Optikem International, Inc.

During an inspection of your firm located at 2172 S. Jason St. in Denver, CO, on 2/26/24 through 3/1/24, investigators from the United States Food and Drug Administration (FDA) determined that your firm is a manufacturer of the Sereine brand ophthalmic medical device solutions. 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 you dated 3/18/24 concerning our investigators’ 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, your Process Validation procedure is inadequate. Your firm failed to perform aseptic media fills annually, and there is no procedure governing how to validate the mixing and heat treatment step used as part of sterilization of your medical devices.

For example, the Process Validation procedure dated 12/11/1998 is missing requirements per 820.75 including: -820.75(b)(1) that validations are performed by qualified individuals; -820.75(b)(2) the procedure requires validations be documented but does not require all specifics of this regulation such as date performed, and where appropriate, the individuals performing and equipment used are documented.

Your Environmental Controls procedure dated 1/27/2013 requires aseptic media fills (b)(4) to verify effectiveness of clean room disinfection. You stated you have not performed media fills since 2021.

You told our investigators the “mixing process confirmation” should be performed (b)(4) but that this is not documented in a procedure and hasn’t been done since 2021. This process includes the (b)(4) treatment step intended to help sterilize ophthalmic device products.

We reviewed your firm’s response and conclude that it is not adequate. You state you will perform aseptic media fill validation and mixing process confirmation but provide no timeline (except to say “in 2024”) or evidence of corrective action or containment, nor do you address how product manufactured prior to revalidation will ensure it meets specifications. Please review 820.75 and update your procedure and processes to meet all requirements. Please ensure future validation activities include clearly pre-defined acceptance criteria.

Specifically, your Inspection, Measuring and Testing Equipment procedure dated 2/2/2003 is inadequate because it doesn’t include specific directions and limits for accuracy and precision, or remedial action when such limits are not met for all applicable equipment. You also have not implemented the procedure as evidenced by your firm not performing calibration on all applicable equipment.

The (b)(4) Temperature Recorder located on the (b)(4) used to (b)(4) devices during mixing has not been calibrated since 2016. This was cited during our 2017, 2022, and current 2024 inspections.

We reviewed your firm’s response and conclude that it is not adequate. You state you will pursue the issue but provide no timeline, corrective action plan, or if you plan to address this prior to further manufacturing.

Specifically, your Design Controls procedure dated 12/11/1998 was not implemented for the Class II, Sereine Extra Strength Daily Cleaner ophthalmic medical device product. The design file does not include: design input, design output, design review, design verification, design validation, design transfer, or risk analysis for this product.

We reviewed your firm’s response and conclude that it is not adequate. You state you will “enumerate the design as part of finished product acceptance”, reconstruct a risk analysis, and attempt to reconstruct the design verification. You did not provide any timeline or evidence of corrective actions, nor do you address how product manufactured prior to these actions will ensure it meets specifications. Please review 820.30 and ensure your procedure and design files meet all requirements.

Specifically, your CAPA procedure dated 10/19/2007 is not adequate and has not been implemented since 2010. For example, it does not include requirements to: -Analyze sources of quality data to identify existing and potential causes of nonconforming product. -Verify or validate corrective and preventive action to ensure such action is effective and does not adversely affect the finished device. - Ensure information related to quality problems or nonconforming product is disseminated to those directly responsible. -Document all corrective and preventive action activities and their results.

Your firm has been cited for significant quality system deficiencies in the last two FDA medical device inspections in 2017 and 2022, yet your firm has not performed a CAPA since 2010.

We reviewed your firm’s response and conclude that it is not adequate. You state you will “expand CAPA to include all corrections.” You provided no timeline, details of your corrective action plan. Please review 820.100 and ensure your procedure and related records meet all requirements.

Per 21 CFR 807.81(a)(3)(i), a new premarket notification is needed for a change or modification in the device that could significantly affect the safety or effectiveness of the device, e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process. Although the subject devices were initially authorized under PMA, transitional contact lens care products were reclassified in June 1997 to Class II. See 62 FR 30988. Therefore, any changes should be made through the 510(k) process by submitting a new 510(k) when required by 21 CFR 807.81(a)(3)(i). (Link to Reclassification Order: https://www.govinfo.gov/content/pkg/FR-1997-06-06/pdf/97-14751.pdf)

Our inspection also revealed that the Hard Contact Lens Soaking and Cleaning Solution, Sereine Contact Lens Wetting and Soaking Solution, and the Sereine Hard Contact Lens Wetting Solution are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because for these devices your firm does not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g). The devices are also misbranded under section 502(o) of the Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of its intent to introduce the devices into interstate commerce for commercial distribution, in that a notice or other information respecting the modification to the device was not provided to the FDA as required by section 510(k), 21 U.S.C. 360(k), and 21 CFR 807.81(a)(3)(i).

Specifically, you have modified the Sereine Hard Contact Lens Soaking & Cleaning Solution, Sereine Contact Lens Wetting and Soaking Solution, and the Sereine Hard Contact Lens Wetting Solution. These products do not appear to be covered under the approvals provided by your firm during the inspection.

