VISUAL AID #1: "IND Submission Components" Checklist Infographic
Format: A3-size poster or digital printable PDF
Visual Style: Vertical flowchart with checkboxes
Content Layout:
═══════════════════════════════════════════════════════════════
✓ IND APPLICATION COMPONENT CHECKLIST
21 CFR 312.23 - Complete Submission Sequence
═══════════════════════════════════════════════════════════════
COMPONENT 1: FORM FDA-1571 (COVER SHEET)
├─ Sponsor name, address, contact info
├─ Monitoring person (name/title)
├─ Safety review person (name/title)
├─ Clinical phase(s)
└─ ✓ Commitment signatures
COMPONENT 2: TABLE OF CONTENTS
└─ Detailed index of all materials
COMPONENT 3: INTRODUCTORY STATEMENT & GENERAL INVESTIGATIONAL PLAN
├─ Drug name, class, structure
├─ Formulation & route of administration
├─ Previous human experience (US & foreign)
├─ Objectives & planned duration
└─ Prior withdrawal history (if applicable)
COMPONENT 4: INVESTIGATOR'S BROCHURE (IB)
├─ Physical/chemical/pharmaceutical properties
├─ Pharmacology & ADME
├─ Toxicology (acute, subacute, chronic)
├─ Previous clinical experience
└─ ✓ Must be updated with significant new info
COMPONENT 5: CLINICAL PROTOCOL(s)
├─ Study objectives & design
├─ Investigator qualifications
├─ Inclusion/exclusion criteria
├─ Protocol procedures & duration
├─ Adverse event reporting plan
└─ Statistical considerations
COMPONENT 6: CHEMISTRY, MANUFACTURING & CONTROLS (CMC)
├─ Drug substance description & synthesis
├─ Manufacturing & analytical methods
├─ Drug product description & controls
├─ Stability data
└─ Environmental assessment or categorical exclusion claim
COMPONENT 7: PHARMACOLOGY & TOXICOLOGY
├─ Pharmacology studies (ADME, pharmacological effects)
├─ Acute toxicity (≥2 species, ≥1 non-rodent)
├─ Repeat-dose toxicity (≥1 species, duration ≥proposed clinical duration)
├─ Reproduction/developmental toxicity (if reproductive-age subjects)
├─ Genotoxicity
└─ Carcinogenicity (if chronic use proposed)
COMPONENT 8: PREVIOUS HUMAN EXPERIENCE
├─ Prior US investigations
├─ Prior foreign investigations
├─ Marketing history (if any)
└─ Safety data compilation
COMPONENT 9 (IF APPLICABLE): CLINICAL MICROBIOLOGY
└─ For anti-infective agents only
COMPONENT 10 (IF APPLICABLE): CASE REPORT FORMS (CRFs)
└─ Specimen CRFs for Phase 2/3 studies
═══════════════════════════════════════════════════════════════
⚠️ CRITICAL: All components must be COMPLETE and IN ORDER
If ANY component is missing or out of sequence:
→ FDA declares application INCOMPLETE
→ 30-day clock RESTARTS upon corrected resubmission
═══════════════════════════════════════════════════════════════
Design Notes:
- Use checkboxes to encourage learners to verify completeness
- Color-code Phase 1-specific vs. Phase 2/3-specific requirements
- Include small regulatory citations (21 CFR 312.23(a)(#))
- Add tip box: "Most commonly forgotten: Environmental Assessment documentation"
VISUAL AID #2: "Safety Reporting Timelines" Visual Decision Tree
Format: Flowchart diagram (landscape, fits on one page)
Visual Style: Diamond decision boxes with "YES/NO" branches leading to timelines
Content:
EVENT OCCURS
|
Does sponsor BECOME AWARE?
/ \
NO YES
| |
NO REPORT Sponsor Awareness Clock ➡️ START
|
Is event FATAL or LIFE-THREATENING?
/ \
YES ✓ NO
| |
Is it UNEXPECTED? Is event SERIOUS?
