US FDA Expanded Access for Medical Devices

Expanded access pathway allows the manufactures or physician to use an investigational medical product to use the patients with a serious or life-threatening disease or condition when there are no available alternative options.

There are three below options are available,

• Emergency Use
• Compassionate Use (or Individual Patient/Small Group Access)
• Treatment Investigational Device Exemption (IDE)

Emergency use

During emergency, investigational device can be used immediately, to treat an individual patient life-threatening situation (there are no alternative options and no time to use existing procedures to get FDA approval for the use).

Physician shall follow the patient protection procedures as possible. Some of the protection procedures are getting concern from patient (Informed consent process), Concurrence from Institutional Review Board (IRB) chairperson and Authorization from the device manufacturer.

Reporting of Emergency use

• Criteria: Devices with IDE    
• Who report: IDE sponsor
• Timelines: within 5 days
• Information to be submitted: IDE Report

• Criteria: Devices without IDE
• Who report: physician 
• Timelines: within 5 days
• Information to be submitted: a description of device used, details of the case, and the patient protection measures that were followed

Compassionate Use (or Individual Patient/Small Group Access)

If there is investigational device is the only option to treat a patient faced with a serious or life-threatening disease or condition.

First device manufacturer shall agree to provide the device under compassionate use.

Approval process for devices with IDE

IDE sponsor should submit an IDE supplement requesting approval for a compassionate use.

IDE supplement contents,

• Patient conditions and circumstances necessitating treatment
• why alternative therapies are unsatisfactory
• deviations from approved clinical protocol to treat the patient
• Patient protection measures

Approval process for devices without IDE

Physician or manufacturer shall submit the compassionate use request to FDA with above information and along with a description of the device provided by the manufacturer

Timelines for review

 IDE supplements have the same statutory 30-day review cycle. Average timelines are within 15 days of receipt.

FDA Actions: Approve, Approve with conditions, or Disapprove the request.

Follow-up Report: Within 45 days, the person who submitted the request shall provide the below details to FDA,

• Patient outcome
• If any problems occurred because of device use

Treatment Investigational Device Exemption (IDE)

If an approved IDE is extended under new IDE to include additional patients with life-threatening or serious diseases. This is called a treatment IDE.

Treatment IDE Application contents are listed below,

1. Name, address, and telephone number of the sponsor
2. Intended use of the device, the criteria for patient selection, and a written protocol describing the treatment use
3. Rationale for use of the device
4. Description of clinical procedures, laboratory tests, or other measures that will be used to evaluate the effects of the device and to minimize risk
5. Procedures for monitoring the treatment use
6. Name and address of the monitor
7. Instructions for use for the device and all other Labeling 
8. Information that is relevant to the safety and effectiveness of the device for the intended treatment use
9. A statement of the sponsor's commitment to meet all applicable responsibilities under the IDE regulations
10. Example of the agreement to be signed by all investigators participating in the treatment IDE and certification that no investigator will be added to the treatment IDE before the agreement is signed
11. Device price (if sold) and a statement indicating that the price is based on manufacturing and handling costs only

FDA actions:Approve, Disapprove or withdrawal of approval of treatment IDEs

Follow-up Report:

• To whom reported: IRB and FDA    
• Who report: Sponsor
• Timelines: Semi-annual basis
• Information to be submitted: Progress reports      

References:

Expanded Access

Expanded Access for Medical Devices

 

 

 

 

US FDA Custom device

 Regulatory Authority: Section 520(b) of the Food, Drug, and Cosmetic Act (FD&C Act) provides the basis for the Custom Device Exemption Program.

Types of Custom devices,

Patient-centric: Device is made to treat a patient’s sufficiently rare condition

Physician-centric: Device is made to satisfy a physician’s unique special need remains with that physician for use in his/her practice

Also note that a single device cannot be patient- and physician-centric.

To qualify as a custom device. The following requirements needs to be followed. The following figure shows the FDA requirements.

Custom devices are exempt from 510(k) and Premarket Approval (PMA) submissions.

