FDA Warning Letters


Page 5 of 2512345678910...20...Last »
  1. Warning Letter: Failure to validate software (ucm465665)

    Tags: | |

    “Failure to validate computer software for its intended use according to an established protocol when computers or automated data processing systems are used as part of production or the quality system, as required by 21 CFR 820.70(i).

    For example, your firm uses the software [redacted], developed by [redacted], to document, maintain, and track customer complaints electronically. However, as stated by your firm’s Director of Quality Assurance (QA) & Regulatory Affairs (RA) during the inspection, the software does not generate time-stamped audit trails to independently record the date and time of operator entries and actions that create, edit, or modify electronic records.”

    View the original warning letter.


    Recommended Solutions

    Compliance Training >>

    Recommended Solutions

    ExcelSafe >>

    Recommended Solutions

    Ofni Clinical >>

    Recommended Solutions

    Part 11 Toolkit >>

    Recommended Solutions

    Part 11 Advisor >>

    Recommended Solutions

    MedWatch Reporter >>

    Recommended Solutions

    Computer Validation >>

    Recommended Solutions

    Custom Programming >>

    Recommended Solutions

    Validating MS Excel Spreadsheets >>

    Recommended Solutions

    Access Databases >>

  2. Notice of Concern from World Health Organization: Company Failed to Ensure Integrity of Data

    Tags:

    ” Quotes from the Notice:

    The company failed to ensure the integrity of data:…
    Batch numbers were not electronically recorded…
    Hundreds of trial injections… in sequence… were seen in folder c:…
    Data was found to be deleted for several runs…
    The backups could not be restored during the inspection.
    Instrument audit trails were not available…
    An analyst was seen in process of taking tablet weight data from a calculation spreadsheet in Excel and writing the values down in his analytical test sheet as if these were the raw weighing values.”

    View the original Notice of Concern.


    Recommended Solutions

    Compliance Training >>

    Recommended Solutions

    ExcelSafe >>

    Recommended Solutions

    Ofni Clinical >>

    Recommended Solutions

    Part 11 Toolkit >>

    Recommended Solutions

    Part 11 Advisor >>

    Recommended Solutions

    MedWatch Reporter >>

    Recommended Solutions

    Computer Validation >>

    Recommended Solutions

    Custom Programming >>

    Recommended Solutions

    Validating MS Excel Spreadsheets >>

    Recommended Solutions

    Access Databases >>

  3. FDA Warning Letter: Validations of software processes not completed (ucm458487)

    Tags: |

     
    “”CAPA QS-13-006 identified corrective actions to your firm’s software validation procedure and identified 50 software processes that were not validated. Your firm closed the CAPA as effective on April 15, 2015; however, the validations for 38 of the identified software processes were not completed [Kurihara-shi, Miyagi].

    The adequacy of your firm’s responses cannot be determined at this time. Your firm initiated a CAPA to address the above deficiencies. However, your firm has not completed implementation of its corrective actions and CAPA effectiveness verifications for this observation.”

    View the original warning letter.


    Recommended Solutions

    Compliance Training >>

    Recommended Solutions

    ExcelSafe >>

    Recommended Solutions

    Ofni Clinical >>

    Recommended Solutions

    Part 11 Toolkit >>

    Recommended Solutions

    Part 11 Advisor >>

    Recommended Solutions

    MedWatch Reporter >>

    Recommended Solutions

    Computer Validation >>

    Recommended Solutions

    Custom Programming >>

    Recommended Solutions

    Validating MS Excel Spreadsheets >>

    Recommended Solutions

    Access Databases >>

  4. Warning Letter: Informal documentation in emails and on a spreadsheet (ucm458008)

    Failure to establish and maintain procedures for validating the device design, as required by 21 CFR 820.30(g).

    “From 11/9/2014-5/25/2015, a total of 125 complaints were received and documented informally in emails and on a spreadsheet.  Complaint form, #211.2.A, which is required to be completed per your Complaint Handling procedure, was not completed for each of these complaints…

    Data sources are not being analyzed to identify existing and potential causes of nonconforming product or other quality problems, as required by 21 CFR 820.100(a)(1)…

    Your response is not adequate.  Although it states that data sources will be reviewed by management on a regular basis as part of management review, you do not address conducting a retrospective review of these data sources to determine if there are any existing and potential causes of nonconforming product or other quality issues that have not been identified.  Also, you did not provide a copy of the applicable procedures that address the type of statistical analysis that will be performed on each data source.”

