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

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 EU Commission has updated their guidance on Phtalates for Medical devices: ​
  • 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
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​


Brexit

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

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