The Shop

Our Latest Posts

Basics | U.S., Regulatory Basics
The IVD Product Types: RUO, IUO, GPR, ASR

IVD Product Types: RUO, IUO, GPR, ASR

Definitions

21 CFR Part 809.3 defines the in vitro diagnostics (IVDs) products as ”reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body’‘.

IVDs are devices as defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), and may also be biological products subject to section 351 of the Public Health Service Act (PHS Act). Like other medical devices, IVDs are subject to premarket and postmarket controls. IVDs are generally also subject to categorization under the Clinical Laboratory Improvement Amendments (CLIA ’88) of 1988.

The U.S. regulations define four other IVD types: RUO, IUO, GPR and, ASR products.

The "Special" IVD Types

Reseach Use Only (RUO) products

RUO products are IVD products in the research laboratory phase of development. They can be under evaluation (e.g. for design evaluation, test usability) and being evaluated for developing a future commercial IVD product.

RUO products can also be used in a nonclinical laboratory context to conduct scientific research. In this case these RUO products are not intended use for further development for a clinical diagnostic use. 

RUO products are not considered to be effective IVDs products (21CFR809.10(c)) and can be shipped or delivered for an investigation not subjected to an Investigational Device Exemption (IDE) as per 21CFR812.

RUO products are not subject to device classification.

RUO products shall bear the statement, prominently placed: “For Research Use Only. Not for diagnostic procedures”.

Investigational Use Only (IUO) Products

IUO products are intended be to used for product testing prior to full commercial marketing (for example, for use on specimens derived from humans to compare the usefulness of the product with other products or procedures which are in current use or recognized as useful) (21CFR809.10(c)(2)(ii).

IUO products are reagents, instruments, or test systems being used in a clinical investigation or research involving one or more subjects to determine a device’s safety and effectiveness (21CFR 812.3(h)).

IUO products are not considered to be effective IVDs products (21CFR809.10(c)) and can be shipped or delivered for an investigation not subjected to an Investigational Device Exemption (IDE) as per 21CFR812.

IUO products shall bear the statement, prominently placed: “For Investigational Use Only. The performance characteristics of this product have not been established.”

General Purpose Reagent (GPR) Products

GPR products are chemical reagents having a general laboratory application (e.g. pH buffers, isotonic solutions), used to collect, prepare, and examine specimens from human body for diagnostic purposes, and not labeled or otherwise intended for specific diagnostic application (21CFR864.4010(a)).

GPRs are medical devices that are regulated by FDA

GPR products can be individual substances or multiple substances which can be part of a diagnostic test procedure or system constituting a finished IVD test.

Most of the GPR products are classified as Class I (General Controls) and exempt from premarket notification (21CFR864.9).

GPR products shall be labeled with basic identifying information, storage conditions, warnings and precautions and shall bear the following statement: “For Laboratory Use” (21CFR809.10(d)).

Analyte Specific Reagent (ASR) Products

ASR products are “antibodies, both polyclonal and monoclonal, specific receptor proteins, ligands, nucleic acid sequences, and similar reagents which, through specific binding or chemical reactions with substances in a specimen, are intended for use in a diagnostic application for identification and quantification of an individual chemical substance or ligand in biological specimens.” (21 CFR 864.4020(a)).

ASRs are medical devices that are regulated by FDA.

Most of the ASRs are Class I and exempt from premarket notification. These products are subject to general controls, including current Good Manufacturing Practices (cGMPs) (21 CFR Part 820) as well as the specific provisions of the ASR regulations (21 CFR 809.10(e), 809.30, 864.4020).

There are some ASRs that are Class II and Class III and that must be cleared or approved by FDA before they can be marketed in the United States.

An ASR is a Class II device if the reagent is used as a component in a blood banking test of a type that has been classified as a Class II device (e.g., certain cytomegalovirus serological and treponema pallidum nontreponemal test reagents) (21 CFR 864.4020(b)(2)).

An ASR is a Class III device if the reagent is intended as a component in tests intended either:

• to diagnose a contagious condition that is highly likely to result in a fatal outcome and prompt, accurate diagnosis offers the opportunity to mitigate the public health impact of the condition (e.g., human immunodeficiency virus (HIV/AIDS) or tuberculosis (TB)); or

• for use in donor screening for conditions for which FDA has recommended or required testing in order to safeguard the blood supply or establish the safe use of blood and blood products (e.g., tests for hepatitis or for identifying blood groups) (21 CFR 864.4020(b)(3)). FDA considers ASRs intended to be used as a component in tests for diagnosis of HIV (including monitoring for viral load or HIV drug resistance mutations) to be Class III ASRs.

Class I ASR products shall bear the statement: “Analyte Specific Reagent. Analytical and performance characteristics are not established.”

