Recipient NamePraful Patel
- Texas Longhorn RX, LLC
5900 Balcones Dr, STE 100
Austin, TX 78731
- Issuing Office:
- Office of Pharmaceutical Quality Operations, Division II
Date: August 29, 2022
Case #: 639220
Dear Mr. Patel:
From October 18, 2021, to November 2, 2021, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, Vita Pharmacy, LLC dba Talon Pharmacy of Boerne, located at 1430 South Main Street, Suite 105, Boerne, Texas 78006. During the inspection, the investigator noted serious deficiencies in your practices for producing drug products intended or expected to be sterile, which put patients at risk.
FDA issued a Form FDA 483 to your firm on November 2, 2021. FDA acknowledges receipt of your facility’s response, dated November 15, 2021. 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
The FDA investigator noted that drug products intended or expected to be sterile 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,
1. Your facility is designed and operated in a way that may permit the influx of lesser quality air into a higher quality air area, in that:
a. The (b)(4) curtain separating the ISO5-classified area from the surrounding ISO7-classified space is not adequately sealed.
b. There is a visible crack in the (b)(4) separating the ISO7-classified cleanroom from the adjoining ISO8-classified space.
2. You handled hazardous drug products without providing adequate containment and segregation to prevent cross-contamination in that hazardous drug products are produced in an ISO5-classified biological safety cabinet (BSC), which is located in the same ISO7-classified cleanroom where non-hazardous drug products are produced.
3. The ISO-classified areas had visibly dirty equipment and difficult to clean surfaces. Specifically, an unknown foreign substance was observed adhered to the plastic grille of a HEPA filter in your ISO5-classified area.
4. Your firm did not disinfect materials during transfer from the ISO7-classified cleanroom into the ISO5-classified area.
5. Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO5 area. Specifically, smoke studies have never been performed in your ISO5-classified BSC.
6. Your media fills were not performed under the most challenging or stressful conditions. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility.
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.
C. Corrective Actions
We have reviewed your firm’s response to the Form FDA 483. Although one of your proposed corrective actions appears adequate, others are deficient. For example,
1. Facility design/airflow concerns:
a. Regarding the visible gap between the (b)(4) curtain and the ceiling of your ISO7-classified cleanroom, your response notes your commitment to properly sealing the (b)(4) to the ceiling to prevent the influx of lower quality air into the ISO5-classified area. However, you did not describe in any detail the manner in which the (b)(4) curtain will be sealed to the ceiling, or the materials to be used. Furthermore, it is likely that a modification to the ISO5 classified area would necessitate recertification of the ISO5 area, and possibly the surrounding ISO7-classified cleanroom.
Your response makes no reference to recertification. Lastly, your response does not provide any time frame by which the modification will be completed, or whether production of sterile drug products will be suspended until such modification is complete.
b. Regarding the crack in the (b)(4) separating the ISO7-classified cleanroom from ISO8-classified space, your response describes a plan to either replace the (b)(4) wall or seal the crack. However, you fail to specify exactly how the repair will be made, and how the suitability of the ISO7 cleanroom and ISO5 area contained within will be assured following the repair. For example, it is likely the ISO7 area, and possibly the ISO5 area within will require recertification following the modification. Your response makes no mention of any such requirement. Furthermore, if you choose to seal the crack instead of replacing the (b)(4), you must ensure the suitability of the material used to seal the crack, as well as verify the effectiveness of such repair.
2. Regarding your response to producing hazardous drug products without adequate controls to prevent cross-contamination, you state you will relocate the BSC to a separate, negatively pressured cleanroom. While moving the BSC to a dedicated, negatively pressured cleanroom may be an effective long-term solution, it fails to address the existing cross-contamination risk as you do not commit to immediately ceasing all hazardous drug production, and you did not provide a time frame by which the relocation of the BSC will be complete. It should be noted that when moved, the BSC and room in which it will be housed, as well as the ISO7 area from which it is removed will need to be qualified and appropriately certified/re-certified prior to operation.
3. Regarding your response to the presence of an unknown substance on the plastic grille of a HEPA filter in the ISO5-classified area, you note the “dark residue” was cleaned and the “stain” removed. You also state the substance was cultured, and no growth was recovered. However, you failed to determine the identity or source of the substance. Consequently, there’s no assurance the underlying problem has been effectively eliminated. Additionally, you did not describe if/how the HEPA filter was evaluated to ensure it was not adversely impacted by the substance (e.g., no filter integrity/leak testing, and airflow/velocity testing were conducted). Consequently, it is not known whether the environment is suitable for sterile drug production.
4. Regarding your response to the failure of personnel to adequately disinfect materials as they are transferred from the ISO7-classified area to the ISO5-classified area, you state staff will be retrained in proper sterile compounding procedures, adding this training will be documented accordingly. However, you did not provide any specific details on the cleaning steps in which staff will be trained. Consequently, there is no assurance the outer packaging of materials and supplies will be adequately and routinely disinfected upon transfer from areas of lower air quality to areas of higher air quality. Lastly, your response does not describe the disposition of the lot of drug product being prepared when the observation was made.
5. Regarding the failure to perform airflow visualization (“smoke”) studies in the ISO5-classified BSC where hazardous drugs, intended to be sterile, are produced, you indicate smoke studies will be performed. However, you do not describe in any detail the manner in which smoke studies will be performed, or how they will be evaluated to determine the adequacy of HEPA-filtered airflow within the BSC. You do not state when the studies will be performed or a time frame by which the results will be evaluated. Additionally, your response does not commit to suspending the production of hazardous sterile drugs until the BSC can be adequately certified, to include the completion of acceptable airflow visualization (“smoke”) studies.
Furthermore, it is noted that your Sterile Compounding Suite Certification Reports from January 2021 and July 2021 do not include any reference to the BSC. Consequently, the BSC does not appear to be subject to any routine certification/re-certification requirements such as non-viable particle counts, HEPA filter leak & integrity tests, or viable air and surface sampling. Consequently, the ISO5 classification of your BSC cannot be verified, nor can its suitability to produce hazardous drug products intended to be sterile.
6. Regarding the failure to conduct aseptic process simulation (“media fills”) under the most challenging, stressful conditions, your response indicates you will perform media fills that more closely correlate with the (b)(4) batch sizes. However, your response does not describe in any detail the specific manner in which media fill studies will be performed to ensure they simulate the most challenging, stressful conditions associated with actual drug production activities. While your response suggests steps are being taken to address variables such as batch size, it fails to address other production activities that may represent most challenging, stressful, or worst-case scenarios such as sterile (b)(4), filling, and stoppering & capping of vials, etc.
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 address 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 in which you will do so.
Your written notification should refer to case number 639220.
Please electronically submit your reply, on company letterhead, to Shawn Larson, Compliance Officer, at ORAPHARM2_RESPONSES@fda.hhs.gov and Shawn.Larson@fda.hhs.gov
If you have questions regarding the contents of this letter, you may contact Dr. Larson via phone at 214-253-5216 or email at Shawn.Larson@fda.hhs.gov.
Monica R. Maxwell
Program Division Director
Office of Pharmaceutical Quality Operations,
David Hall – Pharmacist in Charge
Vita Pharmacy, LLC dba Talon Pharmacy of Boerne,
1430 South Main Street, Suite 105, Boerne, Texas 78006