DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION

Note: Although this FDA-483 is an accurate representation of the original FDA-483 issued to the firm, it is not an exact copy. Slight modifications to the original FDA-483 have been made to accommodate its conversion to the HTML format.

QUALITY ASSURANCE

1. Failure to establish and implement procedures requiring root cause analysis and implementation of corrective actions to prevent recurrence of deviations involving donor safety. For example, the following deviations were recorded as "events." BSD 92.103T, "Deviations," version 1.1, April 2001 does not require a root cause determination or implementation of a preventive action for events, and tracking and trending of events is optional. The following are example of deviations related to donor safety that were managed as events: 

a) There were 70 documented overbleeds (29) and overweight units (41) between 10/22/01 and 4/23/02. These deviations were managed as events, which require no root cause analysis or action to prevent reoccurrence: For example,

 i) WBN [REDACTED]-11/5/01, Deviation #2002-053-002150, 740 grams.

ii) WBN [REDACTED]-11/9/01, Deviation #2002-053-002280, 700 grams.

iii) WBN [REDACTED]-4/5/02, Deviation #2002-053-002292, 670 grams.

iv) WBN [REDACTED] collected 4/11/02, Deviation #2001-053-006112, 685 grams.

v) WBN [REDACTED]-4/12/02, Deviation #2001-053-006047, (no weight documented)

 b) A review was made of deviations between 10/22/01-4/23/02. There were approximately 33 deviations documented regarding donors donating before 56 days. For example:

 i) Deviation Form #2001-053-006718, dated 12/1/0, showed that the donor of WBN [REDACTED] donated within a 37 day interval.

ii) .Deviation Form #2001-053-006101, dated 11/9/01 showed that the donor of WBN [REDACTED] donated within a 53 day interval.

iii) .Deviation Form #2001-053-006163, dated 11/9/01 showed that the donor of WBN [REDACTED] donated within a 55 day interval. 

2. Failure to ensure resolution of identified deviations. Deviation report 2002-053-000726, discovered on January 28, 2002, provides details of the donor hold deviation related to WBN [REDACTED] and states that 33 other donors with DDH1 holds were not resolved in a timely manner. FDA’s review of records related to those 33 donors revealed the deviations were not fully resolved, in that the supervisory review of donor hold deassertions, required by BSD 43.301M, "Donor Suitability Supervisory Functions," was not performed for 23 of the donors until after FDA requested the records on May 15, 2002. 

3. .Failure to review records to ensure completeness and accuracy of donor record research for donor file check. For example,

a) The quality control unit failed to detect that the donor file check research has, on an ongoing basis, been conducted by using only the donor’s SSN, when provided.

b) The quality control unit failed to detect that an incorrect SSN was used to search for prior donation records for donor [REDACTED]. Donor [REDACTED] was identified in a list attached to BSL 01-289, "Donor File Check," dated December 27, 2001. The error was detected by FDA on May 22, 2002.

 4. Failure of the quality control unit to determine root cause and prevent recurrence of significant deviations related to BSD 73.200M, "Shipping" version 1.7 January 2001. Between October 22, 2001 and April 23, 2002, the Chesapeake Region recorded 20 LCTs involving shipment of 28 components physically, but not electronically. In that BSD 92.103T, "Deviations" version 1.1 April 2001 does not require a root cause analysis or implementation of preventive action for deviations that are classified as LCTs, no action was taken by the Chesapeake Region to determine root cause and prevent recurrence until April 26, 2002, when FDA investigators discussed their concerns about such deviations. On April 29, 2002, the Chesapeake Region implemented the requirement for a second party manual count of units in each shipment. There have been 4 additional deviations, since implementation of that corrective action. [Handwritten annotation: "STET NLR 6/21/02 GJO 06212002" ] 

5. Failure to determine the root cause and prevent recurrence of inventory reconciliation deviations. FDA reviewed deviation and LCT records for the period October 22, 2001 through May 31, 2002 and found 15 LCTs and 2 deviations related to inventory reconciliation problems. For example,

a) LCT 2001-053-005138, discovered October 9, 2001, states that a Quality Assurance Associate reviewed inventory reconciliation for October 9, 2001 and found that documentation was inconsistent or missing. The corrective action was to provide instructions to the supervisor to review reconciliation each day on a priority basis and to issue a memo to staff, clarifying requirements. The root cause was determined to be insufficient supervisory oversight of reconciliation and insufficient guidance provided to technicians who perform reconciliation tasks. Subsequent LCTs report document continuing failures to perform daily or weekly reconciliation or to produce and review daily product disposition reports (2001-053-005589, 2001-053-005647, 2001-053-006417, 2001-053-005649, 2001-053-005675, 2002053-000063, 2002-053-000409).

