Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
R AUL S OTO, MS C, CQ E
IVT A PRIL 2015 P HILADELPHIA
ABOUT THE AUTHOR
• Contact information:
• Raul Soto rasove_21@yahoo.com
2
TABLE OF CONTENTS
1. REGULATORY PERSPECTIVE
2. SPREADSHEET VALIDATION
4. HANDS-ON EXERCISES
SCOPE
SPREADSHEET
• Microsoft Excel file that may contain:
• mathematical calculations
• Statistical analysis
• Graphing
4
PART 1: REGULATORY
PERSPECTIVE
REGULATIONS GOVERNING SPREADSHEETS 5
WHICH SPREADSHEETS NEED TO BE
VALIDATED?
If the spreadsheet supports any activity governed by
applicable regulations, it should be validated
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FDA 483S AND WARNING LETTERS
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FDA 483
http://www.contractormisconduct.org/ass/contractors/18/cases/305/221/f
da-warning-letter.pdf
FDA WARNING LETTERS
http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm
369409.htm
FDA WARNING LETTERS
http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2006/u
cm075766.htm
FDA WARNING LETTERS
http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2011/ucm2
56498.htm
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FDA WARNING LETTERS
http://www.ofnisystems.com/media/g3667d.pdf
FDA WARNING LETTERS
http://www.ofnisystems.com/Resources/Warning_Letters/g4452d.pdf
FDA WARNING LETTERS
http://www.ofnisystems.com/media/g1483d.pdf
MEDICAL DEVICES
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MEDICAL DEVICES
• Section 6.0
• “Many other commercial software
applications, such as word processors,
spreadsheets, databases, and
flowcharting software are used to
implement the quality system. All of
these applications are subject to the
requirement for software validation, but
the validation approach used for each
application can vary widely.”
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MEDICAL DEVICES
• Section 6.1
• “Numerous commercial software
applications may be used as part of the
quality system (e.g., a spreadsheet or
statistical package used for quality system
calculations, a graphics package used for
trend analysis, or a commercial database
used for recording device history records or
for complaint management). The extent of
validation evidence needed for such
software depends on the device
manufacturer's documented intended use of
that software.”
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PHARMACEUTICALS
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BIOLOGICS
• Clause 7.5.2.1
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ISO 13485 : 2015
DESIGN AND MANUFACTURE OF MEDICAL DEVICES
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FDA LAB MANUAL OF QUALITY PROCEDURES
• http://www.fda.gov/ScienceResearch/FieldScience
/LaboratoryManual/ucm174286.htm
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4.5.3 VALIDATION OF SPREADSHEETS
SUMMARY
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COMMON SPREADSHEET ISSUES FOUND BY
FDA IN INDUSTRY
• Spreadsheet files not maintained, some deleted
• Rounding errors
• Formulas don't match (Excel vs source, Excel vs manual
calculation)
• Conversion factors issues
• Spreadsheet doesn't show specs or limits
• Unclear documentation
• Units not labeled
• Weights described as volumes, areas as ratios
• Security and data integrity issues
• Cells not locked
• Regressions that inverted X and Y axis
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PART 2: VALIDATING THE
SPREADSHEET
VALIDATION PLAN, EXECUTION, REPORTING 29
VALIDATING YOUR SPREADSHEET
• Validation :
Provide documented
evidence that the
spreadsheet does what it
is intended to do,
correctly, and consistently
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TYPICAL VALIDATION ELEMENTS
• Validation Plan
• Requirements Specification You can use
• Design Specification separate documents
• Traceability Matrix for each
• Testing
• Development -OR-
• Installation Qualification
• OQ / PQ -or- A single Validation
• System / User Acceptance Protocol that
includes ALL
• Validation Report
validation elements
• Procedures & Governance
• Templates 31
GOVERNANCE
• Training
32
GENERAL INFORMATION
• Spreadsheet name
• References
• Analytical methods, SOPs, etc.
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REQUIREMENTS
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REQUIREMENTS
• Input cell and formula cell requirements
• Formatting (colors, font size and type, etc.)
• Data validation (field type, size, etc.)
• Page formatting
• Titles
• Headers
• Footers
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REQUIREMENTS
• Charts and Graphs
• Title and Description of each
• Required labels for each axis
• Security requirements
• Password protection
• Output requirements
• Color printer, PDF-creating software
• Specific folder in a specific shared drive
• Automatic eMail to specific people
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DESIGN SPECIFICATION
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TRACEABILITY MATRIX
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DEVELOPMENT TESTING & DRY RUNS
• Recommended!
