Order to Cease Manufacturing of HCT/Ps - Vista Cord, LLC

Order to Cease Manufacturing of HCT/Ps - Vista Cord, LLC
September 24, 2009

HAND DELIVERED

Aubrey B. Allen
CEO and Owner
Vista Cord, LLC
1405 Frye Road
Starkville, Mississippi 39759

Dear Mr. Allen:

Your firm Vista Cord, LLC (Vista Cord or Establishment), located at 1405 Frye Road, Starkville, Mississippi, manufactures 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 July 13 and 27, 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 reveal significant violations by Vista Cord 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 the Establishment is in violation of 21 CFR Part 1271, the Establishment does not provide adequate protections against the risks of communicable disease transmission. The agency has also determined that there are reasonable grounds to believe there is a danger to health and accordingly, this Order to Cease Manufacturing is effective immediately. The Order relates to conduct occurring on or after May 25, 2005, the effective date of the applicable regulations. We note that FDA retains authority to pursue other actions and remedies.

Therefore, pursuant to 21 CFR 1271.440(a)(3), both you individually, and Vista Cord 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 which are in your possession in compliance with the requirements at 21 CFR 1271.260.

Additionally, we request that you immediately notify, by copy of this Order, all individuals who intend to or have stored umbilical cord blood with Vista Cord since May 25, 2005. This includes, but is not limited to, any and all individuals who have signed a Cord Blood Storage Agreement and Informed Consent. We further request that you provide FDA with a copy of the cover letter, if any, you include with the copy of the Order and a list of the individuals you notify.

FDA’s inspection and record review noted significant noncompliance with the federal regulations in many areas of Vista Cord’s operations including, but not limited to, the following:

A. DONOR ELIGIBILITY:

1) Failure to conduct required donor screening on at least 130 cord blood units designated as ‘Allogenic [sic] Related’ [21 CFR 1271.75]. Specifically:

The FDA investigator reviewed -(b)(4)- donor files relating to cord blood processed from February to July 2009, and noted that the only donor screening conducted was a self-administered questionnaire titled Vista Cord Health History. However, this questionnaire is inadequate in that it does not screen for all risk factors associated with communicable disease agents and diseases including Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV), Treponema pallidum (syphilis), and human transmissible spongiform encephalopathy, including Creutzfeldt-Jakob disease (CJD).

2) Failure to determine whether a donor is eligible based on the results of required donor testing for communicable diseases [21 CFR 1271.50(b)(2)]. Specifically:

During the inspection, the investigator reviewed 25 donor record files for donors from whom HCT/Ps may be used in first or second degree relatives. Four of those donor record files failed to contain any results of required testing for evidence of infection due to relevant communicable disease agents. Nine of those 25 donor record files failed to contain test results for HIV and HCV by -----------(b)(4)--------------. Five of those 25 donor record files did not contain test results for syphilis testing.

3) Failure to establish and maintain procedures for all steps performed in testing, screening and determining donor eligibility [CFR 1271.47(a)]. Specifically:

You failed to establish and maintain procedures to evaluate whether plasma dilution of maternal samples was sufficient to affect the results of communicable disease testing, [21 CFR 1271.80(d)], and failed to establish and maintain procedures for governing the release of HCT/Ps when a donor tests reactive for cytomegalovirus [21 CFR 1271.85(b)(2)].

B. CURRENT GOOD TISSUE PRACTICE

Procedures

1) Failure to establish and maintain procedures appropriate to meet core current Good Tissue Practice (GTP) requirements for all steps performed in the manufacture of HCT/Ps, [21 CFR 1271.180(a)], and to have those procedures reviewed and approved by a responsible person [21 CFR 1271.180(b)]. Specifically:

You have failed to establish and maintain adequate written procedures relating to: facilities, environmental control, equipment, supplies and reagents, recovery, processing and process controls, labeling controls, storage, receipt and distribution.

2) You failed to establish and maintain procedures for reviewing, evaluating and documenting complaints [CFR 1271.320].

