FDA 'Advice' on Using Spreadsheets
GxP records generated by spreadsheet calculations are electronic records
and should comply with FDAâ€™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:.
- 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.
- Each spreadsheet is product specific and has a separate validation
- 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.
- 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
- Revised SOP "QA/QC Computer Spreadsheet Validation," contains
directions for testing new and existing spreadsheets prior to use in
- The spreadsheets are checked monthly by a familiar analyst with
previously entered data.
- The check results are compared to the originals to make sure that
corruption of the file has not occurred
- The firm now saves the spreadsheets in read-only form to compact
discs, specific to product. Changes to spreadsheets cannot be saved in
- Two sets of CDs were made, one Set for the daily laboratory use and
one master copy containing all spreadsheets.
- lf one spreadsheet an a CD is changed, then a new CD is burned and
the old one is archived.
- 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
- Follow written standard procedures when developing and using
spreadsheet applications. The focus should be on data integrity and
- Follow written standard procedures for the validation of spreadsheet
- Learn about and use all functions that are part of the standard
software, such as Excel.
- 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
seminar reference material.
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
ExcelÂ® Spreadsheets in Regulated Environments
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