ARC Warning Letter and 483

ARC Warning Letter and 483

January 17th, 2012 // 2:09 pm @ jmpickett

http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicReadingRoom/UCM287834.pdf

Mr. J. Chris Hrouda Executive Vice President Biomedical Services American National Red Cross 2025 E Street, N. W. Washington, D.C. 20006

RE: United States v. American National Red Cross, Civil Action No. 93-0949 (JGP)

Dear Mr. Hrouda:

From April through October 2010, United States Food and Drug Administration (FDA) investigators inspected sixteen American National Red Cross (ARC) Blood Services facilities and observed significant violations ofthe law, regulations, and the Amended Consent Decree ofPermanent Injunction, entered on April15, 2003 (Decree). At the conclusion ofeach inspection, the investigators issued Forms FDA 483, Inspectional Observations (FDA 483), attached hereto (Attachment A). FDA is now, pursuant to paragraph VIII ofthe Decree, notifying ARC ofits determination that ARC has violated the Federal Food, Drug, and Cosmetic Act, FDA regulations, and the Decree, specifically 21 U.S.C. § 351(a)(2)(B), paragraphs IV.A., IV.B.l, IV.B.IO, and XIX ofthe Decree and Title 21, CFR § 210-211 and § 600-680.

The 2010 inspections cited herein were conducted at the following ARC facilities on the following dates:
Badger Hawkeye Region, 4860 Sheboygan Avenue, Madison, WI, 4/5-23/10 Great Lakes Region, 1800 East Grand River Avenue, Lansing, MI, 4/5-27110 Penn Jersey Region, 700 Spring Garden Street, Philadelphia, P A, 5/24/10 -6/4110 Connecticut Region, 209 Farmington Avenue, Farmington, CT, 5/4110-6115/10 Detroit National Testing Laboratory, 100 Eliot Street, Detroit, MI, 5/25/10-6/16/10 Indiana-Ohio Region, 1212 East California Road, Ft. Wayne, IN, 7/12-21/10 Southwest Region, 10151 East 11th Street, Tulsa, OK, 7/26/10-8/9110 Appalachian Region, 352 Church Avenue, SW, Roanoke, VA, 8/3-13/10 Heart ofAmerica Region, 405 West John H. Gwynn Jr. Avenue, Peoria, IL, 6/21/10-8/18/10

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Northern California Region, Fixed Collections/Distribution Site, 2731 North First Street, San Jose, CA,
917-13110

The Decree requires ARC to establish and properly implement appropriate quality assurance (QA) and quality control (QC) measures. Proper QA and QC programs by blood establishments include measures to prevent, detect, investigate, evaluate, and correct errors. The goals ofthese programs include preventing the distribution ofunsuitable blood products, and preventing the causes ofrecurrent problems. The proper implementation ofa strong QA program is essential to ensure the safety ofthe nation’s blood supply.

Violations observed and/or documented during the 2010 inspections include the items listed below. This is not intended to be an all-inclusive list ofviolations in ARC facilities.

DECREE VIOLATIONS:
Decree Violations: Inadequate Managerial Control
1. Failure to establish, implement and continuously maintain managerial control over QA in all regions and laboratories as required by paragraph IV.A.2. The development of written procedures and processes that are appropriately managed and implemented are essential components ofan effective QA

1 Decree paragraph III.B.57 defines the QNQC program as the “written SOPs for quality assurance and quality control that ARC must establish, implement, and continuously maintain under paragraph IV ofthis Order to ensure that bloodand blood components are collected, manufactured, processed, packed, held, and distributed by ARC in accordance with the law, ARC SOPs, and this Order, and have thepurity that they purport or are represented to possess.” (The italics in the quotations from the Decree are in the original and indicate that the italicized word is defined in paragraph Ill ofthe Decree.)

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ARC management, however, merged certain QA functions into centralized facilities without ensuring that the new facilities were adequately staffed to perform these functions in a timely or effective manner.
Beginning May 2008, ARC began to consolidate certain donor management activities,2 which were previously performed in 35 ofits 36 regional offices, into the Donor Client Support Center (DCSC). The DCSC is located in two facilities, one in Charlotte, North Carolina, and one in Philadelphia, Pennsylvania. The consolidation began in May 2008 and was completed in March 2010. During the consolidation, multiple internal audits and Problem Management (PM)/QA assessments were performed at the two DCSC facilities.3 The results ofthe internal audits and assessments and the subsequent internal investigations indicated that the DCSC was chronically understaffed and lacked the process controls to ensure timely and adequate performance ofthe donor management functions. In response to the internal audits, the DCSC repeatedly promised corrective actions, some ofwhich had not been completed or were ineffective at the time ofthe FDA inspection in September and October 2010.

During the consolidation phase, ARC had periodic senior management meetings, Quality and Compliance Oversight Committee (QCOC) meetings, and Board of Governors meetings in which the DCSC consolidation project was discussed. 4 Quarterly and annual QA and training reports were also submitted to ARC’s senior management.5 The meeting minutes indicate that ARC management was aware ofthe audit findings and the staffing and training deficiencies and that the QCOC was monitoring the situation to determine whether the consolidation should continue as scheduled. Despite the repeated, significant internal audit findings, the consolidation was permitted to continue with only one delay. After the consolidation was completed in March 2010, the meeting minutes indicate that ARC management continued to have concerns about the DCSC performance. The DCSC continued to be understaffed and had a backlog of what ARC reported as being approximately 18,000 donor management cases6 that had not been process-verified as required in Work Instruction 11.3.028, Process Verification, Version 1.1, and Forml5.4.frm015, Donor Reaction and Injury Record, Version 1.2.

Additional internal records that detail the DCSC’s management control deficiencies include the following:
2 Activities being performed at the DCSC include donor care and qualification functions, such as answering eligibility questions from the donors; donor deferrals; post donation and call back activities, donor complications and complaints; receipt oftest results and entry of the results into the NBCS software; management offollow up testing with the donor; donor reentry/reinstatement; deferral and surveillance management; managing donor requests for test results and blood types; donor notification of reactive test results and donor counseling; and military, state, and health department notifications. DCSC also performs client support services that include the management ofblood product retrievals; consignee notification for the release of unsuitable blood components; case investigations for possible transfusion transmitted infections, adverse reactions and bacterial contaminations; lookbacks; and serving as the liaison for regional/divisional medical directors. DCSC’s data management functions include the management of the National Donor Deferral Registry and the Donor File Check process. Problem management tasks for the Philadelphia DCSC are performed in Philadelphia as well as in the Charlotte DCSC and includes the detection, investigation, evaluation, correction, and monitoring ofall problems, trends, and system problems. 3 Facility Audits: 10/14-17/08 (Philadelphia), 10/14-16/08 (Charlotte), 3124-27/09 (Charlotte), 612-5/09 {Philadelphia), 12115/09-1/6/10 (Philadelphia), 10/622/09 (Charlotte), 4/20-22110 (Charlotte), 5/18-21110 (Charlotte); Problem Management Assessment 4/9/1 0; Quality Assurance Assessment 4/10. 4 Management Review Minutes for Collections and Donor Management: 2110/09, 5/15/09, 8nt09, 1218/09, 3/19/10, and 6/8/10; QCOC Meetings: 6127/08, 5/19/09, 8/27/09, 9124/09, 10/9/09, 10122/09, 11/13/09, 12111/09, 2/25/10, 3124/10, 4/9/10, 4122110, 6/11110, 6/24/10 and 8/13/10; Board ofGovernors’ Meetings: 4/23/08,6/6/08,3/26/09,5127/09,6/18/09,7122109,8127/09,9/23/09, 10/5/10, 12/14/09, 1127/10,2124/10,3124/ 10,4120/10,6/9/10 and 8/25/10 5 Quarterly QA Reports: ApriVJune 2008, 2008 Annual QA Report October 2007/September 2008, October/December 2008, January/March 2009, April/June 2009, 2009 Annual QA Report October 2008/September 2009, October/December 2009 and January/March 20I 0; Quarterly Training Reports: April/June 2008, July/September 2008, October/December 2008, January/March 2009, April/June 2009, July/September 2009, October/December 2009 and January/March 2010. 6 At the time ofFDA’s inspection ofthe DCSC, FDA determined that the backlog ofdonor management cases requiring process review was approximately 15,000 (II,531 in the Charlotte facility and 3,552 in the Philadelphia facility) and approximately 5,200 unreviewed DRIRs ( 4,949 in the Charlotte facility and 306 in the Philadelphia facility).

