International regulatory news in brief

This post covers international regulatory news in brief. It is updated on an ad hoc basis.

For ease of navigation, a tab has been added for each region/topic (below). Click on the respective tab to view the news for that region/topic.

Turkey
22 May
Guideline on Auxiliary Medicinal Products for Human Use

The Guideline on Auxiliary Medicinal Products for Human Use was prepared within the scope of the “Regulation on Clinical Research of Medicinal Products for Human Use” and entered into force on 20.05.2024.

The purpose of this guideline is to clarify the definition and provide information on the use of ancillary human medicinal products in accordance with national and international standards.

You can view/download the guideline here.

15 May
Guidance: Apply for a licence to market a medicine in the UK

The MHRA has added a new webinar video on the established medicines licensing process. You can view it here.

Source: MHRA

13 May
Guidance: Good manufacturing practice and good distribution practice

The MHRA has updated the contact form accompanying this guideline.

Source: MHRA

30 April
The MHRA sets out its strategic approach to Artificial Intelligence

The MHRA has today set out its strategic approach to artificial intelligence (AI) via the publication of the Policy Paper entitled Impact of AI on the regulation of medical products.

As a science-led organisation, the MHRA has a key role to play in enabling the UK to be a science and technology superpower by 2030. The agency is considering the opportunities and risks of Artificial Intelligence (AI), which has been identified as one of the five critical technologies in the UK Science and Technology Framework, from three different perspectives.

1. As a regulator of AI products

2. As a public service organisation delivering time critical decisions

3. As an organisation that makes evidence-based decisions that impact on public and patient safety, where that evidence is often supplied by third parties

The Policy Paper more detail on each of the above three perspectives.

Source: MHRA

29 April

The British Pharmacopoeia recently launched new Advanced Therapy Medicinal Products (ATMP) best practice guidance for T Cell and NK Cell Characterisation Assays

With complexity and risk associated with each stage of assay development, the Advanced Therapy Medicinal Products (ATMP) best practice guidance offers a practical and phase-appropriate validation tool to help your cell and gene therapy programme succeed. The ATMP guidance includes:

  • Application of Flow Cytometry
  • Vector Copy Number
  • Characterisation of the Capsid Particle Population for rAAV products
  • T Cell and NK Cell Characterisation Assays

The guidance is phase appropriate, trusted, and practical. Developed and approved by the British Pharmacopoeia (BP), in partnership with experts from the cell and gene therapy community including industry, NHS and academia, this guidance offers:

  • reliable, phase appropriate support to every stage of assay development
  • practical translation of regulation to support both new and experienced users
  • enables the development of robust internal procedures for data acquisition and documentation
  • flexible in how the user applies the guidance to their own environment
  • harmonisation with – and links to – existing industry guidance for an understanding of regulatory expectations

You can download the guidance by registering on this page

Source: pharmacopoeia.com

22 April
Lorenz Docubridge validation tool

The MHRA has updated both of the guidances below to include information on the Lorenz Docubridge validation tool

  1. Guidance: Apply for a licence to market a medicines in the UK
  2. Guidance Medicines: Apply for a variation to your marketing authorisation

The MHRA checks that eCTD submissions are technically valid using the Lorenz Docubridge validation tool which strictly aligns validation against ICH international standards and eCTD 3.2 regional requirements. It recommends that you use a validation tool to check your submission.

You can check the validation of your submission before making it using the LORENZ eValidator Basic validation software for eCTD and more. Your MHRA agent will use the Lorenz docuBridge eCTD tool to technically validate the submission against ICH international standards, eCTD 3.2 EU regional requirements, once we receive it.  

Source: MHRA

17 April
Updated Guidance: Medicines MA Holders submission of nitrosamine risk evaluation, risk assessment and confirmatory testing

The following updates have been added to this guidance:

  • Updated information following the passing of the deadline for the submission of steps 1, 2 and 3.
    • The deadlines of the call for review (steps 1, 2 and 3) for medicines containing chemically synthesised and biological active substances have passed.
    • Any MAH that has not notified the MHRA about identified nitrosamine impurities should report them as a matter of priority in line with the CHMP’s Article 5(3) opinion as well as any updates to previous notifications, using the response templates and available reporting mechanisms previously established.
  • Guidance has been added for MAHs regarding step 2 submission requirements where nitrosamines are determined to be non-mutagenic.
    • For nitrosamine impurities that are classified as non-mutagenic based on in-vivo mutagenicity studies, the submission of step 2 confirmatory testing is not required, and these impurities should be controlled according to ICH Q3A and ICH Q3B guidelines.
    • To allow nitrosamine outcomes to be correctly recorded for each Marketing Authorisation, Marketing Authorisation Holders are asked to continue making step 2 submissions for these products. The cover letter should indicate that the identified nitrosamine is non-mutagenic and that therefore no test data are provided.
  • Additional guidance about lifecycle management is provided under the heading Lifecycle Management. MAHs are expected to continue to review and re-visit the outcome of the risk evaluation as and when new information becomes available. This includes:
    • Changes to known root causes which may also affect the product in question, including when a new Acceptable Intake (AI) limit is published for the product in question.
    • Changes in the product lifecycle that may require a revision of the risk evaluation and may change the outcome of the risk evaluation.

Further information is available at the link below.

Source: MHRA

Updated Guidance: Rolling review for marketing authorisation applications

For the above procedure, the email address used to request pre-submission advice AcceleratedandRollingReview@mhra.gov.uk has been replaced with presubmission@mhra.gov.uk.

Source: MHRA

15 April
MHRA RegulatoryConnect update

On 15 April, MHRA added a link to a webinar on RegulatoryConnect.

On 25 March, The MHRA launched RegulatoryConnect, a service which provides the capability to track applicattons and view live authorisation details.

The functionality will let industry users log in using existing MHRA submission credentials and access RegulatoryConnect, where they will be able to:

  • Use the Applications page to track the status of an application and see which stage it is at.
  • Use the Current Granted View page to view live authorisation details, including status, key data and documents held against existing licences.

These services are available to those making applications to the MHRA on behalf of their organisation as an administrator or user.

