Recommendations for the Bioanalytical Method Validation of Ligand-Binding Assays to Support Pharmacokinetic Assessments of Macromolecules
- 1.3k Downloads
Purpose.With this publication a subcommittee of the AAPS Ligand Binding Assay Bioanalytical Focus Group (LBABFG) makes recommendations for the development, validation, and implementation of ligand binding assays (LBAs) that are intended to support pharmacokinetic and toxicokinetic assessments of macromolecules.
Methods. This subcommittee was comprised of 10 members representing Pharmaceutical, Biotechnology, and the contract research organization industries from the United States, Canada, and Europe. Each section of this consensus document addresses a specific analytical performance characteristic or aspect for validation of a LBA. Within each section the topics are organized by an assay's life cycle, the development phase, pre-study validation, and in-study validation. Because unique issues often accompany bioanalytical assays for macromolecules, this document should be viewed as a guide for designing and conducting the validation of ligand binding assays.
Results. Values of ±20% (25% at the lower limit of quantification [LLOQ]) are recommended as default acceptance criteria for accuracy (% relative error [RE], mean bias) and interbatch precision (%coefficient of variation [CV]). In addition, we propose as secondary criteria for method acceptance that the sum of the interbatch precision (%CV) and the absolute value of the mean bias (%RE) be less than or equal to 30%. This added criterion is recommended to help ensure that in-study runs of test samples will meet the proposed run acceptance criteria of 4-6-30. Exceptions to the proposed process and acceptance criteria are appropriate when accompanied by a sound scientific rationale.
Conclusions. In this consensus document, we attempt to make recommendations that are based on bioanalytical best practices and statistical thinking for development and validation of LBAs.
Unable to display preview. Download preview PDF.
- 1.V. P. Shah, K. K. Midha, S. V. Dighe, I. J. McGiveray, J. P. Skelly, A. Yacobi. T. Laylogg, C.T. Viswanathan, C.E. Cook, R.D. McDowall, K.A. Putman, and S. Spector. Analytical methods validation: bioavailability, bioequivalence, and pharmacokinetic studies. J. Pharm. Sci. 81:309-312 (1992).Google Scholar
- 2.V. P. Shah, K. K. Midha, S. Dighe, I. J. McGilveray, J. P. Skelly, A. Yacobi, T. Layloff, C. T. Viswanathan, C. E. Cook, R. D. McDowall, K. A. Pittman, and S. Spector. Analytical methods validation: bioavailability, bioequivalence, and pharmacokinetic studies. Pharm. Res. 9:588-592 (1992).Google Scholar
- 3.J. W. A. Findlay, W. C. Smith, J. W. Lee, G. D. Nordblom, I. Das, B. S. DeSilva, M. N. Khan, and R. R. Bowsher. Validation of Immunoassays for bioanalysis: A pharmaceutical industry perspective. J. Pharm. Biomed. Anal. 21:1249-1273 (2000).Google Scholar
- 4.C. M. Riley and T. W. Rosanke. Development of validation of analytical methods: progress in pharmaceutical and biomedical analysis (vol 3) Elsevier (Pergamon), NY 1996.Google Scholar
- 5.V. P. Shah, K. K. Midha, S. Dighe, I. J. McGilveray, J. P. Skelly, A. Yacobi, T. Layloff, C. T. q Viswanathan, C. E. Cook, and R. D. McDowall. Analytical methods validation: bioavailability, bioequivalence and pharmacokinetics studies. Conference Report. Eur J Drug Metabol Pharmacokinetics 16:249-255 (1991).Google Scholar
- 6.Guideline on validation of analytical procedures: definitions and terminology International Conference of Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use Geneva 1995 (1996).Google Scholar
- 7.V. P. Shah, K. K. Midha, J.W.A Findlay, H. M Hill, J. D. Hulse, I. J McGilvary, G. McKay, K. J. Miller, R. N. Patnaik, M.L. Powell, A. Tonnelli, C. T. Viswanathan, and A. Yacobi. Bioanalytical method validation. A revisit with a decade of progress. Pharm. Res. 17:1551-1557 (2000).Google Scholar
- 8.K. J. Miller, R. R. Bowsher, A. Celniker, J. Gibbons, S. Gupta, J. W. Lee, J. S. J. Swanson, W. C. Smith, and R. S. Weiner. Workshop on Bioanalytical Methods Validation for Macromolecules: Summary Report. Pharm. Res. 18:1373-1383 (2001).Google Scholar
- 9.Guidance for the Industry. Bioanalytical Method Validation US Department of Health and Human Services FDA (CDER) and (CVM) May 2001.Google Scholar
- 10.J. O. Westgard. Points of care in using statistics in method comparison studies. Clin. Chem. 44:2240-2242 (1998).Google Scholar
- 11.H. Hubert, P. Chiap, J. Crommen, B. Boulanger, E. Chapuzet, N. Mercier, S. Bervoas-Martin, P. Chevalier, D. Grandjean, P. Lagorce, M. Lallier, M. C. Laparra, M. Laurentie, and J. C. Nivet. The SFSTP guide on the validation of chromatographic methods for drug analysis: from the Washington Conference to the laboratory. Analytica Chimica Acta. 391:135-148 (1999).Google Scholar
- 12.R. Kringle and D. Hoffman. Stability methods for assessing stability of compounds in whole blood for clinical bioanalysis. Drug Info J. 35:1261-1270 (2001).Google Scholar
- 13.U. Timm, M. Wall, and D. Dell. A new approach for dealing with the stability of drugs in biological fluids. J. Pharm. Sci. 74:972-977 (1985).Google Scholar
- 14.D. Rodbard, Y. Feldman, M. L. Jaffe, and L. E. M. Miles. Kinetics of Two-Site Immunoradiometric (Sandwich) Assays-II. Immunochem. 15:77-82 (1978).Google Scholar
- 15.B. D. Plikaytis, P. F. Holder, L. B. Pais, S. E. Maslanka, L. L. Gheesling, and G. M. Carlone. Determination of parallelism and nonparallelism in bioassay dilution curves. J. Clin. Microbiol. 32:2441-2447 (1994).Google Scholar
- 16.R. L. Placket and J. P. Burman. The design of optimum multifactorial experiments. Biometrica 33:305-325 (1946).Google Scholar
- 17.J. M. Bland and D. G. Altman. Measuring agreement in method comparison studies. Stat Meth Med Res 8:135-160 (1999).Google Scholar
- 18.C. Hartmann, J. Smeyers-Verbeke, W. Penninckx, Y. Vander Heyden, P. Venkeerberghen, and D. L. Massart. Reappraisal of hypothesis testing for method validation; Detection of systematic error by comparing the means of two methods or two laboratories. Analytical Chem. 67:4491-4499 (1995).Google Scholar
- 19.S. R. Searle, G. Casella, and C. E. McCulloch. Variance Components Chapter 3. John Wiley & Sons, Inc, New York, NY (1992).Google Scholar
- 20.R. W. Mee. β-expectation and β-content tolerance limits for balanced one-way ANOVA random model. Technometrics 26:251-254 (1984).-Google Scholar