Warning Letter: Audit trail data for system is inconsistent with printed records (ucm560653)

Your firm does not exercise appropriate controls over computer related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel [21 C.F.R. 211.68(b)]. For example:

A. Your “Processed By” dates and times listed on printed chromatograms do not always show the same “Processed By” dates and times listed on the system chromatograms.

B. Your data in the audit trails does not always show the same data listed on your printed chromatograms.

Your response states you have not observed any test result data discrepancies between your printed versions of the test results. However, this does not address adequate electronic data controls to prevent inconsistencies between the printed and electronic data. Your responses for 2A and 2B above are not adequate in that your firm did not provide any corrective action addressing the assessment of all relevant data in the audit trails.

C. Your firm enters data into [redacted] files to complete plate assay calculations but they are not locked from editing once the file has been reviewed.

Your response fails to include any corrective action to ensure that there is no further access or ability to save over test results in [redacted] spreadsheets once reviewed and approved.

D. Your firm did not give unique sample set names to different sequences of samples run on different instruments on the same day.

Your response is not adequate. Your firm did not address the concern of the possibility of sample sets with the same name overwriting each other during the data backup process…

Your procedure is to then enter the raw data into document number MIC-0066-13-01 titled “[redacted]”, Attachment 1. On the completed form, the [redacted] test results for the [redacted] zones were not the same as observed by our Investigator; the range was 11.4 to 15.1. Your firm used an Excel spreadsheet to calculate the potencies of Tri-Otic Ointment lots H610 and H6514 as [redacted] and [redacted], respectively.

Your response does not provide documentation of the January 26, 2017 handwritten zone diameter results for Tri-Otic Ointment (Lots H6510 and H6514), which you allege differ from our investigators’ direct observation. We note your response acknowledges that you should have provided our Investigator a copy of the handwritten zone diameter results. You have not subsequently verified complete raw data was maintained.

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Warning Letter: Failure to adequately review and evaluate complaints on a spreadsheet (ucm540783)

Review of a spreadsheet of all the complaints [redacted] received from January 2016 through April 2016 revealed that eighty-six (86) out of 233 separate complaint entries were for issue codes that your firm does not routinely review and evaluate.  Of these eighty-six (86) complaint entries there were eight (8) entries that describe “high” blood glucose readings.  You have stated that unexpected “high” glucose readings are a concern because if the reading is false the patient may administer insulin when it is not needed, which could lead to possible overdose and potential organ failure.

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Warning Letter: Failure to control spreadsheets, data integrity (ucm538068)

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Warning Letter: Inadequate spreadsheet (ucm406826)

Also, your firm tracks complaint data on a spreadsheet that contains free form text fields that are not standardized, resulting in an inability to adequately trend the data. For example, when using complaint data from January 1, 2011 to February 19, 2014 to trend for “Description of Failure” for “6090,” fourteen complaints are shown. However, the spreadsheet contains several different descriptions of the same part failure that when totaled resulted in a total count of forty complaints related to the inline coupler, part #6090.”

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483 from BioQuality, Vol. 14(9): Use of Uncontrolled Excel Spreadsheet

“Uncontrolled Excel spreadsheet is used for: • issuance of deviation numbers • tracking deviations to closure • trending deviation data This has resulted in: • CAPAs not always being linked to associated deviations • Deviation priority levels not always being consistent Validation of QC lab software failed to demonstrate adequate security: • Analysts have the ability to overwrite original data • No individual user names and passwords limiting access to the system “

Warning Letter: Lack of spreadsheet controls (UCM 311326)

Specific violations observed during the inspection include, but are not limited, to the following: 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, properly identified to show the specific component, drug product container, closure, in-process material, or drug product, and lot tested [21 CFR 211.194 (a)(4)]. Specifically, 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.

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Warning Letter: Failure to validate Excel Spreadsheet (ucm256498)

Failure to validate software used as part of production or the quality system for its intended use according to an established protocol, as required by 21 CFR 820.70(I). For example, your firm did not validate use of an Excel spreadsheet used to calculate the Moisture Vapor Transmission Rate (MVTR) per test procedure [redacted] Revision B.

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Warning Letter: Spreadsheet data entry cells not locked (ucm229262)

We observed 8 of 9 worksheets where one or more tabs with formula cells were not locked. These worksheets were used for analyzing raw data from drug component and product samples, including [redacted]. Your firm’s SOP 100-G-0110, “Creation and Use of Templates,” stated that cells, in which data is entered, must be locked within their electronic template.

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Warning Letter: No Procedures for Controlling Worksheets (ucm218221)

Your firm has no procedures for controlling laboratory worksheets including changes to worksheets, issuance of laboratory worksheets, and reconciliation of laboratory worksheets. The worksheet “Internal Communication – Batch Release Information” by the warehouse, which is used to identify released product, was created after [redacted] documented release of finished product for Heparin I.V. Flush Syringes and Normal Saline I.V. Flush Syringes prior to obtaining media fill results. This sheet is used to communicate batch release information to warehouse operations. Use of this sheet is not documented in any Medefil procedure nor is control over this sheet documented.

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Warning Letter: Spreadsheet Calculations not Verified or Documented (ucm174100)

Your laboratory records did not include a record of all calculations performed in connection with laboratory tests as required by 21 CFR § 211.194(a)(5). For example, laboratory notebook #7, page 49, documents the assay results, but not the calculations performed in Test number DSFS D-13 and Test number TG 521 for the analysis of [redacted], lot #HI7908. The notebook does not document reference to the spreadsheet calculation used to generate the results. In addition, the assay results generated by the spreadsheet were not verified for accuracy. Your response dated February 16, 2009, states that you have established procedures to ensure that calculations of method validation studies are recorded. The Records Management SOP, Section 5.7.4.7, states that the procedures shall define what and how data is to be recorded in respective logbooks. However, this SOP omits instructions to include in the notebook the reference to the spreadsheet calculation used to generate the results, as well as the raw data and calculations. In addition, you continued to release products based on assay results generated by the spreadsheet that have not been verified for accuracy.

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