LiquidCapsule Manufacturing, LLC

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, LiquidCapsule Manufacturing, LLC, FEI 3006676534, at 9216 Palm River Road, Suite 203, Tampa, Florida, from June 25 to July 3, 2025.

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21, Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

We reviewed your July 25, 2025, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

During our inspection, our investigator observed specific violations including, but not limited to, the following.

1. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).

You failed to conduct adequate identity testing on incoming components used in the manufacture of your over-the-counter (OTC) drug products. For example, you failed to adequately test each shipment of each lot of (b)(4) for (b)(4).

See FDA’s guidance for industry (b)(4).

Identity testing for the high-risk drug component (b)(4) includes a limit test in the United States Pharmacopeia (USP) to ensure the component meets the relevant safety limits for (b)(4). Because you did not perform adequate identity testing using the USP identification test that detects this hazardous impurity, you failed to ensure the acceptability of the component for use in the manufacture of your drug products.

Additionally, you relied on your suppliers’ Certificates of Analysis (COAs) without establishing the reliability of each of your component supplier’s test analysis at appropriate intervals.

In your response, you state that you will establish or revise raw material specification sheets for appropriate comprehensive testing of all incoming materials, and you will review your program for periodically validating supplier COAs for all raw materials.

Your response is inadequate because it does not provide sufficient details to ensure adequate remediation of your incoming materials testing program, and it lacks a retrospective review, analysis, and risk assessment for previously distributed drug products that are within expiry.

Without adequate testing and confirmation of the reliability of supplier test results, you lack scientific evidence that the components used in your drug products conform to appropriate specifications before their use in the drug products you manufacture.

In response to this letter, please provide a comprehensive, independent review of your material system, including but not limited to:

The chemical and microbiological quality control specifications you use to test and release each incoming lot of components for use in manufacturing.

A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COAs instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct the specific identity tests for each incoming component lot.

A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your SOP that describes this COA validation program.

A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.

2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).

Your firm failed to demonstrate that your test methods were appropriate to assure that your product conforms to appropriate standards of identity, strength, quality, and purity. For example, your firm performs assay for (b)(4) using a (b)(4) method. The data you provided to support equivalency of the (b)(4) method to the USP compendial method consisted of assay results for (b)(4) lot of material tested by (b)(4) third-party laboratories. A protocol or report describing the (b)(4) method and its validated state, or criteria for determining its equivalency with the USP method, was not provided. Additionally, you have not adequately qualified the third-party laboratories used to perform your analysis.

In your response, you stated that you would cease use of the (b)(4) method until its equivalence to the compendial method is scientifically demonstrated.

Your response is inadequate because it did not evaluate the distributed batches on which you used the (b)(4) method for your (b)(4) assay test.

Test methods must be validated to show that they are suitable for their intended use and are equivalent to or better than applicable USP compendial methods. The reproducibility of your test methods is essential to determine if your drug products meet established specifications.

In response to this letter, please provide the following:

The method validation protocol, report, and supporting data for your (b)(4) assay method, and any revised methods. Include the scientific rationale for its use as release and stability indicating tests.

A comprehensive assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.

A list of chemical and microbial test methods and specifications used to analyze each lot of your drug product before making a lot disposition decision, and the associated written procedures.

Your firm does not have an adequate stability testing program to demonstrate that the chemical and microbiological properties of your drug products meet established specifications, and that they remain acceptable for the duration of their labeled shelf lives (b)(4). For example, you failed to revise the SOP for your stability program, issued March 23, 2020, as you previously committed to do, and the procedure does not address ongoing stability testing to monitor your drug’s quality attributes throughout its shelf life.

Without an appropriate stability program, you lack adequate scientific evidence to support whether your drug products meet established specifications and retain their quality attributes through your labeled expiry.

In your response, you stated that you will segregate and identify stability samples from retain samples for each manufactured batch, and that you will conduct a thorough inventory and assessment of all existing retain samples to identify batches requiring immediate stability evaluation.

Your response is inadequate because you did not provide suitable justification that the selection of retain samples is adequate to support all existing distributed batches through labeled expiry.

In response to this letter, please provide the following:

A comprehensive assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:o Stability indicating methodso Stability studies for each drug product in its marketed container-closure system before distribution is permittedo An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valido Detailed definition of the specific attributes to be tested at each station (timepoint)

All procedures that describe these and other elements of your remediated stability program.

