Delivery Method:
VIA Electronic Mail
Product:
Animal & Veterinary
Drugs
Recipient:

Recipient Name

Mr. Jaime Della Polla

Recipient Title

President and Owner

Rapid Equine Solutions, LLC

31a Mount Pleasant Rd
Aston, PA 19014-1407
United States

Issuing Office:
Division of Pharmaceutical Quality Operations I

United States

WARNING LETTER
CMS# 595556

June 12, 2020

Dear Mr. Della Polla:

This letter concerns the animal drugs you compound from bulk drug substances at Rapid Equine Solutions, LLC. From July 22 - August 9, 2019, the U.S. Food and Drug Administration (FDA) conducted an inspection of your compounding pharmacy located at 31a Mount Pleasant Road in Aston, Pennsylvania. This inspection was initiated following the death of three horses that were given an animal drug compounded by your pharmacy. The animal drug was an oral paste containing toltrazuril and pyrimethamine.

As described below, FDA's inspection revealed that animal drug products compounded by your firm are adulterated and misbranded under the Federal Food, Drug, and Cosmetic Act (FD&C Act). You can find the FD&C Act and its associated regulations on the Internet through links on the FDA's web page at www.fda.gov.

On August 9, 2019, FDA issued a Form FDA 483 to you, listing our inspectional observations. FDA acknowledges receipt of your facility's responses to the Form FDA 483, dated August 30, 2019, September 27, 2019, October 15, 2019, and November 15, 2019. Additionally, we
acknowledge your firm's May 24, 2019, actions to voluntarily recall the toltrazuril/pyrimethamine paste drug product, Lot#20190509-11.

1. Adulteration

a. Insanitary Conditions
The animal drugs you compound are adulterated within the meaning of section 501(a)(2)(A) of the FD&C Act, 21 U.S.C. § 351(a)(2)(A), in that they are prepared, packed, or held under insanitary conditions whereby they may be contaminated with filth, or whereby they may be rendered injurious to health. Specifically, during the inspection FDA observed:

  • Approximately three insects in the laboratory room as operators were preparing vials for the (b)(4). Two were located on the viewing window of the sterile production room and a third was observed to be within the nonsterile anteroom. FDA also observed a roll of flying insect tape hanging from the ceiling next to the sink in the laboratory room. Vermin (e.g., insects) are unacceptable in a production environment for both sterile and non-sterile drugs and can contribute to contamination in drug products.
  • An unknown white film on the floor in the sterile production room and debris in the corners of the room, which has the potential to contaminate drug products in your facility.
  • Clothing of personnel engaged in the production of drug products is not appropriate for the duties they perform, such as engaging in aseptic processing after leaving the cleanroom and re-entering from a non-classified area without first replacing gowning apparel (e.g., gowns, mask, goggles, foot covers, gloves). Personnel moving in and out of the cleanroom without re-gowning may bring contaminants from non-classified areas into the cleanroom.

b. Potency Issues
In addition, the toltrazuril/pyrimethamine paste drug product that you compounded was adulterated under Section 501(c) of the FD&C Act, 21 U.S.C. § 351(c), in that its strength differed from, or its purity or quality fell below, that which it purported or was represented to possess.

Our inspection revealed that on May 9, 2019, you compounded the toltrazuril/pyrimethamine paste drug product, Lot#20190509-11, with a Beyond Use Date of November 5, 2019. (b)(4)of (b)(4) units were distributed. The label for this product stated it contained 416 mg/ml of toltrazuril and 17 mg/ml of pyrimethamine. FDA collected samples of this product to conduct an analysis. FDA analytical results of one of the samples contained 13.5 mg/mL of toltrazuril, which is 3% of the declared concentration, and 361 mg/mL of pyrimethamine, which is 2122% of the declared concentration. Another sample contained 11.2 mg/mL of toltrazuril, which is 3% of the declared concentration, and 307 mg/mL of pyrimethamine, which is 1808% of the declared concentration.

2. Misbranding

The toltrazuril/pyrimethamine paste drug product, Lot#20190509-11, with a Beyond Use Date of November 5, 2019, compounded by your firm on May 9, 2019, was also misbranded within the meaning of Section 502(a) of the FD&C Act, 21 U.S.C. § 352(a), because the labeling was false and misleading.

As discussed above, the product sample test results indicate that the toltrazuril/pyrimethamine paste drug product was sub-potent with respect to toltrazuril and super-potent with respect to pyrimethamine compared to the amounts declared on the label, which makes the labeling false. Under section 301(a) of the FD&C Act, 21 U.S.C. 331(a), the introduction or delivery for introduction into interstate commerce of adulterated or misbranded drugs is prohibited. Further, under section 301(k) of the FD&C Act, 21 U.S.C. 331(k), the causing of drugs to become adulterated or misbranded while the drugs are held for sale after shipment of one or more of their components in interstate commerce is prohibited.

Corrective Actions

In your responses dated August 30, 2019, September 27, 2019, October 15, 2019, and November 15, 2019, you state that you have, among other actions, hired pest control services, revised your cleaning and disinfectant practices, arranged to provide garbing for aseptic processing areas, and implemented garb and fingertip testing protocols. We are unable to evaluate the adequacy of your garbing, cleaning, and disinfectant practices or testing because you did not provide supporting documentation such as validation summaries or test results. You also state that you determined that the root cause of the subpotency and superpotency in the toltrazuril/pyrimethamine paste drug product was a mix-up in the weighing of the two active pharmaceutical ingredients (API). You state that you have revised your standard operating procedures to prevent this mix-up in the future, including a requirement (b)(4) of the API on the scale to the compounding record, a requirement to have a second staff member check and verify weights prior to mixing, and third-party vendor testing under certain circumstances. We are unable to evaluate the adequacy of your testing approach because of the lack of supporting documentation to show how you determined the batch size and number of APIs for third-party testing. We note that you had a requirement for a secondary check in place at the time of the mix-up. We will evaluate the adequacy of your corrective actions at the next inspection.

The violations cited in this letter are not intended to be an all-inclusive list of violations at your facility. As a pharmacy engaged in distributing drugs in interstate commerce you are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence or the occurrence of other violations. It is your responsibility to assure that your firm complies with all requirements of federal law, including FDA regulations.

You should take prompt action to correct the violations described in this letter and to establish procedures to ensure that these violations do not recur. Failure to address this matter may result in legal action without further notice, including, without limitation, a seizure or an injunction.

In addition, we provide the following comments on your corrective actions:

  • You should ensure that your (b)(4) processes, including the (b)(4) process and the (b)(4) process for injectable drugs, produce drug products with an acceptable sterility assurance during your validation.
  • You should ensure your facility controls can address conditions that can negatively impact the final drug product, including vermin, unknown substances on the floors, and depyrogenation controls. Further, your cleaning methods should be capable of removing residuals of API and cleaning and sanitizing agents and objectionable organisms from multi-use equipment and utensils used to produce sterile products.

Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct these violations. Please include an explanation of each step being taken to prevent the recurrence of these violations, as well as copies of related documentation. If you cannot complete the corrective actions within 15 working days, state the reason for the delay and the time within which you will complete the correction. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration.

Send your electronic response to orapharm1_responses@fda.hhs.gov. Please identify your response with FEI #3006708880 and refer to Warning Letter CMS# 595556.

If you have any questions, contact Compliance Officer Juan Jimenez at juan.jimenez@fda.hhs.gov or call 1-518-453-2314 X-1014.

/S/
Diana Amador-Toro
Program Division Director/District Director
U.S. Food and Drug Administration
OPQO Division I / New Jersey District