/ \ / \
YES ✓ NO YES ✓ NO
| | | |
Is it a Include Is it No expedited
suspected in annual UNEXPECTED? report
adverse report / \
reaction? YES ✓ NO
/ \ | |
YES ✓ NO Is it a suspected
| | adverse reaction?
| | / \
| | YES ✓ NO
| | | |
| No report REPORT TYPE → ANNUAL
| DETERMINED REPORT
| |
REPORT TYPE ├─ 15-DAY WRITTEN REPORT
DETERMINED │ (Due within 15 calendar days
| │ of sponsor awareness)
| │
➡️ 7-DAY REPORT └─ If LIFE-THREATENING/FATAL:
(Phone + Written Follow-up) Phone call within 7 days
Written within 15 days
TIMELINES USE CALENDAR DAYS (weekends & holidays COUNT)
PHONE CALL DEADLINE: 7 calendar days from awareness
WRITTEN REPORT DEADLINE: 15 calendar days from awareness
FOLLOW-UP REPORT: 15 calendar days from obtaining new info
ANNUAL REPORT: Within 60 days of IND anniversary
═══════════════════════════════════════════════════════════════
KEY DECISION POINTS:
1. Unexpected? Check Investigator's Brochure
2. Serious? Must meet SAE definition (death, life-threatening,
hospitalization, disability, congenital anomaly, important
medical event)
3. Suspected adverse reaction? Reasonable possibility of
relationship to study drug
═══════════════════════════════════════════════════════════════
Design Notes:
- Use bright colors: RED for 7-day fast-track, YELLOW for 15-day, BLUE for annual
- Include clock icons next to timelines
- Add small "CFR citation" boxes (21 CFR 312.32(c))
- Consider printing in color for maximum visual impact
- Include note: "This applies to INDs. IDEs use WORKING days, not calendar days"
VISUAL AID #3: "Sponsor vs. Investigator Responsibilities" Matrix Poster
Format: Two-column comparison table, poster size (24" x 36" or 8.5" x 11")
Visual Style: Responsibility matrix with clear responsibility ownership
Content:
┌─────────────────────────────────┬─────────────────────────────────┐
│ SPONSOR RESPONSIBILITIES │ INVESTIGATOR RESPONSIBILITIES │
│ (21 CFR 312.50-57) │ (21 CFR 312.60-70) │
├─────────────────────────────────┼─────────────────────────────────┤
│ │ │
│ ✓ Select QUALIFIED │ ✓ Conduct study PER PROTOCOL │
│ investigators │ (or emergency deviations) │
│ (312.53(a)) │ │
│ │ ✓ Ensure IRB REVIEW & │
│ ✓ Provide updated │ APPROVAL before enrollment │
│ Investigator's Brochure │ (312.60, 312.66) │
│ (312.55) │ │
│ │ ✓ Obtain INFORMED CONSENT │
│ ✓ Ensure investigators │ (312.60, 21 CFR Part 50) │
│ are qualified via │ │
│ Form 1572 (312.53(c)) │ ✓ IMMEDIATELY REPORT adverse │
│ │ events to sponsor │
│ ✓ Monitor investigations │ (312.64) │
│ to ensure protocol adherence │ │
│ (312.56) │ ✓ Maintain DRUG │
│ │ ACCOUNTABILITY records │
│ ✓ Report Safety Events to FDA │ (312.61) │
│ - 7-day (fatal/life-threat) │ │
│ - 15-day (serious/unexpected) │ ✓ Maintain ACCURATE RECORDS │
│ - Annual reports │ (source docs, CRFs) │
│ (312.32) │ (312.62) │
│ │ │
│ ✓ Submit IND AMENDMENTS for │ ✓ Assure COMPLIANCE with │
│ significant changes │ informed consent & IRB │
│ (312.30) │ requirements │
│ │ │
│ ✓ Maintain RECORDS for │ ✓ Allow sponsor MONITORING │
│ 2 years post-approval/ │ and FDA INSPECTION │
│ discontinuation │ (312.68) │
│ (312.57) │ │
│ │ ✓ Complete & sign FDA Form │
│ ✓ Ensure Quality Assurance │ 1572 (commitment to comply) │
│ & Data Integrity │ (312.53(c)) │
│ │ │
│ ✓ REMAIN ULTIMATELY │ ✓ Report FINANCIAL INTERESTS │
│ ACCOUNTABLE (cannot │ (potential conflicts) │
│ transfer accountability via │ │
│ CRO delegation) │ ✓ Maintain INVESTIGATOR │
│ │ records 2 years post-approval │
│ │ (312.62(b)) │
│ │ │
└─────────────────────────────────┴─────────────────────────────────┘
SHARED RESPONSIBILITIES:
• Protecting human subjects (both have obligations under different regulations)
• Safety assessment (sponsor determines reporting; investigator identifies events)
• Protocol compliance (sponsor oversees; investigator implements)
• Record-keeping (each maintains their own records)
═══════════════════════════════════════════════════════════════
CRITICAL PRINCIPLE:
CROs can PERFORM work on behalf of sponsors, but CANNOT transfer
regulatory accountability. Sponsor remains liable for inadequate
monitoring, data integrity issues, and safety reporting failures.
