Source Plasma Safety Plasma May 15-19, 2017 George Schreiber, ScD, PPTA Director, Epidemiology
Three components: Plasma Product Safety Donor Quality Manufacturing Pool Quality Fractionation Process Safe High Quality Plasma Products Slide 2
Relative Risk Plasma Quality Steps Donor selection Testing donations NAT testing Inventory Hold (where applicable) Virus inactivation / removal steps Finished product From Donor to Patient Therapy Slide 3
Plasma Quality Steps Important Plasma Quality Steps Donor Screening Medical history and physical examination (protects donor health and reduces recipient risk) Laboratory Testing Qualified Donors (Source Plasma) 60 Day Inventory Hold (Source Plasma) Residual Risk Assessments Epidemiological [viral marker] standards Slide 4
Donor Selection National Donor Deferral Registry (U.S. Source Plasma) Reactive donors entered in national database for HIV, HBV, HCV Prospective donors must be checked in database before allowed to donate Community- Based Donor Standard No donors without permanent address. Donors must reside within defined recruitment area Valild photo ID Donor Education Standard Donors must be educated regarding HIV/AIDS Assessment of comprehension for new donors Slide 5
International Quality Plasma Program Donor Selection Standards Lowered Risk Viral Marker Standard Center s viral marker rates compared to industry average Centers repeatedly exceeding Alert Limits subject to lose IQPP certification Qualified Donor Standard New donors must pass 2 medical screenings and testing Reactivated donors (Qualified with > 6 month lapse) must requalify Slide 6
Quality Standards of Excellence, Assurance & Leadership QSEAL Standards Lowered Risk Inventory Hold Standard Plasma held in inventory for at least 60 days after donation Allows for interdetection and destruction of plasma based on post-donation disqualifiers NAT Testing Standard Requires NAT for HIV, HBV and HCV at minipool and at First Homogeneous Pool level Requires in-process testing for HAV and Parvovirus B19 Slide 7
Viral Marker Standard A statistically reliable system to ensure collection from quality Source Plasma collection centers, based on viral marker rates. In place for over a decade Serves as a guide for quality improvement Marker specific for HIV, HCV, and HBV Academic peer-reviewed Approach endorsed by FDA Slide 8
Viral Marker Alert Limits Alert Levels allow for identification of centers with higher than expected viral positivity rates. Allows for continuous epidemiological evaluation at individual plasma collection centers together with an annual update of the assessment. Reference rates based on overall industry averages for donors contributing to the pool, measured in a defined time period with the most appropriate testing technology. Slide 9
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Donations (10 6 ) 13,233,773 13,824,545 12,644,462 10,317,674 10,368,480 12,442,214 15,326,821 18,817,869 22,028,860 19,807,473 23,573,488 26,214,019 29,391,097 32,550,293 35,464,612 38,296,234 40 30 20 10 0 Slide 10
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 # Centers 295 299 315 342 349 397 406 407 389 399 401 404 411 427 478 530 601 Number U.S. Centers 600 Number of US Source Plasma Centers 500 400 300 200 100 0 Slide 11
Qualified Donor Positivity Rates Slide 12
Residual Risk Estimates of a potentially infectious unit being released for fractionation or transfusion Slide 13
Residual Risk Residual Risk of Viral Agent Entering the Manufacturing Pool The presence of certain viruses in asymptomatic donors who are negative on the screening tests (window period donations) constitutes the major risk of viruses entering the fractionation process. The Residual Risk is the estimated probability of a potentially infectious plasma unit entering the manufacturing pool. Accounts for industry inventory hold. Used to assess the impact of industry safety initiatives. Can be used to estimate pool viral load. The viruses of concern are: HCV, HIV, and HBV. Slide 14
