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Blood Action Plan
FDA/CBER is responsible for regulatory oversight of the
U.S. blood supply. FDA promulgates and enforces standards for
blood collection and for the manufacturing of blood products,
including both transfusible components of whole blood,
pharmaceuticals derived from blood cells or plasma, and
related medical devices. FDA also inspects blood
establishments and monitors reports of errors, accidents and
adverse clinical events. CBER works closely with other parts
of the Public Health Service (PHS) to establish blood
standards, and to identify and respond to potential threats to
blood safety or supply.
CBER initiated a Blood Action Plan in July 1997, to
increase the effectiveness of its scientific and regulatory
actions, and to ensure greater coordination with our PHS
partners. The Action Plan addresses highly focused areas of
concern such as emergency operations, response to emerging
diseases, and updating of regulations. The Department of
Health and Human Services (HHS) accepted this plan in March
1998. The plan is being jointly implemented by CBER, other FDA
components (i.e., Office of Regulatory Affairs, Office of
Chief Counsel, and Office of Policy), the Centers for Disease
Control (CDC), the National Institutes of Health (NIH), and
the Health Care Financing Administration (HCFA).
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ISSUE
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Updating Blood Regulations
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FDA needs to update obsolete requirements, provide certain
product standards, and convert some guidance into
regulation.
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PROPOSED SOLUTION
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FDA will be undertaken to completely review, revise and rewrite
the blood regulations.
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NECESSARY STEPS
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a) CBER will create a database of all regulations, guidance and
other instructions for industry;
b) CBER will create a list of needed, but currently
non-existent regulations;
c) FDA will prioritize the list;
d) In the priority order each document will be
reviewed, revised, up-dated written or rewritten; and
e) CBER will explore ways of rapidly producing and
disseminating new regulation to industry.
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COMPLETED TASKS
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a) The database of all existing documents was
completed by September, 1997;
b) The list of needed regulations was completed by
September, 1997;
c) An initial priority list was developed by October,
1997;
d) The priority list will be reassessed annually to
identify emerging needs;
e) FDA has completed the list of highest priority
regulations; and
f) FDA published several proposed updates of the
blood regulations by October 31, 1999.
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PRESENT INITIATIVES
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a) FDA is reviewing the comments to the proposed
regulations;
b) FDA is developing several additional regulations
to incoporate existing guidance documents and identified
needs; and
c) FDA continues to assess and prioritize needed
regulations.
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OUTCOME
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a) Reduce the number of exemptions to outdated
regulations;
b) Reduce the number of guidance documents lacking
enforceability through regulations; and
c) Increase Industry’s compliance with standards.
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ISSUE
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Reinvention of Blood Regulation
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The current application process is administratively complex and
inefficient. There is a need to develop streamlined
application procedures and to increase self-auditing of
quality assurance by industry.
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PROPOSED SOLUTION
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Implement a simplified Biologics License Application (BLA) for
blood products in lieu of application review. In
addition, develop product and manufacturing standards.
Educate the industry and take effective compliance
actions to insure adequate quality assurance and full
compliance with good manufacturing practices by the
industry.
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NECESSARY STEPS
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a) CBER will develop the information technology infrastructure to
support introduction of a simplified BLA;
b) FDA will identify the manufacturing and product
standards for blood products for which regulatory
standards and regulations would be appropriate in lieu
of application submissions; and
c)FDA will develop an industry education and
compliance program to support expedited application
review and industry’s full compliance with GMPs.
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COMPLETED TASKS
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a) The first phase was to implement a simplified BLA. This was
completed prior to December 1999. CBER has also written
and published guidance for industry on how to use the
simplified BLA for both plasma derivatives and blood
components;
b) The second phase was to develop additional
manufacturing and product standards in lieu of detailed
application submissions. An inventory of suitable
product standards and procedures has been developed. A
proposed pilot program for Gamma Irradiation of Blood
and Blood Products was published January 1998 to
determine the feasibility of this approach. The final
rule for this pilot program was published in March 1999.
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PRESENT INITIATIVES
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a) A proposed pilot program for Red Blood Cell Immunization is
being developed;
b) If these pilot programs are successful other
programs which contain suitable standards and procedures
will be added.
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OUTCOME
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a) More rapid and efficient application review;
b)Decreased number of submissions to FDA; and
c)Improved execution of GMPs and quality assurance by
the industry.
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ISSUE
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Emerging Infectious Diseases
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There are constantly emerging potential threats to the blood
supply which require timely action and a coordinated
approach. Examples include new HIV variants; new
hepatitis agents; human herpes virus type 8;
Creutzfeld-Jakob Disease; human parvovirus B19; and
bacterial contamination of blood products.
