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
February 6, 2004
ADVERSE DETERMINATION LETTER
BY FACSIMILE &
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Mr. Alan McCurry
Interim 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. McCurry:
This letter responds to the American National Red Cross’s
(ARC’s) submission dated October 27, 2003, and hand delivered
to the Food and Drug Administration’s (FDA) Baltimore
District on October 28, 2003, by ARC representatives. Your
submission is ARC’s response to FDA’s July 22,
2003 Adverse Determination Letter issued to ARC under Paragraph
VI.B. of the Amended Consent Decree of Permanent Injunction
(Decree), entered on April 15, 2003. In that letter, FDA stated
the bases for its determination that ARC failed to comply with
Paragraph IV.B.1. of the Decree in the Problem Management standard
operating procedure (SOP) it submitted on June 3, 2003. Paragraph
IV.B.1. of the Decree requires that ARC establish and submit
to FDA SOPs to detect, investigate, evaluate, correct, and
monitor all problems, trends, and system problems.
Paragraph VI.B. of the Decree requires FDA to advise ARC in
writing whether the revised Problem Management SOP, which consists
of SOPs covering four areas -- policies, directives, work instructions,
and reference materials -- appears to be adequate to bring
ARC into compliance with the law and the Decree. FDA has reviewed
the revised Problem Management SOP and has again determined
that the revised Problem Management SOP continues to be inadequate
to fulfill the requirements in Paragraph IV.B.1. of the Decree.
Although ARC has corrected some of the deficiencies cited in
the July 22, 2003 Adverse Determination Letter, FDA found that
ARC still has failed to correct significant deficiencies. FDA
has set forth below the bases for this determination:
- The revised Problem Management SOP fails to comply with
Paragraph IV.B.1. of the Decree (page 14), because it does
not require that all trends be adequately corrected, and
it does not include an adequate risk assessment procedure.
The
revised Problem Management SOP also 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 “…commensurate
with the nature of the problem, [to] promptly, thoroughly,
and adequately
investigate, correct and take steps to prevent the recurrence
of each problem….” Specifically, ARC’s
revised Problem Management SOP does not include an adequate
risk assessment
procedure and does not ensure that, commensurate with their
nature, problems will be corrected to prevent their recurrence.
For example,
- Revised Problem Management SOP Work Instruction 10.3.2, “Assessing
Risk” and Job Aid 10.4.ja2, “Biological Product
Deviation Codes”: The risk assessment procedure
described in Work Instruction 10.3.2 is used by ARC to determine
risk
indicators, which in turn are used to “…determine
the level of investigation and extent of corrective actions
and preventive actions…” for problems. (See Bates
page 030470.) To assist the regions and laboratories in assigning
risk indicators, ARC has established a list in Job Aid 10.4.ja2
of Biological Product Deviation (BPD) codes that includes
pre-assigned risk indicators to “assure that each problem
will be addressed commensurate with the nature of its risk.” (See
Bates page 030549-030607.) Based on the directions in the
Work Instruction and the Job Aid, ARC calculates risk indicators
by [REDACTED] Job
Aid 10.4.ja2 (at Bates page 030550) states, [REDACTED] However,
neither the Job Aid nor the Work Instruction provides instructions
to ensure that ARC regions and laboratories will consistently
identify those situations and will properly recalculate the
risk indicator in order to assign the appropriate priority
to resolving such problems. Additionally, neither the Job
Aid nor the Work Instruction provides instructions regarding
recalculation
of risk indicators based on factors such as frequency, duration,
scope of problems, and distribution of unsuitable blood or
blood products as a result of problems.
Because critical decisions regarding the extent of ARC’s
investigations and corrective actions will be based on
risk indicators, it is important that the values listed in
Job Aid
10.4.ja2 be reliably scored using appropriate criteria
and that the scoring process used to develop the Job Aid
be adequately
controlled to ensure that values included therein are reliable.
In its review of the Job Aid, FDA found that some problems
were assigned risk indicators that appear to be too low
or otherwise questionable. (See related questions and comments
in item 2.a. through 2.e. on pages 7 and 8 of this letter.)