  • According to the MHRA video demo:
    • The service will be available to customers from the end of March 2024. The video demo is well worth watching as it provides further useful information.
    • The intention with this service is that it will become the single front door to the agency and will enable a single customer identity to engage across all regulatory services So this will replace the PCL portal and the human medicines portal and longer term, for devices too.
  • You can get more guidance on this service via this page.
  • Future functionality and features will be added to RegulatoryConnect later in the year, including the ability to submit applications and variations to the MHRA through the service.
  • You can access the RegulatoryConnect Portal here.

Source: MHRA

11 April
Updated Guidance: Medicines Reclassify your product

The MHRA have updated the Reclassification Guidance Document and Flowchart diagram for Reclassification Applications. No other details are provided.

Source: MHRA

5 April
DSUR Submissions and Fees are Changing from 1 June 2024

The process for submitting Annual Safety Reports (ASRs) for Clinical Trials of Investigational Medicinal Products (CTIMP) to the MHRA is changing.

From 01 June 2024

  • ASRs such as the Development Safety Update Report (DSUR) will not be considered valid unless you provide proof of payment of the DSUR Review Fee with your submission.
  •  The payment associated with submission of annual safety reports to the MHRA will only be accepted via our online portal MHRA Pay.
  • A receipt generated via MHRA Pay will be sent by email upon completion of payment and must be included in the submission of the annual safety report as proof of payment.

The cover letter accompanying the submission must include:

  • a listing of all the IRAS IDs and/or EudraCT numbers of trials covered by the annual safety report
  • an email address for correspondence
  • the submission reference number in the format: ‘DSUR-[5 digit MHRA company number]-[IMP name]-[Payment date DD/MM/YYYY]’

Ensure that those submitting Annual Safety Reports/ DSURs to the MHRA are aware of this requirement ahead of 01 June 2024, and review your organisation’s processes for regulatory submissions to ensure this change has been incorporated.

A review of your current clinical trial portfolio and DSUR submission due dates may be useful to identify which DSUR submissions will be affected by this change and require additional oversight to ensure their submission to the MHRA is valid.

Further detailed information is available on this page.

Source: MHRA

Guidance: Disapplication of Falsified Medicines Directive Safety Features: Requirements for Parallel Imports

The MHRA has published the guidance, Disapplication of Falsified Medicines Directive Safety Features: Requirements for Parallel Imports. You can view it here.

  • From 1 January 2025, the EU Falsified Medicines Directive (FMD) will no longer apply in Northern Ireland.
  • EU FMD safety features will therefore not apply to parallel import licences. 
  • PLPI licence holders must still ensure packs are decommissioned correctly and cannot re-enter the EU supply chain.
  • Any 2D barcode encoding an alphanumeric character sequence (as referred to in EU Regulation 2016/161) that has been uploaded to the European repositories system should be fully removed or covered. 
  • Packs must comply with the requirements in section 6 of the Windsor Framework guidance on labelling and packaging requirements.
  • A separate variation is not required to remove the FMD label details from PLPI artwork.

Source: MHRA

1 March
MHRA grants first approval via the new International Recognition Procedure (IRP)

Launched on 1 Jan 2024, the IRP allows the MHRA to accelerate the assessment of new medicines by taking into account the expertise and decision-making of trusted regulatory partners in the authorisation process. As a result, medicines that have been approved in other countries with stringent regulators will get to UK patients without delay, resulting in a more rapid, efficient, and cost-effective process for life sciences companies.

A new formulation for XGEVA (denosumab) i.e. a 120 mg solution for injection in a prefilled syringe, a treatment used in adults to prevent serious bone-related complications caused by bone metastasis and to treat giant cell tumour of bone in adults and adolescents, is the first product to be authorised by MHRA on 29 February 2024 via the new International Recognition Procedure (IRP). The product was authorised in 30 days, providing UK patients with earlier access to this treatment thanks to international recognition

The product was initially reviewed by the European Medicines Agency (EMA) and received a positive opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP) on 25 January 2024. The MHRA considered the assessment made by the European regulator as part of its own review, facilitating a rapid approval process.

You can read more about the IRP in this blog post.

Source: MHRA

20 May
AEMPS launches an accelerated evaluation procedure for clinical trials

AEMPS has launched an accelerated evaluation procedure or fast-track with the aim of making Spain a more attractive environment for research into innovative medicines.

In general terms, Regulation (EU) No. 536/2014 on clinical trials of medicinal products for human use establishes the maximum deadlines for validation and evaluation of applications for authorization of trials submitted in the European Union. However, this procedure will allow the deadlines to be reduced for studies that meet the following criteria:

  • Be a phase I clinical trial.
  • Research advanced therapy medications.
  • Study seriously debilitating diseases or diseases that endanger the patient’s life and have no therapeutic alternative.
  • Submit through the EU clinical trials database  CTIS  ( Clinical Trial Information System )only in Spain.

In addition, the Drug Research Ethics Committee (CEIm) selected by the promoter must be one of the CEIm adhered to the fast-track procedure . The contact details of these CEIm are available in the Directory of CEIm accredited in Spain .

  • Those interested in taking advantage of this procedure must contact the AEMPS prior to submitting the application by writing to aecaem@aemps.es . This email will indicate the expected date of shipment, the evaluating CEIm and the characteristics of the trial: title, indication, investigational drug, population and additional information that justifies compliance with the requirements to access the accelerated evaluation procedure.
  • If you meet the requirements, once you have the fast-track acceptability approval from the AEMPS, the application will be evaluated within 26 days from validation . If it is not necessary for the agency to seek any clarification, a trial could be authorized by the AEMPS within a period of 31 days.
  • When submitting an application, it must be indicated in the accompanying letter that adherence to the fast-track procedure has been accepted by the AEMPS.

Source: AEMPS

6 May
AEMPS implements a new application for payment of clinical trial fees

AEMPS has implemented a new application to pay the fees for clinical trials in Spain. It becomes effective immediately.

  • The new procedure aims to make it easier for the user to pay the fee, reduce errors and reduce corrections.
  • The new method must be carried out through the ECMI portal, through the AEMPS headquarters
  • The Agency has prepared a manual for users with the aim of simplifying the payment of clinical trial fees through this new system, providing a series of instructions.

