DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Baltimore District Office
Central Region
6000 Metro Drive, Suite 101
Baltimore, MD 21215
Telephone: (410) 779-5454
FAX: (410) 779-5707
July 22, 2003
ADVERSE DETERMINATION LETTER
BY FACSIMILE &
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Mr. Ramesh Thadani
Executive Vice President & CEO
Biomedical Services
American National Red Cross
2025 E Street, NW
Washington, D.C. 20006
RE: United States v. American National Red Cross, Civil Action
No. 93-0949 (JGP)
Dear Mr. Thadani:
Paragraph IV.B.1. of the Amended Consent Decree of Permanent
Injunction (Decree), entered on April 15, 2003, requires the
American Red Cross (ARC) to establish and submit to the Food
and Drug Administration (FDA) within 90 days of entry of the
Decree standard operating procedures (SOPs) to detect, investigate,
evaluate, correct, and monitor all problems, trends, and system
problems. ARC submitted BSD 92.103T, “Problem Management,” version
1.3, June 2003 (the SOP) on June 3, 2003. Paragraph VI.B. of
the Decree requires FDA to advise ARC in writing whether each
SOP submitted, pursuant to Paragraph VI.A. (including those
SOPs filed pursuant to Paragraph IV.B.1.), appears to be adequate
to bring ARC into compliance with the law and the Decree.
FDA has reviewed ARC’s submission and has determined that
the SOP is not adequate to comply with the requirements of
the law and the Decree. The specific bases for FDA’s determination
are set forth below.
- The SOP does not comply with Paragraph IV.B.1.a.i. of
the Decree (Page 15), because it does not require that “each
region and laboratory shall scrutinize, at a minimum, ARC’s
Clarify reports” and “compliance-related FDA correspondence” to “identify
all problems that the Problem Management System must address.” Problem
is defined in Decree Paragraph III.B.52. (Page 8), as “any
deviation from the law, ARC SOPs, or this Order, however
discovered, recorded, or reported, including, but not limited
to deviations reported in ARC Clarify reports” and “FDA-483s,
compliance-related FDA correspondence, … .”[1] (SOP
pages 7-A-1 and 7-A-2; Bates pages 028830 and 028831)
- The SOP fails to comply with Paragraph IV.B.1.a.ii. of
the Decree (Page 15), because it does not require each ARC
region and laboratory to, “commensurate with the nature of
the problem, promptly, thoroughly, and adequately investigate,
correct, and take steps to prevent the recurrence of each problem.” (emphasis
added) Instead, the SOP provides instructions to classify
problems and to investigate, correct, and prevent only
certain problems. [See also 21 CFR 606.171(f), which
states “all biological product deviations … should be investigated
in accordance with the applicable provisions of parts 211,
606, and 820 of this chapter.] For example:
- The SOP provides a guideline for ARC to classify problems based
on “severity level and type.” Specifically, the SOP provides that
[REDACTED] Page 3-4 of the SOP “summarizes the actions
to take according to the type of problem.” This summary requires no investigation
and no corrective
action plan to prevent recurrence of [REDACTED] problems.
(SOP pages 3-2, 3-3, and 3-4; Bates pages 028809 through 028811)
- This same error of omission is repeated by the SOP when it states
that ARC may close “events” [REDACTED] “following
completion of immediate action” and “LCTs” [REDACTED] “following
completion of immediate actions and approval.” (SOP page 4-5; Bates
page 028817) However, “immediate action,” as defined on page 2-4 of
the SOP (Bates page 028806), does not require any investigation or
development of
a corrective action plan to prevent recurrence. Furthermore, BSD92.103T\JA22
(6/03), “Problem Management Timing Guidelines,” which is a section
of the SOP submitted under Paragraph IV.B.1. of the Decree, states
that the steps, “investigate including root cause analysis” and “develop
corrective action” are “NA”(not applicable) to “events” [REDACTED] and “LCTs” [REDACTED].
