1Laboratory and QC controls
Failure to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity [21 CFR 211.160(b)]. For example, your firm has not established appropriate specifications and test procedures to assure that your amniotic fluid products conform to appropriate standards of identity, strength, quality, and purity. Your finished product testing is limited to a visual examination.
2Environmental monitoring
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 been already distributed [21 CFR 211.192]. For example, between October 30, 2020, and July 30, 2021, you failed to investigate approximately 90% of your excursions for microbiological monitoring of the cleanroom environment, including two excursions in the critical processing area (i.e., inside your BSCs). While you identified the contaminating organisms, you did not thoroughly investigate the excursions to determine the root cause, product impact, and corrective and preventive actions. Examples of microorganisms identified in your cleanroom include Bacillus species non-anthracis, Fictibacillus species, Bacillus pumilus , Gram Positive Cocci, fungi, and Bacillus megaterium .
3Aseptic processing and sterility assurance
Your aseptic processing areas are deficiently designed in that the floors are not smooth, hard surfaces that are easily cleanable in order to prevent contamination [21 CFR 211.42(c)(10)(i)]. For example, your cleanrooms floors have seams and gaps rendering them difficult to clean and disinfect.
4Quality unit oversight
Failure to ensure that each lot of components, drug product containers, and closures are withheld from use until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit [21 CFR 211.84]. For example: a. Your firm used (b)(4) to manufacture approximately (b)(4) batches of MyOwnSkin™ and MySkinRestore™ between June 27, 2019, and September 24, 2021, even though such components had not been examined and released for use by the quality control unit. These components are labeled for research use only. b. Your firm used (b)(4) , to manufacture MyOwnSkin™ and MySkinRestore™, even though such components had not been examined and released for use by the quality control unit. The labeling of those components advises against their use in “Human or Animal Drugs.” c. Your firm lacks evidence, such as testing, to demonstrate that these components meet all specifications of identity, strength, quality, and purity.
5Equipment and facility
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 BSCs. b. Your firm has not adequately established and followed written procedures for cleaning the (b)(4) BSCs used to manufacture your products. For example, your written procedure for cleaning does not include the (b)(4) when (b)(4) is used to clean the BSCs during (b)(4) cleanings.
6Stability and storage
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 appropriate storage conditions and expiration dates [21 CFR 211.166(a)]. Specifically, your firm has assigned a twelve-month expiration date to your amniotic fluid products and a 24-hour expiration date to your skin products without supporting data from stability testing. We have reviewed…
7Environmental monitoring
Failure to establish and follow written procedures describing in sufficient detail the methods and materials used for sanitation [21 CFR 211.56(b)]. For example: a. Your firm failed to validate the cleaning process for your cleanrooms. b. Your firm has not adequately established and followed written procedures for cleaning the cleanrooms used to manufacture your products. For example: i. In accordance with your cleanroom cleaning procedure, a (b)(4) cleaning of all contact…
8Process validation
Failure to establish written procedures for production and process controls 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, your firm has not validated the manufacturing processes for Fluid GF™, Restore GF™, Fluid Flow™, Amnio Restore™, (b)(4) , Stimuleyes™, MyOwnSkin™, and MySkinRestore™.
9Aseptic processing and sterility assurance
Failure to establish 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. You failed to validate the aseptic processes used to manufacture over (b)(4) units of Fluid Flow™, Amnio Restore™, (b)(4) , Stimuleyes™, Fluid GF™, and Restore GF™ (i.e., by performing media fill simulations) since…
