Inspections, Compliance, Enforcement, and Criminal Investigations
Oklahoma Blood Institute 19-Aug-05
Department of Health and Human Services
Public Health Service
August 19, 2005
RETURN RECEIPT REQUESTED
Ronald O. Gilcher, M.D.
Medical Director and President/CEO
Oklahoma Blood Institute
1001 North Lincoln Boulevard
Oklahoma City, Oklahoma 73104-3299
Dear Dr. Gilcher:
The Food and Drug Administration (FDA) conducted an inspection of your firm, Oklahoma Blood Institute, located in Oklahoma City, Oklahoma, from April 11 through May 6, 2005. During the inspection, the FDA investigator documented violations of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2)(B)] and Title 21, Code of Federal Regulations (21 CFR) Parts 600-680. These violations represent observations noted on the Form FDA-483 issued at the conclusion of the inspection.
1. Your firm failed to perform a thorough investigation and make a record of the conclusions and follow-up of an unexplained discrepancy [21 CFR 606.100(c)].
Specifically, the causes of the donor screening errors were not determined or, if determined, were not adequately described. The Event Reporting Form (ERF) dated 09/20/1999 has no provision for documenting the cause of the event being reported . This.form was in use during the time period of 09120/1999 until 07/07/2004 . During this time period, no causes of the events were documented on the ERF for any of the events being reported.
The Event Reporting Form (ERF) was revised on 07107/2004. On the new form, under Root Cause, the cause is checked as either Equipment, Behavior, System/Process, or Knowledge. However, the exact description of the cause is not documented. In addition, the Corrective/Short-term actions and Corrective/Long-term actions only have boxes to check to identify the categories such as notified medical, additional training, and other. Again, there is no description of the actions taken.
The evaluation of the effectiveness of preventive long-term actions is not adequately performed or if performed, is not adequately responded to. For example, to reduce the number of events where donors gave information that warranted deferral, but were not deferred, for travel to an area endemic for malaria, a new tool was created to assist screeners in the determination of endemic areas for malaria. However, the evaluation of the number of events, after the new tool was introduced, resulted in no decrease in the number of these events.
In some of these cases, your firm determined the cause to be the screeners' failures to defer the donors. However, the causal factor, or factors, that led to the failure of the screener to defer donors correctly when the donors gave history that warranted deferral or follow-up was not adequately determined.
Furthermore, your firm does not have a uniform system for initiating corrective actions for donor screening errors, and corrective action is not initiated for all employees who make donor screening errors. Failure to adequately implement corrective actions can result in recurring errors. Recurring donor screening errors were noted during this inspection.
Therefore, your firm failed to adequately investigate, determine the causes, correct the causes of donor screening errors, and document actions taken and their effectiveness . As a result, improperly screened and non-deferred donors were entered in the firm's donor pool, and unsuitable blood products were collected, distributed, and subsequently recalled.
2. Your firm failed to include written descriptions of criteria used to determine donor suitability, including acceptable medical history criteria, in your written standard operating procedure (SOP) [21 CFR 606.100(b)(1)].
Specifically,, the SOP, Medical History, revision dated 12/20/04 does not have adequate descriptions of the criteria used to determine the suitability of the donor. Some examples are: a. The SOP does not prompt the screener to defer the donor if the screener is unable to determine if the donor's response to a screening question is acceptable to allow a donation, or if the response should cause the donor to be deferred.
b. The criteria for deferral is not always clearly described for each question such as "Are you in good health?" This question lists various conditions to be considered but does not clearly state that the conditions described should cause a deferral of the donor or for how long the donor should be deferred. Also the question, "Are you taking medication prescribed by a doctor?" refers to the Medication List for the deferral status for various medications. However, the screener is not adequately prompted to defer the donor if the donor is unsure of the drugs being taken; or, if the drug can not be found in the medication list, to defer the donor until the deferral status can be obtained from the Medical department.
c. The job aid, Malaria Information, does not define and describe the endemic malarial areas in enough detail and is not user friendly.
The malaria risk areas and the malaria free areas are divided into 2 separate tables that require the screener to perform 2 separate table searches to determine the malaria status of a country.
Individual cities in highly visited countries such as Mexico are not listed making the determination of malaria risk more difficult.
Maps of individual Mexican states are provided in the job aid to be used in the identification of areas the donor may have traveled to.
However, most donors are not able to identify the state in Mexico that they may have traveled to.
Malarial endemic areas are not always clearly defined.
3. Your firm failed to always follow standard procedures and methods for determining the suitability of a donor as a source of Whole Blood [21 CFR 640.3(a)(1)].
Specifically, the medical history screener asks the donor the question from the SOP, Medical History, if the donor has ever lived in or traveled to Europe since 1980. If the donor answers "Yes" to the question, then the screener must ask four additional vCJD questions required by the SOP. However, the screener does not always ask the four additional questions.
Review of the donor registration forms revealed that four donors were allowed to donate, however, these donors all answered "Yes" to the general travel question . The screener did not ask the four additional required vCJD questions.
4. Your firm failed to establish adequate provisions for monitoring the performance of laboratory instruments [21 CFR fi06.140(b)].
Specifically, the SOP for Equipment Quality Control has directions to level the stand with both the adjustable and the plumb screws until the oil bubble is centered and the installation manual for the equipment says that the scale must be level to function properly. However, seven adjustable automatic donor scales used on the mobile and one donor scale in the main donor room had been placed on ring stands that had no provision to check the level of the donor scale or to adjust the level of the scale.
The manufacturer does allow, and even displays in promotional literature, mounting scales on ring stands. However, your firm did not have a validated procedure documented to ensure that the scales were level' and operated as designed. If an alternative method is used for the installation and operation of the equipment, then the alternative procedures must be validated to ensure that the equipment performs as it was designed by the manufacturer. Failure to validate this procedure could result in the collection and distribution of unsuitable blood products.