═══════════════════════════════════════════════════════════════
Design Notes:
- Use distinct colors (blue for sponsor, green for investigator)
- Add CFR citation next to each responsibility
- Include callout box emphasizing CRO accountability principle
- Consider laminating for durability/reusability
- Add QR code linking to full 312.50-312.70 regulations
VISUAL AID #4: "Form FDA-1572 Obligations" Annotated Guide
Format: Digital PDF or printed handout with form sections annotated
Visual Style: Form sections with margin annotations and color-highlighting
Content Layout:
═══════════════════════════════════════════════════════════════
FDA FORM 1572: Investigator's Commitment and Qualifications
═══════════════════════════════════════════════════════════════
PART A: INVESTIGATOR INFORMATION
┌─ Field: Name, Address, Phone ┐
├─ PURPOSE: FDA to communicate directly │
├─ REQUIREMENT: Must be complete and current │
└─ COMPLIANCE TIP: Update if you relocate ┘
┌─ Field: Qualifications (CV/Resume) ┐
├─ PURPOSE: Demonstrate training & experience │
│ relevant to the investigation │
├─ REQUIREMENT: Required per 21 CFR 312.53(a) │
├─ SOCRA TEST: Expect questions on qualification│
│ verification │
└─ COMPLIANCE TIP: Attach current CV; use ┘
specific clinical experience
═══════════════════════════════════════════════════════════════
PART B: COMMITMENTS (KEY FOR SOCRA EXAM)
┌─────────────────────────────────────────────────────────────┐
│ COMMITMENT #1: Personal Conduct │
│ "I will personally conduct or supervise the │
│ investigator's investigational plan." │
├─ MEANING: You cannot delegate your responsibilities │
├─ VIOLATION: If you allow untrained staff to conduct study │
└─ CONSEQUENCE: FDA can cite both you and sponsor │
├─ CFR: 21 CFR 312.60 │
└─ EXAM Q: "What is an investigator committing to?" │
┌─────────────────────────────────────────────────────────────┐
│ COMMITMENT #2: Protocol Adherence │
│ "I will conduct the investigation in accordance with │
│ the protocol." │
├─ MEANING: Follow the approved protocol as written │
├─ EXCEPTION: Emergency deviations to protect safety are │
│ permitted but must be reported immediately │
├─ VIOLATION: Implementing non-emergency changes without │
│ IRB approval = Form 1572 violation │
└─ EXAM Q: "Can an investigator deviate from protocol?" │
┌─────────────────────────────────────────────────────────────┐
│ COMMITMENT #3: IRB Review & Approval │
│ "I will ensure that the Institutional Review Board (IRB) │
│ has reviewed and approved the investigational protocol." │
├─ MEANING: IRB must approve BEFORE first subject enrollment │
├─ REQUIREMENT: Ongoing IRB approval must be maintained │
├─ VIOLATION: Enrolling subjects without active IRB approval │
│ = serious compliance violation │
└─ EXAM Q: "Can a study start before IRB approval?" │
┌─────────────────────────────────────────────────────────────┐
│ COMMITMENT #4: Informed Consent │
│ "I will ensure that all subjects provide informed │
│ consent in accordance with 21 CFR Part 50." │
├─ MEANING: Obtain written IC from subjects before research │
├─ YOUR JOB: Personally obtain consent (or authorized staff) │
├─ DOCUMENTATION: Signed consent forms required │
└─ EXAM Q: "Who obtains informed consent?" │
┌─────────────────────────────────────────────────────────────┐
│ COMMITMENT #5: Adverse Event Reporting │
│ "I will immediately report to the sponsor adverse events, │
│ particularly serious and unexpected adverse reactions." │
├─ MEANING: All AEs reported to sponsor immediately │
├─ TIMELINE: SAEs especially serious/unexpected = urgent │
├─ DOCUMENTATION: Written report to sponsor per protocol │
└─ EXAM Q: "How quickly must adverse events be reported?" │
┌─────────────────────────────────────────────────────────────┐
│ COMMITMENT #6: Drug Accountability │
