SOP-M6
Sponsor-Investigator Studies (IND/IDE Holder)
- Number
- SOP-M6
- Category
- Module
- Edition
- Lean Edition 2.0
- Approx. pages
- 6
- Reference Edition source
- 800
[YELLOW] the site fills in. [DEFAULT: green] a value the site may keep or change.
On this page
1. Purpose
This module describes the gate [SITE NAME] applies before an investigator takes on the sponsor role for a clinical investigation, the sponsor quality system that must exist before enrollment, and the sponsor steps that follow: the IND or IDE decision and submission, sponsor oversight, safety and progress reporting to FDA, and ClinicalTrials.gov registration and results.
2. Scope
Adopt this module only if [SITE NAME] conducts investigator-initiated trials of FDA-regulated drugs, biologics or devices in which a site investigator is the sponsor-investigator, whether or not an IND or IDE is needed and whether or not a company supplies product or funding.
It does not apply to industry-sponsored studies or to studies where another institution or a CRO holds the IND or IDE. The core SOPs continue to apply to the investigator side of the study. Sponsor obligations are product-specific; this module sets the gate and the reporting steps, and the sponsor procedures themselves are the ones named under 5.2. Follow FDA, the IRB, a funder or a product supplier where they are stricter than this module.
3. Responsibilities
| Role | Responsibilities |
|---|---|
| Sponsor-Investigator (the PI) | Holds all sponsor and investigator obligations. Signs FDA submissions. May delegate sponsor tasks to qualified people or providers but keeps responsibility for them. |
| Site Director | Approves taking on the study, provides resources for sponsor functions for the full study and retention period, and approves provider contracts. |
| Quality Lead | Signs the sponsor quality plan before submission, includes the study in the annual internal audit plan (SOP-14) and reviews the sponsor deadline calendar at each quarterly quality review. |
| Regulatory Coordinator | Prepares and tracks FDA, IRB and ClinicalTrials.gov submissions, keeps the sponsor regulatory file and the sponsor deadline calendar. |
| Regulatory consultant or CRO | Performs contracted sponsor tasks (for example IND or IDE preparation, monitoring, safety review, data management), overseen under SOP-M1. |
| Finance / Contracts Lead | Negotiates agreements with funders and product suppliers. |
4. Definitions
| Term | Definition |
|---|---|
| Sponsor-investigator | An individual who both initiates and conducts a clinical investigation, and under whose immediate direction the investigational product is administered, dispensed or used. Not a corporation or agency. Holds the obligations of both sponsor and investigator (21 CFR 312.3(b); 21 CFR 812.3(o)). |
| Sponsor quality plan | The written record, signed before IND or IDE submission, naming the procedure that governs each sponsor function in 5.2.1. |
| Significant risk (SR) device | An investigational device that is an implant, supports or sustains life, is of substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise presents a potential for serious risk (21 CFR 812.3(m)). |
| Nonsignificant risk (NSR) device study | A device study that is not SR. With IRB agreement and the abbreviated requirements met, it is treated as having an approved IDE (21 CFR 812.2(b)). |
| IND safety report | The sponsor's expedited report to FDA and all participating investigators of potential serious risks (21 CFR 312.32(c)). |
| Applicable clinical trial (ACT) | A trial that must be registered and report results on ClinicalTrials.gov (42 CFR 11.22). |
5. Procedure
5.1 Gate before agreeing to sponsor
5.1.1
The PI presents the proposed study to the Site Director and Quality Lead with the draft protocol, the product and its source, funding, the expected pathway (IND, IDE, NSR or exempt), and the sponsor tasks the PI will perform or contract out.
5.1.2
The Site Director decides whether the site can resource the sponsor functions for the study's full duration and retention period: protocol and consent development, statistics and data management, monitoring by a qualified person outside the study team, safety review and expedited reporting, regulatory submissions and annual reports, product supply and labeling, sponsor liability insurance and participant injury coverage, and ClinicalTrials.gov. The decision is recorded on F-200-01 Study Feasibility Assessment, which a site adopts with this module where it has not adopted SOP-M2.
5.1.3
Unless an investigator or staff member has documented sponsor experience, the site contracts a qualified regulatory consultant or CRO for IND or IDE preparation, safety review and monitoring.