For example, ARC has assigned risk indicators that deem
the
following types of problems as [REDACTED] donor
safety problems (Bates page 030559); many of the donor
screening problems
(Bates pages 030560-030570); donor deferral problems (Bates
pages 030575-030577); donor file check problems (Bates
page 030565); hepatitis B, HTLV I/II, syphilis, and cytomegalovirus
donor sample testing problems (Bates page 030588); and
misbranding
problems, such as products not meeting leukoreduction criteria
labeled as leukoreduced and antigen-positive products labeled
as antigen-negative (Bates page 030592).
- Revised Problem Management SOP Work Instruction 10.3.3,” Investigating
Problems” and Revised Problem Management SOP Work Instruction
10.3.4, “Developing Corrective Action Plans and Effectiveness
Checks”: In Work Instruction 10.3.3, ARC established [REDACTED] levels
of investigations that it believes are commensurate with
the level of risk posed by problems. Specifically, the
Work Instruction designates [REDACTED] Work
Instruction 10.3.3 requires that investigations for [REDACTED] problems
include determining the probable cause, correcting the problem,
documenting the rationale in the automated problem-management
system, and forwarding to QA for closure. (See Bates
page 030478, item 8.) Work Instruction 10.3.4 only requires
development
and implementation of a thorough corrective action to prevent
recurrence of [REDACTED] (See Bates page
030480.) Work Instruction 10.3.4 does not provide any information
regarding which [REDACTED] It also fails
to direct ARC regions and laboratories to develop and implement
corrective actions to prevent recurrence of [REDACTED] problems
that are identified as trends. (Paragraph III.B.64 of the
Decree (page 10) defines a trend as “the recurrence or multiple
contemporaneous occurrences of the same or similar problems
in one or more than one ARC region and/or laboratory.”)
At Bates page 030478, Work Instruction 10.3.3 asks in item
12, [REDACTED] The Work Instruction
should state clearly that such a “no fault” determination
must be based not only on review of the circumstances of an
individual problem but also on trending information for similar
problems. Few, if any, of the problems related to ARC’s
manufacture of blood and blood products should be regarded
as [REDACTED] For
example, the Work Instruction mentions post-donation information
as a type of problem beyond ARC’s control. Although it
is true that a donor’s failure to provide information
relevant to required deferral from donation may be beyond ARC’s
control, a trend of increasing post-donation information reports
should trigger an ARC investigation to determine whether there
is a problem with health historian interviews or a problem
related to a particular blood donation record question. Such
circumstances are within ARC’s control, and ARC is
obligated to identify, correct, and prevent recurrence of
those problems.
In item 2 of the July 22, 2003 Adverse Determination Letter,
FDA stated that ARC’s Problem Management SOP submitted
on June 3, 2003, failed to comply with Paragraph IV.B.1.a.ii.
of the Decree because it provided instructions to categorize
problems and to only investigate, correct, and prevent categories of
problems. ARC has not fully addressed that failure in this
revised Problem Management SOP. Instead, the revised Problem
Management SOP requires an investigation of all problems,
but does not require that they be corrected in a manner to
prevent
recurrence. Although FDA accepts the approach that genuinely “minor” risk [REDACTED] problems
may be, in addition to logged and tracked, corrected without
use of a formal corrective action
plan (as defined in the revised Problem Management SOP),
FDA fully expects ARC to ensure reliable and accurate risk
assessment
and to implement corrective actions that prevent recurrence
of the problems that are identified as trends by a region,
laboratory or BHQ.
- Revised Problem Management SOP Work Instruction 10.3.4, “Developing
Corrective Action Plans and Effectiveness Checks”:
Work Instruction 10.3.4 requires a [REDACTED] However,
the Work Instruction provides no indication of what types
of [REDACTED] problems trigger a directive by ARC to develop and
implement a [REDACTED] corrective action.
