With an ever-increasing regulatory landscape, it is important to know what is coming next. Looking into regulatory world – we are aware of some changes that are coming along the way and we are certain that these will affect many of us. Therefore, it is crucial to be prepared for all the changes. We at Cunesoft believe in the importance of sharing knowledge and helping each other to prepare for upcoming regulations. Therefore we would like to share with you the summary of some important regulatory activities that are coming next year and beyond.
New EU rules on medical devices
Since late 1990s, where European Union laid down rules on the safety and performance of medical devices, some inconsistencies were detected in their interpretation across Europe. To reflect the progress over the last 20 years EU has revised the legal framework on medical devices and introduced 2 new regulations on April 5, 2017: medical devices (hip implants, x-ray machines, etc.) and in vitro diagnostic medical devices (medical devices that are used to perform various tests: pregnancy test, HIV test, etc.).
These new regulations should improve the quality, safety and reliability of medical devices. This includes higher risk control on devices such as implants, previously unregulated aesthetic products & a new system for risk classification in line with international guidelines for in vitro diagnostic medical devices. It should also strengthen transparency of information for customers & enhance vigilance and market surveillance.
Mentioned regulations took effect on May 25, 2017 and will progressively replace the existing directives. The new regulations will be fully applicable in May 26, 2020 for medical devices and May 2022 for in vitro diagnostic medical devices.
eCTD will be mandatory for all CEP applications from 1st January, 2020
CEP or Certification of Suitability to the Monographs of the European Pharmacopoeia is the certification confirming that pharmaceutical substances or active pharmaceutical ingredients (API) are produced according to the monographs of the European Parliament.
According to the European Directorate for the Quality of Medicines & HealthCare (EDQM) – the organisation responsible for the procedure of CEP – submissions for CEP must be in the eCTD format beginning the January 1, 2020.
The new directive applies to:
- Notifications, revisions, renewals & new applications (will no longer be accepted in NeeS format)
- Exceptions applies to TSE only submissions, where PDF continues to be a standard format accepted.
Health Canada Master File
A Master File (MF) is a reference that provides information about specific processes or components used in the manufacturing, processing, or packaging of a drug.
Even though Health Canada published a Guidance Document on the preparation of drug regulatory activities in eCTD format a few years ago, some deadlines have been altered since then.
To align with the latest Health Canada’s notice – as of January 1, 2020 all DMF holders must use eCTD format for all Master Files:
New Type I Active Substance Master File (ASMFs)
New Type II Container Closure System Master Files (CCS MFs)
New Type III Excipient Master Files (Excipient MFs)
New Type IV Dosage Form Master File
For already existing Master Files, Health Canada is recommending conversion to eCTD Format, but this is not mandatory.
Health Canada is still offering an exemption of DMF file submission in eCTD, but this will be considered on case-by-case basis by Health Canada.
As the authority continues to move towards a harmonized intake process, additional regulatory activity types will be mandatory in eCTD format. Health Canada will inform stakeholders in advance of making such requirements.
Regulatory activity types for the following product lines currently remain out of scope for filing in eCTD format; they must be filed in “non-eCTD electronic-only” format:
- Medical Devices
- Veterinary Drugs
FDA: Type III Drug Master File
Drug master files (DMFs) are submissions to the U.S. Food and Drug Administration (FDA) used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products.
The FDA require all Type III DMF files holders (Packaging material) submit their DMFs in eCTD as of May 5, 2020.
EU’s CESSP phase 1 project
CESSP is a programme included in the eSubmission programme which will eventually result in the implementation of the Common European Single Submission Portal. The system will be implemented within the current Common European Submission Portal (CESP) as a new module called CESP Application Dataset Management Module (CESP Dataset Module)
CESSP Phase 1 is ongoing project and is a first milestone which will deliver a new tool for creation of Marketing Authorisation Application (MAA) forms with the goal to replace the relevant PDF forms with a web based interface and to enhance the current PDF based electronic application form (eAF) for both Human and Veterinary.
