IV. INJUNCTIVE RELIEF: ARC; its President and Chief Executive Officer; the Executive Vice President and Chief Executive Officer, Biomedical Services; the Senior Vice President and Chief Operating Officer, Biomedical Services; the Vice President and Chief Operating Officer, Plasma Services, Biomedical Services; Director of Training, Biomedical Services; the Vice President and Chief Scientific Officer, Biomedical Services; the Chief Information Officer; the Senior Vice President, Quality and Regulatory Affairs, Biomedical Services; Customer Business Unit Vice Presidents, Biomedical Services; Regional and Laboratory Chief Executive Officers, Biomedical Services; and all of ARC’s other officers, agents, employees, attorneys, and those persons who have received actual notice of this Order and who are in active concert or participation with any of the foregoing persons, shall, within the time frames set forth below, establish, implement, and continuously maintain adequate methods, facilities, systems, and controls to ensure that ARC does not collect, manufacture, process, pack, hold, or distribute any article of drug as defined in 21 U.S.C. § 321(g), including any article of blood, blood component, or other biological product as defined in 42 U.S.C. § 262, that is adulterated, within the meaning of 21 U.S.C. § 351(a)(2)(B); misbranded, within the meaning of 21 U.S.C. § 352(a) or 42 U.S.C. § 262(b); or otherwise in violation of the FD&C Act, the PHS Act, and regulations promulgated thereunder, including, but not limited to, 21 C.F.R. Parts 210-211 and Parts 600-680. Such methods, facilities, systems, and controls shall include, but not be limited to, the following:

1. Management Controls.
   1. Within the time frames specified in this Order, ARC shall take steps necessary to ensure continuous compliance with this Order, the law, and ARC SOPs, including, but not limited to BSDs, BSLs, local operating procedures, and any other written instructions used by ARC in connection with the collection, manufacture, processing, packing, holding, or distribution of blood and blood components.
   2. ARC shall establish, document, and continuously maintain managerial control over training and quality assurance in all regions and laboratories. Managerial control shall include continuous employment of a director of quality assurance and a director of training. In the event that either such director ceases to act in the aforesaid capacity, ARC shall, within 10 days after such cessation, appoint an interim director and shall notify FDA of such appointment. In the event that either director notifies ARC of an anticipated extended period of absence of more than 30 days, ARC shall within 10 days of such departure, appoint an acting director and shall notify FDA of such notification and appointment within 10 days of notification and appointment.
      
      The director of quality assurance shall, by reason of his or her background, training, experience, and education, be qualified to establish, implement, and continuously maintain a QA/QC program to ensure that blood and blood components are collected, manufactured, processed, packed, held, and distributed in compliance with the law, ARC SOPs, and the provisions of this Order. The director of training shall, by reason of his or her background, training, experience, and education, be qualified to establish, implement, and continuously maintain a training program to ensure that ARC personnel are properly trained, regularly evaluated to determine whether they are qualified to perform their assigned duties, and, when necessary, retrained. The duties and responsibilities of such persons shall include the following:
      
