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September 15, 2020

Case #: 610639

WARNING LETTER

Mr. Schneider:

From February 6, 2019 to February 14, 2019, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, Intrathecal Compounding Specialists, LLC, located at 206A Jacob’s Run, Scott, Louisiana 70583. 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 February 14, 2019. FDA acknowledges receipt of your facility’s responses, dated February 20, 2019 and March 4, 2019. Based on this inspection, it appears that you produced drug products that violate the 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)]. 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 [21 U.S.C. § 351(a)(2)(A)]. For example:

1. Your firm continued to produce and distribute sterile drug products during and after maintenance on the HVAC system, which included the replacement of the (b)(4) for the sterile suite, without cleaning and recertification of the room following the installation.

2. Your firm failed to maintain adequate pressure differentials between areas of higher quality and lower quality air.

3. Your firm failed to routinely use a sporicidal agent as part of your disinfection program for the aseptic processing area.

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 intended to be sterile within your facility.

5. Firm personnel donned and reused gowning apparel improperly, which may have caused the gowning apparel to become contaminated.

6. Firm personnel were observed using poor aseptic technique that included leaning into the ISO 5 laminar flow hood.

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. Regarding your responses related to the insanitary conditions, some of your corrective actions appear to be 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 response to Observation 1, you included the actions taken associated with the drug products produced on 2/7/19 and 2/8/19 prior to the sterile suite recertification on 2/9/19. However, you did not provide the results of the sterility and endotoxin testing and final product dispositions for the (b)(4) products made on 2/8/19 that were not destroyed. In addition, you did not include an adequate evaluation of the (b)(4) products prepared and/or dispensed on 2/6/19. Contrary to your assertion in the response that there were no out of specification readings during the HVAC repairs on 2/6/19, a review of the electronic monitoring data reveals that the temperature in the Buffer Room was above your specification of (b)(4)° F on 2/6/19 from 8:54:51 to 12:17:25. Also, in your response to Observation 1, you state that a (b)(4) clean of the sterile suite was conducted on 2/8/19. However, the contact times for the agents used were not documented.

2. In response to Observation 5, you stated that the use of sterile masks will be implemented. Your response includes the updated procedure for Sterile Lab/Cleanroom Attire, but it does not specify the process (where and how) for donning the sterile face masks. The implementation timeframe was not provided for the use of the sterile face masks, nor was the updated gowning procedure submitted with the response. In addition, your response did not address the continued reuse of sterile gowning or poor aseptic technique of leaning into the ISO 5 hoods that was cited in Observation 5, as well as during the previous inspection in 2017.

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

1. The revised media fill procedures outlined in your response to Observation 4 are still not representative of your firm’s routine production practices. The updated media fill procedure includes (b)(4). However, your firm’s routine production processes consist of (b)(4) used in the preparation of single dose finished drug product syringes. In addition, your current media fill uses (b)(4) even though your firm does not routinely use (b)(4) in the preparation of your sterile drug products.

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 # 610639.

Please electronically submit your reply, on company letterhead, to John Diehl, Director, Compliance Branch, at [email protected] and [email protected]. In addition, please submit a signed copy of your response to [email protected].

If you have questions regarding the contents of this letter, you may contact Rebecca Asente, Compliance Officer, via phone at (504) 846-6104 or email at [email protected].

Sincerely,
/S/

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