Title 21, Part 312 - Investigational New Drug Application (IND) Flashcards
Contract Research Organization
Definition ONLY
a person that assumes, as an indpendent contractor with the sponsor, one or more of the obligations of a sponsor, e.g., design of a protocol, selection of monitoring of investiations, evaluation of reports, and the preparation of materials to be submitted to the Food and Drug Administration
Act
Definition ONLY
Federal Food, Drug, and Cosmetic Act
Independent Ethics Committee (IEC)
Definition ONLY
a review panel that is responsible for ensuring the protection of the rights, safety, and well-bbeing of human subjects involved in a clinical investigation
*An IRB is one type of IEC
Investigator
Definition ONLY
an individual that actually conducts a clinical investigation
Sponsor
Definition ONLY
an individual who takes responsibility for and initiates a clinical investigation
Direct Costs
Definition ONLY
costs incurred by a sponsor that can be specfically and exclusively attributed to providing the drug for the investigational use for which FDA has authorized cost recovery
Indirect Costs
Definition ONLY
costs incurred primarily to produce the drug for commerical sale (e.g., costs for facilities and equipment used to manufacture the supply of the investigational drug
Who submits IND to FDA
Sponsor submites IND to FDA if the sponsor intends to conduct a clinical investigtion with an investigational new drug
How many Phases of an Investigation can an IND be submitted for?
IND may be submitted for one or more phases of an investigation
Phase 1
-introduction of drug to human subjects
-tests for safety, dosage
-studies are usually closely monitored
-20 - 80 subjects
Phase 2
-tests for efficacy and side effects of the drug
-usually well controlled, closely monitored, and conducted in a small number of subjects (no more than several hundred subjects)
Phase 3
-tests for effectiveness
-compares drug to other standard treatments
-involves several hundred to several thousand subjects
What is the FDA’s primary objective in reviewing an IND?
-Assuring the **safety and rights of subjects **
-Assure the quality of the scientific evaluation
IND Application -
Order of Contents Within Application
Order of Contents Within Application
1) Cover Sheet
2) Table of Contents
3) Introductory Statement and General Investigational Plan
4) [reserved]
5) Investigator’s Brochure
6) Protocols
7) Chemistry, Manufacturing, and Control Information
8) Pharmacology and Toxicology Information
9) Previous human experience with the investigational drug
10) Additional Information
11) Relevant Information
IND Protocol Amendments
-Sponsor submits any amendments
-A protocol amendment will need to be submitted for any change in:
1)Phase 1 protocol that significantly affects the safety of subjects
2)Phase 2 or 3 protocols that significantly affect the safety of subjects, the scope of the investigation, or the scientific quality of the study
IND Safety Reporting
Adverse event
Definition ONLY
-Any untoward medical occurrence associated with the use of a drug in humans, whether or not considred drug related
IND Safety Reporting
Life-Threatening Adverse Event or Life-Threatening Suspected Adverse Reaction
Definition ONLY
-Considered “life-threatening” if, in the view of the investigator or sponsor, its occurrence places the patient or subject at immediate risk of detath
*Does not include an adverse event that, that it occurred in a more seve
IND Safety Reporting
Serious Adverse Event or Serious Suspected Adverse Reaction
Definition ONLY
An event/reaction is considered serious if any of the following happens:
1) death,
2) a life-threatening adverse event,
3) inpatient hospitalization,
4) persistent incapacity or disruption to conduct normal life functions,
4) a congenital anomoly/birth defect
IND Safety Reporting
Suspected Adverse Reaction
Definition ONLY
-Any adverse reaction which there is a reasonable possibility that the drug caused the adverse event
*reasonable possiblity suggests a causal relationship b/t the drug and a
IND Safety Reporting
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction
Definition ONLY
-Unexpecrted if the reaction/event is..
1) not listed in the IB or not listed at the specificity or severity that has been observed
2) the IB is not required or available
3) not consistent with the risk information described in the investigation plan
IB - investigator’s brochure
Who notifies the FDA about safety reports and when?
The sponsor most notify FDA and all participating investigators ASAP or no later than 15 calendar days after the sponsor determines the information is qualified to report
When should Unexpected fatal or life-threatening suspected adverse reaction reports be submitted? Who reports to who?
-The sponsor must notify FDA ASAP, or no later than 7 calendar days from the sponsor’s initial reciept of the information
Who submits an Annual Report and When?
-A sponsor shall submit an annual report within 60 days of the anniversary date that the IND went into effect
Who can withdraw an IND application?
A sponsor may withdraw an IND at any time
Who is notified if an IND is withdrawn?
FDA is notified, as well as all clinical investigators
All drugs are returned to the sponsor or otherwise disposed of
General Responsibilites of a Sponsor - IND Application
- Selecting qualified investigators
- providing investigators with information they need to conduct the investigation thoroughly
- ensuring proper monitoring
- Ensuring the investigation is conducted in accordance with the general investigational plan and protocols within the IND
- Maintain an effective IND
- Ensuring the FDA and all investigators are promptly informed of significant new adverse effects/risks with respect to the drug
General Responsibilities of an Investigator - IND Application
- ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations;
- protecting the rights, safety, and welfare of subjects under the investigator’s care
- Care for the control of drugs under investigation.
- Obtaining the informed consent of each human subject to whom the drug is administered
When does an IND go into effect
- 30 days after FDA recieves IND, unless FDA notifies the sponsor that the IP is under an investigational hold
- On early notification by FDA that the clinical investigations in the IND may begin
Who monitors the progress of all clinical investigations being conducted under its IND
the sponsor
Record Keeping and Retention in an IND Application - Sponsor
- maintain records showing the receipt, shiption, or other dispostion of the drug
- maintain complete and accurate records showing any financial interest
- retain the records and rports required by this pat for TWO years after an IND app is approved
- retain any reservce samples of any test articiale
Who takes care of the unused supply of an investigational drug and what to do they need to do with the drug
The PI is ultimately responsible for the proper handling and disposition of all unused investigational drugs at the study site.
sponsor maintains written records of the disposition of the drug
Record Keeping and Retention in an IND Application - Investigator
-responsible for maintaining adeuqate records of the dispostion of the drug
-maintain case histories of the drug
-records should be mainteined for a** period of 2 years following the date of a marketing application is approved for the drug, or until 2 years after the investigation is disconinuted and the FDA is notified**
Who submits progress reports?
Investigator submits progress reports
who submits annual reports within an IND inviestigation
sponsor
who submits final report of an investigation
investigator to sponsor
Financial Disclosure - IND
-submitted by the investigator to the sponsor
-investigator should update this information over the course of the investigation and for 1 year following the completion of the study
Investigator’s Brochure Contents
- Summary of the drug substance and formulation
- summary of pharamcological and toxicologiccal effects of the drug in humans/animals
- summary of pharamacokinetics and biological dispoisiton of the drug in humans/animals
- summary of safety and effectiveness (from prior studies)
- Description of possible risks and side effects
IND Content
- Cover Sheet (form 1571)
- Table of Contents
- Investigator’s statement (form 1572)
- Reserved
- Investigator’s brochure
- Protocols
- Chemisty, manufacturing, and control information
- Pharmacology and toxicology information
- previous human experience with the drug
- additional information
