Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|New England District Office|
One Montvale Avenue, 4th floor
Stoneham, MA 02180
CMS # 473641
UNITED PARCEL SERVICE
October 28, 2015
Stuart E. Rosenberg, President and CEO
Johnson Memorial Cancer Center
142 Hazard Avenue
Enfield, CT 06082-4520
Dear Mr. Rosenberg:
From July 16, 2014, to August 5, 2014, U.S. Food and Drug Administration (FDA) investigators conducted an inspection of your facility, Johnson Memorial Cancer Center, located at 142 Hazard Avenue, Enfield, CT 06082-4520. During the inspection, the investigators observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, the inspectors observed insanitary conditions such as filth, chipping paint, water stains in the ceiling within the classified ISO 7 preparation space, dirty equipment, and discoloration by a contaminant of unknown origin on HEPA filters used to filter air in the classified area where compounded sterile drug products are prepared. In addition, deficiencies with environmental monitoring were observed including the lack of microbial identification, lack of testing in the hoods within the rooms, and inadequate differential pressure monitoring. Therefore, your products may be produced in an environment that poses a significant contamination risk.
FDA acknowledges that on July 8, 2014, your firm ceased on-site sterile drug production operations. FDA further acknowledges that, during the inspection, you informed FDA investigators that the firm would voluntarily transfer all patient treatment activities to your main hospital.
FDA issued a Form FDA-483 to your firm on August 5, 2014. Based on this inspection, it appears that you are producing drugs that violate the Federal Food, Drug, and Cosmetic Act (FDCA).
A. Violation of the FDCA
The FDA investigator observed that your sterile drug products were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health. Examples of insanitary conditions observed during our inspection include:
1. Your firm recovered 55 environmental monitoring results of mold, 1 cfu and above, from classified ISO 7 areas (surface and air) during the reconstitution of sterile injectable drugs. In addition, you have not provided evidence that a health hazard evaluation was conducted to assess the potential quality impact of isolates present during aseptic processing of drug products intended to be sterile.
2. Your firm had filth, chipped paint, water stains and unsealed openings in the ceiling drop tiles of your ISO-classified rooms, allowing non-HEPA filtered air to enter into these rooms from the plenum.
3. Your firm did not provide evidence to demonstrate that environmental monitoring occurs within the ISO 5 hoods where drugs intended to be sterile were produced. You provided no assurance the cleaning, disinfecting, personal hygiene and garbing practices create a microbial environment within the aseptic processing areas that is suitable for the production of drug products intended to be sterile.
4. Your firm’s pressure differentials between the anteroom and the uncontrolled office space were minimal, which creates the risk of dirtier air mixing with cleaner air within the aseptic processing areas.
5. Personnel monitoring is limited to the assessment of the pharmacy technician’s fingers, and this sampling is only done on an (b)(4) basis. There is no assurance that hygiene practices were consistently suitable to prevent microbial contamination during the production of drug products intended to be sterile.
6. Investigators observed dirty equipment noting yellow discoloration on the chemotherapeutic room’s HEPA filters used to prepare sterile drug products and you took no corrective action.
As such, all sterile products you manufacture are adulterated within the meaning of section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)] of the FDCA. It is a prohibited act under section 301(k) of the FDCA 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 of the components used to make the drug and results in the drug being adulterated.
B. Corrective Actions
As noted previously, your firm ceased on-site sterile drug production operations, and during the inspection, you informed FDA investigators that the firm would voluntarily transfer all patient treatment activities to your main hospital.
However, we also note that your firm committed to FDA in its August 21, 2014 response to the Form FDA 483 to correct the above deviations listed in the Form FDA 483 and indicated your intention to resume production of sterile drugs. If you decide to resume production of sterile drugs, FDA strongly recommends that your management immediately undertake a comprehensive assessment of your operations, including facility design, procedures, personnel, processes, materials, and systems. In particular, this review should assess your aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise could be useful 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 and 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 working days of receipt of this letter, please notify this office in writing if you have taken any specific steps 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 the corrective actions cannot be completed within fifteen working days, state the reason for the delay and the time frame within which corrections will be completed.
In addition to taking appropriate corrective actions, you should notify this office prior to resuming production of any sterile drugs in the future.
Your written notification should be addressed to:
Karen Archdeacon, Compliance Officer
FDA New England District Office
U.S. Food and Drug Administration
One Montvale Avenue
Stoneham, MA 02180-3500
If you have questions regarding any issues in this letter, please contact Ms. Archdeacon via email at firstname.lastname@example.org or by phone at 781-587-7491.
Joseph Matrisciano, Jr
Acting District Director
New England District Office