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a.
Two DCSC staffing documents (July and September 2009) state that “the organization is currently operating under the fa<;ade that the DCSC is self supportive in its QA and PM functions...Regions routinely provide support in problem closure and quality process review, both of which are major functions ...over 50% ofall problems are closed by non-DCSC QA staff located in the regions....any time something occurs in the field that strains the regional resources, assistance has to be withdrawn...this can immediately cause the DCSC to become unsustainable and fall into a backlog...another large concern is that every five weeks additional regions continue to transfer to the DCSC. Therefore, the situation is escalating to a point where the field will not be able to support the volume." Despite these staft1ng concerns, ARC management allowed the consolidation to continue. b. In April 2010, the Biomedical Headquarters (BHQ)/QCOC meeting minutes indicate that the DCSC had a backlog of approximately 18,000 donor management cases that had not been processverified as required by ARC's Work Instruction 11.3.028, Process Verification, Version 1.1. c. ARC's report from the April2010 DCSC problem management audit states that the root cause ofthe repeat observation pertaining to timely problem management is, "The DCSC Problem Management Department does not have the resources to consistently manage problems in a timely manner." d. The May 2010 Donor Client Service Specialist (DCSS) staffing report indicates that "without additional staff dedicated to answering eligibility calls, the DCSS position would be understaffed. This understaffing could create a situation ofa continually growing backlog, overtime pay required, and a decreased ability to handle natural spikes in incoming work." e. In July 2010, ARC senior management placed the DCSC on a Compliance Improvement Strategy (CIS) because it was determined to be a "high compliance risk" based on internal audits and FDA 483s received since March 2009. The CIS was not fmalized until 9/29/10, after FDA began the Philadelphia DCSC inspection. The final CIS states, ''Numbers and proficiency of staff are not adequate to effectively execute assigned tasks and responsibilities in a compliant manner; inadequate supervision and oversight." The CIS further states, "The Back-log Plan will provide the details ofhow any back-log will be managed and monitored, including defined commitments for reducing the back-log while appropriately managing new cases." In its 12/ 15110 response to the FDA 483, ARC stated, "BHQ did not effectively manage consolidation of the donor management functions into the DCSC. BHQ managed the donor management consolidation using existing mechanisms, including the system Quality and Compliance Oversight Committee (QCOC) and the Field Operations Group (FOG), to provide oversight. However, in retrospect, these mechanisms proved to be inadequate ...." The response also states that ARC "now recognizes that the DCSC management reports were insufficient in determining a complete and accurate picture ofDCSC performance." Decree Violations: Inadequate QA 2. Failure to comply with paragraph IV .A.2.a., which requires that the "director ofquality assurance shall be responsible for all ARC Biomedical Services quality assurance functions including, but not limited to, ensuring the establishment, implementation, and continuous maintenance of comprehensive QA/QC programs .. .. " Specifically, the BHQ and DCSC QA programs were not Page 5 - Mr. J. Chris Hrouda adequate to ensure that all regulated donor management operations were being performed effectively at the Philadelphia DCSC. Proper management oversight is essential to effectively implement a QA program; without it, the causes oferrors may not be promptly corrected and unsuitable blood products may be released. For example, a. At the beginning ofthe September -October 2010 inspection, the DCSC had a backlog of open cases that had not received the required review. Donor Status Change Records, Component Status Change Records, and Component Information Forms are required to have process verification prior to closure ofa case per ARC's Work Instruction 11.3.028, Process Verification, Version 1.1. A backlog of 3,552 cases, dating as far back as July 2009, existed at the Philadelphia DCSC facility. Additionally, Donor Reaction/Injury Records (DRIRs) require a Medical Director (MD) review and a final quality review. A backlog of306 open DRIRs, dating as far back as August 2009, existed at the Philadelphia DCSC facility. The backlogs were even larger at the Charlotte DCSC facility --11,531 DRIR.s requiring process verification and 4,949 DRIRs requiring MD review and/or final quality review. b. Quality Process Reviews have not been consistently performed by the DCSC QA staff since the Philadelphia DCSC was created in 2008. Quality Process Reviews are required in Directive 02.2.012, Quality Process Reviews, Version 2.1 , and are to be conducted by the QA staff on an ongoing basis to review the systems and processes being performed by the DCSC operations staff. In addition, these reviews are to "identify process improvement opportunities, possible procedure or compliance violations, and confirmation ofprocesses operating in a state ofcontrol." During the inspection ofthe DCSC, FDA repeatedly requested documentation that Quality Process Reviews had been completed at the DCSC, but no documentation was provided. ARC stated that only some ofthe reviews were completed through December 2009 and that others were not completed due to loss ofQA staff. c. The Quarterly QA reports, required by paragraph IV.A.2.b. to be submitted in writing by the QA director to ARC senior management and ARC Biomedical Services senior management, did not portray the seriousness ofthe staffing and proficiency problems occurring in the DCSC and identified by ARC internal audits and other internal assessments. For example, eight Quarterly QA reports were submitted to ARC senior management and ARC Biomedical Services senior management beginning in April 2008 through March 2010. However, it was not until the October-December 2009 report that the "capacity for problem management" and the backlog ofopen problems were mentioned in the quarterly QA report. In its 12/15/10 response to the FDA 483, ARC acknowledged that the "seriousness ofthe DCSC issues were not clearly documented in the Red Cross Quarterly Quality Assurance reports until the January -March 2010 report." d. A QA Assessment ofthe DCSC was performed in October 2009 and a PM Assessment ofthe DCSC was performed in November 2009. The reports identified staffing and workload issues due to the continuous consolidation ofmore regions into the DCSC. One report identified that the QA staff in Philadelphia had no donor management experience; some QA staff members already employed at the DCSC for six months were not fully trained; and staff was "struggling" with a lack ofsupport from QA management. The reports also indicate that there had been inadequate planning and inadequate change control associated with the consolidation ofdonor management functions from the regions into the DCSC. Despite these conditions, ARC continued with the consolidation until it was completed in March 2010. The QA and PM assessment reports were then issued to ARC senior management in April2010. In multiple Board ofGovernors Committee meeting notes, ARC's QA (through the QCOC) stated that it was closely monitoring all corrective actions related to internal DCSC audit Page 6 - Mr. J. Chris Hrouda observations and ensuring that staffing levels were adequate to continue merging the regions' donor management functions into the DCSC. FDA reviewed numerous problems opened as a result ofthe internal audit findings and observed that corrective actions were not developed and/or implemented promptly. However, the merging ofregions into the DCSC continued. For example, FDA' s review of ARC' s internal audits ofthe DCSC problem management function found the following deviations from the Decree and the Problem Management Standard Operating Procedure (PM SOP) 7: i. ARC's October 2008 audit ofthe Philadelphia and Charlotte DCSC facilities cited untimely problem management. In response, the DCSC opened Exception E-0455175 (Issue I00 17862-FC) (discovered 10/22/08 and closed on 3/31110) and determined root causes that included inadequate staffing levels, inexperienced staff, inadequate training, and a lack of tracking mechanisms to ensure timely problem management. The corrective action plan included hiring and training additional staff, developing tracking queries for the DCSC, and establishing a group to manage post donation information problems. QA approved the corrective action plan on 2/3/10 and implementation is documented as having been completed on 2/4/10 and 3/23/10. Issue I-0017862-FC states that the effectiveness check would be performed under Exception E-0680169 (Issue I-0017441-FC). ARC took approximately 17 months (from 10/22/08 to 3/23/1 0) to approve and implement a corrective action to address untimely problem management at the DCSC. ii. ARC' s June 2009 audit ofthe Philadelphia DCSC facility cited untimely management ofproblems. The audit report indicated that staff had been hired and that all moderate and major risk problems were being managed in Charlotte because Philadelphia was not fully staffed. It further stated that the DCSC continued to have a backlog ofproblems. In response, the DCSC opened Exception E-0595168 (Issue I-0015324-FC) (discovered 6/5/09) and determined that root causes included inadequate monitoring processes, lack ofstaffing proficiency, and a heavy workload. QA approved the corrective action plan on 8/24/09 after two corrective action plan extensions. The corrective action plan was not fully implemented until 2/24/10. The final effectiveness check had not been completed as of 10/11/10, approximately 16 months after discovery ofthe problem, and the problem remained open. 111. ARC' s January 2010 audit ofthe Philadelphia DCSC facility cited untimely management ofproblems. The DCSC response referred to previously developed corrective action plans documented in Issue I-0017862-FC (the corrective action plan for the October 2008 audit) and Issue I-0017441-FC (the corrective action plan for the October 2009 audit). The root cause described in the DCSC response was a lack ofresources to consistently manage problems in a timely manner. The corrective action plan included hiring staff, including a problem management manager, and establishing a separate post donation information problem group. iv. ARC's March 2009 audit ofthe Charlotte DCSC facility cited untimely management ofproblems. The auditor reported a backlog ofmore than 200 minor, moderate, and major risk problems. In response, the DCSC opened Exception E-0551794 (Issue I0013588-FC) (discovered 3/27/09, closed 5/4/10) and determined that the root causes included inadequate staffmg, noting that only two staff members had experience with moderate and major The two DCSC facilities have overlapping problem management responsibilities; therefore, BHQ audit observations and corrective actions affected both locations. For example, one audit report states that all moderate and major problems were being managed in Charlotte because Philadelphia was not fully staffed. QA management also stated that all post donation information problems are managed by staff in Philadelphia. 7 Page 7- Mr. J. Chris Hrouda risk problems and a lack ofoversight by the DCSC. The corrective action plan included training more staff to handle moderate and major risk problems, assigning oversight responsibilities, and tracking the age ofproblems. QA approved the corrective action plan on 4/29/09. Issue 10013588- FC documented the corrective action plan as implemented between 4/30/09 and 7/30/09. The sustained effectiveness check was not completed until 4/16/10, more than a year after discovery ofthe problem. ARC deemed the corrective action plan effective at that time. v. ARC's October 2009 audit of the Charlotte DCSC facility cited untimely management ofproblems. The DCSC opened Exception E-0680 169 (Issue I -0017 441-FC) (discovered 1 0/23/09, closed 6/111 0) and documented the root causes as lack ofan adequate tracking mechanism, problems not always being assif:,7Jled as they were discovered, and the outsourcing ofproblem management cases due to staffing levels. The proposed corrective action plan included developing tracking mechanisms and hiring QA and problem management staff by 12/1/09. QA approved the corrective action plan on 11/30/09. One tracking mechanism was implemented on 10/26/09 and a second was implemented on 1/29/10. Staff positions were opened on 1/29/1 0. The effectiveness check was completed on 5/3/10 and the problem closed 6/1/10, eight months after the problem was discovered. f. ARC's June 2009 audit ofthe Philadelphia DCSC facility cited observations pertaining to the DCSC failure to review donor management records in a timely manner. For example, i. ARC's internal audit report includes the observation that post donation information and donor ca11 back cases were not being process-verified in "a reasonable time period." In response, the DCSC opened Exception E-0595192 (Issue 1-0020482-FC) (di:;covered 615109, still open as of 10/8/1 0) and determined the DCSC did not consider process verification a priority because there is no deadline, there were competing priorities, and there was a lack of staffproficiency. The DCSC audit response states that they were already aware ofthe process verification backlog and had developed a plan to address it. The corrective action plan included slowing down the consolidation and changing the work flow. The proposed effectiveness check states that QA would do periodic case reviews to ensure that process verification is timely and that cases are completed. QA approved the corrective action plan on 7/20/10. Only one part of the corrective action plan is documented as having been completed on 8/30/10. The Exception Report states that the corrective action plan was ineflective, but at the time ofthe FDA inspection, there was no documentation of any fo llow-up corrective action investigation to address this problem. ii. ARC's internal auclit report includes the observation that the DCSC failed to ensure timely and accurate management ofDRIRs. The DCSC opened Exception E-0595184 (Issue I-0011152-NF and Issue I-0020136-FC) (discovered 6/5/09, closed 8/3/1 0). (The problem was later linked to Exception E-0794874, Issue I-0010881-FC, which addresses the FDA 483 observation issued at the Badger Hawkeye Region on 4/2311 0.) The DCSC determined the root cause included Lack ofstaff proficiency and lack of a well defmed process. The DCSC response stated that it was aware of the problem and had held workshops and proposed to establish a DRIR group by 8/1/09, and to conduct another workshop. Additionally, the corrective action plan included time studies by a 'lean engineer,' development of a backlog plan, clarifying DRIR time frames, and the hiring of. staffmembers to handle donor eligibility calls. QA approved the corrective action plan on 6/2/10. Issue I-0020136-FC indicates the corrective action plan was Page 8 - Mr. J. Chris Hrouda not fully implemented until 7/21110. There was no due date documented for one ofthe effectiveness checks, which was not completed as of912110, 15 months after the problem was identified. Decree Vwlations: Failure to Comply with Reporting Requirements 3. Paragraph XJX requires ARC to report in writing to FDA any partial or complete suspensions of operations ofone or more regions and/or laboratories. On 5/10/10, ARC notified FDA ofa complete suspension ofoperations at a mobile blood drive held in the Connecticut Region on 5/8/10 (Exception E0802346). The report stated that the collections operations were suspended at 1 :30 p.m. due to extreme temperature conditions, two donor reactions, and stafffeeling ill. However, during an inspection ofthe Connecticut Region in May-June 2010, FDA discovered that the 5/10110 report was inaccurate because the operations had not been suspended and ARC collected 16 blood donations at that drive between 1:30 and 2:59p.m. Decree Violations: Inadequate National Donor Deferral Register8 4. Decree paragraph IV.B.lO requires ARC to maintain a National Donor Deferral Register (NDDR) that contains an accurate and complete list ofall ARC nationally deferred donors from each region. The safety of the blood supply depends on effective screening ofdonors to identify risk factors for diseases transmissible by blood and blood components, and the deferral ofhigh-risk potential donors. Because of the mobility ofthe population of potential donors, the effective implementation ofa national register ofdeferred donors is necessary to help ensure that accurate and current deferral information is available to ARC facilities nationwide. During an inspection ofthe Southern California Region in August-September 2010, FDA's review ofrecords pertaining to permanently deferred donors revealed that ARC has not established an accurate and complete list ofall permanently deferred donors, as required at 21 CFR 606.160( e). Information pertaining to permanently deferred donors from each ARC region is sent-to the DCSC to be incorporated into the ARC's NDDR. The NDDR was created because the ARC's National Blood Computer System, which services its 36 regional facilities, does not share donor deferral information among regions. The-ufdates to the NDDR are shared with all regions in a table format referred to as an NDDR "pushed table" so that any region can identify pem1anently deferred donors during the donor registration process, regardless ofwhich region deferred the donor. ARC NDDR is not adequate because, for example: (1) permanently deferred donors may not be identified during donor registration at the regions because the NDDR "pushed tables" only contain the donor's current infonnation and not the "before images"10 for donors who previously donated under different names; and (2) permanently deferred donors usjng hyphenated names may not be identified if attempting to donate using just one part ofthe hyphenated last name. FDA's record review identified nine permanently deferred donors listed on pushed tables that did not include their previously used last names. The absence ofsuch information prevents ARC from performing an adequate evaluation ofits NDDR records in order to prevent the distribution ofsubsequently donated blood products from donors whose blood should not be accepted for donation. For example, 8 21 CfR§ 606.1 60(c) requires lhlll a record be available from which oosuitable donors may be identitied so that products made from the blood ofsuch individuals will not be distributed. ACR refers to this record as the Donor Deferral Register. 9 "Pushed tables" are the mecllanism used to share information on permanently deferred donors among regions. If that information is not shared, regions are unaware when another region has pennanenlly deferred donors. 10 A "before image" is a historical record ofchallges made to the donor record in National Biomedical Computer System. Page 9 - Mr. J. Chris Hrouda a. A donor with a merged record had a newer identity under the initials-and an original identity under the initials. However, the NDDR contains the donor's current name only (initials -b. Donors with hyphenated names are assigned multiple soundex codes.11 For example, the soundex code for Dono~ho has a hyphenated name, is different for the first part, second part and entire hyphenated name.~three parts ofDonor. s name were given different soundex codes. Therefore, the NDDR only contains the donor's current information. Decree Violations: Inadequate Problem Management 5. Paragraph IV .B.l. requires ARC to establish and submit to FDA a PM SOP to detect, investigate, evaluate, correct, and monitor all problems, trends, and systemic problems.12 The Decree directs that the PM SOP include specific instructions to implement and document problem management requirements at ARC's BHQ as well as at the regional and laboratory facilities. Decree Violations: Problem Management [Management of Suspect Blood Products] Failure to promptly implement adequate corrective actions to prevent recurrence ofthe failure to control suspect13 blood or blood components. FDA has repeatedly cited ARC for this deviation, in letters issued pursuant to paragraph VI.A. ofthe original Consent Decree of Permanent Injunction entered on May 12, 1993, and in ADLs issued pursuant to the Decree entered on April15, 2003. ARC has repeatedly promised to implement and monitor corrective actions, but the corrective actions have not prevented recurrence ofthe problem. 14 The failures described below are particularly serious because the failure to control suspect products and to correct the causes oferrors increases the likelihood that unsuitable blood products will be transfused. For example, a. The DCSC identified trends related to the improper management ofsuspect blood products and inventory management, but failed to promptly and thoroughJy correct the problems. For example, i. A trend was identified for Biological Product Deviation (BPD) code QC-96-01-25 (product in wrong physical location, wrong electronic location) in October 2009. The trend was discovered on 11/30/09, and Exception E-0707671 (Issue 1-00 18721-FC) was created. The problem was closed on 2/1 8/10. The docwnented root cause was "Current process flows and functional roles do not meet System 11 requirements as they include hand-offs with steps that should be performed consecutively and immediately." The Issue report states that no formal A soundex code is a. igit code. The soundcx algorithm calculates a~l'-!!111..'1!1~~····..........~ 12 Paragraph 01.8.52 defines "problem" as "any deviation from the law, ARC SOPs, or this Order, however discovered, recorded, or reported, including, but not limited to deviations rep011cd in ARC Clarify repons (andlor in any other successor or similar deviation-reporting systems andlor reports), biological product deviation reports, internal deviation reporu, trends, adverse reaction reports, lookhack cases, cases ofsuspectedtran.sfusion·fran.smifted disease, potential system (systemic) problems, system (systemic) problems, SUpply and equipment problem reports, FDA-483s, compliance·rclatcd FDA correspondence, internal and extcmol audit reports, and retrievals." Paragraph lll.S.63 defines "system (systemic) problem" as "a problem that results from a defect in ARC policies, procedures, equipmen~ or supplies and affects either more than oneARC region and/or laboratory, or warrants corrective action which, when implemented, could affect more than oneARCregion andlor /aborOU>ry.” Paragraph 111.8.64 defines ”trend” as “the recurrence or multiple
