and minutes of its Meeting of the Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG) - 29 January 2024. In particular, it is reported that DG HERA provided an update on the vulnerability analysis for the first tranche of medicines from the Union list of critical medicines, including the criteria to select the first tranche, the proposed methodology to conduct the supply chain vulnerability assessment, the roadmap and the list itself which consists of 11 active substances.
  - MHRA
    The UK MHRA is announcing the launch of a new pilot called 'Single Inspection Program' (SIP), a global approach to GMP inspections of third country manufacturers. Health Canada, TGA, MHRA, all PIC/S members, ICMRA and Access Consortium, have begun the pilot, which aims to establish a coordinated global approach to GMP inspections of foreign manufacturing sites of common interest. Using their collective inspection resources, each authority has agreed to cover the scope of the other where possible, reducing the need for multiple inspections of the same site.
  - FDA
    The U.S. Food and Drug Administration (FDA) is announcing a virtual public workshop titled Accreditation Scheme for Conformity Assessment (ASCA) Expansion on Wednesday, April 17, 2024.
    The U.S. Food and Drug Administration (FDA) is reminding sponsors of device studies and manufacturers of devices (“device firms”) to carefully evaluate the third parties they engage to conduct performance testing and to independently verify all testing results before submitting to the FDA.
    On 02/06/2024, FDA updated the draft guidance "Notifying FDA of a Discontinuance or Interruption in Manufacturing of Finished Products or Active Pharmaceutical Ingredients Under Section 506C of the FD&C Act.”
  - ICH
    The final version of the ICH Guidelines Q2(R2) Analytical Validation now available on the ICH website
    The ICH updated the ICH harmonized guideline "Impurities: Guideline for Residual Solvents Q3C(R9)" on 01/24/2024. As part of the maintenance process, the regulatory members of the ICH Assembly adopted a minor revision to section 3.4. including consideration of solvent volatility for analytical methods, (section 3.4., page 4) under Step 4. LINK for access to the full guideline.
    The ICH Q12 Implementation Working Group has published the much-anticipated Module 8 training case studies.
  - OTHERS
    Planned update to manufacturing principles for medicines, active pharmaceutical ingredients and sunscreens
    The changes in version 16 relate to Annex 13 and Annex 16.
    Annex 13 – This annex has been amended and contains information and requirements to address specific issues related to the manufacture of investigational medicinal products.
    Annex 16 – Australia is now adopting Annex 16 which provides information and requirements on the certification by an authorised person and on batch release of medicinal products.
    Adoption planned to commence on 3 June 2024
    On 03/04/2024 The European Federation of Pharmaceutical Industries and Associations (EFPIA) has published the infographic on PFAS (per-and polyfluoroalkyl substances)
- Feb 2024
  - European Commission
    The Commission has published on its ‘have your say’ webportal, the legal text of the draft amendment to the variation regulation. Pharmaceuticals – changes to marketing authorisations (review of EU rules) (europa.eu). Feedback due by the 29 February 2024
    The draft European Union general pharmaceutical legislation released in April 2023 shows promise for improving the ability to bring combination products to market in Europe, according to experts at the Combinations Products in the EU Summit jointly held by the Drug Information Association and the Regulatory Affairs Professionals Society.
  - EMA
    EMA Quality Q&A (Part 2) - Parenteral products: in-use shelf life after opening/reconstitution. This updated Q&A provides additional information to the original 1998 guidance document. In particular, the updated information provides clarity on which dossier data are needed to substantiate in-use shelf-life claims recommended by the NfG, wording.
    On November 30, 2023, EMA announced that there will be public webinar for regulators and medicines developers interested in learning more about what the Agency's Product Lifecycle Management (PLM) value stream is working on and what it aims to achieve. Illustrated the interconnections between the various digital products being delivered. A video recording of the event is now available at this link.
    EMA issued “Human medicines: highlights of 2023” on 16 January 2024. In 2023, EMA recommended 77 medicines for marketing authorisation. Of these, 39 had a new active substance which had never been authorised in the European Union (EU) before. Among these are a number of medicines that stand out due to their contribution to address public health needs or the innovation they represent.
    EMA posted the guidance entitled “Q14 Guideline on Analytical Procedure Development.” It will become effective for EMA on 14 June 2024.
    At the beginning of 2024, the EMA added 4 new questions and answers to its catalogue of frequently asked questions on GMP/GDP, all 4 pertains to Annex 1
    This joint HMA/EMA workshop on Artificial Intelligence was held on November 20, 2023, and followed on from the 2021 workshop where stakeholders provided their views on the priority AI-related topics. If you would like to view a recording of the workshop, please follow this link.
  - MHRA
    The UK MHRA announced and published a new InternationalRecognition Procedure . From 1 January 2024, the EC Decision Reliance Procedure (ECDRP) will be replaced by the new International Recognition procedure (IRP) in the UK. The Mutual Recognition/Decentralised Reliance Procedure (MRDCRP) will be incorporated under the umbrella of IRP.
  - WHO
    PIC/S announced that 19 January 2024 marked the inaugural kickoff meeting of the PIC/S-EMA-WHO Joint Implementation Working Group, bringing together experts from WHO, EMA, and PIC/S Participating Authorities. The goal is to achieve harmonized interpretation of the newly released PIC/S-EU GMP Annex 1 on Sterile Manufacturing. https://picscheme.org/en/news/pics-ema-who-joint-implementation-working-group
    WHO publication ‘Quality assurance of pharmaceuticals: a compendium of guidelines and related materials; Tenth Edition, Volume 2 - Good manufacturing practices and inspection’ https://iris.who.int/bitstream/handle/10665/375869/9789240086081-eng.pdf.
  - FDA
    FDA has announced the availability of a final guidance for industry entitled “Q5A(R2) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin.”
    Joint US FDA – Health Canada ICH Public Meeting - Free Webinar. FDA and Health Canada will be co-hosting a regional public meeting to provide information to stakeholders and solicit input prior to the next ICH Biannual Assembly meeting scheduled for June 4-5, 2024. This public meeting will include presentations by FDA, Health Canada, PhRMA, and BIO experts on ICH guidelines recently reaching significant ICH milestones. To register for this event, click here.
    FDA is making available a revised draft guidance entitled “Conducting Remote Regulatory Assessments (RRA) — Questions and Answers.” The document clarifies the agency’s answers provided in a 2022 draft guidance