│ "I will take responsibility for the investigational drug │
│ supplied to me, ensuring its proper storage, security, │
│ and use." │
├─ MEANING: Account for all drug received, used, destroyed │
├─ RECORDS: Maintain drug logs with receipt/destruction │
├─ VIOLATIONS: Missing drug, improper storage = DEA/FDA issue│
└─ EXAM Q: "What must be documented for drug accountability?"│
┌─────────────────────────────────────────────────────────────┐
│ COMMITMENT #7: Record Maintenance & Inspection │
│ "I will maintain adequate and accurate case records that │
│ are available for FDA inspection." │
├─ MEANING: Source documents support all case report entries │
├─ RETENTION: Keep records for 2 years post-approval/ │
│ discontinuation │
├─ ACCESS: Allow monitor, sponsor, and FDA inspectors access │
└─ EXAM Q: "How long must an investigator keep study records?│
Design Notes:
- Use color highlighting for different commitment types
- Include small "WARNING" boxes for common violations
- Add "EXAM ALERT" callouts next to SOCRA-tested commitments
- Include hyperlinks (if digital) to full CFR text
- Suggest laminating for reference during study sessions
VISUAL AID #5: "7-Day vs 15-Day Reports" Comparison Chart
Format: Side-by-side comparison chart, poster size
Content:
┌──────────────────────────────────┬──────────────────────────────────┐
│ 7-DAY REPORT CRITERIA │ 15-DAY REPORT CRITERIA │
│ (Immediate Escalation Path) │ (Standard Expedited Path) │
├──────────────────────────────────┼──────────────────────────────────┤
│ │ │
│ TRIGGER EVENT: │ TRIGGER EVENT: │
│ ✓ FATAL or LIFE-THREATENING │ ✓ SERIOUS (but not life- │
│ + UNEXPECTED │ threatening/fatal) │
│ + SUSPECTED adverse reaction │ + UNEXPECTED │
│ │ + SUSPECTED adverse reaction │
│ DEFINITION: │ DEFINITION: │
│ • Fatal = death from event │ • Serious = meets one SAE │
│ • Life-threatening = immediate │ criterion: │
│ risk of death if treatment not │ - Hospitalization │
│ received │ - Disability/incapacity │
│ │ - Birth defect │
│ │ - Important medical event │
├──────────────────────────────────┼──────────────────────────────────┤
│ │ │
│ TIMELINE: │ TIMELINE: │
│ ➡️ PHONE CALL to FDA: │ ➡️ WRITTEN REPORT to FDA: │
│ Within 7 CALENDAR DAYS │ Within 15 CALENDAR DAYS │
│ │ │
│ ➡️ WRITTEN FOLLOW-UP: │ ➡️ NO separate phone call │
│ Within 15 CALENDAR DAYS │ (written only) │
│ of initial awareness │ │
├──────────────────────────────────┼──────────────────────────────────┤
│ │ │
│ EXAMPLES: │ EXAMPLES: │
│ • Patient dies from study drug │ • Subject hospitalized for │
│ (unexpected, not in IB) │ serious infection (not in IB) │
│ • Subject suffers cardiac arrest │ • Subject develops unexpectedly │
│ thought to be drug-related │ severe liver injury requiring │
│ (unexpected, not in IB) │ admission │
│ • Life-threatening anaphylaxis │ • Unexpectedly severe allergic │
│ (unexpected reaction to drug) │ reaction requiring │
│ │ hospitalization │
│ │ │
├──────────────────────────────────┼──────────────────────────────────┤
│ │ │
│ STARTER: │ STARTER: │
│ Event + Unexpected + Related + │ Event + Unexpected + Related + │
│ (Fatal OR Life-threatening) │ (Serious & NOT life-threatening) │
│ │ │
│ = 7-DAY REPORT REQUIRED │ = 15-DAY REPORT REQUIRED │
│ │ │
├──────────────────────────────────┼──────────────────────────────────┤
│ │ │
│ WHEN TO USE: │ WHEN TO USE: │
│ RARE (most expedited reports │ COMMON (majority of expedited │
│ are 15-day; 7-day reserved for │ reports; covers most serious │
│ most urgent safety signals) │ unexpected events) │
│ │ │
└──────────────────────────────────┴──────────────────────────────────┘
KEY DISTINCTION FOR SOCRA EXAM:
════════════════════════════════════════════════════════════════════════
Is the event EXPECTED (listed in Investigator's Brochure)?
