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  1. Warning Letters

WARNING LETTER

Les Emballages Facoteck Inc MARCS-CMS 547755 —


Delivery Method:
VIA UPS
Product:
Drugs

Recipient:
Recipient Name
Mr. Martin Fortin
Recipient Title
General Manager and Co-owner
Les Emballages Facoteck Inc

35 Victoria West
Scotstown QC J0B 3B0
Canada

Issuing Office:
Center for Drug Evaluation and Research

10903 New Hampshire Avenue
Silver Spring, MD 20993
United States


Warning Letter 320-18-71

 

August 21, 2018

 

Dear Mr. Fortin:

 

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Les Emballages Facoteck Inc. at 35 Victoria West, Scotstown, Quebec, from November 27 to December 1, 2017.

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).

In addition, your drug products, as formulated and labeled, neobourne Anti-Fungal Topical Foot Care Spray, Brioschi Effervescent Antacid, and neobourne Diaper Rash Spray, are misbranded under section 502(c) of the FD&C Act, 21 U.S.C. 352(c).

We reviewed your December 11, 2017, response in detail and acknowledge receipt of your subsequent correspondence.

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

1.    Your quality control unit failed to follow written responsibilities and procedures applicable to the quality control unit (21 CFR 211.22(d)).

Our investigator documented that your quality unit failed to follow your firm’s procedures. For example, your procedure for non-conformities states that the quality assurance/control manager will open non-conformance reports for non-conformities in your processes. However, during the inspection, your quality assurance/control manager stated that she did not open non-conformance reports for out-of-specification (OOS) percentage of theoretical yield when packaging processing yields were OOS. For example, OOS for theoretical yield percentages were obtained and non-conformance reports were not generated for the following products: (b)(4)% for (b)(4) batch (b)(4) and (b)(4)% for (b)(4) batch (b)(4) (theoretical yield percentage specification (b)(4)%).

In another example, your procedure for product release, (b)(4), states that the quality assurance/control manager will review batch records prior to releasing a batch. However, our inspection found that your quality unit failed to note that the batch record for (b)(4) batch (b)(4) was missing the cleaning record for (b)(4) ID #95, and that the equipment registry document did not record the use of (b)(4) ID #95 and the (b)(4) used to manufacture lot (b)(4).

In your response, you committed to open investigations into the process deviations cited on the Form FDA 483 and to retrain your personnel on the written procedures. Your response was deficient because you did not retrospectively investigate batch records for products within expiry to determine if other process deviations were not investigated or inadequately investigated.  You also did not commit to review all batch records for U.S. products to determine which lacked complete documentation.

Your firm must provide the quality unit with the appropriate authority, sufficient resources, and staff to carry out its responsibilities and consistently ensure drug quality.

In response to this letter, provide:

  • Your investigation and corrective action and preventive action (CAPA) plan to ensure your quality unit executes its responsibilities.
  • Your retrospective investigation of all batch records of drug products for the U.S. market remaining within expiry to ensure that they are complete, all deviations are investigated, and CAPA are both implemented and shown to be effective.

2.    Your firm failed to ensure that its drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).

You lack data supporting the labeled expiration date for three drug products distributed in the United States: Brioschi Effervescent Antacid, (b)(4).

In your response, you committed to performing a stability study on Brioschi Effervescent Antacid. You also stated that your (b)(4) products will not continue to be offered for distribution into the United States until the observations noted are adequately resolved. Your response is inadequate because you did not provide the stability protocol for Brioschi Effervescent Antacid, and you did not indicate any actions taken to ensure that the distributed (b)(4) products will maintain their purported quality attributes through their labeled expiry.

In response to this letter, provide:

  • The stability testing protocol for Brioschi Effervescent Antacid. If the protocol has been executed or is in the process of being executed, provide an update and any testing results.
  • Your CAPA plan to ensure that (b)(4) products distributed in the United States will maintain their purported quality attributes through their labeled expiry. 
  • A comprehensive review and CAPA plan to ensure your stability program is fully remediated to support initial distribution and ongoing stability of all products distributed by your firm.

3.    Your firm failed to establish and follow required laboratory control mechanisms, and used instruments, apparatus, gauges, and/or recording devices that did not meet established specifications (21 CFR 211.160(a) and (b)(4)).

The Gardco 100 mL densitometer used to determine the density of your (b)(4) OTC drug products, (b)(4), was not calibrated, however it was used to calculate the specific volume dispensed during filling operations. Your firm also lacks calibration procedures for this equipment.

In your response, you stated the densitometer was used for informal purposes before you sent samples to a third-party laboratory for testing. You further stated the results from the densitometer were “not reported or relied upon for any GMP determination.” Your response is inadequate because multiple batch records reviewed during the inspection identify this densitometer as specifically used to calculate fill volumes in filling operations.

In response to this letter, provide your plan to ensure that all instruments used to manufacture drug products are appropriately calibrated.  Also provide a comprehensive evaluation of your overall testing equipment maintenance program, and include a CAPA that ensures full remediation.

4.    Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)).

