LS Promotions Inc. MARCS-CMS 685889 — August 05, 2024

WARNING LETTER

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• Delivery Method: Via Email
• Product: Drugs

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• Recipient: Mr. Lesley Stier; Owner; LS Promotions Inc.; 530 West John Street; Hicksville, NY 11801; United States

• Issuing Office: Division of Pharmaceutical Quality Operations I; United States

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Warning Letter 685889

August 5, 2024

Dear Mr. Stier:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, LS Promotions Inc., FEI 3002657228, at 2905 Veterans Memorial Highway, Suite 3, Ronkonkoma, NY, from April 24 to May 2, 2024.

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 May 15, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

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

1. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release, and for each batch of drug product required to be free of objectionable microorganisms, appropriate laboratory testing, as necessary (21 CFR 211.165(a) and 211.165(b)).

Your firm failed to adequately test your over-the-counter (OTC) drug products, including the identity and strength of each active ingredient, prior to release and distribution into the U.S. market. You also failed to ensure adequate microbiological testing for each batch of your drug products prior to release. This includes your sun protection factor (SPF) 15 lip balm, SPF 30 sunscreen, and hand sanitizer drug products.

Testing is essential to ensure that the drug products you manufacture conform to all pre-determined quality attributes appropriate for their intended use. Because you lacked adequate testing of each batch of your drug products, you do not know whether they conform to all appropriate finished product specifications and are suitable for release to consumers.

In response to this letter, provide a list of chemical and microbial specifications, including test methods, used to analyze each batch of your drug products before a batch disposition decision.

• An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.

• A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.

2. 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)).

Your firm did not have adequate stability data to demonstrate that the chemical and microbiological properties of your drug products met established specifications and remain acceptable throughout their assigned shelf-life.

Your firm purchases and fills bulk liquid drug products into smaller containers. While you applied an expiration date that did not exceed the expiration date provided by your suppliers, this practice is not acceptable without adequate supporting data. Liquid drug products are substantially more susceptible to degradation compared to other dosage forms. You did not have data to demonstrate the stability of these products in their finished containers throughout their shelf-life.

Notably, you also further manipulate your supplier’s SPF 15 lip balm bulk drug product by adding additional ingredients prior to filling. You did not have data to demonstrate the stability of this product in its finished containers throughout their shelf-life.

Your response is inadequate. While your firm committed to conducting a shelf-life study for your SPF 15 lip balm drug product, you did not provide supporting documentation to include a description of your analytical tests and specifications, or a timeframe for completion. You also did not commit to conducting shelf-life studies for your other drug products which include your SPF 30 sunscreen and hand sanitizer drug product.

Without appropriate stability studies, you do not have scientific evidence to support whether your drug products meet established specifications and retain their quality attributes through their
labeled expiry.

In response to this letter, provide a comprehensive assessment and corrective action and preventive action (CAPA) plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:

• Stability-indicating methods.

• Stability studies for each drug product in its marketed container-closure system before distribution is permitted.

• 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 valid.

• 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.

3. 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, and your firm’s quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)).

Your firm failed to adequately validate the manufacturing processes used for the production of your drug products, including qualifying your manufacturing equipment. Your firm also lacked a bulk hold time study for your SPF 15 lip balm drug product which you stated could be held up to (b)(4) days prior to filling. Additionally, you failed to demonstrate that your cleaning procedure is sufficient to adequately clean each type of equipment (including filling equipment which is shared for multiple drug products) in a reproducible and effective manner.

Your response is inadequate. You did not commit to conducting process validation for your drug product manufacturing operations performed at your facility or for validating your cleaning procedure to ensure it is reproducible and effective. While we acknowledge your commitment to qualify your drug manufacturing equipment, you did not provide a timeframe for completion or supporting documentation to demonstrate implementation.

Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and ensure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure that you maintain a stable manufacturing operation throughout the product lifecycle.

See FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/media/71021/download.

In response to this letter, provide:

• 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 (PPQ), and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.

• A timeline for performing appropriate PPQ for each of your marketed drug products.

• Include your process performance protocol(s), and written procedures for qualification of your equipment and facility.

• 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.

• Appropriate improvements to your cleaning validation program, with special emphasis on incorporating conditions identified as worst-case in your drug manufacturing operation. This should include, but not be limited to, identification and evaluation of all worst-case:
  o Drugs with higher toxicities
  o Drugs with higher drug potencies
  o Drugs of lower solubility in their cleaning solvents
  o Drugs with characteristics that make them difficult to clean
  o Swabbing locations for areas that are most difficult to clean
  o Maximum hold times before cleaning

• In addition, describe the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new product.

• A summary of updated standard operating procedures that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.

4. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).

Your quality unit (QU) did not provide adequate oversight for the manufacture of your drug products. For example, your QU failed to ensure the following:

• Establishment of adequate procedures describing the QU’s responsibilities (21 CFR 211.22(d)).

• At least one test to verify the identity of each component of a drug product (21 CFR 211.84(d)(1)).

• Strict controls over labeling issued for use in drug product labeling operations (21 CFR 211.125(a)).

Your response is inadequate. While you state that you will revise your QU procedures, you did not provide further details including supportive documentation and evidence of implementation.

Your firm’s quality systems are inadequate. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help in 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.

In response to this letter, provide a comprehensive assessment and remediation plan to ensure that your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:

• A determination of whether procedures used by your firm are robust and appropriate.

• Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.

• A complete and final review of each batch and its related information before the QU disposition decision.

• Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all drug products.

CGMP Consultant Recommended

Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPAs before you pursue resolution of your firm’s compliance status with FDA.

Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

Conclusion

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 promptly. 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.

Please send your firm’s response electronically to orapharm1_responses@fda.hhs.gov. Also, please identify your correspondence with FEI 3002657228, and WL 685889. If you have any questions, please contact Samina Khan, Compliance Officer, at samina.khan@fda.hhs.gov.

Sincerely,
/S/

Lisa Harlan
Program Division Director
Office of Pharmaceutical Quality Operations Division I