IRB continuing review
Conduct continuing review of research requiring review at intervals appropriate to risk, not less than once a year
45 CFR 46, 21 CFR 56
Reporting of suspension / termination of IRB approval
Suspension / termination shall be reporting promptly to the investigator, institutional officials, department or agency head
45 CFR 46
IRB records retention
The records required by this policy shall be retained at least 3 years, and records relating to research that is conducted shall be retained for at least 3 years after completion of the research.
45 CFR 46, 21 CFR 56, ICH E6(R2)
Posting of informed consent
The infromed consent form must be posted on the Federal Web site after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject
45 CFR 46
IRB Registration renewal and changes
Registration is effective for 3 years and must be renewed every 3 years.
Registration information must be updated within 90 days after changes of contact person who provided IRB information or the IRB chairperson.
Decision to disband IRB must be reported to OHRP in writing within 30 days after premanent cessation of IRB’s review.
Decision to review new types of FDA-regulatied products or to discontinue reviewing clinical investigations regulated by FDA must be reported within 30 days of the change.
All other changes may be reported when the IRB renews its registration.
45 CFR 46, 21 CFR 56
General informed consent requirements exception
If immediate use of the test article is, in investigator’s opinion, required to preserve the life of the subject, and time is not sufficient to obtain the required independent determination (if and why the consent form cannot be obtained) in advance of using the test article, the determination of the clinical investigator shall be made and, within 5 days after the use of the article, be reviewed and evaluated in writing by a physician who is not participating in the clinical investigation.
The documentation shall be submitted to the IRB within 5 working days after the use of the test article.
Applies also to investigational in vitro diagnostic devices used to identify chemical, biological, radiological, or nuclear agents.
21 CFR 50
IRB exceptions from informed consent documentation
IRB determinations and documentation of
* approving investigation without requiring informed consent and
* not being able to approve clinical investigation because it doesn’t meet criteria for the exception
must be retained by the IRB for at least 3 years after completion of the clinical investigation.
Records shall be accessible for inspection and copying by FDA.
21 CFR 50
IRB cannot approve clinical investigation with exception to informed consent requirements
If an IRB cannot approve a clinical investigation because it does not meet the criteria in the exception or because of other relevant ethical concerns, the IRB must document its findings and provide these findings promptly in writing to the clinical investigator and to the sponsor.
The sponsor must promptly disclose this information to FDA, other clinical investigators and other IRBs which are part of the clinical investigation.
Disclosure Statement
(Financial interest)
Information in form FDA 3455 shall be promptly updated by the investigator if any relevant changes occure in the course of the investigation or for 1 year following completion of the study.
21 CFR 54, 21 CFR 312, 21 CFR 812
Financial records retention for marketing application
An applicant who has submitted a marketing application containing covered clinical studies shall keep on file complete records showing
* any financial interest or arrangement paid to investigator
* significant payments of other sorts maby by the sponsor to the investigatos
* any financial interests held by clinical investigators
for 2 years after the date of approval of the application.
21 CFR 54
Records for clinical investigations conducted outside USA
A sponsor or applicant must retain the records required by this section for a clinical investigation conducted outside the United States as follows:
1. If the investigation is submitted in support of an IDE, for 2 years after the termination or completion of the IDE
2. If the investigation is submitted in support of a premarket approval application, a notice od completion of a product development protocol, a humanitarian device exemption application, a premarket notification submission, or a request for De Novo classification, for 2 years after an agency decision on that submission or application
21 CFR 812
Emergency deviation from clinical investigation plan
The requirements for FDA approval of a supplement for changes to the clinical investigation plan do not apply in the case of a deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency.
Such deviation shall be reported to FDA within 5 working days after the sponsor learns of it.