5.1.4
The Finance / Contracts Lead negotiates any agreement with the company supplying product or funding, covering who holds the IND or IDE, a letter of authorization to cross-reference the company's IND, IDE or master file, supply and return of product, exchange of safety information, publication and data ownership.
5.1.5
No IND, IDE or NSR submission is made until the sponsor quality plan under 5.2 is signed.
5.2 Sponsor quality system minimum
5.2.1
Before the IND or IDE is submitted, and in any case before the first participant is enrolled, the sponsor-investigator has written procedures, specific to the study or general, for each of these sponsor functions (ICH E6(R3) Annex 1, section 3, including 3.9 Sponsor Oversight, 3.10 Quality Management, 3.11 Quality Assurance and Quality Control, 3.13 Safety Assessment and Reporting and 3.16 Data and Records):
- monitoring: a written, risk-based monitoring plan (5.5.3)
- data management: a data management plan covering data capture, review, queries, database lock and computerized systems (ICH E6(R3) Annex 1, section 4)
- safety management: receipt, assessment and expedited reporting of safety information as sponsor (5.6)
- trial master file: which sponsor records are kept, where and for how long (5.9.2)
- service provider oversight: selection, agreements and oversight of any CRO, monitor, laboratory or other provider used for sponsor activities (SOP-M1 applied to sponsor functions)
- a sponsor SOP set or index listing these procedures, under version control (SOP-01)
5.2.2
The procedures may be the CRO's or consultant's SOPs adopted by reference, or site sponsor SOPs. The site's investigator SOPs do not cover these functions.
5.2.3
The PI records the sponsor quality plan on F-306-01 Note to File in the sponsor file, naming where each procedure in 5.2.1 is kept. The Quality Lead signs the plan after checking that each function has a named procedure and owner.
5.3 Drug and biologic studies: is an IND needed?
5.3.1
The PI, with the regulatory consultant if engaged, assesses whether the study is exempt under 21 CFR 312.2(b) and records the assessment in the sponsor file. A study of a lawfully marketed drug is exempt only if all of these apply:
- it is not intended to support a new indication or other significant labeling change, or (for a prescription drug) a significant change in advertising
- it does not use a route, dose, population or other factor that significantly increases the risks
- it complies with 21 CFR 56 and 21 CFR 50
- it complies with 21 CFR 312.7 (no promotion or commercialization)
5.3.2
Studies of unapproved drugs, and studies using an exception from informed consent (21 CFR 50.24), are not exempt.
5.3.3
The PI follows the IRB's process where the IRB reviews the exemption. If the PI or IRB is uncertain, the PI asks FDA for advice (21 CFR 312.2(e)) and files the response.
5.4 Device studies: risk determination and pathway
5.4.1
The PI records whether the study is exempt under 21 CFR 812.2(c) and the basis.
5.4.2
If not exempt, the PI proposes an SR or NSR determination with a written rationale under 21 CFR 812.3(m). For a proposed NSR study, the PI presents the rationale to the IRB, which makes the determination; FDA's determination is final if FDA is consulted. If the IRB determines SR after the PI proposed NSR, the PI reports this to FDA within 5 working days (21 CFR 812.150(b)(9)).
5.4.3
An IRB-approved NSR study follows the abbreviated requirements of 21 CFR 812.2(b): labeling (812.5), IRB approval maintained, consent under 21 CFR 50, monitoring (812.46), the sponsor and investigator records and reports listed in 812.2(b), and the prohibitions in 812.7.
5.4.4
An SR study needs an FDA-approved IDE (21 CFR 812.20) and IRB approval before it begins (21 CFR 812.42). The PI considers an FDA Pre-Submission before submitting.
5.5 Submission and sponsor oversight
5.5.1
The regulatory consultant or Regulatory Coordinator prepares the IND with the PI using FDA's current forms (Form FDA 1571, protocol, Form FDA 1572 for each investigator including the PI, investigator's brochure or product information, chemistry and manufacturing information or a cross-reference letter, pharmacology and toxicology information or cross-reference, previous human experience, Form FDA 3674). The PI signs as sponsor.
5.5.2
An IND goes into effect 30 days after FDA receives it unless FDA places a clinical hold, or earlier if FDA says the study may begin (21 CFR 312.40(b)). The PI does not administer the drug before the IND is in effect and the IRB has approved the study. The Regulatory Coordinator files FDA's acknowledgment and any comments and records the effective or approval date in the sponsor file and on the sponsor deadline calendar.