Payers will be able to complete the form with the information of the clinical trial for which they wish to pay the fee and begin the payment process. This action can be carried out through electronic payment or by downloading form 317 by bank transfer or cash.

Source: AEMPS

20 May

The European Medicines Regulatory Network (EMRN) as been designated as WHO Listed Authority (WLA) by the World Health Organization (WHO). This means that the network, composed of the European Commission, EMA and the 30 national authorities of the European Economic Area Member States, are recognised as meeting international regulatory standards, guidelines and practices.

Source: EMA

Ireland
10 May
Guide to Combining Multiple Presentations of a Parenteral Product in One Product Authorisation

This document has been updated. Whilst there are several changes throughout the document, none of them appear to be major.

Here, you can view the track changed and clean (10 May 2024) versions of the document.

Source: HPRA

15 April
Updated Guide to Attainment of Qualified Person Status in Ireland

This guide has been updated substantially. Here, you can view the track changed and clean versions of the document.

Source: HPRA

3 April
Guide to Submitting a Request for Ireland to Act as RMS in a DCP for Human Medicines

This guide has been updated substantially. Here, you can view the track changed (29 Oct 2014) and clean (2 April 2024) versions.

Source: HPRA

Guide to Submitting a Request for a New National Application Procedure for a Human Medicinal Product

The above guide has been published and you can view it here.

Source: HPRA

26 April 2024
Simultaneous National Scientific Advice 

On 19 April, the EMA held a webinar entitled Simultaneous National Scientific Advice – information and training webinar. You can view the webinar here. Information was provided under the following headings:

Welcome and opening remarks – 0:006:52

Overview of the SNSA concept –6:5311:00

Update on SNSA pilots to date 11:0131:54

SNSA procedural outline including recent changes –31:551:01:45

Planned next steps for SNSA – 1:01:461:31:40

Q&A and Discussion –1:31:412:16: 59

Closing remarks – 2:17:002:17:56

You can read more about SNSA in the following posts:

EU Simultaneous National Scientific Advice update (Aug 2021)

EU launches Phase 2 of the Simultaneous National Scientific Advice (SNSA) pilot (Nov 2022)

Source: EMA

23 April 2024
New recommendations to strengthen supply chains of critical medicines

EMA has published a number of recommendations to address vulnerabilities in the production and delivery of medicines included in the Union list of critical medicines and strengthen their supply chain.

These recommendations have been developed by EMA’s Medicines Shortages Steering Group (MSSG) and will facilitate the availability and supply of critical human medicines for which vulnerabilities in the supply chain have been identified.

Measures considered by the MSSG will be selected according to the risks posed to the supply chain and the type of medicine, and include:

  • Possible recommendations to marketing authorisation holders (MAHs) to increase manufacturing capacity and diversify the suppliers in the supply chain (e.g. through the addition of alternative manufacturing sites), and to monitor forecasts of supply and demand of medicines and available stocks in the entire supply chain.
  • Recommendations to certain actors in the supply chain, such as MAHs, and the European Commission to stockpile medicines to protect against fluctuations in demand or supply.
  • The possibility to request a MAH to establish a shortage prevention plan for medicines in the Union list of critical medicines. EMA will publish guidance and templates for shortage prevention plans in June 2024.
  • Provision of scientific and regulatory support to address vulnerabilities in the supply chain, including assistance to small and medium-sized enterprises.

Source: EMA

11 April 2024
Parliament adopts its position on EU pharmaceutical reform

MEPs adopted their proposals to revamp EU pharmaceutical legislation, to foster innovation and enhance the security of supply, accessibility and affordability of medicines.

The legislative package, covering medicinal products for human use, consists of a new directive (adopted with 495 votes in favour, 57 against and 45 abstentions) and regulation (adopted with 488 votes in favour, 67 against and 34 abstentions)

You can read more about this here or in this blog post.

Source: European Parliament

Canada
13 May
Filing submissions electronically: Guidance documents, notices and supporting documents

On 10 MAy 2024, a small yet important update has been applied to this guidance under the heading Non-eCTD format only.

Source: Health Canada

2 May
Updated Guidance Document: Regulatory Requirements for Drug Identification Numbers (DINs)

This is an administrative changes update, done on 1 May 2024. You can view/download the updated document here.

Updates have been made to Regulatory Activity Types and Regulatory Transaction Descriptions and minor revisions have been made throughout the document.

Source: Health Canada

2 April
Organization and document placement for Canadian module 1

Health Canada has updated the organization and document placement for Canadian module 1 to reflect recent changes.

  • This document contains a table outlining the Canadian module 1 sections and subfolders, with a list of possible documents.
  • Sponsors must use this table to determine where to put documents provided as part of a regulatory transaction to Health Canada.
  • Health Canada will reject the transaction if sponsors don’t adhere to this structure.
  • Sponsors must use the table when filing in either electronic common document (eCTD) or non-eCTD formats for:
    • master files
    • disinfectants
    • clinical trial applications for human drugs
    • biologics and radiopharmaceuticals for human use
    • prescription and non-prescription pharmaceuticals for human use

The information in the table takes precedence over other publications concerning the placement of documents within a regulatory activity or transaction.

Due to ongoing changes in regulatory requirements, this list of documents isn’t exhaustive. This document is subject to periodic updates with additions, relocations or removals of documents. Sponsors are responsible for monitoring the posting date of the updated document.

Source: Health Canada

14 April
About the CDER Center for Clinical Trial Innovation (C3TI)

CDER established the CDER Center for Clinical Trial Innovation (C3TI) in April 2024 to enable and amplify innovative approaches to clinical trials that are designed to improve the efficiency and effectiveness of drug development. 

