We are inviting applications for Associate Role – Regulatory Affairs
No. of positions: 05
Experience Level
Entry & Mid-Level
Mid-Level: 2-5 years of experience In this role, you will be expected to have the following attributes: • Work on deadlines • Highly professional • Excellent Microsoft Outlook, Excel, Word, and PPT skills • Basic knowledge of medical devices • English speaking, writing, and listening skills are highly desired • Attention to details • Individual contributor with minimal supervision • Enthusiasm to learn more and grow rapidly • Highly confident and self-motivated • Optimistic and problem-solving thought process
Educational Background: • B.E/B. Tech Degree in Biomedical Engineering / Medical Electronics / Medical Instrumentation /equivalent domain • Good academic Record of >70% in High school and a Degree
Prepare technical documentation for regulatory compliance (EU MDR, 510(K), UKCA)
Works in close collaboration with external stakeholders and is able to support and manage multiple projects at a time.
Ability to manage deliverables in a dynamic environment in a timely manner
Ensures compliance with global regulatory requirements and adherence towards internal policies and processes
Provides high-quality regulatory support for assigned products/projects Ability to work with cross-functional project members and respond to regulatory queries
𝐓𝐨𝐩 𝐒𝐤𝐢𝐥𝐥 𝐒𝐞𝐭𝐬:
Experience with any medical device industry or service is MUST
Experience in regulatory affairs and good technical documentation skills
Regulatory compliance knowledge towards EU MDR, and USFDA is required
Exposure/experience in any of the post-market plans, Clinical Evaluation procedures, risk management, and labelling are a plus
Knowledge on ISO 13485, ISO 14971, MEDDEV 2.7/1 Rev. 4, and IEC standards are preferred
Knowledge on Medical Device Regulations for different global markets
Experience with FDA submission is a plus
Ability to self-learn and adapt to the dynamic regulatory environment
You will be part of a rapidly growing organization, with an opportunity to work alongside the best minds in the industry. Competitive compensation and rewards, an opportunity to grow with a young company.
Intern – Regulatory Affairs
Opportunities for budding young engineering talents to join the industry
We are inviting applications for Intern – Regulatory Affairs
No. of positions: 06
Experience Level
Entry level : Graduate to 1 year
In this role, you will be expected to have the following attributes: • Work on deadlines • Highly professional • Excellent Microsoft Outlook, Excel, Word, and PPT skills • Basic knowledge of medical devices • English speaking, writing, and listening skills are highly desired • Attention to details • Enthusiasm to learn more and grow rapidly • Highly confident and self-motivated • Optimistic and problem-solving thought process
Educational Background: • B.E/B. Tech Degree in Biomedical Engineering / Medical Electronics / Medical Instrumentation /equivalent domain • Good academic Record of >70% in High school and a Degree
𝐉𝐨𝐛 𝐑𝐨𝐥𝐞: Internship (6 months & confirmation based on the performance) Nature: Full-time – Remote Based
𝐉𝐨𝐛 𝐑𝐞𝐬𝐩𝐨𝐧𝐬𝐢𝐛𝐢𝐥𝐢𝐭𝐢𝐞𝐬:
Manage country registrations (EU, Swiss, global)
Prepare technical documentation for regulatory compliance (EU MDR, 510(K), UKCA)
Works in close collaboration with external stakeholders and is able to support and manage multiple projects at a time.