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PROPOSED SOLUTION
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A specific scientific and regulatory strategy will be developed
for each identified potential threat. The agency, in
collaboration with CDC and NIH, will actively engage in
the scientific investigation of the emerging infectious
agents, which would include assessment of the risk to
the blood supply, diagnostic methods, standards
development, and regulatory controls.
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NECESSARY STEPS
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a) CBER will develop and maintain a database characterizing the
effort underway to manage potential threats to the blood
supply;
b) FDA will work closely with NIH and CDC to develop
for each recognized emerging agent strategies that lead
to appropriate studies, risk assessment, communication,
and any needed prevention strategies or regulatory
controls to protect the blood supply;
c) Proposed prevention strategies or regulatory
controls will be brought to public meetings and Advisory
Committees as appropriate to assess implementation
proposals; and
d) CBER will meet with PHS agency and other public
representatives to discuss current risk assessment every
6 months.
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COMPLETED TASKS
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a) A current database of potential threats to the blood supply
has been developed and includes appropriate teams to
address each threat;
b) Proposed regulatory actions will be presented as
appropriate at the monthly conference call.
c) A chronicle of actions taken by PHS Agencies,
since the beginning of the Blood Action Plan, has been
developed.
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PRESENT INITIATIVES
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The chronicle of actions taken by PHS Agencies will be reviewed
and updated annually.
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OUTCOME
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a) Improved coordination of FDA efforts with other PHS efforts to
address emerging infectious diseases, and
b) Prevention of transfusion transmitted disease.
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ISSUE
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Insuring Compliance of Plasma Fractionation Establishments
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The routine inspection of blood and plasma collection
establishments has been the responsibility of ORA for
many years. As part of a broader plan to transfer
responsibilities for biologic inspections to the field
the responsibility for inspection of plasma
fractionators has been transferred effective November
1996. Additional training in compliance needs to be
developed to enhance the transfer.
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PROPOSED SOLUTION
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a) Complete the transfer of the biologics inspection to ORA;
b) Program guidance will be developed and training
will be planned and conducted; and
c) A systematic process for reviewing all blood
related inspectional findings will be developed to
assure that any industry wide problems are quickly
identified and addressed.
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NECESSARY STEPS
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a) FDA will complete draft Team Biologics Action Plan;
b) FDA will implement Team Blood as defined in the
Team Biologics plan;
c) FDA staff will be trained in the newly defined
procedures and develop compliance programs as needed to
implement Team Blood; and
d) The existing transition will require periodic
oversight. The Deputy Director, CBER and the ACRA will
meet with appropriate staff until all blood related
regulatory activities are in conformance with ORA
standards.
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COMPLETED TASKS
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a) The Team Biologics Implementation Plan has been completed;
b) Team Blood has been implemented; and
c) All Fractionation and Blood Establishments have
been inspected by the appropriate cadre of
investigators.
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OUTCOME
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a) Improve industry compliance with FDA regulations, and
b) Improve agency consistency and efficiency in
compliance actions.
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ISSUE
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Notification and Lookback
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Recipients of blood and plasma products are not routinely
notified in a timely manner when products are recalled.
Permanently deferred donors are not routinely notified
of the medical conditions resulting in their deferral.
Current look-back requirements address only a narrow
range of conditions.
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PROPOSED SOLUTION
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a) FDA will develop regulations and other effective strategies
that will clarify the responsibility of industry to be
able to notify product end-users in recall and look-back
situations;
b) FDA will re-evaluate the circumstances under which
direct patient notification is appropriate; and
c) CBER will develop regulations to require medical
notification of permanently deferred donors. (Assigned
to the updating Blood Regulations Group)
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NECESSARY STEPS
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a) Regulations will be written by FDA that require adequate
record keeping and an effective mechanism to identify
and notify recipients when a product is implicated in a
health hazard;
b) Regulations will be written that require
"look-back" for relevant infectious agents.
The list of "relevant" infectious agents will
be developed by a team of FDA, NIH, and CDC scientists
and reviewed by the appropriate Advisory Committees; and
c) CBER will develop a regulation for notification of
permanently deferred donors. (Assigned to the
Updating Blood Regulations Group)
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COMPLETED TASKS
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a) A notice of proposed rulemaking for "recipient
notification" was published by FDA August 19, 1999;
b) The list of relevant infectious agents potentially
qualifying for "look-back" was developed by an
interagency team and presented to appropriate Advisory
Committees. The proposed regulation was published by FDA
on August 19, 1999;
c) FDA has published proposed regulations for the
notification of permanently deferred donors on August
19, 1999. (Assigned to the Updating Blood
Regulations Group)
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PRESENT INITIATIVES
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Comments to the proposed regulations are being
reviewed.