C3TI serves as a central hub to:

  • Facilitate coordination across CDER innovation programs to more easily engage in cross-program and cross-center collaborations. Existing CDER clinical development innovation programs will continue to operate according to their established processes, with C3TI serving to synthesize lessons learned across those programs.
  • Manage a demonstration program that will expand opportunities for sponsors of innovative clinical trials to interact with CDER staff and for these trials to serve as case examples to spur further innovation. More information on the demonstration program can be found on the C3TI Demonstration Program webpage. 
  • Provide CDER staff, drug developers, and other interested parties with a single CDER point of contact to assist with non-product-specific questions related to clinical trial innovation. 
  • Support knowledge sharing through various mechanisms, such as public workshops, discussion forums, communications and a website to centralize information on existing and new CDER clinical trial innovation efforts. More information can be found on the C3TI Knowledge Repository webpage.

Source: FDA

Brazil
5 May
Anvisa will use analysis from equivalent foreign authorities for GMP inspection and the certification process

Anvisa published Normative Instruction (IN) 292/2024 , which establishes the optimized procedure for the purposes of analyzing Good Practices certification of Manufacturing and the criteria for defining Equivalent Foreign Regulatory Authorities (AREE) for the inspection process of medicines, biological products, cannabis products for medicinal purposes and active pharmaceutical ingredients (IFA). Regulatory trust – reliance – will bring more agility to the entire certification process.

  • The regulations define that authorities that are members of the Pharmaceutical Inspection Cooperation Scheme (PIC/S) and the International Council for Harmonization of Technical Requirements for Medicinal Products for Human Use (ICH) will be considered AREE. Currently, forty-two (42) authorities meet the AREE requirement for inspection purposes and are listed in Annex I of this IN.
  • The optimized analysis procedure aims to speed up the analysis of Certification requests filed with the Agency, without renouncing the technical rigor necessary to conclude compliance with the GMPs.

Three levels of regulatory confidence are defined in the regulations and were based on documents from the PICs reliance working group: 

  • Partial, when a complete analysis of the AREE inspection report or equivalent document is carried out to evaluate compliance with GMPs, which can be adopted unilaterally by Anvisa.
  • Full, when a simplified analysis of the ARRE inspection report is carried out to evaluate the service provided by PBFs, which can be adopted unilaterally by Anvisa.
  • Mutual Recognition, when, based on a regulatory trust program and signature of a mutual bilateral Agreement, Anvisa and AREE will accept the inspection report or GMP certificate from the counterparty.

The standard comes into force on 1 June 2024 and companies interested in adopting the optimized analysis procedure will be able, using a specific subject code, to use this analysis route.

2 May
Anvisa and Health Canada sign new Confidentiality Agreement

Anvisa signed a Confidentiality Agreement with the Regulatory Operations and Enforcement Branch of the Canadian Department of Health (Health Canada).

  • The new agreement aims to strengthen the exchange of technical information and inspection reports on good manufacturing practices for medicines, biological products, active pharmaceutical ingredients and medical devices.
  • Anvisa and Health Canada already had signed instruments in the areas of consumer safety and medicine and food regulation.
  • The signed instrument will allow progress in Anvisa’s bilateral relationship with the Canadian authority and will facilitate the establishment of possible regulatory trust mechanisms.

Source: Anvisa

30 April
Anvisa to draft Public Consultation for regulation on clinical trials for drug registration

Anvisa approved today, the opening of the Public Consultation (CP) to review Collegiate Board Resolution No. 9, of 2015. This Resolution deals with the Regulation for conducting clinical trials aimed at registering medicines in Brazil.

For the director reporting on the topic, Meiruze Freitas, “the guiding pillar for the review of RDC nº 9, of 2015, was to improve Anvisa’s regulatory performance in the approval and monitoring of clinical trials, based on health risk.

During the same meeting, the Regulatory Impact Analysis Report (AIR) was presented, which, after an in-depth analysis, confirmed the need to review current legislation, aiming to adapt it to innovative scenarios and ensure the harmonization of Brazilian regulations with international standards.

The Public Consultation (CP) marks a significant advance by proposing the adoption of reliance mechanisms as a strategy to improve processes and optimize the analyzes conducted by Anvisa.

The CP period will be 45 days, allowing an opportunity for all interested parties including the population in general to contribute their considerations and suggestions on the topic under discussion.

Source: Anvisa

9 April
Anvisa launches pioneering program to support startups for drug innovation

Anvisa launched Call Notice n. 1 dated April 5, 2024, which aims to support the development of new synthetic medicine and biological product of interest in health services.

  • This innovative initiative recognizes the need for new medicines and the importance of fostering innovation in the Brazilian healthcare ecosystem.
  • The notice is specifically aimed at Brazilian startups , strengthening the role of regulation in promoting innovation and development in health in the country.
  • The program is aligned with the guidelines of the National Strategy for the Development of the Health Economic-Industrial Complex and Anvisa’s Innovation Policy, and aims to accelerate market access to new medicines, meeting the urgent medical needs of the population.

Three startups will be chosen , each developing, respectively, a herbal medicine, a new synthetic medicine and a biological product, to participate in the regulatory evaluation pilot project. The primary objective is to support these companies in navigating health regulations, from the initial phases of product development.

The initiative seeks to offer specific regulatory support, aiming to facilitate compliance with health requirements and accelerate the process of innovation in medicines in the country. Additionally, the aim is to gather lessons that will contribute to improving Anvisa’s guidance and support strategies for innovations in the medicine sector. 

Source: Anvisa

24 April
Nitrosamine impurities acceptable intakes update

The TGA has published updated acceptable intake (AI) information for nitrosamine impurities in medicines consistent with recent updated information from the European Medicines Agency The changes include minor editorial amendments, increases to the AI limit for a nitrosamine impurity and inclusion of recently internationally determined AI limits for numerous nitrosamine impurities in medicines.

Sponsors and manufacturers are expected to be familiar with the current acceptable intakes (AI) for nitrosamine impurities in medicines that TGA consider acceptable. This is detailed on the TGA website.

2 April
Updated guidelines for Assessed listed medicines

The TGA has published updated Assessed listed medicines evidence guidelines to aid sponsors in preparing their product applications.