Ability to manage deliverables in a dynamic environment in a timely manner
Ensures compliance with global regulatory requirements and adherence towards internal policies and processes
Provides high-quality regulatory support for assigned products/projects
Ability to work with cross-functional project members and respond to regulatory queries
𝐓𝐨𝐩 𝐒𝐤𝐢𝐥𝐥 𝐒𝐞𝐭𝐬:
Strong fundamental knowledge about medical device(s)
High learning attitude
Proactive and take initiative at work
Basic knowledge about Ethical behaviour at work
Basic Knowledge on ISO 13485, and ISO 14971 is desired
Basic Knowledge on Medical Device Regulations (minimum EU, FDA)
MDCG guidance on vigilance terms and concepts of EU MDR| 14 February 2023
The MDCG 2023-3 guidance document clarifies some of the essential terms and concepts in Section 2 of Chapter VII of the Regulation (EU) 2017/745 on medical devices (MDR). The topics covered in the guidance document are as follows:
Difference between Incident and Serious incident
Reportability under EU MDR
Definition of malfunction or deterioration in the characteristics or performance of a device with examples
Use error vs abnormal use
Timelines to report an incident
MDCG Guidance on Classification of IVD under IVDR | 10 February 2023
The MDCG 2020-16 rev.2 guidance addresses the requirement for the classification of IVDs under the classification rules set out in Annex VIII. This document’s primary purpose is to guide manufacturers, notified bodies and health institutions on how to classify an IVD before placing it on the market, making it available on the market or putting it into service in the Union. It is also intended to inform regulators and other stakeholders when assessing the class attributed to an IVD by a manufacturer or a health institution. More information about IVD classification rules can be found here.
CZECH REPUBLIC
Guidance on implementation of Article 97 in Czech Republic | 02 February 2023
If you supply the Czech market with a medical device to which the procedure according to Article 97 of the MDR has been applied by the competent authority of another Member State due to the expiry of the validity of the EC certificate issued according to Directive 93/42/EEC or 90/385/EEC and the not yet existing EC certificate according to the MDR , it is necessary to request a decision of the competent authority on this procedure from the manufacturer of the medical device in question. This decision temporarily replaces the missing EC certificate and declaration of conformity, by which the manufacturer proves the conformity of the medical device with the relevant legislative requirements
BfArM Guidance on Companion diagnostics (CDx) | 08 February 2023
A companion diagnostic (CDx) is defined in article 2(7) of IVDR 2017/746 as follows:
“companion diagnostic” means a device which is essential for the safe and effective use of a corresponding medicinal product to:
Identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicinal product; or
Identify, before and/or during treatment, patients likely to be at increased risk of serious adverse reactions as a result of treatment with the corresponding medicinal product
Whether an IVD fulfils the criteria of a CDx depends on whether detecting the biomarker status is necessary for the therapy decision to ensure the safe and effective use of the medicinal product. The analytical quality of detecting a certain biomarker is not a sufficient criterion for a CDx.
The guidance further introduces the special regulatory requirements, consultation procedure, risk assessment and performance studies with companion diagnostics. Further information can be found here.
IRELAND
HPRA process for Article 97 and notified body certificates | 13 February 2023
In December 2022, the Medical Device Coordination Group published Guidance (2022-18) on the use of Article 97 of the Medical Devices Regulation (MDR). The guidance allows for a controlled period of non-compliance for certain devices affected by the capacity challenges of notified bodies under specific conditions. Health Products Regulatory Authority (HPRA) has developed a process to use Article 97 for expiring or expired Directive certificates subject to meeting specific criteria. It will be used as a short-term measure to avoid disrupting the supply and availability of medical devices and healthcare in Ireland. Irish-based manufacturers or authorised representatives who meet the criteria can submit a request form for each certificate affected and pay the relevant fee. This process will continue until the EU Commission’s proposed legislative amendment to Article 120 of the MDR is adopted.
ITALY
Clinical trials of medicinal products and medical devices | 08 February 2023
European Regulation 536/2014 on clinical trials is fully implemented for medicinal products and medical devices. Specifically, with the Decree of the Minister of Health of 26 January 2023, subject to agreement in the State-Regions Conference, the 40 territorial Ethics Committees are identified that have the task of evaluating clinical trials on medical devices and medicines for human use, also thanks to the virtuous synergy developed between the Ministry, AIFA, Regions and Autonomous Provinces.
The Decree of the Minister of Health of 27 January 2023 also regulates the transitional phase in relation to the evaluation activities and the methods of interaction between the Coordination Centre, the territorial Ethics Committees, the Ethics Committees of national importance and the Italian Medicines Agency.
