Clinical investigation creates a set of clinical data that is crucial to understanding the effectiveness of a medical device. Clinical Investigation is done for devices that are previously UKCA / CE / CE UKNI marked or for research medical devices.
It is governed by a clinical investigation plan with an objective, methodology, and record keeping.
Steps involved in Clinical Investigation in UKCA
Step 1:
Ensure all the information necessary to demonstrate compliance with all the relevant essential requirements is available. Appoint an Authorised representative/Responsible person.
This representative communicates to the Medicines and Healthcare products Regulatory Agency (MHRA) on behalf of Manufacturers.
Step 2:
Please provide the MHRA with advanced notice of your intention to submit a clinical investigation by emailing [email protected] with some basic details about the investigational device, the intended population, the type of study, and the estimated application date.
They conducted in Great Britain must follow UKCA Medical Devices Regulations MDR 2002. Clinical Investigations in Northern Ireland must meet the requirements of the EU MDR and be submitted to MHRA.
Complete the CI Application form and submit the list of documents. Submission of documents should be in English. If the documents are in other languages, translation into English should be made available. Supported format PDF only.
List of Documents required
• Cover letter on headed paper
• Clinical investigation plan or CIP
• Investigator’s brochure
• Participant information sheet
• Consent form from participants
• CVs of UKCA clinical investigators
• Details of the device
• General Safety and Performance Requirements (GSPR) or Essential requirements checklist
• Biological safety assessments of patient contact materials (if any)
• Information on animal tissues (if any)
• Information of any medicine or human blood derivative, or non-viable human tissues and cells incorporated into the device
• Research ethics committee opinion (if available)
Step 4:
Payment of Fees
Devices are categorised according to risk as a Group A or B device: Group A includes class I, IIa, and IIb devices other than implantable/long term invasive. Group B has class IIb implantable/long term invasive, class III, active implantable devices.
MHRA fees and guidance on making a payment for the application of clinical investigation are available on the MHRA website.
Step 5
The review process by MHRA /Assessment procedure.
When the MHRA has validated the documents, within five working days, a response is obtained. It will confirm that the 60-day assessment has started or response to issues.
If issues are raised, the 60-day evaluation will start when MHRA receives a valid response. Day 1 of the 60 days is the first working day that follows the date of receipt of a valid Notification.
Experts will check the safety and performance of your device. The MHRA will write to you if they require further information. A letter will be sent on the 60th day with a decision (‘objection’ or ‘no objection’) if the clinical investigation can be carried out or not.
If any severe events occur during the assessment, they should be reported using the MEDDEV 2.7/3 or MDCG 2020-10/2 Reporting Table.
Step 6
Notification of Amendments (if any)
Once a letter of no objection is received after the review process, you must notify the MHRA of proposed amendments to the investigation. You must wait until another letter of no objection before implementing the changes.
Any changes made to the following must be notified:
the device under investigation
study documentation, including the clinical investigation plan
investigators or investigating institutions
changes requested by an ethics committee
The following document must be presented for notification of amendments.
covering letter with:
Reference number allotted by MHRA for the CI and a table with a summary of each proposed change with the reason for the individual changes.
FAQs
Is the procedure the same for Northern Ireland and Great Britain?
The overall procedure remains the same, but the documents required may vary. This is due to the regulations followed in both regions. Northern Ireland follows EU Medical Devices Regulations 2017/745, whereas Great Britain follows UK MDR (Medical Devices Regulations) 2002.
What happens if amendments are not notified to MHRA?
All modifications should be notified to MHRA. However, only some are substantial. Manufacturers/Sponsors must notify else; they are liable to prosecution. More details can be found here.
Regulatory Pathway for Clinical investigation creates a set of clinical data that is crucial to understanding the effectiveness of a medical device.
Clinical Investigation is done for previously CE marked devices or for research medical devices. Clinical Investigation is governed by a clinical investigation plan with an objective, methodology, and record keeping.
Top 5 Steps involved in Clinical Investigation
Step 1
Appointment of a Representative- Appoint a legal representative.