    View the original warning letter.


    Recommended Solutions

    Compliance Training >>

    Recommended Solutions

    ExcelSafe >>

    Recommended Solutions

    Ofni Clinical >>

    Recommended Solutions

    Part 11 Toolkit >>

    Recommended Solutions

    Part 11 Advisor >>

    Recommended Solutions

    MedWatch Reporter >>

    Recommended Solutions

    Computer Validation >>

    Recommended Solutions

    Custom Programming >>

    Recommended Solutions

    Validating MS Excel Spreadsheets >>

    Recommended Solutions

    Access Databases >>

  5. Warning Letter: No records demonstrating the software was validated (ucm459656)

    Tags: |

    “Failure to establish and maintain design validation procedures to ensure that devices conform to defined user needs and intended uses and shall include testing of production units under actual or simulated use conditions, as required by 21 CFR 820.30(g).

    During an inspection of your firm located in Round Rock, Texason June 16, 2015 through July 2, 2015, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a manufacturer of the ECG Check Application and ECG Check Wireless Lead Cardiac Monitor (ECG Check Monitor)…

    Your firm’s “Design Validations” procedure Revision 1 dated May 22, 2015, states software should be tested according to a test plan and requires the results of this software validation to be maintained in the design history file (DHF). Your firm does not have any records demonstrating the ECG Check Application software was validated.”

    View the original warning letter.


    Recommended Solutions

    Compliance Training >>

    Recommended Solutions

    ExcelSafe >>

    Recommended Solutions

    Ofni Clinical >>

    Recommended Solutions

    Part 11 Toolkit >>

    Recommended Solutions

    Part 11 Advisor >>

    Recommended Solutions

    MedWatch Reporter >>

    Recommended Solutions

    Computer Validation >>

    Recommended Solutions

    Custom Programming >>

    Recommended Solutions

    Validating MS Excel Spreadsheets >>

    Recommended Solutions

    Access Databases >>

  6. FDA Warning Letter: There is no assurance that you maintain complete electronic raw data for laboratory instruments and data acquisition software (ucm455345)

    Tags:

    “Failure to record activities at the time they are performed and destruction of original records.

    Specifically, your employees completed batch production records entries days after operations had ended, released lots before the proper approvals, and failed to maintain original manufacturing data for critical steps in the batch production records.  For example,

    a) Our investigators found that some of your operators used “rough notes” (unbound, uncontrolled loose paper) to capture critical manufacturing data and then destroyed these original records after transcription into the batch production records. For example, the [redacted] chemist recorded original manufacturing data as rough notes and left these rough notes for the [redacted] chemist to transcribe into the batch production records.  The next morning, the [redacted] chemist signed the batch production records and destroyed the original rough notes.  We interviewed employees during the inspection who confirmed your firm’s practice of transcribing data to batch records and destroying original records

    b) Additionally, our investigators found backdated batch production records dated February 10 to February 25, 2014, signed by your Production Manager and Technical Director in the “Batch Manufacturing Record Reviwed [sic] by” section. The Technical Director stated that he was not in the facility on these dates and was “countersigning” for another person who allegedly performed these review activities.  However, these records did not contain signatures (contemporaneous or otherwise) of the alternate reviewer who purportedly conducted the review. Furthermore, the Technical Director backdated his own signature to the date the quality unit (QU) reviewed and released your drug product.  His backdated signatures are on [redacted] batch records for lots [redacted]; and [redacted] batch records for lots [redacted].  You released these batches before the Technical Director returned to the facility and backdated his signatures.  The batch records, therefore, do not demonstrate that you completed your required review before releasing your products…

    Failure to prevent unauthorized access or changes to data, and to provide adequate controls to prevent omission of data.

    Your laboratory systems lacked access controls to prevent raw data from being deleted or altered. For example,

    a) There is no assurance that you maintain complete electronic raw data for your Gas Chromatography (GC) instrument. FDA investigators observed multiple copies of raw data files in the recycle bin connected to the GC instrument QC-04 even in the presence of “Do Not Delete Any Data” notes posted on two laboratory workstation computer monitors.

    b) Employees were allowed uncontrolled access to operating systems and data acquisition software tracking residual solvent, and test and moisture content. Our investigators noted that there was no password functionality to log into the operating system or the data acquisition software for the GC, the High Performance Liquid Chromatography (HPLC) instrument QC-17, or the Karl Fischer (KF) Titrator QC-13.

    c) HPLC SpinChrome and GC Lab Station data acquisition software lacked active audit trail functions to record changes in data, including original results, who made changes, and when.

