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Order to Cease Manufacturing of HCT/Ps: Newborn Blood Banking, Inc.

February 19, 2010

HAND DELIVERED

Jon G. Suits
CEO and Owner
Newborn Blood Banking, Inc.
22327 Carson Drive
Land O Lakes, Florida 34639-5128

Dear Mr. Suits:

Your firm Newborn Blood Banking, Inc. (Newborn Blood Banking or Establishment), located at 22327 Carson Drive, Land O Lakes, Florida, processes and stores umbilical cord blood containing stem cells, and therefore is a manufacturer of human cells, tissues, and cellular and tissue-based products (HCT/Ps). The Food and Drug Administration (FDA or agency) conducted an inspection of your Establishment between October 14-28, 2009, and at the conclusion of the inspection, the FDA investigator issued you a Form FDA- 483, Inspectional Observations. Our review of the information and records examined and collected during the inspection revealed significant violations by Newborn Blood Banking of Title 21, Code of Federal Regulations, Part 1271 (21 CFR 1271) issued under the authority of Section 361 of the Public Health Service Act (PHS Act) [42 United States Code (USC) 264]. The agency has determined that because your Establishment is in violation of 21 CFR Part 1271, your Establishment does not provide adequate protections against the risks of communicable disease transmission through the use of these HCT/Ps. The agency has also determined that there are reasonable grounds to believe these violative HCT/Ps pose a danger to health, and, accordingly, this Order to Cease Manufacturing is effective as of the date of this Order. This Order to Cease Manufacturing relates to conduct occurring on or after May 25, 2005, the effective date of the applicable regulations. FDA retains authority to pursue other actions and remedies.

Therefore, pursuant to 21 CFR 1271.440(a)(3), both you individually, and Newborn Blood Banking must:

1) Immediately cease all manufacturing (including receipt of in-transit cord blood units) until compliance with the regulations in 21 CFR 1271 has been achieved and you have been provided written authorization from FDA to resume operations. Under 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;

2) Not distribute any HCT/Ps recovered on or after May 25, 2005, which are in your possession or received after the date of this order; and

3) Continue to store all HCT/Ps recovered on or after May 25, 2005, which are in your possession or received after the date of this order. These HCT/Ps must be stored in compliance with the requirements at 21 CFR 1271.260.

Additionally, this is to advise you that FDA will notify, by copy of this Order, all individuals who intend to or have stored umbilical cord blood with Newborn Blood Banking since May 25, 2005. This includes, but is not limited to, any and all individuals who have signed a Registration Form and Informed Consent.

FDA’s inspection and record review noted significant noncompliance with the federal regulations in all areas of your Establishment's operations including, but not limited to, the following:

A. DONOR ELIGIBILITY

1) Failure to establish and maintain procedures for all steps performed in determining donor eligibility [21 CFR 1271.47(a)]. For example: 

a) There is no written procedure for determining donor eligibility, including procedures for obtaining relevant medical history and a history of relevant social behavior to screen for risk factors for, and clinical evidence of, relevant communicable disease agents and diseases, including but not limited to Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV), as required under 21 CFR 1271.75(a).

b) There is no written procedure specifying time frames for collecting blood samples from the birth mother for relevant communicable diseases, as required under 21 CFR 1271.80(b).

c) There are no written procedures to ensure that laboratories performing communicable disease testing, which is then used in determining donor eligibility, are using appropriate FDA licensed, approved, or cleared donor screening tests, as required under 21 CFR 1271.80(c).

d) There are no written procedures to ensure that test laboratories performing communicable disease testing and interpreting test results are using tests in accordance with the manufacturer’s instructions, as required under 1271.80(c).

e) There are no written procedures to ensure that testing is performed by a laboratory that is certified to perform such testing under the Clinical Laboratory Improvement Amendments of 1988 and 42 CFR Part 493, or that meets equivalent requirements as determined by the Centers for Medicare and Medicaid Services, as required under 1271.80(c).

2) Failure to screen donors by reviewing the donor’s relevant medical records for risk factors for, and clinical evidence of, relevant communicable disease agents and diseases, as well as communicable disease risks associated with xenotransplantation (21 CFR 1271.75(a)(1) and (2)). For example, 16 donor records reviewed by the investigator for cord blood processed from 2007 through 2009 had no record of screening of the donor’s relevant medical history or relevant social behavior for risk factors for, and clinical evidence of, communicable disease agents and diseases or communicable disease risks associated with xenotransplantation.

