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1、 Bioanalytical Method Validation 05/24/18 Bioanalytical Method Validation Guidance for Industry U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) May 2018 Biopharmaceutics Bioanalytical Method
2、 Validation 05/24/18 Bioanalytical Method Validation Guidance for Industry Additional copies are available from: Office of Communications, Division of Drug Information Center for Drug Evaluation and Research Food and Drug Administration 10001 New Hampshire Ave., Hillandale Bldg., 4th Floor Silver Sp
3、ring, MD 20993-0002 Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 Email: druginfofda.hhs.gov http:/www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm and/or Policy and Regulations Staff, HFV-6 Center for Veterinary Medicine Food and Drug Administration 7500 Stan
4、dish Place, Rockville, MD 20855 http:/www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) May 2018 Biop
5、harmaceutics Contains Nonbinding Recommendations Bioanalytical Method Validation 05/24/18 TABLE OF CONTENTS I. INTRODUCTION 1 II. BACKGROUND 2 III. BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION . 4 A. Guiding Principles 4 B. Bioanalytical Parameters of CCs and LBAs 5 1. Reference Standards and Cri
6、tical Reagents 5 2. Calibration Curve. 6 3. Quality Control Samples 7 4. Selectivity and Specificity. 7 5. Sensitivity 8 6. Accuracy, Precision, and Recovery . 8 7. Stability 9 8. Dilution Effects .10 9. Partial and Cross Validations11 C. Validated Methods: Expectations of In-Study Analysis and Repo
7、rting 12 IV. INCURRED SAMPLE REANALYSIS 14 V. ADDITIONAL ISSUES 15 A. Endogenous Compounds 15 B. Biomarkers .15 C. Diagnostic Kits 16 D. Bridging Data From Multiple Bioanalytical Technologies .17 E. Dried Blood Spots 18 VI. DOCUMENTATION . 18 A. Summary Information18 B. Documentation for Method Vali
8、dation and Bioanalytical Reports .19 VII. APPENDIX. 20 Table 1. Recommendations and Acceptance Criteria for Bioanalytical Method Validation and In-Study Conduct. .20 Table 2. Documentation and Reporting 28 Table 3. Example of an Overall Summary Table for a Method Validation Report* or a Clinical Stu
9、dy Report.33 Table 4. Example of Summary Analytical Runs for a Bioanalytical Study Report36 VIII. GLOSSARY . 37 Contains Nonbinding Recommendations Bioanalytical Method Validation 05/24/18 1 Bioanalytical Method Validation Guidance for Industry1 This guidance represents the current thinking of the F
10、ood and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, con
11、tact the FDA office responsible for this guidance as listed on the title page. I. INTRODUCTION This guidance helps sponsors of investigational new drug applications (INDs) or applicants of new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologic license applications (BLAs),
12、and supplements validate bioanalytical methods used in human clinical pharmacology, bioavailability (BA), and bioequivalence (BE) studies that require pharmacokinetic, toxicokinetic, or biomarker concentration evaluation.2 This guidance can also inform the development of bioanalytical methods used f
13、or nonclinical studies that require toxicokinetic or biomarker concentration data. For studies related to the veterinary drug approval process such as investigational new animal drug applications (INADs), new animal drug applications (NADAs), and abbreviated new animal drug applications (ANADAs), th
14、is guidance may apply to blood and urine BA, BE, and pharmacokinetic studies. The information in this guidance applies to bioanalytical procedures such as chromatographic assays (CCs) and ligand binding assays (LBAs) that quantitatively determine the levels of drugs, their metabolites, therapeutic p
15、roteins, and biomarkers in biological matrices such as blood, serum, plasma, urine, and tissue such as skin. This final guidance incorporates public comments to the revised draft published in 2013 and provides recommendations for the development, validation, and in-study use of bioanalytical methods
16、. The recommendations can be modified with justification, depending on the specific type of bioanalytical method. This guidance reflects advances in science and technology related to validating bioanalytical methods. In general, FDAs guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 1 This guidance has been prepared by the Office of Clinical Pharmacology in the Ce
