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Warning Letter 320-24-47

June 18, 2024

Dear Mr. Gomez:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Laboratorio Magnachem International, FEI 3003320065, at Avenida Jose Francisco Pena, Esquina Calle K, Haina, San Cristobal, from November 7 to 10, 2023.

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).

In addition, the drug products Broncochem Kids COLD & FLU SYRUP, Broncochem COLD & FLU CAPLETS, Broncochem EXPECTORANT SYRUP, Broncochem Kids MAXIMUM COUGH, and Broncochem MAXIMUM COUGH are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a), and are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(d) and (a) of the FD&C Act, 21 U.S.C. 331(d) and (a). These violations are described in more detail below.

We reviewed your December 1, 2023 response to our Form FDA 483 in detail.

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

1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

You failed to conduct adequate investigations into out-of-specification (OOS) stability testing results and missing stability intervals for your multiple drug products. For example, our investigator observed failing assay results for Phenylephrine at 3 month and 6 month timepoints for your drug product Broncochem Kids Cold and Flu Syrup, batch (b)(4). Additionally, your stability data for this product was missing analytical and microbial analysis at several intervals. In your response, you attribute the OOS stability results to storage condition and test methods. You claim that the storage temperature for the drug products should be 25°C instead of 30°C. Also, you state that your stability test methods were not validated with the updated software and did not yield reproducible results.

Your response is inadequate. Your investigations lack sufficient rigor and scope in determining root causes and the extent of impact to other batches and products. You do not identify or implement corrective action and preventive action (CAPA), nor do you conduct a risk assessment for products on the U.S. market and within expiry. Additionally, no documentation is provided for the missing stability testing timepoints.

It is necessary to conduct a thorough investigation to evaluate all potentially affected batches and implement a timely and effective CAPA. Inadequate investigations can lead to unidentified root causes, ineffective CAPA, and recurring problems that compromise the ability to manufacture safe and effective drug products.

FDA held a teleconference with your firm on February 9, 2024, to discuss our concerns regarding your Broncochem Cold and Flu drug products and recommended a voluntary recall of five batches in the U.S. market due to stability testing failures. We acknowledge you have initiated the recall of Broncochem Cold and Flu Syrup Kids (batches 223063 and 223002) and Broncochem Cold and Flu Tea (batches 123255, 123256, and 123637) drug products. You also committed to conduct retrospective testing on all batches of products using retention samples with the updated validated method and expand the recall scope if any additional failures are observed.

For more information about handling failing, out-of-specification, out-of-trend, or other unexpected results and documentation of your investigations, see FDA’s guidance document Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production at https://www.fda.gov/media/158416/download.

In response to this letter, provide:

• A retrospective, independent review of all invalidated OOS (including in-process and release/stability testing) results for U.S. products currently in the U.S. market and within expiry as of the date of this letter and a report summarizing the findings of the analysis, including the following for each OOS:
  o Determine whether the scientific justification and evidence relating to the invalidated OOS result conclusively or inconclusively demonstrates causative laboratory error.
  o For investigations that conclusively establish laboratory root cause, provide rationale and ensure that all other laboratory methods vulnerable to the same or similar root cause are identified for remediation.
  o For all OOS results found by the retrospective review to have an inconclusive or no root cause identified in the laboratory, include a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history). Provide a summary of potential manufacturing root causes for each investigation, and any manufacturing operation improvements.

• A comprehensive review and remediation plan for your OOS result investigation systems. The CAPA should include but not be limited to addressing the following:
  o Quality unit oversight of laboratory investigations
  o Identification of adverse laboratory control trends
  o Resolution of causes of laboratory variation
  o Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identified
  o Adequately scoping of each investigation and its CAPA
  o Revised OOS investigation procedures with these and other remediations

• Your action plan to address any product quality or patient safety risks for your drug products in U.S. distribution, including potential customer notifications and recalls.

• A revised test method validation procedure and protocol.

• List of all batches released to the U.S. market with specifications and results for release and stability.

• A retrospective testing and review of all batches using retain samples with the revised validated method.