Step 2
The application is made electronically via EUDAMED. A single identification number for the clinical investigation is generated. Within ten days of receiving the application, the Member State concerned shall notify the sponsor if the clinical investigation is within the scope of this Regulation and whether the application dossier is complete.
Until the EUDAMED is fully functional, contact the EU Commission authority of the individual member state for the complete set of procedures to be followed. A list of contact persons for Clinical Investigations can be found here.
Step 3
Assessment by the Member States
Conditions based on which the acceptance or refusal of Clinical investigation is mentioned in Article 71 of EU MDR.
Step 4
Proceed with Clinical investigation.
Step 5
Submission of results
Irrespective of the clinical investigation outcome, within one year of the end of the clinical investigation, the sponsor shall submit a clinical investigation report to all the Member States.
Documents required for application
The MDCG guidance document on Clinical Investigation also has the template for the list of documents required and the GSPR. Annex XV Chapter II of EU MDR also contains the complete list of documents required for submission.
The list of documents needed before the application of clinical investigation is as follows:
Name, address, and contact of the sponsor and, if applicable, name, address and contact details of its contact person or legal representative following Article 62(2) established in the Union.
name and other details of the manufacturer
Investigator’s Brochure
Clinical Investigation Plan
Other information
A statement by the natural or legal person responsible for the manufacture of the device under investigation that it conforms to the general safety and performance requirements.
Where applicable, according to national law, copy of the opinion or opinions of the ethics committee or committees concerned.
Proof of insurance cover
Documents to obtain informed consent include the patient information sheet and the informed consent document.
Full details of the available technical documentation, detailed risk analysis or any test reports, shall, be submitted to the competent authority reviewing an application upon request.
Modification of information in Clinical Investigation Plan
Modifications of the clinical investigation plan, investigators brochure, the subject information sheet, and other clinical investigation documentation may or may not be considered substantial modifications. The sponsor or representative must submit a notification of substantial modification following Article 75 of the EU MDR as soon as a clinical investigation is allowed to start.
It is not recommended to submit another substantial modification while the previous assessment is still ongoing. It is also essential to consider if national procedures may apply regarding modifications to clinical investigations.
Reporting Of Adverse Events
The sponsor or representative shall report, without delay, to all Member States in which the clinical investigation is being conducted. Sponsors or representatives should report the following:
any adverse event identified as critical to the results of that clinical investigation.
Any serious or adverse event.
Any device deficiencies that might have led to an adverse event if appropriate action had not been taken.
Any new findings of any event referred to in points 1-3.
Regulatory Pathway for Other Clinical Investigations (If the investigation is conducted not for conformity purpose)
Step: 01
Appoint a Legal Representative who is placed within the European Union. All communications relating to CI will be handled by the legal local representative.
Step: 02
Get an expert panel opinion from the Ethics Committee. This opinion from the Ethics Committee is valid within the entire Member State and the final opinion must not be a negative opinion.
For research purpose investigations, each Member State shall define any additional requirements for such investigations, as appropriate for each Member State concerned.
Hence the Manufacturer must approach each Member state committee contact points to identify their local Investigation requirements.
Step: 05
Conducting Clinical Investigation
Clinical investigations shall be designed and conducted in such a way that the rights, safety, dignity and well-being of the subjects participating in a clinical investigation are protected and prevail over all other interests and the clinical data generated are scientifically valid, reliable and robust.
Clinical investigations shall be subject to scientific and ethical review. The ethical review shall be performed by an ethics committee in accordance with national law. Member States shall ensure that the procedures for review by ethics committees are compatible with the procedures set out in this Regulation for the assessment of the application for authorisation of a clinical investigation. At least one lay person shall participate in the ethical review.
Step: 06
Submit Clinical Investigation Report
Within 1 year of completion of the CI, the Sponsor (manufacturer) must submit the CI report to the concerned Member states.
Source of Information
EU MDR Article 82 states the Requirements for Research only Clinical Investigation (not for conformity purpose)
Article 62 (2) and (3), points (b), (c), (d), (f), (h), and (l) of Article 62(4) and Article 62(6).
FAQs
What are the obligations of a legal representative in Clinical investigations?
