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Key words: biomaterials, database, compendium, medical devices
The Beta test of the compendium data collection software is in progress. Beta Software was sent to 62 manufacturers with the expectation that over 100 records of previously approved devices representing different biomaterials would be completed by the end of March 1997. To date, OST has received a response from one manufacturer. DMMS participated in a series of meetings on the Compendium on March 19-20, 1996, in Memphis where industry concerns were voiced and discussed. Details of the discussions are available in a trip report. OST sent follow-up correspondence to the 62 companies in early April to encourage greater response. Through this effort, only three additional replies have been received. Additionally, OST has entered into discussions with DCRND to have a reviewer extract materials data for previously reviewed PMAs and to use the biomaterials data sheet format to obtain pre-PMA and pre-IDE data on new products. Further, OST scientists have worked with the American Chemical Society (ACS) to obtain a crossreference listing of CAS (Chemical Abstract Service) numbers to the generic materials listed in the Compendium. A cross-reference list of ASTM and ISO standards to the listed materials is also being generated. Both of these lists will be made available to the review staff through the CDRH MIS system.
During the past year, the Biomaterials Compendium was used to help catalogue medical products, including foods, drugs, biologics, and veterinary products regulated by FDA that are derived from a bovine source. This effort was in response to concerns that BSE ("Mad Cow") disease might be transmitted to humans through these products. The utility of the Biomaterials Compendium database was such that CVM and CBER are also interested in using it.
Progress is well underway to have the Compendium posted on the Center's intranet, and a query program has been written to the database. At present, the BSE database of 260 records is being used as the prototype. A revision of the data sheet program is being done by CB Tech. The system will be built so as to be on the Internet. [PreME, PostMS, Stds]
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Key words: Biotechnology Working Group
Primarily through the CDRH Biotechnology Working Group and the FDA InterCenter Tissue Engineering Working Group (TEWG), programs continue to provide the Center and Agency with program guidance, priorities, and planning options through 1) a broad scope of technology research monitoring and assessment; 2) options development for evaluating technological applications in medical devices; 3) promotion of science for regulatory decision making; and 4) formulation of science and regulatory policy recommendations. The primary objectives are to support regulatory activities and program development. The Center coordinator for Biotechnology and Chair of the TEWG has provided leadership in the organization of and active participation in several national and international biotechnology and tissue engineering forums. Several products are providing a strong knowledge base for the Center and the facilitation of scientific and regulatory review of new biotechnology-derived and tissue engineered products. These products include 1) a Draft Proposal for Discussion on International Regulatory Harmonization of Tissue Engineered Products, presented at the Tissue Engineering (TE) Workshop of the 5th World Congress on Biomaterials which was organized by an international committee; 2) incorporation of the Tissue Engineering Knowledge Base (TEKB), i.e., White Paper and Experts Registry, in the FDA FIRSt system, and development of a Draft Proposal for updating, expanding, and accessing the TEKB across FDA Centers; 3) the Spring 1996 Tissue Engineering (TE) Course, "TE: Current Challenges in Discovery, Development, and Review," and a planned course series with the Spring '97 course devoted to "TE and Clinical Issues"; and 4) a research proposal, "Test Methods for Tissue Engineered Products Standards" in response to the FDA Office of Science Priority Initiatives Process. [PreME, ProA]
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Key words: aortic valve allografts, leaflet cells, explants
This laboratory study was designed to investigate the histologic and pathologic changes which occur as a consequence of tissue processing and implantation of cryopreserved aortic valve allografts. Histologic, ultrastructural, and immunostaining studies were conducted on explanted aortic valve allografts retrieved from a preclinical animal model (juvenile sheep model: descending thoracic aorta) or clinically during reoperations secondary to congenital heart reconstructions. Preclinical allograft valves were investigated following 2, 10, 30 and 140 days of implantation in the descending thoracic aorta (juvenile sheep model), while clinical specimens were obtained following greater than 5 years' use in cardiac reconstructions of the right ventricular outflow tract.
The histologic findings of this investigation indicate that a significant reduction in the number of leaflet cells (i.e., fibroblasts, myofibroblasts, endothelial) occurred through the first 30 days of implantation in the juvenile sheep model. In addition, a marked reduction in cellularity and mitotic potential (as assessed by the presence of proliferative cell nuclear antigen) of the remaining leaflet cells were also noted following 30 days of implantation. Doppler echocardiography conducted following 20 weeks of implantation demonstrated complete immobilization of the allograft leaflets against the aortic wall. Histopathologic studies of the 20-week explants indicated that the formation of an extensive fibrous sheath (i.e., myofibroblasts, type I collagen) was responsible for the restricted leaflet motion. The thickness of the fibrous sheath is generally greater on the inflow side of the leaflet. The inflammatory response within the leaflet consisted of a limited number of macrophage, while few cells with mitotic potential remained within the leaflet tissue. The extracellular matrix components (principally type III collagen and elastic fibers) remained intact without evidence of significant calcification. Calcification was restricted to the aortic wall component of the allograft valve conduit. Clinical explants studies following at least 5 years' use demonstrated similar histologic and pathologic findings. [ProA]