1Aseptic processing and sterility assurance
Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes [21 CFR 211.113(b)]. Your firm has not adequately validated the aseptic processes used to manufacture Regener-Eyes® PRO and Regener-Eyes® LITE since commencing manufacturing operations for these products in December 2021. For example…
2Complaint and recall handling
Your firm failed to maintain production, control, or distribution records specifically associated with a batch of a drug product for at least one year after the expiration date of the batch [21 CFR 211.180(a)] For example, according to your Chief Strategist, the last batch of your Regener-Eyes® product containing amniotic fluid was manufactured in June 2021. Given that this product was labeled with a two-year expiration date, this batch would have expired in June 2023. You would have been required to maintain records until June 2024. However, during the inspection on June 22, 2023, in response to a request for records pertaining to this amniotic fluid-derived Regener-Eyes® ophthalmic solution product, (which your Chief Strategist claims was discontinued in June 2021), your Chief Strategist stated that she could not locate any records such as complaint records, distribution records, receiving records, storage records, and manufacturing records. She further stated that she could not remember where the records went or whether they were destroyed or not.
3Stability and storage
Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates [21 CFR 211.166(a)]. For example, your stability studies for Regener-Eyes® PRO ophthalmic solution do not support storage of the product at room temperature for 24 months as provided on product labeling. The stability studies you conducted as per protocol STB-22-0029 and STB-22-0030 titled "Stability Study Protocol for Regener-Eyes® Ophthalmic Solution, (b)(4) Professional Strength" failed to meet defined objectives, such as (b)(4) failures under (b)(4) conditions at (b)(4) and (b)(4) time points and pH values exceeding defined range under room temperature conditions at (b)(4) .
4Documentation and records
Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced, including specific identification of each batch of component or in-process material used [21 CFR 211.188(b)(3)]. For example, during the inspection on June 20, 2023, you stated that the “tonicity solution” manufactured as an intermediate for your Regener-Eyes® PRO and Regener-Eyes® LITE products contains only sterile (b)(4) sodium chloride. However, completed batch records for your Regener-Eyes® PRO and Regener-Eyes® LITE products do not identify that sterile (b)(4) sodium chloride is used as a component within the manufacture of your Regener-Eyes® PRO and Regener-Eyes® LITE products.
5Laboratory and QC controls
Your firm failed to retain an appropriately identified reserve sample that is representative of each lot or batch of drug product [21 CFR 211.170(b)]. For example, according to your Chief Strategist, your firm discontinued manufacturing your Regener-Eyes® product containing amniotic fluid in approximately June 2021. Given that this product had a labeled two-year expiration date, any batches that your firm manufactured in June 2021 would have expired in June 2023 based on…
6Aseptic processing and sterility assurance
Failure to have an adequate system for monitoring environmental conditions in an aseptic processing area necessary to prevent contamination or mixups [21 CFR 211.42(c)(10)(iv)]. For example, i. You did not establish appropriate written procedures for environmental monitoring (EM) in the aseptic processing areas where your ophthalmic products are manufactured. For example, EM alert or action levels are not defined for viable microorganism monitoring such as active air sampling, surface sampling, and personnel monitoring within your procedures. Further, the action level for viable microorganism EM located in form R-MICRO-F006 “Cleanroom Environmental Sample Incubation Log” is listed as “N/A”. ii. Your environmental monitoring data for viable microorganisms in your aseptic processing area used to manufacture your ophthalmic products was not reliable because your firm did not conduct growth promotion testing for media utilized. Growth promotion testing demonstrates whether the media is capable of supporting the growth of microorganisms that may be present.
7Aseptic processing and sterility assurance
Your firm failed to conduct at least one test to verify the identity of each component of a drug product [21 CFR 211.84(d)(1)]. For example, your firm does not conduct identity tests when receiving lots of sterile (b)(4) sodium chloride, an ingredient used to manufacture the “tonicity solution” and glycerin contained in your Regener-Eyes® PRO and Regener-Eyes® LITE products.
8Aseptic processing and sterility assurance
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, you had not validated your process for cleaning and disinfecting the Biological Safety Cabinets (BSCs) and supporting cleanrooms where your ophthalmic products were manufactured.
