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WARNING LETTER

April 15, 2021

Dear Mr. Wise:

From June 12, 2019, to June 21, 2019, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, Joe Wise Pharmacy, Inc. dba Wise Pharmacy, located at 6179 S. Balsam Way, Ste 150, Littleton, CO 80123. During the inspection, the investigator noted serious deficiencies in your practices for producing sterile and non-sterile drug products, which put patients at risk.

FDA issued a Form FDA 483 to your firm on June 21, 2019. FDA acknowledges receipt of your facility’s responses, dated July 15, 2019, and February 20, 2020. We also acknowledge that on July 10, 2019 your firm initiated a voluntary recall of all drug products intended to be sterile within expiry due to lack of processing controls. In addition, we acknowledge that your firm ceased sterile compounding as of July 10, 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

B. Violations of the FDCA

Adulterated Drug Products

The FDA investigator noted that drug products intended or expected to be sterile as well as non-sterile 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. Your facility design allows the influx of lower quality air into an area intended to have higher quality air in that:

  a. Your ISO 5-classified workstation, used to produce drug products purporting to be sterile, is located and operated in a non-classified area.
  b. Compounding of non-sterile drug products is conducted in the same non-classified room where the ISO 5 workstation is located.

2. The non-classified room in which your ISO 5 workstation is operated contains a sink and dishwasher, both of which are potential sources of microbial contamination.

3. Your practices for cleaning are deficient in that your (b)(4) hoods, in which both hazardous and non-hazardous bulk drugs are handled, is cleaned with only (b)(4). Consequently, hazardous drugs are not adequately deactivated, posing a contamination risk to non-hazardous drug products, as well as other hazardous drug products.

4. Your firm failed to confirm that the quality of water was suitable for its intended use in the production of non-sterile drug products.

5. 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.

6. Your routine environmental monitoring (EM) is inadequate in that EM samples collected from the ISO 5 surface are “incubated” at uncontrolled room temperature on a counter in the non-classified compounding room.

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 written responses to the Form FDA 483, dated July 15, 2019 and February 20, 2020, respectively. We acknowledge that effective July 10, 2019, your firm ceased production of sterile drug products, and initiated a recall of all sterile drug products within expiry.

Regarding your responses related to the insanitary conditions, some of your corrective actions appear adequate; however, we cannot fully evaluate the adequacy of the corrective actions proposed to address the following deficiencies:

• Operation of an ISO 5-classified workstation in a non-classified room
• Presence of water sources (i.e. sink, dishwasher) in same room as ISO 5 workstation
• Failure to perform smoke studies under dynamic conditions
• Failure to conduct adequate routine environmental monitoring of ISO 5 area

Specifically, your February 20th response indicates you plan “… to construct a new aseptic processing facility…” and that you “… will not seek to resume production of compounded sterile products… until the compounding pharmacy has formal procedures and means in place to properly address [o]bservations ….” However, the status of this construction and corresponding procedures is unclear.

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, including the condition on receipt of a prescription for an identified individual patient prior to compounding and distributing drug products.

FDA strongly recommends that if you decide to resume production of sterile drugs, your management first 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 if you have taken any specific steps to correct the violations cited in this letter. If you intend to resume production of sterile drugs in the future, please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. In addition to taking appropriate corrective actions, you should notify this office fifteen (15) days prior to resuming production of any sterile drugs in the future. If you do not intend to resume production of sterile drugs, you may state that in your response. If you do not believe that the products discussed above violated the FDCA, include your reasoning and any supporting information for our consideration.

Please send your electronic reply to [email protected] 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: 613927

If you have questions regarding the contents of this letter, please contact Andrew Haack, Compliance Officer via email at [email protected] or telephone at 206-340-8212.

Sincerely,
/S/

Lance De Souza
Acting 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.