Class II and III ASR products must bear the statement: “Analyte Specific Reagent. Except as a component of the approved/cleared test (Name of approved/cleared test), analytical and performance characteristics of this ASR are not established”.

Recommended Reading and References

Distribution of In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only, Guidance for Industry and FDA Staff, November 2013

Commercially Distributed Analyte Specific Reagents (ASRs): Frequently Asked Question, Guidance for Industry and FDA Staff, September 2007

Guidance for Industry and FDA Staff Commercially Distributed Analyte Specific Reagents (ASRs): Frequently Asked Questions, September 2007

Democratizing MedTech Regulatory Knowledge

#regulatoryandmore

The Shop
Share
Facebook Twitter Linkedin Whatsapp Envelope

Follow Us

Linkedin Twitter Facebook Instagram
Basics | EU, Regulatory Basics
Claims under the MDR and the IVDR (Art. 7/7)

Claims under the MDR and the IVDR (Art. 7/7)

Overview

Purpose (+) Scope

Marketing and advertising requirements for medical devices and IVDs are covered in the article 7 of the EU MDR 2017/745  and EU IVDR 2017/746. These requirements target any documentation, practice and statements such as product labeling, instructions for use, and product advertising.

Claims Requirements

MDR requirements and IVDR requirements are strictly similar. No differences between their articles 7 are noted.

The requirements prohibit the use of text, names, trademarks, pictures and figurative or other signs that may mislead the user or the patient regarding the device’s intended purpose, safety and performance by:

    • Ascribing functions and properties to the device which the device does not have;
      • e.g. Advertising that a device intended to be used for pulmonary cancer detection only can be also be used for stomach cancer detection.
    • Creating a false impression regarding treatment or diagnosis, functions or properties which the device e does not have;
      • e.g. Claiming that a device has a accuracy of 99% accuracy without having clinical evidence.
    • Failing to inform the user or the patient of a likely risk associated with the use of the device in line with its intended purpose;
      • e.g. Failing to inform that a device can cause an electrical shock in some circumstances.
    • Suggesting uses for the device other than those stated to form part of the intended purpose for which the conformity assessment was carried out.
      • e.g. Suggesting that a device intended to be used by professional only can be also used by laid person.

Comparison Table

Differences are in orange

EU MDR – Regulation (EU) 2017/745
EU IVDR – Regulation (EU) 2017/746

Article 7

Claims

Article 7

Claims

In the labelling, instructions for use, making available, putting into service and advertising of devices, it shall be prohibited to use text, names, trade marks, pictures and figurative or other signs that may mislead the user or the patient with regard to the device’s intended purpose, safety and performance by:

(a) ascribing functions and properties to the device which the device does not have;

(b) creating a false impression regarding treatment or diagnosis, functions or properties which the device does not have;

(c) failing to inform the user or the patient of a likely risk associated with the use of the device in line with its intended purpose;

(d) suggesting uses for the device other than those stated to form part of the intended purpose for which the conformity assessment was carried out.

In the labelling, instructions for use, making available, putting into service and advertising of devices, it shall be prohibited to use text, names, trademarks, pictures and figurative or other signs that may mislead the user or the patient with regard to the device’s intended purpose, safety and performance by:


(a) ascribing functions and properties to the device which the device does not have;


(b) creating a false impression regarding treatment or diagnosis, functions or properties which the device does not have;


(c) failing to inform the user or the patient of a likely risk associated with the use of the device in line with its intended purpose;


(d) suggesting uses for the device other than those stated to form part of the intended purpose for which the conformity assessment was carried out.

Recommended Reading

Mariusz Malinowski. Advertising of Medical Devices and Principles of Claim Substantiation in European Union. Am J Bi–omed Sci & Res. 2021 – 12(4). AJBSR.MS.ID.001777. DOI:10.34297/AJBSR.2021.12.001777.

References

Consolidated text: Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC

Consolidated text: Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU

Share on facebook
Share on twitter
Share on linkedin
Share on whatsapp
Share on email
Best Sellers
Related Posts

Follow Us

Linkedin Facebook Twitter Instagram

#regulatoryandmore

Basics | U.S.
The Investigational Device Exemption (IDE)

The Investigational Device Exemption (IDE)

Overview

Purpose (+) Scope

An Investigational Device Exemption (IDE) is a regulatory submission allowing, if approved, the use of a device (called in this context a investigational device) to be used in clinical investigation (clinical study/clinical trial) in order to collect safety and effectiveness data.

As per 21 CFR 812.1, ” an approved investigational device exemption (IDE) permits a device that otherwise would be required to comply with a performance standard or to have premarket approval to be shipped lawfully for the purpose of conducting investigations of that device”. 