(See Bates page 030480.) In addition to thoroughly correcting
and preventing
recurrence of [REDACTED] problems,
FDA expects ARC, at a minimum, to thoroughly correct and
prevent recurrence of all trends related to [REDACTED] problems.
As stated above in item 1.a on page 2 of this letter, FDA
finds that reliance on Job Aid 10.4.ja2 to determine a
risk indicator, which is then used, according to Work Instruction
10.3.4, to determine the extent of corrective actions,
may
result in ARC’s failure to prevent recurrence of
potentially significant problems.
Additionally, FDA finds that the time frames for completion
of corrective action plans, as defined on Bates page 030615,
listed in Work Instruction 10.3.4 (at Bates page 030480 through
030482) fail to comply with the Decree requirement “commensurate
with the nature of the problem…[to] promptly… correct,
and take steps to prevent the recurrence of each problem….” For
example, the Work Instruction allows 90 days to complete
corrective action plans for [REDACTED] and
150 days for [REDACTED] problems. (See Bates
pages 030482.) FDA finds unacceptable a policy that allows
longer time frames for completion of corrective
action plans for all [REDACTED] problems
than for lower risk problems. ARC must give a higher priority
to expeditious resolution of “major” risk problems.1
Additionally, (at Bates page 030484) step 9 of Work Instruction
10.3.4 directs the regions and laboratories to assign a new
problem number when the effectiveness check indicates that
a problem was not solved, following the implementation of
the corrective action plan. Although Directive 10.2.1, “Problem
Management” (at Bates page 303443), requires linkage
of a new problem number to an “existing” problem
number for unresolved problems, there is no assurance that all previously
assigned numbers will also be linked. In order for ARC and
FDA to readily evaluate the adequacy of prior investigations
and corrective actions related to unresolved problems, ARC
must clearly link all numbers previously assigned to a problem
that remains unresolved after ARC implemented multiple ineffective
corrective actions.
- The revised Problem Management SOP fails to comply with Paragraph
IV.B.1.b.,
because it is not designed to adequately identify trends.
(Paragraph III.B.65 of the Decree
(page 10)
defines a trend as “the recurrence or multiple contemporaneous
occurrences of the same or similar problems in one or more
than one ARC region and/or laboratory.”) For example
(at Bates pages 030528 to 030533), the revised Problem Management
SOP Work Instruction 10.3.13, “Identifying Trends,” requires
use of [REDACTED] to identify trends in
a single facility and [REDACTED] to identify
system-wide trends. The revised SOP does not provide sufficient
information
regarding limits and use of [REDACTED] Although
FDA acknowledges that [REDACTED] may be
used for trending, it sees limited applicability in the manufacture
of blood and blood products, particularly
when use of those charts may result in ARC’s acceptance
of a level of non-compliance with the law, ARC SOPs, or the
Decree. For example, [REDACTED] are not
an appropriate trending mechanism if used in a manner that
results
in establishing an acceptance
limit for lost blood products because the law clearly requires
that the disposition of each blood product must be traceable.
(See 21 CFR § 606.165(a).) Moreover, such problems must
be trended in a manner that requires more detailed analyses
than that required by either chart. Such analyses should
include, but are not limited to: 1) a review of the number
of problems
reported by regions and laboratories; 2) a review of root
causes determined by regions and laboratories; 3) an evaluation
of
the appropriateness of corrective actions implemented by
regions and laboratories; and 4) an evaluation of the significance
of the individual problems being analyzed, including whether
unsuitable blood products have been released.
- The revised Problem Management SOP fails to comply with Paragraph IV.B.1.
of the Decree, because it does not ensure that each region
and laboratory will “detect, investigate,
evaluate, correct and monitor all problems, 2 trends, and system
(systemic) problems” reported through external complaints.
FDA notified ARC in item 1 of the July 22, 2003 Adverse Determination
Letter that the Problem Management SOP ARC submitted on June
3, 2002, was deficient in this respect. FDA has determined
that your revised Problem Management SOP does not correct that
deficiency, because Work Instruction 10.3.11, “External
Customer Complaint Management,” only provides instructions
for handling direct complaints directly related to a product,
not complaints relating to process, procedures or employee
performance.
