- Delivery Method:
- Return Receipt Requested
Recipient NameStephen S. Laddy
Recipient TitleChief Executive Officer
- MasterPharm LLC
115-02 Liberty Avenue, Suite 200
South Richmond Hill, NY 11419-1902
- Issuing Office:
- Division of Pharmaceutical Quality Operations I
July 19, 2021
Dear Mr. Laddy:
From May 28, 2020 to June 15, 2020, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, MasterPharm LLC, located at 115-02 Liberty Avenue, Suite 200, South Richmond Hill, New York 11419. During the inspection, the investigator noted serious deficiencies in your practices for producing drug products, which put patients at risk.
FDA issued a Form FDA 483 to your firm on June 15, 2020. FDA acknowledges receipt of your facility’s response, dated June 28, 2020. Additionally, FDA acknowledges that your firm voluntarily ceased dispensing drug products in capsule dosage form until corrective actions are implemented and, on July 2, 2020, voluntarily recalled compounded products within expiry that were prepared by (b)(4) of your firm’s technicians with initials “(b)(6), (b)(7)(C).” from (b)(4), due to cross contamination with other drug products, super-potency issues, and lack of processing controls. Based on this inspection, it appears that you produced drug products that violate the Federal Food, Drug, and Cosmetic Act (FDCA).
A. Compounded Drug Products Under the FDCA
Section 503A of the FDCA describes the conditions under which human drug products compounded by a licensed pharmacist in a State licensed pharmacy or a Federal facility, or a licensed physician, qualify for exemptions from three sections of the FDCA: compliance with current good manufacturing practice (CGMP) (section 501(a)(2)(B)); labeling with adequate directions for use (section 502(f)(1)); and FDA approval prior to marketing (section 505) [21 U.S.C. §§ 351(a)(2)(B), 352(f)(1) and 355(a)].
B. Violations of the FDCA
Adulterated Drug Products
FDA received MedWatch reports in April 2020 regarding adverse events experienced by 74 patients associated with Finasteride Plus capsules produced by your firm that were labeled as containing 1.25 mg per capsule. FDA analysis of a sample of this product found that it contained an average of 1.49 mg of finasteride per capsule. Additionally, FDA analysis of this sample found that the capsules contained undeclared minoxidil, an antihypertensive drug, at an average of 127.86 mg per capsule, which greatly exceeds the amount found in FDA approved products. Under section 501(c) of the FDCA [21 U.S.C. § 351(c)], a drug is deemed to be adulterated if it is unrecognized in an official compendium and its strength differs from, or its quality or purity falls below, that which it purports or is represented to possess. The strength of your finasteride capsules differed from and exceeded the labeled amount of finasteride the product was purported to possess and contained an undeclared active drug ingredient causing it to be adulterated under section 501(c) of the FDCA.
In addition, the FDA investigator noted that drug products were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA. For example, the investigator observed that:
1. The ISO classified aseptic processing areas have difficult to clean and visibly dirty equipment and surfaces.
2. Non-microbial contamination was observed in your production area.
3. Your firm handled hazardous drug products without providing adequate containment, segregation, or cleaning of work surfaces and utensils to prevent cross-contamination.
4. Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination.
5. Gloved fingertip sampling was conducted immediately after an operator disinfected their gloved hands. Therefore, these results may not provide meaningful data.
6. Your facility is designed and operated in a way that may permit the influx of lesser quality air into a higher quality air area.
Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, It is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.
Misbranded Drug Products
Under section 502(a) of the FDCA [21 U.S.C. § 352(a)], a drug product is misbranded if its labeling is false or misleading in any particular. As noted above, analyses showed that your Finasteride Plus oral capsules, with a labeled strength of 1.25mg, contained an average 1.49 mg per oral capsule. Additionally, labels for your Finasteride Plus oral capsules did not disclose that this product contained the antihypertensive drug, minoxidil, in an amount that greatly exceeds the amount found in FDA approved products. Because the labeling of this drug product was false or misleading, it was misbranded under section 502(a) of the FDCA.
It is a prohibited act under section 301(k) [21 U.S.C. § 331(k)] of the FDCA to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being misbranded.
C. Corrective Actions
We have reviewed your firm’s responses to the Form FDA 483. Additionally, FDA acknowledges that your firm voluntarily ceased dispensing drug products in capsule dosage form and on July 2, 2020 voluntarily recalled compounded products within expiry that were prepared by (b)(4) of your firm’s technicians with initials “(b)(6), (b)(7)(C)” from (b)(4).
Regarding your responses related to the insanitary conditions, some of your corrective actions appear adequate; however, we cannot fully evaluate the adequacy of the following corrective actions described in your response because you did not include sufficient information or supporting documentation:
1. In your response, you stated: “All smoke studies are performed dynamically with MasterPharm’s operators performing Aseptic Process Simulation (b)(4) and observed by supervisory staff from MasterPharm.” However, a review of smoke study videos, dated March 26th, 2020, collected during the inspection found that the smoke studies did not include all processing steps performed and equipment used within ISO 5 areas during aseptic drug production. The March 2020 smoke studies only evaluated air flow patterns for (b)(4) of vials and syringes. Other aseptic processing steps your firm performs in the ISO 5 areas, including but not limited to, use of mechanical pumps, transfer of materials, and vial stoppering were not simulated in the smoke study videos. Furthermore, your response did not include documentation of any new smoke studies conducted since March 2020.
2. In your response, you stated: “we are currently in the process of making necessary changes to the ISO7 hazardous negative pressure room to add a pressure gauge to measure the pressure differential between the Clean Room (b)(4), which houses the BSC/(b)(4), and (b)(4).” You also provided a purchase order for the gauge. However, it is unclear if the pressure gauge has been installed because you did not provide updated information such as the installation date and/or a photo of the installed gauge.
Please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether drug products you compound meet the conditions of section 503A.
FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third-party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation.
The violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.
You should take prompt action to correct any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.
Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. This letter notifies you of our concerns and provides you an opportunity to address them. If you believe your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.
Your written notification should refer to the Warning Letter Number above (WL #612401). Please send your reply to: ORAPharm1_responses@fda.hhs.gov.
If you have questions regarding the contents of this letter, please contact Jose O. Hernandez-Guzman at firstname.lastname@example.org or cell # 240-802-0912.
Program Division Director/District Director
Office of Pharmaceutical Quality Operations, Division I