Ok.  Anyone who knows me, has read this blog for a while or has seen me speak knows I love to use movies as transferable concepts to try to explain supposedly complicated scientific concepts.

What can the 1985 classic movie “Fletch” teach us about method validation?

Just like when “Gordo” said in the above clip “Awww, come on guys, it’s so simple. Maybe you need a refresher course. [leans arm on hot engine part] Hey! It’s all ball bearings nowadays..”,

We say to the lab people “Awww, come on guys, it’s so simple. Maybe you need a refresher course… Hey! It’s all validation nowadays.”

Method validation has received considerable attention in the literature and from industrial committees and regulatory agencies.

• The U.S. FDA CGMP (1) request in section 211.165 (e) methods to be validated: The accuracy, sensitivity, specificity, and reproducibility of test methods employed by the firm shall be established and documented. Such validation and documentation may be accomplished in accordance with Sec. 211.194(a). These requirements include a statement of each method used in testing the sample to meet proper standards of accuracy and reliability, as applied to the tested product. The U.S. FDA has also proposed an industry guidance for Analytical Procedures and Methods Validation (2).
• ISO/IEC 17025 includes a chapter on the validation of methods (3) with a list of nine validation parameters. The ICH (4) has developed a consensus text on the validation of analytical procedures. The document includes definitions for eight validation characteristics. ICH also developed a guidance with detailed methodology (5).
• The U.S. EPA prepared a guidance for method’s development and validation for the Resource Conservation and Recovery Act (RCRA) (6). The AOAC, the EPA and other scientific organizations provide methods that are validated through multi-laboratory studies.

Here is the whole point and my logic proof…

1.       I assume that there is a truly scientifically validated and robust method for the analysis undertaken in the forensic lab.  (To be sure of the usefulness of their analysis, we want to examine the lab’s validation studies so as to not make this basic assumption.  Otherwise, what’s the point…  Without this basic principle satisfied that there is a valid method, the lab should not be performing tests)

2.       Universally, if one follows the validated method and only if one religiously follows the validated method with no deviation, we get a valid result that is true (or more correctly put as valid and as true a result as scientifically possible)

3.       The converse of that is not 100% true.  If we deviate from the validated method in some way or in any way, we MAY get a true result or we MAY not.  We don’t know without studying the impact of that deviation.  We do know that the deviation has caused the result to be not a validated result.  Not an invalid result, but rather a result that is not validated according to the valid method.

4.       As most of the validation studies begin with “Take the filled 10mL grey tube top….”  This would connote that the method was created using precisely that a “filled 10mL grey tube top”.  It is the raw material, if you will.  It is like a condition precedent.

5.       If you do not have the condition precedent (i.e., the 10mL grey tube top), then you are missing a part of the validated conditions and you have by definition a deviation from the validated method.

6.       Ergo, you have a result that is not validated and may or may not be valid and may or may not be true.

To learn more about method validation, I would commend to you http://www.labcompliance.com/tutorial/methods/default.aspx

The tutorial is based upon the book Validation and Qualification in Analytical Laboratories, published by Infoma in 2007 which I highly recommend as the easiest and best resource that I have come across that explains the importance of method validation, the method of establishing a validated method, the consequences of method validation and the consequences of deviating from the validated method.

DEFINITIONS USED IN THIS POST:

Invalid: proven to be not valid, not the same as “not validated” as “not validated” means that it may be valid or it may be invalid.

True: the value that characterizes a quantity perfectly in the conditions that exist when that quantity is considered. It is an ideal value, which could be arrived at only if all causes of uncertainty (Type A error and Type B error) are eliminated.

Type A error: a method of evaluation by statistical analysis of a series of observations.

Type B error: anything that is not Type A error; a method of evaluation by any means other than statistical analysis of a series of observations.

Valid: documented proof that the process undertaken is suitable for its intended use and achieves the intended reported result correctly and uniquely as free from possible from issues of precision and bias as possible.