As the Tissue Banking Industry Readies Itself for Increased Regulatory Oversight, a New Comparative Study Proves How a Once Controversial Allograft Sterilization Method Evolved into a Major Technological and Commercial Advance.

LOS ANGELES -- Clearant Process(R) Assures Complete Microbial Sterility and Allograft Performance

It is well-established that conventionally processed human tissue implants carry an inherent risk of contamination, including infections at the surgical site(1). Due to the adverse patient consequences that can result from communicable disease transmission, as well as the increasing use of allografts for orthopedic surgical procedures, U.S. regulatory authorities have called for development of new methods of sterilizing tissue that do not adversely affect the functioning of the tissue when transplanted into patients(2). Historically, this kind of call-to-action would have posed a real challenge for tissue banks since the choice of currently available processing techniques required some degree of compromise between safety and efficacy. Now, however, tissue banks have a new avenue open to them. As results from a recently published study in the journal Biomaterials confirms, the Clearant Process(R) sterilization method eliminates risk of disease transmission in human allografts while maintaining the strength and elasticity of the tissue(3).

Conducted by research scientists from Clearant, Inc., a biotechnology company, and AlloSource, one of the nation's largest non-profit providers of human tissue allografts, the study is the first randomized, dose-dependent analysis to compare conventional low-dose gamma irradiation to Clearant's optimized, high-dose gamma irradiation method.

"Clearant's technology solves a longstanding dilemma for tissue banks and surgeons," said Fred D. Cushner, M.D., attending orthopedic surgeon at the Insall Scott Kelly Institute and team physician for the New York Knicks' basketball team.

Dr. Cushner continued, "The trade-off no longer has to be between use of traditional high-dose gamma irradiation - which destroys pathogens and sterilizes tissue but compromises graft performance - or conventional low-dose irradiation that maintains tissue viability but is incapable of eliminating the bacterial spores and viruses that can result in serious morbidity and death. Clearant Process-treated tissue provides unparalleled safety and sterility with performance equal to or better than low-dose irradiated allografts."

Allograft-Associated Infections: How Real Is The Threat?

Last year, cases of allograft-associated infections were reported from 20 states, involving 12 different tissue processors. Moreover, the Centers for Disease Control and Prevention (CDC) recently stated that this kind of passive surveillance system, which relies on clinicians to proactively report problems to public health authorities, often provides incomplete information and fails to capture many cases(4).

To illustrate this point, one recent study, which analyzed data from 39 U.S. tissue procurement agencies, estimated that as many as 350 hepatitis C virus (HCV)-infected musculoskeletal tissue specimens may be distributed each year.(5) Application of low-dose gamma irradiation (between 10-to-25 kiloGrays) cannot substantially inactivate this virus or any other, including HIV.

"The threat to tissue safety can only be mitigated through sterilization methods that prevent transmission of communicable diseases. As this study demonstrates, the Clearant Process represents an opportunity for the industry to meet the sterilization criteria for implantable medical devices and tissue allografts. Consistent with what we have found in separate studies of several hundreds of hard and soft allografts, these findings represent further evidence that Clearant's technology maintains the biomechanical integrity of allograft implants," said Alain Delongchamp, Chief Operating Officer, Clearant, Inc.

Optimized, High-Dose Gamma Irradiation: Study Methodology and Conclusions

The bacteria and viruses tested were collaboratively selected by the study authors based on clinical importance; occurrence as a contaminant in tissue products; resistance to inactivation by gamma irradiation; and recommendations from the United States Pharmacopoeia for sterility testing.

Cancellous bone dowels, provided by AlloSource, were randomly divided into a non-irradiated control group (n=24), a 50kGy optimized irradiation group pre-treated with a radioprotectant solution (n=24), as well as a third group irradiated by AlloSource (n=10) to a targeted dose of 18kGy using their standard practices.

Conclusions from the study demonstrated that 50kGy of gamma irradiation when performed under optimized conditions (that is, the Clearant Process) maintains compressive strength and elasticity equal to both non-irradiated control grafts and conventionally irradiated (18kGy) grafts, and virtually eliminates viruses and bacteria from tissue to the levels required by the U.S. Food and Drug Administration for other biological products.

Mr. Delongchamp concluded, "The need for sterility is not occasional, it is universal. A tissue implant sterilized in its final packaging under the Clearant Process conditions provides the sterility assurance of high dose gamma irradiation without any change in biomechanical quality."

About Clearant, Inc.

Clearant, Inc., a biotechnology company headquartered in Los Angeles, California, is a leader in pathogen inactivation for biological products. Clearant, Inc. has developed the patent protected Clearant Process(R), designed to substantially reduce all types of pathogens in biological products while maintaining a high degree of the underlying protein. Various sterilization methods on the market today only kill specific types of pathogens, such as bacteria or lipid-enveloped viruses, for specific products. The Clearant Process(R) can substantially reduce all types of pathogens for products across many market segments including plasma proteins, tissue implants, recombinant products and blood products, and can be applied at various stages of product processing/manufacturing, including in the final container.

References

(1) FDA Center for Biologics Evaluation and Research (CBER). FY 2003 Annual Report: Innovative Technology Advancing Public Health. Published March 2004. Available at www.fda.gov/cber/inside/annrpt.htm. Accessed October 6, 2004.

(2) Tissue Banks: The Dangers of Tainted Tissues and the Need for Federal Regulation: Statement of Jesse L. Goodman, M.D., M.P.H., FDA Center for Biologics Evaluation and Research, before the U.S. Senate Committee on Governmental Affairs. May 14, 2003. Available at http://www.fda.gov/ola/2003/tissuebanks0514.html. Accessed October 4, 2004.

Grieb TA, Forng RY, Stafford RE, Lin J, Almeida J, Bogdansky S, Ronholdt C, Drohan WN, Burgess WH: Effective use of optimized, high-dose (50kGy) gamma irradiation for pathogen inactivation of human bone allografts. Biomaterials (article in press). Available at http://www.sciencedirect.com. Accessed October 4, 2004.

(3) CDC Response to Infections Related to Human Tissue Transplantation: Statement of Steven L. Solomon, M.D., CDC Division of Healthcare Quality Promotion, before the U.S. Senate Committee on Governmental Affairs. May 14, 2003. Available at http://www.cdc.gov/washington/testimony/ps051403.htm. Accessed October 6, 2004.

(4) CDC Response to Infections Related to Human Tissue Transplantation: Statement of Steven L. Solomon, M.D., CDC Division of Healthcare Quality Promotion, before the U.S. Senate Committee on Governmental Affairs. May 14, 2003. Available at http://www.cdc.gov/washington/testimony/ps051403.htm. Accessed October 6, 2004.

(5) Archibald LK. Risk of HCV-Infected Allografts. Infectious Diseases Society of America 41st Annual Meeting: Poster 372. Presented October 10, 2003. Reported in Medscape Medical News, October 13, 2003. Available at http://www.medscape.com/viewarticle/462909. Accessed October 7, 2004.