# Presentation: 807247

## Regulation of PBSC and DLI from Unrelated Donors: Meeting the Needs of the U.S. Public

**John P. Miller, MD PhD**
**Senior Medical Director, NMDP**
**March 30, 2007**

## Issues in Unrelated PBSC Regulations

- The safety and efficacy of unrelated PBSC, related PBSC and bone marrow are similar, yet they are regulated differently (351, 361, HRSA)
- If licensure of unrelated PBSC is required, requirements must reflect current data on safety and efficacy and be feasible to implement in different types of apheresis centers
- Importation of PBSCs is essential to meet the needs of US transplant patients; the regulatory framework needs to allow continued importation of these products without becoming burdensome

## NMDP’s Proposal for FDA Consideration: Like Products Should be Treated Alike

- FDA will regulate *unrelated* *donor *PBSC and DLI products that are...
- Minimally manipulated,
- Homologous use,
- HLA-matched, and
- Used for hematopoietic reconstitution...
- in same manner as *related* *donor *PBSC and DLI.

## Level and Type of Regulation Should be Commensurate with the Risk Posed by the Product Characteristics

- Only relevant controllable risk associated with collection of unrelated PBSC & DLI is *transmission of communicable disease*
- PBSC & DLI are very different from traditional biological drugs:
- Patient-specific, with a high degree of HLA matching
- Minimally manipulated and infused fresh
- Manufacturing beyond the apheresis collection is minimal
- Quality is uniformly high; variability is dependent on donor factors, not the manufacturing process
- Product will be infused no matter what
- Thus, the provisions in 21 CFR 1271 through donor eligibility & GTPs adequately cover the risk of communicable disease transmission

## NMDP U.S. Product Collection Sites

- 88 FDA-registered domestic tissue establishments currently collect PBSC and DLI products
- 	- 63 of 88 (72%) are hospital-based
- 	- Only 3 of 63 are licensed biologics establishments*
- 	- The 60 unlicensed establishments collected 1053/1371 	(77%) of the products in 2005
- Primary activities of these centers include: related donor PBSC and DLI; platelet apheresis and therapeutic plasma apheresis
- Many of these centers would stop collections if licensure is required

- *www.fda.gov/cber/ep/part1.htm, 5/23/06

## Consequences of 351 Regulation

- Fewer sites will collect these products, both domestically and internationally
- Donors will need to travel to distant collection sites and, consequently, donor participation will decline
- Costs for collection will increase
- Importation of products will decrease
- Patients will no longer have access to their best HLA-matched donors

## HLA and the Need for HLA-Matching Drives the International Exchange of Hematopoietic Stem Cells

**Why is Importation of unrelated PBSC Products so Prevalent and Essential?**

## 2005 Global Unrelated Donor PBSC and Bone Marrow Collections

**2005 Global Unrelated Donor PBSC and Bone Marrow Collections**

**Home Country****4,842 (61%)**

**International****3,079 (39%)**

**n = 7,921**

## Conclusions

- We recommend that unrelated PBSCs be regulated under 361 based on the safety and efficacy data; risk is communicable disease
- Alternatively, licensure requirements should reflect current understanding of PBSC safety and efficacy and not be so burdensome as to risk loss of PBSC collections by some apheresis centers
- Any proposed regulatory framework needs to accommodate importation of products essential to meeting patients’ need for HLA-matched products