- Created: Friday, 09 September 2016 19:35
Updated Oct. 3, 2016
Recent scientific and public press reports have heightened awareness of the emergence of Zika virus (ZIKV) in the Americas1,2 and the causal relationship between prenatal ZIKV infection and microcephaly and other severe fetal brain defects3,4.
ZIKV infection has also been associated with an increased incidence of Guillain–Barré syndrome (GBS). PPTA is aware that persons who use plasma protein therapies are understandably concerned about whether these therapies remain safe with respect to the ZIKV.
ZIKV is a Flavivirus that is primarily transmitted by infected Aedes mosquitoes5, however, transmission may also occur by sexual contact, from a pregnant woman to her unborn child during pregnancy or during birth6,7,8 or by transfusion of infected blood9,10.
ZIKV is of intermediate size (approximately 40–60 nm in diameter), has a lipid envelope and is therefore similar to other Flaviviruses such as West Nile (WNV), Dengue (DENV), Yellow Fever (YFV) and Japanese Encephalitis (JEV) viruses. This group of viruses is highly susceptible to manufacturing steps with virus inactivation and removal capacity as typically used in the production of plasma derived medicinal products, such as caprylate- or solvent-detergent (S/D) treatments, low pH incubation, pasteurization, dry-heat treatments, nanofiltration or plasma fractionation processes. The effectiveness of these processes has been clearly demonstrated using closely related lipid-enveloped model viruses belonging as ZIKV to the Flavivirus family, e.g., Bovine viral diarrhea virus (BVDV), or Tick-borne encephalitis virus (TBEV), or WNV11-16.
In addition, donor screening procedures make it highly unlikely that any person showing disease symptoms typical of ZIKV would be accepted for donation.
PPTA member companies have established convincing evidence to support the capacity of their plasma product manufacturing processes to effectively eliminate Flaviviruses, in case they would be present in the plasma. Given the scientific data, and aligned with guidance from European17,21 and U.S.18 health authorities, PPTA is assured that existing manufacturing methods are also fully effective against ZIKV, and consequently, the safety of plasma protein therapies is not affected by ZIKV.
PPTA is aware that there are recommendations by regulatory agencies and blood collection organizations to defer potential donors of blood components3,17-20 who are at risk for ZIKV infection and, in some cases, to halt blood collections in ZIKV risk areas1,17-20. In August 2016, the FDA revised its earlier recommendations to advise that all states and U.S. territories screen individual units of donated whole blood and blood components with a blood screening test authorized for use. Alternatively, steps with pathogen reduction or inactivation capacity can be used for some components18.
According to recommendations from U.S. and European health authorities17,18,21 measures such as halting collections, donor deferral or testing are not necessary for plasma, which is further manufactured into plasma protein therapies as these are safe with regard to ZIKV.
Based on robust virus clearance capacity during manufacturing of plasma-derived products and current regulatory guidance in Europe and the U.S., PPTA does not consider that deferral of donors or donation testing is necessary for plasma used for further manufacturing into plasma-derived therapies.
- Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika Virus and Birth Defects--Reviewing the Evidence for Causality. N Engl J Med. 2016 May 19;374(20):1981-7.
- European Centre for Disease Prevention and Control. Zika virus infection (factsheet for health professionals) [Internet]. Stockholm: ECDC; 23 June 2016 http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/factsheet-health-professionals/Pages/factsheet_health_professionals.aspx
- D'Ortenzio E, Matheron S, de Lamballerie X, Hubert B, Piorkowski G, Maquart M, Descamps D,Damond F, Yazdanpanah Y, Leparc-Goffart I. Evidence of sexual transmission of Zika virus. N Engl J Med. 2016 Apr 1
- Atkinson B, Hearn P, Afrough B, Lumley S, Carter D, Aarons EJ, et al. Detection of Zika virus in semen [letter]. Emerg Infect Dis. 5 May 2016
- Musso D Nhan T, Robin E, Roche C, Bierlaire D, Zisou K, Shan Yan A, Cao-Lormeau VM and Broult J. Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014. Euro Surveill. 2014;19(14):pii=20761. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20761
- Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, Stanfield SM, Duffy MR. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 2008; 17:1232-1239
- Dichtelmüller HO, Biesert L, Fabbrizzi F, Gajardo R, Gröner A, von Hoegen I, Jorquera JI, Kempf C, Kreil TR, Pifat D, Osheroff W, Poelsler G. Robustness of solvent/detergent treatment of plasma derivatives: a data collection from Plasma Protein Therapeutics Association member companies. Transfusion. 2009 Sep;49(9):1931-43
- Caballero S, Diez JM, Belda FJ, Otegui M, Herring S, Roth NJ, Lee D, Gajardo R, Jorquera JI. Robustness of nanofiltration for increasing the viral safety margin of biological products. Biologicals. 2014 Mar;42(2):79-85
- Remington KM, Trejo SR, Buczynski G, Li H, Osheroff WP, Brown JP, Renfrow H, Reynolds R, Pifat DY. Inactivation of West Nile virus, vaccinia virus and viral surrogates for relevant and emergent viral pathogens in plasma-derived products. Vox Sang. 2004 Jul;87(1):10-8
- Kreil TR, Berting A, Kistner O, Kindermann J. West Nile virus and the safety of plasma derivatives: verification of high safety margins, and the validity of predictions based on model virus data. Transfusion. 2003 Aug;43(8):1023-8
- Stucki M, Boschetti N, Schäfer W, Hostettler T, Käsermann F, Nowak T, Gröner A, Kempf C. Investigations of prion and virus safety of a new liquid IVIG product. Biologicals, 2008, 36(4):239-47. doi: 10.1016/j.biologicals.2008.01.004. Epub 2008 Mar 12.
- Dichtelmüller HO, Biesert L, Fabbrizzi F, Falbo A, Flechsig E, Gröner A, von Hoegen I, Kempf C, Kreil TR, Lee DC, Pölsler G, Roth NJ. Contribution to safety of immunoglobulin and albumin from virus partitioning and inactivation by cold ethanol fractionation: a data collection from Plasma Protein Therapeutics Association member companies. Transfusion. 2011 Jul;51(7):1412-30).
- European Centre for Disease Prevention and Control Scientific Advice. Zika virus and substances of human origin. [Internet]. Stockholm: ECDC; July 2016 http://ecdc.europa.eu/en/publications/Publications/Zika-virus-safety-of-substances-of-human-origin.pdf
- Guidance for Industry: Revised Recommendations for Reducing the Risk of Zika Virus Transmission by Blood and Blood Components, FDA, August 2016. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM518213.pdf
- Lanteri MC, Kleinman SH, Glynn SA, Musso D, Keith Hoots W, Custer BS, Sabino EC, Busch MP. Zika virus: a new threat to the safety of the blood supply with worldwide impact and implications. Transfusion. 2016 Jul;56(7):1907-14
- European Medicines Agency (EMA) Biologics Working Party (BWP): BWP Report on viral safety of plasma-derived and urine-derived medicinal products with respect to Zika virus/ EMA/CHMP/BWP/596747/2016/; [Internet]. London: EMA; 15 September 2016 http://www.ema.europa.eu/docs/en_GB/document_library/Report/2016/09/WC500213035.pdf