|
┌───────────┴───────────┐
YES NO (UNEXPECTED)
| |
NO EXPEDITED Continue assessing
REPORT REQUIRED for 7-day or 15-day
| |
Include in Is it LIFE-THREATENING?
ANNUAL REPORT / \
YES NO
| |
7-DAY REPORT Is it SERIOUS?
REQUIRED / \
YES NO
| |
15-DAY ANNUAL
REPORT REPORT
════════════════════════════════════════════════════════════════════════
REGULATORY CITATIONS:
21 CFR 312.32(c)(1)(i) — 7-day reports
21 CFR 312.32(c)(1)(ii) — 7-day written follow-up
21 CFR 312.32(c)(2) — 15-day reports
21 CFR 312.32(c) — Overview of all safety reporting requirements
Design Notes:
- Use traffic light colors: RED for 7-day (urgent), YELLOW for 15-day, GREEN for annual
- Include timeline visual (clock icons) showing day-counting examples
- Add small "⚠️ COMMON MISTAKES:" boxes
- Consider creating a digital interactive version (clickable decision tree)
STUDY TOOL #1: 70-Card Flashcard Set
Card Format: 3" x 5" index cards or digital flashcard app (Anki, Quizlet)
Card Distribution:
FLASHCARD SET: IND Regulations & Responsibilities
Total Cards: 70
SECTION A: IND SUBMISSION COMPONENTS (12 cards)
─────────────────────────────────
Card A1: Q: "What is Component 1 of the IND application?"
A: Form FDA-1571 (Cover Sheet) with sponsor contact,
commitment signatures, phase identification
CFR: 312.23(a)(1)
Card A2: Q: "What is the purpose of the Investigator's Brochure?"
A: Provides investigators with scientific/safety info
about the drug (pharmacology, toxicology, human data)
to make informed decisions about participation
CFR: 312.55
Card A3: Q: "When must CMC (Chemistry, Manuf., & Controls) be most detailed?"
A: Phase 3 - must be comprehensive, similar to NDA level
Phase 1 can be limited; Phase 2 intermediate
CFR: 312.23(a)(7)
Card A4: Q: "What is the correct sequence of these components:
Protocol, CMC, IB, Intro Statement?"
A: Intro Statement → IB → Protocol → CMC
(Follows 312.23(a)(3-8) order)
CFR: 312.23
Card A5: Q: "What must be done if an IND is incomplete?"
A: FDA issues deficiency letter; sponsor resubmits;
NEW 30-day clock STARTS from resubmission date
CFR: 312.40(b)
[Continue with A6-A12 covering: Environmental Assessment,
Pharm/Tox requirements, Protocol detail requirements, etc.]
───────────────────────────────────
SECTION B: SPONSOR RESPONSIBILITIES (18 cards)
─────────────────────────────────
Card B1: Q: "Per 312.53(a), what is the sponsor's key
responsibility regarding investigators?"
A: Select QUALIFIED investigators and take measures
to ensure they are qualified and will conduct
investigation per protocol
CFR: 312.53(a)
Card B2: Q: "Can a sponsor transfer accountability to a CRO?"
A: NO - Sponsor can hire CRO to DO work but retains
ultimate regulatory accountability to FDA
CFR: 312.50
Card B3: Q: "What information must sponsors provide to
investigators per 312.55?"
A: Updated Investigator's Brochure containing safety,
pharmacology, and toxicology data before study begins
and whenever new significant info emerges
CFR: 312.55
Card B4: Q: "What is the sponsor's monitoring obligation per
312.56?"
A: Monitor as frequently as necessary to ensure subject
safety, data integrity, and protocol adherence
(Risk-based frequency, not prescriptive)
CFR: 312.56
Card B5: Q: "How long must sponsors retain IND records?"