The obligation of a Legal representative includes:
Submitting documents to the local authorities.
Notification of clinical investigation.
Reporting any adverse or serious events.
Who is responsible to report adverse events other than during Clinical investigations?
The sponsor is responsible to report adverse events only during Clinical Investigations. In case of general adverse events occurring in the field, the manufacturer is responsible.
What are the supporting documents required for applying Clinical Investigation request?
Mandatory documents:
Cover letter
Application form
Investigator’s brochure
Clinical Investigation plan
Clinical Evaluation plan
Synopsis
Statement of Conformity
Labels (examples)
Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data/ personal information
List of General Safety and Performance Requirements
Listed below are as Applicable
Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data/ personal information
Risk management documentation
Test reports
Proof of Clinical Investigation Insurance
Suitability of investigational sites and investigation site team
Manufacturer’s Instructions for Use
Suitability of the investigators
Recruitment procedures and advertising materials
Documents to obtain informed consent, informed consent procedure, all written information to participants, payments and compensation of participants
Summary of Safety and Clinical Performance (SSCP) acts as a vital document that allows the public to access information quickly. The information in the SSCP can be sourced entirely from the technical file.
The technical file consists of the Post Market Surveillance (PMS), risk assessment, post-market clinical follow-up (PMCF) plans and reports. The SSCP document is required for high-risk devices only-this includes Class III and all implantable devices.
Manufacturers of custom-made or investigational devices need not produce this document. Implant card together with SSCP enables an efficient system to access device information.
SSCP for medical devices under MDR
Under MDD, the information on medical devices was not easily attainable. Therefore, the end-users of most medical devices were deprived of information regarding even high-risk medical devices.
As a result, medical devices under the directives lacked clarity. The main reason why SSCP is introduced is that MDR, unlike the directives, brings accessibility of information into account.
The SSCP should be made available on the EUDAMED website for easy access. It should be assigned an identifier that remains the same throughout the document’s lifetime. This identifier is not subjected to changes even when the content of this document is revised.
Language and readability requirements
SSCP follows the MDR language requirements like the other technical documents, such as Instructions for Use. All intended users within the EU understand no single language.
Therefore, language translations should be made available to intended users and patients. The SSCP should be translated into the languages accepted in the Member States where the device is intended to be sold.
Healthcare professionals widely understand English. Having an English translation available is essential, even if it is not available in selecting the official languages of each Member State. This enables the access to information that EU MDR strives to achieve.
While preparing SSCP, readability is an essential factor. The manufacturers must bear in mind to produce two sections. One part for intended users/healthcare professionals, and a second part for patients if applicable.
It is recommended to use an appropriate method to confirm that the document is understandable to the member of both categories. Further guidance on the readability, translations and other factors involved in SSCP can be found in the MDCG guidance on Summary of safety and clinical performance.
Sections of Summary of Safety and Clinical Performance
Article 32 of the EU MDR states some sections that are a must. The manufacturer may add further information from the Technical Dossier/File if relevant to the users.
The following sections are mandatory in an SSCP for healthcare professionals:
Details of the device and manufacturer (including UDI details).
Intended use of the device.
Description of the device and its components. Previous variants of the device.
Indications, contraindications, and target demographic.
Details of residual risks, undesirable effects, warnings, and precautions
Risks, undesirable effects, and warnings should be mentioned in SSCP. Other relevant aspects of safety, serious events, and a summary of any field safety corrective action must be included if applicable.
A summary of the Clinical Evaluation of the device.
This section is intended to summarise the clinical evaluation results and the clinical data, the evaluation of undesirable side-effects, and the benefit-risk ratio’s acceptability.
It is an objective and balanced summary of the clinical evaluation results of all the available clinical data related to the device. It should comprise favourable, unfavourable, and inconclusive data.
Conclusions based on evidence and the safety and performance of the device.
Suggested profile and training for users
Applied harmonised standards
All commonly applied specifications and international standards harmonised and adopted monographs should be listed in SSCP.
Revision history
Revision history should contain details such as revision validated by Notified Body (NB) and the language of SSCP validated.
