Clinical Database Validation

Disambiguation: Clinical database validation is making sure that clinical databases perform the functions required for 21 CFR 11 and other regulations. Clinical data validation, i.e. checking clinical data for problems, is on another page.

• More information on the disambiguation.
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What is Clinical Database Validation?

Validation of a clinical database is a structured, documented process to show that the database follows regulatory requirements and performs other functions it needs to perform. This is sometimes summarized as making sure clinical databases are fit for their intended use. In general, database validation is a type of software validation.

Why do Clinical Databases have to be Validated?

There are a number of regulations and guidances requiring validation of electronic health records systems, which include clinical databases – see below for a list of the more important ones. The underlying reason for the regulations is that clinical databases affect clinical data, which affect treatment decisions, which affect patient health. Since the patient population in question is virtually all of the United States and a significant fraction of the rest of the world, making sure that clinical databases are fit for their intended use is very important.

What is the Validation Process?

Validation is a complex process with many possible variations and options, so specifics vary from database to database, but the general outline is:

• Requirement Gathering
  • The Sponsor decides what the database is required to do based on regulations, company needs, and any other important factors.
  • The requirements are documented and approved.

• System Testing
  • Procedures to test the requirements are created and documented.
  • The version of the database that will be used for validation is set up.
  • The Sponsor approves the test procedures.
  • The tests are performed and documented.
  • Any needed changes are made. This may require another, shorter round of testing and documentation.

• System Release
  • The validation documentation is finalized.
  • The database is put into production.

More information on software validation documents and projects is available here.

Regulations and Guidances

• 21 CFR 11.10 – The primary FDA regulation requiring validation of electronic records systems, which includes clinical databases. The text says “procedures and controls [for electronic records systems] shall include the following (a) Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records.”
• Guidance for Industry Part 11, Electronic Records; Electronic Signatures – Scope and Application – The guidance outlining the FDA’s approach to enforcement of 21 CFR Part 11.
• Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance – The International Conference on Harmonisation guidance on Good Clinical Practice, which is also an FDA guidance. Section 5.5.3 states “When using electronic trial data handling and/or remote electronic trial data systems, the sponsor should: (a) Ensure and document that the electronic data processing system(s) conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistent intended performance (i.e., validation).”
• General Principles of Software Validation; Final Guidance for Industry and FDA Staff – The guidance outlining the FDA’s thinking on software validation.
• Annex 11 – The European equivalent of 21 CFR Part 11. While this technically only applies to companies with clinical operations in the European Union, some of the ideas incorporated in Annex 11, such as risk management, are part of best practices for software validation even when not stated as such in regulations.

Other References

• GAMP® 5: A Risk-Based Approach to Compliant GxP Computerized Systems – A widely-used industry reference on software validation.
• Computerized Systems in Clinical Research: Current Data Quality and Data Integrity Concepts – A general guide to clinical data systems. It includes validation information.