A: 2 years after the LATER of: (1) Marketing approval,
or (2) Investigation discontinuation
CFR: 312.57(b)
[Continue with B6-B18 covering: IND amendments, CRO oversight,
Data integrity, Quality assurance, Safety assessment, etc.]
───────────────────────────────────
SECTION C: INVESTIGATOR RESPONSIBILITIES (14 cards)
─────────────────────────────────
Card C1: Q: "What is an investigator committing to on Form 1572?"
A: Conducting investigation per protocol, ensuring IRB
approval, obtaining informed consent, immediately
reporting adverse events, maintaining drug
accountability, maintaining records
CFR: 312.53(c), 312.60
Card C2: Q: "Must an investigator conduct the study in person,
or can they delegate to staff?"
A: Investigator personally conducts or DIRECTLY SUPERVISES.
Cannot delegate to untrained staff
CFR: 312.60
Card C3: Q: "What is the investigator's deadline for reporting
a serious adverse event to the sponsor?"
A: IMMEDIATELY, especially for serious/unexpected events;
exact timeline depends on event severity and
investigator's clinical assessment
CFR: 312.64
Card C4: Q: "Per 312.61, what must investigators do with
investigational drug?"
A: Maintain complete accountability (received, used,
destroyed, returned); maintain drug logs; account
for ALL drug
CFR: 312.61
Card C5: Q: "How long must investigators keep study records?"
A: 2 years following the LATER of: (1) Marketing approval,
or (2) Investigation discontinuation
(Parallels sponsor retention per 312.57/312.62)
CFR: 312.62(b)
[Continue with C6-C14 covering: IRB coordination, Protocol
deviation procedures, Informed consent, Source documentation,
Investigator qualifications verification, Financial disclosure, etc.]
───────────────────────────────────
SECTION D: SAFETY REPORTING TIMELINES (16 cards)
─────────────────────────────────
Card D1: Q: "What is a 7-day report trigger per 312.32?"
A: Event that is FATAL or LIFE-THREATENING + UNEXPECTED +
SUSPECTED adverse reaction (related to drug)
CFR: 312.32(c)(1)(i)
Card D2: Q: "What is a 15-day report trigger per 312.32?"
A: Event that is SERIOUS (not fatal/life-threatening) +
UNEXPECTED + SUSPECTED adverse reaction
CFR: 312.32(c)(2)
Card D3: Q: "When calculating a 7-day safety report timeline,
are weekends included?"
A: YES - 312.32 uses CALENDAR DAYS (not working days).
Weekends and holidays COUNT toward the 7-day deadline
CFR: 312.32(c)
Card D4: Q: "An event is serious and suspected related but LISTED
in the Investigator's Brochure. What report is required?"
A: NO expedited (7-day/15-day) report. Event is EXPECTED,
so include in ANNUAL REPORT only
CFR: 312.32(c)
Card D5: Q: "What is the difference between 'severity' and
'seriousness' in safety reporting?"
A: Severity = intensity of symptom (mild/moderate/severe)
Seriousness = outcome (hospitalization, disability, death)
A severe headache can be not serious if it resolves
CFR: 312.32(a); ICH GCP E2A
Card D6: Q: "If a 7-day phone report is submitted on Day 3, when
is the written follow-up due?"
A: Within 15 CALENDAR DAYS of sponsor's INITIAL AWARENESS
(not 15 days from the phone call date)
CFR: 312.32(c)(1)(ii)
Card D7: Q: "Must investigators report adverse events directly to
FDA or to the sponsor?"
A: To the SPONSOR. The sponsor then determines if it meets
FDA reporting criteria and reports to FDA per 312.32
CFR: 312.64
Card D8: Q: "When new information about an already-reported event
becomes available, what must the sponsor do?"
A: Submit a FOLLOW-UP REPORT within 15 days of obtaining
the new information, even if already reported
CFR: 312.32(e)
Card D9: Q: "For the purposes of determining a safety report timeline,
when does 'sponsor awareness' START?"
A: When sponsor FIRST LEARNS OF the event (not from event date,
hospitalization date, or investigator awareness date)
CFR: 312.32(c)
Card D10: Q: "An event occurs in a foreign study site. Does the
US sponsor have to report to FDA?"
A: YES - Safety info about INDs must be reported regardless
of geographic source per 312.32(f).
