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FDA 'Advice' on Using Spreadsheets

GxP records generated by spreadsheet calculations are electronic records and should comply with FDA’s 21 CFR Part 11. For critical records Part 11 controls should be implemented. Most critical are data integrity and data accuracy. Currently there are no specific industry FDA guidelines on using spreadsheets in regulated environments. On the other hand spreadsheet applications have been audited as part of FDA inspections and many warning letters have been issued.

While 483's and warning Letters only cite deviations and provide little value value for correct implementation, FDA's establishment inspection reports (EIRs) are much more valuable. They not only include deviations but describe how critical requirements have been implemented.

Here are some excerpts from a 'follow up' inspection report (EIR). While the original inspection resulted in several observations and a warning letter, the findings from the follow up have been accepted and can be considered as good practices for using spreadsheets in FDA regulated environments:.

Testing

 

  1. Each spreadsheet used in calculating analytical results had been put through a battery of tests to examine how the spreadsheet would react. These tests include the entry of the following types of data: aberrant high findings, aberrant low findings, in-specification findings, zeros, negative numbers, and alphanumeric combinations.
  2. Each spreadsheet is product specific and has a separate validation package.
  3. Each package contains the initial testing of the information as entered into the Spreadsheet, a blank spreadsheet, and a spreadsheet showing the calculation formulas used in the appropriate cells.
  4. The package contains a list of the tests conducted and the dates they were performed as well as hand calculations of some trial data for comparison
  5. Revised SOP "QA/QC Computer Spreadsheet Validation," contains directions for testing new and existing spreadsheets prior to use in analytical testing.
  6. The spreadsheets are checked monthly by a familiar analyst with previously entered data.
  7. The check results are compared to the originals to make sure that corruption of the file has not occurred

Integrity

  1. The firm now saves the spreadsheets in read-only form to compact discs, specific to product. Changes to spreadsheets cannot be saved in this format.
  2. Two sets of CDs were made, one Set for the daily laboratory use and one master copy containing all spreadsheets.
  3. lf one spreadsheet an a CD is changed, then a new CD is burned and the old one is archived.
  4. Authenticity of print-outs: The spreadsheet when printed out bears a file path at the bottom to assure it came from the CD

Recommendations from Labcompliance

  1. Follow written standard procedures when developing and using spreadsheet applications. The focus should be on data integrity and change control.
  2. Follow written standard procedures for the validation of spreadsheet applications.
  3. Learn about and use all functions that are part of the standard software, such as Excel.
  4. FDA is using Excel spreadsheets in it's own regulated environments. However, they follow internal guidelines as described in two information bulletins. They are part of the Labcompliance audio seminar reference material.

More Information

You can get more detailed information, e.g., the full EIR, a cost effective strategy to avoid FDA Warning Letters, SOPs for development, validation and use and two FDA Laboratory Information Bulletins in the Labcompliance Audio Seminar: Validation and Use of Excel® Spreadsheets in Regulated Environments

 

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