    FDA is seeking nine drug companies to volunteer to test its new Quality Manufacturing Maturity (QMM) Prototype Assessment Protocol Evaluation Program, the next phase in CDER’s QMM program. A Federal Register announcement (Jan 25, 2024) says the protocol is used to evaluate an establishment’s level of QMM.
    FDA's Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) announced the recently accepted new submission into the Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program. This new submission is the first artificial intelligence-based and digital health technology-based project and the first project in neuroscience to be accepted into ISTAND.
    FDA's CBER posts agenda of guidance documents it plans to publish in 2024; CDER has released its 2024 Guidance Agenda covering the guidance documents it potentially plans to release in 2024
  - OTHERS
    The EPA is expected to finalize new regulations in March that would limit ethylene oxide emissions from companies that sterilize medical devices. Some useful references:
    https://www.medtechdive.com/news/ethylene-oxide-medical-device-regulations-epa-fda/700742/
    https://www.fda.gov/medical-devices/general-hospital-devices-and-supplies/ethylene-oxide-sterilization-facility-updates
- Jan 2024
  - European Commission
    This new guidance, "MDCG 2023-7: Guidance on exemptions from the requirement to perform clinical investigations pursuant to Article 61(4)-(6) MDR and on ‘sufficient levels of access’ to data needed to justify claims of equivalence" opens up strategies and pathways that many assumed were blocked off under EU MDR.
    EU draft regulation on the proposal on harmonised rules on artificial intelligence, the so-called artificial intelligence act (AI Act). The framework covers all sectors, including healthcare. The Act aims to ensure AI systems used in the EU are safe, transparent, traceable, ethical, reliable, and environmentally friendly.
  - EMA
    EMA has published their (long awaited) Questions and Answers on the use of X-ray sterilisation processes for Single Use Systems (SUS) used in pharmaceutical manufacturing.
    The EMA has updated their Brexit-related guidance for companies. In particular, the questions and answers to stakeholders on the implications of Regulation (EU) 2023/1182 for centrally authorised medicinal products for human use has been revised (Northern Ireland).
    FDA and the European Medicines Agency (EMA) published the "EMA–FDA joint Q&As on Quality and GMP aspects of PRIME/Breakthrough therapy applications" document supporting quality development for FDA’s Breakthrough Therapy (BT) designation and EMA's Priority Medicines (PRIME) scheme programs for patients with unmet medical needs.
  - FDA
    FDA issued a new guidance to help drug manufacturers limit consumers’ and patients’ exposure to unacceptable levels of benzene in drug products. In 2020, FDA identified the potential for unacceptable levels of benzene in certain carbomers (which may be used as thickening agents in drugs)
    The FDA published the draft guidance "Potency Assurance for Cellular and Gene Therapy Products," to provide recommendations to help assure the potency of human cellular therapy or gene therapy products at all stages of the product lifecycle.
    FDA launched a new search function on FDA’s Office of Pharmaceutical Quality webpage to improve access to drug quality resources and web content. The new search webpage scans existing FDA guidance documents, manuals of policies and procedures (MAPPs), and compliance programs to provide users with relevant and up-to-date resources and information.
2023
- Dec 2023
  - European Medicines Agency (EMA)
    EMA has provided update to Acceptable intakes established for N-Nitrosamines: Appendix 1: Acceptable intakes established for N-nitrosamines (updated 11/15/2023)
    The EMA has published for the first time a EU list of Critical Medicines, as part of the EU’s effort to address shortages of medicinal products. QRP's note: There is no specific requirements attached to the List right now, however, early next year, this will link to EU analytical work on supply chain vulnerabilities, which may in turn lead to policy measures.
    The European Medicines Agency working party is looking to revise the current scientific guideline on Regulatory acceptance of 3R (replacement, reduction, refinement) testing approaches. A concept paper on the revision of the guideline has been made available for your review and inputs.
    The EMA has organised a virtual webinar on the revision of the pharmaceutical legislation end November 2023, intended to raise awareness of the proposed changes that will mostly impact small and medium-sized enterprises. The presentation gives a good summary from the EU Commission DG SANTE perspective.
  - MHRA
    EU and MHRA extend GMP and GDP Certificates
    The validity of the GMP and GDP certificates has already been extended until the end of 2023. The GMP/GDP inspectors' working group has now decided to continue the extension of the validity date until 2024 or until the completion of the next on-site inspection, whichever comes first, unless otherwise stated in the document.
  - FDA
    The FDA published final guidance titled, "Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs;" this is a final guidance with respect to Verification Systems and key stakeholders will review. The document describes FDA’s interpretation of the requirements of the Act and it provides recommendations for robust verification systems for the determination, quarantine and investigation of suspect products, as well as the quarantine, notification and disposition of illegitimate products.
    legacy medical devices - The Food and Drug Administration asked MITRE to develop a white paper that builds on the healthcare sector work to address the challenges posed by legacy medical devices, devices which still perform their primary function but may be vulnerable to cybersecurity risks
    A sweeping executive order on AI was released entitled, Executive Order on the Safe, Secure, and Trustworthy Development and Use of Artificial Intelligence. This has major implications for the medical device industry. The order describes the need for new industry standards and safety measures related to AI and AI-enabled medical devices
  - ICH
    CH Q5A(R2) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin was finalized at the ICH meeting in October, 2023 and is now published on the ICH website.
  - OTHERS
    2023 Combination Products Summit held by the Association of Food and Drug Officials/Regulatory Affairs Professionals Society (AFDO/RAPS) Healthcare Products Collaborative discussed Divergent global regulatory frameworks that make it difficult for manufacturers to move forward with innovative combination drug/device products.
    The ICMRA collaborative hybrid inspection pilot (CHIP) explores how existing technologies and virtual inspection methods can support stronger collaboration among regulators and maximize the use of limited resources. The pilot is open for new applications from industry. To support potential applicants, ICMRA has published a paper on inspection expectations for CHIP participants which outlines benefits, requirements and processes for hybrid inspections.