(Bates page 028966)
- Yet another example where the SOP fails to appropriately manage
problems occurs when the SOP provides a list of “areas of concern in
which any denoted problem would be classified as a Level 3 investigative
problem, regardless of the point of discovery, severity, or safety,
quality, identity, potency, or purity (SQUIPP) implication.” The list
includes “staff performing tasks without training” but states that “this
does not include documentation problems with training records.” (BSD92.103T\JA23
(6/03; Bates page 028971) (emphasis added) Not only does a training
documentation problem require investigation and corrections pursuant
to Paragraph IV.B.1.a.ii., but also Paragraph IV.C.5.a. of the Decree
specifically requires documentation of employee training as a method
of ensuring that each employee has successfully completed his or her
training program prior to assuming any duties. Additionally, the October
19, 2001 letter issued to ARC, pursuant to Paragraph VI.A. of the Consent
Decree of Permanent Injunction entered May 12, 1993, (VI.A. letter)
as a result of inspectional observations made at ARC's Lewis and Clark
Region, cites deficiencies in training documentation, as does the VI.A.
letter issued to ARC on February 9, 1998, as a result of inspectional
observations made at several ARC regions.
Although the Decree defines “problem” and explicitly requires investigation
and correction of each problem, as noted above, this SOP provides
ARC staff with instructions for exempting certain problems from the requirement
to investigate and correct. FDA finds that, in this respect, this SOP is
not materially different from its predecessor (which FDA also found deficient),
in that it requires classification of a problem based primarily on when
the problem was discovered and whether blood or blood components were distributed.
The results of an adequate risk assessment are not utilized to determine
the nature of the problem, nor is consideration given to the health hazard
associated with the problem. Absent an adequate risk assessment and consideration
of health hazard in this problem classification process, it is impossible
to ensure that health hazards will be immediately identified and handled
appropriately.”
- The SOP also fails to comply with Paragraph IV.B.1.a.ii. of
the Decree (Page 15), because it does not require that each
region and laboratory “thoroughly and contemporaneously document
each step it takes to investigate, correct, and prevent recurrence
of each problem” and that “such documentation shall be maintained
at the appropriate region or laboratory.” For example:
- The SOP does not require ARC regions and
laboratories to thoroughly and contemporaneously document
investigations
or to identify the quality assurance staff member(s) who
reviewed and approved the investigation. (SOP page 4-3;
Bates page 028815)
- The SOP does not require ARC regions and laboratories
to document each step taken to develop a corrective action.
(SOP page 4-4; Bates page 028816)
- The SOP does not require ARC’s regions and laboratories
to document their review and approval of corrective action
plans or results of effectiveness checks. (SOP page 4-5;
Bates page 028817)
- The SOP states, “Note: Documentation should be transferred
[REDACTED] as soon as possible.
Maintenance of the initial paper documentation is not required
after all necessary information has been entered into [REDACTED] (SOP
page 2-5; Bates page 028807) In FDA’s view, this “note” is
objectionable, because the records that were created contemporaneously
with the steps performed may not be maintained. Paragraph
IV.B.1.a.ii. of the Decree explicitly requires thorough
and contemporaneous documentation and availability of such
documentation for FDA review. [See also 21 CFR 606.160(a)(1),
which requires that “records shall be maintained concurrently
with the performance of each significant step in the collection,
processing, compatibility testing, storage, and distribution
of each unit of blood and blood components so that all
steps can be clearly traced.”]
- The SOP fails to comply with Paragraphs IV.B.1.a.iv.
and IV.B.1.a.v. of the Decree (Pages 16 and 17), because
it does not require the monthly Summary Problem Report
to include all elements set forth in the Decree. For
example:
- The SOP does not require the Summary Problem Reports
to state “the nature of the problem(s), including,
but not limited to, whether they constitute deviations
from the law, ARC SOPs, or this Order;” “the frequency
with which those problems have occurred in that region
or laboratory since entry of this Order or the prior
24 months, whichever is shorter;” and “whether the
problems may be potential system (systemic) problems.” [Decree
Paragraphs IV.B.1. iv.A., IV.B.1.iv.C., and IV.B.1.iv.D.]
- The SOP does not require that the first Summary
Problem Reports “shall include the categories of fully
corrected problems that have been initially discovered
after entry of this Order.” [Decree Paragraph IV.B.1.a.iv.]
