In September 2013, the United States Pharmacopeial Convention (USP) published a stimulus to the revision process to adopt
quality-by-design principles for the development, validation, and operation of analytical procedures used for good manufacturing
practice (GMP) analysis. In February 2014, this was followed by a draft Food and Drug Administration (FDA) guidance for industry
on validation of analytical procedures. Also, the FDA issued a new draft that updates their 2001 guidance for industry on
bioanalytical method validation. Are the approaches the same? What do you think?
I live in London and we have a saying here: You wait a long time for a bus and then three turn up at once. Recently, in method
validation a similar thing has occurred and three draft documents for method validation have been issued over a relatively
short time span. Two of these method validation documents are intended for laboratories following good manufacturing practice
(GMP) principles and one is for bioanalytical laboratories following good laboratory practice (GLP) principles.
The three documents are
- G.P. Martin and colleagues, "Lifecycle Management of Analytical Procedures: Method Development, Procedure Performance Qualification,
and Procedure Performance Verification," published in Pharmacopeial Forum in September 2013 (1);
"Analytical Procedures and Methods Validation for Drugs and Biologics," draft Food and Drug Administration (FDA) guidance
for industry issued in February 2014 (2); and
- "Bioanalytical Method Validation," draft FDA guidance for industry dated September 2013 focused on GLP (3).
We devote this column to reviewing the contents of each of these documents, and comparing and contrasting their approaches
to a critical subject for quantitative analysis: the validation of analytical methods or procedures. I will spend most of
the column looking at the United States Pharmacopeial Convention (USP) proposal for method development and validation of analytical
procedures (1) because this is the most encompassing and radical of the three approaches. Some of these publications refer
to analytical procedures and analytical methods — from my perspective the terms are equivalent, and I will use them interchangeably.
Analytical method development, procedure validation, and transfer to other laboratories to carry out routine analysis are
key parts of the traditional analytical process. This starts, if you're lucky, with defining what you want the method to do
and ends up with the operational use of the procedure. In the middle is the stuff that should be done properly, but usually
is not, as evidenced by how poorly a method operates in routine use. This oversight typically occurs because the method development
and validation is performed by one group and the operation of the procedure is carried out by another group. In many instances,
the two groups rarely talked to each other except when things went wrong — and blamed each other for the problems. Of course,
this never happens in your organization, does it?
In the Beginning . . .
Method validation is not new because there have been a number approaches over the years in both GMP and GLP quality disciplines.
Validation of GMP analytical procedures was harmonized with the agreement of the International Conference on Harmonisation (ICH) quality publications Q2A and Q2B covering the text and methodology of validation of analytical procedures respectively (4,5) in 1994 and 1996, respectively.
These two publications were merged into a single document with the revision as ICH Q2(R1) in 2005 without changing any text (6). The first bioanalytical methods validation conference was held in 1990 (I was a co-chair
of one of the sessions), sponsored by the FDA and the American Association of Pharmaceutical Scientists (AAPS), that drew
up the first guidelines for bioequivalence and bioavailability studies typically carried out under GLP (7). This led to the
FDA issuing a guidance for industry on bioanalytical methods validation in 2001 (8).