Harmonization of strategies for the validation of quantitative analytical procedures: A SFSTP proposal—part I

https://doi.org/10.1016/j.jpba.2004.07.027Get rights and content

Abstract

This paper is the first part of a summary report of a new commission of the Société Française des Sciences et Techniques Pharmaceutiques (SFSTP). The main objective of this commission was the harmonization of approaches for the validation of quantitative analytical procedures. Indeed, the principle of the validation of theses procedures is today widely spread in all the domains of activities where measurements are made. Nevertheless, this simple question of acceptability or not of an analytical procedure for a given application, remains incompletely determined in several cases despite the various regulations relating to the good practices (GLP, GMP, …) and other documents of normative character (ISO, ICH, FDA, …). There are many official documents describing the criteria of validation to be tested, but they do not propose any experimental protocol and limit themselves most often to the general concepts. For those reasons, two previous SFSTP commissions elaborated validation guides to concretely help the industrial scientists in charge of drug development to apply those regulatory recommendations. If these two first guides widely contributed to the use and progress of analytical validations, they present, nevertheless, weaknesses regarding the conclusions of the performed statistical tests and the decisions to be made with respect to the acceptance limits defined by the use of an analytical procedure. The present paper proposes to review even the bases of the analytical validation for developing harmonized approach, by distinguishing notably the diagnosis rules and the decision rules. This latter rule is based on the use of the accuracy profile, uses the notion of total error and allows to simplify the approach of the validation of an analytical procedure while checking the associated risk to its usage. Thanks to this novel validation approach, it is possible to unambiguously demonstrate the fitness for purpose of a new method as stated in all regulatory documents.

Introduction

The present paper is the first part of a summary report resulting from a new Société Française des Sciences et Techniques Pharmaceutiques (SFSTP) Commission on the harmonization of approaches for the validation of quantitative analytical procedures. The whole report has been published in the French journal of the SFSTP [1]. The different sectors aimed by this commission report are: (1) the corporation's contractors of services; (2) the regulatory bodies; (3) the official quality laboratories; and (4) the industries of various sectors, namely chemistry, pharmacy, bio-pharmacy, food processing, environment, cosmetology, etc. The main references of the SFSTP commission report are: (1) regulatory bodies documents [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]; (2) ICH documents (Q2A and Q2B) [5], [6]; (3) FDA documents (guidance for industry) [5], [6], [10], [11]; (4) ISO documents [12], [13], [14], [15], [16] especially 5725 (AFNOR X06-041) document [13] and ISO 17025 document [14]; and (5) Commission Decision 2002/657/EEC (SANCO) [17].

As can be seen in the bibliography, the validation of the assay procedures is a vast subject that interests the scientific and regulatory worlds since many years [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45]. Among these documents, the following documents were also used to support the present guide: (1) SFSTP ‘92 guide [20], SFSTP ‘97 guide [21], [22] and publications related to the Conference of Washington (1990) [11], [18], [19], [21], [22].

The different regulations concerning to the good practices (GLP, GMP, GCP, and others) as well as the normative or regulatory documents (ISO, ICH, EMEA, and FDA) suggest that all procedures have to comply with acceptance criteria. This request imposes, therefore, that these procedures must be validated. There are several documents defining the validation criteria to be tested, but they do not propose experimental approaches and limit themselves, most often, to the general concepts. It is why the members o the SFSTP have contributed to the elaboration of consensus validation guides to help the pharmaceutical industry to validate their analytical procedures (pharmaceutical specialties) [20] and bio-pharmaceutical procedures (procedures implied in pharmacokinetics and bioequivalence studies) [21], respectively.

Today, one can say that these two guides have significantly contributed to make progress the validation of the analytical procedures. Nevertheless, the first guide (SFSTP ‘92) [20] has been considered to be too exclusively dedicated to the pharmaceutical specialties and has showed weaknesses regarding the objective of the validation. For example, the analyst could be penalized when its method was too precise. In addition, he was confronted to a lot of statistical tests generally complicating his decision rather than helping him. This paradoxical situation comes from the confusion between the diagnosis rules and decision rules. Same confusion could be observed in the second validation guide (SFSTP ‘97) [21] devoted to bio-analytical procedures. However, the first bases of accuracy profile was proposed in the second guide. This concept could be extended to other activity sectors such as environment or food analysis but that document was only dedicated to biopharmaceutical analysis [22], [44].

For these different reasons, the goal of the new SFSTP document [1] is mainly to reconcile the objectives of the validation with those of the analytical procedure. It also aims to provide a simple decision tool based on the total error (bias + standard deviation) of the procedure. This approach allows to considerably minimize the risk to accept a procedure that would not be sufficiently accurate or, to the opposite, to reject a procedure that would be capable. Concurrently to these general concepts, the others objectives of the new SFSTP guide are to propose a consensus on the norms usually recognized, while widely incorporating the ISO terminology, and to insist on the validation of the analytical procedure in the same way as it will be used in routine. It also presents experimental strategies for the validation of quantitative procedures, regardless of the industrial sector, to optimally use experiments performed, to extract a maximum of information from the results and to minimize in routine the risks to re-analyze samples. Since it is impossible to synthesize this important work in a single document, the present paper is limited to general concepts and the experimental strategies will be presented in a second paper [46].

