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Via UPS                                                                                 Warning Letter 320-19-24

Return Receipt Requested

 

May 31, 2019

           

Mr. B. M. Chopra

Owner and Chairman

Glint Cosmetics Pvt. Ltd.

C-216-218, TTC Industrial Area

MIDC Turbhe, Navi Mumbai

Maharashtra

India

 

Dear Mr. Chopra:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Glint Cosmetics Pvt. Ltd. at C-216-218, TTC Industrial Area, MIDC Turbhe, Navi Mumbai, Maharashtra, from December 17 to 22, 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).

Your firm manufactures Wish Vaporizing Chest Rub (4 oz) and Wish BLUE THERAPEUTIC ICE GEL (8 oz) that are unapproved new drugs 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).

Your firm also manufactures AmeriDerm Ointment with Vitamins A&D (15 oz), MedPRIDE Zinc Oxide Ointment (1 oz), GeriGentle Bacitracin Ointment USP (1 oz), GeriGentle Zinc Oxide Ointment (1 oz and 2 oz), GeriGentle Vitamin A&D Ointment (4 oz, 4 oz (12 tubes), and 5 g), geri gard (4 oz), MedPRIDE Vitamins A&D Ointment (4 oz and 1 oz), MedPRIDE En-Shield (3.5 oz), MedPRIDE White Petrolatum (720 g), AmeriDerm PeriShield (3.5 oz), and Wish products (original, cocoa butter, baby, aloe, and lavender (6 oz and 12 oz) that are misbranded under section 502 of the FD&C Act, 21 U.S.C. 352. Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). 

We reviewed your January 11, 2019, response in detail and acknowledge receipt of your subsequent correspondence.

Your response stated “…we have decided to suspend exports to the USA until all corrections have been made.” However, your drug products were shipped to the United States after this response via your distributor, (b)(4).

FDA placed your firm on Import Alert 66-40 on April 17, 2019.

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

CGMP Violations

1.  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).

During the inspection, our investigator observed that your quality unit (QU) did not provide adequate oversight for the manufacture of your over-the-counter (OTC) drug products. For example, your QU failed to ensure the following:

• all testing was performed and reviewed prior to batch release;
• contract testing laboratory was adequately qualified;
• staff completed records accurately and contemporaneously for activities they performed;
• adequate controls were in place for storage of rejects and raw materials; and
• stability program was established.

Your response indicated that you hired a consultant to audit your operation. However, your response did not adequately address the impact of inadequate QU oversight for the manufacture of drug products already on the market.

In response to this letter, provide a comprehensive assessment with corrective actions and preventive actions (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; and
• your consultant’s evaluation of your operations.       

2.  Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).

Your firm uses non-dedicated equipment to manufacture multiple topical OTC drug products without a validated cleaning process for drug product changeover to prevent cross-contamination between products.

Our investigator observed dried white (b)(4) throughout the facility, including on utensils, the door of the dispensing room, and the (b)(4) protecting the laminar air flow booths used for dispensing and sampling.

Our investigator also observed that your employees pre-filled and signed logbooks for cleaning and falsified the recorded duration of equipment cleaning. For example, the cleaning of two “scoops” was documented at the exact same time, and for a duration of (b)(4) each day from September to December 2018, despite the facility being closed on some of those days.

Your response stated dedicated scoops will be used and included “SOP for Use and Cleaning of (b)(4) AF Workstations” which indicated the frequency of cleaning the laminar air flow booths is “(b)(4) whenever required.” However, your response did not adequately address cleaning between different OTC drug products to prevent cross-contamination. Inadequate cleaning of non-dedicated equipment may result in cross-contamination between products.

In response to this letter, provide the following:

• a comprehensive plan to evaluate cleaning procedures and practices and validation studies for each piece of manufacturing equipment used to manufacture more than one product; and
• a summary of updated standard operating procedures that ensure an appropriate program is in place for verification and validation of cleaning procedures for new products, processes, and equipment.

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)).

Our investigator observed that laboratory equipment and computers in the quality control (QC) laboratory lacked restricted access. For example, your laboratory employees share the QC Manager login and password to access the high-performance liquid chromatography (HPLC) instrument.

Additionally, electronic documents and spreadsheets, including Certificates of Analysis (COA) can be manipulated or deleted from laboratory computers. The COA for the OTC drug product (b)(4) (Batch No: (b)(4)) was accessible in an unprotected electronic document that could be modified with no record of changes.

