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Warning Letter
CMS # 657340

February 13, 2024

Dear Mr. Arumugam:

The U.S. Food and Drug Administration (FDA) inspected your facility, Delsam Pharma LLC, FEI 3018035065, located at 55 E. Gun Hill Road, Bronx, New York, from March 6 to March 24, 2023, after an FDA inspection revealed violative conditions at Global Pharma Healthcare Private Limited, a contract manufacturing organization (CMO) used to manufacture ophthalmic drugs for Delsam Pharma LLC. The FDA inspection of this foreign facility revealed significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211 (21 CFR Parts 210 and 211), causing these drug products to be adulterated, including within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act).¹ Because these products were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, these drug products are also adulterated within the meaning of section 501(a)(2)(A) of the FD&C Act, 21 U.S.C. 351(a)(2)(A).

The inspection of your facility revealed that you operate as a distributor of Delsam Pharma’s Artificial Tears and Delsam Pharma’s Artificial Eye Ointment. Your receipt in interstate commerce of adulterated drugs, and the delivery or proffered delivery thereof, is a violation of section 301(c) of the FD&C Act, 21 U.S.C. 331(c), and your distribution of adulterated drugs violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).

In addition, Delsam Pharma’s ARTIFICIAL TEARS and Delsam Pharma’s ARTIFICIAL EYE OINTMENT are misbranded under section 502(j) of the FD&C Act, 21 U.S.C. 352(j), and Delsam Pharma’s ARTIFICIAL EYE OINTMENT is further misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a). Introduction or delivery for introduction of misbranded products into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.

We have not received a response from your firm stating the actions you are taking to address the deficiencies identified during the inspection and cited on our Form FDA 483.

Pseudomonas aeruginosa Outbreak and FDA Testing of Samples

In December 2022, FDA began collaborating with the Center for Disease Control and Prevention (CDC) on an investigation into the multistate outbreak of antibiotic-resistant Pseudomonas aeruginosa infections that ultimately affected more than 80 patients and led to 4 patient deaths and at least 14 cases of vision loss. As part of this investigation, FDA collected finished product samples of Artificial Tears and Artificial Eye Ointment batches that were manufactured for Delsam Pharma LLC by Global Pharma Healthcare Private Limited, and we sent the samples for sterility testing at FDA laboratories. Our analysis of intact (unopened) units found that four batches of Delsam Pharma’s Artificial Tears were non-sterile.² In addition, we also sampled a batch of your Artificial Eye Ointment product, and this batch was also found to be non-sterile. The testing of these intact units revealed that your ophthalmic drug products were intrinsically contaminated with microorganisms. These test results demonstrate that these batches are adulterated under section 501(a)(1) of the FD&C Act, in that they consist in whole or in part of a filthy, putrid, or decomposed substance.

Significantly, the contamination of the drug products manufactured at Global Pharma Healthcare Private Limited, as indicated by FDA sample results, also demonstrates that the drugs made for you at Global Pharma Healthcare Private Limited are adulterated under 501(a)(2)(A) of the FD&C Act as they have been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health.

FDA’s laboratory also performed container closure integrity testing of Delsam Pharma’s Artificial Eye Ointment, batch (b)(4), manufactured for your firm. FDA tested 20 units, and 1 unit was found to allow microbiological ingress, which confirmed that your container-closure system lacks integrity and is insufficient for maintaining sterility. Notably, batch (b)(4) was also found to be non-sterile through FDA testing.

Inspection of your CMO

An inspection of Global Pharma Healthcare Private Limited, conducted from February 20 to March 2, 2023, revealed multiple CGMP violations, including but not limited to, the use of filling equipment that was inadequate for its intended use; the failure to validate the sterilization processes used to render ophthalmic drug products sterile; the lack of container closure integrity for multidose ophthalmic drugs that purport to be sterile; and the manufacture of multidose, over-the-counter (OTC) ophthalmic drugs that lack antimicrobial properties to preserve the formulation. Global Pharma Healthcare Private Limited was placed on Import Alert 66-40 on January 3, 2023, and received a Warning Letter (WL# 320-24-03), dated October 20, 2023, documenting the egregious CGMP violations. FDA sent you a copy of the warning letter issued to Global Pharma Healthcare Private Limited.