The regulatory harmonization decree was also signed, which regulates, in particular, the functions of the Ethics Committees, the criteria for the division of competences between territorial Ethics Committees and Ethics Committees of national importance, the criteria for the composition of the Ethics Committees, in order to ensure that the members are in possession of documented knowledge and experience in clinical trials of medicinal products and medical devices, also in order to guarantee its independence.
Breast implant national registry | 02 February 2023
On 2 February 2023, the Regulation establishing the National Register of Breast Prosthetic Implants, comes into force.
The National Register of Breast Prosthetic Implants feeds on data from regional registers. The Regions and Autonomous Provinces have 180 days from 2 February to establish regional and provincial registers. By 01 August 2023, the National Register of Breast Prosthetic Implants will receive data from each area of the territory.
Italy is the first country in the world that has a mandatory feeding register by surgeons who implant or remove prostheses on the national territory. Even the economic operators who distribute these devices in Italy are required to transmit the data relating to each individual breast implant marketed and intended to be implanted, both for aesthetic and reconstructive purposes.
RUSSIA
Amendment of Federal Law of the Russian Federation about advertising | 20 February 2023
Federal service for Surveillance in Healthcare (Roszdravnadzor) has amended the Federal Law of the Russian Federation dated 13.03.2006 No. 38-FZ about advertising. The law is applicable to medical devices supplied in the Russian market. The objectives of this Federal Law are:
To develop markets for goods, works and services on the basis of compliance with the principles of fair competition,
To ensure the unity of the economic space in the Russian Federation,
To exercise the right of consumers to receive conscientious and reliable advertising,
To create favourable conditions for the production and distribution of social advertising,
To prevent violations of the legislation of the Russian Federation on advertising,
To suppress the facts of improper advertising.
UNITED KINGDOM (UK)
Impact of extension of Medical Device Regulations transitional period and the validity of certificates in the EU | 20 February 2023
The EU is introducing more time to certify certain medical devices under EU Medical Device Regulation (“EU MDR”). The proposal recognises the challenges in capacity across notified bodies. Key changes include:
Extend the transitional period for higher-risk devices (class III and certain class IIb implantables) such as pacemakers to comply with EU MDR requirements until 31 December 2027, subject to certain conditions.
Extend the transitional period for medium and lower-risk devices (other class IIb devices, class IIa, class Im, Is and Ir devices) such as syringes to comply with EU MDR requirements until 31 December 2028
Extend the validity of certificates issued by notified bodies under Directive 90/385/EEC and 93/42/EEC that were valid on 26 May 2021
The UK Medicines and Healthcare products Regulatory Agency ( MHRA ) is carefully considering the implications of these revisions for the acceptance of CE-marked medical devices on the Great Britain (GB) market. At present, a device with a valid CE mark can be placed on the GB market until 30 June 2023. That would include certificates valid under the latest EU’s revised transitional arrangements if they are adopted as proposed. There are plans to extend acceptance of the CE marking in GB, but the official MHRA announcement is yet to be released.
UNITED STATES OF AMERICA (USA)
FDA Guidance on Adult Portable Bed Rail Safety | 27 February 2023
Many people use adult portable bed rails to help create a supportive and assistive sleeping environment in homes, assisted living, and residential care facilities. The guidance provides information on the risks of adult portable bed rails, recommendations for their safe use, alternatives to bed rails, and how to report medical device problems to the FDA.
Consumers can purchase many adult portable bed rails on websites and in stores without a prescription and without the recommendation of a health care provider. Adult portable bed rails marketed for medical purposes, such as those intended to assist individuals who are disabled, injured, or recovering from surgery or hospitalized with transfer in and out of bed or repositioning, intended to reduce the risk of falling or fracture or mitigate the risk of falling due to the effects of balance disorders or other medical conditions are considered medical devices regulated by the U.S. Food and Drug Administration (FDA) (see 21 CFR 890.5050 Daily activity assist device, product code, QTC Adult Portable Bed Rails for Medical Purposes).