Residual Risk / 10 6 Donations HIV and HCV Residual Risk 5 4.6 4.5 4 3.87 HIV HCV 3.5 3 2.66 2.5 2 1.95 2.22 2.08 2.06 1.74 1.58 1.56 1.58 1.96 2.0 1.97 1.9 1.5 1 0.5 1.51 1.52 0.83 1.47 0.96 1.37 1.35 0.98 0.78 0.87 0.85 0.97 0.89 0.92 0.97 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Slide 15
Residual Risk / 106 Donations HBV Residual Risk 35 30.95 30 28.78 25 20 15 13.57 14.01 12.74 13.92 13.9 11.98 12.91 10.41 10 9.77 9.29 7.42 8.97 8.15 5 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Slide 16
Odds of Dying: What we Should Fear Odds versus Risk Odds per 1,000,000 Cancer (lifetime) 142,857 Hospital Infection (lifetime) 26,316 Complications of Medical Surgical Care (lifetime) 762 Exposure to Forces of Nature (lifetime) 574 Drowning in a Bathtub (lifetime) 90 Killed by a dog (lifetime) 9 Asteroid Impact (Lifetime) 5 Struck by Lighting (year) 2.5 Versus Risk of: A Potentially Infectious Source Plasma Unit Making it to the Manufacturing Pool 1-8 Slide 17
Key Points to Remember Residual risk for Source Plasma not the same as RR for whole blood. WB is risk of transmission by transfusion. Source Plasma is risk of a POTENTIALLY contaminated unit entering manufacturing pool. Potentially contaminated units have detection levels below that of the NAT test. All manufactured Source Plasma derived products have virus removed or inactivated. Residual risk of transmission is then reduced to zero. Slide 18
Effectiveness of Inventory Hold in Reducing Residual Risk (per 10 6 ) Inventory Hold 2014 Residual Risk 2015 Residual Risk Hold 0-Day Hold 60-Day No Hold /60-Day % Reduction Hold 0-Day Hold 60- Day No Hold /60 days % Reduction HIV 9.68 0.92 10.5 90.5 9.87 0.97 10.2 90.2 HCV 25.42 1.97 12.9 92.3 25.12 1.90 13.2 92.4 HBV 86.84 8.97 9.7 89.7 73.36 8.15 9.0 88.8 Slide 19
Residual Risk Percent Percent of Residual Risk - 2015 (Incidence Donor / Total) No Hold 60-day Hold HIV 93.1 29.3 HCV 94.2 23.3 HBV 90.7 15.9 Percent of Residual Risk due to Incidence donors, by Inventory Hold. Slide 20
I ll pause for a moment so you can let this information sink in. Slide 21
Viral Load in Manufacturing Pool Viral Load Detection limit (96 minipool) Residual Risk Chance of WP donation in pool Viral Load 1 WP/pool (6000 donations) Viral Load if ALL donations are WP HCV 675 IU/mL 1.9 0.01 0.11 IU/mL 675 IU/mL HIV 4420 IU/mL 0.97 0.005 0.74 IU/mL 4420 IU/mL HBV 220 IU/mL 8.15 0.05 0.04 IU/mL 220 IU/mlL Slide 22
Effects on Viral Load Effect of Viral Inactivation / Removal on Viral Load Viral Load (IU/mL) 1 WP donation in pool All WP donations in pool 9 logs reduction 12 logs reduction 9 logs reduction 12 logs reduction HCV 1.1 / 10 10 1.1 / 10 13 6.8 / 10 7 6.8 / 10 10 HIV 7.4 / 10 10 7.4 / 10 13 4.4 / 10 6 4.4 / 10 9 HBV 4.0 / 10 11 4.0 / 10 14 1.1 / 10 7 1.1 / 10 10 Assuming one WP donation in the manufacturing pool, viral load reduction is complete. Even assuming all donations are WP, an impossible scenario, viral inactivation/removal steps guarantee product safety. Slide 23
Inherent Truths Demographic variations in infectious disease prevalence and incidence exist. Viral removal and inactivation are key to ensuring the safety of fractionated plasma products. Risk of a potentially infectious unit entering the plasma manufacturing pool is small. Viral inactivation and removal significantly reduces the residual risk in finished plasma products. Slide 24
Differences exist in how patients, regulators and industry view the importance of donor quality compared to product quality but all stakeholders recognize the importance of product safety. Plasma derived products have never been safer as a result of the rigorous efforts of the industry to ensure quality donors, sensitive testing, and virus inactivation/removal technologies. Inherent Truths There has been no confirmed case of transmission of viral infection in more than two decades, attesting to the safety of plasma derived products. Slide 25