5.5.3
Monitoring follows the written monitoring plan (21 CFR 312.50; 21 CFR 812.46; ICH E6(R3) Annex 1, 3.11.4), carried out by a person outside the PI's study team. Independence is site practice; the regulations require monitoring but not an independent monitor. Monitoring reports go to the PI and the sponsor file.
5.5.4
For each other participating investigator, the PI obtains a signed 1572 or device investigator agreement, CV and financial disclosure information, with a commitment to update it during the study and for one year after completion (21 CFR 312.53; 21 CFR 812.43). The PI informs investigators of new observations, especially adverse effects and safe use (21 CFR 312.55), and ends an investigator's participation and notifies FDA where compliance cannot be secured (21 CFR 312.56).
5.5.5
The PI arranges product supply, labeling (21 CFR 312.6, including "Caution: New Drug - Limited by Federal (or United States) law to investigational use"; 21 CFR 812.5 for devices), storage and accountability under SOP-06, keeps sponsor records of receipt, shipment and disposition (21 CFR 312.57), and arranges return or authorized disposition of unused product (21 CFR 312.59).
5.5.6
The site's conflict of interest process also applies to the PI and investigators (SOP-02).
5.6 Safety reporting as sponsor
5.6.1
The investigator duties in SOP-09 still apply. As sponsor, the PI reviews all safety information promptly (21 CFR 312.32(b)).
5.6.2
A second qualified physician (for example a medical monitor contracted through the CRO) reviews each serious event for expectedness and reportability within [DEFAULT: 2 business days of the PI's awareness], and the review is filed in the sponsor file.
5.6.3
The PI submits an IND safety report to FDA and all participating investigators no later than 15 calendar days after determining that information qualifies (serious and unexpected suspected adverse reactions; findings from other studies or animal or in vitro testing suggesting significant human risk; a clinically important increase in the rate of serious suspected adverse reactions), and no later than 7 calendar days after initial receipt for an unexpected fatal or life-threatening suspected adverse reaction (21 CFR 312.32(c)).
5.6.4
As investigator, the PI also submits each IND safety report to the IRB under the IRB's procedures (21 CFR 312.66; FDA guidance Investigator Responsibilities: Safety Reporting for Investigational Drugs and Devices, December 2025; SOP-09).
5.6.5
Device studies: the PI evaluates any unanticipated adverse device effect and reports the results to FDA, all reviewing IRBs and participating investigators within 10 working days after first notice (21 CFR 812.46(b); 21 CFR 812.150(b)(1)), in NSR and SR studies.
5.6.6
The Regulatory Coordinator logs each sponsor safety report and its due date on F-501-01 SAE Reporting Tracker in the FDA submission columns.
5.7 Amendments and periodic reports
5.7.1
The Regulatory Coordinator enters every sponsor deadline in the sponsor deadline calendar at the time it is created. The Quality Lead reviews the calendar at each quarterly quality review (SOP-14).
5.7.2
IND protocol amendments (21 CFR 312.30): a new protocol is submitted to FDA and may begin once submitted and IRB-approved; a change affecting safety, scope or scientific quality is submitted to FDA and implemented after submission and IRB approval, except a change to eliminate an apparent immediate hazard, which is implemented at once and reported afterward; a new investigator is notified to FDA within 30 days of being added.
5.7.3
Information amendments (21 CFR 312.31) report important information not covered by another submission.
5.7.4
The IND annual report goes to FDA within 60 days of each anniversary of the date the IND went into effect (21 CFR 312.33).
5.7.5
Device studies: changes follow 21 CFR 812.35; progress reports go to the IRB at least yearly (and to FDA for SR studies); for SR studies the PI notifies FDA within 30 working days of completion or termination and sends a final report within 6 months (21 CFR 812.150(b)). Other 812.150(b) reports (for example withdrawal of IRB approval within 5 working days, current investigator list every 6 months) are entered on the calendar.
5.8 ClinicalTrials.gov
5.8.1
The PI determines whether the study is an applicable clinical trial under 42 CFR 11.22 and records the determination in the sponsor file.
5.8.2
For an ACT, the PI as responsible party registers no later than 21 calendar days after the first participant is enrolled (42 CFR 11.24), updates the record at least every 12 months and sooner for changes such as recruitment status (42 CFR 11.64), and submits results no later than 1 year after the primary completion date unless a delay is allowed (42 CFR 11.44).
