WARNING LETTER

JT Cosmetics & Chemicals Pvt Ltd. MARCS-CMS 554478 — July 27, 2018

Recipient:: Recipient Name

Mr. Chirag Arora; JT Cosmetics & Chemicals Pvt Ltd.; 53 Kalol GIDC Estate
Panchmahal District
Gujarat 389330
India

Issuing Office:: Center for Drug Evaluation and Research; United States

10903 New Hampshire Avenue
Silver Spring, MD 20993

Via UPS Warning Letter 320-18-66

Return Receipt Requested

July 27, 2018

Mr. Chirag Arora

Administration Director

JT Cosmetics & Chemicals Pvt. Ltd.

53 Kalol GIDC Estate

Panchmahal District

Gujarat, 389330

India

Dear Mr. Arora:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, JT Cosmetics & Chemicals Pvt. Ltd. at 53 Kalol GIDC Estate, Panchmahal District, Gujarat, from February 26 to 28, 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).

JT Cosmetics & Chemicals Private Limited manufactures unapproved new drug and misbranded drug products. Specifically, the over-the-counter (OTC) drug product Diva’s Vaporizing Chest Rub is an unapproved new drug in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a). Furthermore, the OTC drug products Diva’s Blue Ice, Rubbing Alcohol, and Diva’s Vaporizing Chest Rub are misbranded under section 502(x) of the FD&C Act, 21 U.S.C. 352(x). Introduction of Diva’s Vaporizing Chest Rub into interstate commerce is prohibited under 301(d) of the FD&C Act, 21 U.S.C. 331(d) and the introduction of Diva’s Blue Ice, Rubbing Alcohol, and Diva’s Vaporizing Chest Rub into interstate commerce is prohibited under 301(a) of the FD&C Act, 21 U.S.C. 331(a).

In your April 20, 2018, response, you acknowledged the significance of the CGMP observations and stated that your firm expects to complete all corrections within three months. However, you provided no further information and did not commit to any specific corrective actions.

During our inspection, our investigators 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 released your OTC drug products without testing for the identity and strength of active ingredients. Without this testing you cannot determine whether your drug products conform to specifications.

Your personnel also informed our investigators during the inspection that microbiological test results recorded on your certificates of analysis (COA) in support of your decision to distribute drugs were falsified, and the testing had not been performed.

In addition, you lacked procedures for finished product testing that you do perform and records of your testing.

In response to this letter provide:

all chemical and microbial test methods and specifications used to analyze each lot of your OTC drug products prior to a lot disposition decision; and
a summary of test results obtained from testing retain samples of all OTC drug products within expiry that have been distributed in the United States. Include test results for identity and strength of active ingredients, and all other appropriate chemical and microbial quality attributes.

2. Your firm failed to test samples of each component for conformity with all appropriate written specifications for identity, purity, strength, and quality (21 CFR 211.84(d)(1) and (2)).

Your firm failed to test incoming raw materials, including active ingredients, for their identity, purity, strength, or other quality attributes. You also did not establish the reliability of COA from your unqualified suppliers. In addition, your procedures for receiving, handling, storing, sampling, and testing components are inadequate.

In response to this letter provide:

quality control release specifications for all incoming components and the tests you perform for each lot;
a summary of test results obtained from full testing of all your incoming components to validate the COA from each raw material manufacturer;
a summary of your procedures for qualifying and overseeing the adequacy of contract facilities that test the OTC drug products you manufacture;
a comprehensive, independent review of your material system to determine whether all containers, closures, and ingredients from each supplier are adequately qualified, and assigned appropriate expiration or retest dates; and whether incoming material lot controls are adequate to prevent use of unsuitable containers, closures, and components.

3. Your firm failed to establish and follow written procedures for the preparation of master production and control records designed to assure uniformity from batch to batch. Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.186(a) and 211.188).

Your master and batch production records are inadequate. They do not include:

manufacturing instructions;
actual amounts of components weighed and added to the batch;
identification of major equipment and lines used;
sampling information;
yield; and
packaging and labeling records, including inspection of the area before and after use and information pertaining to containers, closures, and labels.

In response to this letter, provide a risk assessment of products released to the U.S. market without adequate and approved production and control documentation. Also provide procedures you have implemented or revised to assure production records are completed as required and reviewed by your quality unit prior to release of products for distribution.

4. Your firm failed to establish a quality control unit and procedures applicable to the 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)).

Your firm lacks an adequate quality unit and failed to have adequate procedures for numerous functions of the quality unit. You had inadequate or non-existent procedures for these manufacturing operations:

quality unit operations;
production;
laboratory testing;
raw material handling;
training;
packaging and labeling;
equipment cleaning; and
stability

In response to this letter, provide a comprehensive assessment and a corrective action and preventive action (CAPA) plan to ensure that you establish an effective quality unit with appropriate authority, responsibilities and resources. Your response should also include a detailed procedure describing your remediated quality unit’s responsibilities.

Quality Unit Authority

Significant findings in this letter indicate that your quality unit is not able to fully exercise its authority and 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. 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/downloads/Drugs/Guidances/UCM070337.pdf.

Data Integrity Remediation

Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. In response to this letter, provide the following.

A. A comprehensive investigation into the extent of the inaccuracies in data, records, and reporting, including results of the data review for drugs distributed to the United States. Include a detailed description of the scope and root causes of your data integrity lapses.

B. A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity, and risks posed by ongoing operations.

C. A management strategy for your firm that includes the details of your global corrective action and preventive action plan. The detailed CAPA plan should describe how you intend to ensure the reliability and completeness of all data generated by your firm, including all laboratory data, manufacturing records, and all data submitted to FDA.