A patient-specific SSCP template follows the same high-level structure as the clinician SSCP but does not include the reference to harmonized standards and common specifications. This decision focused on the information most relevant to patient health.
Validation of SSCP
When the Notified Bodies (NB) have assessed that all the required elements are included in the draft SSCP with the most current version of relevant documents in the TD, the SSCP has been validated by the NB.
SSCP validation may depend on the class of device and the conformity assessment routes chosen. More guidance on validation by NB can be found in the MDCG guidance on SSCP.
Uploading SSCP to EUDAMED
SSCP should be made available online for the users who intend to read the document. It is uploaded in EUDAMED by the Notified Bodies, the only actor managing the SSCPs in EUDAMED.
After each validation process, NB shall upload the updated SSCP by replacing the older version. However, once the ‘master’ SSCP is uploaded, it is up to the manufacturer to upload the translations to EUDAMED.
FAQs
What resources can be used for the SSCP?
The technical files like the design validation report, risk management report, clinical evaluation report (CER), as well as Post-Market Surveillance (PMS) and Post-Market Clinical Follow-up (PMCF) reports.
The Instructions for Use of the device can also be used as information for preparing the SSCP. Please note that SSCP cannot replace the IFU.
How frequently should SSCP be reviewed or updated?
The SSCP should be ideally updated annually. Documents like the PMCF evaluation and periodic safety update reports (PSUR) are updated annually. It is recommended to update SSCP along with the other technical documents.
How can I access the SSCP?
SSCP will be made available with the launch of the EUDAMED database. SSCP is accessible to both healthcare professionals and patients. SSCP has clear information for healthcare professionals with prior knowledge of medical terminologies.
In addition to this, SSCP should also contain a section that patients of different levels of expertise easily understand.
When should a manufacturer of Class III medical devices prepare SSCP?
SSCP should be made available at the time of registration.
Is there a similar requirement under IVDR?
Article 29 of In Vitro Diagnostics Regulation 2017/746 (EU IVDR) describes a requirement like the SSCP: the Summary of Safety and Performance (SSP).
The SSP requirements are almost identical to those of the SSP, replacing ‘clinical’ for ‘performance’ evaluation. Also, it includes a requirement for metrological traceability of assigned values intended for analytes used in IVDs.
For more information on IVDR, read our article on IVDR 2017/746.
Legacy medical devices include all previously regulated devices under the Medical Devices Directives (MDD 93/42/EEC 90/385/EEC) and In-vitro Diagnostic Devices Directive (IVDD 98/79/EC).
There are three terminologies to guide the manufacturers – old devices, legacy devices and MDR devices.
‘Old devices’ were placed on the market before 26 May 2021, holding valid Medical Device Directive Certificates or the AIMDD certificates.
‘Legacy Devices’ are those devices that have a valid CE certificate under the directives MDD and IVDD that were placed after 26 May 2021 or those that require a conformity assessment to be carried out.
A Class III device, for example, can be considered a legacy device because of the conformity tests done and valid CE certificates. Class Is / Im devices with self-declared certificates do not fall under this category.
Legacy devices must be MDR compliant under the prescribed transitional timelines set by the MDR (2017/745). The transitional provisions and timelines can be found in Article 120 of the EU MDR.
‘MDR devices’ are placed on the market as conforming to the MDR other than ‘legacy devices’.
This topic focuses on the Legacy Devices requirements per MDR 2017/745.
EU MDR aims to implement the following aspects of medical devices:
Identification- This is achieved by Unique Device Identifiers (UDI).
Transparency- The Database available in EUDAMED (European Databank on Medical Devices.) ensures that the device description and details of different economic operators are open and easily accessible for users.
Surveillance-Post-Market Surveillance, vigilance reporting and Periodic Safety Update Reports (PSUR) are prime importance under MDR.
Identification of Legacy Medical Devices
To ensure proper identification of medical devices, UDI is implemented under MDR. Read more about UDI in our article on UDI (Unique Device Identification) system. For legacy devices, the identification is made possible with the help of EUDAMED-DI.