    Swissmedic has now published a Q&A document with technical interpretations of existing questions under the title "Interpretation of GMP Annex 1 2022 (Rev. 1)".
- Oct 2023
  - European Commission
    The EU Innovation Network (EU-IN) and the Spanish Agency of Medicines and Medical Devices (AEMPS) organized a multi- stakeholders meeting on September 26, 2023, to promote research and development of innovative medicines and related technologies & methodologies in the European Union. (see agenda here)
    The European Commission issued a Call for Evidence on their planned revision of the variation framework for medicines. This initiative, announced in the 2020 pharmaceutical strategy for Europe, aims to review the current rules setting out the procedures for post-authorisation changes to a marketing authorisation for medicines for human use.
    EMA announced a public webinar for regulators and medicines developers interested in learning more about what the Agency's Product Lifecycle Management (PLM) value stream is working on and what it aims to achieve Date: 30 November 2023
    Time: 14:00 - 16:00 Amsterdam time (CEST) - View registration details
  - European Medicines Agency (EMA)
    Updated ‘guideline on the use of near infrared spectroscopy by the pharmaceutical industry and the data requirements for new submissions and variations’ - Changes within the approved scope of the NIRS procedure are subject to GMP only. Changes outside of the approved scope of the NIRS procedure are subject to variation application. For comments until 22 December.
    Nitrosamines Q&A: Update of Q&A 3 to highlighting the responsibilities of MAH(s)
    Update of Q&A 10 to allow referral to other sources for CPCA categorization and editorial changes
    Other: Appendix 3 : Enhanced Ames Test Conditions for N-nitrosamines Nitrosamine impurities page
    EMA has provided update to Acceptable intakes established for N-nitrosamines
    The EMA published details of the newly created Solidarity Mechanism developed by the EMA's Medicines Shortages Steering Group (MSSG). This voluntary mechanism allows Member States to support each other in the face of a critical medicine shortage.
  - EMEA Regulatory Update - WHO
    WHO-Listed Authorities: The Health Sciences Authority (HSA), Singapore; the Ministry of Food and Drug Safety (MFDS), Republic of Korea; and the Swiss Agency for Therapeutic Products (SwissMedic), Switzerland, are the first three national regulatory authorities (NRAs) listed as WHO-Listed Authorities (WLA). WHO Page.
    WHO is soliciting stakeholder feedback on which WHO guidelines for pharmaceuticals should be reviewed or updated and new topics to develop guidelines or guidance to address gaps in the existing WHO QA guidelines and related texts.
    The WHO is asking for comments for its guideline on Bioanalytical Method Validation and StudySample Analysis.
  - FDA
    FDA has recognized a key consensus standard to support device sponsors as they address cybersecurity concerns: ANSI/AAMI SW96:2023 Standard for medical device security - Security risk management for device manufacturers. Recent legislation and the FDA’s guidance seek to drive the inclusion of cybersecurity risk analysis and mitigation in device submissions.
    The FDA issued the final guidance Cybersecurity in Medical Devices:Quality System Considerations and Content of Premarket Submissions. This guidance provides recommendations on medical device cybersecurity considerations and what information to include in premarket submissions.
    This Draft Guidance: Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications, indicates how the agency will use alternative tools in advance or in lieu of an inspection to remotely evaluate drug manufacturing facilities named in pending applications as part of FDA’s drug review process (PAIs).
    FDA issued a draft guidance, Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities, replacing the guidance issued during the COVID-19 pandemic entitled, Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19 Public Health Emergency
  - ICH
    Press Release ICH Assembly Meeting, Prague, Czech Republic, October/November 2023
    The Assembly adopted the following as final Guidelines:
    Q5A(R2) Guideline on Viral Safety Evaluation as final.
    Q2(R2)/Q14 Guidelines on Validation of Analytical Procedures and Analytical Procedure Development
    Additional updates include:
    ICH agreed to consider a new topic proposal in 2024 for an M7 Addendum for Nitrosamines
    The Management Committee agreed on a timeline to start the previously approved revision of the Q6A/B Guidelines on Specifications in January 2024.
    The ICH Management Committee agreed to launch a task force to assess the possibility for ICH to host a pharmaceutical quality knowledge management platform.
    ICH Q9(R1) Quality Risk Management Training Materials now available on the ICH Website
  - OTHERS
    CHINA:
    Center for Food and Drug Inspection of NMPA issued 5 Documents including the Work Procedures for Drug Registration Inspection (Trial)
    In late September, China's NMPA submitted the formal application to the Pharmaceutical Inspection Co-operation Scheme.
    Icmra/ifpma
    On 20 and 21 July 2023, ICMRA and IFPMA hosted a joint virtual workshop on the development of a global Pharmaceutical Quality Knowledge Management System (PQKMS). During the workshop, both industry and regulators shared feedback on their experiences with the ongoing pilots, highlighting the successes and the challenges. Here you can find a copy of the workshop agenda and the presentations delivered on the day, along with a recording of day one of the workshop.
    Australia - Guideline: General Dossier Requirements was issued in Oct 23
- July 2023
  - European Commission
    EC Guidance for the transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation
    On July 19, 2023, European Commission has issued a guidance on transition the Clinical Trial Directive (CTD) to Clinical Trials Regulation (CTR).
    EU steps up action to prevent shortages of antibiotics for next winter
    The European Commission, the HMA and the EMA are today issuing recommendations for actions to avoid shortages of key antibiotics used to treat respiratory infections for European patients in the next winter season.
    Document connected with HERA initiative to prevent shortages of antibiotics.
    Directive and Regulation
    Proposal for a Regulation laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency (europa.eu)
    This link send you to the page to download both documents Directive and Regulation, and their appendix which need to be improved.
    ISPE comments were due by August 28th.
    Nevertheless the EMA site is still open for comments to day to September 22nd. You can submit in the name of your organization. The delay is due to the requirement of having available the translations in all European Languages.
  - European Medicines Agency (EMA)
    Nitrosamines Update
