Utah Cord Bank LLC dba Utah Cell Bank — FDA Warning Letter Findings

Failure to assign and label each HCT/P that you manufacture with a distinct identification code in accordance with the requirements in 21 CFR 1271.290(c). Specifically, you do not ensure that each HCT/P that you manufacture is assigned and labeled with a distinct identification code that relates the HCT/P to the donor and to all records pertaining to the HCT/P and that labeling includes information designed to facilitate effective tracking, using the distinct identification…

Failure to have separate or defined areas or such other control systems for your operations as are necessary to prevent contamination or mixups during the course of aseptic processing. [21 CFR 211.42(c)(10)]. For example: a. You allow two or more operators to process product within the same (b)(4) . Processing by more than one technician in the same (b)(4) can significantly increase the potential for contamination. b. Your manufacturing facility is not classified with respect to air quality. The (b)(4) , used to process your products, and operator gowning areas are located within an unclassified environment. c. Your firm has not established an adequate system for monitoring environmental conditions in the aseptic processing area where your products are manufactured. d. Your firm does not conduct personnel monitoring of operators working in the aseptic processing area where your products are manufactured. e. Your firm does not have a validated cleaning process for the aseptic processing area where your products are manufactured.

Failure to establish and follow written procedures describing in sufficient detail the receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers and closures [21 CFR 211.80(a)]. For example: a. There are no written procedures describing in sufficient detail the criteria for approval or rejection of incoming human umbilical cord blood or human umbilical cord. b. There are no written procedures describing in sufficient detail the acceptance criteria for components used in manufacturing, including (b)(4) micron and (b)(4) micron filters, (b)(4) (glass) bottles, and (b)(4) , and drug product containers and closures.

Failure to establish and follow a written testing program designed to assess the stability characteristics of drug products and to use the results of such stability testing to determine the appropriate storage conditions and expiration dates [21 CFR 211.166(a)]. Specifically, you assign a two-to-six year expiration date to your products without supporting data.

Failure to prepare batch production and control records for each batch of drug product produced that include complete information relating to the production and control of each batch, including documentation that each significant step in the manufacture, processing, packing, or holding of the batch was accomplished [21 CFR 211.188(b)]. For example: a. Your batch production record does not include documentation of the accomplishment of each significant step in the processing…

Failure to establish and follow written procedures for cleaning and maintenance of equipment used in the manufacture, processing, packing, or holding of a drug product [21 CFR 211.67(b)]. For example: a. Your firm failed to validate the cleaning process for your (b)(4) . b. There are no data or rationale for the cleaning agents used or their rotation for the cleaning of the (b)(4) where manufacturing is performed. c. Your firm has not established written procedures for the (b)(4) sterilization of the (b)(4) filter and the (b)(4) funnel that come into direct contact with your products during processing.

Failure to include in laboratory records complete data derived from all tests necessary to assure compliance with established specifications and standards, including a statement of each method used in the testing of the sample that indicates the location of data that establish that the methods used in the testing of the sample meet proper standards of accuracy and reliability as applied to the product tested [21 CFR 211.194(a)(2)]. Specifically, lot release of your products is based on sterility testing; however, your in-house sterility test has not been validated. Accordingly, your laboratory records do not include a statement that indicates the location of data that establish that your sterility testing methods meet proper standards of accuracy and reliability as applied to your products.

Failure to routinely calibrate, inspect or check automatic, mechanical or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, that are used in the manufacture, processing, packing and holding of a drug product, according to a written program designed to assure proper performance [21 CFR 211.68(a)]. Specifically, you failed to validate the software used to maintain your sterility testing results according to a written program designed to assure the software’s proper performance.

Failure to establish, when appropriate, time limits for the completion of each phase of production to assure the quality of the drug product [21 CFR 211.111]. Specifically, your firm stores (b)(4) product ( (b)(4) ) in a (b)(4) ml glass container in a commercial refrigerator in your unclassified lab area for up to (b)(4) prior to aliquoting the (b)(4) into a (b)(4) ml or (b)(4) ml final container. Your firm failed to validate the time limit the (b)(4) can be stored in such a manner without negatively impacting the final product.

Failure to establish written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess [21 CFR 211.100(a)]. Specifically, the manufacturing processes for your products have not been validated.

Failure to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity [21 CFR 211.160(b)]. For example: a. You have not established scientifically sound and appropriate specifications, standards, sampling plans and test procedures to assure that your products conform to appropriate standards of identity, strength, quality, and purity. b. You do not collect and test sterility samples that are representative of the lot size. You test (b)(4) for sterility and rely on the results of (b)(4) sterility test to determine lot release despite the lot size, which may consist of as many as (b)(4) vials.

Failure to thoroughly investigate any unexplained discrepancy, or the failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed [21 CFR 211.192]. Specifically, from July 2017 to January 2020, you failed to thoroughly investigate 16 sterility failures. The failed lots were discarded; however, there was no further evaluation to identify the contaminating microorganism, determine a root cause or determine if other product lots may have been affected by the failures.

Failure to establish and follow written procedures describing the handling of all written and oral complaints regarding a drug product [21 CFR 211.198(a)]. For example: a. Although your firm received multiple complaints regarding your products, there was no supporting documentation to show that you performed an adequate follow-up and/or investigation of those complaints. We note that these complaints were categorized as adverse events on your complaint log. b. Written procedures describing the handling of all written and oral complaints do not include procedures for review of a complaint to determine whether the complaint represents a serious and/or unexpected adverse experience.

Failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes [21 CFR 211.113(b)]. For example: a. Your firm failed to validate the aseptic processes used to manufacture over (b)(4) vials of your StemVive®, StemMaxx™; StemTru™ and StemCellect™ products (i.e., by performing media fill simulations) since your manufacturing operations began. By the nature of their routes of administration, your products purport to be sterile and are expected to be sterile. b. Your employees use non-sterile personal protective equipment (PPE), for example lab coats, gloves and hair nets, during the manufacture of your products.