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Petra Hygienic Systems Int Ltd MARCS-CMS 572769 —

Delivery Method:

Recipient Name
Mr. Sam Maduri
Recipient Title
Petra Hygienic Systems Int Ltd

86 Moyal Court
Concord ON L4K 4R8

Issuing Office:
Center for Drug Evaluation and Research

10903 New Hampshire Avenue
Silver Spring, MD 20993
United States

­­­Via UPS                                                                                   Warning Letter 320-19-22

Return Receipt Requested


May 7, 2019


Mr. Sam Maduri


Petra Hygienic Systems International, LLC

86 Moyal Court

Concord, Ontario

L4K 4R8



Dear Mr. Maduri:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Petra Hygienic Systems International LLC at 86 Moyal Court, Concord, Ontario, from December 17 to 21, 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).

We reviewed your January 11, 2019, response in detail. Your response is inadequate because it did not provide sufficient detail or evidence of corrective actions to bring your operations into compliance with CGMP.

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

  1. Your firm failed to have, 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 (21 CFR 211.165(a)).

Your firm released over-the-counter (OTC) drug products to the U.S. market without conducting finished product quality testing per National Formulary (NF) monograph requirements. Additionally, your firm uses assay release specifications ((b)(4)-(b)(4)%) that are different than the required NF monograph assay specifications ((b)(4) -(b)(4)%), and thus your specifications allow for super potent drug products.

For example, we observed (b)(4) Bulk lot (b)(4) tested at (b)(4)% of label claim, which is out-of-specification based on the NF monograph for the active (b)(4)%. This lot was released by your firm and distributed to the U.S. market.

In response to this letter, provide an action plan and timeline for testing reserve samples of all finished OTC drug products distributed to the United States within expiry to determine the identity and strength of active ingredients following USP/NF monograph requirements. If such testing reveals that you released drug products that did not meet specifications for identity or strength of active ingredients, indicate what corrective actions you have taken or will take, such as notifying customers or recalling products.

  1. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)).

Your firm failed to test incoming components used in manufacturing your finished OTC drug products to determine identity, purity, strength, and quality.

Instead, your firm used results from your suppliers’ certificates of analysis (COA) without establishing the reliability of your suppliers’ analyses through appropriate validation and without conducting at least one specific identity test on each incoming lot of components. Under 21 CFR 211.84(d)(2), you may not rely on your suppliers’ COA to verify the identity of your components.

During the inspection, you stated that your firm has never validated your vendor’s test results provided on the COA.

In response to this letter, describe in detail how you plan to test each component lot for conformity with all appropriate written specifications for identity, purity, strength, and quality. If you accept your suppliers’ COA in lieu of testing each component lot for purity, strength, and quality, describe how you plan to establish the reliability of your suppliers’ test results for these attributes at regular intervals and include a commitment to test every incoming component lot at least for identity. Also, provide your revised procedure remediating these deficiencies.

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

You have not validated the methods you use to clean your equipment. Inadequate removal of residues from manufacturing equipment during cleaning can lead to cross-contamination of products subsequently manufactured on the non-dedicated equipment.

In response to this letter, provide:

  • Your cleaning validation summary report demonstrating the adequacy of your cleaning procedures.
  • Your evaluation of all drug product lots, within expiry and in distribution, identifying the effects of any cross-contamination that may have occurred.
  1. Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit and to follow such written procedures (21 CFR 211.22(d)).

You lacked adequate written procedures for various functions, including, but not limited to:

  • Quality Unit responsibilities
  • Vendor audits
  • Corrective actions and preventive actions

Additionally, you do not always follow the procedures you have. For example, during your inspection, you stated your firm does not perform a historical review and (b)(4) as part of the annual product review. Your procedure “Quality Control - Annual Product Review (QC-021)” requires your firm to perform a (b)(4).

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.

In response to this letter, provide your comprehensive plan for establishing, supporting, and sustaining a robust quality system consistent with CGMP regulations. Include timelines in your plan.

Repeat observations at facility

In previous inspections, dated March 20, 2012, and December 19, 2014, FDA cited similar CGMP observations. You proposed specific remediation for these observations in your response. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.


We acknowledge your commitment to (b)(4).

In response to this letter, provide the (b)(4). Additionally, explain how you will (b)(4).  


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 March 25, 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 Petra Hygienic Systems International, Ltd. at 86 Moyal Court, Concord, Ontario, 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:

Kevin Maguire

Compliance Officer

U.S. Food and Drug Administration

White Oak Building 51, Room 4359

10903 New Hampshire Avenue

Silver Spring, MD 20993


Please identify your response with FEI 3002869527.




Francis Godwin


Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research

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