PFDA, Blood Community Representatives Meet to Discuss Priorities
Reviews issues discussed during a recent meeting of FDA and blood community representatives where the two groups presented and reviewed issues important to their operations.
On Oct 04, 2007, Food and Drug Administration (FDA) staff met with AABB’s FDA Liaison Committee in Bethesda, MD, to discuss topics of mutual concern in the areas of donor and patient safety. The committee includes liaisons from AABB, the American Red Cross (ARC), America’s Blood Centers (ABC), Advanced Medical Technology Association (AdvaMed), the College of American Pathologists (CAP) and the U.S. Department of Defense (DoD).
FDA Outlines Current Initiatives and Priorities
A number of rules and guidance documents released in recent months by FDA address critical issues, including the classification of in vitro human immunodeficiency virus (HIV) drug resistance genotype assays, minimum sensitivity standards for hepatitis B surface antigen (HBsAg) assays, informed consent for plasma donors participating in plasmapheresis and immunization programs, revisions to some requirements for blood and blood components, final requirements and recommendations for hepatitis C virus (HCV) Lookback and draft recommendations for computer crossmatches. FDA also provided an update on pending documents of particular importance to the transfusion medicine community. The many comments received on the March 2003 proposed rule on safety reporting requirements, in particular to the proposed definition for serious adverse reactions, are being considered within the context of FDA’s efforts to improve the safety of a broad range of human drugs and biological products, including blood and blood components. The agency continues to work on final issues related to the July 2003 proposed rule on revisions to labeling and storage requirements for blood and blood components, including source plasma.
FDA acknowledged the importance to the blood community of two draft guidance documents addressing 1) platelets collected by automated methods (September 2003) and 2) pre-storage leukocyte reduction of whole blood and blood components (January 2001), emphasizing that the documents have been the subject of public meeting discussions. The agency has invested effort into developing a statistical framework for quality control that will provide statistically meaningful data while not being overly burdensome to the reporting facility. This quality control framework is important to both documents. Regarding the draft guidance for nucleic acid testing (NAT) for HIV-1 and HCV testing, product disposition and donor deferral and reentry (June 2000), FDA noted the complexity of the issues being addressed. Careful evaluation of comments received to the docket has guided development of a comprehensive set of recommendations. The agency also noted that it is actively working on recommendations for deferrals relating to malaria. A draft guidance document for malaria was issued June 2000 and a workshop was held July 2006. Finalizing recommendations for variant Creutzfeldt-Jakob disease (vCJD) risks associated with transfusion in France (August 2006) is also receiving priority attention from the agency.
Other priority considerations for FDA include: donor screening for Chagas’disease, West Nile virus NAT testing, TRALI, the abbreviated donor history questionnaire (DHQ), management of donors with risks for HIV group O, validation of blood establishment computer software (BECS) and deferral issues relevant to recipients of a xenotransplant. An update was provided on the activities of CBER’s Blood Safety Team. Primary goals of the cross Office team are to improve CBER’s response to blood safety issues, improve the value of safety information and broaden public and regulated industry access to the information, improve the processing of blood safety information, and enhance external outreach, evaluation and risk communication. Current activities include development of the first annual donor fatality report, as well as assessing the relative significance of blood product deviation events as they are currently reported. The team is also looking at ways to obtain ‘denominator’ data to extract value from currently collected data and is assessing the value of developing a post donation information workshop.
Biovigilance activities are coordinated within a larger Health and Human Services initiative focused on blood, tissues and organs. A gap analysis has been completed to identify strengths, weaknesses, opportunities, and threats within the following areas: donor events and outcomes, recipient events and outcomes, product deviations, emerging infectious disease (EID) monitoring, and ability to track denominator data. Opportunities identified include development of policies to improve donor and patient safety, exploring options to collect denominator data for products and units transfused, developing statistical modeling for blood usage, evaluating the usefulness of some reporting categories currently used, and increasing the use of technologies such as barcoding and radio frequency identification.
Pandemic planning activities are focused on regulatory considerations in the face of pandemics, including potential interventions, triggers and pathways for implementation, and how to maintain flexibility while preserving public safety. FDA staff and the AABB Interorganizational Task Force on Pandemic Influenza and the Blood Supply met in June to discuss such issues. One possible intervention under discussion is decreasing the 56-day donation interval, in combination with routine hemoglobin level checks of donors. The task force agreed that this intervention could have a substantial and positive impact on the blood supply. (FDA indicated willingness to consider how decreased intervals between donations might also extend to double-red cell collections and suggested that the AABB TF should develop a proposal for consideration by the agency.) Temporary modifications related to other deferrals, including travel, have been estimated to have only a modest impact on the available inventory. FDA cited the importance of defining trigger mechanisms for turning the intervention(s) on and off. FDA noted that advance planning and having guidance in place prior to the actual need is the ideal, although pathways utilized in prior emergency situations have included issuance of emergency guidances and use of enforcement discretion. FDA internal planning includes a CBER level continuity of operations (COOP) plan. Mathematical modeling of blood supply impact by a pandemic and geographical information systems to identify blood establishments affected during an emergency are being explored and FDA plans to test some of these models with blood establishments in the near future.