- Work Instruction 10.3.9, “Suspension of Activities,” provides
instructions for reporting suspension of activities. (See Bates
Pages 030511 through 030513.) However, those instructions do
not comply with the requirements for reporting partial or complete
suspensions in Paragraph XIX of the Decree. In Work Instruction
10.3.9, the criteria for reporting suspension of operations
are “completely stopped activity for 24 hours or more,
or partially suspended (work slow down) for 24 hours or more
because of any compliance issue.” However, the Decree
states that “ARC shall take all actions necessary to
accomplish the objectives of this Order, including personnel
actions…and partial or complete suspension of operations
of one or more regions and/or laboratories. ARC shall notify
FDA within 24 hours of any such suspensions of operations….” ARC
is required to notify FDA of all partial or complete
suspensions of operations. To ensure compliance with Paragraph
XIX, FDA
expects ARC to revise all other references to the partial
or complete suspensions of operations in the revised Problem
Management
SOP, such as the Job Aid: Glossary of Terms, found at Bates
page 030617.
***
In addition to the deficiencies cited in items 1 through 4
above, FDA’s review of ARC’s revised Problem Management
SOP revealed additional problems that raise serious questions
about its adequacy and about ARC’s compliance with other
provisions of the Decree. Therefore, FDA has the following
comments and requests for additional information:
- Work Instruction 10.3.10, “Managing Material Review
Boards,” provides instruction for determining the disposition
of non-conforming materials, including distributed blood
prod
ucts. It instructs the quality assurance (QA) staff to
check ARC’s [REDACTED] to determine
whether a precedent case exists and, if so, “disposition the
products according to the precedent case, approve, and close….” However,
the Work Instruction does not direct the QA staff to use
current standards to evaluate the precedent case, prior
to deciding whether to retrieve unsuitable blood products
from
the marketplace. For example, precedent actions taken early
in the evaluation of the white particulate matter found
in donor bags may or may not be appropriately applied to
more
recent occurrences. ARC must ensure that QA staff not only
consult the [REDACTED] but also consider all
available relevant information to determine whether to retrieve
distribute unsuitable blood products. The Work Instruction
only provides for periodic review of [REDACTED] precedent cases and quarterly updates of the
[REDACTED] with results of those periodic reviews.
Given its use of the [REDACTED] in making critical
decisions, ARC should establish a required frequency for
its review of [REDACTED] precedent cases.
- FDA requests the following additional information
related to Job Aid 10.4.ja2, “Biological Product
Deviation Codes, which is found at Bates pages 030549-030607:
- Please explain the inconsistent risk indicators
and [REDACTED] ratings for BPD codes
LA-81-12, “irradiation status incorrect
or missing,” and BPD code LA-81-14, “irradiation
and leukoreduction status incorrect.” (See Bates page
0300592.) Also explain why BPD code LA-81-14 is assigned
a risk indicator of [REDACTED], while
at Bates page 030550, the [REDACTED] states
that when a blood product is labeled as irradiated, but irradiation
was not performed, the problem
will be tracked as high risk no matter what the circumstances.
Additionally, at Bates pages 030603, ARC’s rationale
for the [REDACTED] is that “product
not irradiated…” will always receive “a high
[REDACTED] rating regardless of the circumstance.” However,
QC-97-02 “product not irradiated” is assigned
a [REDACTED]. Please explain this discrepancy.
- FDA classified 594 ARC recalls in 2003. Of that
number, 144 were ARC recalls associated with donor screening
(DS) BPD
codes. ARC has assigned a [REDACTED] to
many of its DS BPD codes because the problems are [REDACTED] (See
Bates page 030471.) If DS errors are easily detectable,
please explain why ARC did not detect
DS problems that led to the 144 recalls in 2003.