Facilities

1) Failure to provide plumbing, drainage, and access to sinks and toilets that are adequate to prevent the introduction, transmission or spread of communicable disease [21 CFR 1271.190(a)]. Specifically:

a) The only functioning hand-washing sink and toilet available for use by employees is located in a public restroom. The entry door is located on the outside of the processing facility and at the time of the inspection, the restroom was not equipped with soap or paper towels;

b) A two-compartment sink located adjacent to the processing area had no drainage access. The sink was used to prepare bleach and alcohol solutions for sanitizing purposes.

2) Failure to utilize a suitable facility maintained in a good state of repair, adequate to prevent contamination of HCT/Ps [21 CFR 1271.190(a)]. Specifically, the FDA investigator observed the following:

a) A hole in a section of the processing area ceiling, which opens to the exterior;

b) Several water-stained ceiling tiles located directly above storage shelves containing processing supplies and in other parts of the facility.

3) Failure to maintain the processing facility in a clean, sanitary, and orderly manner to prevent the introduction, transmission, or spread of communicable disease [21 CFR 1271.190(b)(1) and (2)]. Specifically:

a) Dust, dirt, trash and various dead insects were found throughout the processing and storage areas (including beneath the laminar flow hood; in a centrifuge used during processing, and on a table which contained unused processing equipment);

b) Particles of dirt and dust were observed on a digital scale used to weigh products during processing; the top of the incubator used in bacterial contamination testing; the counter surface located directly behind the incubator; the vent cover of a fan on top of a refrigerator/freezer, and the inside surfaces of the refrigerator/freezer used to store reagents and samples for donor testing;

c) The lid was open on a large sharps receptacle containing used processing material. This was located adjacent to the laminar flow hood;

d) An electric fan and window unit air conditioner were in use in the processing area.

4) You failed to document, and maintain records of, all cleaning and sanitation activities performed to prevent contamination of HCT/Ps as required by 21 CFR 1271.190(d)(2). Specifically:

For the period June 7 to July 14, 2009, a review of receiving and storage records revealed that the Establishment received, processed, and placed in storage at least -(b)(4)- units of HCT/Ps. However, during this time period you failed to document any weekly cleaning/sanitation activities for the processing area.

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 of HCT/Ps or equipment [21 CFR 1271.195(a)]. Specifically:

The facility is cooled by a window unit air conditioner located in the processing area. Unfiltered air is drawn from outside and blows onto the side of the laminar flow hood where aseptic processing is performed.

2) Failure to inspect each environmental control system periodically to verify that the system is adequate and functioning properly and to take corrective action if necessary [CFR 1271.195(b)].

The Establishment monitors only the processing room and storeroom temperatures on a routine basis. The storage temperatures in the refrigerator and freezer, where maternal samples are stored, are not routinely monitored.

3) Failure to monitor environmental conditions where they could reasonably be expected to cause contamination or cross-contamination of HCT/Ps [21 CFR 1271.195(c)].

Equipment

1) Failure to establish and maintain adequate procedures for cleaning, sanitizing, and maintaining equipment to prevent malfunctions, contamination or cross contamination or accidental exposure of HCT/Ps to communicable disease agents [21 CFR 1271.200(b)].

2) Failure to routinely calibrate according to established procedures and schedules all automated, mechanical or other equipment used for inspection and testing to prevent malfunctions [CFR 1271.200(d)]. Specifically:

Apart from the digital scale, no equipment used for inspection and testing has been calibrated to a reference standard.

3) Failure to document and maintain records of all equipment maintenance, cleaning, sanitizing, and calibration and other activities [21 CFR 1271.200(e)]. Specifically:

For the period June 7 to July 14, 2009, a review of receiving and storage records revealed that the Establishment received, processed, and placed in storage at least -(b)(4)-cord blood units. However during this time period there was no documentation of weekly cleaning/sanitation for equipment used in processing such as tube racks, scissors and clamps.

