Findings citing 21 CFR 210.1

You did not commit to revising the minor defect classification for “[f]oreign (unusual) material, e.g., cardboard trapped between stopper ribs” to account for the criticality of the foreign material. While you noted that any units exhibiting this defect are rejected, the defect rate limit applied to minor defects ( (b)(4) %) is not appropriate for adequately investigating, trending, and performing corrective actions, as necessary, to mitigate this contamination risk. You did not provide adequate documentation to demonstrate that foreign materials are contained within the ribs of the syringe stoppers in non-product-contact area and will not pose contamination risks to the drug product. In addition, the syringe filling process demonstrates that the foreign material does come into contact with product-contact area of the syringes. For example, any cardboard particles trapped within the syringe ribs may be pressed against the inner syringe wall during filling, potentially introducing particles onto a surface that subsequently contacts the drug product solution. In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. [See 21 CFR 210.1(b), 21 CFR 200.10(b).] FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third-party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation. D.

Your response acknowledges the lack of validated mixing and (b)(4) parameters but treats full process validation (CAPA-2025-0013) as conditional, only to be prioritized if future potency variability or out of specification (OOS) events occur. You provided no root-cause analysis explaining why critical process parameters remained undefined and operator-dependent for an extended period despite a prior OOS investigation. You also submitted no supporting documentation for PLANDEV-2025-0028, no revised master production records or executed batch record examples showing the new parameters, and no completion date or detailed validation plan for CAPA-2025-0013. In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. [See 21 CFR 210.1(b), 21 CFR 200.10(b).] FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third-party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation. D.

Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)). Under section 301(a) of the FD&C Act [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FD&C Act [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated. Unapproved New Drug Products You do not have any FDA-approved applications on file for the ineligible drug products that you compounded. 5 Under sections 505(a) and 301(d) of the FD&C Act [21 U.S.C. § 331(d)], a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FD&C Act is in effect for the drug. Marketing of these products, or other applicable products, without an approved application violates these provisions of the FD&C Act. Misbranded Drug Products The ineligible drug products you compounded are intended for conditions not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layman can use these products safely for their intended uses. Consequently, their labeling fails to bear adequate directions for their intended uses. 6 Accordingly, these ineligible drug products are misbranded under section 502(f)(1) of the FD&C Act. The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FD&C Act. It is also a prohibited act under section 301(k) of the FD&C Act to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being misbranded. D. Corrective Actions We have reviewed your firm’s response to the Form FDA 483. Regarding your response related to the insanitary conditions, some of your corrective actions appear adequate; however, we cannot fully evaluate the adequacy of the following corrective actions described in your response because you did not include sufficient information or supporting documentation. Specifically, your response states that the smoke study under Rev. 005 was executed March 30 – April 3, 2026, but the April 2026 study is still under post-execution review and has not been finalized or provided to FDA. Per your response, the study “remains in controlled post-execution review.” It is unclear whether your firm has completed the post-execution review, as no final formal summary report has been provided. Regarding your response related to the insanitary conditions, the following corrective actions appear deficient. With respect to your aseptic media fill simulation executed in January 2026, we note that the summary states, “Following the 14-day incubation period, all vials were visually inspected for turbidity or microbial growth. No contamination was observed in any of the (b)(4) vials, confirming the sterility assurance of the process.” However, our review of the media fill test records and the vials documented across the (b)(4) revealed gaps and discrepancies. The summary report does not appear to match the number of vials inspected per the documents provided in the media fill test records. Specifically, based on the vials recorded across all the (b)(4) records, it appears up to (b)(4) vials were examined. No explanation was provided for the discrepancy in the total number of vials. The documents provided show no records for (b)(4) . Furthermore, the records document results for (b)(4) , with no documentation or explanation for (b)(4) . It is unknown if these (b)(4) exist. Additionally, upon review of the documents, multiple (b)(4) were labeled as “N/A.” It is unknown what the designation “N/A” means, as it is not defined or explained in the records. Based on the documents provided, it is unclear how your firm counted and determined that no contamination was present in a total of (b)(4) vials. There appears to be a gap in the documentation with no explanation provided. The summary report claims all vials were inspected and none showed contamination; however, based on the information provided the claim cannot be supported if records do not clearly demonstrate that all vials were accounted for and inspected. Finally, our review also noted multiple media fill records were transcribed on Form Revision 3 because the original results were documented on the wrong form. Transcribing original data onto a different document, even if done for legitimate administrative reasons, must be carefully controlled, documented, and justified. Without a clear audit trail showing why results were rewritten and who authorized it, this practice raises concerns about whether the data accurately reflects what actually occurred during the media fill. Please be aware that section 501(a)(2)(A) of the FD&C Act concerning insanitary conditions applies regardless of whether drug products you compound meet the conditions of section 503A, including the condition that drug products that are essentially copies of commercially available drug products not be compounded regularly or in inordinate amounts. Should you continue to compound and distribute drug products that do not meet the conditions of section 503A, the compounding and distribution of such drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the drug CGMP regulations.…

Regarding your failure to establish an adequate system for monitoring environmental conditions in aseptic processing areas: We acknowledge your response regarding the failure to adequately perform active and passive air sampling within the ISO 5 area during aseptic operations, including your plan to initiate active air monitoring during filling operations. We recognize the importance of conducting effective environmental monitoring while minimizing the risk of contamination…

Regarding the textured panels in your cleanroom suite, the manufacturer’s Technical Data sheet indicates the panels with textured or smooth surface have fire, mold and mildew resistance. However, there is no statement in the Technical Data sheet supporting the panel’s suitability for cleanroom applications, especially for pharmaceutical manufacturing facilities producing products intended to be sterile. Your response is inadequate because you have not evaluated the risk…

Regarding your firm’s failure to establish the reliability of your component supplier’s test analyses (i.e., Certificates of Analysis) at appropriate intervals, as well as your failure to conduct at least one test to verify the identity of each shipment of every lot of components: We acknowledge the actions your firm has taken in response to the failure to conduct at least one identity test on each shipment of every lot of components, including APIs. Specifically, we note…