contemporaneous occurrences ofthe same or similarproblems in one or more than one ARC region and! or laboratory.”
ll ARC defines “suspect” blood products as those which “may or may not meet safety, quality, identity, purity, and potency (SQUJPP) requirements and are
potentially non-confonning.” Directive: Mismanagement ofSuspect Products, 11.2.002, version 1.6.
14 See Attacb01tnt B for details ofcompliance history related to failure to control suspect blood or blood component~.
11
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corrective action will be taken due to the corrective actions implemented under another problem on 11/18/09 (Exception 0599613/lssue 1-0015339-FC) which QA approved on 2/16/10.
ii.
A trend was identified for the same BPD code in February 2010. The trend was discovered on 3/24/ 10, and Exception E-0774042 (Issue 1-0019647-FC) was created. As of 10/1110, the problem was still open. The documented root cause was, “Due to the original design ofthe Donor and Client Support Center (DCSC) workflow, there is a waiting period from the point when unsuitable components are identified to the time when they are managed or retrieved.” The Issue report indicates that QA approved the corrective action plan on 5/27/10, and it was implemented the same day; however, the approved corrective action plan is only a reference to corrective actions related to another problem. The interim effectiveness checks were deemed effective on 7/27/1 0; however, as of 10/111 0, there was no record that the sustained effectiveness check, which was due 8/26/10, was completed. Additionally, the records related to the other referenced problem indicate that implementation ofthe corrective action plan was not fully completed until10/5/10.
m.
A trend was identified for BPD code QC-90-0 1-05 (failure to adequately manage potentially non-conforming products, product not released) in May 2010. The trend was discovered on 6/30/10, and Exception E-08311 04 (Issue I -00 11219-NF) was created. The problem was closed on 8/2/10. The root cause was identified as, “The original process flows associated with these gain control and retrieval processes did not provide staff with the experience and responsibility to perform their required functions as a suspect product identifier.” The problem was closed without developing a corrective action plan, but instead referenced corrective actions and effectiveness checks addressed under four other Issue reports (Issue 10020891-FC, Issue 1-0016426-FC, Issue 1-0019143-FC, and Issue 1-0019389-FC). A review of Exception E-0625538 (discovered 7 /31109) and Exception E-0780785 (discovered 3/31/1 0), which are both associated with Issue 1-0019389-FC, found that a corrective action plan extension was approved for both problems on 4/30/10 and an additional corrective action plan extension was reque&ted for Exception E-0625538 on 8/17/09. QA approved the corrective action plan under Issue 1-0019389-FC on 5/19/10. One part ofthe corrective action plan was implemented by 5/31110, but the other three parts were not implemented until 10/5/1 0. Both problems remained open as of 10/ 14/10–one for more than 15 months and one for more than six months.
b. ARC discovered approximately 18 major risk problems coded as QC-90-01-05 (failure to manage potentially non-conforming products, product not released) that occurred at the Philadelphia DCSC facility during calendar year 2010. A review ofthose problem records found problem management deficiencies. For example,
i. ARC did not conduct an adequate root cause analysis, develop an appropriate corrective action plan, or conduct an effectiveness check for Exception E-0790730 (Issue 10020041-FC), which was discovered on 4/ 16110 and remained open as of 10/7/10. The problem description states that a hold was not applied to an in-date product for a donor with an XW3 assertion. 15 The root cause is described as “Due to the peculiarity ofthis case, [a supervisor] was puzzled which resuited in unclear guidance to a new staff.” The corrective action plan stated that the supervisor “recognizes how to appropriately handle these types ofcases so that he can better
15 An XW3 assertion is ARC’s donor indefinite deferral code for donors with a history of hepatitis, bleeding conditions, blood diseases and/or who tested positive for the HIV/AIDS virus by a non-ARC facility.
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communicate to staff the appropriate actions that are required.” QA approved the corrective
action plan on 5/21/10 and Issue I-0020041-FC states the corrective action plan was
implemented on 5/21/10; however, a corrective action plan was not listed in the report. The
effectiveness check was due on 8/27/10, but as of 10/7/10 had not been completed.
ii. ARC failed to implement a corrective action plan in a timely manner for Exception E-0751845 (Issue 1-0019143-FC), which was discovered 2/17/10 and remained open as of 10/7/ 10. The problem description states that no immediate effort was made to regain physical control ofthe blood products for a possible DRJR-related infection. The documented root cause was that the staff is feeling overwhelmed and frustrated. The corrective action plan was to develop a process to ensure a more structured management ofDRJR cases and to develop a phone schedule. QA approved the corrective action plan on 3/17/ 10, but it was not implemented until9/27110.
111. ARC failed to implement a corrective action plan and complete an effectiveness check in a timely manner for Exception E-0746476 (Issue I-0018941-FC), which was discovered on 2/5/10 and remained open as of 10/8/10. The problem description states that no hold was applied and the receiving region was not notified to gain physical control ofa component imported from another ARC region. The documented root cause was the staff failed to identify the importance ofgaining physical and electronic control ofthe component, “due to her lack of knowledge with the American Red Cross and DCSC.” The corrective action plan was that staff will be counseled and will continue to gain experience; and the training department will develop a communication to all staff and will conduct a training refresher. QA approved the corrective action plan on 3110/10. Implementation ofall corrective actions was not completed until 7/27/10, more than five months after discovery. Effectiveness checks due dates were 9/7/ 10 and 919110, but were not completed as of 10/8/10, more than eight months after discovery ofthe problem.
6. Failure to promptly, thoroughly, and adequately investigate and correct problems in accordance with the Decree and with ARC’ s PM SOP. For example,
Decree Violations: Problem Management [Donor Reaction/Injury Records (DRIRs)]
a. During the inspection ofthe DCSC, FDA observed that ARC identified trends16 related to DRIRs beginning in June 2009, but failed to promptly and thoroughly correct and prevent recurrence of DRIR documentation problems. For example:
i. On 9/30/09, ARC identified a trend, which occurred in June 2009, related to BPD code BC-40-01-02 (adverse reaction donor: incorrect/missing documentation on Donor Reaction/Injury Reports). Exception E-0664347 was created on 9/30/09. The root cause investigation and corrective action plan development (Issue I-0018632-FC) did not begin until 2/5/10, four months after discovery ofthe trend problem. An extension ofthe 30-day corrective action plan development time frame was granted by QA on 2/6/10. The documented justification for the extension was that the original corrective action plan was due on 10/30/09, but the problem was not assigned to a Problem Investigator untill/12/10. The root cause is documented
16 “Trend” is defmed in note II above. The DCSC began trending in accordance with the Decree and with WI 1 0.3. 13, Trend Identification by Facilities, in September 2009.
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as “staffare hurried and rushing to complete the form and overlook errors and omissions. The DRJR is filled out electronically and it is easy to overlook omissions on the form.” The Issue further states that “no additional corrective actions are necessary at this time” and refers to corrective actions implemented on 11/24/09 and 1/31/10 under BHQ system trend Exception E0603 257. The DCSC Q A staff approved the proposed corrective action plan on 2/1811 0 and closed the trend on 2/24110, five months after the trend was discovered.
ii. ARC BHQ system trend (referenced in 6.a.i above) was discovered on 6/23/09. Exception report E-0603257 (Issue I-0000334-EFC) was created on 6/23/09 and was closed on 6/29/10. The described problem is incomplete or incorrect documentation ofDRIRs. The root causes cited in Issue I-0000334-EFC include: “donor adverse reactions are rare stressful events and staff busy attending to the donor fail to document all required information…;” “staff inattention to detail and lack offocus … ; misinterpretation ofthe Work Instructions; failure to refer to the form instructions; gaps in DRJR instructions; and the format ofthe DRIR form.” The corrective action plan was approved by QA on 12/2/09, approximately five months after discovery ofthe trend. The corrective action plan included the release ofa communication in November 2009 to remind staffofrequirements and clarify instructions. The effectiveness check success criterion was -mprovement. On 6/15110, ARC used data from 2/1110 through 4/30/10 to perform the effectiveness check. They deemed the corrective action effective with only a 41% improvement. However, 41% is not sufficient and. is clearly inadequate as a goal.
111. On 5/25/10, a trend was discovered again at the DCSC for BPD code BC-40-0 102 (adverse reaction donor: incorrect/missing documentation on Donor Reaction/Injury Record). The trend occurred in April2010. Exception E-0811555 (Issue I-0020944-FC) was created and was still open as of I 0/1/10. The root causes cited include staffnot reviewing their work and “shortage ofdedicated DRIR staff.” An extension for the corrective action plan development was requested on 6/17110 and was granted by the DCSC QA the same day. A second extension was requested on 7113110 and was granted on 7/14/10. The corrective action plan, which was approved by QA on 9/8110, included a reminder to affected staffofthe DRJR requirements, hiring additional DRIR staff, and providing refresher training to other staffmembers that perform DRJR tasks. The staffreminder is documented as completed on 9/27/10, four months after discovery ofthe trend.
Decree Violations: Problem Management [DRIRs Failing to Reach the DCSC from the Regions]
b. On 7/911 0, ARC discovered a problem related to missing DRIRs that were sent by the regions to the DCSC. Exception E-0836426 was created on 7/12/10. As of 10/8/10, ARC had not completed an investigation into the root cause ofmissing DR1Rs and had granted two extensions for the development ofa corrective action plan untilll/12/1 0, four months after initially discovering the problem. A record review was completed in July 2010 for the period 12/1109 through 6/30/10. and identified 292 donor adverse reaction or injury cases with missing DRIR.s. The safety ofdonors depends on the prompt investigation into the causes ofdonor injuries and reactions, to correct causes ofsuch injuries where possible, and to implement training for appropriate staffintervention. The mismanagement ofrecords interferes with that process.
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Decree Violations: Problem Management [Confirmatory Test Results and the Donor Deferral Register]
c. During the inspection ofthe DCSC, FDA observed that ARC identified trends related to management ofconfirmatory infectious disease test results and Donor Deferral Registry (DDR) entry, but failed to promptly and thoroughly investigate, correct, and prevent the problems. For example,
i. On 10/29/09, ARC identified a trend for BPD code DD-30-01-10 (confirmatory results/DDR entry not performed/not timely) that began in September 2009. Exception E0683307 (Issue I-00 17599-FC) was created and was closed on 2/23110. The root causes were cited as inattention to detail due to staff being new, not understanding, or rushing. The proposed corrective action plan refers to corrective action taken under another problem (Issue I-00 16921FC). QA approved the corrective action plan on 12118/09 and the Issue report shows the corrective action plan was implemented on 12/18/09. It is described as “Reiterate the need for staff to slow down and pay closer attention to information being entered and to make sure that they go back and review entries prior to moving to the next step.” The corrective action plan also required supervisors to observe the involved staff while performing test result entry. The effectiveness check was performed and the corrective action was deemed effective by ARC on 2/19/10. However, the records for Issue I-0016921-FC, which was referenced as the corrective action plan for the trend problem, indicate that it was not fully implemented until4/27110 and the effectiveness check was not completed until 6/23/ 10.
ii. On 10/29/09, ARC identified a trend for BPD code DD-30-01-12 (incorrect/no computer property/assertion applied, no product released) for September 2009. Exception E0683302 (Issue I-00 17306-FC) was created 10/29/09. The root causes included misinterpretation ofinstructions, staff new to task, staff not aware they could remove assertions, and limited experience with holds. The investigation did not address why staff had been released to perform tasks they did not understand, yet QA approved the corrective action plan on 11118/09. The Issue report shows that the corrective action plan included the development ofa communication document for staff as well as the development and implementation of a new operational team. The problem was closed on 5/ 11110. However, because ofthe inadequacy ofthe corrective action plan, the DCSC subsequently had a trend recurrence for BPD code DD-30-01-12 in August 201 0.
Decree Violations: Problem Management [Consignee Notification17]
d. During the inspection ofthe DCSC, FDA observed that ARC identified trends related to consignee notification, but failed to promptly and thoroughly correct and prevent the problems. Prompt notification to consignees regarding the distribution ofunsuitable blood products is essential to preventing such products from being transfused. For example,
i. On 9/30/09, ARC identified a trend for BPD code MI-00-01-19 (48 hour notification to consignee not performed/complete/timely for distributed expired products) in June
17 Paragraph X.E ofthe Decree requires ARC to notify consignees and FDA’s Baltimore District Office within 48 hours after initially learning that a unit of unsuitable blood or blood component has been distributed. Paragraph X.F. ofthe Decree requires ARC, within 10 days ofinitially discovering a problem that may have resulted in the release for distribution of units ofunsuitable blood or blood components, to review and document the review ofall records necessary to determine whether distribution ofunits ofunsuitable 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.
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2009. Exception E-0664458 (Issue I-0020096-FC) was created on 9/30/09 for missed 48 hour
consignee notification and missed follow up timelines. Corrective action plan development
extensions were approved by QA on 10/20/09, 12/1/09, and 4/28/10. The justification for the
4/28/10 extension was “staff issues and lack of good tracking mechanisms ….” No investigation
ofthe trend problem was documented until 5/18/10. QA approved the corrective action plan on
7/611 0, ten months after discovery of the trend. The root causes are cited as “poor work
practices/work flow including poor follow-up, insufficient reviews, and oversight.” The
described corrective action plan included restructuring the DCSC into functional teams and
revising work flows to standardize gain control activities. Approximately one year after
discovery ofthe trend, the corrective action plan has not been fully implemented. Functional
teams were not implemented at the Philadelphia DCSC as late as June 2010 and at the Charlotte
DCSC as late as September 2010, as described in the Issue report. The status ofthe work flow
revisions is not documented. The trend problem remained open as of 10/1/10, twelve months
after identifying the trend.
ii. On 9/24/ 10, ARC identified a trend for MI-00-01-23 (recall/market withdrawal records incorrect/incomplete/not timely, including late follow up letters to consignees) in August 2010. Exception E-0878847 was created on 9/27/10. The problem description refers to the June 2009 MI-00-01-19 trend being managed under Exception E-0664458, as described in the item above. The trend problem remained open as of 10/1/ 10, twelve months after identifying the trend, with no documentation ofan investigation or corrective action.
Decree Violations: Problem Management [Lookback Investigations]
e. During the inspection ofthe DCSC, FDA observed that ARC had discovered problems related to the management oflookback cases dating back to 3/ 15/10, but failed to promptly correct those problems. When a person donates blood early in an infection, screening and testing may not detect the presence ofan infectious agent (the “window period”). After the infection is discovered, it is important to identify and “lookback” at prior donations that might have been collected during the “window period” in order to identify, notify and test any recipient ofa transfusion ofblood or blood components collected during the “window period.” Such process is necessary for the protection ofblood product recipients. For example, ·
i. Issue I-0019746-FC was created 4/26/10 to implement a formal corrective action for 17 different problems involving management of lookback investigations. The oldest ofthose problems was discovered on 3/15/10, yet a corrective action plan was not approved by QA until 6/25/10, more than three months after the initial date ofdiscovery. The root causes ofthese problems are identified as “supervisors are not consistently reviewing with their staff the open cases report generated from the Access Lookback Log” and “Operations Staff ofthe involved Supervisors may not have been trained to generate and use reports in the Lookback log database.” The effectiveness checks were not due until 12/10/10, nine months after the oldest problem was discovered.
ii. A trend related to the management oflook back investigations was discovered on 6/30/10. Exception E-0831094 (Issue I-0011220-NF) was created on 6/30/10 and was closed on 8/2/10. No formal corrective action plan was required by ARC and the Issue report references the formal corrective action implemented in Issue I-0019746-FC discussed in the item above. However, Issue I -00197 46-FC remained open at the time ofthe September-October 2010
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inspection because the effectiveness checks were not due until 12/10/10, nine months after the oldest problem involving the management oflookback investigations was discovered.
111. On 8/31/10, ARC discovered another trend related to the management of lookback investigations. Exception E-0864242 (Issue I-0011479-NF) was created on 8/31/10. The Issue report also referenced the formal corrective action implemented in Issue I-0019746FC, discussed in the item above, which remained open at the time ofthe September-October 2010 inspection, because the effectiveness checks were not due unti112/10/10, nine months after the oldest problem involving the management oflookback investigations was discovered.
Decree Violations: Problem Management [Failure to Meet Established Timeframes]
f.
During the DCSC inspection, FDA investigators requested a search ofARC’s automated problem management system for the period 111110 through 9/22/10. A review ofthe results revealed that the DCSC does not always meet the established time frames required in ARC’s PM SOP and in the Decree. For example, FDA observed that the query showed 90 problems in which the DCSC failed to comply with the paragraph X.E requirement to notify consignees within 48 hours “after initially learning that a unit ofunsuitable blood or blood component has been distributed.”
g.