Supplies and Reagents

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]. Specifically:

a) During the recent FDA inspection, the investigator reviewed the Establishment's supply/reagent record file and found no verification records (Certificate of Analysis) available for the following: -(b)(4)-transfer/freezer bag processing set; -----(b)(4)------and -----(b)(4)------sterile pipettes, and ---(b)(4)---- processing solution:

b) When adding -----------(b)(4)------------ to the final cord blood product, -----(b)(4)---- is used to seal the connection between the pipette and entry port without any verification that the -----(b)(4)---- is sterile.

Processing and Process Controls

1) Failure to process each HCT/P in a way that does not cause cross contamination during processing [21 CFR 1271.220(a) and (c)]. Specifically during the recent FDA inspection, the investigator observed:

a) An employee performing cord blood processing placing pieces of non-sterile cardboard inside the centrifuge along with the product (i.e. transfer/freezer bag processing set and HCT/Ps);

b) An employee performing cord blood processing, routinely removing the product from the sterile field of the laminar flow hood, placing it on a digital scale outside the hood, and returning it to the hood;

c) Dried reagent, utilized in previous HCT/P processing, spotting the surface of the laminar flow hood.

2) Failure to ensure that each in-process HCT/P is controlled until the required tests have been completed [21 CFR 1271.220(c)]. Specifically:

a) A review of 24 processing records revealed the dates/times of the bacterial/fungal contamination testing results were not recorded. The associated units of cord blood were stored in available inventory.

b) Cord blood units are routinely processed and stored in available inventory without being quarantined pending completion of bacterial/fungal testing and testing for evidence of relevant communicable diseases. For example, on July 15, 2009, the investigator observed that a unit of cord blood was received, processed and stored in available inventory prior to completion of bacterial/fungal testing.

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)]. Specifically, Vista Cord has not validated or documented the validation of any of the processes used during processing including:

a) The two HCT/P processes in use since January 2008 for red blood depletion of cord blood using hydroxyethyl starch;

b) The two test methods for detection of bacterial/fungal contamination in use since January 2008;

c) A rework which involved transferring the contents of two freezer bags into 5ml vials when the tube sealer was unable to completely seal the tubing on the bags.

Labeling Controls

Failure to establish and maintain procedures to control the labeling of HCT/Ps as required by 21 CFR 1271.250, to ensure each HCT/P is labeled in accordance with all applicable labeling requirements including those in 1271.55, 1271.60, 1271.65, 1271.90, 127.290 and 1271.370.

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)]. Specifically:

a) On July 15, 2009, the investigator observed that no evaluation for the presence and significance of microorganisms was performed on an incoming unit of cord blood, nor was the unit inspected for damage and contamination.

b) On July 15, 2009, when the investigator observed receipt by the Establishment of an incoming unit of cord blood, no procedures were available regarding evaluation and inspection of each incoming unit for the presence and significance of microorganisms and inspection for damage and contamination, nor were such procedures available at any time during the inspection.

On September 11, 2009, we received your undated written response to the FDA 483 issued to Vista Cord at the close of the inspection. We have reviewed the corrective actions outlined in the response and we have determined that they are inadequate. You admit that many areas of your firm’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 or can be successfully implemented. Our specific comments regarding your response will be sent under separate cover.

This letter confirms the telephone conversation on September 24, 2009, in which notice was given that, pursuant to 21 CFR 1271.440(a)(3), both you individually and Vista Cord 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 which are in your possession, in compliance with the requirements at 21 CFR 1271.260.

Additionally, we request that you immediately notify, by copy of this Order, all individuals who intend to or have stored umbilical cord blood with Vista Cord since May 25, 2005. This includes, but is not limited to, any and all individuals who have signed a Cord Blood Storage Agreement and Informed Consent. We further request that you provide FDA with a copy of the cover letter, if any, you include with the copy of the Order and a list of the individuals notified.

Instructions were given during the telephone conversation not to process or distribute HCT/Ps and to continue to maintain existing HCT/Ps in storage. 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 GTP 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).

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: 9/24/2009 Time: 10:08 am

abrir aquí:
Order to Cease Manufacturing of HCT/Ps - Vista Cord, LLC