Your response indicated users were assigned unique logins and changes were made to limit access to folders and prevent users from deleting files. Your response also included a general “SOP for security access and data control” you established. However, your response lacked supporting documentation, including evidence to support that the computer security controls were effective at preventing data and document manipulation. You also did not perform a retrospective risk assessment of the impact and scope of inadequate system controls at your firm, including evaluating whether CGMP data were improperly modified or deleted.

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. See FDA’s guidance document Data Integrity and Compliance With Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/119267/download.

We acknowledge that you are using a consultant to audit your operation and assist in meeting FDA requirements.

In response to this letter, provide the following:

 

a.  A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include:

• A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.
• Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.
• An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity lapses.
• A comprehensive retrospective evaluation of the nature of the testing and manufacturing data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all 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 analyses of the 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. Your strategy should include:

• A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate including analytical data, manufacturing records, and all data submitted to FDA.
• A comprehensive description of the root causes of your data integrity lapses including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data at your firm.
• 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 lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.
• Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.
• A status report for any of the above activities already underway or completed.

Unapproved New Drugs

Wish Vaporizing Chest Rub

Wish Vaporizing Chest Rub (4 oz) 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.

Examples of claims observed on the product label that establish the intended uses of the product as defined in 21 CFR 201.128 include, but may not be limited to, the following:

Label Claims

“COUGH SUPPRESSANT. TOPICAL ANALGESIC. NASAL DECONGESTANT… helps temporarily relieve cough as may occur with common cold and minor bronchial irritation. For the temporary relief of pain associated with minor skin irritation”

OTC drug products such as Wish Vaporizing Chest Rub (4 oz) that are intended for nasal decongestant and cough suppressant indications are subject to the Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use Final Rule (cough/cold final rule) (21 CFR 341). As such, Wish Vaporizing Chest Rub (4 oz) 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.

Wish Vaporizing Chest Rub (4 oz) is indicated, in part, for use as a nasal decongestant and, in part, as a cough suppressant. 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 (21 CFR 341.20) nor do the product’s active ingredients meet the requirements for a permitted combination of cough suppressant active ingredients described in 21 CFR 341.40(u). Wish Vaporizing Chest Rub (4 oz) contains an amount of eucalyptus oil that is greater than is allowed to be combined with camphor and menthol under the cough/cold final rule. 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. However, Wish Vaporizing Chest Rub (4 oz) is labeled to contain 2.6% eucalyptus oil. Additionally, the final rule requires that topical cough suppressants contain 2.6% to 2.8% menthol, see 21 CFR 341.74(d)(2)(ii). However, the product is formulated with menthol 1.2% which is below the permitted range established in the cough/cold final rule. 

Thus, as formulated and labeled, Wish Vaporizing Chest Rub (4 oz) does not comply with the final rule described above. Furthermore, we are not aware of sufficient evidence to show Wish Vaporizing Chest Rub (4 oz) 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, Wish Vaporizing Chest Rub (4 oz) 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). Wish Vaporizing Chest Rub is not the subject of an FDA-approved application, and therefore, the current marketing of this product in the United States is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d) and violates section 505 of the FD&C Act.

Wish BLUE THERAPEUTIC ICE GEL

Wish BLUE THERAPEUTIC ICE GEL (8 oz) 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 an external analgesic.

Examples of claims observed on the product label that establish the intended uses of the product as defined in 21 CFR 201.128 include, but may not be limited to, the following:

Label Claims

“Temporary Pain Relief … temporarily relieves minor aches and pains of muscles and joints associated with ∙ arthritis ∙ simple backache ∙ strains ∙ bruises ∙ sports injuries ∙ sprains”

OTC drug products such as Wish BLUE THERAPEUTIC ICE GEL (8 oz) that are intended for external analgesic indications such as the temporary relief of minor aches and pains of muscles and joints are being evaluated as part of the OTC Drug Review. They have been proposed to be classified as generally recognized as safe and effective and not misbranded under the Tentative Final Monograph (TFM) for External Analgesic Drug Products for Over-the-Counter (OTC) Human Use (48 Federal Register (FR) 5852, February 8, 1983) if they meet each condition in the TFM and each general condition in 21 CFR 330.1. Pending the promulgation of a final rule, the agency generally does not intend to pursue regulatory action against products marketed in accordance with the conditions proposed in the TFM and each general condition in 21 CFR 330.1. Such marketing, however, is subject to the risk that a final rule may require reformulation and/or relabeling or FDA approval through the “new drug” procedures of the FD&C Act (section 505).

