Development of Stability Program at a Cord Blood Bank

Transcription

1 Developmet of Stability Proram at a Cord Blood Bak SAFA KARANDISH CELL THERAPY LABORATORY MD ANDERSON CANCER CENTER HOUSTON, TEXAS

2 Backroud Curret practice does ot require assii expiratio date to cord blood uits Limited published data: Broxmeyer, HE, et al, Hih-efficiecy recovery of fuctioal hematopoietic proeitor ad stem cells from huma cord blood cryopreserved for 15 years. Proc Natioal Academy of Sciece. Ja 21;100(2): , 2003 Kobylka P, et al, Preservatio of immuoloical ad coloy formi capacities of lo-term (15 years) cryopreserved cord blood cells. Trasplatatio. May 15;65(9):1275-8, 1998

3 Backroud New York Blood Ceter Data (bei preseted at ASH meeti)- Persoal commuicatio: Dr. Machi Scardavou Outcome data for patiets receivi NYBC uits: Uits stored for >8 years (N=43, media storae time: 9.2 years) compared to uits stored <2 years (N=300, media storae time: 1.1 years) Time to ANC recovery, raft failure rate ad overall survival were o differet betwee the two roups

4 Why the Recet Iterest i CB Stability? Draft FDA Guidace- December 2006: Applicable to Miimally Maipulated, Urelated, Alloeeic Placetal/Umbilical Cord Blood Iteded for Hematopoietic Recostitutio i Patiets with Hematoloical Maliacies Recommedatios for maufacturers for submissio of a bioloical licese applicatio (BLA)

5 Backroud Draft FDA Guidace- December 2006: Stability Testi (21 CFR ) There must be a writte testi proram desied to assess the stability characteristics of HPC-C. Stability proram should iclude aalyses of product potecy, iterity ad sterility..results of such testi must be used i determii appropriate storae coditios ad expiratio dates Proram must iclude: Sample size ad test iterval Storae coditio Reliable, meaiful ad specific test methods Testi of the HPC-C i the same cotaier-closure system as that i which the HPC-C is marketed Adequate umber of HPC-C must be tested to determie a appropriate expiratio date

6 WHAT SHOULD WE DO NOW? Sed your commets to FDA o the draft uidace ad hope for the best Start developi a pla

7 Product Iformatio Cord blood collected from voluteer doors Processed ad stored withi 48 hours of collectio Buffy coat separatio performed usi hydroxyethyl starch Cryopreservatio i Pall bas with fial DMSO cocetratio 10% Semets (~ 0.1mL each) 20mL fractio 5mL fractio

8 Product Iformatio Fial volume i ba: 25 ml Over-wrapped Cotrol-rate freezi usi Bioarchive system (Thermoeesis) Stored i liquid phase of Liquid Nitroe

9 Challees Two buffy coat processi methods Maual cetrifuatio Automated Sepax (Biosafe SA) Cell cocetratio (wide rae) Oldest uit i bak is 28 moths old (Bak established April 2005, >2900 uits baked) Limited # of uits available that are >2 years old Pla will result i sacrifici uits from miority doors

10 Testi & Aalysis Pre-cryopreservatio ad Post-thaw Sterility (Bactec) Nucleated cell cout (automated cell couter) CD34 aalysis Viability (flow cytometry, 7AAD) Coloy formi uit assay Visual ispectio

11 3-Part Proposed Pla Part I: Retrospective testi Evaluati uits already stored Part II: Prospective testi Stori uits for purpose of stability evaluatio Part III: Cliical Outcome Aalysis As data becomes available o trasplated uits

12 Variables Automated versus Maual Processi Method Not icluded i pla- data from both methods has show equivalet products Cell Cocetratio To avoid loss of uits with hih ucleated cell cout, majority of uits selected for testi may have lower cell cocetratio

13 Part 1: Retrospective Testi # of uits to be tested for each year: 10 (oldest uit: 2 years) Use either the 20% or 80% fractio Some later time, will use the other fractio Quality cotrol parameters evaluated over time, up to 10 years: Total of 100 uits eeded Usi the two fractios for evaluatio, reduces the # to 50 May be used to compare results from two fractios If 10 year data acceptable, cotiue for additioal years Additioal uits tested yearly

14 Part 2: Prospective Testi Projected # of uits to be collected aually: 2500 # of uits to be stored for testi: 25 (1% of total) Withi 30 days from stori: Semet thaw for viability ad CFU testi- Baselie Year 5: 5mL fractio thaw (5-year stability) Year 10: 20mL fractio from same uit tested (10-year stability)

15 Part 3: Cliical Outcome Data Evaluatio of eraftmet data Aalysis based o uit ae Exteded over several years to obtai sufficiet umber of data

16 Uit Selectio Cocers Loss of uits from miority doors Goal is to store as may as possible. Should radom selectio of uits be avoided? If excluded, ca stability data apply to these uits as well? MD Aderso Miority Allo Trasplat % 59% Caucasia No-caucasia BM ad PBPC Trasplats (=3038) CB Trasplats (N=105)

17 Uit Selectio Cocers Loss of uits with hih TNC Acceptable uits for HRSA must have >0.9x10 9 Total Nucleated Cells. Should radom selectio of uits be avoided? If excluded, ca stability data apply to these uits as well?

18 Pla Implemetatio Esure pla meets the requiremet for BLA submissio Advace review ad acceptace of pla by FDA

19 Summary Stability testi proram at each Cord Blood Bak may be differet. Number of uits available, ae ad type of uits should be cosidered i proram developmet. Sice each uit is truly a sile batch, baks face uique challees whe developi a stability proram. Early discussio with FDA is extremely importat. Miimizi loss of very valuable uits for cliical trasplatatio should be cosidered. Ca published cliical outcome data be used i support of stability testi?