    Both EMA and HC have published major updates to their nitrosamine documents (rev 16 of EMA’s Q&A and HC guidance, here the HC overview). The updates include a simple scientifically based framework for establishing acceptable intakes for new nitrosamines (CPCA framework) and a protocol for an enhanced Ames test (EAT).
    Guidance on good manufacturing practice and good distribution practice: Questions and answers
    The EMA has published new Q&As on the Guidance on good manufacturing practice and good distribution practice: Questions and answers | European Medicines Agency (europa.eu) on remote batch certification/ confirmation by the Qualified Person (QP), on EU residency of the QP and whether direct contract agreement are a requirement.
    The use of Artificial Intelligence (AI) in the medicinal product lifecycle
    EMA is seeking stakeholder feedback on the draft reflection paper on the use of Artificial Intelligence (AI) in the medicinal product lifecycle via an open consultation concerning human and veterinary medicines. This consultation aims to initiate the dialogue with all groups of stakeholders in this fast-evolving field. During the consultation a workshop will be organized by EMA on 20-21 November 2023 on AI in the context of medicines. The comments are due to the EMA by 31-Dec-2023
    ISPE will comment this document call fro comments should be released September. We recommend several COP and regulatory groups provide comments or candidate for the Comment Lead team.
  - EMA
    Fifth Industry Standing Group (ISG) meeting
    EMA hold the fifth meeting of the Industry Stakeholder Group (ISG) late June, and presentations are now available.
    EMA presentations
    EMA has made public several presentations recently used in workshops and meetings. These cover a wide range of topics, including shortages, nitrosamines, real world eata quality, clinical trial regulation and implementation update, etc; examples:
    Presentation: Presentation - Update on activities linked to presence of N-nitrosamines in human medicines (A. Azevado, R. Ruepp, EMA)
    Presentation: Presentation - Implementation of the Good practice guide on prevention of shortages (I. Abed, EMA)
    Presentation: Presentation - Pilot on reporting of shortages by eligible patients and healthcare professional organisations (I. Abed, EMA)
    Concept paper on the development of a guideline on the quality aspects of mRNA vaccines
    EMA has published for consultation a Concept Paper on the development of aGuideline on the quality aspects of mRNA vaccines.
  - MHRA
    Timeframe for accepting CE marked medical devices in Great Britain extended -
    CE marked medical devices will continue to be accepted on the Great Britain market beyond 30 June 2023
  - EMEA Regulatory Update - WHO
    QAS/23.929 WHO guideline on biopharmaceutics Classification System - based Biowaivers
    WHO wants to align its bioequivalence classifications with other global guidelines by reducing the number of in vivo studies required to prove bioequivalence with a reference product. If adopted, the draft working document, "Biopharmaceutics Classification System-Based Biowaivers," would align the agency's policies with those adopted by the ICH's 2019 M9 Biopharmaceutical Classification System-Based Biowaivers guideline. Health Canada implemented the guideline in 2020, and the FDA adopted it in 2021. The WHO is seeking public comment on the draft working document until 31 August 2023.
  - OTHERS
    Turkish Medicines and Medical Devices Agency publishes new guideline on GDP inspections
    The Turkish Medicines and Medical Devices Agency (TITCK) has published a new revision of its guidelines related to inspections regarding the storage and distribution of medicinal products for human use. The first version of the guideline with the identifier IDD-KLVZ-01 came into effect in February 2022, then the document was first revised in November 2022. The effective date for the second revision, which has now been published, was 20 June 2023.
    The purpose of the document is to provide guidance on inspections related to the storage and distribution of medicinal products for human use. It is also about to ensure that audits are carried out in accordance with the national legislation in force and to standardise the way inspections are performed. The original document in Turkish is available for download as a PDF document on the website of the authority.
  - FDA
    FDA updates internal policy for Risk-Based Site Selection Model
    FDA Manual of Policies and Procedures (MAPP) 5014.1, UnderstandingCDER’s Risk-Based Site Selection Model, outlines how the Office of Pharmaceutical Quality (OPQ) will manage the Site Selection Model (SSM) to prioritize manufacturing sites for routine quality-related (i.e., cGMP) surveillance inspections.
    FDA Discussion paper for AI / ML
    Artificial Intelligence Discussion Paper (fda.gov) Manufacturing
    Using Artificial Intelligence & Machine Learning in the Development of Drug and Biological Products (fda.gov)
    These 2 documents have been commented by ISPE
  - ICH
    ICH Assembly Meeting, Vancouver, Canada, June 2023
    ICH issued a press release following the ICH Assembly Meeting held in Vancouver, Canada in June 2023. ICH welcomed EDA, Egypt as the first African Regulatory Authority to join ICH as a Member, along with NAFDAC, Nigeria as a new ICH Observer.
    Publication of revised Annex I as part of the PIC/S GMP Guide (PE 009-17)
    PIC/S has published the updated PIC/S GMP Guide (PE 009-17), which now includes the revised Annex 1 on the manufacture of steriles. Both documents will enter into force on 25 August 2023 (except for point 8.123 of Annex 1 which is postponed until 25 August 2024). In the meantime, the current version of the PIC/S GMP Guide (PE 009-16) remains in force. View both versions of the PIC/S GMP Guide.
- June 2023
  - European Commission
    The European Commission (EC) has issued a request that its Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) update guidelines on the benefit-risk assessment of the presence of phthalates in certain medical devices. The request targets phthalates that are carcinogenic, mutagenic, toxic to reproduction (CMR) or have endocrine-disrupting properties.
    EC Has released April 26 a proposal for a new directive and regulation for pharmaceutical legislation.
    Reform of the EU pharmaceutical legislation (europa.eu)
    Directive proposal com_2023_193_1_act_en.pdf (europa.eu)
    Directive Annexes 090166e5fb0aef6d (4).pdf
    Regulation proposal com_2023_192_1_act_en.pdf (europa.eu)
    Regulation Annexes 090166e5fb0afd5c (4).pdf
    These documents can be commented. The plan is to make targetted comments on
    Products availability in the Regulation
    Decentralised Manufacturing sites in the directive.
  - European Medicines Agency
    The EMA's Quality Innovation Group (QIG) has organised its first listen-and-learn focus group meeting in March 2023 to discuss innovative approaches for the development, manufacture, and quality control of medicines. The aim of such meeting is to share knowledge and experience and identify together with stakeholders what are their challenges and possible solutions. The EMA has published the report from this meeting.
    A following workshop will take place in October considering Pharma 4.0
  - MHRA