The updated guidelines:

  • have been improved based on industry feedback, consultation with the Advisory Committee of Complementary Medicines (ACCM), and TGA’s experience with applications that have been received to date.
  • include information on the Data Protection SchemeComparable Overseas Body (COB) process, how to change an assessed listed medicine, and other helpful information for sponsors preparing their application.
  • also include changes to increase flexibility for evidence requirements and standards, as well to improve readability and clarify technical concepts.
  • now provide more general information and refer to established international and TGA adopted guidelines. This means that the guidelines will need less updating and align with internationally accepted standards, providing a good balance of general information with good references for sponsors who are not very familiar with this information.
  • also include editorial and minor changes to remove repetitive information and update links to current documents, making it easier to prepare an assessed listed medicine application.

Source: TGA

8 May
Revision of timelines for variation applications of registered products pharmaceutical products, a pilot study

The NPRA continuously works towards improving efficiency, not only for pre-marketing product assessments but also for post-approval changes.

To provide greater clarity and more effective monitoring, the NPRA to revise the current timelines for variation applications outlined in the Malaysian Variation Guideline for Pharmaceutical Products (MVG) and Malaysian Variation Guideline for Biologics (MVGB).

For information, NPRA is continuously working towards improved efficiency, not only for pre-marketing product assessments but also for post-approval changes. To provide greater clarity and more effective monitoring, we are in the plan to revise the current timelines for variation applications outlined in the Malaysian Variation Guideline for Pharmaceutical Products (MVG), Malaysian Variation Guideline for Biologics (MVGB), and Malaysian Variation Guideline for Natural and Health Supplement Products.

Before finalising these new timelines, a pilot study with a duration of 1 year will be conducted, starting on June 1, 2024.

Please view Table 1 on this page to better understand how to plan variations for this pilot.

  • All PRHs are advised to plan their submissions in accordance with these new timelines.
  • Please note that NPRA will not reject variation applications that exceed the maximum number of permitted variation types per registered product as listed in Table 1. Instead, the timelines may be extended beyond the new timelines.

Source: NPRA

7 May
HSA Signs MoU with the Ministry of Health, Malaysia

Singapore’s HSA and the Ministry of Health, Malaysia signed a Memorandum of Understanding (MOU) for continued cooperation in matters pertaining to pharmaceutical products and cosmetics including post-market vigilance, enforcement and Good Clinical Practice for clinical trials on 6 May 2024.

This MOU is a renewal of the MOU signed in 2012 and marks an important milestone in solidifying ties between the two regulatory authorities.

Source: HSA

30 April
NEX2US Newsletter Issue 10 – April 2024

The HSA has published Issue 10 of its NEX2US report which is packed with a variety of regulatory news on medicines and medical devices.

Source: HSA

28 April
SAHPRA And Botswana Medicines Regulatory Authority (BoMRA) sign MoU To Enhance Medicines Regulation In The Region

The South African Health Products Regulatory Authority (SAHPRA) and the Botswana Medicines Regulatory Authority (BoMRA) have signed a memorandum of understanding (MoU) that will see the two regulators partner on various areas to improve access to new medicines and therapies, the control of falsified and substandard medicines and the sharing of best practice and regulatory information, amongst others.

The MoU between SAHPRA and BoMRA will allow the regulators to develop a cooperative partnership towards ensuring access to safe, quality, and effective health products in the respective countries.

  • The partnership paves the way for the two regulators to collaborate and share information on the assessment of medicines and health products, which will result in efficiencies in the medicine approval processes in both South Africa and Botswana.
  • This agreement also enables information sharing on the post-marketing monitoring of medicines for adverse drug reactions, resulting in more robust safety and efficacy monitoring in the interest of the health of the citizens of both countries.
  • The MoU also formalises joint port of entry operations between SAHPRA and BoMRA aimed at protecting the citizens of both countries from the illegal importation of unregistered, falsified and substandard medicines and health products.

Source: SAHPRA

21 May
MHRA announces a proposed framework for international recognition of medical devices

The MHRA:

  • has today published a statement of policy intent for international recognition of medical devices. It describes how the UK Government intends to recognise regulatory approvals from other countries (see CRCs below)depending on device type, class, and prior approval.
  • continues to review the list of comparable regulator countries and is in active discussions with the Pharmaceuticals and Medical Devices Agency (PMDA) to explore the recognition of medical device approvals from Japan.
  • statement of policy intent focuses on ensuring safe access to quality-assured medical devices and reducing the duplication of assessments by comparable regulators to enable resource to be focused on more innovative products for the benefit of patient health.

The proposed framework is still in draft, and the final version would be integral with the future core regulations.

With reference to the intended policy on international recognition, the comparable regulator countries (CRCs) for the proposed framework will be:

CountryAgency
AustraliaTGA
CanadaHealth Canada
European UnionNational competent authorities in the member states of the EU/ European Economic Area (EEA)
USAFDA

On this page, you can see the eligibility criteria for the framework and the exclusions from international recognition.

Source: MHRA


MHRA announces consultation on improved safety for high risk in vitro diagnostic devices  

The MHRA has today launched a four-week consultation which will support improved safety for certain high risk in vitro diagnostic (IVD) devices.

The new policy that the MHRA is consulting on would require manufacturers to comply with additional measures for certain high risk IVDs, such as blood tests used to identify blood type before transfusions or tests which identify life-threatening diseases, introducing harmonised requirements for these products.  

The agency is also seeking views on the removal of the Coronavirus Test Device Approval (CTDA) process to avoid duplication of regulatory requirements for COVID-19 tests against the Common Specification requirements.   

The consultation is for the MHRA to seek views on the possible amendments to the Medical Devices Regulations 2002 to include Common Specification requirements for manufacturers of high-risk IVD devices.

This consultation builds upon public views after an initial consultation in November 2021 and will help inform further policy decision-making in this area. The scope of this consultation is specific to the Common Specification requirements for high-risk IVD devices. 

You can respond to the consultation online here.

The deadline to complete this consultation is Friday, 14th June 2024.

Source: MHRA

9 May
MHRA launches AI Airlock to address challenges in regulating medical devices that use Artificial Intelligence

The MHRA has launched AI Airlock, its new regulatory sandbox for AI as a Medical Device (AIaMD).

Last month, the MHRA set out its strategic approach to AI in response to a white paper published in 2023 by Government.