You failed to ensure that batch records are complete, and that all manufacturing activities and operations are recorded contemporaneously.

For example, the batch record for batch (b)(4), manufactured in December 2024, approximately 6 months before the inspection, did not contain complete information including the full results of in-process testing, and shows multiple instances where initials and dates were pre-filled without documentation of performance, or evidence of performance. Information provided by your firm for batch (b)(4) indicates that this batch was distributed on (b)(4), although the “QA Checklist” for batch record review and release was not completed.

In your response, you state that you conducted a review of the (b)(4) batch production records to identify any other similar documentation omissions or discrepancies and to assess their potential impact on product quality or safety.

Your response is inadequate because you did not expand your review to all drug products, in individual configurations, for lots previously distributed and within expiry. You also did not include an investigation to determine the root cause of the incomplete documentation or assess the impact on finished batches.

Complete and accurate batch production and control records are necessary to ensure that manufacturing processes are consistently followed and are reproducible. Additionally, incomplete manufacturing records deprive you of the ability to reliably conduct batch record review, to adequately investigate deviations and batch failures, and to ensure a continued state of validation processes.

In response to this letter, please provide the following:

A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient.

A detailed CAPA plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.

5. 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)).

Inadequate Process System Validation

Your firm failed to adequately validate the manufacturing process for your drug products. The validation data provided from 2017 does not include the filling and packaging of your drug product into the final containers. You had previously committed to providing a retrospective validation report; however, to date there does not appear to be any evaluation or documentation establishing equivalency between your validation data from 2017 and your current manufacturing process, including the difference in batch size.

In your response, you stated that you would retrospectively assess the 2017 bulk manufacturing process validation and evaluate its adequacy, considering current understanding and practices. You also stated that you would perform prospective process validation for each OTC drug product.

Your response is inadequate because it does not address the absence of validation for the filling and packaging process and lacks details regarding your prospective process validation plan.

In response to this letter, please provide the following:

A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification, and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.

A timeline for performing appropriate process performance qualification (PPQ) for each of your marketed drug products. Also provide a risk assessment and any follow up actions to be taken for the distributed drug products produced without performing any process validation studies.

Process performance protocol(s), and written procedures for qualification of equipment.

A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.

Lack of (b)(4) System Validation

You failed to adequately validate your (b)(4) system to ensure it produces (b)(4) that meets appropriate chemical and microbial attributes for use in your OTC drug product manufacturing. In addition, you failed to demonstrate that your (b)(4) system was adequately monitored to ensure it consistently produced (b)(4) that met appropriate chemical and microbial quality standards. For example, you failed to conduct (b)(4) testing, and you did not monitor your (b)(4) system for Burkholderia cepacia complex (BCC).

Furthermore, the COAs you provided for routine testing of (b)(4) samples show that your (b)(4) is tested according to standard methods for (b)(4), and that the specifications listed on the COAs do not match those required by your SOP “MPC-5005 Rev 1 (b)(4) System Monitoring, Testing, and Usage.” For example, the COA requires a total plate count <(b)(4) cfu/g; however, your SOP specifies the acceptable range for total plate count as (b)(4) cfu/g – (b)(4) cfu/g.

(b)(4) must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes. Routine monitoring of microbial counts, with appropriate specifications, and identity of contamination in the system is integral to ensuring oversight of the ongoing state of control and the suitability of (b)(4) for use in manufacturing operations.

In your response, you state that you have initiated a comprehensive validation study of the (b)(4) system and will revise procedures for monitoring to include appropriate chemical and microbiological testing, including for Burkholderia cepacia Complex (BCC).

Your response is inadequate because you did not provide the details of your validation study or the revised procedures and specifications for routine monitoring or usage.

In response to this letter, please provide the following:

A procedure for your (b)(4) system monitoring that specifies adequate, routine microbial testing of (b)(4) to ensure its acceptability for use in each batch of drug products produced by your firm.

The current limits for total counts and objectionable organisms used for your (b)(4) system. Ensure that the total count limits for your (b)(4) are appropriately stringent in view of the intended use of each of the products produced by your firm.

In a previous inspection, dated February 5 to February 9, 2024, FDA cited similar CGMP observations. Following a July 2024 regulatory meeting, you proposed specific remediation to your stability program. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.

Your firm’s quality systems are inadequate. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.

Because you failed to correct repeat violations, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements.

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

Correct any violations. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice, including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts

Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3006676534 and ATTN: Maria Pavco.