Some manufacturers may have implemented UDI to their medical devices. In such cases, the device identifier is obtained from the UDI-DI. Devices that do not have UDI should have a EUDAMED-DI designated by the manufacturer.
The European Commission document on the Management of legacy devices can be used to understand the different device identifiers.
Application of Post Market Requirements to Legacy Devices
All relevant requirements mentioned in MDR apply to legacy devices as well. This includes post-market surveillance, market surveillance and vigilance.
Manufacturers need to keep in mind the information required under Article 83 and Chapter VII of EU MDR while implementing a post-market surveillance system.
The Notified bodies must consider the new requirements applicable to manufacturers resulting from the transitional provisions as part of the surveillance framework.
Application of other MDR requirements to legacy devices
Application of all other requirements should be implemented to contribute to post-market surveillance, market surveillance, vigilance, and registration of economic operators and devices. This ensures an all-rounded and well-functioning surveillance system.
The other MDR requirements applicable to legacy devices are as follows.
Article 10(12-15)
Obligations of manufacturers for market surveillance, field safety notices and vigilance.
Article 11 (3) (c-g) and 11 (7)
Obligations of Authorised representatives.
Article 13 (2,4,5,6,10)
Importer obligations for IFU, labelling, and register of complaints.
Article 14 (2,4,6)
Distributor obligations.
Article 22
Article on system and procedure packs.
Article 29
Article of registration of medical devices and UDI.
Article 31
Article of registration of manufacturers, authorized representatives, and importers.
Article 83-100
Articles 83-88 on PMS, PSUR, vigilance, serious incident reporting, field safety corrections, and trend reporting.
Articles 89-99 on analysis of data, implementing acts, market surveillance activities, electronic system on market surveillance and others.
Articles 98-100 on Preventive health protection measures, Good administrative practice, and electronic system for market surveillance.
FAQs
Should the change of device classification be considered during this transition period for a legacy device manufacturer?
No, a possible change in the risk classification should not be considered during the transition period. Devices subjected to AIMDD should be regarded as Class III devices to apply the relevant MDR requirements during the transition period.
I am a Legacy device manufacturer complying with MDD, and I do not hold a Periodic Safety Update Report (PSUR) since it was not a part of MDD. Does MDR require a PSUR for my legacy device?
Yes, manufacturers of legacy devices are subjected to preparing their PSURs as per Article 86 of MDR. They will need to make PSURs available on request by the competent authorities. In addition to this, the manufacturers shall also make the PSURs available to the Notified Bodies (NBs) included in their surveillance audit framework. The NBs can verify the approved quality system and that the design remains compliant with the certificate issued under the MDD or AIMDD.
Apart from a manufacturer, which other legacy device economic operators get impacted?
The primary role of Importers gets deeper when MDR is in effect. Importers were assumed to be associated only with product handling and taking part in the logistics chain. In MDR, Article 13 details a lot more responsibilities to the Importers where they are obliged to ensure compliance to a certain level. Few duties overlap with the other economic operators’ roles, such as the authorised representative and the distributors.
Does it require changes to the manufacturer’s QMS when transitioning from MDD to MDR for legacy devices?
The fact that QMS is a process approach where the manufacturer may contain numerous products under the existing QMS certification umbrella, and not all of those require transitioning to MDR. The current QMS process may be adequate for some of the devices holding valid MDD CE certification and may not comply with those listed in the MDR Annex IX Chapter I. Hence, the manufacturer needs to upgrade their QMS to meet parallel for the category of devices.
What triggers a re-certification for my legacy device?
This is an essential factor to consider while making updates to the existing MDD certified legacy device design.
Any significant change to the device or change in the device’s intended purpose will trigger a re-certification process (MDR Article 120(3)). The MDCG guidelines here clarify what changes are considered significant change(s) in the device.
Few unexhaustive lists of significant changes include:
Design or performance specification
Software change
Substance changes in material
Sterilisation method
The manufacturer can also approach the Notified Body to determine whether the change(s) made to the design/device constitutes significant in case of doubt.
Medical Device Reporting (MDR) is one of the FDA’s post-market surveillance techniques for monitoring device performance, detecting potential device-related safety concerns, and contributing to device benefit-risk assessments.