In essence, you ask the FDA to allow your device to be used in clinical investigation as you want to collect substantial clinical evidences to support a future FDA submission for in fine placing the device in the U.S. market.

Introduction

An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data. Clinical studies are most often conducted to support a PMA. Only a small percentage of 510(k)s require clinical data to support the application. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated. – The U.S. Food & Drug Administration (FDA).

The Code of Federal Regulations Title 21 Part 812 (21 CFR 812) contains the procedures and requirements governing the IDE and the conduct of clinical research of devices. 

A Pre-Sub meeting may be held prior to the submission of an IDE in order to seek FDA input on the IDE components. As a reminder, a Pre-Sub meeting provides the opportunity for a submitter to obtain FDA feedback prior to an intended premarket submission (i.e., IDE, PMA, HDE, De Novo request, 510(k), Dual, BLA, IND). The Pre-Sub is a type of Q-Submission. If a manufacturer has had a Pre-Sub meeting, the advantage is that it can now tailor the information to what FDA has indicated it expects for the particular device. 

IDE Application

A sponsor of a significant risk device study must submit a complete IDE application to FDA. There are no preprinted forms for an IDE application; however, an IDE application must include certain required information. The sponsor must demonstrate in the application that there is reason to believe that the risks to human subjects from the proposed investigation are outweighed by the anticipated benefits to subjects and the importance of the knowledge to be gained, that the investigation is scientifically sound, and that there is reason to believe that the device as proposed for use will be effective – The U.S. Food & Drug Administration (FDA).

Several required elements must be included in an IDE application such as:

  • A report of prior investigations – containing at least a bibliography of all publication, copies of all published and unpublished adverse information, copies of other significant publications if requested by an Institutional Review Board (IRB) or FDA, a summary of all other unpublished information, if nonclinical laboratory data are provided, a statement that such studies have been conducted in compliance with the Good Laboratory Practice (GLP) regulations or a rational if not.
  • An investigational plan (21 CFR 812.25) – including at least the purpose of the investigation, a protocol, a risk analysis, a justification for the investigation; a description of the patient population, a description of the device, the monitoring procedures and additional records and reports. The investigational plan must be approved by each participating study site’s IRB.
  • A description of the methods, facilities, and controls used for the manufacture, processing, packing, storage, and installation of the device.
  • An example of the agreement to be signed by the investigators and a list of the names and addresses of all investigator.
  • Certification that all investigators have signed the agreement, that the list of investigators includes all investigators participating in the study, and that new investigators will sign the agreement before being added to the study.
  • A list of the names, addresses, and chairpersons of all IRBs that have or will be asked to review the investigation and a certification of IRB action concerning the investigation.
  • The name and address of any institution (other than those above) where a part of the investigation may be conducted
  • The amount, if any, charged for the device and an explanation of why sale does not constitute commercialization
  • Copies of all labeling for the device.
  • Copies of all informed consent forms and all related information materials to be provided to subjects.
  • Any other relevant information that FDA requests for review of the IDE application.

The required content of an IDE is provided in 21 CFR 812.20, including the specific order in which the information should be presented. FDA is, however, somewhat liberal on sequence, as long as all the information is included and presented in a logical fashion. 

As a reminder, a clinical study performed in the U.S. must have a U.S. sponsor (A clinical study sponsor is a person, company, institution, group, or organization that oversees or pays for a clinical investigation and collects and analyzes the data). Therefore, a foreign manufacturer must have a U.S. entity submit the IDE.

Format

The signed IDE application is submitted to FDA in triplicate, either with three paper copies, or with two electronic copies (using the eCopy Program) and one paper copy. The submission must be signed by the sponsor’s authorized representattive and delivered via courier to the document mail center of the Center for Devices and Radiological Health (CDRH).

The paper copy volumes must be paginated and bound in volumes must no more than two inches (about 5 cm) thick. FDA requires standard U.S. letter size paper (8.5 x 11 inches) white paper for all submissions. Specific FDA guidance on the Pre-Sub program can be found in the FDA guidance document Requests for Feedback and Meetings for Medical Device Submissions:The Q-Submission Program.

The electronic copy must conform to the requirements in FDA guidance document eCopy Program for Medical Device Submissions, including requirements for cover letter, file type (.pdf), bookmarks, file naming, file size limitations, etc.

Cover Letter

The FDA specifies that a cover letter describing the submission and/or a Form 3514 (Voluntary form used to help provide basic administrative info for all types of premarket notification submissions) is required to be included in the IDE. The cover letter should include:

  • A statement that the information provided is an original IDE submission.
  • The device information (Device name, intended use)
  • The sponsor contact information
  • The manufacturer information
  • If the organization submitting the application is not the sponsor, such as a consultant or a lawyer, include contact information for the correspondent organization or individual.
  • If applicable, a description of Q-Submission/Pre-Submission meetings, any discussion with the FDA reviewing division, the Q-Sub number and a copy of the written feedback, the name of the FDA contact person and the minutes of the meetings.
  • The identification of any waiver requests and the justification
  • Referenced Files: Identify any files that are referenced in the IDE application, such as Premarket Approval, Premarket Notification 510(k), IDE, or device master files. If files were not submitted by the sponsor, include a letter from the owner of the files that grants FDA permission to reference the files in its review of the current application.

