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May 2, 2019

 

Case #568180

 

WARNING LETTER

 

VIA UPS Overnight

Return Receipt Requested

 

Mr. Liaquat A. Kasi, CEO

AMMD Labs, LLC

1501 Green Rd Ste J

Pompano Beach, FL 33064

 

Mr. Kasi:

 

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, AMMD Labs, LLC (FEI 3010869933), at 1501 Green Rd Ste J Pompano Beach, from September 10 to 14, 2018.

 

This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 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).

 

You did not respond to the Form FDA 483 within 15 business days of the inspection. FDA acknowledges 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 perform, 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 (b)).

 

Your firm manufactures and distributes topical sunscreen and anti-blemish over-the-counter (OTC) drug products. Our inspection found that you did not test your finished drug products to confirm their identity or potency prior to releasing those products to the U.S. market. Specifically, your firm could not provide data to show that identity and potency testing was performed for the active ingredients in your OTC topical products.

 

In addition, your firm lacked adequate testing for microbial attributes. For example, you did not have an adequate program for growth promotion testing of media used for microbial testing. Additionally, during microbial testing prior to release, you failed to inactivate your preservatives.

 

Appropriate testing is essential to determine if the drug products you manufacture meet established specifications for chemical and microbial attributes.

 

Your response stated that you will utilize contract facilities for finished product testing. Your response was inadequate. You failed to include sufficient detail about the selection, qualification, and oversight procedures you will use to engage contract testing laboratories. In addition, you did not provide a corrective action and penetrative action (CAPA) with timelines for testing and reviewing distributed drug products within expiry.

 

In response to this letter, provide:

• A list of chemical and microbial test methods and specifications used to analyze each batch of your drug product before making the batch disposition decision and associated written procedures.
• A summary of results obtained from testing batch retain samples of all drug products within expiry. Include results for identity and strength of active ingredients and all other appropriate chemical and microbial quality attributes.
• A comprehensive review of your laboratory practices, procedures, methods, equipment, and analyst competencies. Based on this review, provide a detailed CAPA plan to remedy your laboratory system. Your plan should include the process you will use to evaluate the effectiveness of the implemented CAPA plan.
• A summary of your hold time studies for keeping your product up to two years and whether it can continue to meet all its attributes.
• Your timeline for the selection of contract laboratories you will rely on to test any component or finished product. Include qualification procedures for your contract laboratories.
• If you find that you released any batch with out-of-specification (OOS) results, indicate the corrective actions you will take, such as customer notifications and product recalls.

2. 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)).

Production process validation

You failed to validate the processes used to manufacture the drugs you distributed. For example, you did not perform process qualification studies, nor did you have a rigorous ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality. Your firm has not demonstrated that you can consistently deliver quality products.  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.

 

Inadequate control of water system

Your firm uses a “(b)(4)” water system that is not appropriately designed. For example, your system contained a dead leg, which can foster the development of biofilms. In addition, you lacked validation studies for this water system. Your firm has not demonstrated that you can effectively design, control, maintain, and monitor the system so it consistently produces pharmaceutical grade water that, at a minimum, meets the USP monograph for purified water and appropriate microbial limits. Water from this system is a component in your drugs.

 

Your response stated that you made changes to unspecified “protocols” and would submit changes at a later date.

 

Your response was inadequate. It is unclear as to which “protocols” you are referring to in your response. Furthermore, we cannot evaluate the adequacy of your “protocols” since you did not include copies. In addition, you failed to describe any remediation to your water system deficiencies. You also failed to assess the impact of water from this deficient system on the quality of your drug products in distribution.

 

In response to this letter, provide:

• A data-driven and scientifically sound program that identifies and controls all sources of variability, such that your production processes will consistently meet appropriate parameters and manufacturing standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, ensuring quality of input materials, and determining the capability and reliability of each manufacturing process step and control.
• Timelines for performing prospective process qualification for your drug products.
• A comprehensive evaluation of the water system design, including a thorough CAPA plan to install and validate a suitable water system.
• An effective program for ongoing control, maintenance, and monitoring that ensures the remediated system consistently produces water that meets USP monograph specifications and appropriate microbial limits.
• A detailed risk assessment addressing the potential effects of the deficient water system on the quality of all drug product lots currently in U.S. distribution within expiry. Specify actions that you will take in response to the risk assessment, such as customer notifications and product recalls.

3. 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)).

You lack adequate stability data to support your three-year expiration dates for your drug products. Your firm could not provide sufficient data demonstrating that the chemical and microbial attributes of your drug products remain acceptable throughout their assigned shelf life. Without an adequate stability program, you cannot confirm that your drug products continue to meet established specifications and all pre-determined quality criteria throughout their shelf life.

 

Your response stated you have created documentation supporting your “period after opening policy.” You also stated that you placed (b)(4) at specific areas in your stability chambers to monitor temperature uniformity. Your response further stated that you “placed packaging on stability” for (b)(4) to verify in-use stability.