FDA guidance on Medical Device Misconnections| 23 February 2023
FDA has recognized voluntary consensus standards for certain medical device connector designs intended to enhance device safety, such as the ISO 80369 series. Many connectors that rely on the ISO 80369 standards are currently available and incorporated into product-specific standards.
Connectors that conform to these standards are designed to help reduce the risk of medical device misconnections.
FDA guidance on Compliance Programs| 23 February 2023
FDA’s compliance programs provide guidance to FDA personnel for activities to evaluate industry compliance with the Center for Devices and Radiological Health. Some key compliance programs are available for Medical devices/Radiological health as follows:
The guidance introduces the Food and Drug Administration’s (FDA) regulatory requirements for compliance with performance standards for laser products. FDA regulates radiation-emitting electronic products, including all types of lasers products. Laser product means any manufactured product or assemblage of components which constitutes, incorporates, or is intended to incorporate a laser or laser system. A laser or laser system that is intended for use as a component of an electronic product shall itself be considered a laser product. The Agency sets radiation safety product performance standards that must be met by manufacturers in order for laser products to be legally sold in the U.S. market. Laser products may fall under both the definition of a medical device and that of an electronic product, of the FD&C Act.
FDA guidance on Medical X-Ray Imaging Devices conformance with IEC standards | 21 February 2023
The guidance introduces the FDA’s policy regarding the regulation of medical x-ray imaging equipment that is subject to the Federal Food, Drug & Cosmetic Act (FD&C Act) and FDA’s regulations that apply to medical devices and electronic products. In this guidance, FDA is seeking to harmonize performance standards prescribed pursuant to section 534 of Subchapter C (Electronic Product Radiation Control (EPRC)) of the FD&C Act with International Electrotechnical Commission (IEC) standards, where appropriate, to help to ensure efficient and consistent regulatory review of submissions for these products.
FDA guidance on Premarket Notification [510(k)] Submissions for Ultrasonic Diathermy Devices| 21 February 2023
This guidance document recommends 510(k) submissions for ultrasonic diathermy devices. Ultrasonic diathermy devices are devices under section 201(h) of the Federal Food, Drug and Cosmetic Act (the FD&C Act). This includes recommendations on using International Electrotechnical Commission (IEC) standards in generating information that can support 510(k) submissions for these devices. This guidance also provides guidance on other FDA documents regarding the specific content requirements and recommendations of a premarket notification (510(k)) submission (also refer to 21 CFR 807.87). Considering the points mentioned in the guidance before submitting a 510(k) submission for such Ultrasonic diathermy devices is crucial.
AUSTRALIA
Updated guidance on Reclassification of medical devices | 28 February 2023
Therapeutic Goods Administration (TGA) has released a guide to assist sponsors of medical devices that are substances for introduction into the body with meeting their obligations and outlines transitional arrangements to help comply with new regulations.
From 25 November 2021, medical devices that are substances for introduction into the body will be required to meet regulatory requirements demonstrating the safety and performance of Class IIa (low-medium risk) or Class IIb (medium-high risk) devices.
This guidance is specific to medical devices composed of substances or combinations of substances intended to be introduced into the body via a body orifice or applied to and absorbed by the skin.
Updated guidance on Essential Principles-consent for non-compliance | 16 February 2023
There are Criminal Offences under section 41MA and Civil Penalties under section 41MAA of the Therapeutic Goods Act 1989 for persons who import, supply or export medical devices that do not meet the Essential Principles for safety and performance.
However, extenuating circumstances may prevent compliance with one or more parts of an Essential Principle for a limited period of time.
In such circumstances, sponsors may request consent to import, supply or export medical devices which do not meet an Essential Principle. The guidance is updated with the lastest requirements for applying for consent for non-compliant products.