- The SOP provides guidance for categorizing problems;
however, the categories established in BSD92103t04.form
(6/03), Appendix 1, which is part of the submitted
SOP, are not sufficiently specific to enable Biomedical
Headquarters (BHQ) to identify trends of particular
problems, which is one of the principal objectives
of this requirement. The Decree states the “categories
shall be specific enough to enable ARC Biomedical Headquarters
to determine whether a trend exists,” but ARC has excluded
significant problems from its list of categories. For
example, there is no category for failure to perform
inventory reconciliation, a significant problem cited
by FDA in VI.A. letters issued to ARC on October 20,
1999, and August 5, 2002, as a result of inspectional
observations made at ARC’s Southern Region and Greater
Chesapeake and Potomac Region, respectively. FDA also
discovered evidence of inventory reconciliation failures
in several regions during its February-April 2000 and
April-December 2002 inspections of ARC BHQ. [Decree
Paragraph IV.B.1.a.iv.]
- The SOP requires regions to submit to BHQ only
one limited section (“Monthly Summary Problem Report
Section 2: For Facility and BHQ Use”) of the monthly
Summary Problem Report and only for categories of problems
that represent 1% of all regional problems. It requires
laboratories to submit to BHQ that same limited section
of the report and only for categories of problems that
represent 10% of all laboratory problems. (SOP pages
7-A-3 and 7-A-4, BSD92103t04.frm (6/03), 7-B-4; Bates
pages 028832 and 028833, 0028837, 29005 and 029006)
FDA finds that ARC’s SOP does not require that regions and laboratories submit
an adequate amount of information pertaining to problems that have occurred
in those facilities to enable BHQ to identify trends and system (systemic)
problems. The portion of the monthly Summary Problem Report intended for
BHQ also excludes such significant information required by the Decree as “whether
the problems could result, or have resulted, in the release for distribution
of unsuitable blood or blood components, and if so, what follow-up action,
such as retrieval, notification, and/or lookback has been implemented.” [Decree
Paragraph IV.B.1.iv.G] Additionally, ARC’s exemption from the reporting requirement
of problems that occur below a specific frequency, not only violates the
Decree, which prohibits any violation of the law, but also may prevent BHQ
from promptly identifying trends and potential system (systemic) problems.
FDA has objected to ARC’s practice of tolerating certain percentages of violations
and has so notified ARC numerous times: in an FDA 483 issued at the conclusion
of FDA’s February-April 2000 inspection of ARC BHQ, in an FDA 483 issued
at the conclusion of FDA’s inspection of ARC’s Greater Chesapeake and Potomac
Region, in the August 5, 2002 VI.A. letter issued as a result of that inspection,
in an FDA 483 issued at the conclusion of FDA’s April-December 2002 inspection
of ARC BHQ, in the VI.A. letter issued as a result of that inspection, and
in compliance-related correspondence issued to ARC on March 13, 2003.
- The SOP fails to comply with Paragraph IV.B.1.b. of
the Decree (Page 17), because it does not require “a thorough
analysis and investigation of each Summary Problem Report
submitted by each region and laboratory to discover trends
and system (systemic) problems.” Nor does the SOP include
all elements required under this paragraph. For example:
- The SOP does not require ARC BHQ to analyze and investigate Summary
Problem Reports.
- The SOP does not require analysis and investigation of certain
problems. As stated in item 4 above, the SOP only requires “analysis
of any category of problem that constitutes one per cent of a regional
facility’s problems or 10 per cent of an NTRL facility’s problems for
the month being reported.” Even if the SOP did include a requirement
to thoroughly analyze and investigate each Summary Problem Report,
BHQ’s reliance on incomplete Summary Problem Reports, as described
in item 4 above, necessarily will result in non-compliance with Paragraph
IV.B.1.b., in that BHQ cannot detect trends, potential system (systemic)
problems, and system (systemic) problems by using only partial reports.
- The SOP does not state that “information contained in a Summary
Problem Report that is classified as a significant risk, according
to the Problem Management SOP, shall be investigated and reported to
ARC Biomedical Services senior management on an expedited basis.” (SOP
pages 7-B-2 through 7-B-4; Bates pages 028835 through 028837)
- The SOP fails to comply with Paragraphs IV.B.1.b.i.
