Safety and Efficacy of Plasma-derived Products

Principal Investigator: Mei-Ying W. Yu, PhD
Office / Division / Lab: OBRR / DH / LPD

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Overview

Public Health Issue: In protecting public health, FDA has a mandate to ensure the safety and efficacy of plasma-derived products, especially, coagulation factors and immunoglobulins (e.g., IGIM, IGIV or IGSC products for treating immunodeficiency disorders, botulinum antitoxins for counterterrorism, or anti-D( Rho) immune globulins for prevention of hemolytic disease of the newborn).

Regulatory Contribution: To increase the safety of plasma derivatives, especially with respect to blood-borne viruses; to improve the assessment of purity and potency profiles of plasma and final products; and to support international harmonization efforts, compliance actions, and studies addressing public health concerns.

Research Approach: Our research spans the following areas: (Ia) developing and using Nucleic Acid-based Testing (NAT) methods to detect and characterize viral contaminants in plasma-derived products and in investigating transfusion-related events; (Ib) developing and calibrating CBER/FDA and international NAT standards for viral pathogens; (Ic) monitoring parvovirus B19 transmission in transfusion recipients of blood and blood products in a prospective study; (II) developing CBER/FDA and international safety and potency standards for product lot release testing of therapeutic immunoglobulins including hepatitis B immune globulin products; (III) assessing and monitoring levels of binding/neutralizing antibodies to B19, HAV, HBV, HCV, and WNV in therapeutic immunoglobulins; (IV) monitoring the molecular integrity of immune globulins, including botulinum antitoxin of human or equine origin.

Mission Relevance & Outcomes: Our research studies have impacted (1)the safety of blood and blood products with respect to viral pathogens in transfusion recipients, (2)the establishment of national, international, or global standards that would ensure the safety and potency of plasma-derived products, (3)the assessment and development of binding/neutralizing antibodies against blood borne pathogens in therapeutic immune globulin products, and (4)integrity and lot consistency of immune globulin products including Botulism Immune Globulins for counter bioterrorism.

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Publications

J Pharmacol Exp Ther 2008 Apr;325(1):146-53
A neuronal microtubule-interacting agent, NAPVSIPQ, reduces tau pathology and enhances cognitive function in a mouse model of Alzheimer's disease.
Matsuoka Y, Jouroukhin Y, Gray AJ, Ma L, Hirata-Fukae C, Li HF, Feng L, Lecanu L, Walker BR, Planel E, Arancio O, Gozes I, Aisen PS

Gene 2007 Oct 1;400(1-2):114-21
Identification of novel suppressors for Mog1 implies its involvement in RNA metabolism, lipid metabolism and signal transduction.
Oki M, Ma L, Wang Y, Hatanaka A, Miyazato C, Tatebayashi K, Nishitani H, Uchida H, Nishimoto T

Transfusion 2007 May;47(5):883-9
Parvovirus B19 DNA in Factor VIII concentrates: effects of manufacturing procedures and B19 screening by nucleic acid testing.
Geng Y, Wu CG, Bhattacharyya SP, Tan D, Guo ZP, Yu MY

Proc Natl Acad Sci U S A 2007 May 15;104(20):8449-54
Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma.
Zhang P, Wu CG, Mihalik K, Virata-Theimer ML, Yu MY, Alter HJ, Feinstone SM

Transfusion 2006 Oct;46(10):1829-35
Quantification of hepatitis B virus genomes and infectivity in human serum samples.
Hsia CC, Purcell RH, Farshid M, Lachenbruch PA, Yu MY

J Infect Dis 2006 Sep 15;194(6):781-9
Measles-virus-neutralizing antibodies in intravenous immunoglobulins.
Audet S, Virata-Theimer ML, Beeler JA, Scott DE, Frazier DJ, Mikolajczyk MG, Eller N, Chen FM, Yu MY

Biologicals 2006 Sep;34(3):209-12
International collaborative study to assess candidate reference preparations to control the level of anti-D in IVIG for use in Europe and the United States.
Thorpe SJ, Fox B, Heath A, Behr-Gross ME, Virata ML, Yu MY

Proc Natl Acad Sci U S A 2006 Jun 13;103(24):9214-9
Neutralization epitope responsible for the hepatitis B virus subtype-specific protection in chimpanzees.
Zhang P, Yu MY, Venable R, Alter HJ, Shih JW

Vox Sang 2005 Jul;89(1):52-8
A World Health Organization International Standard for hepatitis A virus RNA nucleic acid amplification technology assays.
Saldanha J, Heath A, Lelie N, Pisani G, Yu MY; the Collaborative Study Group.

Transfusion 2005 Jun;45(6):1003-10
Parvovirus B19 transmission by a high-purity factor VIII concentrate.
Wu CG, Mason B, Jong J, Erdman D, McKernan L, Oakley M, Soucie M, Evatt B, Yu MY.

Vox Sang 2005 May;88(4):278-87
International collaborative study to evaluate a candidate reference preparation to define an appropriate specified limit of anti-D in intravenous immunoglobulin products.
Thorpe SJ, Fox B, Heath A, Dolman C, Virata ML, Yu MW, Thorpe R.

Proc Natl Acad Sci U S A. 2004 May 18;101(20):7705-10.
Neutralizing antibodies to hepatitis C virus (HCV) in immune globulins derived from anti-HCV-positive plasma.
Yu MY, Bartosch B, Zhang P, Guo ZP, Renzi PM, Shen LM, Granier C, Feinstone SM, Cosset FL, Purcell RH.

Transfusion 2004 Feb;44(2):307-8
HCV core antigen as an alternative to NAT to detect HCV viremia.
Raker CA, Tabor E, Okayama A, Yu MY, Kohara M, Mueller NE, Tsubouchi H, Stuver SO.

Pharmeuropa Bio 2004 Jan;2003(2):9-26
Collaborative study for establishment of a global standard for the potency assay of human anti-D immunoglobulin.
Thorpe SJ, Sands D, Fox B, Schaffner G, Yu MW, Behr-Gross ME.