5.8.3
The PI registers before the first enrollment where results may be published or the IRB requires it. For an ACT, the consent documents include the ClinicalTrials.gov statement exactly as worded in 21 CFR 50.25(c); the NCT number is not part of that statement. The NCT number goes on Medicare claims for qualifying trials (SOP-M2).
5.9 Completion and closure
5.9.1
At completion, the PI completes investigator closeout under SOP-15 and the sponsor steps: final reports to the IRB and, as required, FDA; ClinicalTrials.gov results; withdrawal of the IND (21 CFR 312.38) or request for inactive status (21 CFR 312.45), or the IDE final report and completion notice; and disposition of unused product.
5.9.2
Sponsor records are kept for 2 years after a marketing application is approved or, if none is approved, 2 years after shipment and delivery for investigational use is discontinued and FDA is notified (21 CFR 312.57(c)), or as 21 CFR 812.140(d) states for devices, and longer where state law or agreements require (SOP-12).
5.9.3
FDA inspects sponsor-investigators under Compliance Programs 7348.811 and 7348.810. SOP-13 applies, including 5.5.8.
6. Related Forms and SOPs
- F-200-01 Study Feasibility Assessment
- F-306-01 Note to File
- F-501-01 SAE Reporting Tracker
- F-105-01 Service Provider Qualification and Oversight Record
- SOP-01 SOP Control, Training and Qualification
- SOP-02 Roles, PI Oversight, Delegation and Conflicts of Interest
- SOP-06 Investigational Product Management
- SOP-09 Safety Reporting (AEs, SAEs, IRB-Reportable Events, Pregnancy)
- SOP-12 Privacy, Electronic Systems and Record Retention
- SOP-13 Monitoring, Audits and Inspections
- SOP-14 Quality Control and Quality Review
- SOP-15 Study Closeout
- SOP-M1 Service Providers and Vendors
- SOP-M2 Feasibility, Contracts, Budgets and Research Billing
7. References
| Reference | Title |
|---|---|
| 21 CFR 312.2, 312.3 | IND applicability and exemptions; definitions |
| 21 CFR 312.6, 312.7 | Labeling; promotion of investigational drugs |
| 21 CFR 312.30 to 312.33 | Protocol amendments; information amendments; IND safety reports; annual reports |
| 21 CFR 312.38, 312.40, 312.45 | Withdrawal; when an IND goes into effect; inactive status |
| 21 CFR 312.50 to 312.59 | Responsibilities of sponsors |
| 21 CFR 312.66 | Assurance of IRB review |
| 21 CFR 812.2, 812.3, 812.5, 812.7 | Device applicability, definitions, labeling, prohibitions |
| 21 CFR 812.20 to 812.47 | IDE application, approval and sponsor responsibilities |
| 21 CFR 812.140, 812.150 | Device records and reports |
| 21 CFR 50, 54, 56 | Consent; financial disclosure; IRBs |
| 42 CFR 11 | Clinical Trials Registration and Results Information Submission |
| ICH E6(R3) Annex 1, sections 3 and 4 | Sponsor; data governance |
| FDA Guidance (2013) | Investigational New Drug Applications (INDs): Determining Whether Human Research Studies Can Be Conducted Without an IND |
| FDA Draft Guidance (2015) | IND Applications Prepared and Submitted by Sponsor-Investigators |
| FDA Guidance (December 2025) | Sponsor Responsibilities: Safety Reporting Requirements and Safety Assessment for IND and Bioavailability/Bioequivalence Studies |
| FDA Guidance (December 2025) | Investigator Responsibilities: Safety Reporting for Investigational Drugs and Devices |
| FDA Guidance (2013) | Oversight of Clinical Investigations: A Risk-Based Approach to Monitoring |
| FDA Information Sheet Guidance (2006) | Significant Risk and Nonsignificant Risk Medical Device Studies |
| FDA Compliance Programs 7348.811 and 7348.810 | Bioresearch Monitoring: clinical investigators and sponsor-investigators; sponsors, CROs and monitors |
Independent Site SOP Library. Licensed CC BY-NC 4.0 by the American Institute for Medical Research (AIMR), with added permission for any site's internal use (license terms). Not legal advice: each adopting site confirms state law, IRB and sponsor requirements with its own counsel and owns every step it approves.