    The Medicines and Healthcare products Regulatory Agency (MHRA) have embarked upon an ambitious programme of reform to ensure that medical device regulation is fit for purpose for software, including artificial intelligence (AI).
    MHRA announces new recognition routes to facilitate safe access to new medicines with seven international partners. These recognition routes, which have been facilitated by existing international partnerships such as those developed through the Access Consortium and Project Orbis, mark the start of a new international recognition framework for medicines that will be in place by the first quarter of 2024.
  - OTHERS
    Health Canada launched a 60-day consultation (comments due 20-Jul) with Canadians on how the Government and its stakeholders and partners can better prevent and mitigate shortages of drugs and other health products: Consultation guide on improving access to drugs and other health products in Canada
    The PIC/S Committee has invited Bulgaria’s Bulgarian Drug Agency (BDA) and Saudi Arabia’s Saudi Food and Drug Authority (SFDA) to join the PIC Scheme. Thus, Bulgaria BDA will become PIC/S’ 55th Participating Authority, and Saudi Arabia SFDA respectively the 56th as from 1 July 2023.
    Amended SAHPRA (South Africa) guideline – Quality and Bioequivalence Version 8 that has been published for implementation. This guideline is intended to provide recommendations to applicants wishing to submit new registration applications as well as variations. View the guidelines and the implementation date is May 2023.
    The Govt of India has made it mandatory the testing of Cough syrups for exports; the testing is to be done in Govt approved Central Drug Testing Labs across India and it’s a result of the contamination of cough syrups with ethylene glycol and diethylene glycol that resulted in death of children. Express Pharma article.
  - FDA
    FDA submitted its annual Report on Drug Shortages to Congress for calendar year 2022. The report indicates that the year 2022 was a challenging year for shortages, as drug manufacturers continued to experience quality issues and struggle with capacity constraints. There were also dramatic and rapid changes in demand for certain medications used to treat patients with infectious diseases, including COVID-19, RSV, and influenza, which made it harder for FDA and manufacturers to avoid shortages.
    FDA has published the International Council for Harmonization M9 Biopharmaceutics Classification System-Based Biowaivers Questions and Answers guidance. The document has questions and answers covering the Introduction/Scope, Biopharmaceutics Classification of the Drug Substance, Eligibility of a Drug Product for a BCS-Based Biowaiver, and an annex with questions and answers linked to the respective sections of the M9 guidance.
    FDA is implementing Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol guidance immediately to alert the industry to the potential public health hazard of DEG and EG contamination for certain drug components in excess of the safety limit for drug products. The final guidance for industry replaces the 2007 guidance and provides advice on how industry can comply with applicable regulatory requirements. All containers and all lots of certain additional excipients must now be tested, and many others should be.
    Federal Register, May 4, 2023 - FDA announced a new docket for public comments [Docket No. FDA-2023-N-1585] pertaining to N-nitrosamine drug substance related impurities (NDSRIs). FDA has asked for specific feedback on several issues pertinent to ongoing workstreams within the Nitrosamine Taskforce including:
    “Short-term” carcinogenicity testing (e.g., 6-month transgenic mouse model)
    Extending the October 1, 2023, deadline for confirmatory testing of drug products
    Efforts to establish recommended acceptable intake limits
    Comments are due to FDA on Monday, July 3rd.
    FDA has released as well a document on AI ML “Using AI/ML for Development of Drug & Biological products
    Using Artificial Intelligence & Machine Learning in the Development of Drug and Biological Products (fda.gov)
    Comments are due by July 10th to ISPE .
    On May 31 and June 1, 2023 U.S. Food and Drug Administration, in partnership with the Health and Environmental Sciences Institute (HESI), held a workshop titled " FDA/HESI Research Roadmap Planning on Hazard and Risk Assessment of Nitrosamine Impurities in Drugs."
    May 3, 2023, Federal Register: Filing of Color Additive Petition From Environmental Defense Fund, et al.; Request To Revoke Color Additive Listing for Use of Titanium Dioxide in Food - FDA is announcing that they have filed a color additive petition, submitted by Environmental Defense Fund, et al., proposing that FDA repeal the color additive regulation providing for the use of titanium dioxide in foods. Please note record ID# 823 on Health Canada - Food Directorate's State of the Science of Titanium Dioxide (TiO2) as a Food Additive Report gives TiO2 a clean bill of health in Canada for use in foods.
  - ICH
    The ICH M7(R2) Guideline on “Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk” reached Step 4 of the ICH Process in April 2023. Following the adoption of this Guideline, a Step 4 Introductory Training Presentation and a Training on the Questions and Answers were made available.
- May 2023
  - EC
    On 26 April 2023, the EU Commission has published a proposal to revise the EU's pharmaceutical legislation - to make it more agile, flexible, and adapted to the needs of citizens and businesses across the EU. The objectives of the revision is to make medicines more available, accessible and affordable.
    Directive proposal
    Directive Annexes
    Regulation proposal
    Regulation Annexes
  - EMA
    The EMA has published the Annual report of the Good Manufacturing and Distribution Practice Inspectors Working Group 2022 (IWG),
    Revised version of the Work plan for the Good Manufacturing Practice / Good Distribution Practice Inspectors Working Group 2021-2023.
    The EMA has revised and published the updated List of critical medicines for COVID-19 public health emergency (PHE) under Regulation (EU) 2022/123. Under this regulation, supply and demand of the medicines included in the list are closely monitored by EMA so that potential shortages can be avoided or managed early. Notification from the MAH are performed via their i-SPOC.
  - OTHERS
    Australia's TGA released guidance intended to provide information regarding the regulation in Australia for software and apps that meet the legislated definition of a medical device. Therapeutic Goods Administration
    The updated APEC Supply Chain Security Toolkit is now available on the US FDA website. The toolkit contains training materials intended to educate regulators, industry, health care professionals, and others on a particular part of the supply chain in 10 categories
    Japan's PMDA posted information on the fifth subcommittee on software as a medical device using artificial intelligence and machine learning, which took place on 4 April 2023.
  - FDA
