introduction to test method validation (tmv) - ddl · always lead with the disclaimer: test method...

Introduction to Test Method Validation (TMV)

Always lead with the disclaimer:

Test Method Validation is a complex topic that cannot possibly be covered in a handful of slides. This is intended to be a high level overview.

View from 30,000 ft.

As defined by the Code of Federal Regulations Title 21, Part 820 – Quality System Regulation: Validation is the confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use are fulfilled.

Specifically, Test Method Validation (TMV) is: the process of establishing the performance characteristics and limitations of a method and the identification of influences which may change these characteristics.

• In some fields, validation of methods is a regulatory requirement

• It is an important element of quality control.

• Validation helps supply assurance that a measurement will be reliable.

• New method is developed

• Established method is used outside its normal scope

• When validated methods are used in (or transferred to) different test facilities

• For comparison of methods

In the medical device market, the device risk index or harm classification help define the minimum level of statistical confidence required.

Business risk, cost of validation vs. potential for patient harm, is also considered.

• Qualification is documented evidence that a specific equipment, facility or system is fit/ready for intended use.

• Validation is documenting that the processes and procedures are appropriate for their intended use.

Test methods (processes) are validated using qualified equipment.

What type of data is collected? • Variable: a numerical result is obtained – e.g., peel

strength, length, burst pressure. • Attribute: pass/fail, go/no-go results – e.g., does it leak, is

it smooth?

… and within the these two groups, the tests can be:

• Destructive: samples are destroyed in the process of testing.

• Non-destructive: samples are not damaged or destroyed in the process of testing.

• Standard: validation of a lab version of an industry standard test method

• Standard with modifications: validation of a version of a standard, with modifications

• In-house: validation of a method developed specifically for the test lab, to cover a requirement not sufficiently met by a standard

• “Customer need” specific: validation of a method developed to satisfy a specific customer need

• Accuracy: closeness of agreement between the average of test results and an accepted reference value

• Bias: a consistent or systematic difference between a set of test results and an accepted reference

• Precision: the closeness of agreement among test results obtained under prescribed conditions.

• Repeatability: the closeness of the agreement between the results of successive measurements of the same sample carried out under the same conditions of measurement

• Reproducibility: the closeness of the agreement between the results of measurements of the same sample carried out under changed conditions of measurement.

A good test method must measure the intended attribute or variable precisely and accurately – part of establishing fitness for intended use.

Precise but not Accurate

Accurate but not Precise

Precise and Accurate

Example of Bias

• Determination of test specifics and protocol development (sampling plan, acceptance criteria…)

• Perform testing per protocol • Result analysis – are acceptance criteria met • Refine the test protocol and procedure if initial

testing does not meet pre-determined acceptance criteria

Acceptance criteria are the levels that the test method performance characteristics must meet. Examples:

• Gage resolution • Gage bias • Gage repeatability and reproducibility • Pass/fail, go/no-go

A revalidation is necessary whenever a method or its scope has changed.

The frequency and extent are determined using a risk-based approach.

• TMV is a risk based activity • TMV establishes method suitability for intended

use • TMV defines performance characteristics and

limitations • Validation facilitates internal QC/QA review • Validation demonstrates reliability of device or

packaging verification/validation data