      1. The director of quality 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 as described in paragraph IV.B below. The director of quality assurance shall also be responsible for ensuring that specific quality assurance responsibilities are assigned to appropriate, qualified individuals at ARC Biomedical Headquarters and at each region and laboratory to accomplish the foregoing objectives within specified time frames. In addition to other reporting requirements set forth in this Order, the director of quality assurance shall report to ARC senior management and ARC Biomedical Services senior management pursuant to paragraph XI herein all FDA-483 observations reported to ARC following inspection of ARC facilities, and conditions or practices described in compliance-related FDA correspondence issued to any ARC facility, within 5 business days of receipt.
      2. The Quarterly Quality Assurance Report. Commencing with the date of entry of this Order, the director of quality assurance shall, in addition to other reports required under this Order, prepare and submit quarterly quality assurance reports in writing to ARC senior management and ARC Biomedical Services senior management, pursuant to paragraph XI herein, that completely and accurately: (i) describe the steps that have been and will be taken, with specific dates for implementation of each step, to establish, implement, and continuously maintain the QA/QC program; and (ii) describe all unresolved potential system (systemic) problems, system (systemic) problems, and trends and their corrective action status; and (iii) assess whether ARC is in compliance with the law, ARC SOPs, and this Order.
      3. In assessing compliance with the law, ARC SOPs, and this Order, the director of quality assurance shall evaluate all relevant information bearing upon these issues, including, but not limited to, ARC Clarify reports (and/or any other successor or similar deviation-reporting systems and/or reports), biological product deviation reports, internal deviation reports, trends, adverse reaction reports, lookback cases, cases of suspected transfusion-transmitted disease, potential system (systemic) problems, system (systemic) problems, supply and equipment problems, FDA-483 observations, compliance-related FDA correspondence, internal and external audit reports, retrievals, and reports required elsewhere in this Order. With respect to information suggesting possible non-compliance with the law, ARC SOPs, or this Order, the director of quality assurance shall assess, among other factors, whether the information includes evidence of potential public health risks, and whether the information is the same or similar to information that has come to ARC’s attention through compliance-related FDA correspondence since entry of the May 12, 1993 Consent Decree.
      4. The Director of Training shall be responsible for all biomedical training functions, including ensuring the establishment, implementation, and continuous maintenance of a comprehensive training program as described in, and within the time frames set forth in, paragraph IV.C below. The director of training shall also be responsible for ensuring that specific training responsibilities are assigned to appropriate, qualified individuals at ARC Biomedical Headquarters and at each region and laboratory to accomplish the foregoing objectives.
      5. The Quarterly Training Report. The director of training shall, commencing with the date of entry of this Order, prepare and submit quarterly progress reports in writing to ARC senior management, pursuant to paragraph XI herein, fully describing the steps that have been and will be taken, within specified time frames, to establish, implement, and continuously maintain the training program.
2. Quality Assurance/Quality Control Programs. ARC shall review, modify if necessary, and continuously maintain its comprehensive QA/QC program to ensure that blood and blood components are collected, manufactured, processed, packed, held, and distributed by ARC in compliance with the law, ARC SOPs, and this Order, and have the purity that they purport or are represented to possess. The QA/QC program shall include, among other things, the following programs and program assessments:
   1. Problem Management SOPs. Within 90 days after entry of this Order, ARC shall establish and submit to FDA SOPs to detect, investigate, evaluate, correct, and monitor all problems, trends, and system (systemic) problems. The procedures for SOP, report, and plan submission, review, and implementation in paragraph VI of this Order apply, except that ARC shall have 90 days to implement the Problem Management SOPs once FDA notifies ARC that such SOPs appear adequate. If all of these SOPs are submitted to FDA in fewer than 90 days after entry of this Order, the unused days will be added to the implementation time of 90 days. Such SOPs shall contain, at a minimum, a risk assessment procedure, a procedure for the immediate identification and handling of urgent health hazards, and the following requirements:

      a. Problem Management Systems Within Regions And Laboratories: The Problem Management SOPs shall require that:

