Regulatory Jeopardy (Before the Trial)

21 CFR part 812

100

Title of 21 CFR part 812

Investigational Device Exemptions

200

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)

300

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

400

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.

500

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

EURO DANCE BEATS

100

German competent authority who responds by email to questions about devices used in trials

BfArM

200

This plan needs to be coordinated with pharma partners prior to the trial start

adverse events reports/surveillance/vigilance plan

300

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)

400

All these documents are included in an Annex XIV application form

list is here: https://lexparency.org/eu/32017R0746/ANX_XIV/

500

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: 

• data allowing identification of the device in question, 
• an evaluation plan stating in particular the purpose, scientific, technical or medical grounds, scope of the evaluation and number of devices concerned, 
• the list of laboratories or other institutions taking part in the evaluation study, 
• the starting date and scheduled duration for the evaluations and, in the case of devices for self-testing, the location and number of lay persons involved, 
• a statement that the device in question conforms to the requirements of the Directive, apart from the aspects covered by the evaluation and apart from those specifically itemised in the statement, and that every precaution has been taken to protect the health and safety of the patient, user and other persons. 

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

So you want to go global?

100

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.

200

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

300

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)

400

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

500

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

Documents you include in your IRB submission

100

This is an example template for an informed consent form

verified example (either posted by IRB as template or approved by IRB during review)

200

Website of Predicine's central IRB

https://www.wcgirb.com

300

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

400

Typical number of days it takes for IRB to complete its review

Any number within 10-20 days

500

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)