There are mainly two groups of reporters of which the mandatory group includes the manufacturer, importers and device user facilities, and the voluntary group includes healthcare professionals, caregivers, patients, consumers
Once submitted, the FDA reviews the MDR and validates the totality of the given information
The MDR submission by itself cannot act as evidence that the medical device reporting is responsible for a particular adverse event unless the reporter believes that the adverse event has or may have occurred due to the device or the medical device reporting has a role in the mentioned event
What Event Qualifies to be Reported?
A medical device reporting placed in the market contributes to a death or a serious injury
A medical device reporting has malfunctioned and is likely to cause death or a serious injury if the malfunction were to recur
Who can Report an Adverse Event to FDA?
It is considered mandatory for the manufacturers, importers, and device user facilities) of reporters to report any adverse event through form FDA 3500A.
The summary of Requirements for Mandatory Reporting:
Reporter
Description
FDA Form(s)
Report to
When to Report
Manufacturer
30-day reports of deaths, serious injuries, and malfunctions
Within 30 calendar days of becoming aware of an event
5-day reports for an event designated by FDA or an event that requires remedial action to prevent an unreasonable risk of substantial harm to the public health
The voluntary reporting can be done through MedWatch Online reporting Form or by requesting for assistance by calling 1-800-332-1088:
Healthcare professionals are advised to report through form FDA 3500
Patients/Consumers are advised to report through form FDA 3500B
In case of Emergencies, reporting can be done by contacting the FDA Office of Crisis Management, Emergency Operations Centre.
Who is Responsible to carry out Corrective Action for the Reported Event?
For any reportable or reported adverse events, the manufacturer is obliged to carry out a corrective action such that the implemented corrective action and preventive action aims to eliminate any medical device reporting malfunctions related to patient safety.
The manufacturers, importers and the user facilities are primarily responsible for carrying out a corrective action whose goal is to gather data, evaluate it, detect and investigate product and quality issues, and then take suitable and effective corrective action to keep them from happening again.
Top 5 Medical Device Safety Action Plan Objectives
FDA carries out inspections to ensure that the corrective actions undertaken by the manufacturer are well adequate to eliminate any recurring adverse events.
The Key objectives of such inspections are:
To create a medical device patient safety net in the United States of America
To put forward a system to check on the latest regulatory options to implement postmarket mitigations
To guide innovations to make a safer medical device
Bring Improvements in medical device cybersecurity
Integrate the premarket and post-market offices and operations of the Centre for Devices and Radiological Health (CDRH) to promote the implementation of a TPLC (Total product life cycle) approach to device safety
Corrective and Preventive Action (CAPA) Procedure
Every manufacturer is mandated to establish and maintain a CAPA process as per the FDA’s Quality System Regulation (QSR) 21 CFR 820.100.
The process must well contain the requirements on input data sources, decision criteria of non-conformance, investigational procedure, root cause analysis, actions to address the non-conformance, effectiveness verification procedure, implement actions to eliminate recurring problems taking into consideration about the in-house product design changes as well as the impact to existing products in the market.
The FDA requires all these activities to be documented and recorded.
Manufacturers are required to create a report as per 806.10 of any corrective actions implemented on the device and submit it to the FDA
Manufacturers and Importers must also keep records of the corrective actions that are not required to be reported to the FDA. Voluntary submission of such a report can be done based on 21 CFR 7
FDA’s Inspection Operation
On various grounds, the FDA performs inspections such as scheduled investigations, surveys, or a response to a reported problem. FDA’s Office of Regulatory Affairs (ORA) leads all such inspectional operations.