Custom Devices are not exempt from any other requirements, including, but not limited to,

• Quality System Regulation, including Design Controls (21 CFR Part 820)
• Medical Device Reporting (21 CFR Part 803)
• Labeling (21 CFR Part 801)
• Corrections and Removals (21 CFR Part 806)
• Registration and Listing (21 CFR Part 807)

Clinical investigations of custom  devices cannot be practically conducted because they are used to treat sufficiently rare conditions or rare physician needs.

In addition to 21 CFR 801 labeling requirements, Custom device shall have below information,

• a statement that the device is a custom device
• the name of the ordering physician
• identifying information for the patient (if applicable) whom the device is intended to treat
• indications for use
• sterilization status
• relevant composition information (materials, components, etc.)
• storage conditions.

Click here to know European MDR Custom made device.

 References:

CDRH Learn Custom device

CustomDevice Exemption-Guidance 

 

Software

European Union: 

Software is defined as a set of instructions that processes input data and creates output data.

Software definitions per MDCG 2019-11 given,

 How to qualify the software as a medical device/in vitro diagnostic medical device software

Shall meet the definition of software according to the MDCG 2019-11 and the definition of a MD/IVD  according to Article 2(1) of MDR/IVDR

 MDR classification rules: Rules 9, 10, 11, 12, 13, 15 and 22 Annex VIII

IVDR Classification rules:To classify in vitro diagnostic medical device software all rules shall be considered.

EU Regulations References:

Is your software a Medical Device? Info graphic

MDCG 2019-11 Qualification and classification of software - Regulation (EU) 2017/745 and Regulation (EU) 2017/746

US FDA Software as Medical Device (SaMD)

“software intended to be used for more than one or more medical purposes that perform these purposes without being part of a hardware medical device.”

 How to qualify the software as a medical device/in vitro diagnostic medical device software

Meet the definition of software according Federal Food Drug & Cosmetic (FD&C) Act section 201(h) device definition.Some of the software functions are excluded from device definition.

 IMDRF Guidance documents.

Softwareas a Medical Device (SaMD): Key Definitions (IMDRF/SaMD WG/N10FINAL:2013)

Softwareas a Medical Device (SaMD): Possible Framework for Risk Categorization andCorresponding Considerations (IMDRF/SaMD WG/N12FINAL:2014)

Softwareas a Medical Device (SaMD): Application of Quality Management System (IMDRF/SaMD WG/N23 FINAL:2015)

Software as a Medical Device (SaMD): Clinical Evaluation(IMDRF/SaMD WG/N41FINAL:2017)

 

US FDA Export Certificates

  

When should an Export certificates are requested: To export a medical device to foreign government

 Prerequisites of export certificates,

Export Certificates type	Legally marketed devices in the United States	Establishment Registration	Device Listing	Labelling	QSR	Comply with laws of exporting country
Certificate to Foreign Government (CFG)	Yes	Yes	Yes	Yes. applicable labeling requirements	Yes	Yes
Certificate of Exportability: Section 801(e)(1)	No	Yes	May be	Device labeled as “intended for export” or “for export only	No	Yes
Certificate of Exportability: Section 802	No. Devices meet performance standards per Section 514 of the FD&C Act –for Class II and III devices not legally marketed	Yes	May be	Establishments substantially conform to CGMPs   Device is not adulterated Devices are in accordance with specifications of foreign purchaser	No	Yes. Devices are marketed in the countries listed in Section 802 (b)(1)(A)(i) and (ii) of the FD&C Act

  Other export certificates are,

• Non-Clinical Research Use Only Certificate
• Export Permit Letters (EPL) per Section 801(e)(2) for Class III, investigational
•  Simple Notifications per Section 802(g)

 From whom CFG is obtained: CDRH

The Center for Devices and Radiological Health (CDRH) is responsible for issuing export certificates for medical devices. To obtain an export certificate, a request must be submitted and CDRH will provide approval or denial of the request.

 How to obtain a CFG: CDRH Export Certification and Tracking System (CECATS)

FDA Unified Registration and Listings System (FURLS) have  CDRH Export Certification and Tracking System (CECATS) System. CECATS allows manufacturers to request export documents, including Certificates to Foreign Governments.

