- Delivery Method:
- Electronic Email
Recipient NameAlan Theriault
Recipient TitlePharmacy Manager
- Infuscience, Inc. dba Bioscrip Infusion Services
4151 Lafayette Center Drive, Suite 600
Chantilly, VA 20151-1230
- Issuing Office:
- Division of Pharmaceutical Quality Operations I
AMENDED WARNING LETTER
WL # 285620
December 21, 2020
Dear Mr. Theriault:
We are amending our Warning Letter of August 13, 2020 to correct the name of your firm’s Pharmacy Manager.
From July 23, 2019 to July 30, 2019, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, InfuScience, Inc. dba BioScrip Infusion Services, located at 4151 Lafayette Center Drive, Suite 600, Chantilly, VA 20151. 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 July 30, 2019. FDA acknowledges receipt of your facility’s response, dated August 19, 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 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. For example, the investigator observed that:
1. Personnel did not disinfect and change gloves after high-risk activities, prior to resuming aseptic processing operations in the ISO 5 classified hood, to prevent contamination. Activities included pushing trash down into a trash receptable and touching objects and surfaces in ISO 7 classified areas.
2. 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.
3. The facility design was observed to allow the influx of air from a lower quality, unclassified area into a classified area via (b)(4) that directly connect the ISO 7 classified area surrounding the ISO 5 classified LAF hoods to unclassified areas.
4. Your firm produced beta-lactam drugs without providing adequate segregation, cleaning of work surfaces and cleaning of utensils with a deactivating agent prior to producing non-beta-lactam products to prevent cross-contamination.
5. Personnel positioned equipment and supplies in an area that blocked the movement of first pass air around an open unit, either before or after it was filled with sterile product, during aseptic production inside the ISO 5 classified hood.
6. Materials or supplies were not disinfected prior to entering the ISO 5 classified aseptic processing areas from the ISO 7 classified areas.
7. Disinfectant contact time and coverage of the item intended to be disinfected were inconsistent with the manufacturer’s and firm’s instructions and there was no assurance that adequate levels of disinfection were achieved.
8. The ISO 5 classified LAF hoods had a visibly dirty surface. Specifically, the HEPA grates on the back of the ISO 5 hoods had visible white “staining.”
9. Adequate personnel monitoring was not performed in your aseptic processing areas.
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. Regarding your responses related to the insanitary conditions, some of your proposed corrective actions appear adequate.
However, you did not address certain observations related to insanitary conditions, for example:
1. You have not demonstrated unidirectional airflow in your ISO 5 classified LAF hoods under dynamic conditions (i.e. typical operating conditions) and therefore have not demonstrated that aseptic processing operations maintain sterility assurance.
2. You do not maintain the (b)(4) under ISO 7 conditions to ensure that contamination is not introduced into the ISO 7 IV Compounding Room through material flow or provide evidence of additional controls that mitigate the risk associated with the material flow.
Regarding your responses related to the insanitary conditions, the following corrective action appears deficient:
1. In response to the gloved technician who continued aseptic processing operations after pushing trash down in the trash receptable without replacing their gloves, you did not evaluate the impact that potentially contaminated gloves had on sterility assurance and therefore no action was taken regarding TPN 3-in-1 sterile product ((b)(6)) that was produced with these gloves.
Furthermore, our review of the data collected during the inspection revealed that your firm’s personnel monitoring program is inadequate. Specifically, your firm does not require fingertip testing and media fill qualifications for nurse employees who produce sterile drug products in the ISO 5 LAF hoods. Additionally, your firm does not perform gown sampling during personnel monitoring of your employees involved in aseptic operations. In response to this letter, provide your actions to address this insanitary condition.
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.
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 electronic response to ORAPHARM1_responses@fda.hhs.gov. Your written notification should refer to the Warning Letter Number above (# 285620).
If you have questions regarding the contents of this letter, please contact Nancy Scheraga, Compliance Officer at 973-331-4910 or by email at Nancy.Scheraga@fda.hhs.gov
Program Division Director/District Director
Office of Pharmaceutical Quality Operations
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.