      1. The Quality Assurance Unit at ARC Biomedical Headquarters ensures that each region and laboratory has a Problem Management System that shall be used for logging, tracking and trending all problems. To identify all problems that the Problem Management System must address, each region and laboratory shall scrutinize, at a minimum, ARC’s Clarify reports (and/or in any other successor or similar deviation-reporting systems and/or reports), biological product deviation reports, internal deviation reports, trends, adverse reaction reports, lookback cases, cases of suspected transfusion-transmitted disease, potential system(systemic) problems, supply and equipment problem reports, FDA-483s, compliance-related FDA correspondence, internal and external audit reports, and retrievals.
      2. Each ARC region and laboratory shall, commensurate with the nature of the problem, promptly, thoroughly and adequately investigate, correct, and take steps to prevent the recurrence of each problem, and shall determine whether the problem resulted in the release for distribution of any unsuitable blood or blood components and, if so, whether consignees were notified. Each region and laboratory shall thoroughly and contemporaneously document each step it takes to investigate, correct, and prevent recurrence of each problem, and to determine if the problem resulted in the release for distribution of any unsuitable blood or blood components. Such documentation shall be maintained at the appropriate region or laboratory, shall reflect the identity of the regional or laboratory quality assurance staff member who reviewed and approved the problem investigation and the date on which that approval occurred, and shall be available for review by ARC Biomedical Headquarters and FDA.
      3. Every 30 days, each ARC region and laboratory shall evaluate all problems that occurred after entry of this Order that the region or laboratory has not previously evaluated and fully corrected, as well as all problems that existed at the time this Order was entered that have not been fully corrected.
      4. Summary Problem Reports. In addition, each ARC region and laboratory shall, every 30 days, submit a Summary Problem Report to ARC Biomedical Headquarters. The Summary Problem Report shall, at a minimum, include each category of problems that occurred since the last Summary Problem Report and all categories of problems that occurred prior to the last Summary Problem Report that have not been fully corrected. The first report shall include the categories of fully corrected problems that have been initially discovered after entry of this Order. The categories shall be specific enough to enable ARC Biomedical Headquarters to determine whether a trend exists. The Problem Management SOP shall set guidelines for categorizing problems, including, but not limited to, categories of problems that have not previously occurred at ARC. For each category of problem, the Summary Problem Reports must state, at a minimum: (A) the nature of the problem(s), including, but not limited to, whether they constitute deviations from the law, ARC SOPs, or this Order; (B) the number of problems within the category; (C) the frequency with which those problems have occurred in that region or laboratory since entry of this Order or the prior 24 months, whichever is shorter; (D) whether the problems may be potential system (systemic) problems; (E) the potential or actual causes of the problems; (F) the status of the corrective actions; and (G) whether the problems could result, or have resulted, in the release for distribution of unsuitable blood or blood components, and if so, what follow-up action, such as retrieval, notification, and/or lookback, has been implemented. Each Summary Problem Report shall also identify the region or laboratory, and the person completing the report, and shall state the date the report was completed.
      5. Specific persons within the Quality Assurance unit at ARC Biomedical Headquarters (to be identified by ARC in writing by position within 20 days after entry of this Order) shall be responsible for receiving all relevant information in the Summary Problem Reports, reviewing it for completeness, and maintaining it in an accurate, complete, and current log (all relevant information shall be entered in the log within 48 hours of receipt).

      b. Analysis and Investigation Group and Reports. Specific persons within the Quality Assurance unit at ARC Biomedical Headquarters (to be identified by ARC in writing by position) shall be responsible for initiating, within specific time frames, and completing, within specific time frames not to exceed the due date for the next Summary Problem Reports, a thorough analysis and investigation of each Summary Problem Report submitted by each region and laboratory to discover trends and system (systemic) problems. Information contained in a Summary Problem Report that is classified as a significant risk, according to the Problem Management SOPs, shall be investigated and reported to ARC Biomedical Services senior management on an expedited basis. On a quarterly basis, this group shall complete the analysis and investigation of each Summary Problem Report submitted during the quarter and issue an Analysis and Investigation Report to ARC Biomedical Services senior management pursuant to paragraph XI herein. On a quarterly basis, ARC Biomedical Service senior management shall complete a summary of the most recent Analysis and Investigation Report, which summary shall be included in the Quarterly Quality Assurance Report described in paragraph IV.A.2.b.

      1. For each trend that the Analysis and Investigation Group discovers, the Analysis and Investigation Report shall, at a minimum, state: (A) the nature of the trend; (B) the scope of the same or similar trends (number of regions and laboratories in which the same or similar trends have been reported and the number of same or similar trends within each region and laboratory); (C) the probable or actual causes of each trend; (D) for each trend, whether it or any of its causes poses a health risk such that the time frames related to the Corrective Action Plan and the Corrective Action Monitoring Reports should be shortened; (E) the steps taken to determine whether the trend may result or has resulted in the release for distribution of unsuitable blood or blood components; (F) whether the trend resulted in the release for distribution of unsuitable blood or blood components, and, if so, whether appropriate follow-up action, such as retrieval, notification, and/or lookback, is required; and (G) for each trend, whether it or any of its causes is a system (systemic) problem.
      2. If the Analysis and Investigation Group determines that a trend, or any of its causes, is a system (systemic) problem, the Analysis and Investigation Report shall identify all systems that potentially or actually contributed to the system (systemic) problem, shall follow the established risk assessment procedures, and shall assign a risk factor to each system (systemic) problem.
      3. If the trend is determined not to be a system (systemic) problem, the Analysis and Investigation Group shall document and explain in detail the reasons for that determination.
      4. Analysis and Investigation Reports shall be signed and dated by the authors and by ARC’s most senior quality assurance officer or qualified temporary designee within 5 days of completion.