The FDA Amendments Act (FDAAA), was signed into law on September 27th. The Act will be important in setting FDA priorities, including regulations and guidance. FDAAA reauthorized the Prescription Drug User Fee Act and Medical Device User Fee and Modernization Act, and included a strong focus on pediatrics (including biologics). Other provisions include the creation of a foundation (Reagan-Udall) through which additional funds could be obtained to modernize product development, accelerate innovation, and enhance product safety: expansion of the clinical trial registries that reside on the National Institutes of Health web site; provisions intended to enhance drug safety; and food safety.
On an international level FDA interacts with various standards setting organizations. Among these is the World Health Organization, and as a WHO Collaborating Center for Biological Standardization. FDA assists in the development of international standards and/or reference materials for areas such as in vitro diagnostic tests including NAT, plasma proteins, and blood group reagents. FDA is also a member of the newly formed WHO Blood Regulators Network. Members of the BRN each have comprehensive regulatory schemes with international influence. Goals of the network include enhanced communication, rapid regulatory response, and a convergence of regulatory thinking, although harmonization per se is not within the scope of Network goals. OBRR participates with the Council of Europe and is involved with updates to the Guide for Preparation, Use and Quality Assurance of Blood Components.
AABB Current Initiatives and Priorities
AABB continues to be focused on a myriad of issues related to donor and patient safety. Activities related to TRALI, biovigilance, availability of tests for donor screening, implementation of ISBT 128, and bacterial contamination of platelet components were highlighted at the meeting.
AABB Association Bulletin #06-07 Transfusion-Related Acute Lung Injury contains recommendations to further reduce the risk of TRALI in blood and blood component recipients. The association bulletin recommends that blood centers minimize the preparation of high plasma-volume components from certain donors; implementation of appropriate evidence-based hemotherapy practices; and the need for monitoring of the incidence of reported TRALI and TRALI-related mortality. Follow-up to the bulletin includes distribution of a member survey requesting information on progress and barriers to efforts to mitigate the risk of TRALI.
Active biovigilance programs include the Chagas’ and West Nile virus surveillance systems on the AABB web site. In addition, the Emerging Infectious Diseases (EID) subgroup of AABB’s Transfusion Transmitted Diseases committee is nearing the completion of a project to compile fact sheets on approximately 65 EID agents – evaluating each for potential transfusion transmission. AABB has created two biovigilance working groups – the Recipient Biovigilance WG is working with CDC to develop a national hemovigilance system using the model of the National Health Surveillance Network, and the Donor Biovigilance WG will develop definitions for events to be captured in a surveillance system.
Another growing concern is the lack of availability of donor screening test kits and reagents.
AABB facilities are working towards implementation of ISBT 128 in May, 2008, with several blood systems having already implemented.
The proposed 25th edition of Standards for Blood Bank and Transfusion Services contains a requirement for diversion pouches, in addition to other steps that facilities have undertaken to limit and detect bacterial contamination in blood products.
Discussion of Agenda Items
FDA explained the process the agency is considering to respond to this need for a regulatory pathway for the one-way conversion of apheresis FFP (prior to expiration) to a licensed concurrently collected plasma product for further manufacture. FDA is considering the standards for the new plasma product and is working on a framework for the necessary regulatory revisions. While the new regulations are under development, FDA could consider the use of variances to existing regulations, providing an interim regulatory pathway for conversion of apheresis FFP to concurrent plasma for further manufacture. Any such pathway would be made publicly available through issuance of a guidance document. Another option, currently available to all facilities, is to obtain a source plasma license (infrequent plasmapheresis program).
Chagas ’ disease
Circular of Information
Donor History Questionnaire, full-length
Donor History Questionnaire, abbreviated
BECS WorkshopThe Alliance of Blood Operators (ABO), representing members in North America and Europe, has asked FDA to consider different regulatory strategies to BECS. In Europe blood establishment computer software is not regulated and vendors with products currently used throughout the European Union do not want the burden of submitting a 510(k) in the US. Within the US there are few new vendors entering the market, and existing vendors are slow to update their software. ABC has offered to host the workshop. FDA is considering the workshop and noted that reviews of software submitted via the 510(k) process often identify problems with the software that are then corrected prior to clearance. This concern is applicable to BECS submissions from small and large vendors. FDA has requested that ABO undertake several initiatives and address several issues prior to the workshop.
Reprinted with permission of AABB, Bethesda, Md., Copyright (year) AABB. All rights reserved. To receive your own copy of AABB News each month and read articles similar to this one, visit www.aabb.org and click on “Join AABB.”