During an inspection ofthe Indiana-Ohio Region in July 2010, FDA discovered that ARC failed to promptly correct a problem related to the late entry ofa donor into the NDDR. For example, a donor was confirmed positive for anti-HTL V on 116/10, but the result was not promptly entered into ARC’s National Biomedical Computer System until4/4/10 and was not promptly submitted for entry into the NDDR by the DCSC until4/5/ 10. Exception E-0781884 was opened on 4/6/10. It was merged with 27 other problems (in Issue I-0019116-FC, created 3/ 11/10) involving similar occurrences in other regions. The investigation determined the root causes were a lack ofdefined processes and misinterpretation oftimeframes for reconciliation oftest results. QA approved the corrective action plan on 5/11110, yet there was no documentation that the corrective action plan was implemented as of 7/16/10, four months after Issue I-0019116-FC was created. The corrective action plans that were approved by QA did not adequately address the identified root causes and the effectiveness checks were not adequate to assess effectiveness ofthe corrective action plan.
Decree Violations: Problem Management {Overweight Units]
h. During an inspection ofthe Heart ofAmerica Region in June-August 2010, FDA’s review ofmonthly trend records for BPD code BC-43-03 ( overbleed; not discovered prior to component preparation) in December 2009 revealed that ARC did not follow Work Instruction 10.3.013, Trend Identification by Facilities, Version 2.1, when analyzing data for the effectiveness checks for the corrective action plans implemented for Exception E-0717565 (discovered in December 2009) (Issue I0018377-FC). For example, the effectiveness check query found 13 additional overweight units during the queried period. ARC eliminated six ofthose occurrences from its effectiveness check calculation because their failure modes were “unknown.” ARC deemed the corrective action plan effective and closed the trend problem. FDA requested a query for March through June 2010 and found there were five additional occurrences ofoverweight units.
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Decree Violations: Failure to Follow Standard Operating Procedure
7. Failure to comply with paragraph IV.A.l., which requires “continuous compliance with this Order, the law, and ARC SOPs.” For example, during an inspection ofthe Southwest Region in JulyAugust 2010, FDA observed that ARC did not follow its written procedures pertaining to consignee notification in order to determine the fmal disposition of a blood product. The region held 25 imported components out ofcontrolled storage in excess of30 minutes. The region opened Exception E-07 48767 (Issue I-0004237) and Biological Product Deviation Report E-0748767 was opened on 2/12/10 and the region notified the DCSC to manage the components. The DCSC placed holds on the components and notified consignees. FDA’s review ofth~file from the DCSC found that the DCSC had no final disposition for five components and two components had a final disposition of”Q” (quarantine). According to Work Instruction 11.3.011, Sending Retrieval Letters and Notifications, Version 1.5, ifthe consignee does not respond to the first notification, a second notice must be sent in order to obtain the final disposition ofthe recalled component. The DCSC failed to send the second letters. Additionally, FDA noted during a subsequent review ofthe records that the Component Status Change Record for the recall found that it had not been process-verified five months after being created.
GMP VIOLATIONS:
GMP Violations: Inadequate System for the Distribution or Receipt of Blood Products
8. Failure to establish and maintain a distribution and receipt procedure that includes a system by which the distribution or receipt of each unit of blood can be readily determined to facilitate its recall, if necessary [21 CFR § 606.165(a)]. This procedure is necessary to ensure that unsuitable products are promptly recalled and not transfused. For example,
a. During an inspection ofthe Heart of America Region in June-August 2010, FDA discovered that on 12/15/08, ARC changed the manner in which it assigns a unique number to the label ofeach unit ofpooled cryoprecipitate. Prior to that date, each unit was assigned a four digit number, and after that date a nine digit number was assigned. The nine digit unique number is applied to the label on each unit ofpooled cryoprecipitate~ however, the computer record for each such unit continued to use the four digit format. ARC’s relevant written procedures still do not provide adequate instructions to ensure that staffresponsible for blood product retrieval and consignee notification consider whether the unit was distributed prior to or after the change to the numbering format.
Beginning February 2009, the Heart ofAmerica Region’s donor management functions, including blood component retrieval and consignee notification, were consolidated with the DCSC. FDA’s review of records pertaining to consignee notification for units ofpooled cryoprecipitate found that the DCSC notified consignees using the incorrect unit number format for four units. For example, pooled cryoprecipitate unit 2399 was distributed on 5/30/08. It was subsequently determined to require retrieval by ARC due to high risk behavior by one ofthe donors. On 12/2/2009, the DCSC notified the consignee ofthat unit by letter, using the erroneous nine-digit number 040C02399. The DCSC documented the unit’s final disposition on a Component Status Change Record (CSCR) as discarded; however, the FDA investigator was informed during the inspection that the documentation to support that final disposition was misplaced. During the inspection, ARC again notified the consignee with the correct four digit unit number and the consignee responded that the unit had been transfused into a patient on 6/26/08.
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During the inspection, ARC reported to FDA that as a result ofthis observation, it had opened an investigation and identified an additional 62 cases that were managed by the DCSC using the wrong unit number format. Those cases involved regions other than the Heart ofAmerica. In its 9/8/10 response to the FDA 483, ARC stated that the problem was caused by a procedural gap and that it was a systemwide problem.
b. During an inspection ofthe Northern California Region in September 2010, FDA discovered that the DCSC was unable to locate documentation for the final dispositions of31 Red Blood Cell units that were subject to retrieval. A Material Review Board decided to retrieve the products after it was discovered that the storage temperature ofthe units, documented at the time ofreceipt, was unacceptable. ARC contacted the consignee ofthe units to request a copy ofthe missing notification documentation. The CSCR form documented that all 31 units were destroyed. However, the consignee reported that eight units had been transfused into patients. The CSCR, with the incorrect dispositions, had been process-verified by the DCSC on 3/4/10, but the discrepancies were not detected.
GMP Violations: Failure to Follow Manufacturer’s Instructions
9. Failure to ensure that supplies are used in a manner consistent with the manufacturer’ s instructions, as required at 21 CFR § 606.65(e); and failure to prepare the phlebotomy site using a method that gives maximum assurance ofa sterile container ofblood [21 CFR § 640.4(f)]. For example,
During an inspection ofthe Southern California Region in August-September 2010, FDA observed collection staff placing hand warmers directly on Whole Blood donors’ arms over prepared phlebotomy sites. Only a piece ofgauze separated the hand warmer from the area where the venipuncture was performed. This action may have compromised sterility during the collection procedure. FDA’ s review ofthe manufacturer’s instructions for the hand warmer found that they specifically stated, “***Do not use***on parts ofthe body other than the hand***.” ARC’s 11/4/ 10 response to the FDA 483 acknowledged that this use ofhand warmers was inappropriate and could bum donors’ skin.
GMP Violations: Failure to Maintain and/or Follow Written Procedures
10. Failure to establish, maintain and follow written procedures that include all steps to be followed in the collection, processing, compatibility testing, storage, and distribution ofblood and blood components for transfusion and further manufacturing purposes [21 CFR § 606.1 OO(b)]. For example,
a. During the inspection ofthe DCSC, FDA reviewed ARC’s management ofrecipient complication cases, in which a patient had difficulty with a blood transfusion. ARC’ s Job Aid 11.4.ja056, Timing Guidelines for Recipient Complication Investigations, Version 1.0, requires that the DCSC complete a recipient complication case investigation within three months ofit being opened or document why the case remains open. In addition, the Job Aid requires that a monthly review ofeach opened case file be performed, to ensure that actions are being appropriately managed. However, FDA reviewed nine recipient complication investigations during the inspection ofthe Philadelphia DCSC facility and discovered the following:
i. Case ID DCSC-P-053-TR-TRL00375 was opened on 11/04/09 and was closed 5/25/10, 202 days later. The case file did not have a justification for exceeding the 90 day time frame documented in the case notes until2/ 16/ 10, the date ARC documented why the case was
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open for more than three months. The file also contained no documentation that the case was reviewed on a monthly basis to “ensure that actions are being appropriately managed.”
ii.
Case ID DCSC-P-053-TII-HBV00429 was opened on 12/28/09 and was closed 5/25/10, 158 days later. The case file did not have ajustification for exceeding the 90 day time frame documented in the case notes until 5/25/10, the date ARC documented why the case was open for more than three months. The file also contained no documentation that the case was reviewed on a monthly basis to “ensure that actions are being appropriately managed.”
m.
Case ID DCSC-P-053-TTI-HBV00651 was opened on 4/28/10 and was closed during the inspection on 10/611 0, 157 days later. The case file contained no j ustification for exceeding the 90 day time frame documented inthe case notes Wltil 8/12/10, the date ARC documented why the case was open for more than three months.
b. During an inspection ofthe Southeastern Michigan Region in August -September 2010, FDA reviewed 26 transfusion reaction/recipient complication cases and discovered 11 that were not managed according to ARC’s written procedures. For example,
i. The DCSC opened a transfusion reaction/recipient complication case on 7/9/09 and closed it on 5/22/10, without justification for why the case was open for more than three months.
ii The DCSC documented inaccurate final component dispositions on CSCRs.
Form 11.4.frm9, Component Status Change Records, Version 1.1, provides a component fmal
disposition section and states that ifus~d, it mu::;L b~ compl~t~d with “a valid disposition to the
fmal disposition.” DCSC-C-013-TR-ORX00246 indicates that one component was marked
destroyed, but had in fact been shipped to a consignee. Another component was marked as
expired in-house, but in fact had been destroyed by the consignee.
c.
During the inspection ofthe DCSC, FDA discovered that the DCSC has not established adequate procedures to ensure that donor health history deferred reports are generated daily and that failure to generate such reports will be detected promptly. According to the DCSC management, it has been operating with only draft work flows for the health history deferred report review process. During the inspection ofthe Philadelphia DCSC facility, FDA requested health history deferral records for July 2010 for three regions. The DCSC informed FDA that it had failed to generate five requested reports; therefore, it failed to conduct a review ofeach listed donor with prior donations for potentially unsuitable blood components requiring quarantine, retrieval, and consignee notification, when necessary. Upon discovery during the inspection, the DCSC opened Exception report E-0869169 to address the problem and review the omitted reports. Their review found that, due to the omission, prior donations from five donors had not been managed appropriately. In addition, ARC discovered an additional 18 omitted donor health history reports.
d.
During an inspection ofthe Greater Alleghenies Region in September 2010, FDA observed that during the blood donation process, the region provided donors with hand warmers prior to collecting a blood sample using the finger stick method. The blood samples were collected for hemoglobin determination as part ofthe donor health assessment to determine su~ ~on’s management said the hand warmers are used in the winter with the —–ARC bas not established a written standard operating procedure for use ofhand warmers to
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increase blood flow when a donor’s hands are cold. In addition, ARC has not provided training to the collections staff regarding their use.
e. During an inspection ofthe Heart ofAmerica Region in June-August 2010, FDA observed that ARC does not consistently follow Work Instruction 10.3.011, External Customer Complaint Management, Version 1.1 and Directive 10.2.9, Managing Customer Concerns, Version 1.0. For example, ARC’s recruitment staffdistributes “Blood Drive Sponsor Satisfaction Survey” forms to mobile blood drive coordinators and/or chairpersons. A portion ofthe survey requests feedback regarding the ARC blood drive staffing level. It also includes a space for comments. FDA’s review of survey forms found that complaints related to FDA-regulated functions were not investigated as concerns or complaints, in accordance with established written procedures as required by 21 CFR § 211.100(b) and 21 CFR § 606.100(b). For example,
Survey cards for two mobile blood drives conducted on 11/4/09 and 12111/09 reported complaints pertaining to a donor sprayed with blood and pertaining to donor injuries during phlebotomy.
During the inspection, ARC informed the FDA investigator that it believes complaints on the survey cards are not complaints because they are solicited information and that Directive 1 0.2.9 only applies when the donor takes the initiative to inform the staff ofthe complaint. Yet, Work Instruction 10.3.011 states that a complaint is “any written, electronic, or oral communication that alleges deficiencies related to the identity, durability, reliability, safety, effectiveness, or performance ofany device, blood component, blood product, process, procedure, or employee performance that impacts donor or product safety.” ARC also solicits donor feedback through the internet and does not evaluate those to determine whether there is an issue that should be managed as a concern or complaint, in accordance with its written procedures and regulations. In its 9/8110 response to the FDA 483, ARC maintains that the surveys are “proactive methods to improve business,” that they are not “designed to assess regulatory compliance,” and that they are “outside the scope ofthe Problem Management SOPs.” The response further states that subsequent to the Heart ofAmerica inspection, it modified the survey to remove the comment section and to add a statement directing the user to report donor issues to the collections lead and to provide a contact number. ARC’s response does not state how it modified the survey with respect to complaints about staffing or how it will address staffing complaints that may appear on future surveys.
f.
During the inspection ofthe Penn Jersey Region in May-June 2010, FDA observed a failure ofthe DCSC to follow written procedures to obtain final dispositions (January 2009 and March 201 0) for four components that were subject to retrieval because they were collected from a male donor who was registered as a female. The DCSC also had no documentation to support the final dispositions for the components. One CSCR had been process-verified, but the errors were not detected by the staff performing the verification.
g.
During inspections ofnine ARC regions and the Philadelphia DCSC, FDA discovered multiple failures by ARC to follow written procedures pertaining to managing adverse donor reactions, as required by 21 CFR § 606.170(a). For example,
i. During an inspection ofthe Heart ofAmerica Region in June-August 2010, FDA discovered that the region failed to conduct a thorough investigation ofeach reported adverse reaction, as required by 21 CFR § 606.170(a). For example, on 5/20/10, ARC received a report ofan adverse donor reaction from a high school blood drive coordinator regarding a blood drive
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on 5/19/10. During the blood drive, a 16-year-old donor’s hemoglobin test result was
unacceptable and a second blood sample was collected to re-test the donor’ s hemoglobin level.
The donor was accepted for donation based on the results ofthe second test. The donor lost
consciousness and hit his/her head after a unit ofblood was collected. The report included
injuries sustained by the donor subsequent to falling in the canteen area. In an ARC document, a
collection staffmember stated he/she had concerns about the donor’s weight and was aware of
the loss of consciousness, but did not believe a DRIR was necessary. Even after the region
received the report from the high school coordinator on 5/20/10, it failed to document the event
on a DRIR and investigate the adverse reaction. It was not until 6/29/10, after FDA reviewed the
complaint from the high school, that the region addressed the adverse reaction and the failure to
document and investigate it. At that time, the region opened a problem report to investigate the
failure to initiate a DRIR upon receipt ofthe 5/20/10 report, but the problem report did not
address the failure ofthe collection staff to initiate a DRIR on 5/19/1 0, when the event occurred
at the collection site. ARC’s 8/9/10 response to the FDA 483 states the root cause ofthe failure
to initiate a DRIR at the collection site is that the staff was focused on providing care to the
donor, which caused the failure to document the reaction. The root cause ofthe failure ofstaff at
the region to initiate a D RIR on 5/20/1 0 is that they “may not be familiar with recognizing all
aspects ofa donor reaction. These staff members focus primarily on the customer service
aspects ofthe concern and do not consistently identifY a potential donor reaction.”
ii. During the inspection ofthe Heart ofAmerica Region, FDA also reviewed Concern/Complaint forms for 2009 and 2010 and observed that eight ofthe forms included complaints related to adverse donor reactions. There were no DRIRs initiated in response to those complaints and there were no investigations ofthe reported adverse reactions. The reports pertained to bruising and swelling at the venipuncture site, painful needle sticks, and injury to arms and back subsequent to a donor fainting. In its 9/8/10 response, ARC stated that staff responsible for investigating the donor reaction “may not be familiar with recognizing all aspects ofa donor reaction. These staff members focus primarily on the customer service aspects ofthe concern and do not consistently identifY a potential donor reaction.”
111. During the inspection ofthe Heart ofAmerica Region, FDA also reviewed DRIRs completed during the period 3/1/10 through 5/2/10, and found three that had an untimely Medical Director’s review and/or final quality review. For example, a donor experienced a large hematoma after donating on 3/15/10. The final quality review was not performed unti16/25/10. The donor donated three more times before that final quality review was performed and experienced another hematoma following one ofthose donations.
iv.
During an inspection ofthe Badger Hawkeye Region in April2010, FDA reviewed DRIRs initiated in 2009, and found 13 without the final quality review and five missing the Medical Director review and the fmal quality review. On 5/3/2010, ARC reported a Significant Corrective Action (Issue 1-0010881-NF) following its investigation ofthis FDA 483 observation issued to the Badger-Hawkeye Region in April2010. ARC reported to FDA in this Significant Corrective Action that the DCSC facility in Charlotte had a backlog ofapproximately 2,000 DRIRs open for more than 60 days, demonstrating that the violations observed in the Badger Hawkeye Region were only a small part ofa larger issue. ARC’s corrective action was to assign and train more staff, to approve overtime, to do a time study, and to change the filing system.
Page 21 – Mr. J. Chris Hrouda
v.
During an inspection of the Great Lakes Region in April2010, FDA reviewed 47 DRIRs initiated during November 2009, and discovered that three had no final quality review and two had untimely reviews.
vi. During an inspection ofthe Indiana-Ohio Region in July 2010, FDA reviewed 24 DRIRs and discovered that three had no Medical Director review and eleven with no final quality review.
vii. During an inspection ofthe Appalachian Region in August 2010, FDA’s review ofDRIRs found five initiated in 2010 with no Medical Director’s review or final quality review. An additional 12 DRIRs (two initiated in 2009 and ten initiated in 201 0) had no final quality review.
vm. During an inspection ofthe Northern Ohio Region in August-September 201 0, FDA reviewed DRIRs initiated in 2010 and discovered that six had no final quality review. Additionally, one DRIR was not reviewed by a supervisor and a Medical Director and had no final quality review until eight months after the donor reaction. Only one attempt was made by the DCSC to re-contact the donor, eight months after the reaction.
ix.