The formulation for Wish BLUE THERAPEUTIC ICE GEL (8 oz) is not consistent with the TFM for External Analgesic Drug Products that describes acceptable active ingredients and dosage strengths for external analgesic drug products (48 FR 5852 at 5868, February 8, 1983). Specifically, the label for Wish BLUE THERAPEUTIC ICE GEL (8 oz) is not compliant with the TFM because the product is labeled as a counterirritant that contains menthol 1% and camphor 0.5%, which falls below the 3%–11% dosage range for camphor and the 1.25%–16% dosage range for menthol proposed in the TFM for counterirritants (48 FR 5852 at 5868, February 8, 1983).

Furthermore, we are not aware of any adequate and well controlled clinical trials in the published literature that support a determination that Wish BLUE THERAPEUTIC ICE GEL (8 oz) is generally recognized as safe and effective for its labeled indications. Additionally, we are not aware of a similar OTC product as formulated and labeled that was available in the United States market on or before the inception of the OTC Drug Review.

Thus, as formulated and labeled, Wish BLUE THERAPEUTIC ICE GEL (8 oz) is a new drug within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p) because it is not generally recognized among scientific experts as safe and effective for the drug uses described in its labeling. “New drugs” may not be introduced or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FD&C Act is in effect for the drug. Wish BLUE THERAPEUTIC ICE GEL (8 oz) is not the subject of an approved new drug application; therefore, marketing this product in the United States is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d) and violates section 505 of the FD&C Act.

Misbranded Drugs

AmeriDerm Ointment with Vitamins A&D (15 oz), MedPride Zinc Oxide Ointment (1 oz), GeriGentle Bacitracin Ointment USP (1 oz), GeriGentle Zinc Oxide Ointment (1 oz and 2 oz), GeriGentle Vitamin A&D Ointment (4 oz, 4 oz (12 tubes), and 5 g), geri gard (4 oz), MedPride Vitamins A&D Ointment (4oz, 5 g, and 1 oz), MedPride En-Shield (3.5 oz), MedPride White Petrolatum (720 g), AmeriDerm PeriShield (3.5 oz), and Wish products (original, cocoa butter, baby, aloe, and lavender (6 oz and 12 oz))

All of the products listed above 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. The labeling for each of these products bears a Drug Facts panel and includes various intended uses such as skin protectant, diaper rash treatment, and first aid antibiotic. The labeling for such drugs, like all OTC drugs, 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). However, the product labels do not meet these requirements for the reasons described below.

AmeriDerm Ointment with Vitamins A&D (15 oz), GeriGentle Bacitracin Ointment USP, GeriGentle Vitamins A&D Ointment (4 oz, 4 oz (12 tubes), and 5 g), geri gard (4 oz), MedPRIDE Vitamins A&D Ointment (4 oz and 1 oz), and Wish products (original, cocoa butter, baby, aloe, and lavender (6 oz and 12 oz)) are misbranded within the meaning of section 502(c) of the FD&C Act, 21 U.S.C. 352(c), because the labels fail to bear a complete statement of identity as required under 21 CFR 201.61. In the case of a drug that has an established name, the statement of identity must contain the established name and the general pharmacological action(s) or principal intended action(s) of the drug in the principal display panel (PDP). The labels for these products fail to include either the established name and/or the principle intended use of the drug as part of the statement of identity. For example, the AmeriDerm Ointment with Vitamins A&D (15 oz) label does not list the established name nor does it identify the product as a skin protectant. Similarly, Wish Baby Skin Protectant does not list white petrolatum on the PDP, and GeriGentle Bacitracin Ointment USP does not include the established name bacitracin zinc on the PDP.

All of the products listed above are also misbranded under section 502(x) of the FD&C Act, 21 U.S.C. 352(x), because the product 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 the immediate container label as well as on the outside container label if one exists.

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

Cosmetics

Your facility is also used to produce cosmetic products. Under 21 U.S.C. 321(i), cosmetics are defined as: “(1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof, for cleansing, beautifying, promoting attractiveness, or altering the appearance, and (2) articles intended for use as a component of any such articles; except that such term shall not include soap.” Information on the manufacture and labeling of cosmetic products can be found on FDA’s website at https://www.fda.gov/cosmetics. You are encouraged to review your cosmetic manufacturing process to ensure compliance with all applicable cosmetic laws and regulations.

Conclusion

Violations 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 April 17, 2019.

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 Glint Cosmetics Pvt. Ltd. at C-216-218, TTC Industrial Area, MIDC Turbhe, Navi Mumbai, Maharashtra 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 [email protected] or mail your reply to:

Lynnsey Renn, Ph.D.

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 3009729392.

 

Sincerely,

/S/

Francis Godwin

Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research

 

(b)(4)