    FDA is seeking comments on the second chapter of the draft document entitled “PharmaceuticalQuality/Chemistry Manufacturing and Controls (PQ/CMC) Data Elements andTerminologies,” which is intended for use with PQ/CMC data submitted electronically. The goal of the U.S. Food and Drug Administration’s (FDA or Agency) Pharmaceutical Quality/Chemistry Manufacturing and Controls (PQ/CMC) project is to support structuring eCTD product quality concepts that are amenable to structuring and bring value to the quality review process as structured data elements
    FR April 14, 2023 – Workshop on Advancing the Utilization and Supporting the Implementation of Innovative Manufacturing Approaches, June 8.
    On 01 February 2023, the United Pharmacopoeia (USP) published a new general chapter <1083> Supplier Qualification in USP-NF 2023 (issue 2) Online publication for implementation by 01 August 2023: This chapter provides a quality risk-based approach on how to select, assess, approve, and monitor suppliers of ingredients, packaging materials, and other components and services. For more details and for your review/assessment, the chapter can be accessed here.
- Febuary 2023
  - EC
    EC delays deadline for MDR compliance
    The European Commission has approved a proposal to delay the deadline for companies to comply with the Medical Devices Regulation in order to prevent shortages of lifesaving equipment to end 2027/2028 depending on risk class). The proposal now needs to be adopted by the European Parliament and Council through an accelerated process.
  - EMA
    The EMA has amended its good distribution practises (GDPs) advice to explain how the rules apply to brokers operating outside of the European Economic Area (EEA).
    Two new questions about GDP needs are included in the paper. The new issues cover whether a broker can broker operations between parties outside the EEA, as well as whether a broker can broker activities for medicinal products without an EEA marketing license but with an EEA marketing authorization. The answer is no to both queries.
    News from EDQM “Ph. Eur. Commission adopts revised general monographs 2034 and 2619 after inclusion of new paragraph on control of N-nitrosamines”
    The European Pharmacopoeia (Ph. Eur.) Commission adopted the updated general monographs Substances for pharmaceutical use (2034) and Pharmaceutical preparations (2619) at its 174th session in November 2022. These monographs now include a section outlining the Ph. Eur. approach to N-nitrosamine impurities. The updated monographs will appear in Ph. Eur. Supplement 11.3 and go into effect on January 1st, 2024.
    Source: Ph. Eur. Commission adopts revised general monographs 2034 and 2619 after inclusion of new paragraph on control of N-nitrosamines – European Directorate for the Quality of Medicines & HealthCare
    EMA Statement on Shortages of Antibiotic Medicines
    EMA, the European Commission and the Heads of Medicines Agencies (HMA), through the Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG), are closely monitoring and responding to current shortages of antibiotics affecting the EU. They published a Joint statement via the MSSG on shortages of antibiotic medicines. In brief, the route causes seem to be a combination of geopolitical events or trends (such as the war in Ukraine, the energy crisis and high inflation rates) and epidemiological situation (flu and covid).
  - MHRA
    Brexit update: UK maintains Acceptance of Batch Testing and EU Certification
    In a communication published at the end of last year, the UK Department of Health & Social Care clarifies that it remains committed to the acceptance of batch testing and certification by a Qualified Person (QP) carried out in the EU.
  - Who
    The WHO has published its 56th Report of the Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP), on 22 December 2022, Technical Report Series (TRS) 1044.
    Several new guidance texts were adopted and recommended for use eg Guidelines and guidance texts adopted by the Expert Committee on Specifications for Pharmaceutical Preparations; Points to consider when including Health Based Exposure Limits (HBELs) in cleaning validation; Good manufacturing practices: water for pharmaceutical use; Guideline on data integrity, etc
  - Others
    Brazil CP 1135/2022: specific criteria and procedures for the definition of Equivalent Foreign Regulatory Authorities for the GMP inspection process
    ANVISA published the public consultation (CP) #1135-22 (here in Portuguese). Open until 06-Mar-2023. It establishes the Regulatory Trust Building Program, which is a process applicable to Regulatory Authorities members of PIC/s or ICH only, aiming at mutual recognition of health inspection practices. This program will determine levels of regulatory trust for the EFRAs: partial, full, recognition.
    New Guidance Documents on Good Distribution Practice
    PIC/S has adopted and published the following two guidance documents for GDP inspectors: an ‘Aide-Memoire on the Inspection of Good Distribution Practice for Medicinal Products in the Supply Chain’ (PI044-1) and a ‘Questions & Answers (Q&A) document regarding the PIC/S GDP Guide’ (PS/INF 22/2017).
    ECA QP Association issued VERSION 9.0 of the Code of Practice for QPs
    The EU Directives and the EU Guide to GMP define some detailed requirements to be met by the Qualified Person (QP). The new version 9.0, launched in January 2023 now also comprises a new chapter "Ethics for the Qualified Person – A Professional Code of Conduct".
  - FDA
    MRA between the Swiss Confederation and the US Relating to Pharmaceutical GMP
    FDA and the Swiss Agency for Therapeutic Products (Swissmedic) will be able to utilize each other’s good manufacturing practice inspections of pharmaceutical manufacturing facilities, avoiding the need for duplicate inspections. Announcement
    FDA Recognizes First AI-Focused Document, AAMI CR34971:2022, in List of Consensus Standards
    In January 2023, the U.S. Food and Drug Administration (FDA) recognized AAMI CR34971:2022, Guidance on the Application of ISO 14971 to Artificial Intelligence and Machine Learning, as a guidance document “appropriate for meeting requirements for medical devices under the Federal Food, Drug, and Cosmetic Act.”
  - ICH
    ICH Q9 (R1) on Quality Risk Management has reached step 4 as of 18 January 2023 and is now proceeding to the implementation phase.
2022
- 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)
  - 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
  - OTHERS
    Access Consortium commits to demonstrate greater inspection reliance and accept GMP inspection outcomes held amongst their members
    China CDE released the Technical Guidelines for Microbial Limits Study of Non-sterile Chemicals and Excipients - Draft version
  - 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
    Press Release: ICH Assembly Meeting, Incheon, Republic of Korea, November 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
    UK& Canada Expand Scope Of Mutual Recognition Of GMP Inspections (informa.com)
  - 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
- 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)
  - 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
- 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.
  - 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.