During an inspection ofthe Arizona Region in September 2010, FDA reviewed records related to a potential donor complication that involved a phlebotomist who stuck herself with a needle, then stuck a donor with the same needle and collected a unit ofblood. For more than a month, the DCSC did not notify a Medical Director and the donor was not deferred. In its 10/29/10 response to the FDA 483, ARC stated the DCSC staff member who managed the DRIR associated with this incident was not aware ofthe need to immediately notify a Medical Director.
x.
During the inspection of the Arizona Region in September 2010, FDA also reviewed 13 DRIRs and discovered that 11 had no final quality review or an untimely final quality review. Four DRIRs also had an untimely or late Medical Director’ s review
xi. During an inspection ofthe Greater Alleghenies Region in September 2010, FDA discovered five DRIRs that were initiated in 2010 and had no final quality review. Another DRIR had the final quality review six months after the donor reaction.
xii. During an inspection ofthe Southeastern Michigan Region in August-September 2010, FDA reviewed DRIRs for the period 11/18/09 through 2/13/10, and discovered that 22 had no final quality review.
xm. During the DCSC inspection, FDA reviewed 13 DRIR case files that were opened
in the DCSC in January, February, and March 2010, but had not been process-verified as of
September 2010, as required by ARC’s written procedures. FDA also found that six ofthe
DRIRs had no final quality review and six had no Medical Director review.
GMP Vwlations: Inadequate Training and Staffing Levels
11. Failure to ensure that the personnel responsible for the collection, processing, compatibility testing, storage, or distribution ofblood or blood components are adequate in number, educational background, training, and experience to assure competent performance oftheir assigned functions and to
Page 22 – Mr. J. Chris Hrouda
ensure that the final product has the safety, purity, potency, identity, and effectiveness it purports or is represented to possess [21 CFR § 606.20(b)]. For example,
a. During an inspection ofthe Heart ofAmerica Region in June-August 2010, FDA’s review ofadverse donor reaction procedures and cases revealed that ARC permitted Medical Director designees located in the DCSC, who had no apparent medical training, to perform the required Medical Director’s review for major donor complications. The Medical Director’ s review includes a determination regarding donor suitability and a decision as to whether product quarantine or retrieval is necessary as required in Form 15.4,frm015 , Donor Reaction and Injury Record, Version 1.2. Job Aid 14.4.ja164, Final Case and Donor Suitability Assessment Code and Case Types, Version 1.0, permits designees to perform the Medical Director’s review. For example, ARC permitted DCSC staff with no medical degree, certificate or medical training to perform the Medical Director’s reviews for the following adverse donor reactions:
i. An adverse donor reaction that was reported on 9/17/09, and included seizures/convulsions.
ii. An adverse donor reaction that occurred on 12/3/09, and included a long loss ofconsciousness and loss ofbowellb~adder control.
111. An adverse donor reaction that occurred on 1/28110, and was reported to ARC as a large hematoma (6″x3″).
In its 9/8/ 10 response, ARC states that when it began consolidating donor management functions in the DCSC, it decided to eliminate the requirement to have a Medical Director review all DRIRs because minor reactions account for most ofthe post-donation reports. ARC further states that it trained DCSC case investigators to serve as Medical Director designees for adverse reactions, including minor complications, arterial punctures, large hematomas, and long loss ofconsciousness. However, ARC states that, at the recommendation ofthe BHQ Medical Office, it decided to require a Medical Director’ s review ofall major complications, except large hematomas. The implementation ofthat requirement was scheduled for 9/15/10.
FDA also notes that despite permitting designees with no medical training, certification, or experience to perform the reviews, ARC’s 9/8/10 response states, “The practice ofmedicine requires physicians to use available resources as necessary to make their medical assessment that may or may not include an assessment ofprior reactions or other medical history. Medical evaluation of donor reactions requires a case-by-case approach and medical judgment; consequently, medical practice is not defined in ARC procedures.”
b.
During an inspection ofthe Detroit National Testing Laboratory (NTL) in May-June 2010, FDA discovered that ARC did not thoroughly investigate a problem that it had detected. For example, proficiency test records for January-December 2009 were found by ARC to lack the signature oftwo employees on attestations that they had received the training. The NTL opened a minor risk problem (Exception E-0744002). FDA review ofthe records for that period found an additionall3 employees had not signed attestations. FDA also found an additional seven employees had not signed their attestations for the period 11/1/08-12/31108.
Page 23 – Mr. J. Chris Hrouda
c.
During an inspection ofthe Detroit NTL in May-June 2010, FDA discovered that annual competency reviews18 and/or QA reviews did not detect that employees were not correctly performing all steps oftesting blood samples. One test was repeatedly performed incorrectly by many employees beginning 2007, and another test was repeatedly performed incorrectly by many employees since April 2008. FDA’s review ofthe competency assessments for those employees performing those tests found that none failed the assessment. FDA’s review ofthe quality process review for one ofthe tests found that the errors were not detected.
d.
In addition to understaffing issues noted during review ofrecords at the Philadelphia DCSC during the September-October 2010 inspection discussed in paragraphs 2(d) and (e) above, FDA observed collection staffing issues during inspections at the Heart ofAmerica Region in June-August 2010. For example, FDA observed donor survey cards for three mobile blood drives conducted on 11/6/09, 1/12/10 and 1113/10, each ofwhich reported dissatisfaction with ARC’s staffing levels. FDA’s review of the operation reports and staffing matrices for those three drives found that staffing for both was below the staffing matrices.
GMP Violations: Inadequate Recordkeeping
12. Records are not maintained and/or not as detailed as necessary to contain a complete history of work performed as required by 21 CFR § 606.160. For example,
During the August-September 2010 inspection ofthe Southern California Region, FDA reviewed reports ofpotential duplicate donors and determined that investigations ofpotential duplicate donors are incomplete and/or not fully documented and lack documentation necessary to assess whether corrections were made. Duplicate donors are of concern because multiple donor records for the same donor may result in the release for distribution ofunsuitable blood products. Therefore, it is very important to correct duplicate records as soon as possible because each day the incorrect information remains in the system increases the likelihood that an unsuitable blood product will be released. For example, Soundex Reports for 2/1110-2/8/10, 2/9/10-2/16/10, 2/2/10-2/9/10, 3/22/10-3/29/10,2/8/10-2/15/10, 3/81103/15110, 1/31/10-2/6/10,2/10/10-2/17/10, and 2/4/10-2/11/10 state multiple donor pairs were determined to be false duplicates based on review ofBDRs. The specific information noted during ARCs review of the related BDRs and used as the basis for the false duplicate determination is not documented.
This is not intended to be an all-inclusive list ofviolations in ARC facilities.
* * *
ORDERS
Paragraph VIII ofthe Decree provides that “[i]n the event that FDA determines, based upon inspection… review ofARC records, or other information that comes to FDA’s attention … that ARC is not following any SOP that may affect donor safety or the purity or labeling of blood or any blood component …; has violated the law; has failed to fully comply with any time frame, term, or provision ofthis Order …; then FDA may order ARC to come into compliance with the law, ARC SOPs, or this
18 Paragraph IV.C.5 requires competency reviews to “be conducted and documented, at least annually, to evaluate each employee’sjob performance including, when appropriate, actual performance oftesting and data entry in controlled situations.”
Page 24 – Mr. J. Chris Hrouda
Order, assess penalties, and/or take any step that FDA deems necessary to bring ARC into compliance with the law, ARC SOPs, or this Order.” FDA directs ARC to do the following:
1.
Within 60 days ofreceipt ofthis letter, provide a status report ofeach issue noted during internal audits ofthe DCSC since the beginning ofconsolidation in May 2008 and whether each issue has been effectively corrected. Please provide a justification for any open problems created as a result ofan internal audit. Explain why they were not addressed promptly when the auditors found each issue.
2.
Within 30 days ofreceipt ofthis letter, provide a list and a complete description ofeach functional team in the DCSC, including a complete list ofall supplemental sites assisting with Philadelphia and Charlotte DCSC activities. Provide a status report ofthe staffhiring plan described in your 12/15/10 response to the Philadelphia DCSC FDA 483 issued on 10/29110.
3.
Within 90 days ofreceipt ofthis letter, re-examine the DCSC response to the ARC BHQ audit observations related to training. Report to FDA what ARC is doing to strengthen its DCSC training program given the audit observation and the lack ofa corrective action plan to address training at that point in time. Explain why obvious training deficiencies were not addressed promptly and adequately at the time oftheir discovery by the auditors. Also, explain ARC’ s methodology for evaluating the adequacy ofits DCSC training program.
4.
Within 45 days ofreceipt ofthis letter, provide a thorough description ofARC’s system for determining the staffing levels for the mobile collection drives and submit the written procedure that describes this system.
5.
Within 60 days ofreceipt ofthis letter, provide a thorough description ofthe DCSC’s operation for answering donor eligibility calls from collection sites, including the number ofstaff assigned to this function. Explain the use ofinexperienced DCSC personnel answering donor eligibility calls from collections sites. Describe what controls ARC has implemented to ensure DCSC personnel provide accurate answers to donor eligibility calls.
6.
Within 45 day ofreceipt ofthis letter, establish and implement a time frame for the Medical Director’ s review ofDRIRs. A timely review is critical to donor safety due to the seriousness ofsome donor reactions. In order to ensure that the safety ofthe donor is not compromised, the Medical Director’s review should be completed prior to allowing a donor who has experienced a donor reaction to return for additional donations.
7.
Within 45 days ofreceipt ofthis letter, communicate to all collection staff personnel and management the regulatory and procedural requirements for managing and documenting donor adverse reactions. Ensure that all collection staff is adequately trained to perform this task. Report to FDA your plan to accomplish this order.
8.
Within 60 days ofreceipt ofthis letter, develop a work around to assess whether a donor has prior names in the NDDR to ensure that unsuitable blood products are not distributed from donors who have prior names in the NDDR.
9.
Within 60 days ofreceipt ofthis letter, perform a retrospective review ofsurvey cards, since the time they were first issued to the date ofthis letter, to identify all complaints or concerns that are related to FDA regulated functions and, as required by the Decree, manage any regulated complaints/concerns
Page 25 – Mr. J. Chris Hrouda
as problems. Identify all regions that issue such survey cards. Additionally explain how ARC manages such complaints and concerns that are received through the internet.
10.
Within 30 days ofreceipt ofthis letter, provide copies ofall Quality Process Reviews conducted at the DCSC since the DCSC began merging of the regional donor management operations. This material was requested numerous times during the September-October 2010 Philadelphia DCSC inspection. Provide a detailed explanation why the completed Quality Process Reviews were not provided to the FDA investigators during the inspection.
11.
Within 60 days ofreceipt ofthis letter, provide a status report on ARC’s 12/15/10 response to the Philadelphia DCSC FDA 483 issued on 10/29/10.
12.
Within 30 days ofreceipt ofthis letter, provide a copy and complete description of the Modified Compliance Improvement Strategy (MCIS) that the DCSC was placed on in January 2011, as well as the status of the MCIS.
13.
Within 60 days ofreceipt ofthis letter, develop and implement an SOP to require complete documentation ofall information evaluated during review ofany utility report including the soundex reports. Provide a copy ofthis SOP to FDA and include the effective date ofits implementation.
14.
Within 30 days ofreceipt ofthis letter, provide an explanation for the use ofBPD Code QC-9001-05 [failure to adequately manage potentially non-confirming product (product not released)] when ARC’s investigation into problems determined that blood products were actually distributed. FDA noted this during the review ofException Reports E-0780785 and E-0790730.
15.
Within 60 days ofreceipt ofthis letter, review the contents ofthe quarterly and annual QA reports to ensure that such reports adequately convey to ARC’ s Biomedical Services senior management that serious problems or deficiencies are developing and/or have occurred. This would enable senior management to be aware of the potential risk ofthe developing problems/deficiencies to public health and the impact on ARC’s compliance with the law and the Decree.
16.
Within 45 days ofreceipt ofthis letter, provide a list ofall facilities using the hand warmers during the blood collection process. Include details regarding: when the facilities began utilizing the hand warmers, the purpose oftheir use is, and why they were in use without training and a written procedure.
17.
Within 45 days ofreceipt ofthis letter, evaluate the process for performing annual competency assessments and determine the reason they consistently fail to identify employees who do not perform tasks in accordance with written procedures or manufacturer’ s instructions. Report to FDA what steps you plan to take to ensure the assessments are adequate.
* * *
FDA has determined that ARC did not comply with the law, ARC SOPs, and the Decree, and, under paragraph IX ofthe Decree, FDA is fining ARC a total of $9,592,200.19 In previous Adverse
19 Paragraph IX.F.5. ofthe Decree states that “All penalties assessed under this Order shall be based on the year in which the violative conduct occurred. The annual cap amounts described in paragraph IX.F.l ofthis Order shall also be attributed solely to the year in which the violative conduct occurred.” To document compliance with that provision, FDA provides the
Page 26- Mr. J. Chris Hrouda
Determination Letters (ADL), FDA fmed ARC $10,000 for each day on which one or more violations occurred without regard to the number ofviolations that occurred on a particular day. This was the method used to calculate the fine in the October 2009 Problem Management ADL. However, as FDA noted in that letter, the Decree authorizes alternate methods ofcalculating fines. For example, paragraph
IX.A authorizes FDA to assess penalties for “each violation.” Thus, FDA can charge a per diem fme for each violation instead ofthe single per diem charge for all ofthe violations collectively. Because many ofthe violations continued for an extended period oftime, there were many days on which several violations occurred simultaneously, and thus an assessment for each violation will be considerably higher that a single per diem rate.
For the reasons explained below, FDA is assessing per diem fines separately for each ofthe violations as described by the following chart:
ADL Item
Violation
Violation Timeframe
Amount ner Dav
Total $2,437,500
l .a-e
Decree: Inadequate Managerial Control
375 days [912110 (date FDA 482 issued to the Philadelphia DCSC) back to 1216109 =270 days; 912110 to 12115110 (date of ARC’s FDA 483 response) =105 days; 270 days + 105 days =375 days]
$6,500
2.a-f
Decree: Inadequate Quality Assurance
375 days (912110 (date FDA 482 issued to the Philadelphia DCSC) back to 1216109 = 270 days; 912110 to 12115110 (date of ARC’s FDA 483 response) = 105 days; 270 days + 105 days =375 days}
$6,500
$2,437,500
3
Decree: Failure to Comply with Reporting Requirements
58 days [5110110 (date of ARC ‘s Suspension Report) to 7/6110 (date of ARC ‘s FDA 483 response) = 58 days}
$1,000
$58,000
4.a-b
Decree: Inadequate National Donor Deferral Register
358 days [8/9110 (date FDA 482 issued to the Southern California Region) back to 11112109 = 270 days; 819110 to 1114110 (date ofARC ‘s FDA 483 response) =88 days; 270 days + 88 days = 358 days}
$2,000
$716,000
5.a-b 6.a-h
Decree: Inadequate Problem Management
375 days (912110 (date FDA 482 issued to the Philadelphia DCSC) back to 1216109 = 270 days; 912110 to 12115110 (date of ARC’s FDA 483 response) = 105 days; 270 days + 105 days = 375 days}
$4,000
$1,500,000
7
Decree: Failure to Follow SOP
146 days (413110 (date final notification feller should have been sent) to 8/26110 (date ofARC ‘s FDA 483 response) = 146 days/
$1 ,600
$233,600
8.a-b
GMP: Inadequate System for the Distribution or Receipt ofEach Unit ofBlood
288 days [1213109 (date the DCSC notified the consignee with the incorrect unit number) to 918110 (date ofARC’s FDA 483 response) = 288 days]
$1,600
$460,800
9
GMP: Failure to Follow Manufacturer’s Instructions
83 days [8/1311 0 (date investigators observed use ofhand warmers) to 1114110 (date ofARC ‘s FDA 483 response)= 83 days)
$1,600
$132,800
following information. The penalty period described in this letter includes violations that occurred in 2007, 2008, 2009 and 2010. The penalty amounts assessed as a result ofthe violations for each ofthose years is $81,600 in 2007, $964,382 in 2008, $2,839,578 in 2009, and $5,706,640 in 2010.
Page 27 -Mr. J. Chris Hrouda
l O.a-g
GMP: Failure to Maintain and/or Follow Written Procedures
375 days [912110 (date FDA 482 issued to the Philadelphia DCSC) back to 12/6109 = 270 days; 912110 to 12115110 (date of ARC ‘s FDA 483 response) = 105 days; 270days + 105 days = 375 days]
$1,600
$600,000
II.a-d
GMP: Inadequate Training
357 days [911 7109 (earliest date investigator noted personnel without medical training were permitted to review adverse donor reactions) to 918110 {date ofARC’s FDA 483 response) = 356 days]
$1,600
$571 ,200
12
GMP: Inadequate Recordkeeping
278 days [113111 0 date ofearliest report ofpotential duplicate donors) to 918110 (date ofARC’s FDA 483 response) = 356 days]
$1,600
$444,800
TOTAL
$9,592,200
In arriving at this penalty amount, we have taken the following facts into account:
First, as noted above, proper QA programs by blood establishments are essential to ensure the safety of donors and the nation’s blood supply by properly and promptly investigating and addressing unsafe practices and procedures; preventing the collection, manufacture, processing, packing, holding, and distribution of unsuitable blood and blood components; and identifying and effectively fixing the causes ofrecurrent problems. Many ofthe violations discussed in this letter, when not suitably addressed and corrected, implicate these concerns.
Second, during the period 10/1109 to 12/1/10, FDA completed 42 inspections ofARC regions, National Testing Laboratories, and the DCSC facility. Ofthose inspections, FDA has classified nine as Official Action Indicated (OAI) and 19 as Voluntary Action Indicated; one has not yet been classified. This is the highest proportion ofOAI inspections of ARC facilities since ARC entered the Amended Consent Decree of Permanent Injunction on April15, 2003.
Third, many ofthe violations recounted in this letter are virtually identical to violations charged in previous ADLs. ARC has known ofthese continuing problems and has failed to take adequate steps to correct them.
Fourth, ARC’s Biomedical Services senior management knew or should have had full knowledge ofthe extent ofthe continuous and serious violations regarding the DCSC consolidation and the lapses in QA throughout the ARC facilities no later than October 2008 when the first internal audit ofthe Philadelphia DCSC occurred. (See paragraph IV.B.3 which requires internal audits to be performed and results to be reported to ARC Biomedical Services senior management.) In addition, ARC held periodic senior management meetings, QCOC meetings, and Board of Governor meetings in which the DCSC consolidation project was discussed. Quarterly and annual QA and training reports were also submitted to ARC’ s Biomedical Services senior management. (See paragraph IV.A.2.b. and e.) As ARC acknowledged, it “did not effectively manage consolidation ofthe donor management functions into the DCSC” and the methods it used to oversee the consolidation and operations ofthe DCSC “proved to be inadequate.” (12/15/10 response to the Philadelphia DCSC FDA 483.)
You should note that we have charged a higher per diem rate for the violations related to management oversight and QA to highlight the need for ARC Biomedical Services senior management to accept greater accountability and responsibility with respect to the correction and prevention ofQA problems, as well as a higher per diem rate for the substantial and recurring problem management violations.

