- Delivery Method:
- Via Email
Recipient NameTaylor Cline
- Integrated Health Concepts Inc. dba Conversio Health
720 Aerovista Place, Suite D
San Luis Obispo, CA 93401-8726
- Issuing Office:
- Division of Pharmaceutical Quality Operations IV
September 10, 2020
Dear Mr. Cline:
From August 13, 2019, to September 25, 2019, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, Integrated Health Concepts Inc. dba Conversio Health, located at 720 Aerovista Place, Suite D, San Luis Obispo, California 93401. 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 September 25, 2019. FDA acknowledges receipt of your facility’s responses, dated October 16, 2019, November 8, 2019, November 27, 2019, December 24, 2019, January 10, 2020, and January 17, 2020. We also acknowledge the recall initiated by your firm on November 12, 2019, recalling all sterile drug products within expiry, and your decision to cease sterile operations on that day in order to implement corrective actions. 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.
Specific violations are described below.
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, the investigator observed that:
1. Your firm’s ISO 5 area used for production of sterile drug products and the ISO 7 area, which housed a biological safety cabinet, had vents that opened directly into the non-classified area that might have allowed the influx of lower quality air.
2. 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.
3. Your firm’s ceiling surfaces, located in the ISO 5 cleanroom and ISO 7 anteroom, were not properly sealed and might have allowed the influx of non-classified air into the classified rooms.
4. 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.
5. Your firm did not depyrogenate glassware, utensils, or temporary containers used in the production of products intended to be sterile.
6. Your firm refilled non-sterile spray bottles with (b)(4) that were used in the ISO 5 area after cleaning with disinfectant.
7. Non-sterile wipes were used to clean the ISO 5 surfaces.
8. Your firm’s operator was observed blocking the movement of first pass air while reaching over open vials during aseptic processing.
9. Materials and components used for aseptic processing were not disinfected prior to entering the ISO 5 classified processing 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.
C. Corrective Actions
We have reviewed your firm’s responses to the Form FDA 483. We acknowledge the recall initiated by your firm on November 12, 2019, recalling all sterile drug products within expiry, and your decision to cease sterile operations on that day in order to implement corrective actions. We also acknowledge that your firm resumed sterile operations on February 10, 2020.
Regarding your responses related to the insanitary conditions, although some of your corrective actions appear to be adequate, we intend to confirm the following during our next inspection:
1. Installation of fixed barriers over work areas, new duct work, and relocation of HEPA filters in ISO 5 work areas.
2. Repairs made to improperly sealed ceiling surfaces and the addition of pressure monitoring tubing to your (b)(4) cleaning schedule.
Regarding your responses related to the insanitary conditions, some of your corrective actions appear deficient:
1. You submitted smoke study recordings that were conducted on January 25, 2020. We have reviewed the smoke studies and noted that turbulent airflow was observed underneath the workbench in “(b)(4)” and directly over equipment where open vials are inserted in “Workstation (b)(4).” In addition, the unidirectional air flow was not visible in some recordings as the room was too dark, the smoke appeared heavy and dense, and some recordings were too brief.
2. You committed to submitting a copy of the revised media fill procedure upon completion of media fill testing, however, the revised media fill procedure was not included in your response. It is unclear if all interventions known to occur during normal production as well as worst case situations are represented in your media fills.
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 first undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. 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 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.
Please send your electronic reply to ORAPHARM4_Responses@FDA.HHS.GOV or mail your reply to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
U.S. Food & Drug Administration
19701 Fairchild Road
Irvine, California 92612-2506
Please identify your responses with the unique identifier: CMS 610546.
If you have questions regarding the contents of this letter, please contact Mariza Jafary, Compliance Officer via email at Mariza.Jafary@fda.hhs.gov or by telephone at (949) 608-2977.
CAPT Katherine E. Jacobitz
Acting Director, Division of Pharmaceutical Quality Operations IV
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.