Inspections, Compliance, Enforcement, and Criminal Investigations
PlasmaCare, Inc. 26-Oct-07
Department of Health and Human Services
Public Health Service
Cincinnati District Office
Cincinnati, OH 45237-3097
October 26, 2007
VIA FEDERAL EXPRESS
Mr. Todd Wolsing
Chief Executive Officer
1128 Main Street
Cincinnati, OH 45210
Dear Mr. Wolsing:
From August 8 through 17, 2007, the Food and Drug Administration (FDA) conducted an inspection of your plasma collection facility located at 3840 East Main Street, Columbus, OH. During the inspection, the FDA investigator documented serious deviations from Title 21, Code of Federal Regulations (21 CFR), Parts 600-640. These deviations cause the plasma products to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food Drug and Cosmetic Act (the Act) [21 United States Code 351(a)(2)(B)].
The FDA investigator's findings include:
1. Failure to maintain written standard operating procedures (SOP) including all steps to be followed in the collection, processing, compatibility testing, storage and distribution of blood and blood components for transfusion and manufacturing purposes [21 CFR 606 .100(b)]. For example:
• You failed to follow SOP #6405 entitled "Temperature Management" for initiating corrective and preventive actions (CAPAs). Under the section "Freezer Temperature Monitoring" of your SOP, you are required to generate CAPA reports using form 8520-2 in instances regarding temperature excursions/alarms. However, CAPA reports were not generated on form 8520-2 for five instances of temperature excursions/alarms on 3/6/06, 3/31/06, 5/30/06, 8/12/06, and 6/24/07.
• You failed to follow SOP #7515 entitled, "Plasmapheresis Collection," which requires your employee to scrub the phlebotomy area for a minimum of [redacted] seconds and to allow the gel to dry for a minimum or seconds before performing the venipuncture. However, the FDA investigator observed an employee perform an arm scrub for only [redacted] seconds and then only allow the gel to dry on the prepped arm for less than [redacted] seconds prior to performing the venipuncture.
• You failed to follow SOP #6322 entitled "PCS2 Preventive Maintenance and SystemsChecks." This SOP states that "If a variance is greater/less than the established tolerances of 1000 grams, power the machine down and restart it one time only" and "Occasionally, the displayed weigher value may be observed to fluctuate between two numbers .... For values such as 994 to 995 and 1005 to 1006, the values to be documented should be 994 and 1006, respectively, as these values are out of range and would require the PCS2 machine to be powered off and rechecked again." However, the daily weigher check was not performed according to your procedure. In one instance, the FDA investigator observed an employee restarting the daily weigher check on PCS2 Machine #2 three times prior to obtaining an acceptable result. In another instance, the FDA investigator observed an employee document the daily weigher check result for PCS2 machine #24 as 995-grams whereas the reading on the digital display was fluctuating between the values of 994 and 995-grams.
• Employees qualified under 21 CFR 640 .63(a) failed to follow SOP #7520 entitled "Medical Requirements" for performing medical and physical examinations. Your physician substitute(s) did not adequately perform all the necessary procedures in determining donor eligibility as evidenced by incomplete responses to health and medical screening questions and incomplete reports of physical examinations on several donor medical history and examination forms. • Daily quality control on the Automated PCS2 Haemonetics Plasmapheresis machines and calibration of the thermometers in the plasma storage area and blast freezers were not performed. For example:
-Your SOP #6322 entitled "PCS2 Preventive Maintenance and System Checks" requires that you perform [redacted] weigher check of the Automated PCS2 Haemonetics Plasmapheresis machines. However, you failed to perform the daily weigher check for PCS2 #4 on 2/14/07 and 4/18/07; for PCS2 #12 on 2/14/07 and 4/13/07; and for PCS2 #15 on 2/14/07.
-Your SOP #7625 entitled "Temperature Device Calibration," requires that you calibrate on a semi-annual basis all temperature management devices that are utilized in production. However, you have not calibrated the thermometers in Blast Freezer #1 and Storage Freezer #2 since 9/11/06.
• FDA reviewed 51 of your Adverse Reaction Forms. Of these, five were not completed per your SOP #7521 entitled "Emergency Medical Procedure." On four of these, the center physician did not complete the "reaction cause" evaluation section; and on one, the phlebotomist did not complete the "Equipment Information" section.
