CBER 510(k) Challenges and Strategies Susan Finneran Director of Clinical and Regulatory Affairs

Copyright © 2009 Haemonetics Corp.2 Background on Haemonetics  NYSE traded company  2,070 employees world wide  Based in Braintree, MA.  Hospital and blood collection customers in more than 80 countries Vision: To be the Global Leader in Blood Management Solutions

Copyright © 2009 Haemonetics Corp.3 Blood Collection Processing & Testing Inventory & Distribution Hospital BB Inventory Transfusion Preparation Recruitment & Interview Point of Care Pre Intra Post Hospital Blood Center Blood Use Optimization Reports Dashboards Business Design InSight™ Model Dashboards Automation Nation™ Business Solutions Lean & Six Sigma Blood Collections Optimization Consulting Services Blood Use Optimization Consulting Services Donor Recruitment Programs Cymbal ® PCS  2 MCS  + TEG ® cardioPAT ® OrthoPAT ® Cell Saver® Information Management Devices Services We have a growing portfolio of customer solutions ACP ® 215 3

Copyright © 2009 Haemonetics Corp.4 Haemonetics Devices Automated Apheresis Devices  Equipment, imbedded software and disposable sets  Submitted to CBER  510(k) with clinical studies  Recently down classified (Class II) Autotransfusion Devices  Equipment, imbedded software and disposable sets  Submitted to CDRH  Class II  Laboratory Studies

Copyright © 2009 Haemonetics Corp.5 Types of 510ks submitted to CBER Traditional – 90% Special -10% STED- none Abbreviated- none Third Party- not eligible for CBER devices

Copyright © 2009 Haemonetics Corp.6 Premarket Notification Devices that are submitted to CBER (Hematology Division)  Automated Apheresis (Blood Collection) Systems  Disposables used in blood collection  Laboratory Equipment  Blood Establishment Computer software CDRH (k)s / year CBER (k)s / year

Copyright © 2009 Haemonetics Corp.7 What else does CBER Review?  BLA- Biologic License Applications Blood Centers submit for a license to manufacture blood products  NDA’s- New Drug Applications Anticoagulant and Blood Nutrient solutions  510(k)s- Premarket Notifications Blood collection devices  IDEs/INDs- Investigational Device Exemptions/ Investigation New Drug Devices and solutions  PMAs – Premarket approval Not yet

Copyright © 2009 Haemonetics Corp.8 Substantially Equivalent??? “That’s a CDRH term… that doesn’t apply to CBER devices”

Copyright © 2009 Haemonetics Corp.9 Substantially Equivalent is part of the equation..  But more importantly… must meet Blood quality standards  Hemolysis at the end of storage  Residual White blood cell content  Red cell recovery after filtration  Total hemoglobin in the blood product  platelet count

Copyright © 2009 Haemonetics Corp.10 Blood Quality standards can be found in…  Guidance documents  Memo’s to blood establishments  Prior 510ks  Transcripts from public meetings BUT not in the Code of Federal Regulations??

Copyright © 2009 Haemonetics Corp.11 Scenario #1 Plasma- Secret criteria  Automated device already cleared to collect plasma labeled as FFP (frozen within 6 hours)  Very limited criteria published for plasma  Clinical trial designed to qualify FFP and plasma frozen within 24 hours  FDA has a host of parameters which now must be tested  Communication with competitors reveals everyone has a slightly different list

Copyright © 2009 Haemonetics Corp.12 #2 In vivo recovery: Higher is better  IDE submitted for a trial to qualify an apheresis device for collection of two units of red cells.  Acceptance criteria includes in vivo recovery criteria which has been applied in submissions for 10+ years.  Upon submitting 510(k) FDA informs us there is not more stringent criteria. … public session one slide contained a reference to more stringent criteria  Communication with competitors reveals everyone has a slightly different criteria.

Copyright © 2009 Haemonetics Corp.13 #3 Tell me what you got and them we’ll tell you the criteria  Public meeting a new criteria is revealed for platelets  Pre-meeting with FDA is held concerning acceptance criteria for a clinical study  Statistical boundaries were not defined  FDA asked us to provide analysis with various confidence levels, 90%, 95% and 99%  FDA determines criteria based on our analysis

Copyright © 2009 Haemonetics Corp.14 Effective Strategies  Type C: pre- 510(k) meeting to discuss strategy  Collaboration with competitors- let’s get in a room and hash this out.  Offer to develop guidance documents through a working group  Develop relationships with FDA to get a heads up about what initiatives are in process  IDE submission  Request for meta-analysis of data for products marketed  Fight fire with fire: Statistician as a resource

Copyright © 2009 Haemonetics Corp.15 What can we learn from CBER  Substantial equivalence is an antiquated term  A new model will be developed to ensure safety and effectiveness for non-PMA devices  Performance standards will be developed  FDA may want to raise the bar… but this must be based on reality  In God we trust all… all others bring data  Access to a Statistician is critical  FDA does not have enough resources.. get involved and help to develop standards.

Thanks for your attention Questions?? Comments???

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