North American Custom Laboratories, LLC dba FarmaKeio Superior Custom Compounding

From March 1, 2022, to March 10, 2022, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, North American Custom Laboratories, LLC dba FarmaKeio Superior Custom Compounding, located at 1736 North Greenville Avenue, Richardson, TX 75081. 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 March 10, 2022. FDA acknowledges receipt of your facility’s response, dated March 30, 2022, as well as your subsequent correspondence. FDA acknowledges that your firm initiated a voluntary recall of drug products that are intended to be sterile on April 5, 2022. Based on this inspection, it appears that you produced drug products that violate the Federal Food, Drug, and Cosmetic Act (FDCA).

Section 503A of the FDCA [21 U.S.C. § 353a] 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 B. Violations of the FDCA

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. Your firm used a (b)(4) for the purposes of product sterilization that was not appropriate for pharmaceutical use and the (b)(4) testing was inadequate. Therefore, you do not have assurance that the (b)(4) was integral throughout use.

2. Your firm did not adequately disinfect materials or supplies during transfer from the ISO 8 cleanroom into higher classification areas.

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. 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.

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.

We have reviewed your firm’s response to the Form FDA 483. Regarding your response 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 to Observation 1 of the Form FDA 483, we acknowledge your firm’s statement that you have regained supply of and resumed use of previously unavailable (b)(4) for “immediate use sterile subcutaneous injectable compounding” at your facility. However, you did not provide sufficient evidence of the corrective actions, such as purchase orders, current batch records (i.e., formula work sheets), or (b)(4) testing procedures for the newly acquired (b)(4).

2. Regarding the pink residue on the ceiling, vents, and walls in your production area as described in Observation 5 of the Form FDA 483, you provided your revised SOP, 02-CPCP-12 Non-Sterile Hazardous Compound – Hormone Only and committed to “attempting a deep scrubbing of the room.” It is unclear if this cleaning was attempted and/or effective to remediate this observation or if your revised procedures have prevented reoccurrence.

3. In your response to Observation 7 of the Form FDA 483, we acknowledge your firm’s statement that, “Moving forward, when smoke studies are conducted, footage from video will record, in detail, the dynamic compounding of sterile compounding in a PEC.” However, we cannot fully evaluate your response as you did not provide sufficient supporting documentation, such as an updated smoke study protocol or an updated detailed report, and/or video.

4. In your response to Observation 8 of the Form FDA 483, we acknowledge your firm’s statement that, “(b)(4).” However, we cannot fully evaluate your response as you did not provide sufficient supporting documentation, such updated media fill protocol or results.

In addition, from review of the evidence collected during the inspection, your October 26, 2021, Environmental Monitoring Report lists your action level for the ISO 5 area as (b)(4) cfu/m3 for “Air Test” and (b)(4) cfu/plate for “Surface Test.” Please note that any microbial contamination in the ISO 5 area is a serious concern and considered an insanitary condition. If any ISO 5 recovery occurs, your firm should immediately assess the impact on drug products produced. This assessment should include a thorough evaluation of how contamination could have entered this critical area, and over what period of time the contamination could have existed, as well as drug products that remain on the market that could have been affected.

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 processing 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.

Your written notification should refer to case number 642792.

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.