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INSTALLATION QUALIFICATION (IQ)
• OQ
• Negative testing :
• Use incorrect inputs to ensure
the spreadsheet is robust, able
to handle them without crashing
or producing false or incorrect
outputs, and that it is not
possible to bypass security
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OQ: POSITIVE VS NEGATIVE TESTING
• Field size test: ensure user can only enter the specified
number of characters in a field 46
OQ: POSITIVE VS NEGATIVE TESTING
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OQ: POSITIVE VS NEGATIVE TESTING
• http://www.softwaretestingcl
ass.com/positive-and-
negative-testing-in-software-
testing/
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OQ SECURITY TESTING
• Security testing:
• Ensure it is not possible to:
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OQ PERFORMANCE TESTING
• Performance :
• Multiple users simultaneously
• Open multiple instances of the spreadsheet at the
same time
• Execute spreadsheet while various other
applications are running
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OPERATIONAL QUALIFICATION
• Formula Auditing
• Excel’s Formula Auditing tools allows us to demonstrate that
the inputs come from the expected cells
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TEST EXECUTION
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TEST EXECUTION
• Post-approvals
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CHANGE CONTROL AFTER VALIDATION
• Update Validation documentation
• Additional or changed requirements
• Corresponding design elements changes
• Update Testing
• New or updated test scripts
• Test new functionality (i.e. new/updated formula)
• Regression testing: ensure areas not changed still work
correctly
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PART 3:
BUILDING THE SPREADSHEET
DESIGN A COMPLIANT SPREADSHEET 57
CHANGE CONTROL
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CREATING THE SPREADSHEET
• Spreadsheet Name
• Version number
• Date of last modification
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CREATING THE SPREADSHEET
• Verify formulas against sources
• Use correct units of measurement
• Lock all non-input cells
• Disable column/row add/remove
• Unlock input cells
• Distinguish input, calculation (formula) vs output
cells
• Cell background color
• Font : bold, italics, size, color
• Use conditional formatting on output cells
• Different cell background color and/or font color for results
that pass vs results that fail
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CREATING THE SPREADSHEET
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UNITS CONVERSION
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CHANGE HISTORY
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SECURITY LAYERS
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PART 4: WORKSHOP
HANDS-ON SPREADSHEET WORKSHOP 66
SPREADSHEET CREATION
• 3. Data validation
• 4. Formula auditing
• Trace Precedents and Dependents
• Show and evaluate formulas
• Error checking
• Preventing formulas from being displayed
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1. ID CELL TYPES BY COLOR
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2. CONDITIONAL FORMATTING
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2. CONDITIONAL FORMATTING
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2. CONDITIONAL FORMATTING
• Example 1
• Minimum spec value is 14, maximum is 17
• We want cells to be:
• Lt Green fill and Dk Green text IF value is between min and max
• Lt Red fill and Dk Red text IF value is outside min and max
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2. CONDITIONAL FORMATTING
• Example 1 (cont.)
3. Home / Styles / Conditional Formatting/ Highlight Cell Rules/ Greater
Than => dialog box
4. Select cell where maximum value is listed, and desired formatting:
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2. CONDITIONAL FORMATTING
• Example 2:
• Have a cell that shows PASS or FAIL depending on the value of
another cell
• We want
• PASS: Lt Green fill and Dk Green text
• FAIL: Lt Red fill and Dk Red text
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3. DATA VALIDATION - SETTINGS
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3. DATA VALIDATION – INPUT MESSAGE
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3. DATA VALIDATION – ERROR ALERT
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3. DATA VALIDATION – DATA TYPES
• Types of inputs:
• Any value
• Whole number
• Decimal
• List
• restrict input to items from a specified list
• List should be included in a protected
column in the spreadsheet
• Date
• Time
• Text length
• Custom
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3. DATA VALIDATION
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3. DATA VALIDATION
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3. DATA VALIDATION
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3. DATA VALIDATION
• Custom:
• Example: ensure the entry in a column is a number
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4. FORMULA AUDITING
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4. FORMULA AUDITING
4.1 How to prevent your formulas from being displayed in the formula bar:
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4. FORMULA AUDITING
• Precedents
• 1. Select formula cell
• 2. Formulas / Formula
Auditing / Trace Precedents
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4. FORMULA AUDITING
4.2 How to trace Precedents and
Dependents in your formulas:
• Dependents
• 1. Select formula cell
• 2. Formulas / Formula
Auditing / Trace Dependents
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4. FORMULA AUDITING
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4. FORMULA AUDITING
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4. FORMULA AUDITING
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4. FORMULA AUDITING
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4. FORMULA AUDITING
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4. FORMULA AUDITING
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4. FORMULA AUDITING
• Error Checking will display the cause of the error (wrong data
type in this example)
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4. FORMULA AUDITING
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5. SET PRINT HEADERS & FOOTERS
4. OK
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5. SET PRINT HEADERS & FOOTERS
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5. SET PRINT HEADERS & FOOTERS
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6. PROTECT YOUR WORKSHEET
• BUT someone can still delete, add, and rename worksheets from
the spreadsheet
• => Protect Workbook
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6. PROTECT YOUR WORKSHEET
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7. UNPROTECT INPUT CELLS
1. Review tab / Changes group / Unprotect Sheet
4. When the “Allow Users to Edit Ranges” dialog box opens, click on
NEW
7. Now you can only change the values of the selected input cells 106
7. UNPROTECT INPUT CELLS
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7. UNPROTECT INPUT CELLS
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7. UNPROTECT INPUT CELLS
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8. PROTECT YOUR WORKBOOK
• 2. [√] Structure
• 3. [ ] Windows
• 4. Password: enter and re-enter worksheet password
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8. PROTECT YOUR WORKBOOK
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9. PROTECT AND SHARE WORKBOOK
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9. PROTECT AND SHARE WORKBOOK
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10. TRACKING CHANGES
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10. TRACKING CHANGES
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10. TRACKING CHANGES
• You can get a “report” that will show you all the changes
made to the spreadsheet since the last save
• Review / Changes / Track Changes/ Highlight Changes
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10. TRACKING CHANGES
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10. TRACKING CHANGES
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QUESTIONS
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Thank You !
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