BRAZIL
Anvisa notification to check medical device documentation | 14 February 2023
The latest Resolution of the Collegiate Board (RDC) 751/2022 replaces the older Resolution of the Collegiate Board (RDC) 185/2001. The new standard provides for risk classification, reporting and registration regimes, labelling requirements, and instructions for the use of medical devices.
RDC 751/2022 promotes the internalization of Mercosur GMC Resolution No. 25/2021, which, at the initiative of Brazil, updated the document requirements and classification rules for medical devices applicable to the region. In addition to the internalization of the norm, the text consolidates a series of other regulations issued by Anvisa that deal with the regularization of medical devices.
Malaysia
MDA Guidance on notification of custom-made medical devices products | 01 March 2023
The Medical Device Authority of Malaysia has released a guidance to help the industry and healthcare professionals comply with the Medical Device Act (Act 737) and its regulations. The guidance provides information on the requirements of custom-made medical devices that are eligible to be exempted under the Medical Device (Exemption )Order 2016. The requirements include:
Devices must meet the criteria of the custom-made medical device, including obtaining the written prescription and specific design characteristics from a healthcare professional
Classification of the device according to the device classification as specified in the First Schedule of Medical Device Regulation 2012;
The device is safe and performs as intended.
Pakistan
Notification of Amendment in the Medical Devices Rules, 2017 | 27 February 2023
Medical devices are subject to enlistment and registration under the Drug Regulatory Authority of Pakistan (DRAP). Medical devices are exempt from enlistment and registration requirements under these rules for a period until December 2023 and 2024 under the latest amendment. These exemptions are only applicable establishment licence holders either as importer or local manufacturer if the documentation as per the amendment is available.
Figure: Enlistment and registration extension timelines under MDR,2017
Draft Amendments in the Drugs Rules 1976 and the Medical Device Rules, 2017 | 21 February 2023
The Drug Regulatory Authority of Pakistan (DRAP) has proposed to amend the current version of the Drugs (Licensing, Registering and Advertising) Rules, 1976 and the Medical Device Rules, 2017. These draft amendments are hereby notified, seeking comments from stakeholders.
Stakeholders can submit their comments within 14 (fourteen) days of the publication of this Notification using the prescribed format via email to [email protected], or can be posted at the mailing address, Additional Director, Division of Legal Affairs, Drug Regulatory Authority of Pakistan, 1st floor, TF Complex, 7th Mauve Area, G-9/4, Islamabad. Further information on comments submission can be accessed on this link.
KUWAIT
Extension of grace period for medical device registration | February 2023
The Ministry of Health Kuwait has extended the grace period for the mandatory registration of medical devices to August 2023.
ISO Standards
List of Updated ISO standards for December 2022
ISO 11608-3:2022 Needle-based injection systems for medical use — Requirements and test methods — Part 3: Containers and integrated fluid paths
ISO 21649:2023 Needle-free injection systems for medical use — Requirements and test methods
ISO 5361:2023 Anaesthetic and respiratory equipment — Tracheal tubes and connectors
IEC 80601-2- 59:2017/Amd 1:2023 Medical electrical equipment — Part 2-59: Particular requirements for the basic safety and essential performance of screening thermographs for human febrile temperature screening — Amendment 1
ISO 8600-4:2023 Endoscopes — Medical endoscopes and endotherapy devices — Part 4: Determination of maximum width of insertion portion
ISO 10943:2023 Ophthalmic instruments — Indirect ophthalmoscope
A general device description, including any information on any planned variants
Design drawings, details on the planned method of manufacture, diagram of components, sub-assemblies, circuits etc
Descriptions and explanations are required to understand the abovementioned drawings and diagrams and the operations of the product
Results of risk analysis and a list of standards that are applied in full or part (Standards are referred to in Article 5 MDD)
Description of the solutions adopted to meet the essential requirements of the Directive if standards have not been applied fully. (Standards are referred to in Article 5 MDD)
Sterility information, description, and methods of use of sterile products
Results of design calculations and inspections carried out
If the device is to be connected to other device(s) to operate as intended, then there must be proof provided to indicate that it conforms to the essential requirements when connected to any such device(s) having characteristics specified by the manufacturer
Test Reports
Clinical Reports wherever applicable and Clinical data as per Annex X of MDD
Label and Instructions for use
MDR
All Technical documentation requirements of MDD must be presented for the MDR alongside the below additional list:
Device Description and specifications
Basic UDI-DI
the intended patient population and medical conditions to be diagnosed
contra-indications and warnings
principles of operation of the device and its mode of action
the rationale for the qualification of the product as a device
the risk class of the device and the justification for the classification rule(s) applied
an explanation of any novel features
A description of the accessories for a device, other devices and other products that are not devices intended to be used in combination with it.