Project Phase 2 will be consisting out of replacement of the eAF for Variations and Renewal. In later phases implementation and further integration with SPOR are proposed.
It is expected that the first version of the system will be available for use by end of June 2020. Other milestones include 2020 Q4 as the mandatory use of CESP Application dataset module (eAF MAA for human and veterinary).
Mandatory eCTD submissions in Australia
In 2020 Australia’s Therapeutic Goods Administration will be fulfilling its 3rd stage of eCTD implementation for prescription medicines strategy.
The proposed implementation strategy demands mandatory eCTD from 1st July 2020 for:
- Extension of Indications – Generic Product
- Additional Trade Name
- Category 3 – Variation involving only chemistry, quality control and manufacturing information
- Minor Variations
– MEC – Minor Editorial Change
– SRR – Safety Related Request with or without evaluation of data
– SAR – Self Assessable Request
– 9D(1) – Correction of a Register Entry
- S14 – Consent under S14 to waive compliance
- Master Files
- Periodic Safety Update Reports (PSURs)
Singapore plans to move ahead with their eCTD Implementation during 2020
In efforts to facilitate the movement of regulatory information between pharmaceutical companies and the Singapore’s Health Sciences Authority (HSA), the HSA has announced its plans to implement the electronic Common Technical Document (eCTD) back in 2018. The latest updates can be found on the HSA website. It is expected that Singapore will commence requiring the use of eCTD submissions for new original marketing applications (NDA) and Generic Drug Applications (GDA). We anticipate significant progress on this during 2020.
Update on SPOR & IDMP projects
Currently, two out of the four SPOR services have been implemented by the EMA – the Organizations Management Services (OMS) and Referentials Management Service (RMS). The OMS and RMS are already integrated with Electronic Application Forms (eAF) and supplying organization / referential master data to MAA Human, MAA Vet, Renewal and Variation application forms. Furthermore, the EudraVigilance user registration process also started to make use of organization master data. In future OMS data is expected to support regulatory submissions in Telematics systems such as the Common European Submission Portal (CESP), CT portal and Art.57/xEVMPD.
IDMP / SPOR:
With the deadline for IDMP/SPOR Task Force comments on the version 1 of the EU Implementation Guide already passed in April, the second half of 2019 promises a second consultation on the EU IG within the IDMP/SPOR TF and the final EU IG is planned to be published in 2020. Once the final implementation guide has been made available, expected for 2020, the IDMP enforcement process initiates. Industry will have 12 months from publication of the final implementation guide to initial submissions being accepted by EMA. Assuming implementation guidelines to be completed until mid 2020, as per the current EMA projection, initial IDMP submissions will be accepted from mid 2021 onwards.
China is planning to implement eCTD submissions
In recent months, China’s Center for Drug Evaluation (CDE) has released draft information regarding the future of electronic common technical document (eCTD) submissions in China. Final Implementation Guidelines have been published in Q4 2019 and eCTD is expected to become mandatory in China during H1 2020.
Brexit – UK proposes guidance for no-deal Brexit
On 29 October 2019, the European Council agreed to a further extension of the date for the UK’s withdrawal from the EU. The extension will last as long as necessary and, in any event, no longer than 31 January 2020.
For planning purposes, EMA is working on the scenario that the UK will become a third country after Brexit. Therefore, the UK will no longer be able to engage as (co)-rapporteur for new marketing authorisation applications via the centralised procedure. This is without prejudice to the outcome of the withdrawal negotiations.
The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) published a series of guidance documents for industry and other stakeholders covering proposed arrangements for the regulation of medicines, medical devices and clinical trials, if there is a no-deal Brexit
EMA’s electronical submission roadmap
The final updated version of the eSubmission Roadmap v2.2 was adopted by the HMA on 21 June 2019.