  • This pilot project is a key part of that approach.
  • It will help the Agency to identify and address the challenges for regulating standalone AI medical devices (AIaMD), initially seeking out and supporting 4-6 virtual or real-world projects through simulation.
  • This will allow the Agency to test a range of regulatory issues for these devices when they are used for direct clinical purposes within the NHS.
The AI Airlock

The regulatory sandbox model is a recognised mechanism to help address novel regulatory challenges across sectors.

  • The AI Airlock is a world-leading version in healthcare, designed to assist in safe development and deployment of AIaMDs, and this project will follow that robust process so manufacturers can deliver what is required to ensure the real-world viability of these devices.
  • The MHRA’s regulatory AI Airlock takes into account evidence-based work produced by other bodies with a similar focus and the Agency will work collaboratively with the NHS AI Lab and the Department of Health and Social Care (DHSC).
  • AIaMD products are deployed via NHS infrastructure, making the Devolved Nations crucial to regulatory discussions around deployment and post-market surveillance.
  • The findings from this partnership between government, regulators and industry will inform future AI Airlock projects and influence future UK and international AIaMD guidance, including how we work with UK Approved Bodies on UKCA marking and with trusted regulatory partners on international recognition of medical devices.

You can read more about the AI Airlock here.

Source: MHRA

24 April
MHRA expected to launch recognition framework for devices

At the 2024 Annual Meeting of the Medical Device Manufacturers Association (MDMA) on 19 April, Richard Phillips, executive director of the Association of British HealthTech Industries (ABHI), said that the UK MHRA is preparing to deploy an international recognition framework for medical devices that would allow device makers to bring products to the UK more easily.

Phillips noted that the Chancellor of the Exchequer Jeremy Hunt last year said MHRA would use a “rapid, often near automatic sign-off” system to allow medical products on the UK market if those products were already authorized by regulators in select jurisdictions. He also referenced a blog post from Laura Squire, MHRA’s chief healthcare quality and access officer, from March that indicates that the agency would publish a proposal for international recognition for medical devices this spring.

Source: RAPS

25 March
Updated Guidance on the regulation of medical devices in Northern Ireland

The Medical Devices In Vitro Diagnostic Devices etc. Amendment Regulations 2024 came into force on 21 March 2024 and introduces provisions required for implementing the IVDR in Northern Ireland.

These include the following:

  • penalties (in the form of a criminal offence punishable by imprisonment, a fine or both), powers to impose enforcement notices and an amendment to extend the civil sanctions regime in Schedule 2 to the Medicines and Medical Devices Act 2021 (when that is brought into force) for the infringement of provisions in the IVDR
  • appointing the Secretary of State as the authority responsible for Notified Bodies in relation to the IVDR
  • requirement for certain documentation concerning in vitro diagnostic medical devices to be in English
  • provisions for fees for the designation and monitoring of UK Notified Bodies, and fees for certificates of free sale to continue (at the same level as existing fees) and for fee recovery, refund and waiver under IVDR
  • an arbitration procedure for refused applications for performance studies

You can view a full list of provisions on this page.

Source: MHRA

20 May
Cofepris authorizes first high-tech software for the treatment of myocardial infarction

Cofepris has authorized its first high-tech software that improves the precision and prognosis of the most common treatment for myocardial infarction, marking a milestone in therapeutic innovation in Mexico in favor of the health of millions of patients.

This is the first software that the health authority has authorized as a medical device, which uses an interactive screen that receives, processes and transmits aortic and distal blood pressure signals, providing medical personnel with the ability to personalize treatments and significantly improving patient outcomes.

This authorization was issued based on the equivalence agreement with the US FDA and after the evaluation carried out by Cofepris’ specialized judging team, in accordance with the Guide for obtaining the health registration of medical devices .

Source: Cofepris

17 May
Study supporting the monitoring of availability of medical devices on the EU market – 8th notified bodies survey on certifications and applications (MDR/IVDR)

The European Commission’s Directorate-General for Health and Food Safety (DG SANTE) – through the European Health and Digital Executive Agency (HaDEA) – has commissioned a “Study supporting the monitoring of availability of medical devices on the EU market”.

  • The study started in December 2022 and will be running for 36 months (December 2025). The study has been contracted to a consortium led by the Austrian National Public Health Institute (Gesundheit Österreich GmbH/GÖG), in collaboration with Areté and Civic Consulting.
  • In the context of the study, a dashboard has been developed. The dashboard presents an overview of the data gathered from different stakeholders. In addition, comparable data from previous surveys of notified bodies conducted by the European Commission have been integrated in the dashboard.
  • You can view the latest update on the study here.

Source: European Commission

17 May
Guide to applications for a variation to a manufacturer’s authorisation

HPRA has published a new guide for the above. You can download it here.

Source: HPRA

16 May
Guide to Clinical Investigations Carried Out in Ireland

This guide has been updated. There are changes throughout the document. Here, you can view the track changed (18 Nov 2022) and clean (16 May 2024) versions of the document. The guide:

  • provides an overview of the legislation on clinical investigations (CIs) involving medical devices.
  • also provides guidance on how to submit applications to carry out CIs in Ireland to the Health Products Regulatory Authority (HPRA).
  • is primarily targeted towards CI sponsors (e.g. manufacturers, academic groups, clinical research organisations), who wish to carry out CIs involving medical devices in Ireland. The information may also be useful for ethics committees and other stakeholders.

Source: HPRA

9 May
FDA final rule will include IVDs manufactured by laboratories under FD&C act

The FDA is issuing a final rule to amend its regulations to make explicit that in vitro diagnostic products (IVDs) are devices under the FD&C Act including when the manufacturer of the IVD is a laboratory.

  • In conjunction with this amendment, the FDA is phasing out its general enforcement discretion approach for laboratory developed tests (LDTs) so that IVDs manufactured by a laboratory will generally fall under the same enforcement approach as other IVDs.
  • This phaseout policy:
    • includes enforcement discretion policies for specific categories of IVDs manufactured by a laboratory, including currently marketed IVDs offered as LDTs and LDTs for unmet needs
    • is intended to better protect the public health by helping to assure the safety and effectiveness of IVDs offered as LDTs, while also accounting for other important public health considerations such as patient access and reliance.

