THE UNIVERSITY OF NEW MEXICO ▪ HEALTH SCIENCES CENTER Clinical and Translational Science Center (CTSC) 4/2009.

THE UNIVERSITY OF NEW MEXICO ▪ HEALTH SCIENCES CENTER

Clinical and Translational Science Center (CTSC)http://hsc.unm.edu/research/ctsc/

4/2009

An exemption from the law which otherwise requires that a drug (biologic, device) be approved before it can be transported across state lines

The standard for approval is evidence of safety and efficacy

The IND exemption is granted for purposes of clinical investigation (research)

Affirms a body of knowledge about the manufacturing, pharmacology, and toxicology of the drug to support its use in human testing

Requires that the clinical investigation(s) be performed in accordance with Good Clinical Practice (GCP)

Provides an additional level of protection through FDA oversight

Any of: Article recognized in the U.S. Pharmacopeia,

official Homeopathic Pharmacopeia of the US, or official National Formulary, or any supplement

Article intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals

Any of: Article (other than food) intended to

affect the structure or any function of the body of man or other animals

Article intended for use as a component of any article specified in clauses above

Section 201(g) of the FD&C Act

Any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. For the purposes of this part, an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice

21 CFR 312.3

In general: An IND is required when an unapproved drug (or biologic) is used in a clinical investigation

No IND is needed when an approved product is used in the course of medical practice (even for an indication different from the approved indication)

But an IND may be required when an approved products is used in a clinical investigation

An IND is needed if:The clinical investigation is intended

to be reported to FDA as a well-controlled study in support of a new indication or a significant change in the labeling of the drug

The clinical investigation is intended to support a significant change in advertising for the product

With the above caveats, clinical investigation of an approved product may be exempt from IND requirements if: The investigation does not involve a route of

administration or dosage level or use in a patient population or other factor that significantly increases risks AND

The investigation is conducted in accordance with IRB and informed consent requirements

FDA has generally allowed the IRB to assess whether risk of an approved product is increased for a given protocolBut FDA retains final authority for

such determinations

It is also important to note that shelf chemicals which bear the same “name” as an approved product are not considered as “lawfully marketed” equivalents of the approved productApproval is specific to dose,

formulation, and applicant

Drugs (CDER) Drug Information Branch: (301) 827-

4573

Biological Products (CBER) (301) 827-0373

Medical Devices (CDRH) IDE Staff: (301) 594-1190

Food Safety (CFSAN): (202) 418-3126

GCP Regulations IND/IDE Regulations: 21 CFR Part 312/812

IRB Regulations: 21 CFR Part 56

Informed Consent Regs: 21 CFR Part 50

All are accessible at:www.fda.gov/oc/gcp

IND FormsAvailable on-line through:

(ADD LINK)

General Investigation Plan Investigator’s Brochure Protocol(s): Later protocols submitted as

amendments Chemistry, manufacturing and control

information Animal pharmacology and toxicology

information

Previous human experience Additional information

Dependence and abuse potential Plans for pediatric studies

Amount of information required in each section depends on novelty of the drug, extent studied, and known or suspected safety concerns

IND sponsors are required to obtain a signed FDA Form “1572” from each clinical investigator, containing: Name and address of CI Name and code number of any protocol(s) Name and address of research facility and

any clinical labs Name and address of responsible IRB Names of co-investigators Signed commitment by the investigator

Personally conduct or supervise investigations

Ensure all persons assisting in conduct of studies are informed of their obligations

Ensure informed consent (21 CFR 50) and IRB review, approval , and reporting (21 CFR 56) requirements are met

*(Form FDA 1572: #9. Commitments)

Conduct studies according to relevant, current protocol

Make changes in a protocol only after notifying the sponsor

Maintain adequate and accurate records

Make records available for inspection Agree to comply with all other

requirements in 21 CFR 312*(Form FDA 1572: #9. Commitments)

FDA also has responsibilities under GCP The focus of FDA’s IND Review is on

safety for human research subjects and ensuring that the studies will produce useful information to assess safety and efficacy of the test product

Medical Officer Consumer Safety Officer/Project Manager Statistician Chemist Pharmacologist Human Biopharmaceutics (Microbiologist)

Review team has 30 days to review

Focus of review is always on safety/ human subject protection

No News = Good News

“Clinical Hold” Legal order to delay or stop the study in the U.S. Subjects may not be given the investigational

drug May be imposed if:

Exposure of subjects to unreasonable risk (includes manufacturing problems)

Investigator brochure is misleading, erroneous, or materially incomplete

Investigator is not qualified

Review Team Monitors New Protocols (IND amendments) Safety reports Annual reports Additional chemistry, animal toxicology,

microbiology data Review team is available to consult/meet

with sponsors: advise on protocol design, advise on drug development plan

Studies performed outside of the U.S. may be conducted with or without IND With an IND:

Test article can be exported from the U.S.

Study must conform to U.S. IND regulations (including U.S. IRB and informed consent rules)

Studies performed outside of the U.S. may be conducted with or without INDWithout an IND

May be acceptable for FDA review in support of a marketing application

Export of the test article from the U.S. must conform to FDA regulations

Mechanisms (21 CFR 312.110)FDA authorization of a written

request from the person that seeks to export Adequate information; investigational

purposes only; can be legally used in the importing country for investigation; specifies quantity/frequency of shipment

FDA authorization of a formal request from the government of the receiving country

1996 law also allows drug export for investigational use without prior FDA approval if intended for use in one of 25 countriesAustralia; Canada; Israel; Japan,

New Zealand; Switzerland; European Union Member States (15), Iceland, Norway, and Liechtenstein

Center for Drugs ODE I Cardio-Renal (110)

301-594-5300 Neuropharm (120)

301-594-2850 Oncology (150)

301-594-2473

Center for Drugs ODE II Anesthetic, Critical

Care & Addiction (170) 301-827-7410

Metabolic/Endocrine (510) 301-827-6430

Pulmonary (570) 301-827-1050

Center for Drugs ODE III Medical Imaging &

Radiopharm (160) 301-827-7510

GI & Coagulation (180) 301-827-7310

Repro/Urologic (580) 301-827-4260

Center for Drugs ODE IV Anti-Infective (520)

301-827-2120 Antiviral (530)

301-827-2330 Special Pathogens

& Immunologic (590) 301-827-2336

Center for Drugs ODE V Derm/Dental (540)

301-827-2021 Anti-Inflammatory,

Analgesic & Ophthalmic (550) 301-827-2040

Over-the-Counter (OTC) (560) 301-827-2222

Center for Biologics (CBER) Office of Vaccines Research and Review

(301) 827-0654 Office of Blood Research and Review

(301) 827-3524 Office of Therapeutics Research and Review

(301) 827-5099

OGD Regulatory Support Branch(301) 827-5862

Center for Devices and Radiological Health (CDRH)General, Restorative, and

Neurological Devices: (301) 594-1184

Clinical Laboratory Devices: (301) 594-3084

Cardiovascular and Respiratory Devices: (301) 443-8320

Center for Devices and Radiological Health (CDRH)Ophthalmic and ENT Devices: (301)

594-2205Reproductive, Abdominal, and

Radiological Devices: (301) 594-5072

Dental, Infection Control, and General Hospital Devices: (301) 443-8879

IND sponsors/researchers are required to report serious non-compliance

But anyone can report complaints in FDA-regulated clinical trials to FDA

FDA’s GCP website (www.fda.gov/oc/gcp) highlights where to report complaints in clinical trials