1.
Observation 3.c ofthe FDA 483 Inspectional Observations (FDA 483) issued to ARC’s Biomedical Headquarters (BHQ) on April 26,2000, cited the firm for distribution oftwo unsuitable blood products. The components were not stored correctly and were quarantined. The components were inappropriately released from quarantine, and ARC had to recall them. The Establishment Inspection Report states that for the period, January 1, 1999, through February 2, 2000, the FDA investigators observed 86 reports related to distribution or potential distribution ofunsuitable products. In a July 21, 2000 letter, ARC stated, “Deviation reports are reviewed to determine the frequency of release ofunsuitable product. In addition, QA regional staff is required to report any unsuitable releases to BHQ within 24 hours. Each incident must be immediately and thoroughly investigated, and results reported to BHQ. All information is being closely monitored to determine the existence of any weaknesses not previously identified and verify the effectiveness ofcorrective actions …” In a September 29, 2000 letter, ARC stated that it released a written procedure that included ” … a requirement for 24-hour coverage to gain control ofnon-conforming materials immediately upon discovery …”

2.
On October 19, 2001, FDA issued a VI.A. letter to ARC following FDA’s inspection ofthe Lewis and Clark Salt Lake City facility. The letter cited numerous violations, including the failure to “correct known critical deviations, such as failure to…ensure that unsuitable units of blood are physically and electronically quarantined to prevent distribution of such units.” ARC stated the problem was mismanaged by the Region and that “long term corrective action to prevent recurrence ofthis type ofproblem has been undertaken by Biomedical Services Headquarters.” (Bates pages 025356025357)