This rule becomes effective on 5 July 2024.

15 April
Consultation: Availability of Instructions For Use (IFU) in more flexible formats

The TGA is seeking feedback on how the Instructions for Use (IFU) are provided, and whether they should be made available in more flexible formats. 

  • The IFU is the information provided by the manufacturer for the intended user detailing how the device can be used safely for its intended purpose.
  • Currently, the provision of electronic version of the IFU (eIFU) is allowed only under very specific circumstances. 
  • For medical devices that are limited to use by professional users only and where it is not practicable to provide the IFU directly on the device or the device packaging, the TGA considers it acceptable for the IFU to be provided electronically. 

You can view the consultation paper here and respond to the consultation via this page.

Consultation start Date: 15 April 2024

Consultation end date: 28 May 2024

Source: TGA

15 March
Companion diagnostics guidance update- public consultation

The TGA is seeking feedback on the updated draft Companion Diagnostics (CDx) Guidance document.

The proposed updates aim to provide sponsors and manufacturers of medicines, biologicals and IVD medical devices further clarification regarding the requirements for companion testing, including:

  • A CDx testing identification guide to assist them in identifying whether their medicine or biological indication requires companion testing,
  • An introduction to the concept of the ‘companion testing plan’ to recognise the CDx component evaluations undertaken as part of the medicine application.
  • Improved clarity on clinical and analytical performance requirements for CDx, and
  • Case studies to assist sponsors of medicines and devices on the regulatory process and the technical documentation required for an IVD CDx.

You can respond to the consultation here.

Source: TGA

Consultation start date: 15 March 2024

Consultation end date: 17 June 2024

8 April
Anvisa will use assessments from foreign regulatory authorities to register medical devices

Anvisa published, in the Official Gazette of the Union this Monday (8/4), Normative Instruction (IN) 290/2024 , which establishes the optimized procedure for the purposes of analyzing and deciding petitions for registration of medical devices.  

With this measure, the Agency now has more agility in the evaluation process of products already approved by equivalent foreign regulatory authorities , consolidating a major step in the adoption of regulatory trust mechanisms.  

The text of the IN stipulates that, as of 3 June 2024, medical devices authorised for markets regulated by four equivalent foreign regulatory authorities (Australia, Canada, the USA and Japan) may have their assessments shortened, based on the requesting companies.

To this end, documents must be presented demonstrating that products intended for the Brazilian market have the same production characteristics, indications and intended use approved by the recognized regulatory authority. 

Source: Anvisa

2 April 2024
Scientific Advice Pilot for high risk medical devices

EMA is running a pilot that enables the expert panels to provide scientific advice for manufacturers of high-risk medical devices.

EMA invites EU-based manufacturers or their authorised representatives to apply for a third phase of the pilot by 30 June 2024. They can use the following application form:  

For the third pilot phase, applicants can indicate if they would be willing to have an HTA body observe their project. In such cases, EMA will inform them whether this will be possible.

Source: EMA

21 May
Draft for Comments || Rules and Regulations on the Issuance of Authorization for Registration Applications of Pharmaceutical Products and Active Pharmaceutical Ingredients for Human Use by the Food and Drug Administration

The key changes in the draft include the following:

1. Adoption of terminology harmonized with other FDA issuances being developed (specifically pharmaceutical product and active pharmaceutical ingredient).

2. Updated provisions under definition of terms, general conditions, and types of applications covering the identical pharmaceutical product applications (IPPA) to be established.

3. General provisions allowing bundling of applications for post-approval changes (specific conditions and requirements to be covered by implementing guidelines through FDA Circular).

You can view the draft here and the Annexes at the link below.

All comments may be sent via email to cdrr.sds@fda.gov.ph using the comment form. The deadline for submission of comments is 30 May 2024.

Source: FDA

2 May
Concept paper on revision of the Guideline on Risk Assessment of Medicinal Products on Human Reproduction and Lactation: from Data to Labelling

The concept paper proposes to revise the Guideline on Risk Assessment of Medicinal Products on Human Reproduction and Lactation: from Data to Labelling (EMEA/CHMP/203927/2005)

Comments should be provided using this EUSurvey form.

Start of public consultation: 2 May 2024

End of public consultation: 31 August 2024

12 April
Draft Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and chronic obstructive pulmonary disease (COPD)

This guideline is the 2nd revision of the CHMP Guideline formerly called “Guideline on the requirements for clinical documentation for orally inhaled products (OIP) including the requirements for demonstration of therapeutic equivalence between two inhaled products for use in the treatment of asthma and chronic obstructive pulmonary disease (COPD) in adults and for use in the treatment of asthma in children and adolescents”. It addresses the requirements for demonstration of therapeutic equivalence (TE) between orally inhaled products containing the same active moiety(ies).

Comments should be provided using this EUSurvey form.

Start of public consultation: 12 April 2024

End of public consultation: 30 October 2024

Source: EMA

Draft HMA/EMA guidance document on the identification of personal data and commercially confidential information within the structure of the marketing authorisation application (MAA) dossier

This guidance document is intended to be applicable to information/documents pertaining to the initial and variation of marketing authorisation application (MAA) dossiers of medicinal products for human use for which the regulatory procedure has been finalised, under the national, mutual recognition, decentralised and centralised procedures.

“Finalised” shall mean that the marketing authorisation (MA) has been granted or refused or that the MAA has been withdrawn.

Comments should be provided using this EUSurvey form.

Start of public consultation: 12 April 2024

End of public consultation: 28 June 2024

Source: EMA

Draft Guideline on the pharmaceutical quality of inhalation and nasal medicinal products

This guideline is the first revision of the guideline on pharmaceutical quality of inhalation and nasal 5 products (EMEA/CHMP/QWP/49313/2005 Corr).

The main aim of the first revision is to consolidate the information available in the previous guidance documents, the related published questions and answers, also taking into consideration recent advancements in the field, common practice and new regulations, including the medical device regulation.

Comments should be provided using this EUSurvey form.

