# Presentation: 460655

## The Radioactive Drug Research Committee (RDRC) 

**Society of Nuclear Medicine**
**Philadelphia, Pennsylvania**
**June 19 - 23, 2004**
**O H Suleiman, R Fejka, R Farkas, M Walsh, **
**L Panholzer**

**Notes:**
I want to thank you for giving us the opportunity to discuss one of FDA’s oldest radioactive research program, the Radioactive Drug Research Committee.  The current team consists of the following members, Richard fejka, a nuclear pharmacisit, Maria Walsh, one of our program managers, Maria is a nurse, Lynn Panholzer our other Program Manager, she is a pharmacist, and Ray Farkas, who ran the program until he retired recently.  I am Orhan SUleiman, and I am a physicist.

## Radioactive Drug Research Committee

**Established in 1975**
**Formally codified in 21 CFR 361.1**
**Allows human research with radioactive drugs without an IND when:**
**Research is basic**
**RDRC approves**
**There is no clinically detectable pharmacologic effect from the administered**
**and radiation dose limits as specified are met**

**Notes:**
In 1975 the RDRC committee was established and formally codified in the Code of Federal Regulations Title 21, Part 361.1.

The intent of the regulations was to allow human research to continue without the burden of obtaining an FDA Investigational New Drug Application, or IND, if certain conditions were met.

The research protocol would have to be approved by the committee, and the administered pharmacologic dose would show “no clinically detectable effect”, and certain radiation dose limits could not be exceeded.

This enabled radiotracer research to be conducted in humans.

## Provisions within 21 CFR Part 361.1

**Basic Research**
**Pharmacological dose limits**
**Radiation dose limits**
**Radioactive drug quality**

**Notes:**
In addition to the dose issues, both pharmacologic and radiation, there are specific requirements related to the committee, its membership, and its responsibilites.
... [wait 3 seconds]...such as reviewing and approving protocols, selection of research subjects, and other administrative tasks.......[next SLIDE]

## Provisions within 21 CFR Part 361.1

**Membership qualifications**
**Specific Responsibilities of RDRC to**
**assure research is basic in nature and does not require IND**
**review and approve protocol, human subjects**
**report adverse reactions**
**seek approval of Institutional Review Board (IRB)**
**file required reports with FDA**** **

## Types of Research

**Basic science for advancing knowledge, such as biodistribution of radioactive drug (including kinetics, distribution, localization, physiology, or biochemistry).**
**Not intended... **
**for immediate therapeutic or diagnostic benefit**
**to determine the safety or effectiveness of a drug in humans**
**to circumvent the IND process**

**Notes:**
One of the most critical requirements is that this research be basic in nature, and not be used for patient management or safety and efficacy studies.  These require a formal FDA IND.........

## Slide 6

## Most frequently used radionuclidesIn 2002, 83 FDA approved RDRC’s conducted 280 studies with 2872 human subjects             					

| Imaging
nuclides (75%) |  | Non-imaging nuclides (21%) |
| --- | --- | --- |
|       positron      | gamma | beta |
| C-11 (32%) | Tc-99m (2%) | H-3 (15%) |
| O-15 (20%) | I-123 (1%) | C-14 (6%) |
| F-18 (18%) |  |  |
| N-13 (2%) |  |  |
| Other nuclides (4%): Cu-60, Fe-59, Ca-41, F-17, Fe-55, I-125, I-131,  Ca-45, Ca-47, Cu-62, In-111, Tc-94m, Xe-133 |  |  |

**Notes:**
Looking at the data from a different perspective, there were 280 studies in 2002, using almost 2900 human subjects.

72% of these studies consisted of 4 PET radionuclides, while 3 % used conventiona gamma emitters technetium-99m  and I-123.   Another 21% used tritium and carbon 14.

## 83 “Active” RDRC Committees in 2002

**48 % (40) conducted human research**
**52% (43) did not conduct any research in 2002, although they maintained active status**

## In the “near” future FDA is planning a meeting

**Purpose of this meeting will be to discuss current and future status of RDRC process**
**Specifically......**

**Notes:**
At this meeting FDA will review research where an IND is not required.  All of the RDRC’s have been notified of this meeting, and we hope that they can share their experiences with us regarding the advantages and limitations of this program. 

For more information please go to the following website.
The meeting will be in Gaithersburg, MD.

## FDA issues and concerns

**Are RDRC studies conducted when an IND is required?**
**Should First in Human research of New Molecular Entities (NME’s) be allowed under RDRC? **
**If so, what safeguards are needed?**
**What is meant by “no clinically detectable pharmacologic effect?”**
**Are 1975 radiation dose limits appropriate today?**
**Should RDRC be reengineered with regard to membership, relationship to Institutional Review Boards (IRB’s), and reporting requirements?**

**Notes:**
Our concerns...........?

Are RDRC studies conducted when an IND is clearly called for?  We need to reeducate our community to understand when RDRC research ends, and the IND process takes over.

What do we mean by no clinically detectable pharmacologic effect?  When this line is crossed, the investigated drug now requires an IND.

Are the 3/5/15 rem dose limits for the whole body and certain organs still appropriate today?  Should these limits remain the same?

Should we reengineer the RDRC process, should a nuclear pharmacist be required, should reporting requirements be changed?

........and should new molecular entities be allowed? 

These are questions we are asking ourselves, and will discuss in a public meeting next month..............[NEXT slide]

## Radioactive Drug Research Committee- The Future

**How will RDRC research relate to new FDA initiatives?**
**Low dose imaging - Part of FDA’s Critical Path Initiative to  develop new drugs.**
**Microdosing – European drug industry initiative (“Human Phase 0” trials without an Investigational New Drug Application (IND)).**
**Screening IND **

**Notes:**
And finally, we ask, what is the role of the RDRC in the future?

When I first undertook responsibility for this program, I asked myself what was the value of this program?  I was surprised to hear some of the very positive things, but there was also criticism, not necessarily of the RDRC process, but criticism of the FDA research process.

So, I share with you the following,  there are several initiatives, some are FDA initiatives, other are not, but they need to be related.

Imaging has been rediscovered.

FDA’s Critical Path Initiative will rely on imaging to provide critical biodistribution data, George Mills, whom many of you know, is the New Director of the Division of Medical Imaging and Radiopharmaceutical Drug Products.  I believe Dr Mills will play an active and dynamic role in this initiative.  If the doses are low enough, both pharmacologic and radiation, then we have the RDRC program!

Microdosing, ......last year when I started, I reviewed an article by Dr Colin Garner and his associate advocating “human phase 0” clinical studies.  The more I studied the article, the more I realized RDRC was a subset of microdosing.  An important research tool, but maybe ignored by the drug industry as such.  
And finally FDA is developing a “screening IND”, which may help bridge RDRC research and the IND, but the details are still being worked out.  

## RDRC is both...		

**a process used to conduct basic human radiotracer research studies**
**a tool for obtaining early human pharmacokinetic (PK) data**

**Notes:**
So, these are exciting times, nuclear medicine is being rediscovered again, but more importantly, I believe we need to hear you, get your input.

Is the RDRC a long ignored tool which could benefit drug development?

Or is it simply a process with which the nuclear medicine community can conduct academic type research?

Thanks you for your time.

Our next speaker will be..............    

## The FutureFDA Campus @ White Oak, Silver Spring, Maryland

## The FutureFDA Campus @ White Oak, Silver Spring, Maryland