3.
Observations 21-24 ofthe FDA 483 issued to BHQ on December 20,2002, cited the firm for distribution ofunsuitable blood products. The observation describes ARC’s System Problem 618 opened in January 2002 after discovering that regions were distributing unsuitable blood products. ARC stated that it implemented corrective action and that it would consider implementation effective if the number ofoccurrences was reduced by only-FDA issued a VI.A. letter to ARC that stated, “ARC failed to correct and prevent deviations that resulted in release and/or distribution ofunsuitable blood products.” ARC’s April 14,2003 response to the VI.A.letter stated, “Red Cross recognizes and understands the importance ofpreventing the release ofunsuitable products ….Over the last several years, BHQ has spent considerable time and effort to identify the factors that contribute to the release ofunsuitable products and to institute corrective actions related to these sources of information.” ARC committed to further investigate, develop additional corrective actions, and increase BHQ oversight.” (Bates pages 028681-028683)

1
4.
In a December 2003 submission, ARC reported to FDA that it opened System Problem 702 because “data continues to demonstrate an adverse trend in the release of suspect products. ARC described a corrective action plan that included establishing a task force, identifying the nature ofthe occurrences in facilities, and assessing data to develop appropriate corrective actions. (Bates pages 030099-030101) ARC also reported that it implemented corrective actions for earlier system problems related to mismanagement of suspect products and that the effectiveness checks found that the corrective actions were ineffective. (Bates pages 030733, 031383-031389)