For example:

1) You stated that the Sereine Contact Lens Wetting and Soaking Solution falls under P870051; however, there appears to be a difference in ingredients between P870051 and the batch records for the Sereine Contact Lens Wetting and Soaking Solution. The batch records show the formulation contains (b)(4) and Benzalkonium chloride instead of (b)(4) and EDTA which is found in P870051. The change in ingredients from (b)(4) and EDTA to (b)(4) and Benzalkonium Chloride could significantly affect the safety and effectiveness of the device. For example, Benzalkonium Chloride is a known ocular irritant, or could be at certain concentrations. This change in formulation would need to be assessed for safety and effectiveness, e.g., biocompatibility, lens solution compatibility, and therefore requires a new 510(k) submission.

2) You stated that the Sereine Hard Contact Lens Wetting Solution falls under P870050; however, a comparison of the formulation ingredients between P870050 and the batch record for the Sereine Hard Contact Lens Wetting Solution show that this product does not fall under P870050. It contains different ingredients than what is found in P870050. Specifically, the formulations include the following list of ingredients for those authorized by P870050 and those listed in the batch record for the Sereine Hard Contact Lens Wetting Solution:

P870050 Sereine Hard Contact Lens Wetting Solution (Batch record ingredients)

(b)(4) Water (b)(4) BAK EDTA (b)(4) Water (b)(4) Disodium edetate (EDTA) Benzylkonium chloride (BAK)

The change in ingredients/formulation from what is listed in P870050 to what is found in your batch record for the Sereine Hard Contact Lens Wetting Solution could significantly affect the safety and effectiveness of the device. Changes in the formulation would need to be assessed for safety and effectiveness, e.g., biocompatibility, and lens solution compatibility. Changes to lens parameters could occur, for example, because of absorption of solution components on to the lens material, or because of changes to the osmolality of the solution, which causes shrinking or swelling of the lens material. This change in formulation from P870050 to what is found in your batch record for the Sereine Hard Contact Lens Wetting Solution requires a new 510(k).

3) The batch record for the Sereine Hard Contact Lens Soaking and Cleaning Solution lists the ingredients as (b)(4) water, (b)(4), disodium edetate and benzalkonium chloride. We have conducted a review of our files and have been unable to identify any Food and Drug Administration (FDA) clearance or approval number for the Sereine Hard Contact Lens Soaking and Cleaning Solution containing these ingredients. In order to market this device, you need to submit a 510(k) submission.

For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency. 21 CFR 807.81(b). The kind of information that your firm needs to submit in order to obtain approval or clearance for the devices is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the products may be legally marketed.

The inspection revealed that the Sereine devices are misbranded within the meaning of section 502(c) of the Act, 21 U.S.C. § 352(c), because a word, statement, or other information required by or under authority of section 519 of the Act, 21 U.S.C. § 360i, to appear on the label or labeling of the devices was not prominently placed thereon with such conspicuousness (as compared with other words, statements, designs, or devices, in the labeling) and in such terms as to render it likely to be read and understood by the ordinary individual under customary conditions of purchase and use. In particular, 21 CFR 801.20(a) – which was promulgated under authority of section 519 of the Act, among other provisions – requires, with exceptions not relevant here, that the label and device package of every medical device bear a unique device identifier (UDI) that meets the requirements of 21 CFR Part 801, subpart B, and 21 CFR Part 830. The labels of the Sereine devices do not bear such a UDI.

Specifically, the labels for the Sereine devices do not include a device identifier within the meaning of 21 CFR 801.3 or 830.3, and there is no UDI presented in easily readable plain-text on the label (see 21 CFR 801.40(a)(1)), and there is no UDI presented in machine-readable form that uses automatic identification and data capture (AIDC) technology on the label (see 21 CFR 801.40(a)(2)).

In addition, the Sereine devices are misbranded within the meaning of section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that there was a failure or refusal to furnish any material or information required by or under section 519 of the Act, 21 U.S.C. § 360i, respecting these devices. In particular, 21 CFR 830.300(a) and 830.320(b) – both of which were promulgated under section 519 of the Act, among other provisions – require that the labeler of a device submit electronically to FDA’s Global Unique Device Identification Database (GUDID) the information required by 21 CFR Part 830, subpart E, for each version or model required to bear a UDI. FDA has determined that your firm causes a label to be applied to a device with the intent that the device will be commercially distributed without any subsequent replacement or modification of the label. Optikem is therefore a “labeler” within the meaning of 21 CFR 830.3 and has not submitted to GUDID any information required by 21 CFR Part 830, subpart E, respecting these devices. The failure or refusal to furnish any notification or other material or information required by or under section 519 of the Act, 21 U.S.C. § 360i, also constitutes a prohibited act under section 301(q)(1)(B) of the Act, 21 U.S.C. § 331(q)(1)(B).

Additionally, our inspection revealed you may not have validated your filtration process and that your in-house sterility testing results do not include documented positive controls. Please be sure to document all requirements for future testing and note there are various FDA guidance documents available to help you determine how best to conduct and document testing.

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 to: Jessica Mu, Director of Compliance Branch, at oradevices3firmresponse@fda.hhs.gov. Refer to CMS Case 683606 when replying. If you have any questions about the contents of this letter, please contact: Lauren Priest at Lauren.Priest@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.