  - 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
- 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.
  - 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)
2021
- November
- October
  - EC Consultation - Dec 21st 2021 pharmaceutical legislation
    Towards a reform of EU's pharmaceutical legislation (europa.eu)
  - 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
    Technical workshop on real-world metadata for regulatory purposes (europa.eu)
  - EMA - Big Data HMA-EMA Steering Group
    Big Data Steering Group Workplan 2021-2023 (europa.eu)
    EU Survey - Survey (europa.eu)
  - ICMRA – EMA
    horizon_scanning_report_artificial_intelligence.pdf (icmra.info)
  - EMA - GMP
    Reflection Paper on Good Manufacturing Practice and Marketing Authorisation Holders_final version July 2021 (europa.eu)
    draft-ich-guideline-q13-continuous-manufacturing-drug-substances-drug-products-step-2b_en.pdf (europa.eu)
    Home · IRIS (europa.eu)
  - EMA - Nitrosamines
    Nitrosamines EMEA-H-A5(3)-1490 - Q&A Art. 5(3) Implementation_16 September 21_for CHMP silent adoption (europa.eu)
  - 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
    Medical Device Regulation comes into application | European Medicines Agency (europa.eu)
  - EU – Modification of the Medical Devices ordinance (Switzerland)
    New regulations applicable to medical devices as of 26 May 2021 (swissmedic.ch)
  - EU – Combination products in Switzerland
    Revised requirements for combination products (swissmedic.ch)
  - 17th May – launch of Unique Device Identifier Helpdesk
    EU UDI Helpdesk (zendesk.com)
  - EU – Draft common standard for electronic product information for human medicines
    ePI open consultation (europa.eu)
  - EU – Clinical Trial Information System (CTIS)
    Publication of several guides etc on this new system ahead of its planned launch
    Clinical Trials Information System (CTIS): training programme | European Medicines Agency (europa.eu)
  - EU – New Reflection Paper on forecasting demand for medicines (from EU Steering Group on Shortages)
    Reflection paper Forecasting demand for medicinal products in the EU/EEA (Europa.eu)
  - EU – Artificial Intelligence in Medicines Regulation (report from April Workshop)
    Workshop report of the Joint HMA-EMA Workshop on Artificial Intelligence in Medicines Regulation (europa.eu)
  - EU / Brazil – Working arrangement between EMA and ANVISA for the exchange of non-public information
  - UK – MHRA establishes own GMDP database
    MHRA | MHRA
- May
  - EU – new Q&A on GMPs for ATMPs
    Questions and answers on the principles of GMP for the manufacturing of starting materials of biological origin used to transfer genetic material for the manufacturing of ATMPs (europa.eu)
  - EU – allows importation site to be different to release site
    Microsoft Word - Post Authorisation Guidance-Integrated Version - clean - Apr 2021 (europa.eu)
  - EU and Canada – recognition of extra-jurisdictional GMP inspection outcomes
    Mutual Recognition Agreement between Canada and the European Union (EU) - Canada.ca
  - 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
    Publications (picscheme.org)
- 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
    JAP Compliance Group Mandate - revision March 2021 (europa.eu)
  - 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
    Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19 Public Health Emergency
- 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
    For public consultation - Public Guidance - Parallel application for EU-M4all (Article 58) opinion and Centralised Marketing Authorisation procedure (europa.eu) Connecting Pharmaceutical Knowledge
  - 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
    Guidance Agenda: Guidance Documents CBER is Planning to Publish During Calendar Year 2021 | FDA
    CDER 2021 Guidance Agenda (fda.gov)
- January
  - EU – EUDAMED database for Medical Devices
  - WHO – Regulatory Considerations for RNA Vaccines
    Call for Public Consultation – Evaluation of the quality, safety and efficacy of RNA-based prophylactic vaccines for infectious diseases: regulatory considerations (who.int)
  - WHO – Transfer of Technology in Manufacturing
  - ICMRA – Recommendations on Interoperability of Track and Trace systems
    Supply Chain Integrity | International Coalition of Medicines Regulatory Authorities (ICMRA)
  - ANVISA accepted as member of PIC/S
    Notícias — Português (Brasil) (www.gov.br)
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.
  EU – EMA guideline on Distant Inspections
  WHO – Draft guideline – Good Practices for R+D facilities
- November
  - EU – Agency of Health Security
    Commission proposals to strengthen EU health security framework and reinforce crisis preparedness
  - 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
    GMP Inspection of Manufacturers Compliance with Commission Delegated Regulation
    GDP Inspection of Wholesalers Compliance with Commission Delegated Regulation
    Inspection of Pharmacies* Compliance with Commission Delegated Regulation
  - 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
    MDCG 2020-1 Guidance on Clinical Evaluation (MDR) / Performance Evaluation (IVDR) of Medical Device Software
    MDCG 2020-2 Class I Transitional provisions under Article 120 (3 and 4) – (MDR)
  - 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
    PDEs drafted for 2MeTHF, cyclopentyl methyl ether and t-butanol
    And recorrected PDE for ethylene glycol
  - 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
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)
  - 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
    Detecting drug shortages and notifying regulators of shortages
    Good practice guidance for communication to the public on medicines’ availability issues
  - 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
    Guidance on Article 15 of the Medical Device Regulation and in vitro Diagnostic Device Regulation
    Guidance document Implant Card relating to the application of Article 18 Regulation
  - 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
  - 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.
    GMP clearance guidance
  - 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
    2018 GMP Symposium
    2018 GDP Symposium
  - 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
  - EU – Recognise Korean-manufactured APIs as in line with EU standards
    Adding to Australia, Brazil, Israel, Japan and USA
  - WHO – Guidelines for Implementation
    WHO Technical Report Series 1019 has the outcomes of the 53rd WHO Expert Committee
  - 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
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
- 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)
    2018 Workplans (Quality & Vaccines)
    2018 Workplans (Biologicals)
    2018 Workplans (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
    Changes to API manufacturing site and DP packaging 1
    Changes to API manufacturing site and DP packaging 2
  - EU – Recommendations on improvements to package leaflets
  - WHO – Q&A on Biosimilars
  - Ethiopia – Guidelines for registration of biotherapeutics, vaccines and similar biologic products

