NAC National Advisory Committee Canadian Blood Services Review of Select Distribution Trends April 25, 2013 Toronto Rick Trifunov Director, Plasma Products & Services

Outline Recent Changes Fibrinogen SD Plasma Upcoming Products Product usage Thawed time Upcoming Products Distribution Trends

Recent Changes – Customer Letters Product Change 2013-12 Octagam 10% Introduction of octagam (5g, 10g, 20g) 2013-11 RiaSTAP and Haemocomplettan P Health Canada no longer approving Haemocomplettan P SAP requests due to licensed fibrinogen, RiaSTAP 2013-08 Immune Globulins and Prothrombin Complex Concentrates Annual Letter regarding Immune Globulins, plus the results of the RFP 2013-06 Tretten Introduction of recombinant FXIII 2013-04 RiaSTAP Introduction of fibringoen, RiaSTAP 2013-02 rFVIII Transition of recombinant FVIII 3

Fibrinogen Product Number of vials Jan'13 Feb'13 Mar'13 Apr'13 Haemocomplettan 91 45 6 12 RiaSTAP 50 70 Transition is completing from Haemocomplettan to RiaSTAP, no new requests for Haemo will be approved. Thanks to NAC for the medical review of RiaSTAP and apologies again for the poor communication of the interim use. RiaSTAP review was approved by CBS EMT, now is going to CADTH to begin their economic review. Kathryn is assisting. The CADTH review will be taken by CBS who will form a final recommendation we take back to the PTs. NAC guidelines on usage may follow.

Octaplasma Approval Octaplasma® will be made available for the following patients who require a high volume of transfusion due to: Congenital and acquired Thrombotic thrombocytopenic purpura (TTP) Haemolytic Uremic Syndrome (HUS) Complex and isolated coagulation disorders – both congenital and acquired – where no specific coagulation factor concentrate is available And who: Have experienced an allergic reaction to frozen plasma (FP), or Have a pre-existing lung disorder, or Need FP but a blood group compatible product is not available in a timely manner CAG AGM 2013

Octaplasma Usage Feedback from CAG conference Usage in many provinces is low, the additional order process is perceived as a barrier to some Does the allergic reaction have to be severe? No such wording in the approved use, but approvals for less severe reactions are sometimes not given. There should be more at-risk patients on the list—can we expand indications? Dare we wade into this again?

SD Plasma – Thawed time In December, the NAC asked CBS to investigate the potential to have Octapharma extend the allowable thawed time for Octaplasma, to 5 days. NAC requested the product monograph to be changed to reflect this. In discussion with Octapharma, they are not able to make this change at this time. They would need to present study evidence to Health Canada to substantiate such a change.

SD Plasma – Thawed time studies In 2004, a publication in Vox Sanguinis showed that the stability of coagulation factors in thawed Octaplasma was maintained for 6 days at 4 degrees. In 2011 Keller et al investigated the same topic under the title "Thawed solvent/detergent-treated plasma: too precious to be wasted after 6 hours?". It determined that in-vitro clotting factors remained stable for 24 hours at 4 degrees. From 24 hours to 6 days most clotting factors showed no significant changes, but FVII and FVIII decreased significantly. In late 2011, Octapharma R&D studied the stability of thawed single unit FFP at 4 degrees and room temperature. There was a substantial reduction in several coagulation factors and inhibitors, and other proteins. Based on these data the authors concluded that labelled instructions for Octaplasma should remain as is.

SD Plasma – Octapharma proposed study Octapharma is willing to support a study, and felt that using the same protocol as Dr. Sheffield's study of FFP and CSP was the best way to go. Bill would be willing to conduct this study, but only if it can result in Octapharma changing the product monograph (PM). Octapharma will investigate with HC if such a validity study would allow them to change their PM. They see an extension to 24 hours as being easily achieved, but would not recommend going beyond that if stability of coagulation factor levels cannot be assured. I’ll report back when we see what Octapharma finds out from Health Canada.

Upcoming Products Tretten recombinant Factor XIII A simplified medical review was done. Plasma-derived Factor XIII (Corifact) This product will be licensed towards the end of this year Given the large cost advantage versus Tretten, and that we’ll lose access to the SAP product Fibrogammin, a quick review and perhaps just a CADTH cost comparison review of Corifact versus Tretten should be done. CBS to see if CADTH could begin this review pre-licensure. Long-acting recombinant factor IX, from Biogen. This product just began the licensure process, should take about a year. Full review should be done, cannot start likely until April 2014.