21 CFR 812
Changes to be reported to FDA by the sponsor within 5 working days (medical devices)
A sponsor may make the following changes without prior approval from FDA and provides notice to FDA within 5 working days after making the change:
1. developmental changes in the device that do not constitute a significant change in design or basic principles of operation and that are made in response to information gathered during the course of an investigation
2. changes to clinical protocol that do not affect
* the validity of data resulting from completion of the approved protocol, or the relationship of likely patient risk to benefit ratio
* the scientific soundness of the investigational plan
* the rights, safety, or welfare of the human subjects
12 CFR 812
Reports for medical device investigations by investigator
- Unanticipated adverse device effect - investigator to sponsor and reviewing IRB within 10 working days
- Withdrawal of IRB approval - investigator to sponsor within 5 working days
- Progress reports onthe investigation - investigator to sponsor, monitor, and IRB at regular intervals, no less than yearly
- Deviations from the investigational plan to protect the life or physical well-being of a subject in an emergency - investigator to sponsor and IRB to later than 5 working days after the emergency occured (except when a prior approval is required)
- Use of investigational evice without informed consent - investigator to sponsor and IRB within 5 working days after the use occurs
- Final report after termination or completion of the investigation (or the investigator’s part) - investigator to sponsor and IRB
- Other information requested by IRB and FDA from investigator - accurate, complete, and current
21 CFR 812
Reports for medical device investigations by sponsor
- Evaluation of unanticipated adverse device effects - by sponsor to FDA, IRB(s), investigators within 10 working days after the sponsor first receives notice of the effect. Thereafter additional reports to FDA as requested
- WIhdrawal of IRB approval - by sponsor to FDA, IRBs, investigators within 5 working days after receipt of the withdrawal of approval
- Withdrawal of FDA approval - by sponsor to IRBs and investigators within 5 working days after receipt of notice of the withdrawal
- current investigator list - sponsor to FDA at 6-month intervals, first list 6-months after FDA approval
- Progress reports - sponsor to IRBs, in case of significant risk device also to FDA, regularly at least yearly
- Request of any investigator return, repair, or other disposal of any units of device - sponsor to FDA within 30 days of the request was made and explain why
- Final report for significant risk device - sponsor to FDA notification within 30 working days of the completion or termination of investigation and submit final report to FDA, IRBs and investigators within 6 months after completion or termination
- Final report for non-signification risk devices - sponsor to IRBs within 6 months after completion or termination
- Use of device without informed consent notification by investigator (copy of report) - sponsor to FDA within 5 working days of recipt of notice
- IRB determination of device being significant risk when sponsor proposed non-significant risk - sponsor to FDA within 5 working days of IRB’s determination
- Other information requested by IRB and FDA from investigator - accurate, complete, and current
21 CFR 812
IND amendment submissions
Information amendments to the IND should be submitted as necessary but not more than every 30 days.
21 CFR 312
IND safety reports
(FDA 3500 A form)
The sposnor must notify FDA and investigators in an IND safety report of potential serious risks, from clinical trials or any other source, as soon as possible, but no later than 15 calendar days after the sponsor determines that the information qualifies for reporting under
* serious and unexpected suspected adverse reaction
* findings from other studies
* findings from animal or in vitro testing
* increased rate of occurence of serious suspected adverse reactions (clinically important)
“Follow-up IND Safety Report” - as soon as updated relevant information is available
FDA may request different frequency and/or/format of IND Safety Report.
21 CFR 312
Unexpected fatal or life-threatening suspected adverse reaction reports
Sponsor must notify FDA as soon as possible, no later than 7 calendar days after the sponsor’s initial receipt of the information.
21 CFR 312
Brief report of the progress of the investigation
Sponsor shall submit within 60 days of the anniversary date that hte IND went into effect.
21 CFR 312
Termination of IND by FDA
If FDA proposes to terminate an IND, FDA will notify the sponsor in writing, and invite correction or explanation within a period of 30 days.
If FDA does not accept the explanation or coorection, sponsor may request a regulatory hearing within 10 days of the FDA’s notification of nonacceptance.
21 CFR 312
Inactive status
If FDA places an IND on inactive status, sponsor has 30 days to respond as to why the IND should continue to remain active.
An IND that remains in inactive status for 5 years or more may be terminated.
21 CFR 312
IND record retention
A sponsor shall retain the required records and reports for
* 2 years after a marketing application is approved for the drug or
* if an application is not approved until 2 years after shipment and delivery of the drug for investigational use is discontinued and FDA has been notified
An investigator shall retain required records for
* 2 years following the date a marketing application is approved or
* if no application is to be filed or if the application is not approved until 2 years after the investigation is discontinued and FDA is notified.
21 CFR 312
ClinicalTrials.gov registration
For an applicable clinical trial for which submission of clinical trial registration information is required must be submitted no later than 21 calendar days after the first human subject is enrolled
42 CFR 11
ClinicalTrials.gov results
For applicable clincial trials, results information must be submitted no later than 1 year after the primary completion date
Delayed results submission - in general 30 calendar days after decision on FDA application for approval / licensure / clearance was made (vagely) or decision on extension request
Results will be posted publicly no later than 30 days after submission.
42 CFR 11
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The Nuremberg Code (Oct 1946 - April 1949) - C14
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The Belmont Report 1979- C37
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The Declaration of Helsinki 1964 - C17
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45 CFR 46 (Protection of Human Subjects - Common Rule) - C51
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21 CFR 11 (Electronic records)9
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21 CFR 50 (Protection of Human Subjects, ICF)1
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21 CFR 54 (Financial Disclosure)5
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21 CFR 56 (IRB) - C29
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21 CFR 312 (IND)1
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21 CFR 812 (IDE)1
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ICH GCP Rev21
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ICH GCP Rev3 (on exam from 1/1/2026)1
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ICH E2A (Clinical Data Safety Management, AEs)7
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FDA forms7
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Audits and inspections of clinical trials6
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Definitions13
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Timelines29
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FDA vs ICH0
