21 CFR part 812
Title of 21 CFR part 812
Investigational Device Exemptions
German competent authority who responds by email to questions about devices used in trials
Type of IVD that is easier to use in a global clinical trial instead of a distributed kit in terms of regulatory affairs but still difficult for logistics coordination
LDT out of a single site where sample kits get sent out and need to come back on time without spoiling.
This is an example template for an informed consent form
verified example (either posted by IRB as template or approved by IRB during review)
This is the name of the type of Q-submission FDA reviews to confirm if use of a device in a trial is Significant Risk (SR) or Nonsignificant Risk (NS).
Study Risk Determination pre-sub/Q-sub (if device company submits directly to FDA)
or
Streamlined Submission Process for Study Risk Determination (if pharma company submits SRD for device along with their IND)
This plan needs to be coordinated with pharma partners prior to the trial start
adverse events reports/surveillance/vigilance plan
For devices not yet cleared or approved by FDA, you may need to apply for this document before shipping your devices overseas.
Export Permit Letter
At least one of these four criteria are found in significant risk device studies
1. intended as implant and presents a potential for serious risk to health safety or welfare of a subject
2. for use supporting or sustaining human life and potential for serious risk to health safety or welfare of a subject
3. substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and potential for serious risk to health safety or welfare of a subject
4. otherwise presents a potential for serious risk to health safety or welfare of a subject
Annex XIV of (EU) 2017/746 (IVDR) is applicable for these types of studies
For devices intended to be used in the context of interventional clinical performance studies or other performance studies involving risks for the subjects of the studies. (e.g. prospective CDx enrollment studies or when specimen collection such as fresh biopsy is required for testing)
If an IVD kit is already cleared/approved by FDA, sometimes ex-US countries will ask you for this certificate (similar to Certificate of Free Sale) to clear local customs/regulatory requirements.
Certificate to Foreign Government (CFG)
This team is responsible for IRB submissions to support use of our assays in pharma clinical trials
Clin Dev
or
Clin Ops
or
Clin Affairs
This is the downside of confirming NSR in the fastest way possible.
Two potential responses:
1. Trying to confirm NSR through IRB. IRB may not confirm NSR and then you lose time if you want to confirm again with FDA.
2. Directly submitting an IDE and seeing if FDA declines to review it due to NSR. IDE's take money and resources to prepare and may not always be needed. Also, by submitting an IDE directly you may be pushing FDA to confirm SR designation and then are subject to all the review/requirements of an IDE device.
All these documents are included in an Annex XIV application form
list is here: https://lexparency.org/eu/32017R0746/ANX_XIV/
Two reasons why Program Management/Alliance Management should be kept in the loop about all global RA activities
1. Predicine charges pharma partners for RA work and pass through costs
2. PM/AM team manage the relationship/communication between Predicine and pharma partners
Typical number of days it takes for IRB to complete its review
Any number within 10-20 days
All these documents are included in a typical IDE submission
1. Clinical Trial Protocol
2. Diagnostic Protocol
3. ICF
4. Validation reports
5. IDE main submission summary
6. Test Requisition Form
7. IFU
8. Letter to reference IND
9. Cover letter
10. FDA form 3514
The procedure in this Annex in IVDD Directive 98/79/EC Article 9(4) can be followed until EUDAMED is fully functional to implement Annex XIV of IVDR regarding performance studies
Annex VIII of Directive 98/79/EC states:
For devices for performance evaluation the manufacturer or his authorised representative shall draw up the statement containing the information stipulated in section 2 and ensure that the relevant provisions of this Directive are met.
2. The statement shall contain the following information:
3. The manufacturer shall also undertake to keep available for the competent national authorities the documentation allowing an understanding of the design, manufacture and performances of the product, including the expected performances, so as to allow assessment of conformity with the requirements of this Directive. This documentation must be kept for a period ending at least five years after the end of the performance evaluation. The manufacturer shall take all the measures necessary for the manufacturing process to ensure that the products manufactured conform to the documentation mentioned in the first paragraph.
Annex VIII further states that manufacturers of devices for performance evaluation have to comply to the notification requirements as described in Article 10(1), (3) and (5).4
The reason why you may consider submitting a clinical trial application for your CTA in countries like South Korea or Australia even if it's not required for an LDT
To use the trial data to support local CDx registration later
All these documents are included in a typical IRB submission
1. ICF
2. clinical trial protocol
3. Dx protocol
4. NSR vs SR assessment/rationale
5. inform about any relevant FDA submissions (Q-sub or IDE)