NDA 080041, Amendment 011 - Review of March 18, 2009 Response to Information on Stability Testing - Intersol

United States Public Health Service
Center for Biologics Evaluation and Research

Internal Memorandum

NIH Bldg 29
Room 323
Ph:(301) 496–2577
FAX:(301) 402–2780

Date :	3-31-09
From:	Jaroslav G. Vostal, M.D., Ph.D. Laboratory of Cellular Hematology Division of Hematology, HFM–335
To:	Salim Haddad , MD Laboratory of Cellular Hematology Division of Hematology, HFM–335
Subject	NDA 080041, Amendment 011- Review of 3/18/2009 response to information on stability testing

Original FDA question:

1. Provide rationale and supporting data to justify your proposed acceptance criteria for the -(b)(4)- leachable compounds -----------(b)(4)-------------- in the stability test. .

Letter ready comments

The toxicological evaluation of leachables from PL 2411 plastic platelet additive storage bag should be based on animal studies that defined a toxic dose of an IV administered compound and on the anticipated clinical application of the device. The WHO allowable daily intake for -----------------(b)(4)------------------ applies to oral dosing and is not appropriate for IV application.

Please calculate the safety margin for ----(b)(4)----------- based on toxicity reports (LD50) of an IV administered ---(b)(4)----------. The calculation should be based on leachables from a 500 ml bag stored with platelets for up to 5 days and a 70 kg patient.

Please perform the same calculation for ------(b)(4)------------------------ using an IV toxic dose (LD50) derived in animal experiments.

Please identify the source of -----(b)(4)-----------------------------

Could the ink or the adhesive of the label be a source of these compounds?

Have the ink and the adhesive been FDA- approved for use on other bags?

What is the measured level of ----(b)(4)----------- in a platelet products stored up to 5 days at room temperature? .