Start of public consultation: 12 April 2024

End of public consultation: 31 October 2024

Source: EMA

25 March
Draft Guideline on quality, non-clinical and clinical requirements 4 for investigational advanced therapy medicinal products in clinical trials

The guideline provides guidance on the structure and data requirements for a clinical trial application fo investigational ATMPs. The guideline is multidisciplinary and addresses development, manufacturing and quality control as well as non-clinical and clinical development of ATMPs.

You can view the draft here.

Start of second public consultation: 25 March 2024

End of second public consultation: 31 May 2024

Source: EMA

22 February
ICH E2D(R1) Guideline on post-approval safety data Step 2b – Revision 1

The above revision is currently under public consultation. You can view the consultation document here.

Consultation start date: 22 February 2024

Consultation end date: 22 June 2024

You can read more about the ICH process in this post.

Source: EMA
4 March
Public consultation on ICH Guideline E2D(R1) launched in Switzerland

Swissmedic has launched the public consultation on Guideline E2D(R1) of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH Guidelines)

  • Stakeholders in Switzerland have until 22 June 2024 to comment on the draft of Guideline E2D(R1) “Post-Approval Safety Data: Definitions and Standards for Management and Reporting of Individual Case Safety Reports”.
  • Since the original ICH E2D guideline was agreed in 2003, new sources of post-approval safety information have emerged or are applied more frequently (e.g. social media, market research programmes, patient support and assistance programmes) which vary in terms of their characteristics and their contribution to the quality of post-approval safety information.
  • The definitions and regulatory guidance in ICH E2D are no longer sufficient to provide guidance on current practices and needs.
  • Therefore, the original considerations and standards need to be carefully revisited in order to adapt the existing concepts, principles and definitions of the ICH E2D guideline and to support appropriate safety surveillance and actions in consideration of the new sources of safety information.

Links to the guideline and feedback form can be found on this page.

Consultation start date: 4 March 2024

Consultation end date: 22 June 2024

Source: Swissmedic

13 March
European Parliament formally adopts the EU AI Act

The European Parliament has formally adopted the EU AI Act in a move that brings the proposed legislation to the brink of becoming EU law. This the world’s first ever law on AI.

MEPs voted overwhelming in favour of adopting the regulation on Wednesday – 523 MEPs voted in favour, 46 voted against, and there were 49 abstentions.

Under the EU AI Act, a new risk-based system of regulation applicable to AI will apply across EU member states.

Under the new framework, some uses of AI will be prohibited entirely, while the strictest regulatory requirements are reserved for ‘high-risk’ AI systems and the providers and deployers of such systems.

The EU AI Act was proposed by the European Commission in April 2021. Those proposals were subsequently scrutinised by the European Parliament and Council of Ministers, the EU’s other law-making institution. A compromise text was developed and has now been formally adopted by MEPs, but for the text to become EU law, the Council must also adopt the EU AI Act

Source: pinsentmasons.com

17 May
Publication with the involvement of Swissmedic, on the risk assessment of nitrosamine impurities

A scientific article on the development and application of the “Carcinogenic Potency Categorisation Approach” (CPCA) has been published.

  • With the involvement of experts from Swissmedic, an international working group of representatives of regulatory authorities compiled data and principles that led to the development of a model for the risk assessment of nitrosamines based on chemical structural characteristics. This was published in a scientific journal.
  • The open-access scientific publication:
    • describes the principles of the Carcinogenic Potency Categorisation Approach (CPCA) published at the end of 2023. The method makes it possible to standardise the definition of acceptable intakes (AI) for medicinal products, including complex chemical nitrosamine impurities, specifically nitrosamine drug substance-related impurities” (NDSRI). This speeds up safety assessments of nitrosamine impurities.
    • also uses sample molecules to illustrate how the CPCA is used to determine acceptable intakes for nitrosamine impurities. This allows industry and manufacturing experts in particular to understand the classification into different risk classes.

Source: Swissmedic

3 May
WHO releases two draft appendices to draft guideline on good manufacturing practices (GMPs) for excipients released in 2023

The WHO has released two draft appendices to a draft guideline on good manufacturing practices (GMPs) for excipients released in 2023. Links to both appendices are provided below.

WHO GMP for excipients used in pharmaceutical products – Appendix 3 1: Risk Management in the 4 production and control of excipients used in pharmaceutical products

WHO GMP for excipients used in 3 pharmaceutical products – Appendix 4 2: List of examples of high-risk excipients

Please submit your comments through the online platform, PleaseReview™.Comments should be submitted through the online platform by 9 June 2024.

WHO aims to collect feedback and publish a working document for discussion and possible adoption by its Expert Committee on Specifications for Pharmaceutical Preparations in August or September 2024.

Sources: WHO, RAPS

18 April
Swissmedic receives grant from the Bill & Melinda Gates Foundation

On 27 March 2024, Swissmedic signed a new grant agreement with the Bill & Melinda Gates Foundation,  to continue supporting regulatory authorities in low and middle-income countries for a further three years.

  • The agreement between Swissmedic and the Bill & Melinda Gates Foundation is based on the Memorandum of Understanding (MoU) signed in January 2014 by the Foundation, the Federal Department of Home Affairs (FDHA) and the Federal Department of Foreign Affairs (FDFA) with the aim of strengthening the regulatory systems in low and middle-income countries, thereby improving and accelerating access to healthcare and medicines. Its focus is on countries in sub-Saharan Africa.
  • The overall aim of the project is to bring high-quality, life-saving medicines to patients as quickly as possible.
  • Swissmedic signed its first grant agreement with the Foundation in December 2015. Since then, Swissmedic, the three parties to the MoU and the World Health Organization (WHO) have developed a support programme consisting of three main areas of engagement:
    • Harmonisation: Support for the implementation of the African Medicines Regulatory Harmonization (AMRH) programme at regional and continental level and towards the operationalisation of the African Medicines Agency (AMA)
    • Access: Swissmedic procedure for scientific advice and Marketing Authorisation for Global Health Products (MAGHP)
    • Capacity building: Swissmedic training opportunities for regulatory authorities in low and middle-income countries

Comment: It is interesting to note that the amount of the grant is not mentioned anywhere and where there are any strings attached to such a grant.

Source: Swissmedic