Microspecialties, LLC

During an inspection of your firm located in Middletown, CT, from January 14, 2025, through February 18, 2025, an investigator from the United States Food and Drug Administration (FDA) determined that your firm contract manufactures Class I and II ophthalmic surgical devices such as sterile I-PACK injection kits, punctum plugs, and microkeratome blades. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.

This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.

We received a response from Rick Brinsmade, Quality Assurance and Regulatory Affairs (QA/RA) Manager, dated March 4, 2025 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:

Specifically, you failed to implement section 6.13 of your “Sterilization Process Control” procedure (QA-0041; Rev 3; Effective: 1/27/23) which requires release of sterile products to inventory via Form 0070 once accompanying dosimetry records and certificates of processing (COPs) are received back from the contract sterilizer. For example, you stated that Form 0070 was never utilized to release (b)(4) boxes of I-PACK injection kits (Lot #: P62764979R, P63044983R, P62764965R and P62764970R) into inventory because you fabricated the (b)(4) sterilization COPs ((b)(4) and (b)(4)) as if they originated from the customer-approved contract sterilizer. Subsequently, on 03/21/24, your Director of Quality Assurance released the above nonconforming lots of I-PACK injection kits, which are intended for administration of intravitreal injections during eye surgery, as sterile to your customer on 3/12/24 despite never shipping these products to the customer-approved contract sterilizer (or elsewhere) for sterilization. This event resulted in a Class II recall RES 94794 initiated by your firm on 6/5/24 followed up by a Class I recall by your customer on (b)(4) under RES (b)(4).

The adequacy of the response dated 3/4/25 cannot be determined at this time. Under CAR # 1288 (2/20/25) opened to address the failure to follow QA-0041, you reference CAR # 1261 (5/31/24) for the root cause which pointed to limited resources, lack of effectiveness of training, storage of product in a non-routine location, and lack of (b)(4) sterilization labels. Corrective actions included notification of the nonconforming lots to your customer upon discovery of the error; replacement of your Director of Quality Assurance with a new Quality Assurance and Regulatory Affairs Manager; addition of (b)(4) exposure indication dots to shipping cartons; update of Form 0070 to include verification of (b)(4) indicator dot color changes; update of QA-0041 to restrict product release to QA, President, or Administrative Assistant; update the training procedure (QA-0019) to include effectiveness tests, including a test for sterilization processes; and retrospective review of sterilization and release documentations to verify accuracy. Under CAR # 1289 (2/20/25) opened to address release of nonconforming product, you also reference the root cause(s) and several of the corrective actions above under CAR # 1261 and note additional completed actions which included the requirement for (b)(4) irradiation exposure dots on shipping cartons and process specifications for your new contract sterilizer in QA-0041; addition of integrity requirements to the document, part number, and data control procedure (QA-0020); and a new code of conduct and ethics procedure (QA-0099) for which all employees completed training. By 6/1/25, you plan to also add irradiation exposure dots to each individual carton of trays and microkeratome blades. Please provide updates on the progress of these corrective actions and corrections, including any supporting evidence.

2. Failure to ensure that when the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a).

Specifically:

a. You failed to implement sections 5.1.2 and 5.2.1 of your “Process Validation” procedure (QA-0063; Effective: 11/8/23) which requires that Operations (with input from Quality) determine “***if re-validation is needed for changes to validation manufacturing processes***” and that Quality “***Reviews and approves the assessments of validation needs and revalidation determinations***,” respectively. For example, you authorized the release of lots (b)(4) on 9/4/24; (b)(4) on 10/14/24; and (b)(4) on 11/19/24, containing medical devices, such as punctum plugs, customized injection trays, microkeratome blades, microkeratome tubing, and ophthalmic convenience kits, for distribution without documented justification for why a revalidation was not required, prior to switching to a new contract sterilizer for (b)(4) sterilization of such devices on 3/19/24.

b. You failed to implement sections 1.0 and 2.0 of your “Process Validation” procedure (QA-0063; Effective: 11/8/23) which require validations of processes related to inventory items such as “***a component, material, assembly, packaging, and labeling that is part or will become part of the finished medical device including the finished medical device***.” For example, you did not conduct a validation of the (b)(4) inspection method outlined in section 6.1.2 of the “Seal Inspection” procedure (QA-0042; Effective: 6/30/24) for testing the seal integrity of sterile pouches containing Microkeratome Blades, to ensure that manufacturing employees are able to repeatably and reproducibly able to detect conforming and nonconforming seal pouches with a high degree of assurance as a part of finished device acceptance. These devices are indicated for use during LASIK surgery to shave tissue from sections of the cornea for a lamellar (partial thickness) transplant.

The response dated 3/4/25 is not adequate. Under CAR # 1290 (2/20/25) initiated to address release of sterile products prior to conducting a revalidation for the new contract sterilizer, you state that management did not believe that a revalidation was required because the new contract (b)(4) sterilizer was able to sterilize the product with the specified dose mapping and dose audits and bioburden testing continued. In addition, you point out that your newly hired QA/RA manager determined that a retrospective validation was required such that a comprehensive validation was conducted and formally approved on 12/16/24. However, there were no corrective actions identified to address the primary issue which is that you did not follow your procedure to review and approve your decision not to revalidate the sterilization process at the time these products were released for distribution.

With regards to the lack of test method validation for the seal integrity inspection, you state that you will write a formal process adoption by analyzing the data outputs from the seal validations by 5/1/25. However, there were no corrective actions identified to review whether any other test methods require process validations to demonstrate that that you are able to consistently detect conforming and nonconforming product with a high degree of assurance. Therefore, please provide a response on how you plan to address the above deficiencies.

Specifically, you acknowledged there was no statistical rationale documented for the sampling plan in section 6.1.2 of the “Seal Inspection” procedure (QA-0042; Effective: 6/30/24) to inspect the first (b)(4) pouches for seal integrity.

The response dated 3/4/25 is not adequate. Under CAR # 1290 (2/20/25) initiated to address the lack of test method validation for the seal integrity inspection as well as failure to provide statistically supported evidence when sampling, you state that you will write a formal process adoption by analyzing the data outputs from the seal validations by 5/1/25. However, there were no corrective actions identified to address the concerns relating to lack of valid statistical rationale for the sampling plan employed during sealing inspections of sterile pouches. Therefore, please provide a response on how you plan to address the above deficiencies.

Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.

Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.

Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.

Your firm’s response should be sent via email to Gina Brackett, Establishment Assessment Team 1 (EAT-1) Assistant Director at CDRHEnforcement@fda.hhs.gov. Please include in the subject line, “CMS Case # 707614” when replying. If you have any questions about the contents of this letter, please contact: Sargum C. Morgan, Compliance Officer at sargum.morgan@fda.hhs.gov.

Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.