5. Your firm does not always follow the written standard operating procedures including all the steps to be followed in the collection of blood and blood components for further manufacturing purposes [21 CFR 606.100(b)].
Specifically, your SOP for Equipment Quality Control directs that a check mark indicates that the results are acceptable and a zero indicates that the results are not acceptable. The documentation for the actions should be entered in the "centered oil bubble section"; however, different staff performing quality control made entries such as "N/A", "Not used (Note: scale was used)," and no entry at all. Therefore, equipment quality control is not recorded correctly to indicate that there could be a possible failure that could result in the collection of unsuitable blood products and possible recall of the products.
The SOP "Adverse Donor reactions-Symptoms, Management and recordkeeping" has the directions that no space should be left blank on the form and any sections that are. not applicable should be denoted by drawing. a line through the section and documenting "Not Used" or "Not in Use", the date, and staff ID number. However, several of your Donor Reaction reports had blank spaces for IV order information; Signs observed; Symptoms described/IV Order information ; and Signs observed/Symptoms described/IV order information. Because sections are left blank on your Adverse Donor Reaction forms, pertinent information describing the donor reaction may not be able to be determined and prevention of the recurrence of the reaction may not be able to be identified.
6. Your firm failed to submit biological deviation reports within 45-calendar days as required in 21 CFR 606.171(c). During the time period from May 12, 2004 to April 29, 2005, 29 out of 76 Biological Product Deviation Reports (BPDR) were submitted after 45 days. Three BPDRs were less than 60 days with the remaining number ranging from 60 to 395.
The above identification of violations -is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure that all blood and blood components produced and issued by your blood bank are in compliance with the Act and the cGMP regulations. You should take prompt action to correct these violations. Failure to correct these violations may result in administrative and/or regulatory action without further notice. Such action includes license suspension and/or revocation, seizure and/or injunction.
We received your June 10, 2005 response to the FDA 483, Inspectional Observations that the FDA investigator issued at the conclusion of the most recent inspection of your firm . We have completed our review of your response and have determined that your response appears to be adequate to address all the violations that FDA documented at your firm. Our evaluation follows and is numbered or labeled to correspond to the items as they appeared on the FDA-483 and in your response:
Item 1 a, b, c, d, e, f. The response appears to be adequate to address the noted observation; however, the failure to perform a thorough investigation of an unexplained discrepancy continues to be an observation from the current inspection as well as the inspection of May 2004. The revision of the ERF (1999) and the current ERF (2004) were not evaluated to determine if the ERF captured and correctly documented the information required to decide if the cause and corrective action would prevent further occurrences of the errors.
Item 2 a,b,c,d. The response appears to be adequate; however, you have developed new job aids in the past for corrective action that have not been effective in decreasing screener errors for donor suitability as noted in the current inspection . Furthermore, implementation of logs, reference binders, tra.ining of staff, universal donor questionnaire, and other items listed as corrective action have not always been successful in eliminating errors resulting in BPDRs.
Item 3 a, b. The response appears to be adequate; however as stated under item 2, you have developed new job aids in the past for corrective action that have not been effective in decreasing screener errors. The inspection of May 2004 identified that 14 recalls were related to donors who had traveled to malaria areas but were not deferred. There were also 10 recalls related to donors who traveled to vCJD risk areas but were not deferred. The current inspection identified 19 recalls related to malaria and 15 related to vCJD. In addition, you emphasize that the training of the employees on the importance of following SOPs during manufacturing will be part of your corrective action; however, you continue to have recurring BPDRs for donor suitability.
Item 4. The response seems to be adequate.
Item 5. The response appears to be adequate to address the noted observation; however, you should include confirmation that the corrective action of cGMP training for your employees, to emphasize SOP procedures, was accomplished by July 7, 2005.
Item 6. The response appears to be adequate to address the noted observation; however, the failure to submit biological product deviation reports (BPDR) within 45 days continues to be an observation from the current inspection as well as the inspection of May 2004. In your response, under corrective action, you state that the [redacted] will be modified to send e-mails to an e-mail rou if the BPDR is 30 days old and not reported to FDA. Furthermore, [redacted] will be modified to provide reports to management listing all BPRDs; however, the system that You plan to develop to monitor the status of reportable BPDRs can only be fully evaluated after implementation takes place.
At your request, a meeting between you and the FDA was held on July 28, 2005, at the Dallas District office. You presented an overview of the corrections you have implemented and corrections you will soon be implementing. You explained the investigative process that identified the causes and what corrective actions your firm was taking to correct the identified violations. Some of these corrections have been implemented and some corrections are still in process. Although you presented your current plan for corrective actions to these violations and the actions appear to be adequate, your firm made commitments that these violations would be corrected after the previous inspection in 2004. However, our recent inspection revealed you did not correct the violations in a timely manner.
We request that you notify this office in writing, within fifteen (15) working days of the receipt of this letter, of the specific timelines for all the procedures and changes that you have already implemented to correct these violations. In addition, we request that the projected timelines for implementation of all new procedures and changes in your process that have not yet been completed to correct these violations be included. Please send examples of any documentation showing that corrections have been achieved. If you cannot complete all the requested information before you respond, please explain the reason for your delay and the date that we can expect the requested documentation.
Please send your reply to the Food and Drug Administration, Attention: Carolyn A. Pinney, Compliance Officer, at the above letterhead address. If you have any questions regarding any issue in the letter, please contact Carolyn A. Pinney at (214) 253-5220.
Sylvia Y. Yates for Michael A. Chappell