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 lacked adequate laboratory controls. For example:

Failure to Establish Adequate Test Methods

You failed to adequately establish microbiological test methods for objectionable microorganisms, microbial counts, and detection of Burkholderia cepacia complex (BCC). Your quality unit confirmed that you have not performed adequate method validation and United States Pharmacopeia (USP) method verification to ensure your microbial test methods accuracy and reliability.

In your response you claim that your method is validated and your testing protocol incorporates an assessment of Burkholderia.

Your response is inadequate. You do not provide sufficient evidence to show that your current microbiological testing methods are suitable for your intended use. Additionally, there is no evidence of retrospective review and risk assessment evaluating the products within expiry in the U.S. market.

In the absence of an adequate method validation and USP method verification, there is no assurance that your test method is suitable. Additionally, water systems, when not adequately qualified, maintained, or monitored have been known to be the source of microbial contamination in finished drug products. Pathogenic organisms, including B. cepacia, thrive within inadequate water systems and have caused serious injury and death to consumers.

It is important that your test methods are properly verified or validated, and that you use appropriate test methods to make proper decisions (e.g., batch disposition). Results generated using unverified or unvalidated methods can be misleading and may put consumers at risk. For general principles and approaches that FDA considers appropriate elements of method validation, see FDA’s guidance document, Analytical Procedures and Methods Validation for Drugs and Biologics at https://www.fda.gov/media/87801/download.

Additionally, you manufacture drugs that contain glycerin. The use of glycerin contaminated with diethylene glycol (DEG) has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document Testing of Glycerin for Diethylene Glycol to help you meet the CGMP requirements when manufacturing drugs containing glycerin at https://www.fda.gov/media/71029/download.

In response to this letter, provide:

• A comprehensive, independent 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 specifications, including test methods, used to analyze each batch of your drug products before a batch disposition decision.
  o 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.
  o 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.

• A procedure for your water system monitoring that specifies routine microbial testing of water to ensure its acceptability for use in each batch of drug products produced by your firm.

• A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the system consistently produces water that meets Purified Water, USP monograph specifications and appropriate microbial limits.

• A commitment to provide DEG and ethylene glycol (EG) test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of DEG and EG.

• A full risk assessment for drug products that are within expiry which contain any ingredient at risk for DEG or EG contamination (including, but not limited to, glycerin). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain DEG or EG, including customer notifications and product recalls for any contaminated lots. Identify additional appropriate CAPA that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.

• 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 certificate of analysis (COA) 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 revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of glycerin, propylene glycol, and certain additional high-risk components we note that this includes the performance of parts A, B, and C of the United States Pharmacopeia (USP) monograph. Include your sampling procedure.

• The chemical quality control specifications you use to test each incoming lot of high-risk drug components to determine acceptability for use in manufacturing.

3. Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).

Your laboratory equipment used to generate analytical data for finished drug product release lacked restricted access and sufficient controls. There is no assurance that your systems have the appropriate controls to prevent data deletion and record modifications. For example, you did not establish unique usernames and passwords and laboratory staff had administrator rights allowing uncontrolled access to delete or modify high performance liquid chromatography (HPLC) files. You had no mechanism to facilitate traceability of individuals who deleted or modified data generated by computerized systems. Your HPLC systems are used to test finished products at release and throughout stability. Furthermore, your firm did not adequately maintain backups of data generated by your laboratory equipment.

In your response, you claim you have identified a supplier for managing equipment data, and your HPLC management system is undergoing a (b)(4) evaluation by the supplier. You indicate you have a procedure to address data integrity concerns.

Your response is inadequate. You fail to have interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding batches to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.

It is important to maintain strict control over CGMP electronic data to ensure that all additions, deletions, or modifications of information in your electronic records are authorized and appropriately documented. Without complete and accurate records, you cannot ensure your firm makes appropriate batch release, stability, and other decisions that are fundamental to ongoing assurance of drug product quality.

In response to this letter, provide:

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

• A comprehensive, independent assessment and CAPA plan for computer system security and integrity. Also, describe your interim controls and specify when procedures will be implemented for your CAPAs.

Unapproved New Drug and Misbranding Violations

Broncochem Kids COLD & FLU SYRUP, Broncochem COLD & FLU CAPLETS, Broncochem EXPECTORANT SYRUP, Broncochem Kids MAXIMUM COUGH, and Broncochem MAXIMUM COUGH are “drugs” 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 use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under 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.

