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Gaithersburg, MD, United States

Burgess H.W.,Statseal Inc. | MacKrell J.,Carnegie Mellon University | Toms D.,Carnegie Mellon University | Karunanidhi A.,Carnegie Mellon University | And 4 more authors.
Journal of Biomaterials Applications | Year: 2010

Allograft tissues are used in over one million musculoskeletal procedures per year. Consequently, it is crucial tissue banks use procedures to militate against allograft associated bacterial and viral infections. Recent studies have identified an important pathogen inactivation technology for musculoskeletal allografts that utilizes high-dose gamma irradiation (50 kGy) under controlled conditions. A total dose of 50 kGy assures that the current standard for medical devices for a microbial sterility assurance level of 10- 6 is met. Furthermore, the pathogen inactivation technology results in a greater than four log inactivation of enveloped and nonenveloped viruses. Efficacious clinical outcome from musculoskeletal allografts exposed to this innovative sterilization procedure will require that there is no performance decrement in the allograft's biological properties. Therefore, to validate this objective, we executed a study focusing on remodeling and osteoconduction of bone allografts treated with a high dose of gamma irradiation (50 kGy), radioprotectants and well-defined operating parameters of temperature and water content. A rabbit calvarial model was used to test the hypothesis that remodeling and osteoconduction of allogeneic bone treated with the new pathogen inactivation technology would be equivalent to nontreated allogeneic bone. Results indicated treated bone allografts were comparable to nontreated allografts. We conclude, therefore, that based on this outcome and other reports, that high doses of gamma irradiation under optimized conditions designed to reduce free radical damage to tissue will provide safer allografts.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 98.17K | Year: 2001

DESCRIPTION (provided by applicant): We propose to develop virally safe human plasma for fractionation and transfusion using y irradiation. No comprehensive means of virally inactivating plasma for transfusion exists, and plasma derivatives are vulnerable to viral transmission. Gamma radiation kills all viruses, however a commercially viable application that does not produce unacceptable damage to plasma has not been developed. Clearant's preliminary work with purified proteins demonstrated the effectiveness of our approach, which utilizes several techniques to minimize protein damage without affecting viral inactivation. One of these may both virally-inactivate plasma and make it stable at room temperature. This would be a new form of plasma with significant benefits to patients, particularly in rural areas and on the battlefield. Applying our y irradiation processes to whole plasma is expected to require significant development as plasma is a complex combination of diverse proteins, each of which must be protected. A virally-inactivated plasma for both fractionation and transfusion will improve the risk:benefit calculations inherent to transfusion medicine. The results will be less disease transmission and fewer concerns on behalf of patients and physicians. Room temperature stable plasma will also enhance medical care. Thus the benefits to society, and the commercial potential of this work are significant. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 749.90K | Year: 2003

DESCRIPTION (provided by applicant): The recent transmission of HIV by tested blood and plasma demonstrates the need for viral inactivation technology that can be safely applied to plasma. In Phase I, Clearant demonstrated the feasibility of applying a virucidal dose of irradiation to plasma for transfusion using the Clearant Process TM. On a commercial scale, this will be significantly less expensive than other technologies in development. Clearant proposes to develop methods of utilizing gamma-irradiation to inactivate viruses in single donor units of frozen plasma. The goal is to define and test parameters for irradiation of plasma on a commercial scale to inactivate at least 6xlogl0 of enveloped viruses and 4xlogl0 of non-enveloped viruses while retaining marker protein integrity. Protein recovery and activity will be measured using biochemical techniques. In vivo studies will assess acute toxicity, chronic toxicity, and efficacy of the irradiated plasma when compared to the non-irradiated control. Scale-up will involve preliminary screening of the plasma bag material and development of full-scale irradiation procedures at commercial facilities. Viral inactivation and stability studies will be performed at key milestones during process development. Blood banks will license the technology from Clearant, providing a significant commercial opportunity for all organizations while preventing the spread of viruses

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 252.17K | Year: 2003

DESCRIPTION (provided by applicant): Clearant, Inc. proposes to develop methods of utilizing gamma-irradiation to inactivate prions in plasma-derived protein products while preserving their integrity and functions. The primary goal is to achieve at least 2xlog10 reduction in prion infectivity while retaining >80 percent of protein structure and activity. Clearant's proprietary process minimizes protein damage at doses up to 50 kGy or more in purified proteins and has demonstrated viral inactivation. This process is applicable to solutions, liquid or frozen, powders, and pastes, making it amenable to incorporation into manufacturing processes. Preliminary data also indicates reductions in prion infectivity may occur. Two different plasma proteins, IGIV and PPF, will be irradiated as manufacturing process intermediates. They will be spiked with scrapie and irradiated at several dosages under varying conditions. Prion inactivation will be measured in an in vivo infectivity assay. Protein recovery will be measured using biochemical techniques. Achieving these goals will profoundly impact the safety of plasma-derived therapeutics, which represent a $1.5B market in the U.S. Plasma fractionators, several of which are interested in using this technology on their process intermediates, would license the technology from Clearant, providing a significant commercial opportunity while preventing the possible spread of prion diseases from plasma products.

Smeltzer C.C.,Clearant Inc. | Lukinova N.I.,Clearant Inc. | Towcimak N.D.,Clearant Inc. | Yan X.,Clearant Inc. | And 4 more authors.
Biologicals | Year: 2015

Plasma-originated commercial intravenous immunoglobulin, which is used for a variety of clinical purposes, has been studied to determine the effect of virus-inactivating doses of gamma irradiation on the structural-functional characteristics of the protein. A detailed analysis has been performed in response to a concern that the use of conventional gamma irradiation may damage biologically active proteins. The results demonstrate that although gamma irradiation of the IgG may have some impact on protein structure, the damage can be reduced or even prevented by appropriate irradiation conditions. At the virucidal dose of gamma irradiation (50 kGy) and a temperature of -80 °C, the integrity of the polypeptide chain of immunoglobulin and the secondary structure of IgG can be completely protected, while conformational changes in tertiary structure are significantly minimized to a level that preserves functional activity. The irradiated IgG retains specific antigen-binding properties and Fc-binding activity, indicating that the conformational integrity of the most important structural regions is not affected by γ-irradiation. These results present strong evidence that gamma irradiation treatment can be effectively implemented for inactivation of pathogens in IgG solutions that are used for intravenous injection. © 2015.

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