---

---

---

DATE: 7/1/2020

Case #: 608461

WARNING LETTER

Dear Dr. Shui:

From February 25, 2019, to March 18, 2019, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, Front Door Pharmacy, LLC dba Pure Pharmaceuticals, located at 8973 Interchange Drive, Houston, TX 77054. During the inspection, the investigator noted serious deficiencies in your practices for producing sterile drug products, which put patients at risk.

FDA issued a Form FDA 483 to your firm on March 18, 2019. FDA acknowledges receipt of your facility’s response, dated April 4, 2019. 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)].¹ Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A.

B. Violations of the FDCA

Adulterated Drug Products

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:

1. Personnel engaged in aseptic processing while exposing skin in the ISO 5 laminar airflow (LAF) hood. Specifically, an operator exposed his bare hands by changing gloves inside the ISO 5 LAF hood during aseptic operations. Furthermore, once donned, the gloves did not cover the skin and hair around his wrists.

2. The ISO-classified areas had visibly dirty equipment and difficult to clean surfaces. Specifically, a mixer in the ISO 5 LAF hood had foreign residue on its outer surface, the (b)(4) in the ISO 7 Cleanroom had a black dust-like residue on the top surface, and a stainless-steel table in the ISO 7 Anteroom had surface areas coated in an oily foreign substance and a powder residue. Additionally, the stool covering in the ISO 7 Cleanroom was covered in a cloth-like material that is not easily cleanable.

3. Cleaning and disinfection in the cleanrooms and ISO 5 classified aseptic processing area was inadequate. Specifically, our investigator observed that:
  a. Your firm maintained the ISO 5 LAF hood in a powered-off state until (b)(4) prior to beginning aseptic processing and did not disinfect with a sporicidal agent prior to producing sterile drug products.
  b. Your firm used unlabeled bottles of non-sterile (b)(4) and non-sterile (b)(4) to disinfect the ISO 5 LAF hood.
  c. Your firm did not use a sporicidal agent to disinfect your aseptic processing areas.

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 were produced in an environment that may not provide adequate protection against the risk of contamination.

5. Air vents within your classified areas were located on the ceiling, adjacent to the HEPA filters. This design may prevent the dilution of particle-laden air by the HEPA filtered air. Therefore, your firm had no assurance of proper air circulation within the classified areas.

6. Your firm handled hazardous drug products without providing adequate containment, segregation, and cleaning of work surfaces and utensils to prevent cross-contamination.

7. Personnel touched equipment or other surfaces located outside of the ISO 5 classified aseptic processing area with gloved hands and then engaged in aseptic processing without changing or sanitizing gloves.

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. Regarding your responses related to the insanitary conditions, some of your proposed 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. You state that you now use (b)(4) as a sporicidal agent; however, you did not provide sufficient information about the concentration of the (b)(4) solution, the frequency of use, and the intended contact time. Further, you did not provide an updated copy of your Standard Operating Procedure (SOP) with documentation of retraining personnel.

2. We reviewed the smoke studies that your firm performed in the ISO 7 and ISO 8 classified areas and noted that they did not demonstrate that the current placement of your incoming vents with HEPA filters and return vents are capable of ensuring appropriate ISO classified air conditions. Furthermore, your response did not provide sufficient supporting documentation (e.g., representative sampling for non-viable particulate counts) for our review. Therefore, we remain concerned that the current design may prevent the dilution of particle-laden air by the HEPA filtered air.

3. You state that you will recertify your ISO 5 LAF hood under dynamic conditions; however, supporting documentation, such as a smoke study and non-viable particulate testing within the ISO 5 area under dynamic conditions, were not provided for our review.

4. You state that you will construct a dedicated space for producing hazardous drugs, but you did not provide information about:
  a. protecting the aseptic processing area during construction;
  b. controls to prevent cross-contamination (e.g., using dedicated equipment for producing hazardous drug products and/or changing your procedures to include cleaning agents that will deactivate hazardous drugs).

Regarding your responses related to the insanitary conditions, the following corrective actions appear deficient:

1. You did not commit to discontinuing the practice of exposing skin in the ISO 5 LAF hood nor did you address updating procedures and retraining or requalifying personnel on proper gowning technique.

2. You stated that the mixer surface was burned instead of having a foreign substance but did not address that the burned equipment surface is no longer easy to clean and sanitize and therefore is no longer suitable for its intended use. Additionally, in response to the visibly dirty equipment and difficult to clean surfaces, you did not commit to revising procedures and retraining personnel on proper cleaning and sanitizing techniques as well as equipment maintenance.

3. You have not ensured that the (b)(4) is sterile because you store it (b)(4) in a non-sterile reusable bottle. The use of non-sterile disinfectants increases the risk of contamination in the aseptic processing area.

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.

D. Conclusion

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 the violations identified above 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 the violations cited in this letter. Failure to promptly correct these 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 correct violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you do not believe that the products discussed above are in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot complete corrective action within fifteen (15) working days, state the reason for the delay and the time within which you will complete the correction.

Your written notification should refer to case # 608461.

Please electronically submit your reply, on company letterhead, to Jamillah Selby, Compliance Officer, at [email protected]. In addition, please submit a signed copy of your response to [email protected] and/or [email protected].

If you have questions regarding the contents of this letter, you may contact Jamillah Selby via phone at 214-253-5218 or email at. [email protected].

Sincerely,
/S/

Monica R. Maxwell
Program Division Director
Office of Pharmaceutical Quality Operations, Division II

Cc: Allison Vordenbaumen Benz, Executive Director, Texas State Board of Pharmacy

____________________

1 We remind you that there are conditions other than those discussed in this letter that must be satisfied to qualify for the exemptions in section 503A of the FDCA.