a description or complete list of the various configurations/variants of the device
a general description of the key functional elements, e.g., its parts/components
a description of the raw materials incorporated into key functional elements and those making either direct contact with the human body or indirect contact with the body
Technical specifications
Reference to previous and similar generations of the device
Information to be supplied by the manufacturer
A complete set of labels or labels on the device and on its packaging
the instructions for use in the languages accepted in the country of sale
Design and Manufacturing Information
information to allow the design stages applied to the device to be understood
complete information and specifications, including the manufacturing processes and their validation, their adjuvants, the continuous monitoring and the final product testing
identification of all sites, including suppliers, sub-contractors and manufacturing sites.
General Safety and Performance Requirements
The general safety and performance requirements that apply to the device and an explanation as to why others do not apply
The method or methods used to demonstrate conformity with each applicable general safety and performance requirement
the harmonised standards, CS or other solutions applied
the precise identity of the controlled documents offering evidence of conformity with each harmonised standard, CS or other method applied to demonstrate conformity
Benefit-Risk Analysis and Risk Management
The benefit-risk analysis, the solutions adopted, and the results of the risk management
Product Verification and Validation
The documentation shall contain the results and critical analyses of all verifications and validation tests and/or studies undertaken to demonstrate the conformity of the device with the requirements of this Regulation
Pre-Clinical and Clinical data
Results of tests
If applicable: biocompatibility report, physical, chemical and microbiological characterisation, electrical safety and electromagnetic compatibility, software verification and validation,
stability, including shelf life,
performance and safety
Where applicable, conformity with the provisions of Directive 2004/10/EC of the European Parliament and of the Council (1) shall be demonstrated
Where no new testing has been undertaken, the documentation shall incorporate a rationale for that decision
the clinical evaluation report and its updates and the clinical evaluation plan
the PMCF plan and PMCF evaluation report, and if not applicable, justification of why a PMCF is not applicable
Additional information required in specific cases
Data of the tests conducted to assess safety, quality and usefulness on:
Medicinal product used
Medicinal products derived from human blood or human plasma
Tissues or cells of human or animal origin or their derivatives
Substances or combinations of substances that are intended to be introduced into the human body and that are absorbed by or locally dispersed in the human body
CMR (carcinogenic, mutagenic, or toxic for reproduction) substances
Endocrine-disrupting substances
A description of:
Sterility or defined microbiological condition to be maintained
Methods used in devices with measuring functions to ensure the accuracy as given in the specifications.
