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WARNING LETTER

February 1, 2021

Dear Ms. Krug:

From December 2, 2019, to December 13, 2019, U.S. Food and Drug Administration (FDA) investigators inspected your facility, Hawaii Health Systems Corporation dba Kona Community Hospital Pharmacy, located at 79-1019 Haukapila Street Kealakekua, HI 96750. During the inspection, the investigators 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 December 13, 2019. FDA acknowledges receipt of your facility’s response, dated January 3, 2020, and subsequent correspondence. 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 investigators 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 investigators observed that:

1. You failed to remediate the repeated recovery of microbial contamination from the ISO 7 cleanrooms, ISO 5 biological safety cabinet (BSC), and ISO 5 laminar air flow (LAF) hood where drug products intended to be sterile were prepared. Furthermore, you failed to evaluate whether the identified microbial contamination had any impact on aseptically processed drug products that were prepared in your cleanrooms.

2. Your facility design was deficient because:
(i) the cleanrooms did not have (b)(4);
(ii) the cleanrooms were provided with HEPA filtered air (b)(4). This HEPA filter was not clamped down in the filter housing, had failed leak testing in 2018, and was not tested for leaks during the cleanroom certification performed in June 2019;
(iii) the air returns in the cleanrooms were located in the ceilings in proximity to the air supply vents;
(iv) (b)(4) between the ISO 7 hazardous buffer room and the unclassified area were (b)(4) and (b)(4) were observed opened at the same time;
(v) a differential pressure cascade could not be maintained between rooms of higher air quality and rooms of lower air quality when the doors to the cleanrooms were closed;
(vi) the air supply vents in the ISO 7 non-hazardous drug room and anteroom had accumulated what appeared to be dust.

3. Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 BSC. Therefore, your products intended to be sterile were produced in an environment that may not provide adequate protection against the risk of contamination.

4. Your firm used a non-sterile disinfectant within the ISO 5 aseptic processing area.

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 and subsequent correspondence. We acknowledge that as part of your corrective actions, all drug products intended to be sterile will continue to be assigned a beyond use date (BUD) of 12 hours.

However, regarding your responses related to the insanitary conditions, 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. Your response stated that (b)(4) was intended to be completed by (b)(4). You have not provided details describing the finalized design changes or evidence to demonstrate that the design phase has been completed or that the (b)(4) activities have been planned or performed.

2. You stated that (b)(4) would be purchased for use while the (b)(4). You have not provided evidence to show that this corrective action has been implemented.

3. Your response stated that cleaning the interior of the ISO 5 areas will be performed using sterile (b)(4). However, you did not provide supporting evidence to demonstrate that sterile (b)(4) was purchased or whether any modifications or changes have been made to your cleaning practices.

4. You did not provide additional environmental monitoring data to demonstrate that the ISO 5 BSC, ISO 5 LAF, and the cleanrooms are maintained in a state of control.

5. You failed to evaluate whether the recovery of spore-forming organisms indicated a need for more frequent application of a sporicidal agent as part of your routine disinfection program.

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.

Send your written responses to:

CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
19701 Fairchild Road
Irvine, CA 92612

Please identify your response with unique identifier 611130. Electronic responses may also be submitted to ORAPHARM4_Responses@fda.hhs.gov.

If you have questions regarding any issues in this letter, please contact Mariza Jafary, Compliance Officer, at (949) 608-2977, or Mariza.Jafary@fda.hhs.gov.

Sincerely,
/S/

CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV

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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.