Neobiosis, LLC — FDA Warning Letter Findings

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)]. For example, you have not validated the manufacturing process for your products with respect to identity, strength, quality, and purity. In addition, your firm reprocessed at least three batches of the firm’s amniotic fluid products since production began in (b)(4) . This reprocessing has not been validated.

In response to Form FDA 483 Observation 4, we acknowledge that the stability studies for your existing products have been modified to (b)(4) expiry until additional stability studies can be completed. Additionally, you stated that SOP-81 Product Stability Program (Version 1.0, Effective date: 2023-05-01) is complete. However, SOP-81 is inadequate. For example, it does not include the stability testing intervals, which is critical to a stability program to monitor product…

Failure to have an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions [21 CFR 211.42(c)(10)(v)]. For example, your firm has failed to validate the cleaning process for the ISO 7 clean room and BSCs used in the production of all your products purported to be sterile.

Failure to establish laboratory controls that include scientifically sound and appropriate specifications designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity [21 CFR 211.160(b)]. Specifically, your firm has not established laboratory controls that include appropriate final specifications for testing and release of your products to assure that each batch conforms to appropriate standards of identity and purity during routine production. Your finished product testing is limited to visual inspection, sterility testing, endotoxins testing, and infectious disease testing as measurements of product attributes.

In response to Form FDA 483 Observation 3, you have committed to initiating CAPA-9 to develop a Process Performance Qualification Program which will include critical product attributes and release criteria for product safety, quality, and purity for both your amniotic fluid and umbilical cord derived products. You did not submit documentation of your corrective actions for review. Please submit to the agency evidence of your completed corrective actions.

Failure to have an adequate system for monitoring environmental conditions in an aseptic processing area [21 CFR 211.42(c)(10)(iv)]. Your firm has not established an adequate system for environmental monitoring in the aseptic processing areas where your products are manufactured. For example: a. Prior to October 2022, except for surface settling plates within the biological safety cabinets (BSCs), your firm failed to establish a routine environmental and personnel monitoring…

In response to Form FDA 483 Observation 2, we acknowledge that you have initiated CAPA-8 to address your corrective and preventative actions for your environmental program which includes a revision to SOP-48 "Routine Environmental Microbiological Monitoring Program". This SOP does not define " (b)(4) " as to whether this is in reference to (b)(4) versus (b)(4) , which could result in confusion, and it does not specify whether the samples are to be collected during or at the conclusion of operations to ensure monitoring represents aseptic processing conditions. Furthermore, CAPA-8 does not address the products manufactured in an aseptic processing environment without an established routine environmental and personnel monitoring program prior to October 2022. These products were distributed without verifying their control of microbial hazards in their production environment.

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. The aseptic processes used to manufacture your products have not been validated (e.g., by performing media fill simulations). These products purport to be sterile and are expected to be sterile. b. The (b)(4) sterilization process used for equipment that comes into direct contact with your products has not been adequately validated. For example, you have not defined the optimal parameters and conditions, including the load configuration for sterilizing equipment such as the small instruments (e.g., forceps), glass beakers, and sometimes PPE, used in aseptic processing of your products.

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, you assigned a two-year expiration date to your products without establishing a testing program to determine the stability characteristics. Because your methods, facilities, or controls for manufacturing…