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U.S. Department of Health and Human Services

Animal & Veterinary

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2011 Untitled Letter to First Priority, Inc.

October 24, 2011

Lawrence F. Schneider
Owner and CEO
First Priority, Inc.
1590 Todd Farm Drive
Elgin, Illinois 60123-1287
 

Dear Mr. Schneider:

During our September 13-29, 2010 inspection of your animal drug manufacturing facility located at 1590 Todd Farm Drive in Elgin, Illinois, an investigator from the United States Food and Drug Administration (FDA) identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug product(s) to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.

At the end of our inspection an 11-point FDA-483, Inspectional Observations, was issued. After reviewing your October 2010, November 2010, February 2011, May 2011, and July 2011 responses, these specific violations observed during the inspection have not been adequately addressed:

  1. Your firm has not conducted at least one specific identity test and has not established the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals [21 C.F.R. § 211.84(d)(2)].

    For example, your firm failed to verify the reliability of the Certificate of Analysis (COA) in that (b)(4) USP,  (b)(4), USP,  (b)(4) USP,  (b)(4) solution,  (b)(4) and  (b)(4) raw materials have not undergone complete testing in several years. Your final response dated July 8, 2011 stated at  (b)(4) of the  (b)(4) raw materials successfully completed full testing requirements; however, the remaining  (b)(4) raw materials lacked outside test results. We acknowledge your commitment to complete testing of all of your firm's raw materials. Please include an update on the status of this testing and if testing requirements were met. Furthermore, please describe what appropriate intervals your firm will verify the supplier's test results from the Certificate of Analysis (COA) for each raw material.

    This is a repeat observation from the June 2008 inspection.

  2. Your firm's Quality Control Unit (QCU) failed to ensure a thorough investigation in accordance with 21 C.F.R. § 211.192 with conclusions and any follow up accomplished as required by 21 C.F.R. § 211.198(a).

    For example, your firm's SOP  (b)(4) Out-of-Specification (OOS) Test Results, Rev (b)(4) requires complaint investigations for product integrity issues and adverse experiences; however, the QCU failed to investigate or did not fully investigate complaints in numerous documented instances. Specifically,  (b)(4) consumer complaints were received by your firm from April 13-July 30, 2010, for  (b)(4), for adverse experiences including death. We have concluded your company did not conduct timely, comprehensive investigations. Your firm's management, including the QCU, was not proactive in response to consumer complaints. Quality problems must be thoroughly investigated, root causes determined, and appropriate corrective and preventative actions implemented as quickly as possible to limit exposure to substandard drugs.

    Your corrective action noted in your November 3, 2010 response was limited to completing previous open OOS investigations and revising your current OOS procedure to include steps to properly invalidate results before re-testing or re-sampling. However, you did not review the adequacy of your manufacturing procedures.

    This is a repeat observation from the 2006 and June 2008 inspections.

  3. Your firm did not document deviations of written production and process control procedures for various production and process control functions at the time of performance [21 CFR § 211.100(b)].

    For example, your firm failed to record processing deviations in production batch records for manufacture of the following:  (b)(4) (validation lot (b)(4)) validation lot (b)(4) lot (b)(4) (b)(4) (lot  (b)(4), and Levoxine (levothyroxine) Powder (lot  (b)(4)).

    Your responses indicated three additional products  (b)(4)  (b)(4), and  (b)(4) also lacked QCU approved deviation notices. In addition, your responses stated that your firm ceased manufacturing of these three products and placed all lots on distribution hold. Subsequently, the three products were later released. However, you did not provide your rationale for release, nor include the results of these investitgations.

    This is a repeat observation from the 2006 and June 2008 inspections.

  4. Your firm has not established written procedures to monitor the output and to validate the performance of those manufactured processes that may be responsible for causing variability for the in-process material and the drug product [21 C.F.R. § 211.110(a)].

    For example, the manufacturing process does not include appropriate in-process controls. Specifically, studies that were conducted to support the hold times for bulk drug products between compounding and filling failed to contain sufficient suppportive detail for the established hold times.

    Validation must be appropriately demonstrated for each product and process. This includes justification for why certain tests performed by your firm to validate each product and process are appropriate. For example, suitable tests may include product uniformity tests carried out on samples collected using a validated sampling procedure and particle size measurements for suspension dosage forms.

    Hold times should be validated using appropriate tests before and after the maximum hold time to demonstrate that there is no loss of product quality or uniformity during the hold time.

    Appropriate mixing times are considered an important in-process quality attribute to ensure uniform drug product dosages. The critical controls and processing parameters must be known and shown to be in control, and a demonstration of process reproducibility with objective measure must be made.1

    Your response dated November 3, 2010 included manufacturing hold time retrospective studies for your firm's NADA and ANADA products. Furthermore, you also stated prospective hold time studies would be completed and quarterly updates would be provided on the progress of completion of this testing. However, your final July 8, 2011 response stated that prospective hold time studies for  (b)(4) drug products have not been conducted due to various scheduling reasons. Please provide an update on the status of validation activities and prospective hold time studies including specific timeframes for completion for all of your firm's drug products.

    This is a repeat observation from the 2006 inspection.

We received your correspondence dated October 13, 2010, in which you stated that your firm 1) hired additional personnel and, 2) halted distribution of  (b)(4)  (b)(4) products  (b)(4) and  (b)(4).

We also received your response dated November 3, 2010, regarding corrective actions to the Form FDA 483, containing information regarding recall of  (b)(4)  (b)(4) and your firm's hiring of a consultant to conduct a CGMP audit. Further, we have received your February 4, 2011 letter in which you provided a status chart of your previously proposed corrective actions. Additionally, we received status chart updates dated May 13, 2011 and July 8, 2011, and note that they lack sufficient corrective actions as stated above.

The violations cited in this letter are not intended to be an all-inclusive statement of the violations that exist at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence, as well as occurence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law and FDA regulations. Be advised that FDA is evaluating information you have provided in connection with animal drug applications you have submitted. You will be informed of the outcome of this evaluation under separate cover.

Due to the severity of the violations and the inadequate Form FDA-483 responses, we are requesting that you and/or your representatives come to the Chicago District Office for a meeting and present your corrective action plan  to FDA. Within ten working days, please contact Carrie Ann Plucinski at the number below to schedule a meeting to outline the specific steps you have taken or are taking to correct these violations.

Your reply should be directed to Carrie Ann Plucinski, Compliance Officer, Food and Drug Administration, 550 W. Jackson Blvd., 15th Floor, Chicago, IL 60661. If you have any questions, please contact Ms. Plucinski at 312-596-4224.

Sincerely,

/s/
Scott J. MacIntire
District Director
 

cc: Ms. Tina Perkins, Vice President Quality
First Priority, Inc.
1590 Todd Farm Drive
Elgin, IL  60123-1287
 

 

1Further information on FDA's current thinking on process validation is available in Food and Drug Administration, Draft Guidance for Industry, Process Validation: General Principles and Practices November 2008, available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070336.pdf.