5.
On March 28, 2005, FDA issued an Adverse Determination Letter (ADL) based on violations observed during a July-August 2004 inspection of ARC’s Southern California Region. The inspection revealed that the Region had distributed 20 blood products manufactured after the Region had made the decision that they were to be discarded. Until the inspection, the Region was unaware that the blood products had been distributed. In multiple response letters, ARC described corrective actions, including implementation ofnew procedures. In a November 30,2005 letter, ARC stated ” Although there is some improvement in performance in this area, the initial effectiveness check did not indicate a satisfactory decline in the number ofproblems after implementation ofthe System 11 documents ….ARC will continue to monitor this area and develop further system-wide corrective action based on the analysis ofrecent problems that have occurred in this area” (Bates pages 038567-038568) In a February 7, 2006 letter, ARC discussed the results ofits monitoring. The corrective actions were evaluated to determine effectiveness. Success criteria were defined by ARC as follows: “The corrective action will be deemed efiective ifthere are ~oblems associated with the release of suspect products and ifthere are no more than-roblems associated with mismanagement ofsuspect products during a given month for the EC evaluation period.” (Bate page 039139). ARC also included in the February 7, 2006 Jetter a bar chart showing that it reported to FDA 92 occurrences ofhaving distributed suspect blood products during the nine month period following receipt ofthe ADL, April through December 2005. ARC stated that it developed and implemented additional procedural changes and promised to “continue to evaluate the data to ensure that all root causes for mismanagement ofsuspect products have been identified and appropriate corrective action taken. ARC is working at the system and individual facility level toward a goal of ‘first-time right’ and a continual reduction in the number of suspect products that require management.” (Bates pages 039145 and 039149-039150)
6.
On November 21, 2006, FDA issued an ADL to ARC following the 2005 inspection ofthe New York Penn Region. The ADL cited ARC for failure to control suspect blood products and for fai lure to comply with the Decree problem management requirements during their handling of numerous related problems. ARC promised corrective action.
7.
On October 30, 2009, FDA issued an ADL to ARC following multiple inspections ofARC facilities beginning February through November 2008. The ADL cited ARC again for failure to control suspect blood products and for failure to comply with the
2
Decree problem management requirements during the handling ofnumerous related problems. ARC promised corrective action.
3