Order to Cease Manufacturing and to Retain HCT/Ps

August 18, 2006

HAND DELIVERED

Philip Guyett
Owner
Donor Referral Services
4724 Hargrove Road
Raleigh, NC 27616

Dear Mr. Guyett:

The Food and Drug Administration (FDA or the agency) conducted an inspection of your establishment, Donor Referral Services (DRS or Establishment), at 4724 Hargrove Road, Raleigh, North Carolina 27616, which manufactures human cells, tissues, and cellular and tissue-based products (HCT/Ps), between June 28 and 30, 2006. At the conclusion of the inspection, the FDA investigators issued you a Form FDA-483, Inspectional Observations. In addition to the inspection, the agency conducted concurrent investigations of funeral homes that had referred potential donors of HCT/Ps to you for recovery, and of HCT/P establishments to whom you had provided HCT/Ps for processing. Our review of the information and records examined and collected during the inspection and investigations reveal that significant violations of Title 21, Code of Federal Regulations (21 CFR), Part 1271, issued under the authority of Section 361 of the Public Health Service Act (PHS Act) [42 U.S.C. 264], exist at DRS.

Indeed, the records of each of the eight donors that the agency reviewed as a result of this inspection reveal serious violations under 21 CFR Part 1271. The agency has determined that because of the serious nature of these violations, there are reasonable grounds to believe that they present a danger to public health. This Order to Cease Manufacturing and to Retain HCT/Ps relates exclusively to conduct occurring on or after May 25, 2005, the effective date of these regulations. We note that FDA retains authority to pursue other actions and remedies.

Therefore, pursuant to 21 CFR 1271.440(a)(1) and (3), both you individually, and your Establishment, 1) must immediately cease all manufacturing until compliance with the regulations in 21 CFR Part 1271 has been achieved, and 2) must retain all HCT/Ps recovered on or after May 25, 2005 that are in your possession until they are disposed of as agreed by the agency or until the safety of the HCT/Ps is confirmed. Pursuant to 21 CFR 1271.3(e), "Manufacture" means, but is not limited to, any or all steps in the recovery, processing, storage, labeling, packaging, or distribution of any HCT/P, and the screening or testing of the HCT/P donor.

Deficiencies noted include, but are not limited to, the following:

  1. You failed to create and maintain accurate records, as required by 21 CFR 1271.55(d)(2) and 21 CFR 1271.270(a), and you failed to review the certificate of death of the donors below, which were available and are relevant medical records, regarding risk factors for, or clinical evidence of, relevant communicable disease agents and diseases, as required by 21 CFR 1271.75(a). More specifically, you recovered HCT/Ps from at least the five donors below in which you failed to review valid death certificates. Moreover, when transferring the records with the tissues to a tissue processor, you provided documents purporting to be the certificates of death for these donors, which are not authentic death certificates issued by the state, and are inaccurate. For instance:

    1. The records created or maintained by you for donor --------- are inaccurate in that you state in your Circumstances of Death form that the donor's cause of death was myocardial infarction and that the donor died at home; your Tissue Donor Physical Assessment form states that this donor showed no signs of intravenous drug use; your Tissue Recovery Report states that the cause of death was atherosclerotic cardiovascular disease and hypertension and that the donor had no history of cancer; your Medical Evaluation form states that the donor was not admitted to a health care facility prior to death; the certificate of death that you provided to a tissue processor states that the donor's cause of death was atherosclerotic cardiovascular disease, with other significant contributing conditions being emphysema, coronary artery disease, tobacco abuse and chronic obstructive pulmonary disease.

      2. All of these statements in these records are contradicted by the State of ------------- issued certificate of death, which states that the donor died at ----------- Nursing Center of rectal squamous cell cancer, with other significant contributing conditions being intravenous drug use, coronary artery disease, tobacco abuse and chronic obstructive pulmonary disease.

    2. The records created or maintained by you for donor -------- are inaccurate in that you state in your Tissue Recovery Report that the donor's cause of death was chronic obstructive pulmonary disease; your Donor Demographics form states that the donor's date of birth was -------------; your Circumstances of Death form states that the donor died at home from complications due to chronic obstructive pulmonary disease; your Medical Evaluation form states that the donor was not admitted to a health care facility prior to death; your Tissue Donor Physical Assessment form states that the donor was 72 years of age; and the certificate of death that you provided to a tissue processor states that the donor was 72 years of age and that the cause of death was respiratory distress due to chronic obstructive pulmonary disease.