Timeline starts from when US sponsor BECOMES AWARE
CFR: 312.32(f)
[Continue with D11-D16 covering: Annual report timelines, When NOT
to report expedited, Causality assessment basics, IND amendment
triggers for emerging safety signals, etc.]
───────────────────────────────────
SECTION E: KEY CFR CITATIONS & DEFINITIONS (10 cards)
─────────────────────────────────
Card E1: Q: "What is the purpose of the 30-day rule per 312.40(a)?"
A: IND becomes effective 30 days after FDA RECEIPT unless
placed on clinical hold, allowing FDA to review for safety/
adequacy before human studies start
CFR: 312.40(a)
Card E2: Q: "What is a 'clinical hold' per 312.42?"
A: FDA action to halt clinical investigations due to safety
concerns, inadequate data, or compliance violations.
Sponsor can request reconsideration with additional data
CFR: 312.42
Card E3: Q: "What defines a serious adverse event (SAE)?"
A: Event resulting in: death, life-threatening, hospitalization,
persistent disability, birth defect, or important medical
event (requires intervention to prevent permanent harm)
CFR: 312.32(a); ICH GCP E2A
Card E4: Q: "What is 'unexpected' in safety reporting context?"
A: Adverse event NOT consistent in nature, severity, or
specificity with information in current Investigator's
Brochure
CFR: 312.32(c); ICH GCP E6(R3)
Card E5: Q: "What constitutes adequate drug accountability per 312.61?"
A: Complete records of receipt, use, return, destruction
of investigational drug; ability to account for 100% of
drug supplied
CFR: 312.61
[Continue with E6-E10 covering: Informed consent requirements (Part 50
basics), IRB approval requirement, Financial disclosure, Data integrity,
Source documentation]
Usage Recommendations:
- Review 10 cards per study session (daily)
- Mix sections (don't study all IND requirements, then all safety)
- Use spaced repetition technique (review cards 1, 3, 7, 14, 30 days after first learning)
- Flag difficult cards for extra review
- Create self-explanation: read Q, try to answer before flipping, review explanation
STUDY TOOL #2: Safety Reporting Timeline Calculator
Format: Excel spreadsheet or interactive web tool
Functionality:
═══════════════════════════════════════════════════════════════
SAFETY REPORTING TIMELINE CALCULATOR
21 CFR 312.32 Compliance Tool
═══════════════════════════════════════════════════════════════
INPUT SECTION:
─────────────────────────────────
[Field 1] Select Event Severity:
○ Fatal
○ Life-threatening
○ Serious (hospitalization, disability, etc.)
○ Other adverse event
[Field 2] Select Event Expectedness:
○ Expected (listed in Investigator's Brochure)
○ Unexpected (not listed or more severe than listed)
[Field 3] Select Relationship Assessment:
○ Suspected adverse reaction (reasonable possibility)
○ Unlikely related / Unrelated
○ Unknown
[Field 4] Enter Date Sponsor Became Aware:
[___/___/___] MM/DD/YYYY
[Field 5] Calculate Button: [CALCULATE DUE DATES]
─────────────────────────────────
OUTPUT SECTION:
─────────────────────────────────
REPORT TYPE DETERMINATION:
┌─ Report Type: [7-DAY REPORT]
├─ Report Category: Phone call + written follow-up
└─ Urgency: EXPEDITED
DUE DATES:
┌─ Phone Call Deadline: [DATE]
│ (Within 7 calendar days of awareness)
│ ✓ Click to add to calendar
├─ Written Report Deadline: [DATE]
│ (Within 15 calendar days of awareness)
│ ✓ Click to add to calendar
└─ Days Until Deadline: [#] days remaining
FOLLOW-UP REPORTING:
┌─ Follow-up Deadline IF new info received: [+15 days from new info]
└─ Status: [TRACKING ACTIVE]
REGULATORY CITATION:
└─ 21 CFR 312.32(c)(1)(i)
ERROR CHECKING:
└─ ✓ Entry appears compliant
(No issues flagged)
EXPORT/PRINT OPTIONS:
┌─ [Export to PDF]
├─ [Print Report]
└─ [Email Reminder]
═══════════════════════════════════════════════════════════════
EXAMPLE SCENARIO BUILT-IN:
Patient hospitalized for infection on Jan 10
Sponsor learns Jan 18 (unexpected, suspected related)
→ Tool determines: 15-DAY REPORT REQUIRED
→ Due Date: February 2
→ Days Remaining: [X] (calculates from current date)
Design Notes:
- Include "scenario examples" button showing 5 pre-built scenarios
- Add "uncertainty mode" for borderline cases
- Include tooltip explanations for each field
- Create printable summary with CFR citations
STUDY TOOL #3: IND Amendment Type Decision Tree
Format: Flowchart diagram or interactive online tool
Content:
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IND AMENDMENT TYPE DECISION TREE
21 CFR 312.30 - When & How to Amend an IND
═══════════════════════════════════════════════════════════════
Does the change involve an INVESTIGATIONAL PLAN
(protocol, objectives, population)?