      c. Corrective Action Plans. Specific persons (to be identified by ARC in writing by position), including, but not limited to, a representative from the Quality Assurance unit and operations staff at ARC Biomedical Headquarters and at least one person from an ARC region or laboratory (representing the regions and laboratories, collectively), shall be responsible, within specific time frames not to exceed the due date for the next Analysis and Investigation Report, for reviewing and evaluating the Analysis and Investigation Report, and preparing a written Corrective Action Plan to address the findings set forth in the Analysis and Investigation Report.

      1. The Corrective Action Plan shall, at a minimum, state: (A) in detail all actions to be taken by ARC Biomedical Headquarters to prevent recurrence of each system (systemic) problem, including whether new SOPs must be written to address the system (systemic) problem; (B) whether all regions and laboratories have been notified in writing of the system (systemic) problem; (C) which persons shall be responsible for implementing each action described in the plan; (D) the precise time frame, based on the assigned risk factor, for completing each action; and (E) the corrective action effectiveness criteria, including, but not limited to, the precise length of time that the corrective action will be monitored to evaluate effectiveness.
      2. The Corrective Action Plan shall also confirm or correct the determination in the Analysis and Investigation Report with regard to the retrieval of unsuitable blood or blood components, including expanding the scope of the retrieval, if necessary. The plan shall designate specific persons to monitor, at specific time intervals, ARC's plans, at the region and/or at ARC Biomedical Headquarters, to retrieve unsuitable blood or blood components from the marketplace.
      3. The Corrective Action Plan shall be submitted to ARC Biomedical Services senior management pursuant to paragraph XI herein, within 48 hours of completion. On a quarterly basis, ARC Biomedical Service senior management shall complete a summary of all ongoing Corrective Action Plans and all Corrective Action Plans that have been completed since the last summary, which summary shall be included in the Quarterly Quality Assurance Report described in paragraph IV.A.2.b.

      d. Corrective Action Monitors and Reports. Corrective Action Monitors, identified by ARC in writing by position, shall be responsible for actively, carefully, and at specific time intervals, monitoring each Corrective Action Plan to ensure continuous effectiveness.

      1. The Corrective Action Monitors, at specified time frames (but no less frequently than every 30 days), shall file Corrective Action Monitoring Reports that: (A) clearly state whether or not the Corrective Action Plan is being properly and timely implemented, including details of retrieval, notification of consignee(s) and/or, if necessary, lookback investigation, whether each of the corrective action effectiveness criteria in the Corrective Action Plan is being met, and whether the plan is effective to prevent the recurrence of the system (systemic) problems; and (B) describe in detail any impediments or difficulties encountered that may prevent effective and timely implementation of the Corrective Action Plan and any changes necessitated thereby.
      2. Corrective Action Monitoring Reports shall be signed and dated by the authors, and shall be provided to ARC senior management and ARC Biomedical Services senior management pursuant to paragraph XI herein within 48 hours of completion.

      e. ARC Biomedical Headquarters Review of Reports, Plans, and Correspondence. Commencing with the date of entry of this Order, specific persons at ARC Biomedical Headquarters (to be identified by ARC in writing by position), including the quality assurance director, shall be responsible for, every 90 days :

      1. reviewing all Summary Problem Reports, Analysis and Investigation Reports, Corrective Action Plans, Corrective Action Monitoring Reports, ARC internal and external audit reports, FDA-483 observations, and compliance-related FDA correspondence to identify any problems, trends, and system (systemic) problems that have not been detected, investigated, and effectively corrected within established time frames;
      2. assessing the public health risk of all unresolved problems, trends, and system (systemic) problems identified duringthis review;
      3. ensuring that all problems, trends, and system (systemic) problems identified during this review are promptly resolved;
      4. ensuring that all ARC regions and laboratories have been notified in writing of system (systemic) problems; and
      5. reporting the results of the review in the quarterly quality assurance report as described in Paragraph IV.A.2.b to ARC senior management and ARC Biomedical Services senior management pursuant to paragraph XI herein.
   2. Retrospective Review of Potential System (Systemic) Problems.Within 90 days after the entry of this Order, ARC shall complete a retrospective review of all potential system (systemic) problems reported by ARC regions and laboratories to ARC Biomedical Headquarters between August 1996 or the documented date of regional implementation of the MACS, whichever is later, and September 30, 2002. ARC shall ensure that effective corrective actions have been developed and implemented for all system (systemic) problems, and shall assess the effectiveness of all such corrective actions. Within 30 days after entry of this Order, ARC shall provide to FDA a written list showing the day on which each region implemented MACS.
      
