Transcript IND Review Process

IND Review Process
Seoul National University
Dept. of Manufacturing Pharmacy
2001-14451 Sue Hyun Kim
IND Review Process
Applicant (Drug Sponsor)
IND
Review by CEDR
Medical
Chemistry
Pharmacology/
Statistical
Toxicology
Sponsor Submits
Safety Review
New Data
No
Safety Acceptable for
Study to Proceed?
Clinical
Hold Decision
Yes
No
Complete Reviews
Yes
Notify Sponsor
Reviews Complete
And Acceptable?
No
Sponsor Notified
Of Deficiencies
Yes
No Deficiencies
Study Ongoing*
*While Sponsor answers
any deficiencies
Applicant (Drug sponsor)
The person or entity who assumes responsibility for the investigation of a new drug.
(including responsibility for compliance with applicable provisions of the Federal Food,
Drug, and Cosmetic Act and related regulations)

Usually an individual, partnership, corporation, government agency, manufacturing or
scientific institution.
Investigational New Drug Application
The result of a successful preclinical development program  advances to clinical trials
1’ goal : determine safety for initial use in humans & pharmacological activity for
commercial development  collecting data and information
 collecting data and information
1)
Animal Pharmacology and Toxicology Studies
2)
Manufacturing Information
3)
Clinical Protocols and Investigator Information
IND is not an application for marketing approval. It is a request for an exemption from the
Federal statute that prohibits an unapproved drug from being shipped in interstate
commerce.
Types of IND
Commercial INDs : submitted by companies-obtain marketing approval
Noncommercial INDs : vast majority of INDs. - including Investigational INDs, Emergency
Use INDs, Treatment INDs.
Review Process
•
Medical Review
Exclusively physicians. Medical reviewers are responsible for evaluating the clinical
sections of submissions (i.e., safety of the clinical protocols in an IND or the results
of this testing.)
Lead role in the IND or NDA review,
Responsible for synthesizing the results of the animal toxicology, human pharmacology
and clinical review to formulate the overall basis for a recommended Agency action
on the application.
Evaluate clinical trial protocols to determine
1)
If the participants will be protected from the unnecessary risks
2)
If the study design will provide data relevant to the safety and effectiveness of the
drug
•
Chemistry Review
Reviewing the chemistry and manufacturing control sections of drug applications

Issues related to drug identity, manufacturing control, and analysis.

Evaluates the manufacturing & processing procedures
? Reproducible ? Stable ?
? Any differences b/w the drug product proposed for clinical use & used in the animal
toxicology trials?  should be stated ( whether or not)
•
Pharmacology/Toxicology Review
Evaluate the results of animal testing & attempt to relate animal drug effect to potential
effects in humans.
Pharmacology and Drug distribution
1)
Pharmacologic effects and mechanism(s) of action of drug in animals
2)
ADME Information
 A summary report usually suffices (w/o ind. Animal records or ind. Study results)
Toxicology Data
Integrated summary of the toxicologic effects of the drug in animals and in vitro.
** particular studies needed depend on the nature of the drug and the phase of human
investigation.
•
Safety Review
30 calendar days following review of an initial IND submission  clinical hold? Or not?
Sponsor hears nothing from CDER  continue the study on day 31 after submission
Clinical Hold Decision
When CDER does not believe or cannot confirm that the study can be conducted w/o
unreasonable risk to the subjects/patients

Delay the start of an early-phase trial / stop an ongoing study

Sponsor must address the issue (basis of the hold) before the removal of the order
Clinical holds are reviewed by upper management of CDER  to assure consistency and
scientific quality in the Center’s decisions
Notify Sponsor
Immediate phone call by the division director

A letter send by the division within 5 working days following the phone call
: describe the reasons for hold, signature of the division director

Response of the sponsor to CDER by sending “ IND CLINICAL HOLD RESPONSE”
letter to division

The division reviews the sponsor’s response and decides whether lift the hold or not
(Within 30 calendar days)

If the hold won’t be lifted, the hold decision is automatically sent to the office
director for review  decide within 14 calendar days whether or not to sustain that
decision

 decision to lift the hold sent by the phone call from division to sponsor, & a letter
confirms decision (within 5 working days of the phone call)
Sponsor Notified of Deficiencies
Other deficiencies that are not serious enough to justify delaying clinical studies

Telephone or deficiency letter to the sponsor form the division
Study Ongoing
Expiration of CDER’s 30-day initial review period
 Initiating clinical studies