Examples of claims observed on the Broncochem Kids COLD & FLU SYRUP, Broncochem COLD & FLU CAPLETS, Broncochem EXPECTORANT SYRUP, Broncochem Kids MAXIMUM COUGH, and Broncochem MAXIMUM COUGH product labels that provide evidence of the intended uses (as defined in 21 CFR 201.128) of the products as drugs include, but may not be limited to, the following:

Broncochem Kids COLD & FLU SYRUP
“Drug Facts . . . Uses . . . Bronchial congestion, irritation of the respiratory passages, helps loosen phlegm (mucus) and dilute bronchial secretions, temporarily reduces fever and minor pains associated with cold, headache, and sore throat.” [from the product’s label]

Broncochem COLD & FLU CAPLETS
“Drug Facts . . . Uses . . . Bronchial congestion, irritation of the respiratory passages, nasal congestion. Antitussive, temporary relieve of allergy symptoms including runny nose, sneezing, stuffy nose, itchy nose, itchy throat, irritated and watery eyes, allergy rhinitis.” [from the product’s label]

Broncochem EXPECTORANT SYRUP
“Drug Facts . . . Uses . . . Bronchial congestion, irritation of the respiratory passages, nasal congestion. Helps loosen phlegm (mucus) and dilute bronchial secretions to make coughs more productive. Temporarily relieves allergy symptoms including runny nose, sneezing, stuffy nose, itchy nose, itchy throat, irritated and watery eyes, allergic Rhinitis.”[from the product’s label]

Broncochem Kids MAXIMUM COUGH
“Drug Facts . . . Uses . . . Temporarily relieving cough due to the common cold, upper respiratory tract infections, sinus inflammation, sore throat, or bronchitis. Helps loosen phlegm (mucus) and dilute bronchial secretions to make coughs more productive.” [from the product’s label]

Broncochem MAXIMUM COUGH
“Drug Facts . . . Uses . . . Temporarily relieves cough due to minor throat and bronchial irritation occurring with common cold. Helps loosen phlegm (mucus) and dilute bronchial secretions to make coughs more productive. This new formulation with aloe results in a natural cleanser, penetrates tissue, bactericidal, viruscidal, and fungicidal, enhances normal cell proliferation and moisturizes tissues (this statements are not yet evaluated for the Food and Drug Administration ‘FDA’).” [from the product’s label]

Unapproved New Drug Violations

Based on the above labeling, Broncochem Kids COLD & FLU SYRUP, Broncochem COLD & FLU CAPLETS, and Broncochem EXPECTORANT SYRUP are intended for use as internal analgesic and cold, cough drug products. Additionally, Broncochem Kids MAXIMUM COUGH and Broncochem MAXIMUM COUGH are both intended for use as cold, cough drug products. As described below, these drug products are unapproved new drugs marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C 355(a) and 331(d).

A drug product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), if it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling; and with certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No FDA-approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for the drug products identified above.

Under section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application —commonly referred to as “OTC monograph drugs”— may be legally marketed if they meet applicable requirements. With respect to nonprescription internal analgesic drug products, such as the Broncochem Kids COLD & FLU SYRUP, Broncochem COLD & FLU CAPLETS, and Broncochem EXPECTORANT SYRUP products, in order to be generally recognized as safe and effective (GRASE) and not a new drug, such products must, among other things, conform to the conditions of use set forth in monograph M013: Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use (henceforth “M013” or the “internal analgesic monograph”). Furthermore, with respect to nonprescription cold, cough drug products, such as the Broncochem Kids COLD & FLU SYRUP, Broncochem COLD & FLU CAPLETS, Broncochem EXPECTORANT SYRUP, Broncochem Kids MAXIMUM COUGH and Broncochem MAXIMUM COUGH products, in order to be generally recognized as safe and effective (GRASE) and not a new drug, such products must, among other things, conform to the conditions of use set forth in monograph M012: Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use (henceforth “M012” or the “cold, cough monograph”). However, Broncochem Kids COLD & FLU SYRUP, Broncochem COLD & FLU CAPLETS, and Broncochem EXPECTORANT SYRUP do not conform to the conditions specified in M013 and M012, and Broncochem Kids MAXIMUM COUGH and Broncochem MAXIMUM COUGH do not conform to the conditions specified in M012, for the reasons described below.