Brexit

A list of select Brexit updates compiled by the ISPE Regulatory Quality Harmonization Committee (RQHC)’s Europe-Middle East-Africa Regional Focus Group.

Expand All

2021
- April
  EU – Reliance on GMP Inspections between EU and UK
  - Brexit: the United Kingdom's withdrawal from the European Union | European Medicines Agency (europa.eu)
- 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
2020
- November
  EU / UK – Brexit Update – Northern Ireland extension related to health care expectations
- July/Aug
  - MHRA – taking over oversight of UK Medical Devices from 1/1/21
  - Brexit and Clinical Trials
- February
  UK – Withdrawal from the EU
- 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
2019
- November
- May
  - MHRA procedures for paediatric investigational plans in event of ‘No Deal’ BREXIT
  - MHRA guidance on No Deal Brexit arrangements
    MHRA guidance and publications on a possible no deal scenario
    European authorities working to avoid shortages of medicines due to Brexit – questions and answers
- 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
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
- 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
    Still more work to be done, including on activities of notified bodies (devices)
  - 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
- 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)
    As part of MHRA and making a success of Brexit
  - 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
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Regulatory News & Updates

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EU Commission

EMA

FDA

International ​

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​EU Commission​

EMA

FDA

International ​

​Regulatory Update - OTHERS​

N-Nitrosamines

Brexit

Initiatives & Programs A to Z

International

Latin America Updates

EU Commission

International

Regulatory Update - OTHERS