- At Bates page 030565, ARC has assigned a [REDACTED] for
BPD code DS-26-01-04, “donor
file check, search incorrectly completed” because [REDACTED] Since
the purpose of donor file check is to search ARC’s
[REDACTED] and, when applicable, [REDACTED] for
previous donations from a now-deferred donor, the stated
rationale for the [REDACTED] does not appear
applicable to donor file check. Please state what procedures
ARC has established for review of donor
file check searches that justifies a [REDACTED]
- At Bates page 030588, ARC has assigned the [REDACTED] for “testing
performed incorrectly for” hepatitis B (surface antigen)
and cytomegalovirus (CMV) because [REDACTED] However,
hepatitis B may have long term effects on the liver, such
as cirrhosis, liver failure, or hepatocellular carcinoma.
CMV
may cause death in infants and may result in serious health
consequences for immunosupressed patients. Please explain
ARC’s
rationale for assigning a [REDACTED]
- At Bates page 030592, ARC assigned [REDACTED] for
BPD code LA-82-08-01, “antigen-positive unit labeled
as antigen-negative.” The product would be misbranded,
and consignees generally do not re-check the antigen status.
Such misbranded products could present a serious risk to
recipients. Please explain ARC’s rationale for assigning
a [REDACTED]
- FDA found that the revised Problem Management SOP
is inconsistent and will not assure development and implementation
of thorough
corrective actions for all trends detected at BHQ that involve [REDACTED] problems.
Specifically, although Work Instruction 10.3.4 (at Bates
page 030480) states that [REDACTED] corrective
action plans are required for escalated or systemic problems
and problems identified in the Analysis and Investigation
Report (required under Paragraph IV.B.1.b. (page 17), Directive
10.2.3, “BHQ
Management of Problems,” which addresses managing problems
identified in the Analysis and Investigation Report, provides
directions to follow Work Instructions 10.3.3 to determine
the extent of investigative activities. (See Bates page 030463.)
In turn, Work Instruction 10.3.3 allows [REDACTED] problems
to be closed without a [REDACTED] corrective
action. Therefore, a user following the instructions in Directive
10.2.3
and Work Instruction 10.3.3 may conclude that no [REDACTED] corrective
action is necessary to prevent problems identified as a trend
involving [REDACTED] problems.
-
FDA acknowledges that ARC’s revised Problem Management
SOP states (on Bates page 030419) that [REDACTED] For
that reason, FDA verbally asked ARC to provide several
procedures that ARC referenced in the revised Problem Management
SOP.
ARC provided those procedures on December 1 and 11, 2003.
FDA’s review of the procedures shows that ARC has not
sufficiently reviewed, revised, and fully integrated all of
them into the Problem Management SOP to ensure compliance with
the Decree. FDA is particularly concerned with those procedures
for reports that Paragraph IV.B.1.a. of the Consent Decree
requires to be scrutinized by ARC for the purpose of problem
identification -- specifically, internal deviation reports,
including “hotline” reports, Clarify reports,
and computer-software and hardware problem reports. The following
examples illustrate the need for review and revision of these
related procedures:
- LOP 90.800, [REDACTED] Version
1.0, Version Date: April 17, 2003, provides instructions
for the investigation, resolution, and documentation
of calls to
the [REDACTED] FDA’s review found
that procedures for entering hotline cases into the [REDACTED] (on
page 6 of LOP 90.800) are incomplete because no instructions
are provided
for entering information, including problem type, discovery
information, function, and source code, into the [REDACTED],
as required by Job Aid 10.4.ja7. Additionally, page 6 of
LOP 90.800 states that hotline problem description
entered into [REDACTED] If by this ARC
means that scarce detail will be entered into the [REDACTED] description
field, FDA is concerned that some hotline problems may
be overlooked during trending
and trend analysis. Finally, to ensure that hotline problems
are managed in accordance with the Problem Management SOP
and Decree, ARC should also revise the LOP to provide clear
instructions
regarding who is responsible for determining which hotline
reports are problems that must be logged and tracked in [REDACTED] and
who is responsible for investigating and correcting those
problems, in accordance with Paragraph IV.B.1 of the Decree.