      3. All of these statements in these records are contradicted by the State of -------------- issued certificate of death, which states that the donor died at the age of 82 (with a date of birth of ----------------), at ----------------------------- facility, of aspiration pneumonia due to end-stage Alzheimer's.

    3. The records created or maintained by you for donor --------- are inaccurate in that you state in your Tissue Recovery Report that the donor had no history of cancer and died of a myocardial infarction; your Circumstances of Death form states that the donor expired at home as a result of a myocardial infarction; your Medical Evaluation form states that the donor was not admitted to a health care facility prior to death; and the certificate of death that you provided to a tissue processor states that the donor died of a myocardial infarction due to atherosclerotic cardiovascular disease.

      4. All of these statements in these records are contradicted by the State of --------------- issued certificate of death, which states that the donor died of colorectal cancer at ------------------- Hospital.

    4. The records created or maintained by you for donor ----- are inaccurate in that you state in your Donor Demographics form that the donor's date of birth was ------------------; your Tissue Donor Physical Assessment form states that the donor was 43 years old; and your Tissue Recovery Report states that the donor was 43 years old.

      5. All of these statements in these records are contradicted by the State of --------------------- issued certificate of death, which states that the donor was born on -----------------, and was 49 years old.

    5. The records created or maintained by you for donor --------- are inaccurate in that you state in your Tissue Recovery Report that the donor died at the age of 74; your Tissue Donor Physical Assessment form states that the donor died at the age of 74; your Donor Demographics form states that the donor's date of birth was------------; your Medical Evaluation form states that the donor was not admitted to a health care facility prior to death; and your Circumstances of Death form states that the donor died at home, and that the funeral home removed the body from home.

      6. All of these statements in these records are contradicted by the State of --------------- issued certificate of death, which states that the donor was born on -------------, was 76 years old, and died at -------------- Hospital.

  2. You failed to create and maintain accurate Tissue Donor Physical Assessment forms and Medical Evaluation forms, both records, as required by 21 CFR 1271.55(d)(2) and 21 CFR 1271.270(a). On the Tissue Donor Physical Assessment forms for donors ---------------------------------------, and ----- you represented to a tissue processor that: "[a] review of available medical records & physical assessment findings were completed & found to be acceptable prior to recovery." Furthermore, on the Medical Evaluation forms for each of these donors you represented to the tissue processor that: "The above information was obtained from one of the following sources: Hospital/facility personnel and/or medical social history. I have reviewed the above information and verify that it is complete to the best of my knowledge." However, contrary to your attestations, and as discussed elsewhere in this letter, these forms have provided the tissue processor with an inaccurate and incomplete summary of the records of these donors, of their medical history and of their eligibility for donation.

  3. You failed to review the relevant medical records for several donors, regarding risk factors for, or clinical evidence of, relevant communicable disease agents and diseases, as required by 21 CFR 1271.75(a). You also failed to establish, maintain and implement Standard Operating Procedures (SOPs) regarding testing, screening, and determining donor eligibility for donors who are admitted to health care facilities prior to death, as required by 21 CFR 1271.47(a). More specifically, your Medical Evaluation form describes the following procedure to be followed if a donor was admitted to a health care facility prior to death: "attach the H&P [history and physical], discharge summary, and physician's progress notes for the last five days." You did not implement this procedure for the following donors, and instead recorded that they had not been admitted to a health care facility prior to death. As a result, you did not review relevant medical records regarding risk factors for, or clinical evidence of, relevant communicable disease agents and diseases for these donors. Contrary to your Medical Evaluation forms:

    1. the State of -----------------------issued certificate of death for donor -------- states that at the time of death this donor was a patient at ------------------ Hospital;

    2. the State of --------------issued certificate of death for donor ------------ states that at the time of death this donor was a patient at --------------- Healthcare;

    3. the State of --------------issued certificate of death for donor ------------ states that at the time of death this donor was a patient at ---------- Nursing Center; and

    4. the State of --------------issued certificate of death for donor ------------- states that at the time of death this donor was a patient at -------------- Hospital.

  4. You failed to establish and maintain procedures (SOPs) for all steps that you perform in testing, screening, and determining donor eligibility, as required by 21 CFR 1271.47(a). More specifically, in your affidavit of June 30, 2006, you state that "Donor suitability on donor[s] recovered by Donor Referral Services was made by the receiving institution. Donor Referral Services was not the responsible party in determining the final suitability and release of tissue." Furthermore, you admit that whatever limited donor eligibility evaluation DRS did perform was based on -------------------- criteria, and this was only a "guide" in performing the recovery of tissue. Finally, you failed to document and maintain records regarding whatever such procedures might have existed at your Establishment, as required by 21 CFR 1271.47(a) and (c) and 21 CFR 1271.270(a). When an FDA investigator requested that you provide records of all such procedures, you were unable to do so.