Broncochem Kids COLD & FLU SYRUP

The product’s label states that it contains a combination of the following active ingredients in the following amounts: acetaminophen 325mg, guaifenesin 200mg, and phenylephrine HCl 5mg per 10 mL. Under the heading “Directions,” the label states that “children 2 to 6 years” should take “5 mL or cc every 6 hour [sic]” and that “children 6 to 12 years” should take “10 mL or cc every 6 hour [sic].” The product’s combination of the active ingredients acetaminophen, guaifenesin, and phenylephrine in the amount shown on the label and with the directions specified in the label do not conform with the conditions described in M012 and M013. Specifically, M013 states that the permitted amount of acetaminophen in children 4 to 6 years of age is not the same as the permitted amount of acetaminophen in children 2 to 4 years of age. On the other hand, M012 states that the permitted amount of guaifenesin and phenylephrine HCl does not change for children 2 to 6 years of age. Therefore, the product’s active ingredient amount and directions for use in children 2 to 6 years of age does not conform with the dosing directions and dosage limit requirements for each of the product’s individual active ingredients described in M013 and M012.

In addition, the product’s labeled amount of acetaminophen taken at the dosing interval stated in its directions for use (every 6 hours) is not permitted in M013. Furthermore, the product’s labeled amount of guaifenesin and phenylephrine HCl taken at the dosing interval stated in its directions for use (every 6 hours) is not permitted in M012. For example, the product’s labeled dosages of phenylephrine HCl (5mg every 6 hours) and guaifenesin (200mg every 6 hours) for children from 6 to 12 years of age are not permitted in M012.

Broncochem COLD & FLU CAPLETS

The product’s label states that it contains a combination of the following active ingredients in the following amounts: acetaminophen 325mg, chlorpheniramine maleate 3mg, dextromethorphan HBr 30mg, and phenylephrine HCl 5mg per caplet. Under the heading “Directions,” the product’s label states that adults and children 12 years and over should take “1 caplet every 6 hour [sic].” The product’s labeled active ingredient phenylephrine HCl, combined with the product’s labeled amount of the active ingredient dextromethorphan HBr (30mg) with the directions specified in the label does not conform with the conditions described in M012 and M013. Specifically, M012 states that for adults and children 12 years of age and over, 10mg of phenylephrine HCl is to be taken every 4 hours, but 30mg of dextromethorphan HBr is to be taken every 6 to 8 hours. Therefore, the product’s active ingredient amounts and directions for use do not conform with the dosing directions and dosage limit requirements described in M012.

In addition, the product’s labeled amount of acetaminophen (325 mg) taken at the dosing interval (every 6 hours) stated in its directions for use for adults and children 12 years of age and over is not permitted in M013. Furthermore, the product’s labeled amount of chlorpheniramine maleate (3 mg) and phenylephrine HCl (5 mg) taken at the dosing interval (every 6 hours) stated in its directions for use for adults and children 12 years of age and over is not permitted in M012.

Broncochem EXPECTORANT SYRUP

The product’s label states that it contains a combination of the following active ingredients in the following amounts: acetaminophen 250mg, chlorpheniramine maleate 4mg, dextromethorphan HBr 13.33mg, guaifenesin 200mg and phenylephrine HCl 5mg per 10 mL. Under the heading “Directions,” the label states that “adults and children 12 years and over” should take “10 mL or cc every 6 hour [sic]” and that “children 6 to under 12 years” should take “5 mL or cc every 6 hour [sic].” The product’s labeled combination of the active ingredients chlorpheniramine maleate and guaifenesin is not permitted in M012. Specifically, M012 does not permit an antihistamine active ingredient to be combined with an expectorant active ingredient. In addition, the product’s labeled amount of acetaminophen taken at the dosing interval stated in its directions for use (every 6 hours) is not permitted in M013. Furthermore, the product’s labeled amount of phenylephrine HCl, dextromethorphan HBr, and guaifenesin taken at the dosing interval stated in its directions for use (every 6 hours) are not permitted in M012. For example, the product’s labeled dosage of acetaminophen (250mg every 6 hours) for adults and children 12 years of age and over is not permitted in M013. Additionally, the product’s labeled dosages and dosing interval for phenylephrine HCl (5mg every 6 hours), dextromethorphan HBr (13.33mg every 6 hours), and guaifenesin (200mg every 6 hours) for adults and children 12 years of age and over are not permitted in M012.