Combination/configuration of devices connected to other devices (s) to operate as intended, including proof that it conforms to the general safety and performance requirements when connected to any such device(s) having regard to the characteristics specified by the manufacturer
Post Market Surveillance
Post-market surveillance plan drawn up in accordance with Article 84
Post Market surveillance plan shall address:
Information concerning serious incidents, including information from PSURs, and field safety corrective actions
Records referring to non-serious incidents and data on any undesirable side-effects
Information from trend reporting
Relevant specialist or technical literature, databases and/or registers
Information, including feedback and complaints, provided by users, distributors and importers
Publicly available information about similar medical devices
The post-market surveillance plan shall cover at least:
A proactive and systematic process to collect any information
Effective and appropriate methods and processes to assess the collected data
Suitable indicators and threshold values shall be used in the continuous reassessment of the benefit-risk analysis and the risk management
Effective and appropriate methods and tools to investigate complaints and analyse market-related experience collected in the field
Methods and protocols to manage the events subject to the trend report
Methods and protocols to communicate effectively with competent authorities, notified bodies, economic operators, and users
Reference to procedures to fulfil the manufacturer’s obligations
systematic procedures to identify and initiate appropriate measures, including corrective actions
effective tools to trace and identify devices for which corrective actions might be necessary
a PMCF plan, or a justification as to why a PMCF is not applicable
The PSUR referred to in Article 86 and the post-market surveillance report referred to in Article 85
Disclaimer: Regulations/legislations are subjected to changes from time to time and the author claims no responsibility for the accuracy of information.
Under EU MDR 2017/245 Article 73, the sponsor shall report to all member states about the clinical investigations undertaken by the medical devices through an electronic system in case of any serious adverse events, device deficiency which leads to adverse events or any novel findings with regards to the event. The submission period may vary depending on the severity of the events. An initial incomplete report followed by the complete report shall be provided.
The reporting procedures are applicable for both Pre-market clinical investigations and Post-market clinical follow-up. Pre-market Clinical Investigation is conducted for non-CE marked medical devices, CE Marked devices outside the intended use as per Articles 62 and 74(2).
From 26th May 2021, a new template shall be used for reporting clinical investigation, which must be filled or updated with all adverse events, or any novel findings or occurrences reported. This report must be communicated to all National competent authorities. As per Article 34(3), the transition of reports will be made available on EUDAMED when it is completely available and fully functional. The overview of the table format to be used by the sponsor is given below.
Types of clinical investigation:
As per Article 80(2,3), the clinical investigation may be used for the investigational device for the conformity procedure.
As per Article 80(5,6), the PMCF investigation in case of serious events or invasive procedures
Other clinical investigations regarding National Legislation for Safety reporting
In addition to the above-mentioned clinical investigations, there are some exceptions other than the serious adverse events in the causal relationship between the event and the preceding investigational procedure like
Other relationships unrelated to the preceding investigational procedures need not be reported.
Few events in the relationship between the procedure or the device, as stated in IFU, shall be taken in context with the vigilance as per Article 87-90
A procedure mandated by the Clinical Investigation Plan that occurred prior to (or at the same time as) the major adverse event is referred to as a “preceding investigational procedure.” Both the investigational device application process and any additional onerous or intrusive procedure(s) determine whether the study is subject to notification requirements under MDR article 74.
Reporting Events to other Member States/ Third party countries
The sponsors shall report all the clinical investigations to those Member states. In the case of many Clinical investigations conducted for the same device, the specific CIP code (Clinical Investigation Plan Code) is to be reported to the specific Member state.
Reports from Third party countries shall be received through the National Competent Authorities as soon as the clinical investigation is authorized, and all other events occurring in third-party countries need to be reported.
Reported by whom? To Whom and When?
The sponsor of the clinical trial, the manufacturer, the legal agent, or another person or entity, must disclose any reportable events to the National Competent Authorities (NCA). On the Commission’s website, a list of the phone number of these operational NCAs is published. Member states may also require a supplemental report to the ethics committee(s).
Regarding reporting timelines, investigators must inform sponsors as soon as possible and no later than three days after the investigation site study employees become aware of the incident. The sponsor must adhere to the following reporting timelines based on the type of clinical study and the severity of the adverse event.
Timeline for reporting events
The Investigator’s Brochure, the Clinical Investigation Plan, or the Risk Analysis Report should be consulted during the causality assessment process. All foreseeably serious adverse events and potential risks need to be listed and evaluated during the clinical investigation. MDCG 2020-10/1 provides clear guidance on harmonizing reports, where the serious adverse events are further classified into the following four levels of causality (investigational device, comparator, procedure):
Not related: No relationship to the events related to the investigational device, an event that does not affect the device procedure, the serious adverse event that does not follow any known pattern but is related to other causes like concurrent illness, clinical condition or other risk factors
Possible: The relationship between investigational procedures, devices, or comparator is tenuous but cannot be excluded. Alternative explanations, such as an underlying or concurrent sickness, clinical condition, or course of therapy, are also conceivable. Cases where the relationship cannot be determined or where no information is known should also be categorized as possible.