and IV.B.1.b.ii. of the Decree (Pages 17 and 18) because
it does not include any of the required elements
that must be included in each Analysis and Investigation
Report for each trend discovered. The Decree states that “for
each trend that the Analysis and Investigation Group discovers,
the Analysis and Investigation Report shall, at a minimum,
state: (A) the nature of the trend; (B) the scope of the
same or similar trends (number of regions and laboratories
in which the same or similar trends have been reported
and the number of same or similar trends within each region
and laboratory); (C) the probable or actual cause of each
trend; (D) for each trend, whether it or any of its causes
poses a health risk such that the time frames related to
the Corrective Action Plan and the Corrective Action Monitoring
Reports should be shortened; (E) the steps taken to determine
whether the trend may result or has resulted in the release
for distribution of unsuitable blood or blood components;
(F) whether the trend resulted in release for distribution
of unsuitable blood or blood components, and if so, whether
appropriate follow-up action, such as retrieval, notification,
and/or lookback, is required; and (G) for each trend, whether
it or any of its causes is a system (systemic) problem.” The
Decree further requires that “if the Analysis and Investigation
Group determines that a trend, or any of its causes is
a system (systemic) problem, the Analysis and Investigation
Report shall identify all systems that potentially or actually
contributed to the system (systemic) problem, shall follow
the established risk assessment procedures, and shall assign
a risk factor to each system (systemic) problem.” ARC has
addressed none of these Decree requirements in
the SOP. (SOP page 7-B-5; Bates page 028838) These omissions
are particularly disturbing to FDA because these analytical
elements are all indispensable to fulfilling the quality
assurance functions and complying with the law and are
explicitly called for by the Decree itself.
- The SOP fails to comply with Paragraph IV.B.1.c. of
the Decree (Pages 18 and 19), as follows:
- The SOP does not require that “specific persons
(to be identified by ARC in writing by position), including,
but not limited to, a representative from the Quality
Assurance unit and operations staff at ARC Biomedical
Headquarters and at least one person from an ARC region
or laboratory (representing the regions and laboratories,
collectively), shall be responsible, within specific
time frames not to exceed the due date for the next
Analysis and Investigation Report, for reviewing and
evaluating the Analysis and Investigation Report, and
preparing a written Corrective Action Plan to address
the findings set forth in the Analysis and Investigation
Report.”
- The SOP is also deficient because it does not
state that the Analysis and Investigation Reports,
which as noted in item 6 above, are deficient, are
to be used to develop Corrective Action Plans.
- The SOP also fails to distinguish between specific
procedures to develop corrective action plans at the
region and laboratory level and the specific procedures
to develop Corrective Action Plans at the BHQ level
to address findings set forth in Analysis and Investigation
Reports. (SOP page 4-4, BSD92.103T\JA15 (6/03); Bates
pages 028816 and 028931)
- The SOP fails to comply with Paragraphs IV.B.1.c.i.
and IV.B.1.c.ii. of the Decree (Page 19), because
the SOP does not address specific elements that the Decree
requires ARC to include in Corrective Action Plans. For
example, the SOP does not require Corrective Action
Plans to:
- state “whether all regions and laboratories have
been notified in writing of system (systemic) problem;” [IV.B.1.c.i.B.]
- state “the precise time frame, based on the assigned
risk factor, for completing each action;” [IV.b.1.c.i.D.]
- “confirm or correct the determination in the Analysis
and Investigation Report with regard to the retrieval
of unsuitable blood or blood components, including
expanding the scope of the retrieval, if necessary;” [IV.B.1.c.ii.]
and
- “designate specific persons to monitor, at specific
time intervals, ARC’s plans, at the region and/or at
ARC Biomedical Headquarters, to retrieve unsuitable
blood or blood components from the marketplace.” [IV.b.1.c.ii.]
(SOP page 4-4, BSD92.103T\JA 15 (6/03), pages 1 through
3; Bates pages 028816, 028931 through 028933)
- The SOP fails to comply with Paragraph IV.B.1.d.i.A. of
the Decree (Page 20), because it does not require Corrective
Action Monitoring Reports to include “details of retrieval,
notification of consignee(s) and/or, if necessary, lookback
investigation” that may have been part of the Corrective
Action Plan. When unsuitable blood and blood components have
been distributed, retrieval, consignee notifications, and
lookback investigations are necessary to protect the public
health and are critical elements of a Corrective Action Plan.