- At Bates Page 030462, the Problem Management Procedures
refer the user to BSD 23.110M, “Process for User Support
and Software Releases,” for criteria to identify ARC-supported
computer software and/or hardware-related adverse trends
and problems that must be elevated to BHQ. However, FDA’s
review of BSD 23.110M (Version 1.1, Version Date: November
2000) showed the procedure lacks such criteria.
- BSD 23.111, “Problem Reporting and Tracking,” Version
1.0, Version Date: December 2000 is ARC’s procedure for
tracking calls received from regions and laboratories through
the “Clarify” call tracking system. That tracking
system is separate from [REDACTED]. FDA’s
review of BSD 23.111 shows that it does not provide instructions
to ensure that
problems reported through the Clarify system by regions and
laboratories will also be entered into [REDACTED].
BSD 23.111 also does not provide instructions to ensure that
issues reported
by regions and laboratories through Clarify and, subsequently
identified at BHQ as problems, will be entered into [REDACTED].
The list of ARC procedures requested by FDA is not
an all-inclusive list of those that support or relate
to the Problem Management
SOP, and items 6.a. 6.b., and 6.c. above are not intended
to represent an all-inclusive list of inconsistencies
or potential
deficiencies. ARC should review all related and supporting
procedures and revise them as necessary to ensure integration
with the Problem Management SOP and compliance with the
Decree. Additionally, ARC should determine whether additional
supporting
procedures must be established, such as procedures outlining
the means by which, the frequency of, and the person(s)
responsible for review of FDA 483 observations and FDA
compliance-related
correspondence to identify problems and to ensure those
problems are promptly entered into ARC’s tracking
system.
* * *
Paragraph VI.B. of the Decree provides that if FDA determines
that any SOP, report, or plan submitted under specified paragraphs
of the Decree, including Paragraph IV.B.l., “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 the
ARC's revised Problem Management SOP is inadequate to comply
with the law and the Decree, that the violations are significant,
and that it should invoke the penalty provisions of the Decree.
Indeed, as explained 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 the July 22, 2003 Adverse Determination Letter, 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 revised SOP, but also that FDA regards this SOP as
a first and indispensable step to enable ARC to comply with
current good manufacturing practice. In the revised Problem
Management SOP, ARC has corrected some deficiencies in the
previous SOP; however, the revised SOP falls significantly
short of compliance with the Decree.
FDA hereby orders ARC to revise the Problem Management SOP
in a manner that will correct the violations discussed above
and otherwise comply with the law and the Decree. Pursuant
to Paragraph IX of the Decree, FDA intends to fine ARC $7,500
for 60 days of the period between October 28, 2003, and February
6, 2004. Please note that this period does not include the
period between the date of this letter and your next submission.
(See Decree Paragraph IX.) If the next version of the Problem
Management SOP is inadequate and a fine is imposed, the fine
would include the preceding period.
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) Lee Bowers
Lee Bowers
Director, Baltimore District
cc: Marsha Johnson Evans
President and CEO
American National Red Cross
2025 E Street, N.W.
Washington, D.C. 20006
Mary Elcano
General Counsel
American National Red Cross
2025 E Street, N.W.
Washington, D.C. 20006
David T. McLaughlin
Chairman, Board of Governors
American National Red Cross
2025 E Street, N.W.
Washington, D.C. 20006
[1] FDA also notes that the time frames set forth in Work
Instruction 10.3.4 appear to be inconsistent with the requirements
of Paragraph
X.F. of the Decree (Page 65). Paragraph X.F. requires ARC “…within
10 days of initially discovering a problem that may result
or may have resulted in the release for distribution of units
of unsuitable blood or blood components, to review and document
the review of all records necessary to determine whether distribution
of units of unsuitable blood or blood components in fact occurred
and to identify all related units of unsuitable blood or blood
components that were, may have been, or may be distributed….” While
the Work Instruction does mention (at Bates pages 030474 and
030475) determining whether other blood products have been
affected and notification of consignees, it does not refer
to the 10 day time frame for the Decree requirement above.
[2] 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.”
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