Receipt and Distribution of Adulterated Drugs

Our inspection of your firm and review of your import records indicated that you use Global Pharma Healthcare Private Limited, FEI 3012323885, as your CMO, as evidenced by your receipt of a shipment of Delsam Pharma’s Artificial Tears and Delsam Pharma’s Artificial Eye Ointment, in February 2021. You distributed products in this shipment that were found to be not sterile by FDA testing.

Inspection of Delsam Pharma LLC

Your firm utilized a CMO to manufacture your ophthalmic drug products; however, your firm failed to have adequate procedures to ensure that all ophthalmic drug products produced for your firm met appropriate quality attributes and were free of microbial contamination. You also failed to have adequate supplier qualification procedures to ensure that the drug products received from Global Pharma Healthcare Private Limited were manufactured in compliance with CGMP prior to being distributed in the United States.

FDA is also concerned about your handling of product complaints. For example, you lacked written procedures describing the handling of all written and oral complaints regarding your drug products and failed to document and investigate complaints that were received. As a distributor, it is imperative that you communicate complaints to your CMO in a timely manner for appropriate follow-up.

You are responsible for ensuring that the drugs you distribute are not adulterated and are manufactured in accordance with CGMP requirements.

Provide a detailed plan to ensure you do not receive or deliver adulterated drugs in interstate commerce, in violation of section 301(c) of the FD&C Act, 21 U.S.C. 331(c). Items in your plan should include a full evaluation of your supplier and contact manufacturer qualification program, including a plan to conduct periodic audits of your suppliers, and a full evaluation of your handling of complaints. Also provide your evaluation of your current suppliers and contract manufacturers.

Misbranded Drug Violations

Delsam Pharma’s ARTIFICIAL TEARS and Delsam Pharma’s ARTIFICIAL EYE OINTMENT 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. Specifically, Delsam Pharma’s ARTIFICIAL TEARS is intended for use as an ophthalmic demulcent, and Delsam Pharma’s ARTIFICIAL EYE OINTMENT is intended for use as an ophthalmic emollient.

Examples of claims from your product labeling that provide evidence of the intended uses (as defined by 21 CFR 201.128) of your products as drugs include, but may not be limited to, the following:

Delsam Pharma’s ARTIFICIAL TEARS
“Drug Facts . . . Uses . . . ■ for use as a protectant against further irritation or to relieve dryness of the eye ■ for the temporary relief of discomfort due to minor irritations of the eye, or to exposure to wind or sun” [from your product’s label]

Delsam Pharma’s ARTIFICIAL EYE OINTMENT
“Drug Facts . . . Uses . . . For use as a lubricant to prevent further irritation or to relieve dryness of the eyes.” [from your product’s label]

Delsam Pharma’s ARTIFICIAL TEARS and Delsam Pharma’s ARTIFICIAL EYE OINTMENT are misbranded under section 502(j) of the FD&C Act, 21 U.S.C. 352(j), because they are not sterile. 21 CFR 200.50 states that all preparations offered or intended for ophthalmic use should be sterile, and if not are deemed misbranded under section 502(j) of the FD&C Act.³ However, FDA analysis of samples of Delsam Pharma’s ARTIFICIAL TEARS and Delsam Pharma’s ARTIFICIAL EYE OINTMENT determined that these products were contaminated with microorganisms. For example, microorganisms in your products included but were not limited to the following: Delsam Pharma’s ARTIFICIAL TEARS contained Bacillus species and Delsam Pharma’s ARTIFICIAL EYE OINTMENT contained Burkholderia cepacia complex. There is a reasonable probability that instillation of a bacterially contaminated eye product into the eye may cause a range of ocular infections, from minor to serious, vision-threatening infections which could progress in some cases to life-threatening systemic bacterial infection. Therefore, Delsam Pharma’s ARTIFICIAL TEARS, and Delsam Pharma’s ARTIFICIAL EYE OINTMENT are misbranded under section 502(j) of the FD&C Act, 21 U.S.C. 352(j).