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OUTCOME
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a) Donors are notified of their medical deferral leading to
opportunities for treatment and reduced secondary
transmission, and
b) Recipients are notified of potential transfusion
related risks leading to opportunities for treatment and
reduced secondary transmission.
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ISSUE
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FDA Response to Emergencies and Class I Recalls Affecting Blood
Safety
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FDA needs to use standardized procedures for handling emergencies
affecting blood safety.
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PROPOSED SOLUTION
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FDA needs to implement a standardized procedure for managing
emergencies related to blood safety.
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NECESSARY STEPS
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a) Finalize emergency procedures and develop checklists where
useful;
b) Train FDA staff;
c) Systematically evaluate FDA’s response to blood
emergencies to assure that the process functioned
smoothly and appropriately; and
d) Early decisions on Class I product recalls.
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COMPLETED TASKS
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a) Procedures for responses to Emergencies and Class I recalls
have been finalized;
b) FDA staff has been educated in the changes made in
handling emergency operations; and
c) A team of senior managers to conduct systematic
reviews of blood emergencies has been selected.
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OUTCOME
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a) Increase speed, efficiency, and coordination of FDA response
to an emergency affecting blood safety, and
b) Enhanced public health protection in the face of
threats to blood safety.
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ISSUE
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Monitoring and Increasing the Blood Supply
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PHS Agencies need to monitor and evaluate the adequacy of the
blood supply and take steps to increase supplies as
required.
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PROPOSED SOLUTION
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PHS Agencies will establish and oversee data collection
mechanisms to permit timely prediction of blood
shortages. PHS Agencies will develop and implement
strategies to increase the blood supply.
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NECESSARY STEPS
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a) Monitor the blood supply;
b) Encourage more donations by eligible donors;
c) Improve donor relations as part of recruitment and
retention;
d) Remove restrictions to safe Alternative Treatments; and
e) Address economic issues facing the blood industry.
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COMPLETED TASKS
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a) NHLBI has funded a pilot monthly surveillance program for
three years starting in November 1999;
b) DHHS is committed to continue to encourage and
cooperate with coordinated private sector initiatives on
public service announcements related to blood donor
campaigns. Senior health officials have met with
industry to develop a general statement concerning the
national blood supply. DHHS has developed a plan to
enlist national philanthropic and other private sector
organizations to take a lead role in promoting blood
donations at times of shortage;
c) The first workshop on Donor Incentives was held
February 28, 2000;
d) NHLBI has had internal discussions to explore the
feasibility of initiating studies on the development of
educational programs to encourage blood Alternative Treatments as a
civic responsibility; and
e) The first joint CDC/FDA workshop concerning donor
suitability issues was held on June 26-27, 2000.
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PRESENT INITIATIVES
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a) A decision will be made within PHS by October 1, 2001 whether
to create a long term PHS Agency responsibility for
monitoring the blood supply.
b) FDA will publish guidance on use of Donor
Incentives.
c) NHLBI will continue to support evaluation of blood
donor incentive models to encourage Alternative Treatments through
workshops and studies to be completed by October 1,
2002.
d) FDA will issue draft guidance to industry on
recruitment practices.
e) Based on the results of ongoing NHLBI supported
research, FDA will issue guidance on use of computer
assisted interviews.
f) FDA will coordinate a joint government/industry
initiative on simplifying and abbreviating the donor
questionnaire to commence by January 1, 2001. A workshop
to discuss the donor questionnaire issues will be held
October 16, 2000.
g) FDA will issue guidance on labeling and frequency
exemptions for therapeutic hemochromatosis donations.
h) As funds permit, CDC and FDA have agreed to
continue to co-sponsor workshops in FY2000 and FY 2001
to determine the safety and efficacy of policy changes
regarding current donor suitability criteria, test
requirements and reentry. Where feasible, FDA will issue
guidance to eliminate unnecessary restrictions.
i) FDA and NHLBI will co-sponsor a workshop with
industry to identify and define “best practices” in
donor recruitment on July 6-7, 2000.
j) PHS is committed to bring to discussion at the PHS
AC BSA potential safety measures with significant cost
implications. Funding strategies to address
implementation of NAT screening and leukoreduction are
being addressed. DHHS is working to clarify policies on
reimbursement for blood services and products.
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OUTCOME
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a) Improve the ability to predict and respond to blood shortages;
and
b) Increase the availability and elasticity of the
blood supply.
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