The following information are required for CFG,

• Section 1 - Requestor Information
• Section 2 - Manufacturer Information
• Section 3 - Distributor Information
• Section 4 – Product Information
• Section 5A – Was the product ever recalled?
• Section 5B – INJUNCTION
• Section 5C – SEIZUR
• Section 6 – List Country(ies) for which the Certificates are requested
• Section 7 – Indicate what product information should appear on the certificate.
• Section 8 – Should the country destination be listed on the certificate?
• Section 9 – Exporter's Certification Statement (ECS)
•  

All establishment should register with FDA via FDA Online Account(FDAOAA) 

FDA OAA account ID and password may be used to access or create subaccounts for CDRH Export Certification and Tracking System (CECATS)

CECATS may be accessed after logging into the FDA Unified Registration and Listing Systems (FURLS)

Timelines:

Certificates issued within 20 business days if applicable requirements are met

References

Types of Export Certificates: https://www.fda.gov/medical-devices/exporting-medical-devices/types-export-certificates

 

US FDA Q Submissions

 Manufacturers shall interact with FDA using Q-Submissions program. They can request clarification regarding medical device submissions.

The following feedback mechanism are described in guidance

• Pre-Submissions
• Informational Meetings
• Study Risk Determinations
• Formal Early Collaboration Meetings
•  Submission Issue Meetings
•  Day 100 Meetings for PMA Applicants

Q-Submission requests must be submitted through the Document Control Center (DCC). Two copies are required (One copy must be an electronic copy or eCopy).

FDA shall share the acknowledgement letter containing Q number to the applicant.

Q-Sub Type: Pre-Submissions

• This type of submission used during product development and/or application preparation
• Voluntary program and no user fees required
• Feedbacks are received mainly through in-person meeting, teleconference or email
• Timeframe is 75 to 90 days and FDA will respond with in 21 days for urgent public health issues

Recommended information

• Cover Letter
•  CDRH Premarket Review Submission Cover Sheet (Form FDA 3514)
• Table of Contents
• Detailed Device Description
•  Proposed Intended Use/Indications for Use
• Summary of Previous Discussions or Submissions Regarding the Same Device
•  Overview of Product Development
• Specific Questions for FDA Feedback
• Preferred method to receive FDA Feedback
• Meeting Format, Preferred Dates and Times, Planned Attendees, and Audiovisual Equipment Needs, if meeting or teleconference is requested

Q-Sub Type: Informational Meetings

• Manufacturer will share the information to FDA without expecting any feedback.FDA is in listening mode.
• Timeframe: 90 days

Recommandated information:

• Cover Letter
• CDRH Premarket Review Submission Cover Sheet  
• Brief  Statement
•  Proposed Agenda
• Preferred Meeting Format
• Dates and Times (minimum of three)
•  Planned Attendees
• Audiovisual Equipment Needs, if any

Q-Sub Type: Study Risk Determinations

• Used to determine a study risk determination for not exempt studies.
• FDA will provide a study determination letter and FDA’s determination is final

Recommended information:

• Cover Letter
•  CDRH Premarket Review Submission Cover Sheet
•  Detailed Device Description
•  Study Protocol
•  Description of how the device will be used
•  Description of the population
• Sponsor’s name and contact person(s), including titles, address, phone number, fax number and email address

Q Sub Type-Formal Early Collaboration Meetings

There are two types.

1.Determination Meeting: Applicable for PMA or PDP applicant.

FDA shall determine the type of valid scientific evidence that will be necessary to demonstrate that the device is effective for its intended use.FDA shall assess whether clinical studies are needed to establish effectiveness

2. Agreement Meeting: Applicable for class III product or any implant.

This meeting is conducted to reach agreement on the key parameters of the investigational plan, including the clinical protocol

 Click here to know more about Early Collaboration Meetings Under the FDA Modernization Act (FDAMA); Final Guidance for Industry and for CDRH Staff

Q Sub Type- Submission Issue Meetings

• This meeting is used to discuss the deficiencies identified during premarket applications
• Time frame:21 days

Recommended information:

• Cover Letter
• CDRH Premarket Review Submission Cover Sheet
• Reference to Premarket Submission Number
•  Brief Statement (including purpose, scope, or objectives of meeting)
• Proposed Agenda Including Deficiencies for Discussion
• Focused Questions
• Preferred Meeting Format
• Preferred Dates and Times (minimum of three)
•  Planned Attendees
•  Audiovisual Equipment Needs, if any

Q Sub Type- Day 100 Meetings for PMA Applications

This meeting is to review the status of PMA .

