Spreadsheets in a GxP Environment

I have them, you have them, and chances are they are used in more ways than you know. The spreadsheet is a powerful tool and really ubiquitous. As such, spreadsheets are used in many ways in the GxP environment, which means they need to meet their intended use and be appropriately controlled. Spreadsheets must perform accurately and consistently, maintain data integrity, and comply with regulatory standards such as health agency guidelines and the GxPs.

That said, it can also be really easy to over-control spreadsheets. It is important to recognize that there is no one-size-fits-all approach.

It is important to build a risk-based approach from a clear definition of the scope and purpose of an individual spreadsheet. This includes identifying the intended use, the type of data a spreadsheet will handle, and the specific calculations or data manipulations it will perform.

I recommend an approach that breaks the spreadsheet down into three major categories. This should also apply to similar tools, such as Jira, Smartsheet, or what-have-you.

Spreadsheet Functionality	Level of verification
Used like typewriters or simple calculators. They are intended to produce an approved document. Signatories should make any calculations or formulas visible or explicitly describe them and verify that they are correct. The paper printout or electronic version, managed through an electronic document management system, is the GxP record.	Control with appropriate procedural governance. The final output may be retained as a record or have an appropriate checked-by-step in another document.
A low level of complexity (few or no conditional statements, smaller number of cells) and do not use Visual Basic Application programs, macros, automation, or other forms of code.	Control through the document lifecycle. Each use is a record.
A high level of complexity (many conditional statements, external calls or writing to an external database, or linked to other spreadsheets, larger number of cells), using Visual Basic Application, macros, or automation, and multiple users and departments.	Treat under a GAMP5 approach for configuration or even customization (Category 4 or 5)

For spreadsheets, the GxP risk classification and GxP functional risk assessment should be performed to include both the spreadsheet functionality and the associated infrastructure components, as applicable (e.g., network drive/storage location).

For qualification, there should be a succinct template to drive activities. This should address the following parts.

1. Scope and Purpose

The validation process begins with a clear definition of the spreadsheet’s scope and purpose. This includes identifying its intended use, the type of data it will handle, and the specific calculations or data manipulations it will perform.

2. User Requirements and Functional Specifications

Develop detailed user requirements and functional specifications by outlining what the spreadsheet must do, ensuring that it meets all user needs and regulatory requirements. This step specifies the data inputs, outputs, formulas, and any macros or other automation the spreadsheet will utilize.

3. Design Qualification

Ensure that the spreadsheet design aligns with the user requirements and functional specifications. This includes setting up the spreadsheet layout, formulas, and any macros or scripts. The design should prevent common errors such as incorrect data entry and formula misapplication.

4. Risk Assessment

Conduct a risk assessment to identify and evaluate potential risks associated with the spreadsheet. This includes assessing the impact of spreadsheet errors on the final results and determining the likelihood of such errors occurring. Mitigation strategies should be developed for identified risks.

5. Data Integrity and Security

Implement measures to ensure data integrity and security. This includes setting up access controls, using data validation features to limit data entry errors, and ensuring that data storage and handling comply with regulatory requirements.

6. Testing (IQ, OQ, PQ)

• IQ tests the proper installation and configuration of the spreadsheet.
• OQ ensures the spreadsheet operates as designed under specified conditions.
• PQ verifies that the spreadsheet consistently produces correct outputs under real-world conditions.

Remember, all one template; don’t get into multiple documents that each regurgitate all the same stuff.

Lifecycle Approach

Spreadsheets should have appropriate procedural guidance and training.

They should be under risk-based periodic review.