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 consultant perform a comprehensive audit of your entire operation for CGMP compliance, and evaluate the completeness and effectiveness of corrective actions and preventive actions 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 fully resolving all deficiencies and ensuring ongoing CGMP compliance.

Unapproved New Drug Charges

Diva’s Vaporizing Chest Rub

Examples of claims observed on your product label for Diva’s Vaporizing Chest Rub that establish the intended uses of the product include, but may not be limited to, the following:

“Nasal Decongestant . . . Cough Suppressant . . . Topical Analgesic . . . To temporarily relieve nasal congestion, chest congestion and cough due to the common cold. Temporarily relieves minor aches and pains.”

Based on the above claims Diva’s Vaporizing Chest Rub is a “drug” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because it is intended for 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 it is intended to affect the structure or any function of the body. Specifically, this product is intended as a nasal decongestant, antitussive (cough suppressant), and external analgesic.

OTC drug products such as Diva’s Vaporizing Chest Rub that are intended for nasal decongestant and cough suppressant indications are subject to the Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products final rule (cough/cold final rule), see 21 CFR 341. Diva’s Vaporizing Chest Rub must meet the formulation and labeling requirements described in the cough/cold final rule for both nasal decongestants and cough suppressants. However, the product is not labeled or formulated in accordance with this final rule for reasons explained below.

Diva’s Vaporizing Chest Rub is indicated, in part, for use as a nasal decongestant. However, the labeled active ingredients, menthol, camphor, and eucalyptus oil, are not included active ingredients for nasal decongestant drug products as described in the cough/cold final rule, see 21 CFR 341.20.

Your product also is indicated, in part, as a cough suppressant. The final rule requires that topical cough suppressants contain 2.6% to 2.8% menthol, see 21 CFR 341.74(d)(2)(ii). However, your product is formulated with menthol 1.0%. Furthermore, Diva’s Vaporizing Chest Rub is labeled to contain 1.0% eucalyptus oil. According to 21 CFR 341.40(u), camphor and menthol may be combined with 1.2% to 1.3% eucalyptus oil provided that the product is available in a suitable ointment vehicle labeled in accordance with the allowable indications for cough suppressant drug products. Since Diva’s Vaporizing Chest Rub contains less than the required amount of eucalyptus oil that is allowed to be combined with camphor and menthol, your product’s active ingredients do not meet the requirements for a permitted combination of active ingredients as described in 21 CFR 341(u).

Thus, as formulated and labeled, Diva’s Vaporizing Chest Rub does not comply with the final rule described above. Furthermore, we are not aware of sufficient evidence to show Diva’s Vaporizing Chest Rub as formulated and labeled, is generally recognized as safe and effective. Therefore, this product is a new drug within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p). As a new drug, Diva’s Vaporizing Chest Rub may not be legally marketed in the United States absent approval of an application filed in accordance with section 505 of the FD&C Act, 21 U.S.C. 355(a). Diva’s Vaporizing Chest Rub is not the subject of an FDA-approved application, and therefore, the current marketing of this product violates section 505(a) of the FD&C Act, 21 U.S.C. 355(a)). Introduction of such products into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d).

Misbranding Charges

Diva’s Blue Ice, Rubbing Alcohol, and Diva’s Vaporizing Chest Rub

Examples of claims observed on your product labels for Diva’s Blue Ice, Rubbing Alcohol, and Diva’s Vaporizing Chest Rub that establish the intended uses of the products include, but may not be limited to, the following:

Diva’s Blue Ice:

“Soothing Analgesic Gel . . . Provides temporary relief of minor aches and pains in muscles and joints associated with simple backache, strains, sprains, arthritis and sports injuries”

Rubbing Alcohol:

“First Aid Antiseptic . . . First aid to help prevent the risk of infection in minor cuts, scrapes and burns”

Diva’s Vaporizing Chest Rub:

Based on the above claims, Diva’s Blue Ice, Rubbing Alcohol, and Diva’s Vaporizing Chest Rub 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 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.

As OTC drugs, Diva’s Blue Ice, Rubbing Alcohol, and Diva’s Vaporizing Chest Rub must comply with all of the requirements of section 502 of the FD&C Act and all pertinent regulations found in 21 CFR. However, they do not for the reasons described below.

Diva’s Blue Ice, Rubbing Alcohol, and Diva’s Vaporizing Chest Rub are misbranded under section 502(x) of the FD&C Act, 21 U.S.C. 352(x), because the products’ labels fail to disclose a domestic address or domestic telephone number through which the responsible person may receive a report of a serious adverse event with such drug. Please note that section 201(k) of the FD&C Act defines the term “label” as “...a display of written, printed, or graphic matter upon the immediate container of any article; and a requirement made by or under the authority of the FD&C Act that any word, statement, or other information appear on the label shall not be considered to be complied with unless such…also appears on the outside container….” Therefore, the domestic address or domestic telephone number must appear on your products’ immediate container labels and on the products’ outside container labels if one exists.

The introduction or delivery for introduction of a misbranded drug into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). Therefore, the marketing of Diva’s Blue Ice, Rubbing Alcohol, and Diva’s Vaporizing Chest Rub violates this provision of the FD&C Act.

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.

FDA placed your firm on Import Alert 66-40 on June 11, 2018.

Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.

Failure to correct these violations may also result in FDA continuing to refuse admission of articles manufactured at JT Cosmetics & Chemicals Pvt. Ltd. at 53 Kalol GIDC Estate, Panchmahal District, Gujarat, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Under the same authority, articles may be subject to refusal of 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).

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 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.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov or mail your reply to:

Brooke K. Higgins

Compliance Officer

U.S. Food and Drug Administration

White Oak Building 51, Room 4359

10903 New Hampshire Avenue

Silver Spring, MD 20993

USA

Please identify your response with FEI 3011783104.

Sincerely,

/S/

Francis Godwin

Acting Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research