Click here to know more about Guidance on PMA Interactive Procedures for Day-100 Meetings and Subsequent Deficiencies – for Use by CDRH and Industry

References :

Requests for Feedback on Medical Device Submissions: The PreSubmission Program and Meetings with Food and Drug Administration Staff: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGu idance/GuidanceDocuments/UCM311176.pdf

 

 

Standards for Medical Devices

 Standards is a document, that is prepared by subject matter experts and approved by a recognized body.

This provides guidance on the design, use or performance of materials, products, processes, services, systems or persons.

International Standardisation Bodies 

• ISO: International Standardization Organisation (www.iso.org )
• IEC: International Electrotechnical Commission (www.iec.ch )
• ITU: International Telecommunication Union (www.itu.int )

European Standardisation Bodies

• CEN: European Committee for Standardisation (www.cen.eu)
• CENELEC: European Committee for Electrotechnical Standardisation (www.cenelec.eu)
• ETSI: European Telecommunications Standards Institute (www.etsi.org)

International standards are developed by International Standardisation Bodies.

ISO 14971:2019 Medicaldevices — Application of risk management to medical devices. 

European standards are developed by European Standardisation Bodies.

EN 60601-1-6:2010/A2:2021 Medical electrical equipment - Part 1-6: General requirements for basic safety and essential performance - Collateral standard: Usability

European Harmonised standards

European standard adopted on the basis of a request made by the Commission for the application of Union harmonisation legislation.

Harmonised standards are published in Official Journal of the European Union.

Devices that are in compliance with harmonized standards shall be presumed to be in conformity with the requirements of European Regulation. (Article 8)

US FDA Recognized Consensus Standards

FDA identify or recognize a standard established by a national or international standard developing bodies.Manufacturers of medical devices may submit a declaration of conformity to demonstrate they have met relevant requirements in the Federal Food, Drug, and Cosmetic Act (FD&C Act).

Guidance on Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-consensus-standards-premarket-submissions-medical-devices

US FDA Recognized Consensus Standards Database:

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfstandards/search.cfm

 

References

REGULATION (EU) No 1025/2012

REGULATION (EU) 2017/745

REGULATION (EU) 2017/746

Standards and Conformity Assessment Program: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-consensus-standards-premarket-submissions-medical-devices

US FDA Breakthrough Devices Program

Expedited Access Pathway and Priority Review for medical devices are replaced by Breakthrough Devices Program. (Section 515B(b) of the Federal Food, Drug & Cosmetic Act)

This program speedup the breakthrough technologies development, assessment, and review, while preserving the statutory standards for premarket approval, 510(k) clearance, and De Novo marketing authorization.

This program allows the manufacturer to interact with the FDA's experts to efficiently address topics/issues/concerns as they arise during the premarket review phase.

Devices subject to PMAs, 510(k) or requests for De Novo designation are eligible for breakthrough device designation if both of the following criteria are met: statutory criteria

1. The device provides for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human disease or conditions

2. The device also meets at least one of the following:

a. Represents Breakthrough Technology

b. No Approved or Cleared Alternatives Exist

c. Offers Significant Advantages over Existing Approved or Cleared Alternatives

d. Device Availability is in the Best Interest of Patients

Breakthrough Technology: Consider technological advances or new use of an existing technology. Consider potential to lead to clinical improvement.

Manufacturer can submit breakthrough designation at any time prior to sending your marketing submission  by submitting a "Designation Request for Breakthrough Device" Q-Submission.

Content of Application:

• Device description
• Proposed indication for use
• Regulatory history
• How your device meets the statutory criteria for a Breakthrough Device
• What type of marketing submission you plan to submit to the FDA for your device

Timelines:

Deficiency letter- within 30 days of receiving your request

FDA's decision to grant or deny- within 60 days of receiving your request

References:

Guidance Breakthrough Devices Program:https://www.fda.gov/regulatory-information/search-fda-guidance-documents/breakthrough-devices-program

Device advice Breakthrough Devices Program: https://www.fda.gov/medical-devices/how-study-and-market-your-device/breakthrough-devices-program#s3