There are FDA Forms involved in these inspections,
Form 482 “Notice of Inspection” presented by the FDA immediately prior to inspection
Form 483 is issued to the firm’s management at the conclusion of the inspection if the investigator determines observations that violate the FD&C act rules
Objectives of Inspection after implementation of a Corrective Action
Check if the corrective actions implemented have been well defined and documented
Verify if the right sources of product and quality issues have been found
Check if there are any unfavourable trends in the product and quality information
Verification of the received data based on completeness, accuracy and time of reception
Check if appropriate statistical methods are applied to detect and identify the extent of recurring quality problems
Verify if a failure investigation is carried out and check if there has been a genuine attempt to find the root cause (wherever possible)
Check if there is control for the prevention of distribution of non-conforming products
Verify if appropriate actions have been taken for significant product and quality problems identified from data sources
The effectiveness of the corrective action is validified and verified before implementation by ensuring that the corrective actions do not lead to any adverse effects on the finished device
Check if corrective actions for product and quality problems were implemented and documented
Verify if all non-conforming product and quality problems and corrective actions have been properly disseminated, including dissemination for management review
FAQ
What is the Voluntary Malfunction Summary Reporting Program?
It permits manufacturers to report certain device malfunction medical device reports (MDRs) in summary form on a quarterly basis.
The VMSR program lets the manufacturers submit separate summary reports for each unique combination of the device model, brand name, device model, and problem code(s).
Every summary report is made available to the public in the MAUDE. It is mandatory to submit individual reports of death or serious injury events continue to be required, under sections 803.50 and 803.52, or 803.53, as applicable.
How to report Medical Devices licenced as biological products?
CBER (Centre for Biologics Evaluation and Research) is designated the lead centre in the FDA for regulating in vitro diagnostic (IVD) medical devices intended for screening or confirmatory clinical laboratory testing associated with blood banking practices and other process testing procedures.
IVD devices licensed as biological products are also subject to the applicable regulations under 21 CFR Part 803 – Medical Device Reporting.
Where to search for the medical device Reports?
The Manufacturer and User Facility Device Experience database contains mandatory reports filed by manufacturers and importers from August 1996 to the present, all mandatory user facility reports from 1991 to the present, and voluntary reports filed after June 1993.
The MAUDE database houses MDRs submitted to the FDA by mandatory reporters (manufacturers, importers and device user facilities) and voluntary reporters such as health care professionals, patients and consumers.
What are the data that are not required to be presented for routine review?
In accordance with Agency policy (CPG 7151.02), records regarding the results of internal quality audits, management reviews, third-party audits (including ISO audits), or supplier audits are not required to be presented.
Under both the EU MDR and the EU IVDR, the MDCG rules specify the conditions for a product to qualify as medical device software (MDSW). An MDSW product can enter the market in one of the ways:
As a standalone medical device or
As a component of another medical device regulation.
The former demands a lengthy regulatory process that includes a conformity assessment to determine whether the medical device meets EU MDR requirements. However, that rule does not apply to products in the latter group with the same rigour.
As a result, MDSW, as an integral component of a medical device, can be placed on the market through the medical device’s conformity assessment route.
The term “Software as a Medical Device” (SaMD) is defined as Software intended to be used for one or more medical purposes that perform the below purposes without being part of a hardware medical device.
SaMD is a medical device and includes an in-vitro diagnostic (IVD) medical device regulation.
SaMD is capable of running on general-purpose (nonmedical purpose) computing platforms.
“Without being part of” means Software is not necessary for a hardware medical device regulation to achieve its intended purpose.
The Software does not meet the definition of SaMD if its intended purpose is to drive a hardware medical device regulation.
Examples of Software as a Medical Device
SaMD may be interfaced with other medical devices, including hardware medical devices and other Software such as medical device software and general-purpose Software. The Software provides parameters that become the input for a different hardware medical device or other SaMD. For example, treatment planning software that supplies information used in a linear accelerator is Software as a Medical Device.
Software with a medical purpose that operates on a general-purpose computing platform, i.e., a computing platform that does not have a medical purpose, is considered Software as a Medical Device. For example, Software intended to diagnose a condition using the tri-axial accelerometer that operates on the embedded processor on a consumer digital camera is considered Software as a Medical Device.
Software that is connected to a hardware medical device but is not needed by that hardware medical device regulation to achieve its intended medical purpose is Software as a Medical Device and not an accessory to the hardware medical device regulation.
Software as a Medical Device can run on general-purpose (nonmedical purpose) computing platforms.