│
├─ YES → Is it a SIGNIFICANT change?
│ │
│ ├─ YES → PROTOCOL AMENDMENT required (312.30(b))
│ │ Submit to FDA for review
│ │ Examples:
│ │ • Change primary endpoint
│ │ • Increase max subject population
│ │ • Change route of administration
│ │ • Add new patient population
│ │
│ └─ NO → May be MINOR protocol change
│ Submit as IND amendment per 312.30(a)
│ (Informational, may not require FDA approval)
│
└─ NO → Is the change SAFETY-RELATED?
│
├─ YES → Significant new safety info?
│ │
│ ├─ YES → Form 1571 IND AMENDMENT (312.30(a)(1))
│ │ Alert FDA immediately
│ │ Update all investigators
│ │ Examples:
│ │ • Emerging safety signal
│ │ • New animal toxicology data
│ │ • Increased adverse event incidence
│ │
│ └─ NO → Include in next annual report
│ (No separate amendment needed)
│
└─ NO → Is the change INVESTIGATOR-RELATED?
│
├─ YES → Adding new investigator?
│ │
│ ├─ YES → Submit IND amendment to add
│ │ (Form 1571 with new 1572)
│ │ Ensure new 1572 submitted
│ │ before investigator starts
│ │
│ └─ NO → Investigator discontinuation
│ Note in next annual report
│
└─ NO → Is the change ADMINISTRATIVE?
│
├─ YES → Sponsor phone number change?
│ Contact person change?
│ → Notify FDA (may not need formal amendment)
│
└─ NO → Unclear?
Contact FDA for guidance
(Use pre-submission meeting)
═══════════════════════════════════════════════════════════════
AMENDMENT SUBMISSION TYPES:
1. PROTOCOL AMENDMENT (312.30(b))
• Changes to study design, objectives, populations
• May require FDA review/approval before implementation
• Not all protocol amendments can be implemented immediately
2. IND AMENDMENT - Form 1571 (312.30(a))
• Changes to sponsor info, investigator additions
• Significant safety information
• May be informational (no FDA approval needed)
3. ANNUAL REPORT - Form 1571 (312.32(d))
• Comprehensive safety summary
• Non-urgent updates
• Due within 60 days of IND anniversary
4. IND SAFETY REPORT - Form 1574 (312.32(c))
• Expedited reporting for serious adverse events
• 7-day or 15-day timeline
• Separate from amendments
═══════════════════════════════════════════════════════════════
SOCRA EXAM FOCUS: Questions often test ability to identify
which amendment type is required for a given scenario.
Design Notes:
- Create interactive version with clickable decision points
- Include color-coding for amendment types
- Add time-to-implement estimates for each type
- Include examples of what DOES/DOESN'T need amendment
END OF VISUAL LEARNING AIDS & STUDY TOOLS
All materials formatted for printing, digital display, or online learning platforms. Recommend combining with interactive quiz software for maximum engagement.
MATERIALS SUMMARY FOR PRODUCTION:
| Visual Aid | Format | Size | Purpose |
|---|---|---|---|
| 1. IND Components Checklist | Poster/PDF | A3/Letter | Organizational reference |
| 2. Safety Reporting Timeline | Flowchart | Letter | Decision-making tool |
| 3. Sponsor vs. Investigator | Matrix | Letter | Responsibility tracking |
| 4. Form 1572 Obligations | Annotated guide | Letter | Compliance reference |
| 5. 7-Day vs 15-Day | Comparison | Letter | Timeline reference |
Total Flashcards: 70 cards (print on 3x5 index cards or digital app) Timeline Calculator: 1 Excel/web tool (interactive) Amendment Tree: 1 flowchart (printable or interactive)