- Delivery Method:
- VIA Electronic Mail
Recipient NameEugene A. Woods
Recipient TitlePresident and Chief Executive Officer
- CMC Enterprise Pharmacy
1000 Blythe Boulevard
Charlotte, NC 28203-5812
- Issuing Office:
- Center for Tobacco Products
June 4, 2020
CMS Case # 608036
From March 18, 2019, to March 22, 2019, U.S. Food and Drug Administration (FDA) investigators inspected your facility, CMC Enterprise Pharmacy, located at 4400 Golf Acres Drive, APC Building J, Suite E, Charlotte, North Carolina 28208. 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 March 22, 2019. FDA acknowledges receipt of your facility’s response, dated April 5, 2019. We also acknowledge your firm’s decision to voluntarily cease production of sterile and non-sterile drug products as of April 11, 2019, and to voluntarily recall all sterile drug products within expiry. 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.
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. No action was taken to address non-laminar airflow over seven (7) of ten (10) stainless-steel tables used for aseptic drug production in the ISO 5 classified IV room.
2. Ceiling HEPA filters in the ISO 5 classified IV room, and ISO 7 classified buffer room were not evaluated for leaks during bi-annual certification.
3. The ISO 5 classified IV room had surfaces and equipment that were difficult to clean and contained equipment and surfaces that were particle-generating and visibly dirty.
4. The use of sporicidal agents in the ISO 5 classified IV room was inadequate.
5. Personnel with exposed skin and hair engaged in aseptic processing in the ISO 5 classified IV room.
6. Personnel donned gowning apparel in a way that may have caused the gowning apparel to become contaminated.
7. Poor aseptic technique was used by personnel engaged in aseptic processing. This includes blocking first air to containers during aseptic processing, moving quickly within the ISO 5 classified IV room and placing sterile gloved hands on gowning during aseptic processing.
8. Facility was designed and operated in a way that permits poor flow of personnel and materials.
9. Materials and supplies were not adequately disinfected prior to entering the aseptic processing area.
10. There was a lack of controls to prevent the influx of lower quality air into higher classified areas.
11. 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.
12. Surface sampling was conducted after surfaces had been cleaned. Therefore, surface sampling results are not representative of the aseptic processing environment and may not provide meaningful results.
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. We acknowledge your firm’s decision to voluntarily cease production of sterile and non-sterile drug products as of April 11, 2019, and to voluntarily recall all sterile drug products within expiry.
Your firm’s decision to cease all drug operations at the CMC-Enterprise Pharmacy facility addressed the Agency’s concerns regarding the insanitary conditions observed during our 2019 inspection of this facility.
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 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.
Additionally, should your firm decide to resume sterile and/or non-sterile drug operations at this facility, the Agency would like to remind your firm of some additional measures that should be considered as part of the controls used to prevent the occurrence of insanitary conditions within this facility. These measures were discussed during our April 10, 2019, call and listed in the May 1, 2019, letter sent to your firm. We note that these measures are not an inclusive list and as stated in the above paragraph, we recommend that you work with a third-party consultant with relevant aseptic drug production expertise to help you evaluate your drug operations and implement appropriate controls to prevent the occurrence of insanitary conditions. For convenience, the measures discussed during our call and described in our letter are listed below:
• Ensure that staff understand the information described in certification reports for ISO classified areas.
• Evaluate employee and material flow within the ISO classified areas to minimize the potential for introducing contaminants into the finished sterile drug products.
• Evaluate employee and material movement into and out of the ISO classified areas to ensure that room conditions are not compromised during entry and exit into these areas.
• Evaluate material and/or component storage within the ISO classified areas to prevent “clutter.”
• Evaluate your cleaning program to ensure that cleaning of work surfaces, equipment, walls and floors does not result in corrosion of any surface.
• Evaluate your cleaning program to ensure that employees can recognize visibly dirty surfaces and equipment and report their findings as appropriate.
• Evaluate your disinfection program to ensure that surfaces used to hold disinfected materials does not pose a contamination risk; and ensure consistency between the verbal and written instructions provided to staff on this control.
• Evaluate the effectiveness of your gowning process control to prevent contamination of the aseptic processing environment.
• Ensure that staff understand the controls used to prevent the occurrence of insanitary conditions within your facility.
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.
If you decide to resume sterile operations, 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, or you may inform us that you do not intend to resume production of sterile or non-sterile drugs. If you intend to resume production of sterile or non-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. If you do not believe that the products discussed above violated the FDCA, include your reasoning and any supporting information for our consideration. In addition to taking appropriate corrective actions, you should notify this office fifteen (15) working days prior to resuming production of any sterile or non-sterile drugs in the future.
Your written notification should refer to the Warning Letter Number above (608036). Please electronically submit your reply, on company letterhead, to Mark W. Rivero, Compliance Officer, at ORAPHARM2_RESPONSES@fda.hhs.gov. In addition, please submit a signed copy of your response to email@example.com.
If you have questions regarding the contents of this letter, you may contact Mr. Rivero via phone at (504) 846-6103 or email at firstname.lastname@example.org.
Monica R. Maxwell
Program Division Director
Division of Pharmaceutical Quality Operations,
Director, Pharmacy Services
4400 Golf Acres Drive
APC Building J, Suite E
Charlotte, North Carolina 28208-5968
Ken D. Haynes
President, Greater Charlotte Region
1000 Blythe Boulevard
Charlotte, North Carolina 28203-5812
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.