You have not validated the cleaning procedure for non-dedicated equipment used to manufacture drug products distributed to the United States, including (b)(4) tanks, pumps, (b)(4), and (b)(4). You also use this equipment to manufacture a variety of cosmetics and dietary supplements, including those that include microorganisms as ingredients.

In your response, you committed to validating the cleaning of equipment used to manufacture Brioschi Effervescent Antacid. Your response was deficient in that you did not provide the cleaning validation protocol(s) for these pieces of equipment. You also did not provide a timeframe when the protocol(s) will be completed.

In response to this letter, provide:

  • The protocol(s) you will use to validate the cleaning of drug product manufacturing equipment.
  • The date when you will complete your cleaning validation protocol(s).
  • Your plan to ensure that all manufacturing equipment cleaning processes are validated prior to distributing drug products manufactured on such equipment to the United States.

5.    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)).

Your firm does not have an adequate ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality for drug products you distributed to the United States: Brioschi Effervescent Antacid, (b)(4). 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/downloads/drugs/guidances/ucm070336.pdf.

Additionally, you did not establish acceptable specifications for certain critical process control parameters used to manufacture drug products. For example, the (b)(4) times of (b)(4) are not scientifically justified for steps (b)(4).

In your response, you committed to incorporating appropriate time limits and production controls to the batch record for Brioschi Effervescent Antacid. You also committed to completing the validation of the manufacturing process for Brioschi Effervescent Antacid before distributing the next “new” lot of the product. Your response is inadequate because you did not provide the manufacturing process validation protocol for Brioschi Effervescent Antacid. You also did not commit to ensuring that manufacturing processes are validated for all products intended for distribution in the United States.

In response to this letter, provide:

  • The procedures and protocols you will use to establish time limits and production controls prior to the manufacture and distribution of drug products to the United States.
  • The protocol you will use to validate the manufacturing process for Brioschi Effervescent Antacid.
  • Details of your validation plan for ensuring a state of control throughout the product lifecycle. Include a timeline for performing appropriate process performance qualification (PPQ) for each of your drug products, and describe your program for vigilantly monitoring batch-to-batch variation to ensure an ongoing state of control.  Also include your process performance protocol(s).

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.

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 Charges

Examples of claims observed on the product labels for neobourne Anti-Fungal Topical Foot Care Spray, Brioschi Effervescent Antacid, and neobourne Diaper Rash Spray that establish the intended uses of the products include, but may not be limited to, the following:

neobourne Anti-Fungal Topical Foot Care Spray

  • “Cures most Athlete’s foot.”
  • “Soothes itchy, scaly skin between the toes and itching, burning feet”

Brioschi Effervescent Antacid

  • “For fast relief of: Upset Stomach, Acid indigestion, Heartburn”
  • “For the relief of heartburn, sour stomach, acid indigestion and upset stomach associated with these symptoms.”

neobourne Diaper Rash Spray

  • “Skin Protectant”
  • “Helps treat and prevent diaper rash.”
  • “Protects chafed skin (or minor skin irritation) due to diaper rash and helps protect from wetness.”

Based on the above claims, neobourne Anti-Fungal Topical Foot Care Spray, Brioschi Effervescent Antacid, and neobourne Diaper Rash Spray 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, neobourne Anti-Fungal Topical Foot Care Spray, Brioschi Effervescent Antacid, and neobourne Diaper Rash Spray must comply with all 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, they do not for the reasons described below.

Brioschi Effervescent Antacid, neobourne Anti-Fungal Topical Foot Care Spray, and neobourne Diaper Rash Spray are not labeled in accordance with the Drug Facts labeling requirements described in 21 CFR 201.66. Neobourne Anti-Fungal Topical Foot Care Spray and neobourne Diaper Rash Spray do not meet the content requirements set forth in 21 CFR 201.66(c).

Neobourne Anti-Fungal Topical Foot Care Spray and neobourne Diaper Rash Spray also fail to list the appropriate title, headings, and subheadings and present them in the correct order. Furthermore, neobourne Anti-Fungal Topical Foot Care Spray, neobourne Diaper Rash Spray and Brioschi Effervescent Antacid do not meet the Drug Facts panel graphic specifications as described in 21 CFR 201.66(d). Therefore, these products are misbranded under section 502(c) of the FD&C Act, 21 U.S.C. 352(c), because the information that is required to appear on the labeling is not prominently placed thereon with such conspicuousness, and in such terms, as to render it likely to be read and understood by the ordinary individual under customary conditions of purchase and use.

Brioschi Effervescent Antacid is further misbranded within the meaning of section 502(c) of the FD&C Act 21 U.S.C. 352(c) because the label fails 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. The label for this product fails to include the established name, which is sodium bicarbonate, of the drug as part of the statement of identity.

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 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 refusing admission of articles manufactured at Les Emballages Facoteck Inc. at 35 Victoria West, Scotstown, Quebec, 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:

Jason F. Chancey

Consumer Safety 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 3002955163.

 

Sincerely,

/S/

Francis Godwin

Acting Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research