Top 7 Manufacturer Obligations for Medical Device Regulation
For SaMD manufacturers, the definition in GHTF/SG1/N55:2009 applies: “Manufacturer” means any natural or legal person with responsibility for the design and manufacture of a medical device to make the medical device available for use under his name; whether such a medical device is designed and manufactured by himself or on his behalf by another person(s).
Unless the Regulatory Authority (RA) within that jurisdiction imposes this responsibility explicitly on another person, this ‘natural or legal person’ has ultimate legal responsibility for ensuring compliance with all applicable regulatory requirements for the medical device in the countries or jurisdictions where it is intended to be made available or sold.
The manufacturer’s responsibilities are described in other GHTF guidance documents. These responsibilities include meeting pre-market and post-market requirements, such as adverse event reporting and notification of corrective actions.
‘Design or manufacture’, as referred to in the above definition, may include specification development, production, fabrication, assembly, processing, packaging, repackaging, labelling, relabelling, sterilisation, installation, or remanufacturing of a medical device; or putting a collection of devices, and other products, together for a medical purpose.
Any person who assembles or adapts a medical device already supplied by another person for an individual patient, per the instructions for use, is not the manufacturer, provided the assembly or adaptation does not change the intended use of the medical device.
Any person who changes the intended use of, or modifies, a medical device regulation without acting on behalf of the original manufacturer and who makes it available under his name should be considered the manufacturer of the limited medical device.
An authorised representative, distributor or importer who only adds its address and contact details to the medical device or the packaging without covering or changing the existing labelling is not considered a manufacturer.
To the extent that an accessory is subject to the regulatory requirements of a medical device, the person responsible for the design or manufacture of that accessory is considered to be a manufacturer.
Quality Management Principles
Medical device QMS principles allow the measurement of activities depending on
The type of medical device.
Risk of the product to patients.
Size of the organisation.
Technology or automation is used to manufacture.
And other factors are determined by the manufacturer to control quality and maintain the safe and effective performance of the medical device regulation.
The manufacturing of SaMD, a software-only product, is primarily based on the development lifecycle activities often supported by automated software development tools.
These computerised activities may, in some cases, replace discrete or deliberate actions (e.g., transfer of design to production) typically found in the manufacturing of hardware products.
However, the principles in a QMS that provide structure and support to the lifecycle processes and activities are still applicable and essential to controlling the quality of SaMD.
An effective QMS for SaMD have to include the following principles:
An organisational structure ensures SaMD’s safety, efficacy, and performance by providing leadership, accountability, and governance with enough resources.
A set of SaMD lifecycle support processes that are scalable to the organisation’s size and applied consistently across all realisations and use processes
A set of realisations and use processes that are scalable for the type of SaMD and the organisation’s size takes into account essential elements required for assuring the safety, effectiveness, and performance of SaMD.
FAQs
Does MDSW need to be re-assessed for risk classification when transitioning from MDD to MDR?
Yes, SaMD also requires a re-assessment of risk classification since the new classification rules are more stringent than the MDD. This must be carried out as the first step in the MDR compliance roadmap.
The gap analysis in the technical documentation also needs to be performed while transitioning to MDR.
What are the additional requirements in the technical documentation for MDSW in MDR?
Pre-clinical & Clinical Data, Clinical Evaluation and PMCF requirements, Clinical Investigation and implementation of UDI.
How is Software as a Medical Device considered in MDR?
Software shall be deemed to be an “active device” both in MDR and IVDR.
What are the UDI assignment criteria for a Software only device?
For a Software that constitutes as a device on its own, the UDI shall be assigned at the system level of the Software itself. The UDI that is applied to the physical medium that contains the Software shall be identical to the UDI assigned at the system level.
Are there any guidance documents for Software as a Medical Device by the EU commission?
Yes, Specifically
“MDCG 2019-16 Guidance on Cybersecurity for medical devices” guides manufacturers on how to fulfil the Annex I requirements regarding cybersecurity.
“MDCG 2019-11 Guidance on Qualification and Classification of Software” in Regulation to MDR 2017/745 and IVDR 2017/746
