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Kellie Bodeker, MSHS CCRCRegulatory Manager Department of Radiation OncologyThe University of Iowa

Research…

Research…

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Research…

Research…

Research…

Considerations for an IND(pre & post approval)

Staff & resources required

Considerations for sharing

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Investigational New Drugs

Form 1571

Table of contents

Introductory statement & general investigational plan

Protocol

Chemistry, manufacturing & control

Pharmacology, toxicology

Previous human experience

Additional information

IND Exemptions

Lawfully marketed

Not a well-controlled study for a new indication or labeling change

Not to support a change in advertising

Not intended to promote or commercialize the product

IND Exemptions

Does not involve a:

Route of administration,

Dose,

Patient population, or,

Other factor

…that significantly increases the risk, or decreases the acceptability of the risk.

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Binders…

…or binders

Pre-approval considerations

Who is selling the drug

Designated representative

Generalized plan

Serial numbers

The FDA will reply

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Post-approval considerations

Reasonably safe to proceed

Modify the protocol as needed

IRB approval then resend to FDA

Protocols

Protocol is required for IND application

Criteria for the protocol are specified

Protocol should harmonize with IRB application

Tracked changes and clean versions attached to the IRB application and submitted to FDA.

Key dates

When the 1572 was signed

First subject was screened

First subject signed consent

First administration of test article

Last follow-up of any study subject

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Deviations

Date of deviation

Reason

Notification of investigator

Report to the IRB

Informed consent

Who, how, where

Consent prior to any study procedures

Any IRB conditions or stipulations

ALCOA

Attributable

Legible

Contemporaneous

Original

Accurate

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Delegations…

Financial disclosure

21 CFR 54.4

21CFR§11

Determine the scope and document it

Identify how the data are collected

Identify security and who has access

Obtain a part 11 compliance certificate if possible

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Test article control

Use of an investigational services pharmacy can provide invaluable assistance but does not absolve a sponsor-investigator of responsibilities.

Monitoring

Most common deficiency (483 & warning letters)

Monitor appointed by investigator

Qualifications vague per CFR

Animal studies

Mice are people, too

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Adverse events

Lab findings may need to be reported as serious adverse events.

Annual reports

Once a year, like it or not, the sponsor-investigator has to become painfully familiar with every aspect of the trial.

So… there’s this guy…

Yes, INDs can be “shared”

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Qualified investigator

21 CFR§312.53

SOP for selection

Training

Experience

Obtain CV

Current license(s)

Signed 1572

Define the relationship

Regulatory

Data

Clinical nursing

Discipline

Ethics

Fraud

Paperwork

1571

Protocol

1572

CV of investigator

Investigator’s brochure

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More paperwork

Site binders

Site initiation visit

SOPs

Financial disclosure

Compliance programs

Sponsors and Monitors

Clinical Investigators

http://www.fda.gov/ICECI/ComplianceManuals/ComplianceProgramManual/ucm255614.htm

Compliance programs

http://www.fda.gov/ICECI/ComplianceManuals/ComplianceProgramManual/ucm255614.htm

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Site binders

Historical protocols

Historical consents

IRB approvals

Log of FDA submissions

Reporting structure

Responsibilities

Opening the study

IRB approval

Site initiation

Continuing the study

Communication

Continuing education

Modifications

Reports to sponsor

Updating binder

Annual reports

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Monitoring

Essential

Consider strategy

Regulatory v. clinical

Adverse events

Recordable v. reportable Assignment Collection strategy Analysis

Data and safety monitoring

DSMB External Internal SOP Guidance

documents

http://www.fda.gov/OHRMS/DOCKETS/98fr/01d-0489-gdl0003.pdf

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Closing the study

Notify FDA

Notify investigators

Notify IRB

Retain records

In summary

INDs are sometimes too easy to obtain

Realize you shift from investigator initiated to more of an industry-sponsored documentation technique

Prepare binders ahead of time to reduce stress during an FDA audit

Only put in an SOP what you will actually do, not what you really want done

Resources

FDA replies to good clinical practicehttp://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/RepliestoInquiriestoFDAonGoodClinicalPractice/

FDA Warning Lettershttp://www.fda.gov/iceci/enforcementactions/warningletters/default.htm

BiMo compliance manualshttp://www.fda.gov/ICECI/ComplianceManuals/ComplianceProgramManual/ucm255614.htm

FDA (disqualified) investigator databasehttp://www.accessdata.fda.gov/scripts/sda/sdNavigation.cfm?sd=clinicalinvestigatorsdisqualificationproceedings