In addition, Delsam Pharma’s ARTIFICIAL EYE OINTMENT is further misbranded under section 502(a) of the FD&C Act, 21 U.S.C 352(a), because its labeling is false or misleading. Specifically, the principal display panel (PDP) of the product label purports the product to be “sterile.” However, FDA analysis of samples of Delsam Pharma’s ARTIFICIAL EYE OINTMENT determined that it was contaminated with microorganisms including Burkholderia cepacia complex. Therefore, the labeling for Delsam Pharma’s ARTIFICIAL EYE OINTMENT is false or misleading, because the product is not in fact sterile for its intended use as an ophthalmic emollient drug product, and thus the product is misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a).

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).

Drug Recalls

On February 2, 2023, a voluntary recall was initiated by Global Pharma Healthcare Private Limited for Artificial Tears, including those distributed by Delsam Pharma LLC, based on bacterial contamination and CGMP concerns. Global Pharma Healthcare Private Limited’s recall announcement was posted to the FDA website: https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/global-pharma-healthcare-issues-voluntary-nationwide-recall-artificial-tears-lubricant-eye-drops-due.

On February 22, 2023, FDA held a teleconference with you and Global Pharma Healthcare Private Limited. We recommended you remove batch (b)(4) of Artificial Eye Ointment in U.S. distribution. On February 24, 2023, a voluntary recall was initiated for Delsam Pharma’s Artificial Eye Ointment due to non-sterility. Global Pharma Healthcare Private Limited’s recall announcement was posted to the FDA website: https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/global-pharma-healthcare-issues-voluntary-nationwide-recall-delsam-pharma-artificial-eye-ointment.

Drug Distribution Ceased

We acknowledge that you inactivated your labeler code and discontinued drug listing submissions to FDA. In response to this letter, clarify whether you intend to resume distributing drugs for the U.S. market in the future.

If you plan to resume any drug operations regulated under the FD&C Act, notify this office before resumption. You are responsible for resolving all deficiencies and systemic flaws applicable to your drug operations. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all corrective action and preventive action (CAPA).

Use of Contract Manufacturers

Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.

You are responsible for the quality of your drugs regardless of agreements in place with your contract facility. You are required to ensure that the drugs you distribute are not adulterated. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/media/86193/download.

Conclusion

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist 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. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts. We may re-inspect to verify that you have completed your corrective actions.

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 [email protected]. Your notification should refer to Warning Letter CMS # 657340 and reference FEI 3018035065.

If you have questions, please contact Compliance Officer CAPT Liatte Closs at [email protected].

Sincerely,
/S/

Lisa Harlan
Program Division Director
OPQO Division I

__________________________

1 We also note that 21 CFR 200.50(a)(2) states, in relevant part, “…liquid preparations offered or intended for ophthalmic use that are not sterile may be regarded as adulterated within the meaning of section 501(c) of the Federal Food, Drug, and Cosmetic Act…”, and this regulation extends such adulteration to “all preparations for ophthalmic use regulated as drugs”.

2 The Artificial Eye Ointment sample was found to contain Cytobacillus spp. and Burkholderia Cepacia complex. The Artificial Tears samples were found to contain Bacillus spp., Paenibacillus spp, Cutibacterium spp., and Clostridium spp.

3 21 CFR 200.50(a)(2) states, in relevant part, “liquid preparations offered or intended for ophthalmic use that are not sterile…may be deemed misbranded within the meaning of section 502(j) of the FD&C Act. This ruling is extended to affect all preparations for ophthalmic use. By this regulation, this ruling is applicable to ophthalmic preparations that are regulated as drugs.”