Accordingly, these factors must be monitored to ensure their
completeness and effectiveness. The Decree requires ARC to
monitor those activities, but ARC’s SOP does not. (SOP page
7-B-4, Bates page 028837)
- The SOP fails to comply with Paragraphs IV.B.1.e.,
IV.B.1.e.i., IV.B.1.e.ii., IV.B.1.e.iii., IV.B.1.e.iv.,
and IV.B.1.e.v. of the Decree (Pages 20 and 21), because
it does not require ARC to perform all of the quality assurance
steps listed in the Decree. The Decree requires specific
persons at BHQ, including the quality assurance director,
every 90 days to review “all Summary Problem Reports, Analysis
and Investigation Reports, Corrective Action Plans, Corrective
Action Monitoring Reports, ARC internal and external audit
reports, FDA-483 observations, and compliance-related FDA
correspondence to identify any problems, trends, and system
(systemic) problems that have not been detected, investigated,
and effectively corrected within established time frames.” For
example, the SOP does not require:
- any such review by “specific persons at ARC Biomedical
Headquarters …, including the quality assurance director;” [Decree
Paragraphs IV.B.1.e. and IV.B.1.e.i.]
- such review to include an assessment of “the public
health risk of all unresolved problems, trends, and
system (systemic) problems identified during this review;” [Decree
Paragraph IV.B.1.e.ii.]
- “ensuring that all problems, trends, and system
(systemic) problems identified during this review are
promptly resolved;” [Decree Paragraph IV.B.1.e.iii]
- “ensuring that all ARC regions and laboratories
have been notified in writing of system (systemic)
problems;” [Decree Paragraph IV.B.1.e.iv.] and
- “reporting the result of the review in the quarterly
quality assurance report as described in Paragraph
IV.A.2.b. to ARC senior management and ARC Biomedical
Services senior management pursuant to paragraph IX
herein.” [Decree Paragraph IV.B.1.e.v.]
Review of these reports and plans presents an important opportunity for those
most responsible for quality assurance to ensure that ARC is operating in
compliance with the law, ARC’s SOPs, and the Decree. But the SOP does not
even address this review. Even if the SOP had addressed this BHQ review,
FDA notes that the cumulative effect of ARC’s failure to comply with the
Decree requirements, as described in paragraphs 1 through 11 of this letter,
would be fruitless because of the numerous deficiencies in the reports and
plan.
- The SOP fails to comply with Paragraph IV.B.1. of
the Decree (Page14), because the risk assessment procedure,
included in the submitted SOP, will not ensure that ARC properly
prioritizes problems to ensure those that are a significant
risk problem are corrected expeditiously. The Decree requires
ARC to establish a risk assessment procedure. The Decree
states: 1) that “information contained in a Summary Problem
Report that is classified as a significant risk, according
to the Problem Management SOPs, shall be investigated and
reported to ARC Biomedical Services senior management on
an expedited basis” [Decree Paragraph IV.B.1.b.]; 2) that “for
each trend, whether it or any of its causes pose a health
risk such that time frames related to the Corrective Action
Plan and the Corrective Action Monitoring Reports should
be shortened” [Decree Paragraph IV.B.1.b.i.D.]; 3) that “if
the Analysis and Investigation Group determines that a trend … is
a system (systemic) problem, the Analysis and Investigation
Group … shall follow the established risk assessment procedures,
and shall assign a risk factor to each system (systemic)
problem” [Decree Paragraph IV.B.1.b.ii.]; and 4) that “the
Corrective Action Plan shall, at a minimum, state … the precise
time frame, based on the assigned risk factor, for completing
each action.” [Decree Paragraph IV.B.1.c.i.D.] Despite the
foregoing, the risk assessment procedure ARC included in
the SOP:
- excludes problems related to donor safety. Although the
SOP requires use of a [REDACTED] and a [REDACTED] to determine a risk factor, the SOP states those factors “represent
the potential risk to the recipient of a blood product.” (emphasis
added) The Decree requires ARC to establish an SOP to “detect, investigate,
evaluate, correct, and monitor all problems, trends, and system (systemic)
problems.” The Decree defines “problem” as “any deviation from the
law, ARC SOPs, or this Order.” [Decree Paragraph III.B.52.] Donor
Safety is governed by the law, ARC SOPs, and the Decree, and thus
falls under that definition and must be carefully managed by ARC. [See
also Decree Paragraph IV.B.14 (Page 38) and 21 CFR 640.3, which address
donor safety.] (SOP pages 8-2 through 8-5; Bates pages 028840 through
028843)
- does not clearly describe the use of risk factors in ARC problem
management process, such as how BHQ will use risk factors assigned
to problems to comply with BPD reports, Quality & Regulatory Affairs
(Q&RA) audit observations, and “trend problems” or how ARC will ensure