 

Your response was inadequate. You failed to provide data to support this “period after opening policy.” It is unclear how this policy is capable of monitoring the stability of your drug products marketed in the U.S. for their intended shelf life. Your response also lacked details as to the products you placed on stability and their packaging configuration. Furthermore, you failed to describe testing of retain samples to assess the stability of products currently in distribution.

 

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

• A remediated SOP describing your stability program.
• Stability indicating methods, including validation and qualification of those methods.
• Stability studies for each drug product in its container-closure system to evaluate whether labeled shelf life and distribution are supported.
• 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.
• Specific attributes to be tested at each station.

4. Your firm failed to establish a quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products, including drug products manufactured, processed, packed or held under contract by another company. Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit (21 CFR 211.22(a) and (d)).

You lacked an adequate quality unit (QU). For example, you did not follow your procedure “Responsibilities, Authority and Duties of the Quality Control and Quality Assurance Department” (GP-0002), which details roles and responsibilities of the QU. Your procedure states the QU should “approve or reject all phases of the manufacturing, finished bulk, raw materials, packaging components, in process products / phase of production, labeling components (labels and silk screen packaging) and finished goods.” However, your QU did not adequately test or evaluate raw materials prior to releasing them as components used in the manufacturing your drug products. During the inspection, your firm told our investigator the QU did not have the resources to perform this operation on every incoming shipment, and occasionally compares the manufacture’s labels with the label printed by the receiving warehouse.

 

Because your QU failed to fulfill its role, you lacked assurance that appropriate manufacturing and quality standards are met for each of your drug products.

 

Your response stated that a training gap analysis has been performed for your QU. You also stated you will update and create SOPs relevant to your manufacturing department.

 

Your response was inadequate. You did not adequately detail how your quality function will be improved with respect to oversight of manufacturing quality. You also lacked details for describing your gap analysis and its conclusions. In addition, you failed to assess the impact that your insufficient QU oversight had on product quality.

 

In response to this letter, provide a full list of procedures applicable to your QU and a comprehensive assessment with CAPA to ensure 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 products.

Quality Unit Authority

 

Significant findings in this letter indicate that your quality unit is not fully exercising its authority and/or responsibilities. Your firm must provide the quality unit with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality.

 

CGMP consultant recommended

 

Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. We also recommend that the qualified third party perform a comprehensive audit of your entire operation for CGMP compliance and evaluate the effectiveness of your corrective actions and preventive actions.

 

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

 

Misbranding and Unapproved Drugs

 

Product labels were collected during the inspection. The FD&C Act defines cosmetics and drugs by their use. As such, if a product or ingredient is intended to affect the structure or function of the body, or to have a therapeutic effect, such as treating or preventing disease, it is a drug.

 

Although you purport that your products are marketed as cosmetics, the products’ labeling contains treatment claims such as, but not limited to: prevention of bruising and scarring, blemish treatment, sun protection, and anti-inflammatory properties. Claims such as these meet the definition of a drug as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because they are intended for the diagnosis, cure, mitigation, treatment, or prevention of disease and/or defined by section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because they are intended to affect the structure or any function of the body.

 

For an OTC drug product to be legally marketed it must be the subject of an approved application or must meet the formulation and labeling conditions described in an applicable OTC monograph and meet each of the general conditions set forth in 21 CFR 330.1. The labeling for OTC drug products must comply with all of the requirements of section 502 of the FD&C Act and all pertinent regulations found in Title 21 of the Code of Federal Regulations (21 CFR). If a product does not meet these conditions, then it could be considered an unapproved new drug and/or misbranded. Additionally, please be aware that a product that is both a cosmetic and drug must meet the requirements for both cosmetics and drugs.

 

For more information on the differences between cosmetics and drugs, please see Is It a Cosmetic, a Drug, or Both? (Or Is It Soap) on our website:

https://www.fda.gov/cosmetics/cosmetics-laws-regulations/it-cosmetic-drug-or-both-or-it-soap

 

Conclusion

 

Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations.

 

Until these violations are corrected, we may withhold approval of pending drug applications listing your facility. We may re-inspect to verify that you have completed your corrective actions. We may also refuse your requests for export certificates.

 

After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your violations deviations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion. Please identify your response with FEI 3010869933.

 

Your written notification should refer to Case #568180.

 

Please address your reply to Ms. H.L. Jamillah Selby, Compliance Officer, at 4040 N. Central Expressway, Suite 300, Dallas Texas 75204.  In addition, please submit a signed copy of your response to [email protected] and [email protected].

 

If you have questions regarding the contents of this letter, you may contact Ms. Selby, at 214-253-5218 or [email protected].

 

           

 

Sincerely,

/S/

Monica R. Maxwell

Program Division Director

Office of Pharmaceutical Quality Operations, Division II