    In your response, you state that your laboratory GC, HPLC and KF systems are now password-protected and that you have begun drafting analytical software password procedures for the GC, HPLC and KF laboratory instruments.  However, your response does not state whether every analyst will have their own user identification and password.  You also mention plans to install a validated computer system.  However, you did not provide a detailed corrective action and preventive action (CAPA) plan or conduct a review of the reliability of your historical data to ensure the quality of your products distributed to the U.S. market.

    Inadequate controls of your computerized analytical systems raise questions about the authenticity and reliability of your data and the quality of your APIs.  It is essential that your firm implements controls to prevent data omissions or alterations.  It is critical that these controls record changes to existing data, such as the individuals making changes, the dates, and the reason for changes.

    In response to this letter, provide your comprehensive CAPA plan for ensuring that electronic data generated in your manufacturing operations, including laboratory testing, cannot be deleted or altered.  Also identify your quality control laboratory equipment and any other manufacturing-related equipment that may be affected by inadequate controls to prevent data manipulation.

    View the original warning letter.


    Recommended Solutions

    Compliance Training >>

    Recommended Solutions

    ExcelSafe >>

    Recommended Solutions

    Ofni Clinical >>

    Recommended Solutions

    Part 11 Toolkit >>

    Recommended Solutions

    Part 11 Advisor >>

    Recommended Solutions

    MedWatch Reporter >>

    Recommended Solutions

    Computer Validation >>

    Recommended Solutions

    Custom Programming >>

    Recommended Solutions

    Validating MS Excel Spreadsheets >>

    Recommended Solutions

    Access Databases >>

  7. FDA Warning Letter: It is unclear how adding a “clinical trials link” to your site’s electronic medical record (EMR) to provide access to study information for study staff will ensure that protocol requirements will be met (ucm455217)

     
    “In your January 28, 2015, written response to the violations noted in Items 1.c., 1.d., and 1.e. above, you confirmed that protocol-required laboratory tests were missed for subjects enrolled in the clinical investigations for Protocols [redacted] and [redacted]. You indicated that as a part of your corrective action plan, you have added a “clinical trials link” to your site’s electronic medical record (EMR) to provide access to study information for study staff. You further indicated that you will review with study staff the process of accessing study information and the importance of following the study calendar.

    Your response is inadequate because you did not provide sufficient information to enable us to evaluate the adequacy of your corrective action plan for use in any future clinical research that you may conduct. It is unclear how adding a “clinical trials link” to your site’s EMR will ensure that protocol requirements will be met for studies conducted at your site. You did not provide any details of a corrective action plan to prevent similar violations from occurring in the future, nor have you provided sufficient details regarding your plan to implement additional measures and procedures to address the inspection findings. Without these details, we are unable to determine whether your corrective action plan appears sufficient to prevent similar violations in the future.”

    View the original warning letter.


    Recommended Solutions

    Compliance Training >>

    Recommended Solutions

    ExcelSafe >>

    Recommended Solutions

    Ofni Clinical >>

    Recommended Solutions

    Part 11 Toolkit >>

    Recommended Solutions

    Part 11 Advisor >>

    Recommended Solutions

    MedWatch Reporter >>

    Recommended Solutions

    Computer Validation >>

    Recommended Solutions

    Custom Programming >>

    Recommended Solutions

    Validating MS Excel Spreadsheets >>

    Recommended Solutions

    Access Databases >>

  8. FDA Warning Letter: Multiple instances of delayed monitoring reports and approvals with electronic tracking system (ucm453979)

     
    “In the October 10, 2014 written response to the Form FDA 483, you acknowledged this observation. You stated that prior to January 2013, there was no electronic system to track reporting timelines. You indicated that an electronic tracking system was implemented in January 2013 to track monitoring visits and monitoring report reviews. You noted that CRAs receive automatic e-mail reminders and reconciliation is done once per month by the CPM and AB Science management team.