that significant risk problems, BPD reports, Q&RA audit observations,
and “trend problems” are corrected promptly. (Pages 7-A-3, 92103t04.frm
(6/03); Bates pages 028832, 029005, and 029006)
- includes Job Aid, BSD92.103T\JA15 (6/03), “Problem Solving at
Biomedical Services Headquarters,” that describes steps to be taken “when
assessing potential system problems, trends in problems that were submitted
on the Analysis Investigation Report, or escalated problems,” and includes
one step related to risk. However, the procedure is not consistent
with the risk assessment procedure, in that it defines “significant
risk” as a “hazard or recall that involves more than 100 WBN units.” The
risk assessment procedure does not define the term hazard or refer
to the number of recalled Whole Blood Number units as a factor in determining
risk. Additionally, the Job Aid does not instruct ARC staff to refer
to the risk categories defined in Chapter 8. (BSD92.103T\JA15 (6/03);
Bates page 028931)
- does not require use of the risk assessment procedure to classify
problems. Specifically, Chapter 3 requires classification of problems
[REDACTED] and refers to Chapter 8 and BSD 92.103T\JA03, “Biological Product
Deviation Codes.” However, Chapter 3 does not state how to apply Chapter
8 and BSD92.103T\JA03s to the classification procedures. (SOP pages
3-1 through 3-4; Bates pages 028808 through 028811)
- includes Job Aid, BSD92.103T\JA03, “Biological Product Deviation
Codes,” which includes pre-determined risk factors for specific categories
of BPDs. However, it does not state the basis for those factors, the
manner in which ARC uses those factors, or when use of pre-determined
risk factors is appropriate. (BSD92.103T\JA03 (5/03); Bates pages 028853
through 028908)
- does not require documentation of risk assessment for each problem.
In addition to the deficiencies discussed in items 1 through
11 above, FDA’s review of ARC’s SOP revealed additional problems
that make the SOP inadequate to accomplish its intended purpose,
as follows:
- The manner in which the SOP is organized and the grossly
insufficient level of detail make it difficult for ARC staff
to follow or assure consistency among staff and regions and,
therefore, to ensure compliance with the law and the Decree. For
example:
- Many significant parts of the SOP exist in Job
Aids that are not referenced in the body of the SOP.
- The work flow is not completely described. As
a result, the problem management process described
in the SOP is difficult to follow from beginning to
end.
- The SOP does not adequately address the immediate
handling of urgent health hazards.
- The SOP does not state whether the regions and
laboratories are required to transfer Clarify cases
into the [REDACTED] or whether the regions and laboratories
are required to analyze the problems in Clarify and
[REDACTED] separately for inclusion on the Facility Monthly
Summary Problem Reports.
- The SOP does not address the implementation of
Corrective Action Plans for system problems and trends
identified by BHQ during its review of the Facility
Monthly Summary Problem Report.
- The SOP requires each region and laboratory to establish
local procedures “describing how the Problem Management system
is managed in accordance with policies contained within this
BSD,” as opposed to implementing one SOP to govern problem
management in each region and laboratory, as well as in BHQ.
The lack of detail and the organization of the SOP will likely
result in various interpretations and inconsistent applications
across the regions and laboratories. The requirement to establish
local procedures will also result in a major part of ARC’s
problem-solving system not being reviewed by FDA prior to
implementation as required by the Decree.
- The instructions in Chapter 4, “Managing Investigative
Problems,” are only brief summaries of the intricate processes
of determining root cause and developing corrective actions.
- The risk assessment procedure in the SOP does not state
the manner in which ARC intends to use these procedures throughout
its problem-solving process, or how ARC intends to control
the uniformity of risk factor evaluations.
- BSD92.103T\JA03 (5/03), “Biological Product Deviation
Codes,” which is part of the SOP, includes pre-determined
risk factors for biological product deviations. To further
ensure that similar BPDs are scored uniformly for risk assessment,
the Job Aid must state [REDACTED] scores, as well as the final score. Because the Job
Aid lacks those rating scores, FDA has not performed a comprehensive
evaluation of the validity of predetermined risk factors
assigned to specific BPD report codes listed in that Job
Aid.
- The zip code for FDA’s Baltimore District Office must
be corrected on Bates page 028825. The correct zip code is
21215.
Although FDA has made an effort to identify major deficiencies
in BSD 92.103T, “Problem Management," this letter is not intended
to be an all-inclusive list of FDA's concerns with BSD 92.103T.