3) Failure to maintain documentation of donor eligibility determinations [21 CFR 1271.55(d)(iii)]. Donor records lack evidence of donor eligibility determinations, including the name of the person who made the determination and the date of the determination. Your Establishment is required to determine donor eligibility because the Registration Form and Informed Consent provide that the cord blood unit may be used for related allogeneic use.

4) Failure to collect donor specimens to be used for testing for relevant communicable diseases at the time of or up to 7 days before or after recovery of the cord blood as required under 21 CFR 1270.80(b). For example, communicable disease test results used to determine donor eligibility are not always performed on a sample of blood collected at the time of or up to 7 days before or after recovery of the cord blood. A review of 16 donor records found communicable disease testing was not performed on a sample collected within this time frame for any of the 16 donors.

5) Failure to test donors to adequately and appropriately reduce the risk of transmission of relevant cell-associated communicable diseases including Human T-cell Lymphotropic Virus types I and II (HTLV-I/II) as required under 21 CFR 1271.85(b)(1). For example, of the 23 donor records reviewed during the inspection, none were found to have results for testing for HTLV-I/II.

6) Failure to test a specimen from donors for evidence of cytomegalovirus (CMV) infection, and to establish a procedure governing the release of an HCT/P from a donor whose specimen tests CMV reactive [21 CFR 1271.85(b)(2)]. For example, 

a) A review of 16 maternal donor records showed no results of CMV testing.

c) Your SOPs lack a procedure governing the release of an HCT/P from a donor if the birth mother's specimen tests CMV reactive.

B. CURRENT GOOD TISSUE PRACTICE

Procedures

1) Failure to establish and maintain procedures appropriate to meet core CGTP requirements, as defined in 21 CFR 1271.150(b), for all steps performed in the manufacture of HCT/Ps and to have those procedures reviewed and approved by a responsible person [21 CFR 1271.180(a)-(b)]. For example, 

a) You failed to have written procedures for the cleaning of the facility.

b) You failed to have written procedures for environmental controls such as temperature control and air filtration, and to have written procedures for maintenance of equipment used to control conditions necessary for aseptic processing of cord blood.

c) You failed to have written procedures to ensure that supplies and reagents are verified to meet required specifications.

d) You failed to have written procedures for processing and process controls.

e) You failed to have written procedures for labeling of cord blood prior to storage and at the time of distribution.

f) You failed to have written procedures for long term storage of cord blood.

g) You failed to have written procedures for evaluating cord blood at the time of receipt for possible contamination and damage.

2) Failure to establish and maintain procedures, including release criteria, for the distribution of cord blood you have stored at your facility [21 CFR 1271.265(e)].

Facilities

1) Failure to maintain your facility in a clean, sanitary, and orderly manner to prevent the introduction, transmission, or spread of communicable disease [21 CFR 1271.190(b)(1)]. For example, 

a) The lid of a sharps receptacle (container for biohazardous waste) containing discarded needles that had been used in the processing of cord blood was observed to be open. The uncovered receptacle was sitting in a sink next to the counter work area used during the processing of cord blood.

b) A commercially available insect trap and debris were observed on the window sill directly above the cord blood processing area and a dead insect was observed on the floor near the liquid nitrogen freezer.

c) An accumulation of dirt and dust were observed in the corners of the processing and storage room.

2) Failure to document and maintain records of facility cleaning and sanitation activities [21 CFR 1271.200(e)]. For example, during the inspection no records of cleaning and sanitation activities were available for review.

Environmental Control and Monitoring

1) Failure to adequately control environmental conditions and provide proper conditions for operations where environmental conditions could reasonably be expected to cause contamination or crosscontamination of HCT/Ps or equipment [21 CFR 1271.195(a)]. For example, 

a) the processing of cord blood units is performed on a work counter without the use of any air filtration, such as with the use of a laminar air flow hood; and

b) a wall unit air conditioner located adjacent to the processing area directs a current of air near or onto the processing area where the cord blood is transferred into blood bags prior to freezing.

2) Failure to monitor environmental conditions where environmental conditions could reasonably be expected to cause contamination or cross-contamination of HCT/Ps or equipment and to maintain records of environmental control and monitoring activities [21 CFR 1271.195(c) and (d)]. For example, there were no records documenting the monitoring of microorganisms in the area where cord blood is processed.

Supplies and Reagents

1) Failure to verify that supplies and reagents meet specifications designed to prevent circumstances that increase the risk of introduction, transmission or spread of communicable diseases [21 CFR 1271.210(a)]. For example, there is neither a record of verification nor documentation that a Certificate of Analysis is received with each new lot of -----------(b)(4)---------------, which is added to the cord blood during processing.