Probable: The association with the application of the investigational device, comparator, or procedures appears pertinent, and/or another cause cannot adequately explain the incident.
Causal relationship: The serious adverse event associated with an investigational device, comparator, or procedure when the event has known side effects which involve a body site or organ or if the event follows a responsive pattern or other possible causes that can cause harm to the subject.
The investigator must identify the relationship between the serious adverse event and the procedure, as they can be related to each other, or they can be related only to the procedure or device itself. The health care provider can carry out the above procedure as they manage or handle the medical devices.
The reporting form is study-specific and only applies to a particular clinical investigation as identified by a specific clinical investigation plan. The reporting form should be completed in English. The report file must be compatible with Microsoft Excel before being delivered to the NCAs.
What is a clinical investigational plan for medical devices?
A clinical investigational plan is a document that states the objectives, design, procedure, monitoring and method of recording the clinical investigation for the medical devices. The ability to attain the intended purpose of the medical devices, as claimed by the manufacturer, is called clinical performance.
What is a clinical safety report?
All the data related to the safety information on adverse events, serious adverse events, and other risk factors of the medical devices in the user facility must be recorded into a form which is termed a clinical safety form/report. This report gives awareness to everyone in the workplace.
Why is safety reporting important in clinical trials?
To ensure the safety and quality of the clinical trials conducted by the investigator. These safety reports must be submitted to the respective NCAs through the sponsors during the entire lifecycle of the product trial.
eSTAR (electronic Submission Template and Resource) is an initiative launched by the US Food and Drug Administration in February 2020. It is a free, interactive PDF Form that provides assistance to the applicants in preparing the CDRH medical device submission for 510(k)s and De Novos. The content of the form is automated with an automatic verification feature, and the structure is complementary to the internal review and also harmonized with the IMDRF and guided construction for each submission section.
The US FDA has announced a pilot program in collaboration with Health Canada. The practicability of using eSTAR will be determined by the outcome of 9 participants. The pilot program has eligibility criteria as below:
Sponsorer must be in-process to submit an eSTAR application for the same medical device in Health Canada and US FDA within 6 months of acceptance into the pilot.
The submission must be for a new or significant change amendment to Class III or IV submission of Health Canada OR
A 510(k), De Novo or Pre-market Approval (PMA) original, 180-day, real-time or panel track supplement to FDA
The Sponsorer must complete the eSTAR application
The pilot program is NOT applicable to IVD devices, Combination products, CBER products or an FDA dual 510(k)/CLIA waiver application.
The limitations for the eSTAR pilot:
Health Canada will not accept Regulatory Enrollment Process (REP) submission
Submissions are accepted only in English at present.
Interested device sponsors can send in their participation request at [email protected] and [email protected] with the subject line “Request for participation in eSTAR Pilot”. The participation email should cover the following points:
A statement asking to participate in the pilot
Applicant name
Contact name and title
Device trade name(s) `
The FDA primary product code, Global Medical Device Nomenclature (GMDN) and Preferred Name Code (PNC) of your device
A statement that the same medical device using the eSTAR will be submitted within 6 months of acceptance in the eSTAR pilot to both Health Canada and the FDA:
For Health Canada: specify if it is a new or significant change amendment for a Class III or IV submission
For FDA: specify if it is a 510(k), De Novo or PMA submission (specify if the PMA submission is original, 180-day, real-time or a panel track supplement)
The FDA and Health Canada intend to revert to emails within 3 business days. The file size should be Less Than 1 GB, and images and videos to be submitted in compressed format. The fee structure is as follows:
