Laboratory Data Integrity in FDA Warning Letters 2012

Laboratory Data Integrity in FDA Warning Letters 2012

  1. Test Results / (Raw) Data:
    The test results reported are not considered valid
    HPLC test results were not consistently calculated
    There is no assurance that the assay values reported for these samples are accurate and
    Specifically, indicate if the discarded data pertained to lots shipped to the US and your
    justification for invalidating the data
    Lack of quality oversight and poor CGMP documentation practices at your facility,
    specifically in the area of the disposition and handling of critical analytical data
    In your response, include your remediation plan to ensure that raw data is retained as required,
    along with the written procedure describing the retention and disposition policy for all
    laboratory control records
    Printed copies of HPLC test results from your firm’s systems do not contain all of the
    analytical metadata (for example: instrument conditions, integration parameters) that is
    considered part of the raw data
    Please state the additional preventative and systemic actions you will implement to assure
    integrity of all CGMP records
    Your firm has not established appropriate controls designed to assure that laboratory records
    include all data secured in the course of each test, including graphs, charts, and spectra from
    laboratory instrumentation
    The FDA investigator’s review of the HPLC … raw data verified the existence of three (3)
    HPLC chromatograms generated from batch … . However, only two (2) injection areas were
    used in the calculations

An analytical worksheet for … , lot … , dated January 21, 2011, with no approval signature,
was found in a trash container in the office used by QC personnel. This analytical worksheet
shows calculations of content uniformity for active ingredient of … … %.
Any written report of results (including a certificate of analysis) to your customer should
include a statement that the data was generated by an unvalidated method(s) and should not be
used for establishment of expiration dates, commercial batch release, or other CGMP

(Your firm has) failed to maintain complete records of all testing and standardization of
laboratory reference standards and standard solutions
Given the lack of maintenance records, it was unclear how long the filter light had been on or
if the filters had been replaced since installation

Data is deleted to make space for the most recent test results. You also informed our
investigators that printed copies of HPLC test results are treated as raw data

  1. Written (Control) Procedures:
    Your firm failed to establish and follow written procedures to evaluate, at least annually, the
    quality standards of each drug product to determine the need for changes in drug product
    specifications or manufacturing or control procedures
    Your quality control laboratory has not followed written procedures for testing and laboratory
    The inspection revealed that your firm has not established written procedures to control and
    account for electronically generated worksheets used by analysts to record analytical test
    results. Analysts in your QC laboratory print an uncontrolled number of worksheets from
    computers throughout the QC laboratory without supervision

  2. Computerised Systems:
    Your firm did not put in place requirements for appropriate usernames and passwords to allow
    appropriate control over data collected by your firm’s computerized systems including UV, IR,
    HPLC, and GC instruments
    Also describe your firm’s policy for retaining HPLC raw electronic data associated with
    pending applications
    We also note that your SOP does not have provisions for any audit trail reviews to ensure that
    deletions and/or modifications do not occur
    You have not implemented security control of laboratory electronic data
    There is no system in place to ensure that all electronic raw data from the laboratory is backed
    up and/or retained During the inspection, you informed our investigators that electronic raw data would not exist
    for most HPLC assays over two years old because data is not backed up and storage space is limited The chemist only reported two injection areas to produce the result (according to review of electronic data from testing of …… assay) Without proper documentation, you have no assurance of the integrity of the data or the functionality of the software used to determine test results

Your firm had no system in place to ensure appropriate backup of electronic raw data a