      Within 180 days of entry of this Order, ARC shall report in writing to FDA whether those corrective actions are effective and report the basis for each such determination. ARC shall assess the impact of each system (systemic) problem and each ineffective corrective action on blood or blood component purity, and take appropriate action, as required by the law, ARC SOPs, and this Order. All ineffective corrective actions for system (systemic) problems shall be reported, within 10 days of initial discovery, in writing to ARC senior management and ARC Biomedical Services senior management pursuant to paragraph XI herein and to FDA. Detailed plans, including proposed time frames, to correct and prevent recurrence of each such system (systemic) problem shall, within 30 days of initial discovery, be provided to ARC senior management pursuant to paragraph XI herein and to FDA. ARC shall also report in writing to FDA all blood and blood components retrieved from the marketplace as a result of this review within 30 days after initiation of the retrieval.
   3. Internal Audit System.
      1. Within 30 days after entry of this Order, ARC shall review, modify as necessary, and thereafter continuously follow SOPs to conduct and document internal audits to ensure continuing compliance with all laws and ARC SOPs, including all SOPs created under this Order as they take effect. The audit SOPs shall require an evaluation of all collection (including, but not limited to, donor suitability), manufacturing, processing, packing, holding, and distribution systems that may affect the purity of blood or blood components, or ARC’s compliance with the law, any ARC SOP, or any provision of this Order. Except as provided below, ARC shall also conduct comprehensive audits of each region and laboratory at least annually, or more frequently when demonstrated to be necessary. If, in FDA’s judgment, more frequent audits are necessary for any region or laboratory, FDA will notify ARC in writing. Upon receipt of such notice, ARC shall immediately increase audit frequency as specified by FDA.
      2. The SOPs described in the preceding paragraph shall:
         1. establish specific schedules for the frequency of each type of audit;
         2. establish priorities for resolving deficiencies discovered as a result of audits;
         3. require that audits be conducted with standardized forms that must be used by all personnel when conducting the audits, and that audits include the review of an adequate and representative number of relevant records selected using a defined sampling method, including but not limited to Clarify reports (and/or any other successor or similar deviation-reporting systems and/or reports), biological product deviation reports, internal deviation reports, trends, adverse reaction reports, lookback cases, cases of suspected transfusion-transmitted disease, potential system (systemic) problems, system (systemic) problems, supply and equipment problem reports, FDA-483s and compliance-related FDA correspondence specific to the facility being audited, retrievals, and donor file checks.
         4. require accurate, complete, and contemporaneous entry of data and sign-off and dating by specifically designated, qualified ARC employees who conducted the audits and who can attest to the foregoing attributes of data entry;
         5. require that within 30 days after conclusion of the audit of each ARC Biomedical Headquarters system, and each region and laboratory, a list of all audit citations and a summary of all audit citations shall be reported to ARC Biomedical Services senior management pursuant to paragraph XI herein;
         6. require that within 30 days after receipt of the audit report, the facility Chief Executive Officer shall review the audit data and, in consultation with the appropriate audit and quality assurance personnel, shall develop a plan of corrective action to remedy all problems identified in the audit reviews; the plan shall identify the corrective steps to be taken and provide specific time frames for completion of the steps; and the plan shall be submitted to ARC Biomedical Services senior management pursuant to paragraph XI herein,
         7. specify that on a quarterly basis, the quality audit function shall include in the Quarterly Quality Assurance Report a summary of the results of the audit program and the corrective action taken to remedy identified problems;
         8. require that all completed audit forms, summary reports, and written verification of corrective actions be kept on file for a period of ten years, and be made available as required in paragraph XV herein to FDA for review and copying upon written request by FDA; and
         9. require that as part of the audit review process ARC shall annually reassess the audit process to ensure that there are an adequate number of qualified personnel and funds to conduct audits to identify possible non-compliance with the law, ARC SOPs, or this Order .
   4. Computer Systems and Databases.