Broncochem Kids MAXIMUM COUGH

The product’s label states that it contains a combination of the following the active ingredients in the following amounts: guaifenesin 100mg and dextromethorphan HBr 10mg per 15mL. Under the heading “Directions,” the label states that “children 2 to 6 years” should take “7.5 mL or cc every 6 hour [sic]” and that “children 6 to 12 years” should take “15 mL or cc every 6 hour [sic].” The product’s labeled amount of guaifenesin and dextromethorphan HBr taken at the dosing interval stated in its directions for use (every 6 hours) is not permitted in M012. Specifically, the product’s labeled dosages and dosing interval for guaifenesin (100mg every 6 hours) and dextromethorphan HBr (10mg every 6 hours) for children from 6 to 12 years of age are not permitted in M012. In addition, the product’s labeled dosages and dosing interval for guaifenesin (50mg every 6 hours) and dextromethorphan HBr (5mg every 6 hours) for children 2 to 6 years of age are not permitted in M012.

Broncochem MAXIMUM COUGH

The product’s label states that it contains the following the active ingredients in the following amounts: guaifenesin 200mg and dextromethorphan HBr 30mg per 10mL. Under the heading “Directions,” the label states that “adults and children 12 years and over” should take “10 mL or cc every 6 hour [sic]” and that “children 6 to under 12 years” should take “5 mL or cc every 6 hour [sic].” The product’s labeled amount of dextromethorphan HBr taken at the dosing interval stated in its directions for use (every 4 hours) is not permitted in M012. Specifically, product’s labeled dosage and dosing interval for dextromethorphan HBr (30mg every 4 hours) for adults and children 12 years of age and over, and the labeled dosage and dosing interval for dextromethorphan HBr (15mg every 4 hours) for children 6 to 12 years of age are not permitted in M012. In addition, the Uses section of the product label includes indications that are not permitted under M012. For example, the product label states that the product “results in a natural cleanser, penetrates tissue, bactericidal, viruscidal, and fungicidal, enhances normal cell proliferation and moisturizes tissues.” The use of a disclaimer on the label (i.e. “this statements [sic] are not yet evaluated for the Food and Drug Administration ‘FDA’”), does not change the fact that such statements do not conform with the conditions described in M012.

Therefore, Broncochem Kids COLD & FLU SYRUP, Broncochem COLD & FLU CAPLETS, Broncochem EXPECTORANT SYRUP, Broncochem Kids MAXIMUM COUGH, and Broncochem MAXIMUM COUGH products do not comply with the applicable conditions specified in M012, M013 and have not otherwise been found GRASE. Thus, these products are new drugs within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), and there is no basis under section 505G of the FD&C Act under which these products would be legally marketed without an approved application. Because there are no approved applications in effect for these products, these products are unapproved new drugs marketed in violation of section 505(a) of the FD&C Act, 21 U.S.C 355(a).

Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d).

Misbranded Drug Violations

Additionally, Broncochem Kids COLD & FLU SYRUP, Broncochem COLD & FLU CAPLETS, Broncochem EXPECTORANT SYRUP, Broncochem Kids MAXIMUM COUGH, and Broncochem MAXIMUM COUGH are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because these products are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but do not comply with the requirements for marketing under that section and are not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355.

The introduction or delivery for introduction of misbranded drugs into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).

Quality Systems

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.

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 assist your firm in meeting CGMP requirements.

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 in connection with your products. 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. 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 any violations.

Failure to address any violations may also result in the FDA refusing admission of articles manufactured at Laboratorio Magnachem International, Esquina Calle K, Haina, San Cristobal, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be misbranded may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B) and are misbranded under section 502 of the FD&C Act, respectively.

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 3003320065 and ATTN: Chhaya Shetty.

Sincerely,
/S/

Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research