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May 3, 2001 WOC-1, Conference Room 2 Present: FDA: Jill Warner, Marty Wells, Ruth Solomon, Paula McKeever, Jerry Davis, Astrid Szeto, Areta Kupchyk EBAA: Patricia Aiken O'Neill, Patricia Voljavec, Kurt Weber, Barbara Crow; Dr. Michael Hettinger (by telephone) The Eye Bank Association of America (EBAA) requested this meeting with FDA to discuss the proposed regulation on "Current Good Tissue Practice for Manufacturers of Human Cellular and Tissue-Based Products; Inspection and Enforcement," published for public comment on January 8, 2001, and how it will apply to eye banks. An agenda was distributed at the meeting (Attachment A), as well as the 2000 Eye Banking Statistical Report (Attachment B). EBAA made the following introductory statements. There are approximately 95 eye banks in the U.S. Only one is not a member of EBAA. EBAA supports the framework of the GTPs, but has concerns about certain issues and wants clarification. Eye banks differ from blood banks in that most are small entities that do all their own procuring, processing, and distributing. Much time is spent outside of the bank, to procure eye tissue. The time and cost to adhere to all of the GTPs may be prohibitive for the smaller eye banks. The following issues were discussed: Good Tissue Practices Subcontractors--EBAA explained that eye banks generally have written agreements with subcontractors (e.g., testing laboratories) which require that the lab be CLIA-certified, use FDA-licensed test kits, follow manufacturer's test kit instructions, etc. Is this sufficient, or would each eye bank have to physically audit the subcontractor? An audit would be difficult because of the time, expense, and lack of technical expertise in testing. FDA responded that contracts and agreements are discussed in 1271.270(f). There is no proposed requirement that an eye bank audit the subcontractor. However, the eye bank would be ultimately responsible for ensuring that the final tissue product be in compliance with proposed regulations. It is up to the eye bank to take whatever actions would ensure compliance by a subcontractor so that the final tissue product is in compliance with the regulations. CLIA certification is not sufficient to assure that a facility is in compliance with FDA requirements. In addition, a subcontractor that performs any step in a tissue manufacturing process is required under 21 CFR Part 1271 to register their establishment, list the products, and would be required under the proposed regulations to implement is own quality assurance program, including the performance of a self-audit. Carriers--FDA clarified that carriers (e.g., Federal Express, airlines) are exempt under the proposed and final regulations. Primary Graft Failure Dr. Hettinger discussed the fact that the data given in the economic analysis of the regulation--Estimated Benefits of the Proposed Rule (pages 1539-1540), may not be accurate, in terms of frequency of occurrence of primary graft failure, cost, need for hospitalization. He pointed out that primary graft failure may not be due to the cornea itself, but rather to the surgical technique. EBAA mentioned that primary graft failure is reported to the eye bank, and then to EBAA. FDA responded that EBAA should include in their comments to the docket a discussion of relevant data about primary graft failure. Computers EBAA explained that computers are used in eye banks to provide a backup for hard copy, and to summarize the donor medical history and serology results on a standardized form that accompanies the eye tissue. The software is off-the-shelf, such as FileMaker Pro. The computers are not involved in any decision-making process, such as determination of donor suitability. Would FDA expect computer software used for these purposes to be validated? FDA responded that the proposed regulation states that records be accurate and legible. FDA did not propose to require validation of commercially distributed record keeping software, which is not intended or used to make decisions. Facilities EBAA asked if the statement in 1271.190(a) that adequate toilet facilities shall be provided means that toilet facilities need to be in the eye bank. All eye banks have access to sinks for hand washing in the lab itself. FDA responded that toilets would not have to be physically located in the eye bank, as long as they were available, particularly for hand washing. EBAA suggested that the preamble clarify this. Environmental Control EBAA explained that eye banks do not use clean room techniques. Rather, since the workspace for processing eye tissue is relatively contained, eye banks use laminar flow cabinets. Would this satisfy 1271.195(a)(2)--control and monitoring of ventilation and air filtration? FDA responded that the proposed regulation states that where environmental conditions could reasonably be expected to have an adverse effect on the