    Your written response is inadequate because there are still multiple instances of delayed written reports by the CRAs and delayed approval by the CPM after January 2013.

    You proposed a corrective action plan for implementation in the fourth quarter of 2014 where local labs will be captured and queried immediately at the site in the eCRF, and you will continue to use the central lab in phase III trials in addition to local labs for managing safety information.

    Your written response is inadequate because your proposed corrective actions make no provisions for assessing the effectiveness of and ensuring sustained compliance with your monitoring practices.”

    View the original warning letter.


    Recommended Solutions

    Compliance Training >>

    Recommended Solutions

    ExcelSafe >>

    Recommended Solutions

    Ofni Clinical >>

    Recommended Solutions

    Part 11 Toolkit >>

    Recommended Solutions

    Part 11 Advisor >>

    Recommended Solutions

    MedWatch Reporter >>

    Recommended Solutions

    Computer Validation >>

    Recommended Solutions

    Custom Programming >>

    Recommended Solutions

    Validating MS Excel Spreadsheets >>

    Recommended Solutions

    Access Databases >>

  9. Warning Letter: Failure to provide adequate controls for audit trail, backup, common log-in and password, validation, procedures, and training (ucm448433)

    Tags: |

    “Failure to prevent unauthorized access or changes to data and to provide adequate controls preventing data omissions.

    Our inspection noted that your firm did not retain complete raw data from testing performed to assure the quality of
    [redacted], API. Specifically, our inspection revealed your firm did not properly maintain a back-up of HPLC chromatograms that form the basis of your product release decisions. Our inspection revealed discrepancies between the printed chromatograms and the operational qualification protocol for the High Performance Liquid Chromatography (HPLC) system, which is intended to demonstrate correct operation of the HPLC. These discrepancies included injection sequences and values to calculate relative standard deviation (RSD).

    While investigating these discrepancies, our investigator requested the original electronic raw data. Your quality unit, after consulting with the Information Technology (IT) department, stated they were unable to retrieve the original electronic raw data because back-up discs were unreadable. Your quality unit then stated that back-up disks have been unreadable since at least 2013. Your HPLC system is used to test
    [redacted], API for batch release. However, without complete, accurate, reliable, or retrievable raw data about the HPLC system’s qualification, you lacked complete assurance that the system was operating as intended.

    You also failed to have proper controls in place to prevent unauthorized manipulation of your laboratory’s raw electronic data. Our inspection revealed your HPLC system did not have access controls to prevent alteration or deletion of data. Your HPLC software lacked an audit trail recording any changes to the data, including: previous entries, who made changes, and when changes were made. During the inspection, we also noted that all laboratory employees shared a common log-in and password to access the system.

    This lack of control over the integrity of your data raises questions about your analytical data’s authenticity and reliability, and about the quality of your APIs. We note that the September 2008 FDA inspection uncovered concerns over your handling of raw analytical data, including discrepancies between laboratory notebooks and printed chromatograms.”

    View the original warning letter.


    Recommended Solutions

    Compliance Training >>

    Recommended Solutions

    ExcelSafe >>

    Recommended Solutions

    Ofni Clinical >>

    Recommended Solutions

    Part 11 Toolkit >>

    Recommended Solutions

    Part 11 Advisor >>

    Recommended Solutions

    MedWatch Reporter >>

    Recommended Solutions

    Computer Validation >>

    Recommended Solutions

    Custom Programming >>

    Recommended Solutions

    Validating MS Excel Spreadsheets >>

    Recommended Solutions

    Access Databases >>

  10. Warning Letter: Lack of testing of software interfaces (ucm448655)

    Tags:

    “An analysis to determine if other software products manufactured have had similar failure modes due to lack of testing of software interfaces.”

    View the original warning letter.


    Recommended Solutions

    Compliance Training >>

    Recommended Solutions

    ExcelSafe >>

    Recommended Solutions

    Ofni Clinical >>

    Recommended Solutions

    Part 11 Toolkit >>

    Recommended Solutions

    Part 11 Advisor >>

    Recommended Solutions

    MedWatch Reporter >>

    Recommended Solutions

    Computer Validation >>

    Recommended Solutions

    Custom Programming >>

    Recommended Solutions

    Validating MS Excel Spreadsheets >>

    Recommended Solutions

    Access Databases >>


Page 5 of 2512345678910...20...Last »