Section snippets

Objectives of an analytical procedure

In order to specify the objectives of the validation, it is necessary to go back to the nature itself of an analytical method. Is its objective to demonstrate that the response varies linearly as a function of the concentration, that the bias and the precision are less than x% or rather to quantify as accurately as possible each unknown quantity? These interrogations seem to be the questions of interest. The objective of a “good” analytical procedure is to be able to quantify as accurately as

Objective of the validation

Knowing that the characteristics of “true bias” and of “true precision” are parameters that will always remain unknown but that will be estimated by the measurements obtained in validation phase, what is the objective of validation?

Under these conditions, it seems reasonable to claim that the objective of validation is to give to the laboratories as well as to regulatory bodies “guarantees” that every single measure that will be later performed in routine analysis will be “close enough” to the

Decision rules

The examination of the current situation with respect to the decision rules used in the validation phase [20], [21] shows that the most of them are based on the use of the null hypothesis as follows.H0:bias=0H0:relativebias=0%H0:recovery=100%with the bias = xμT, the relative bias = (xμT/μT) × 100 and the recovery = (x/μT) × 100.

On this basis, a procedure is wrongly declared adequate when the 95% confidence interval of the average bias includes the value of 0 (0% and 100% in the case of

Conclusion

The lack of generalisation between the different validation protocols has conducted several analysts, resulting from different companies but also from previous SFSTP commissions on the validation (1992 and 1997) [20], [21], to elaborate a harmonized approach. Moreover, if the first guides widely contributed to progress the analytical validations, they present, however, weaknesses regarding the conclusions of the tests carried out and thus the decisions to be made on the validity of the

Acknowledgment

The authors wish to thank the members of the SFSTP office for the organization of the meetings.

References (52)

  • V.P. Shah et al.

    J. Pharm. Sci.

    (1992)
  • Ph. Hubert et al.

    Anal. Chim. Acta

    (1999)
  • A.C. Causey et al.

    J. Pharm. Biomed. Anal.

    (1990)
  • G.P. Carr et al.

    J. Pharm. Biomed. Anal.

    (1990)
  • P.A.D. Edwardson et al.

    J. Pharm. Biomed. Anal.

    (1990)
  • A.R. Buick et al.

    J. Pharm. Biomed. Anal.

    (1990)
  • H.T. Karnes et al.

    J. Pharm. Biomed. Anal.

    (1991)
  • J.R. Lang et al.

    J. Pharm. Biomed. Anal.

    (1991)
  • J.R. Lang et al.

    J. Pharm. Biomed. Anal.

    (1991)
  • C. Hartmann et al.

    J. Pharm. Biomed. Anal.

    (1994)
  • D. Dadgar et al.

    J. Pharm. Biomed. Anal.

    (1995)
  • J. Vessman

    J. Pharm. Biomed. Anal.

    (1996)
  • S. Braggio et al.

    J. Pharm. Biomed. Anal.

    (1996)
  • P. Chiap et al.

    Anal. Chim. Acta

    (1999)
  • M. Feinberg et al.

    Anal. Chim. Acta

    (1999)
  • J. Ermer

    J. Pharm. Biomed. Anal.

    (2001)
  • Y. Vander Heyden et al.

    J. Pharm. Biomed. Anal.

    (2001)
  • B. Boulanger et al.

    J. Pharm. Biomed. Anal.

    (2003)
  • J.O. De Beer et al.

    J. Pharm. Biomed. Anal.

    (2003)
  • S. Pinzauti et al.

    J. Pharm. Biomed. Anal.

    (1996)
  • S. Furlanetto et al.

    J. Pharm. Biomed. Anal.

    (1997)
  • Y. Vander Heyden et al.

    J. Pharm. Biomed. Anal.

    (1998)
  • Y. Vander Heyden et al.

    J. Pharm. Biomed. Anal.

    (1998)
  • Ph. Hubert et al.

    STP Pharma. Pract.

    (2003)
  • Commission of the European Communities, Working group of the committee of medical products, explanatory notes...
  • Drugs Directorate Guidelines: Acceptable Methods, Authority of the Minister of National Health and Welfare, Health...
  • Cited by (411)

    • Development and validation of a multiplex HPLC-MS/MS assay for the monitoring of JAK inhibitors in patient plasma

      2023, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
    • Validation of liquid chromatographic methods

      2023, Liquid Chromatography: Fundamentals and Instrumentation: Volume 1, Third Edition
    • Validation of thin-layer chromatographic methods

      2023, Instrumental Thin-Layer Chromatography, Second Edition
    View all citing articles on Scopus
    1

    Member of the SFSTP Commission, 106 rue Monge, F-75005 Paris, France.

    View full text