Devices Studies Types and IDE Study Types

Device studies are categorized into three types according to the regulations of 21 CFR 812:

  • Exempt studies: These studies are exempt from the requirements of 21 CFR 812. Examples of exempt studies include diagnostic device studies (e.g., in vitro diagnostic studies), consumer preference testing, testing of a device modification, veterinary devices, animal studies, custom devices, etc. (see 21 CFR 812.2 (c).
  • Significant risk (SR) device studies: These studies require an approved IDE from the FDA and must comply with the complete regulations at 21 CFR 812.
  • Nonsignificant risk (NSR) device studies: These studies must meet the abbreviated IDE requirements at 21 CFR 812.2(b). 

For SR and NSR device studies, the following IDE Study Types are available:

  • Early Feasibility Study (EFS) – To provide proof of principle and initial clinical safety data with a limited clinical investigation (<15). Study performed usually early in development, typically before the device design has been finalized, for a specific indication (e.g., innovative device for a new or established intended use, marketed device for a novel clinical application).
  • First in Human (FIH) Study – When a specific indication is evaluated for the first time in human subjects. Note that a FIH can be a EFS, but not all FIH studies would be considered EFSs.
  • Traditional Feasibility Study – To capture preliminary safety and effectiveness information on a near-final or final device design. To adequately plan an appropriate pivotal study. Does not necessarily need to be preceded by an EFS.
  • Pivotal Study – To collect definitive evidence of the safety and effectiveness of a device for a specified intended use, typically in a statistically justified number of subjects. May or may not be preceded by an early and/or a traditional feasibility study.

Recommended Reading

FDA guidance document Requests for Feedback and Meetings for Medical Device Submissions:The Q-Submission Program, 2021

Investigational Device Exemption (IDE), FDA web site

Other Clinical Trials and IDE FDA guidance documents

References

Section 520(g) of Federal Food, Drug, and Cosmetic Act (FD&C Act)

Section 601 of Food and Drug Administration Safety and Innovation Act (FDASIA)

Regulations pertaining to the Investigational Device Exemptions (IDE):

Share on facebook
Share on twitter
Share on linkedin
Share on whatsapp
Share on email
Best Sellers
Related Posts

Follow Us

Linkedin Facebook Twitter Instagram

#regulatoryandmore

Basics | EU, Regulatory Basics
Conformity Assessment Options for Products Failing under the MDR

Conformity Assessment Options for Products Failing under the MDR

Overview

Purpose (+) Scope

The conformity assessment route for CE marking varies according to the assigned class of device as describes in MDR Article 52 and in the MDR Annex IX, Annex X and Annex XI depending on the device class, manufacturers have some choice regarding the conformity assessment route.

Conformity Assessment Options

Class I

Annex II and Annex III

Class I (special): With measuring function, sterile, or reusable

Annex II, Annex III and Annex IX, 

or

Annex XI Part A

Class IIa

Annex II, Annex III and Annex IX of each category of devices

or 

Annex X coupled with Annex XI Part A or Annex XI Part B

Class IIb

Annex II, Annex III and Annex IX, of each generic category of devices

or 

Annex X coupled with Annex XI Part A or Annex XI Part B

Class IIb (special): Implantable devices

Paragraph

Class III

Annex II, Annex III and Annex IX

or

Annex X coupled with Annex XI Part A or Annex XI Part B

Custom-made Devices

(a) Not implantable: Annex XIII

(b) Implantable Class III: Additionally Annex IX or Annex XI Part A

Mentionned Annexes

Annex II – Technical documentation

Annex III – Technical documentation on post-market surveillance

Annex IX – Conformity assessment based on a quality management system and assessment of the technical documentation

Annex X – Conformity assessment based on type examination

Annex XI – Conformity assessment based on product conformity verification – Part A: Production Quality Assurance 

Annex XI – Conformity assessment based on product conformity verification – Part B: Product Verification

Annex XIII – Procedure for Custom-Made Devices

References

Regulation (EU) 2017/745 MDR: 02017R0745 — EN — 24.04.2020 — 001.001 (consolidated version)

Share on facebook
Share on twitter
Share on linkedin
Share on whatsapp
Share on email
Best Sellers
Related Posts

Follow Us

Linkedin Facebook Twitter Instagram

#regulatoryandmore

Show More Posts