Indeed, because the BSD establishes and then builds on fundamental
elements which do not include all of those required in Paragraph
IV.B.1. of the Decree, FDA cannot provide a comprehensive review
of the BSD at this time. Additionally, FDA did not review BSD92.103T\JA02
(7/02), “Non-Reportable Biological Product Deviations,” because
that portion of ARC’s submission is not relevant to Paragraph
IV.B.1. of the Decree.
* * *
Paragraph VI of the Decree provides that if FDA determines
that any SOP, report, or plan submitted under specified paragraphs
of the Decree, including Paragraph IV.B1., "appears inadequate,
FDA shall state the specific basis for its determination in
writing, and the penalty, review, and appeal procedures set
forth in Paragraph IX below shall be followed until ARC obtains
a favorable determination from FDA or the Court as to the apparent
adequacy of that SOP, report, or plan." Paragraph VIII of the
Decree provides that if FDA determines that ARC "has failed
to fully comply with any … term, or provision of this Order" or "that
any report, plan, SOP, or other measure implemented by ARC
to comply with this Order is inadequate to comply with the
law, … , or this Order . . . then FDA may order ARC to come
into compliance with the law, … , or this Order, assess penalties,
and/or to take any step that FDA deems necessary to bring ARC
into compliance with the law, ARC SOPs, or this Order."
For the reasons stated above, FDA has determined that ARC's
BSD 92.103T, “Problem Management,” which ARC submitted to FDA
pursuant to Paragraph IV.B.1. of the Decree, is wholly inadequate
to comply with the law and the Decree and that the violations
are severe enough that it should invoke the penalty provisions
of the Decree. Indeed, as expalined elsewhere in this letter,
the omissions in ARC’s SOP are, in most cases, explicitly required
by specific language in the Decree. In other cases, FDA has
brought the particular deficiencies to ARC’s attention in previous
FDA 483s and VI.A. letters. Finally, ARC has been on notice
for several years, not only as to many of the specific deficiencies
in this SOP, but also that FDA regards this SOP as a first
and indispensable step to enable ARC to comply with current
good manufacturing practice.
FDA hereby orders ARC to revise the Problem Management SOP
in a manner that will address the violations discussed above
and otherwise comply with the law and the Decree. For the reasons
stated in the preceding paragraph, pursuant to Paragraph IX
of the Decree, FDA intends to fine ARC up to $10,000 for each
day from June 3, 2003, the date that ARC submitted the inadequate
SOP to FDA, until the date ARC submits to FDA a plan to revise
the Problem Management SOP that addresses the violations discussed
above and otherwise complies with the law and the Decree.
As provided in the Decree, if ARC agrees with this adverse
determination, it shall within 20 days of receipt of this letter,
notify FDA of its intent to come into compliance with the Decree
and submit a plan to do so. If ARC disagrees with FDA’s adverse
determination, it shall respond in writing within 20 days of
receipt of this letter, explaining its reason for disagreeing
with FDA’s determination. Your response must be submitted to
me at the Food and Drug Administration, Baltimore District
Office, 6000 Metro Drive, Suite 101, Baltimore, Maryland 21215,
with a copy to Jesse Goodman, M.D., Director, Center for Biologics
Evaluation and Research, 1401 Rockville Pike, Suite 200 N,
Rockville, Maryland 20852.
Sincerely,
(signed) Nathaniel R. Esaw
for Lee Bowers
Lee Bowers
Director, Baltimore District
cc: Marsha Johnson Evans
President & CEO
American National Red Cross
430 17th Street, NW
Washington, D.C. 20006
Mary Elcano
General Counsel
American National Red Cross
430 17th Street, NW
Washington, D.C. 20006
David T. McLaughlin
Chairman, Board of Governors
American National Red Cross
430 17th Street, NW
Washington, D.C. 20006
[1] In its entirety, the
definition of “problem” in the Decree is “any deviation from
the law, ARC SOPs, or this Order, however discovered, recorded,
or reported, including, but not limited to deviations reported
in ARC Clarify reports (and/or in any other successor or similar
deviation-reporting systems and/or reports), biological product
deviation reports, internal deviation reports, trends, adverse
reaction reports, lookback cases, cases of suspected transfusion-transmitted
disease, potential system (systemic) problems, system (systemic)
problems, supply and equipment problem reports, FDA 483s, compliance-related
FDA correspondence, internal and external audit reports, and
retrievals.” |