b) LCT 2001-053-007159, discovered December 17, 2001, states that reconciliation of A-COMP for frozen transfusable plasma and red blood cells, performed on August 20, 2001 and August 19, 2001, respectively, had incomplete documentation and showed four missing components (three plasma products, [REDACTED], [REDACTED], [REDACTED] and one red blood cell product, [REDACTED]). The supervisor did not review the frozen plasma reconciliation, but did review the red blood cell reconciliation. No supervisory action was taken to address the missing components

c) Deviation 2002-053-000321, discovered 1/15/02, states that during a quarterly QA record review, multiple inconsistencies in weekly inventory reconciliation documentation were noted, such as "no indication that reconciliation occurred in that there’s no check mark or notation by each WBN showing the reconciliation process." The root cause analysis states that the documentation inconsistencies are due to misunderstanding requirements and lack of consensus among departments performing reconciliation as to how to satisfy requirements. The Chesapeake Region’s preventive action was to issue guidelines for documentation of reconciliation in March 2002. Additionally, meetings were held in January and February 2002 to review the reconciliation. Subsequent LCTs show continuing inventory reconciliation deviations, such as failure to review the product disposition report (2002-053-002032), failure to document whether components were located and use of incorrect data to generate inventory reports on 8 days for A-DAUQ (2002-053-002208 and 2002-053-003435).

RE-RELEASE OF UNSUITABLE PRODUCTS

6. Failure to establish adequate procedures to prevent distribution of unsuitable returned blood components. BSD 74.510M, "Receiving Finished Goods" version 1.4 March 2001 requires that supervisory review of returned components include a review of the reason for "return/unsuitability" to determine whether the components "meet reissue criteria." The BSD does not describe "reissue criteria." The Chesapeake Region issued local Job Aid, JAM004.DOC, "Return Product Handling Policies Job Aid," February 2001 to provide the Region’s supervisors with instructions for determining suitability of returned blood components; however, that job aid is also inadequate to prevent distribution of unsuitable returned blood components. For example, 

a) Job Aid JAM 004.DOC indicates that an investigation and evaluation should be performed on blood components returned for a variety of reasons, including but not limited to, hemolysis, contamination, and clotted or clumped red blood cells. The job aid provides no additional instruction, regarding disposal or re-issue of components based on results of those investigations and evaluations.

 b) On April 15, 2002, a returned blood component [REDACTED] product code 04360, CPDA1 leukoreduced red blood cell) was inappropriately distributed following approval for re-issue by a Chesapeake Region supervisor. The component had been returned on April 8, 2002 by the first consignee, because their test results showed a white blood cell (WBC) count that exceeded specifications for leukoreduced red blood cells and because it was positive for sickle cell trait. On that same day, despite evidence that the product failed to meet ARC’s WBC count specifications for leukoreduced red blood cells, the supervisor deemed the component suitable for reissue. It was distributed to a second consignee on April 15, 2002. Upon discovery of the error by a QC Coordinator, the component was recalled on April 16, 2002 (BPD 2002-053-002248). The documented root cause analysis states that the supervisor "misunderstood the reason for return to be due to positive sickle cell only, and did not recognize the significance of the other statements o the form: ‘product labeled as leukoreduced but not; WBC count >2x10 to the 10th by Nageotte chamber’." Job Aid JAM004.DOC indicates that product returned for sickle cell trait is suitable for "return to shelf," but does not provide instructions for handling of leukoreduced components that fail to meet specifications.

DONOR SAFETY

7. Failure to establish procedures for determining donor suitability, in that BSD 51.110M, "Allogeneic, Directed, and Apheresis Donor Screening," version 1.9 June 2001 provides no normal lower blood pressure limit for allogeneic, directed, or apheresis donors. Chesapeake Region management stated that the American Association of Blood Banks has not had lower limits for BPs for 5 years and state that if a donor can walk in then they are alright to have their blood drawn. The following donors were permitted to donate and then had a reaction post-donation:

 a) WBN #[REDACTED], dated 9/27/01. The donor’s pre-donation BP was 88/50 at 1035. After a severe reaction, the BP was 90/56 at 1043.

b) WBN #[REDACTED], dated 4/16/02. The donor’s pre-donation BP was 88/68 and pulse was 80 at 1704. After a severe reaction, the BP was 90/56 and the pulse 50 at 1715. 

