# Presentation: 372843

## Center for Medical Countermeasures Against Radiation

- DAIT Regulatory Affairs

**Christine Czarniecki, Ph.D.**
**Chief, Regulatory and Industry Affairs**
**Division of Allergy, Immunology and Transplantation**
**National Institute of Allergy and Infectious Diseases**
**December 15, 2004**
**National Institutes of Health **
**U.S. Department of Health and Human Services**

## Clinical Research Programs

**Immune Tolerance Network (ITN)**
**Cooperative Clinical Trials in Pediatric Transplantation (CCTPT)**
**Clinical Trials in Organ Transplant (CTOT)**
**Hematopoietic Stem Cell Transplantation (HSCT)**
**Autoimmunity Centers of Excellence (ACE)**
**Inner-City Asthma Consortium (ICAC)**
**Atopic Dermatitis Vaccinia Network (ADVN)**
**Islet Cell Network**
**Center for Medical Countermeasures Against Radiation**

## DAIT, NIAID, NIH
NCI, NIH
FDA Division of Counterterrorism
CDER/FDA
CBER/FDA
DHHS
DHS
Others

**DAIT, NIAID, NIH**
**NCI, NIH**
**FDA Division of Counterterrorism**
**CDER/FDA**
**CBER/FDA**
**DHHS**
**DHS**
**Others**

## DAIT Staff

Contract Research Organization (CRO)

Individual Consultants
GLP toxicology
GMP quality
GMP facilities

**Contract Research Organization (CRO)**
**Individual Consultants**
**GLP toxicology**
**GMP quality**
**GMP facilities**

- Regulatory Affairs

## Drug Development & Approval Process

## Fast Track Designation
Priority review
Subpart H (Accelerated approval using a surrogate endpoint)
Subpart I (the “Animal Efficacy Rule”)
Orphan Drug Designation
Special FDA Programs (e.g. FDA Division of Counter-terrorism - Liaison)

**Priority review**
**Subpart H (Accelerated approval using a surrogate endpoint)**
**Subpart I (the “Animal Efficacy Rule”)**
**Orphan Drug Designation**
**Special FDA Programs (e.g. FDA Division of Counter-terrorism - Liaison)**

- Applicable Regulatory Tools/Strategies

## The “Animal Rule”
Approval of Biological Products (New Drugs) when Human Efficacy Studies are Not Ethical or Feasible

Final Rule:
67 FR 37988 (May 31, 2002)
21 CFR § 601.90-95 (biologicals)
21 CFR § 314.600-650 (drugs)

**Approval of Biological Products (New Drugs) when Human Efficacy Studies are Not Ethical or Feasible**
**Final Rule:**
**67 FR 37988 (May 31, 2002)**
**21 CFR ****§ ****601.90-95 (biologicals)**
**21 CFR ****§ 314.600-650 (drugs)**

## Drugs and biologicals that reduce or prevent serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substances.

Rule does not apply if product approval can be based on standards described elsewhere in FDA’s regulations.

**Rule does **_***not***_** apply if product approval can be based on standards described elsewhere in FDA’s regulations.**

- Scope of the “Animal Rule”

## Human safety has been established, 
	and
“Animal Rule” requirements are met – based on adequate and well-controlled animal studies, the results of which establish that the products is reasonably likely to provide clinical benefit in humans.

**	*****and***
_**“**__**Animal Rule” requirements are met**_** – based on adequate and well-controlled animal studies, the results of which establish that the products is reasonably likely to provide clinical benefit in humans.**

- FDA may approve a product for which...

## All studies subject to this Rule must be conducted in accordance with preexisting requirements under the Good Laboratory Practices (21 CFR §58) regulations and the Animal Welfare Act (7 U.S.C. 2131).

GLP will be required for the definitive/pivotal animal studies – not necessary for the pilot studies.  Also, if the animal study will be mentioned in the label, it should be done according to GLP.

**GLP will be required for the definitive/pivotal animal studies – not necessary for the pilot studies.  Also, if the animal study will be mentioned in the label, it should be done according to GLP.**

- GLP & AWA Requirements

## The label indication. 
Pre-exposure/post exposure.

Endpoints of animal studies. 
 IACUC and EU regs.

Appropriate challenge dose.

Statistical considerations.  
Rodents vs. NHP

**Pre-exposure/post exposure.**
**Endpoints of animal studies. **
** ****IACUC and EU regs.**
**Appropriate challenge dose.**
**Statistical considerations.  **
**Rodents vs. NHP**

- Animal Study Design Challenges

## The “Animal Rule” is new to both industry and to the FDA – collaboration is essential for success.
Multiple interactions with FDA
prior to animal efficacy trials, for concurrence with concepts.

**Multiple interactions with FDA**
**prior to animal efficacy trials, for concurrence with concepts.**

- Conclusions

## FDA Website
http://www.fda.gov

Small Business Assistance
http://www.fda.gov/cder/about/smallbiz/default.htm 

- _[http://www.fda.gov](http://www.fda.gov/)_
**Small Business Assistance**
- _[http://www.fda.gov/cder/about/smallbiz/default.htm](http://www.fda.gov/cder/about/smallbiz/default.htm)__ _

- Information Resources

## IND Regulations: Code of Federal Regulations, Title 21, parts 312 and 50.
ICH E6 Good Clinical Practice: Consolidated Guidance
www.fda.gov/cder/guidance/959fnl.pdf
Formal Meetings with Sponsors and Applicants for PDUFA Products
www.fda.gov/cder/guidance/2125fnl.pdf

**ICH E6 Good Clinical Practice: Consolidated Guidance**
- _[www.fda.gov/cder/guidance/959fnl.pdf](http://www.fda.gov/cder/guidance/959fnl.pdf)_
**Formal Meetings with Sponsors and Applicants for PDUFA Products**
- _[www.fda.gov/cder/guidance/2125fnl.pdf](http://www.fda.gov/cder/guidance/2125fnl.pdf)_

- Information Resources

## Christine W. Czarniecki, PhD
DAIT, NIAID, NIH
Ph. 301-451-3107
E-mail: cczarniecki@niaid.nih.gov

Mary Purucker, MD, PhD
DCT, CDER, FDA
Ph. (301) 827-771
E-mail: mary.purucker@fda.hhs.gov 

**DAIT, NIAID, NIH**
**Ph. 301-451-3107**
**E-mail: **_[cczarniecki@niaid.nih.gov](mailto:cczarniecki@niaid.nih.gov)_
**Mary Purucker, MD, PhD**
**DCT, CDER, FDA**
**Ph. (301) 827-771**
**E-mail: **_[mary.purucker@fda.hhs.gov](mailto:mary.purucker@fda.hhs.gov)_** **

- Contact Information