      a. ARC shall:

      1. within 30 days after entry of this Order, identify and list each ARC computer system used in ARC Biomedical Headquarters and each region and laboratory to collect, manufacture, process, pack, hold, and distribute, and otherwise dispose of, blood or blood components;
      2. within 180 days after entry of this Order: (a) identify and list, for each such currently existing system, every computer software assessment of such systems (including Blood Services quality and regulatory assessment audits, FDA inspections, and any external audit) performed since the date of implementation of MACS , i.e. August 1996, bearing on whether the computer systems and automated databases completely and accurately record, maintain, and report information in compliance with the law, ARC SOPs, and this Order, including, but not limited to, all utility programs and DDRs to determine whether they will repeatedly and reliably accomplish results that are in compliance with the law, ARC SOPs, and this Order; and (b) report to ARC senior management and ARC Biomedical Services senior management pursuant to paragraph XI herein its conclusions regarding whether each system will repeatedly and reliably accomplish results that are in compliance with the law, ARC SOPs, and this Order;
      3. within 30 days after entry of this Order, retain an independent consultant to review all internal deviation reports, biological product deviation reports, computer software defect reports, enhancement requests, and any other reports related to the NBCS, the NDDR, the DMS, the Nucleic Acid Testing Automated System, and any other computer software used in the computer systems identified pursuant to subparagraph (4)(a)(i) above. The review shall be performed to identify computer software defects that may affect the purity of blood and blood components and for which the use of manual workarounds may be appropriate. ARC shall perform a risk assessment to prioritize development and implementation of corrective actions and, when necessary, manual workarounds for each computer software defect identified during this review. The consultant shall then review ARC’s risk assessment for each corrective action and manual workaround to ensure appropriate prioritization of implementation.
      4. within 90 days after completion of the computer software assessment required in paragraph (iii) herein, ensure that such corrective actions and manual workarounds have been developed and implemented and comply with the law, ARC SOPs, and the Order, so that ARC will consistently collect, manufacture, process, pack, hold, and distribute blood and blood components that have the purity they purport or are represented to possess. Within the same 90 day time frame, for corrective actions involving changes to computer software systems, ARC shall ensure that such changes are identified and an implementation plan established that accounts for all 510(k) clearances required and identifies specific implementation timeframes based on the safety risk presented and nature of the design and validation activities required. ARC, through its consultant, shall report in writing the status of these workarounds and corrections to ARC senior management and ARC Biomedical Services senior management pursuant to paragraph XI herein and to FDA;
      5. within 180 days after entry of this Order, report on the status of whether or not all computer system and automated database defects related to complying with the law, ARC SOPs, and this Order that were identified in such computer software assessments have been corrected and, if not, provide the timeline for the implementation plans required by paragraph (iv); and
      6. within 180 days after entry of this Order, submit the foregoing list and report in writing to ARC senior management and ARC Biomedical Services senior management pursuant to paragraph XI herein and to FDA.

      b. Additional Measures for Computer Software Defects. Whenever a computer software defect and/or automated database defect that may adversely affect the purity of blood and blood components collected, manufactured, processed, packed, held, and distributed by ARC is identified, ARC shall, in addition to following the procedures described in this Order:

      1. notify in writing, as soon as practicable, all affected ARC facilities of the computer software defect and/or automated database defect;
      2. implement, as soon as practicable but in no event later than 30 days after identification, a workaround for each such computer software defect and/or automated database defect;
      3. promptly take all steps necessary to ensure that each workaround is consistently followed; and
      4. within 90 days of identification, correct each such computer software defect and/or automated database defect to ensure the purity of blood and blood components and compliance with the law, ARC SOPs, and this Order. For any such computer software defect and/or automated database defect that cannot be corrected within 90 days of identification, ARC shall notify FDA in writing of the computer software defect and/or automated database defect, a proposed time frame for correction, and a justification for the time frame.