The following donors were permitted to donate, but did not have a reaction:

 c) WBN[REDACTED], dated 9/6/01. The donor’s pre-donation BP was 88/54.

d) WBN[REDACTED], dated 3/18/02. The donor’s pre-donation BP was 70/56.

8. Failure to take vital signs periodically until stable after a moderate or severe donor reaction as directed in BSD 51.113M, "Donor Reaction and Injury Management." For example: 

a) WBN[REDACTED], dated 4/12/02. This donor’s pre-donation BP was 92/56 at 1341. After a moderate reaction to the donation, the only BP was documented at 70/56 at 1418.

b) WBN [REDACTED], dated 3/12/02. This donor’s pre-donation BP was 110/60 at 11:30 AM. After a moderate reaction to the donation, the only two (2) BPs documented were 72/40 at 11:38 AM and 90/52 at 11:56.

c) WBN [REDACTED], dated 3/12/02. This donor’s pre-donation BP was 118/68 at 1410. After a severe reaction to the donation, the only two (2) BPs documented were 80/50 at 1445 and 82/50 at 1453.

d) WBN [REDACTED], dated 3/13/02. This donor’s pre-donation BP was 102/74 at 1405. After a moderate reaction to the donation, the only two (2) BPs documented were 90/64 at 1429 and 84/64 at 1435.

e) WBN [REDACTED], dated 3/13/02. This donor’s pre-donation BP was 102/64 at 1338. After a moderate reaction to the donation, the only two (2) BPs documented were 90/48 at 1355 and 80/38 at 1405.

f) WBN [REDACTED], dated 3/25/02. This donor’s pre-donation BP was 100/78 at 1603. After a severe reaction to the donation, the only two (2) BPs documented were 98/70 at 1715 and 80/72 at 1721.

g) WBN [REDACTED], dated 3/27/02. This donor’s pre-donation BP was 110/68 at 1302. After a moderate reaction to the donation, the only two (2) BPs documented were 96/60 at 1320 and 84/54 at 1335.

DONOR SUITABILITY

9. Failure to follow procedures for determining donor suitability, in that blood was collected, processed, and distributed from donors who did not complete all health history questions on their Blood donation Records (BDRs).

 a) During this investigation, a random review was made of approximately 250 blood donation records (BDRs) from 9/01- the present. It was observed that BDR question #33, "Do you have a medical condition not referred to in any question above which requires regular follow-up by a health care professional?" was unanswered on the BDR for whole blood #[REDACTED]. The BDR had gone through 200% review and components were distributed. 

[Handwritten annotation: "GJO 06212002 NLR 6/21/02" ]

b) During this investigation, a random review was made of Deviation Forms from 10/01-the present. It was noted on Deviation Form # 2002-053-002703, dated 4/29/02, that although 3 BDRs had gone through3 levels of review, a fourth level of review found omissions in the health history questions. The firm did not initiate a recall to retrieve the products. BSL 02-009 "American Red Cross Biomedical Services Policies on Management of Products and Donors When BDR Information is Missing or Discrepant," dated 1/29/02 states that "products from an allogeneic donation must be discarded if the donor’s suitability cannot be confirmed in a personal interview with the donor at the collection site on the day of the donation." For example,

 i) WBN [REDACTED] (collected 1/17/02] had no response for question 24, "In the past 12 months have you given money or drugs to anyone to have sex with you?"

ii) WBN [REDACTED] (collected 1/2/02) had no response for question 32, "Have you ever had cancer (except non-melanoma skin cancer or cervical carcinoma in-situ)?"

iii) WBN [REDACTED] (collected 1/6/02) had no response for question 31, "In the past 4 weeks, have you had any vaccination?"

DONOR FILE CHECK

10. Failure to establish adequate procedures to perform donor file check, including a description of methods of performing the records research, requirements to thoroughly document that research, and a requirement to perform a review of the results of that research. ARC Biomedical Headquarters periodically issues donor file check BSLs with lists of unsuitable donors, who were not promptly deferred in the NDDR. The BSLs instruct regions to search their local records to determine whether any of the listed donors have donated in their respective regions during the period that the NDDR was not updated with deferral information.

a) Each donor file check BSL instructs regions to use "the standard search procedure." ARC’s Biomedical Headquarters has not established a standard search procedure for donor file check.

b) The Greater Chesapeake & Potomac Region (Chesapeake Region) issued local operating procedure, LOPRM08, "Protocol For Research Investigations;" obsoleted it on May 3, 2002; and issued no replacement procedure. LOPRM08 did not adequately address donor file check, in that it failed to identify specific search parameters necessary to ensure a thorough search of the NBCS and RBIS.

c) The Chesapeake Region’s Records Management Supervisor, who is responsible for donor file check records research, stated that records are searched using only the donor’s social security number (SSN), and that when no SSN is provided, the search is performed using the donor’s name and date of birth. The Chesapeake Region’s Donor Suitability Manager, who oversees Records Management, stated that the search is performed using the donor’s SSN, when provided, and the name and date of birth.