2. Failure to thoroughly investigate any unexplained discrepancy or the failure of a lot or unit to meet any of its specifications [21 CFR 606.100(c)]. A donor presented for donation on 11/2/05, when your employee completed the Record of Body Marking form to report that the donor had no body markings. The donor subsequently presented for donation on 1/4/07 and again, you recorded no body markings during the physical examination. However, during the physical examination on 1/5/07, the donor reported having at least 11 tattoos or scars, receiving some tattoos as far back as 1975. You identified this discrepancy between the 11/2/05 and 1/5/2007 reports and began your investigation on 4/3/07. However, you had not completed or resolved your investigation by the time of our August 2007 inspection. Nevertheless, despite this unexplained discrepancy in the donor history, you collected at least eight units of Source Plasma from the donor between 4/12/07 and 8/5/07.
3. Failure to notify the donor of the results of tests for evidence of infection due to communicable disease agents that were a basis for deferral within eight weeks after determining the donor was deferred [21 CFR 630.6(c)]. For example, on 5/8/07, your firm received test results indicating that Donor [redacted] tested positive by Hepatitis C NAT testing on 4/11/07. Nevertheless, you made no attempt to notify Donor [redacted] of the positive test and deferral status until 8/9/07.
4. Failure to have a qualified licensed physician examine each donor at intervals of no longer than one year [21 CFR 640.63(b)(1)]. For example, two of the 55 donor record files that were reviewed by the FDA investigator documented that examinations by physicians were performed at an interval that exceeded one year.
5. Failure to submit a biological product deviation report within 45 days from the date you acquired information reasonably suggesting that a reportable event occurred [21 CFR 606.171]. This regulation requires reporting of any event, which has occurred at your facility or another facility under contract with you, that represents a deviation from current good manufacturing practices, applicable standards, or established specifications that may affect the safety, purity, or potency of both unlicensed and licensed blood and blood components, including Source Plasma, which you have distributed. For example:
• On 11/14/06, you became aware that a sexual partner of a donor, who had tested positive for Anti-HIV-1/2, was also donating source plasma at your firm. Thirty-six donations from that partner, collected during that relationship, were previously distributed. However, the event was not reported to FDA as a biological product deviation as of 8/10/07, eight months after you became aware that a reportable event had occurred. • According to your SOP #8305 entitled "Control of Unacceptable Units," you are required to temporarily reject, for 12 months from last contact, sexual partners or individuals (living in the same residence) who have had close contact with donors determined to have hepatitis or HIV risk, or whom you have received post donation information, or are listed in the National Donor Deferral Registry (NDDR), and to destroy any units from subsequent donations. On 6/2/2006, you learned that the spouse of a donor was found to be listed in the National Donor Deferral Registry. You notified consignees of previous donations from this donor, however, the event was not reported as a biological product deviation until 10/8/06, which is 81 days late.
• On 5/8/07, you learned that a donor tested positive for Hepatitis C by NAT testing. You notified consignees of units previously donated by this donor. However, the event was not reported as a biological product deviation until 8/3/07, three months after you learned of this reportable event.
We further note that you failed to perform a lookback within 24 hours of receiving information that two donors had tested positive for Hepatitis C infection, and one donor had tested positive for Hepatitis B infection, all as required by your SOP #8305, "Control of Unacceptable Units."
The above-identified deviations are not intended to be an all-inclusive list of deficiencies at your plasma center. It is your responsibility to ensure that your firm is in compliance with all requirements of the Act and federal regulations.
You should take prompt action to correct the current deviations. Your failure to promptly correct thedeviations may result in regulatory action without fu rther notice. Such action includes the suspension orrevocation of your firm's license, seizure and/or injunction.
Federal agencies are advised of the issuance of all Warning Letters concerning drugs and medical devices so that they may take this information into account when considering the award of contracts.
We acknowledge the receipt of your October 1, 2007 response to the Form FDA-483 that was issued to you at the conclusion of the inspection of your establishment conducted between August 8-17, 2007. In that response, you stated that you have instituted an action plan to address the noted observations, and where possible, you have completed the corrective actions. However, you did not describe in sufficient detail the steps that you have taken, and you have not provided any time frames for proposed corrective actions. We have completed our review of your response and have determined that your response is inadequate to address all the violations that FDA documented at your firm.
Please notify this office in writing within 15 working days of receipt of this letter of the specific steps you have taken to correct the noted violations and to prevent their recurrence. Please provide evidence that you have corrected the problems such as copies of finalized SOPs or new forms that are implemented to correct the problems. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
Your reply should be sent to the Food and Drug Administration, 6751 Steger Drive, Cincinnati, OH
45237-3097 Attn: Stephen J. Rabe, Compliance Officer. Please contact Mr. Rabe if you have any questions.
Carol A. Heppe
Cc : Gregory Gene Rich
President and CEO
2410 Lillyvale Avenue
Los Angeles, CA 90032-3514