function or integrity of the tissue, the environment would need to be controlled and monitored. If the laminar flow cabinet adequately controls and monitors the relevant environment, it could satisfy this requirement. Equipment EBAA asked about 1271.200(a)--any automated, mechanical, electronic, computer, or other equipment used for inspection, measuring, and testing shall be capable of producing valid results. Eye banks use a slit lamp microscope to assess the overall quality of the cornea--there are no measurements made, and the user makes the assessment of the cornea. Would a slit lamp microscope need to be validated, and if so, how? FDA responded that the slit lamp microscope, based on the description provided by the EBAA representatives, does not appear to be capable of validation. A specular microscope, however, which actually counts cells, and produces a measurement, would have to be validated. FDA said that they would consult with CDRH about the slit lamp, and get back with EBAA. Process Validation EBAA asked for clarification on how process validation would apply to eye bank procedures. FDA explained that the proposed regulation for process validation would apply when verification (evaluation) of each individual cornea was not possible. For instance, packaging procedures might need to be validated to ensure that temperature could be controlled during shipment. Other procedures, where each cornea was inspected, would not have to be validated. Tracking EBAA discussed their standards for tracking of tissue to the recipient, and expressed concern that while they had excellent compliance from U.S. ophthalmologists, other ophthalmologists outside the U.S. often did not return information about the recipient. FDA responded that FDA regulations focus on having appropriate procedures in place. The proposed regulations would require establishments to put in place procedures to enable tracking. Establishments would be required to document that consignees agree to comply with tracking requirements. FDA's jurisdiction extends to tissue utilized within the U.S. International physician compliance with reporting recipient information or adverse reactions would remain voluntary. Other comments Effective date --EBAA indicated that there should be a long implementation period, (similar to that provided for hospitals under the recently published "Privacy" rule), before the GTP final rule would become effective, in order to allow small banks enough time to come into compliance. EBAA suggested a 2 year implementation period. FDA responded that EBAA should include this suggestion in their comments to the docket. When asked about the expected date of publication, FDA mentioned that a Unified Agenda, which publishes semi-annually, would contain this information. Future FDA and EBAA interaction --EBAA and FDA discussed how they could best work together in the future. They discussed a possible role for FDA as liaison to the EBAA Medical Advisory Board. EBAA asked how FDA could be more involved in the development of EBAA standards. FDA responded that FDA representatives can act as liaisons to association committees, such as is done with the AATB Standards Committee and Medical Advisory Committee. EBAA said that they would look into formally inviting FDA to provide a liaison to their Medical Advisory Board, which updates their Medical Standards, and possibly also to their Accreditation Committee. EBAA also offered to invite FDA to participate in future EBAA inspections. EBAA further suggested that joint workshops with FDA inspectors and EBAA inspectors would be helpful. FDA agreed and suggested that co-sponsorship of a workshop should be pursued once the GTP regulation is final. Guidance documents --Meeting attendees discussed the general nature of the proposed GTP regulations and the value of guidance specific to particular segments of the tissue industry. FDA suggested that EBAA might want to consider developing guidance on complying with the GTP regulations that would have specific applicability to the eye banking community. EBAA responded that they planned to do so. FDA outlined the process by which interested groups can submit proposed guidance documents to FDA, and if appropriate, FDA can issue such guidance or modified guidance as an FDA document after notice and comment procedures. Amniotic membrane --FDA asked about the use of amniotic membrane for ocular repair. EBAA mentioned that eye banks might occasionally be asked by an ophthalmologist to get him amniotic membrane, and that the eye bank would facilitate this service. FDA mentioned that it considers the use of amniotic membrane for ocular repair a nonhomologous use, and EBAA agreed. EBAA stated that they only knew of a few tissue banks that procured amniotic membrane. At the end of the meeting, the attendees agreed that the discussion had been worthwhile.

Updated May 29, 2001

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