INVENTORY CONTROL

11. Failure to establish and follow distribution procedures that allow the disposition of each blood component to be readily determined.

a) BSD 73.200M, "Shipping" version 1.7 January 2001, which requires that blood components be "shipped using the computer system," and that the number of components in a shipping container be physically counted to ensure consistency with the number of components listed on the related packing slip. FDA’s review of log, correct, trend (LCT) records for the period October 22, 2001 through May 31, 2002 revealed that 33 blood components were shipped to consignees physically, but not electronically. Shipment of blood components physically, but not electronically, results in no record of final component disposition and failure to perform a final component suitability check for components manufactured in the shipping region. For example, the following components were shipped to consignees physically, but not electronically:

i) WBN [REDACTED] (product code 04360, CPDA1 red blood cells, leukoreduced) and WBN [REDACTED] (product code 04710, AS1 red blood cells, leukoreduced) were unaccounted for during a May 2002 weekly inventory reconciliation and were later found at two different hospital blood banks.

ii) WBNs [REDACTED], [REDACTED], and [REDACTED] (product code 18400, fresh frozen plasma<24 hours) were unaccounted for during a March 2002 weekly inventory reconciliation and were later found at a hospital blood bank. On March 1, 2002, a consignee called the Chesapeake Region to report receipt of 4 extra units of fresh frozen plasma <24 hours in a shipping container (WBNS [REDACTED], [REDACTED], [REDACTED], and [REDACTED], product code 18400, fresh frozen plasma <24 hours).

iii) On January 22, 2002, a consignee called the Chesapeake Region to report receipt of an extra leukoreduced red blood cell unit in a shipping container (WBN [REDACTED], product code 04710, AS1 red blood cell, leukoreduced). On January 23, 2002, another consignee also called the Chesapeake Region to report receipt of a leukoreduced red blood cell unit that was not listed on their packing slip (WBN [REDACTED], product code 04750, AS5 red blood cells, leukoreduced).

iv) WBN [REDACTED] (product code 04710, AS1 red blood cells, leukoreduced) was unaccounted for during a daily inventory reconciliation in November 2001 and later found at a hospital blood bank.

 b) FDA’s review of lost product deviations for the period, October 1, 2000 through May 31, 2002 found that 18 lost blood components were reported to Biomedical Headquarters. On April 3, 2001, Biomedical Headquarters issued BSL 01-061, "Update for Measuring Acceptable Quality Limit (AQL) for Components Without Final Computer Disposition (CWOFCD)," which establishes an AQL of less than 0.004% of total products handled each calendar quarter. The BSL does not require Blood Service Regions to investigate or take any action prevent recurrence of lost products unless their individual monthly rate is equal to or greater than 0.004%, or if a region has an upward trend for three consecutive months. For example, the following blood components were lost and recorded as LCTs, which require no root cause analysis or preventive action:

i) WBN [REDACTED] (product code 04710, AS1 red blood cell, leukoreduced), was unaccounted for during daily inventory reconciliation of on December 27, 2001. The component was confirmed as a lost product and moved electronically on January 28, 2002 to Component Reconciliation Tracking Center (CRTC), which is an electronic location for lost products.

ii) WBN [REDACTED] (product code 19601, recovered plasma > 24 hours) was not located during inventory reconciliation on October 10, 2001. The loss was discovered during supervisory review of reconciliation records on November 12, 2001. The component remained lost and was moved electronically to CRTC on November 23, 2001.