  5. You failed to establish and maintain procedures (SOPs) appropriate to meet core CGTP requirements for all steps that you perform in the manufacture of HCT/Ps, as required by 21 CFR 1271.180(a) and (c), and you failed to document and maintain records regarding whatever such procedures might have existed, as required by 21 CFR 1271.47(a) and (c) and 21 CFR 1271.270(a). More specifically, in your affidavit of June 30, 2006, you state that "I have utilized ---------------------------------------------- operation procedures to complete the recovery of tissue from donors." However, when an FDA Investigator requested that you provide records of all such procedures, you were unable to do so.

  6. You failed to retain all records for 10 years after their creation, as required by 21 CFR 1271.270(d), and you failed to retain all records pertaining to a particular HCT/P at least 10 years after the date of its administration, distribution, disposition, or expiration, whichever is latest, as required by 21 CFR 1271.55(d)(4) and 21 CFR 1271.270(d). More specifically, you admit in your affidavit of June 30, 2006 that you ".provided. [a tissue processor with] all eight donor tissue records of tissue that I recovered between March 2005 and March 2006. I did not keep copies of any of the original record tissue records (sic) sent to. [a tissue processor]."

    7. As a result, you have not retained records regarding donors -------------------------------------and -----, including the Personal Data form, the Donor Medical History and Behavioral Risk Assessment form, the Donor Demographics form, the Circumstances of Death form, the Infusion Summary form, the Medical Evaluation form, the Tissue Donor Physical Assessment form, the Tissue Recovery Report, the Certificate of Death, as well as all other records that you may have created for these donors.

The above-identified deficiencies are not intended to be an all-inclusive list of violations by you and your Establishment. Nevertheless, they indicate serious noncompliance with many of the regulations under 21 CFR Part 1271, which are designed to protect against the risks of communicable disease transmission. Of particular concern are the serious deficiencies involving:

1/ your failure to create and maintain accurate records;
2/ your failure to establish and maintain SOPs for all steps that you perform in manufacturing of HCT/Ps; and
3/ your failure to review relevant medical records regarding risk factors for, or clinical evidence of, relevant communicable disease agents and diseases.

Based on the foregoing, the agency finds that there are reasonable grounds to believe that HCT/Ps manufactured by you are violative because they were manufactured in contravention of the regulations under 21 CFR Part 1271 and, therefore, the conditions of manufacture of the HCT/Ps do not provide adequate protections against the risks of communicable disease transmission. Moreover, these deficiencies, including your failure to retain and maintain accurate records, are so serious and widespread that FDA finds there are reasonable grounds to believe that they present a danger to public health.

This letter confirms the telephone conversation on August 18, 2006, in which notice was given that, pursuant to 21 CFR 1271.440(a)(1) and (3), you individually, and your Establishment, 1) must immediately cease all manufacturing, as defined in 21 CFR 1271.3(e), until compliance with the regulations in 21 CFR Part 1271 has been achieved, and 2) must retain all HCT/Ps recovered on or after May 25, 2005 that are in your possession until they are disposed of as agreed by the agency, or until the safety of the HCT/Ps is confirmed. Instructions were given at that time not to recover or ship HCT/Ps. Neither you, nor your Establishment, can resume operations without prior written authorization from FDA [21 CFR 1271.440(d)]. Any shipment of HCT/Ps in violation of this order constitutes a violation of section 368 of the PHS Act [42 U.S.C. ยง 1271], for which criminal penalties may be imposed.

Within five (5) working days from the receipt of this Order to Cease Manufacturing, you may request a hearing on the matter in accordance with 21 CFR Part 16 (copy attached), to Mary A. Malarkey, Director, Office of Compliance and Biologics Quality, Center for Biologics Evaluation and Research, 1401 Rockville Pike, HFM-600, Rockville, MD 20852 (telephone: 301-827-6190).

Failure to request a hearing within the specified time period constitutes a waiver of the right to a hearing. You may also wish to inform yourself with respect to the agency's guidelines regarding electronic media coverage of its administrative proceedings, which can be found at 21 CFR Part 10, Subpart C.

Sincerely,

----- signature -----

Jesse L. Goodman, M.D., M.P.H.
Director
Center for Biologics Evaluation and Research

Effective Date:   August 18, 2006               Time:  9:48 AM Eastern

cc:

Attachments (2)
21 CFR Part 1271
21 CFR Part 16

 
Updated: August 18, 2006