Validation and the 3 Rs in Methods

Validation

• Validation is the process of confirming that a particular requirement for a specified use is fulfilled.
• Scientific community uses validation to assess procedure reliability, determine result conditions, and define limitations.
• Validation demonstrates a procedure follows the ‘3 Rs’ in the hands of the personnel performing the test.
• Method validation establishes performance characteristics and limitations of a method, identifies influences that change characteristics, and defines the extent of these changes.
• The process verifies a method is fit for a purpose, meaning it can be used to solve an analytical problem.

The 3 Rs

• Robust method - successful results a high percentage of the time, with few samples needing to be repeated.
• Reliable method - obtained results are accurate and reflect what is being tested.
• Reproducible method - the same or similar results are obtained for each sample tested.

Robustness

• A measure of an analytical procedure’s capacity to remain unaffected by minor variation in method parameters.
• Provides an indication of a method's reliability during normal usage.
• Ensures that the method won’t fail when only enough material for a single try exists.

Validation Requirements

• Validation is needed before introducing a new method into routine use or when conditions changed for which a method has been validated, such as a new instrument with different characteristics.

Validity Studies

• Hundreds or thousands of samples are required to fully validate an instrument or methodology.
• Each component of a test or process must be validated separately.
• Validation should seek to understand everything that could potentially go wrong with an instrument or technique.

DNA Validation

• Laboratories may only use validated methodologies for DNA analyses.
• Analysts must pass competency tests on a method before using it on case samples.
• Performance of modified procedures must be compared with the original procedure using similar DNA samples.
• Performance checks are required after any modifications or repairs to instruments or analysis software.

Analytical Procedures

• Laboratories must have Standard Operating Procedures (SOPs) reviewed annually by the technical leader in addition to other laboratory audits.
• All reagents, including lot numbers, must be tracked and used solely for their intended purpose.
• Analytical procedures must be monitored through the use of controls.
• Procedures must be checked annually or following substantial changes against appropriate reference materials.
• Written guidelines are required for interpretation of data including:
  • Verification of all controls
  • Inclusion/exclusion policies
  • Proper statistical interpretation of results
• Detection and control of contamination is essential.

Equipment Calibration & Maintenance

• Use equipment suitable for methods being employed.
• Document a program conducting performance checks and calibrations, with a minimum annual check.
• Maintain a schedule for maintenance, including performance checks following repairs prior to being used in casework.
• Quality control refers to specific procedures that are done to ensure that quality results are produced, including controls and calibrations.

NIST

• Founded in 1901 and is part of the US Department of Commerce.
• Authority on standards allows for standardization across laboratories, industries, and countries.

This quiz explores the concept of validation in scientific methods, emphasizing the importance of robustness, reliability, and reproducibility. Learn how these principles ensure that analytical methods are effective and trustworthy in various applications. Test your understanding of how validation plays a critical role in confirming the suitability of a method for specific purposes.