DONOR HOLD

12. Failure to establish adequate procedures to ensure complete and accurate donor records, in that BSD 43.301M, "Donor Suitability Supervisory Functions" version 1.6 March 2001 does not include a time frame for completion of second party review of the manual DDR assertions and deassertions report. Twenty three donors with donor hold assertions were deasserted in February 2002, but no second party review was performed until May 15, 2002, after FDA requested access to those records. For example,

a) The DDH1 on donor [REDACTED] was deasserted on February 1, 2002 by employee [REDACTED]. On May 15, 2002, the first and second reviews of the deassertion were performed by employees [REDACTED] and [REDACTED], respectively. (The donor has an XFF assertion code for AIDS Risk behavior.)

b) The DDH1 on donor [REDACTED] was deasserted on February 4, 2002 by employee [REDACTED]. On May 15, 2002, the first review and second reviews were performed by employees [REDACTED] and [REDACTED], respectively. (The donor has an RR assertion code for HCVAB.)

c) The DDH1 on donor [REDACTED] was deasserted on February 4, 2002 by employee [REDACTED]. On May 15, 2002, the first and second reviews were performed by employees [REDACTED] and [REDACTED], respectively. (The donor has an EE assertion for HBcAB.)

EQUIPMENT VALIDATION AND QC

13. Failure to validate that 19 Pre-Check devices can be downloaded off the pre-check workstation at the same time. Validation was performed to download only one Pre-Check device at a time. The document "Test Procedures for the Access Specialty Equipment," NBC-DI-00002271-2.1.0, dated 4/3/98, pg. 3-17, documents that Test Case #6, Pre-Check Workstation, was validated by connecting the DB25 end of the serial cable to the pre-check unit and the DB9 end to the pre-check workstation and turn on the Pre-Check device. BSD 22.101T, Pre-Check Computer Operations, Version 4/15/94, effective dated 9/11/96, documents on page 11, "connect the handheld computers to the multi-port cable by connecting the first handheld computer to fully pinned ‘terminating’ connector, the most remote port on the multi-port cable from the PC port. Then connect the other handheld computers to any of the other ports."

 14. Failure to establish adequate quality control procedures, in that the daily QC for Pre-Check devices only consists of checking for the numbers of files downloaded from the DDR, but there is no method to determine whether the devices themselves are functioning properly. For example:

 a) On 5/29/02, at the request of FDA investigators, the social security number (SSN) of the donor of whole blood number [REDACTED] was entered into Pre-Check device #053.213. The unit displayed the message that the donor was eligible to donate that day, although he was asserted as a permanent deferral on 9/8/01 due to a positive HBcAB test. When entering the same SSN again, the pre-check unit then displayed that the donor was ineligible to donate that day. When entering the SSN eight (8) subsequent times that day, the Pre-Check device gave conflicting data on the eligibility of the donor.

 b) A donor historian documented on a "Donor Status Change Record," dated 1/9/02, that the Pre-Check device she was using repeatedly stated that she should reenter one donor’s SSN (whole blood number [REDACTED]). The donor’s blood was collected, but subsequently destroyed that same day as the donor had been permanently deferred due to an AIDS risk assertion from a previous donation 12/12/00.

15.. Failure to use proper equipment in the blood collection process. BSD 52.101M, Whole Blood Collections, dated 1/01, documents in Step 2 and 3, of the section, "Positioning the Collection Set" that the primary container is positioned on the scale and the tubing threaded through the scale shut off. The following three (3) units were documented in the event reports as being accidental overdrawn/overweight units due to defective gram scales. Gram scales have no mechanism for threading tubing. For example,

a) WBN [REDACTED]-10/23/01, Deviation #2001-053-005573 was overdrawn at 680 grams.

b) WBN [REDACTED]-10/23/01, Deviation #2001-053-005575 was overdrawn at 680 grams.

c) WBN [REDACTED]-10/31/01, Deviation #2001-053-005793 was overweight at 570 grams.

CONSENT DECREE ISSUE

16. Failure to report to Biomedical Headquarters adverse reactions associated with the collection of blood products.. For example:

a) WBN [REDACTED], dated 9/12/01. The donor was diagnosed with cardiac arrest, CPR started ,and the donor was taken to ER. The donor was diagnosed with vaso-vagal reaction.

b) WBN [REDACTED], dated 2/28/02. The donor was transported to the hospital by ambulance after "prolonged reaction."

c) WBN [REDACTED], dated 2/13/02. Donor passed out approximately ½ hour after donation and was transported to ER by ambulance.

d) WBN#[REDACTED], dated 3/6/02. The donor "slumped over" at dinner the evening of donation and was taken to ER.

[Handwritten correction to original list enumeration: c,d,e,f] 

[Handwritten annotation: "NLR 6/21/02 GJO 06212002" ] 

The observations of objectional conditions and practices listed on the front of this form are reported:

1. Pursuant to Section 704(b) of the Federal Food, Drug and Cosmetic Act, or
2. To assist firms inspected in complying with the Acts and regulations enforced by the Food and Drug Administration.

"Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his judgement, indicate that any food, drug, device, cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."