GTP Scenario # 4 September 17,2005

Scenario # 4 A patient undergoes 2 Autologous PBPC collections. Day 1 = 0.3 x 106 CD34+ cells/kg Day 2 = 4.8 x 106 CD34+ cells/kg The patient begins a marrow suppressive 3 day prep immediately after the Day 2 collection. On Day -1 of transplant, the sterility samples on the Day 2 Collection (post collection & pre-freeze) are positive for gram positive cocci. Pt’s physician wants to infuse both Day 1 and Day 2 Collections and pre-med with antibiotics.

What should be considered? Does release of the Day 2 product meet the definition of “Urgent Medical Need” as defined in 21 CFR1271.3 (u)? Is there no comparable HCT/P available? Would the recipient suffer death or serious morbidity without the product?

What should be considered? Does release of this product meet the 21CFR1271 definition of Urgent Medical Need? No Since this is an autologous product, Urgent Medical Need is not applicable. From a 21CFR1271 point-of-view, Urgent Medical Need is only appropriate for use in a Donor Eligibility Determination.

What else should be considered? Type of product. 361 (GTP) The samples which were contaminated. Post-collection and pre-freeze The fact that the patient has started the preparative regimen. The organism identified is a gram positive cocci on Day 2 of testing.

What Documentation Is Required? Notification of the recipient’s physician. Recipient consent. FDA Deviation: Contaminated HCT/P are FDA reportable.

Variation # 1 What if the collection was 3 weeks before infusion and the patient had not started the preparative regimen. Should the patient be remobilized for additional collections? This should be evaluated based on the organism(s) identified and other risk factors.

Variation # 2 What if the culture-positive product were from the Day 1 collection? Since the product from Day 2 contains an acceptable dose of CD34+ cells, the product from Day 1 does not need to be administered.

Variation # 3 If the product were collected under IND, what should the laboratory do? Since the product is under IND, the laboratory should notify the IND Sponsor. The IND Sponsor should notify the FDA.