When do I need an IND ?

1
When do I need an IND ?

• FDA Guidance for Industry Investigation New
  Drug Applications (INDs) - Determining Whether
  Human Research Studies Can Be Conducted Without
  and IND
• Procedural Draft for Public Comment
• October 2010

2
Investigational New Drug New?

• The FDA uses the filing requirements of the IND
  as the primary mechanisms for ensuring the safety
  of research subjects.
• The term IND can be misinterpreted, leading
  researchers to conclude that if the drug they are
  studying is already approved by the FDA, it is
  not a new drug needing a IND.
• INCORRECT!
• The FDA approves a drug as safe with
  specifications (these indications are spelled out
  in the Investigational Brochure, labeling,
  package insert or in the PDR)
• Route of administration
• Dose/duration
• Form of the drug (e.g. capsule vs. tablet)
• For specific medical conditions
• With concomitant medications or medical
  conditions

3
Research Studies that Require and IND

• Involve a drug
• The research is a clinical investigation
• The clinical investigation is not otherwise
  exempt

4
What is a drug?

• articles intended for use in the diagnosis,
  cure, mitigation, treatment, or prevention of
  disease. and articles (other than food)
  intended to affect the structure or any function
  of the body of man or other animals
• Includes Biologics, compounds administered to
  healthy subjects to blunt or provoke a
  physiologic response (vasopressin) or to study
  the mechanism of action or metabolism of a drug
  (contrast agents, markers).
• Dietary Supplements that affect the structure or
  function of the body and not intended for a
  therapeutic purpose is not a drug.

5
But Off-label use is legal

• In contrast, use of a licensed drug in the
  course of medical practice involves the use in an
  individual patient where the primary intent is to
  treat the patient but not to study the safety or
  effectiveness of a drug is any systematic way.

6
Categories Exempt from IND Requirements

• Otherwise exempt categories
• There are 3
• Certain Research Involving Marketed Drug Products
• 2. Bioavailablity or Bioequivalence Studies in
  Humans
• 3. Radioactive Drugs for Certain uses

7
Exempt from IND

• Clinical investigation of a drug is exempt if all
  of the following criteria are met
• The Drug is licensed and marketed in US
• No intent to report to FDA in support of a new
  indication or any other significant change in the
  product labeling
• The investigation is not intended to support a
  significant change in the advertising for the
  (licensed) drug

8
Exempt from IND

• The investigation does not involve a change in
  the route of administration, dose, population, or
  other factor that
• significantly increases the risk (or decreases
  the acceptability of the risk)
• associated with the use of the drug product.

9
Exempt from IND

• The investigation is conducted in compliance with
  the requirements for review by an IRB (informed
  consent)
• The investigation is conducted in compliance with
  the requirements of 312.7(i.e. , is not intended
  to promote or commercialize the drug )

10
Changes to route, population, dosage

• not intended to require that a drug be used in
  exactly the same dosage form, level, and patient
  population described in the marketed
  labeling.but only permit changes. that do not
  increase the risk to greater than the risk
  presented by the use of the product in
  conformance with its marketed label.

11
Introducing risk - clarification

• Low risk modifications blinding a product by
  changing its color, scoring or capsule size
• Greater risk modifications Products that are
  sensitive to conditions in the environment, may
  create changes to formulation. or primary
  packaging. (examples)
• No comprehensive guide - may request consultation
  with FDA (formal or informal)

12
Introducing risk - clarification

• Risk assessment of a marketed drug
• Oncology setting has been separated out
• IND Exemptions for Studies of Lawfully Marketed
  Drug or Biological Products for the Treatment of
  Cancer

13
Consider

• PI sponsors may have no intent utilize study
  results for changing labeling or advertising but
  the research results may have the potential to do
  so.

14
Example changing the form

• Example Coumadin is very unstable in high
  humidity, which is why the pills are coated.
  Crushing of these caplets can change them
  chemically and result in unanticipated safety
  risks and a lack of efficacy.
• .

15
Example of Manufacturing change

• The packaging of some drugs is very important to
  preserve its chemical composition. Some drugs are
  in blister packs, because they decompose when
  they come in contact with air, dark brown glass
  bottle if photosensitive
• The IUD was produced and marketed in an insertion
  kit which was removed and being inserted with a
  ring forceps . Does this introduce a design
  control (GMP) risk?

16
Lessons Learned

• Charging for investigational products under an
  IND
• Old rule- rarely permitted, required FDA written
  permission
• New rule November 2009 covers charging for
  investigational drugs in clinical trials and
  expanded access use.
• (FDA has not changed its letters to reflect this
  change)
• Take home message PI/ sponsor/ investigator
  researching an approved drug for unapproved use
  can have subject obtain drug and bill third
  party.

17

• IND Decision Support tool by the University of
  Penn
• http//www.med.upenn.edu/ohr/ind/index.html

18
Investigator/Sponsor Responsibilities

• MMC HRPP Web Site
• http//www.mmcri.org/home/webSubContent.php?subCat
  ID36catID2headTypehrppcatLevelsubCat

19
What is a Clinical Investigation?

• CFR 312.3(b)
• ,,,an experiment in which a drug is
  administered or dispensed to, or used involving,
  one or more human subject.
• For the purposes of the IND regs an experiment
  is, any use of a drug approved or not except
  for the use of a marketed drug in the course of
  medical practice.