Inspections, Compliance, Enforcement, and Criminal Investigations
Pentec Health 3/7/14
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
900 U.S. Customhouse
2nd and Chestnut Streets
Philadelphia, PA 19106
RETURN RECEIPT REQUESTED
March 7, 2014
Mr. Joseph C. Cosgrove
Chairman and CEO
Pentec Health, Inc.
4 Creek Parkway, Suite A
Boothwyn, PA 19061-3132
Dear Mr. Cosgrove:
Between March 18, 2013 and April 1, 2013, U.S. Food and Drug Administration (FDA) investigators conducted an inspection of your facility, Pentec Health, Inc., located at 4 Creek Parkway, Suite A, Boothwyn, PA 19061-3132. During the inspection, the investigators observed serious deficiencies in your practices for producing drug products that were intended or expected to be sterile, which put patients at risk. For example, investigators observed breaches of aseptic technique, including placement of supplies and materials in the ISO 5 hood without disinfection, and personnel performing manipulations directly over open containers, which would obstruct unidirectional airflow . Furthermore, our investigators found that your firm failed to demonstrate through appropriate studies that your hoods are able to provide adequate protection of the ISO 5 area in which sterile products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk. For example, your firm did not perform smoke studies under dynamic conditions in your ISO 5 hoods, in which large equipment is used during production that could obstruct the unidirectional airflow.
These observations and others were noted on an FDA Form 483 issued on April 1, 2013. Your firm subsequently recalled 163 units of product that lacked sterility assurance.
A. Adulterated Products in Violation of the FDCA
Under section 501(a)(2)(A) of the FDCA [21 U.S.C. § 351(a)(2)(A)], a drug is adulterated if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth or rendered injurious to health. Numerous subvisible microorganisms and other contaminants are ubiquitous in an ordinary environment.
A firm producing sterile drugs must take certain steps in order to ensure removal of contaminants through various controls that focus on safeguarding drug sterility by assuring the quality of the processing environment (e.g., surfaces, personnel, air) and the materials that go into a drug product. Otherwise, drugs that are intended or expected to be sterile may become contaminated during preparation and, when administered to a patient, may result in infections and/or pyrogenic responses that pose a life-threatening health risk to a patient. Failure to take these steps (when producing drugs that are intended or expected to be to be sterile) causes the drug to be prepared, packed, or held under insanitary conditions.
FDA investigators noted that drug products produced by your firm and 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)]. When prepared under insanitary conditions, such as those described in items 1–2 below, any drugs that are intended or expected to be sterile may become contaminated with filth or rendered injurious to health. Examples of the insanitary conditions at your firm include, but are not limited to, the following:
1. Your aseptic practices are unacceptable. For example, we observed breaches of aseptic technique including placement of supplies and materials in the ISO 5 hood without disinfection and personnel performing manipulations directly over open containers, obstructing unidirectional airflow. The placement of supplies and materials into the ISO 5 environment before disinfection and the manipulations performed directly over open containers create insanitary conditions.
2. Your firm failed to demonstrate through appropriate studies that your hoods are able to provide adequate protection of the ISO 5 area in which sterile products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk. For example, your firm did not perform smoke studies under dynamic conditions in your ISO 5 hoods, in which large equipment is used during production that could obstruct the unidirectional airflow. Without assuring sterile conditions in the ISO 5 environment, your firm cannot ensure that contaminants from the ordinary environment have been removed.
B. Corrective Actions
In your response to the Form FDA 483 dated April 22, 2013, you indicated plans to address our inspectional findings with certain corrective actions and we understand that you hired a consultant. We also acknowledge your action on May 15, 2013, to recall all sterile drug products that were intended or expected to be sterile within expiry that were produced in hood (b)(4). Your planned corrections do not appear to be sufficient to remedy the insanitary conditions at your firm. 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.
Please note that 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 assure 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. FDA may re-inspect to verify corrective actions have been completed.
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 15 working days, state the reason for the delay and the time within which you will complete the correction.
Your notification should be addressed to Ms. Robin M. Rivers, Compliance Officer, U.S. Food and Drug Administration, 900 U.S. Customhouse, 200 Chestnut Street, Philadelphia, PA 19106
If you have questions regarding any issues in this letter, please contact Ms. Rivers at 215-717-3076.
Anne E. Johnson
Acting District Director
Philadelphia District Office
Although sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act (FDCA or the Act) [21 U.S.C. §§ 353a, 353b] provide exemptions from certain provisions of the Act when certain conditions are met, the exemptions do not extend to the FDCA provisions that are discussed in this letter. As a result, this letter does not address whether your firm’s operations meet the conditions set forth in section 503A or section 503B of the Act.