2) Failure to maintain records of the receipt of each supply or reagent, including the type, quantity, manufacturer, lot number, date of receipt, and expiration date, or to maintain a record of the verification of each supply or reagent [21 CFR 1271.210(d)(1)-(2)]. For example, there is no documentation of the receipt of supplies and reagents or documentation of verification, including test results, for the reagents used in processing cord blood.

Equipment

Failure to document and maintain records of all equipment maintenance, cleaning, sanitizing, or calibration [21 CFR 1271.200(e)].

Processing and Process Controls

Failure to process each HCT/P in a way that does not cause cross-contamination during processing [CFR 1271.220(a) and (c)]. For example, you do not perform sampling of HCT/Ps for testing for microbiological contamination.

Process Validation

Failure to validate and approve a process according to established procedures where the results of processing cannot be fully verified by subsequent inspection and tests [21 CFR 1271.230(a)].You have not validated or documented the validation of any of the processes used in cord blood processing to ensure that they do not cause contamination or cross-contamination and that the processes prevent the introduction, transmission or spread of communicable diseases. For example, you did not validate the following processes:

a) The temporary storage of cord blood in a 60 mL syringe using heparin as an anticoagulant;

b) Your aseptic technique for the processing of cord blood;

c) Your method of processing cord blood.

Labeling and Labeling Controls

1) Failure to include required information on HCT/P labels or, where appropriate, in labeling accompanying the HCT/Ps [21 CFR 1271.370]. For example, 

a) During FDA’s inspection, sample labels you provided to the investigator showed that product labels did not include a distinct identification code and a description of the type of HCT/P (e.g. umbilical cord blood).

b) Labeling did not include applicable warnings as required under 21 CFR 1271.370.

2. Failure to establish and maintain procedures to control the labeling of HCT/Ps as required by 21 CFR 1271.250(a) to ensure each HCT/P is labeled in accordance with all applicable labeling requirements including those in 21 CFR 1271.55, 1271.60, 1271.65, 1271.90, 1271.290, and 1271.370 [21 CFR 1271.250(c)]. For example, you have not established any procedures for the labeling of cord blood to include: 

a) Required warnings, if applicable;

b) Name and address of your firm;

c) Storage temperature;

d) Instructions for use ;

e) Distinct identification code affixed to the HCT/P container.

Receipt and Distribution

Failure to evaluate each incoming HCT/P for the presence and significance of microorganisms and to inspect for damage and contamination [21 CFR 1271.265(a)].

On November 19, 2009, we received your written response to the FDA 483 issued to Newborn Blood Banking, Inc. at the close of the inspection. We have reviewed the corrective actions outlined in the response and we have determined that they are inadequate. In your response you admit that many areas of the Establishment's operations are out of compliance with the applicable regulations in 21 CFR Part 1271 and promise to make corrective actions. However, you submitted insufficient data with your response to demonstrate that the necessary corrective actions have been successfully implemented. Our specific comments regarding your response will be sent under separate cover.

This letter confirms the telephone conversation on February 19, 2010, in which notice was given that, pursuant to 21 CFR 1271.440(a)(3), both you individually and Newborn Blood Banking, Inc. must:

1) Immediately cease all manufacturing (including receipt of in-transit cord blood units) until compliance with the regulations in 21 CFR 1271 has been achieved and you have been provided written authorization from FDA to resume operations. Under 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;

2) Not distribute any HCT/Ps recovered on or after May 25, 2005, which are in your possession or received after the date of this order; and

3) Continue to store all HCT/Ps recovered on or after May 25, 2005, which are in your possession, or received after the date of this Order. You must store these units in compliance with the requirements at 21 CFR 1271.260.

Instructions were given at that time of the telephone conversation not to process or distribute HCT/Ps and to continue to maintain existing HCT/Ps in storage, as noted above. Neither you, nor your Establishment, can resume operations without prior written authorization from FDA. Before FDA will issue such an authorization, you must ensure compliance with FDA’s regulations in 21 CFR Part 1271 – including, but not limited to, the Donor Eligibility and current Good Tissue Practice requirements in 21 CFR 1271, Subpart C and Subpart D. Any shipment of HCT/Ps in violation of this order constitutes a violation of Section 368 of the PHS Act [42 USC 271], 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). Should you need additional time in which to request a hearing, please notify us immediately, in writing, of your request for additional time.

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 10, Subpart C.

Sincerely,

/Signature/

Karen Midthun, M.D.

Acting Director, Center for Biologics Evaluation and Research

Effective Date: 02/19/2010 Time: 2:37 PM

Attachments (2)

21 CFR Part 1271

21 CFR Part 16

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Further Information on This Order

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Contact FDA

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Silver Spring, MD 20993-0002