USP Verification of Comp en Dial Procedures CVG CA
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Transcript of USP Verification of Comp en Dial Procedures CVG CA
New USP Chapter: Verification of Compendial ProceduresHoracio N. Pappa, Ph.D. Senior Scientist Department of Standards DevelopmentCVG-TPD 2006 INTERNATIONAL CONVENTION October 5-6, 2006 (Toronto, Ontario, Canada)
The Analytical ProcessPROCESS Laboratory Sample
Sample preparation Aliquout
Analytical Instrument Qualification Measurement Validation of Compendial Procedures Verification of Compendial Procedures Analytical data - interpretation and treatment Reportable value2
Raw data
Validation of Compendial Procedures
Defines analytical performance characteristics (precision, accuracy, etc.) Recommends data for submissions to USP-NF Provides guidance on which analytical performance characteristics are needed based on the type of test Incorporates ICH guidelines Q2A and Q2B No guidance on verifying suitability for use3
Validation of Compendial Procedures
Performance Characteristic
Category I
Category II Quant Limit Test * No Yes Yes No No *
Category III Category IV
Accuracy Precision Specificity LOD LOQ Linearity Range
Yes Yes Yes No No Yes Yes
Yes Yes Yes No Yes Yes Yes
* Yes * * * * *
No No Yes No No No No4
* May be required, depending on the nature of the specific test
Why is needed?
21 CFR 211.194(a)(2): users of analytical methods described in USPNF are not required to validate the accuracy and reliability of these methods, but merely verify their suitability under actual conditions of use. Response to industry inquiries First draft published in PF31(2). Republished in PF32(4)
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Summary
The intent of this chapter is to provide general information to laboratories on the verification of compendial procedures that are being performed for the first time to yield acceptable results utilizing the laboratories personnel, equipment, and reagents. Not intended for retroactive application to already successfully established laboratory procedures. Verification consists of assessing selected Analytical Performance Characteristics, such as those which are described in chapter , to generate appropriate, relevant data rather than repeating the validation process.6
Summary
Companion to Validation of Compendial Procedures Builds on information from Applies to drug substances, drug products, and excipients Biological tests are not included; General Chapter Design and Analysis of Biological Assays and Validation of Biological Assays (in development) provides guidance for validations of these procedures7
Summary
Application: titrations, chromatographic procedures (related compounds, assay, limit tests), spectroscopic tests, etc. General tests do not typically require verification (water, heavy metals, residue on ignition, etc.)
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Summary
Verification of microbiological procedures is not covered in this chapter because it is covered in other USP general chapters, Antimicrobial Effectiveness Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests Sterility Tests Validation of Microbial Recovery From Pharmacopeial Articles9
Data Elements for Verification of Drug Substances and ExcipientsThis table was deleted in the current proposalTechnique Category I Category II Quantitative HPLC/GC Spectro. or colorimet. Titration TLC Gel Electro. P P P ----P, S, LOQ P, LOQ P S, LOQ S, LOQ Limit Test S, LOD S, LOD --S, LOD S, LOD ----------S S --S S10
Category III
Category IV
P=Precision; S=Specificity; L=Linearity; LOD=Limit of Detection; LOQ=Limit of Quantitation;
Data Elements for Verification of Dosage FormsThis table was deleted in the current proposalTechnique Category I Category II Quantitative HPLC/GC Spectro. or colorimet. Titration TLC Gel Electro. P, S, L P, S, LOQ Limit Test S, LOD P S Category III Category IV
P, L
P, LOQ
S, LOD
P
S
P, L -----
P S, LOQ S, LOQ
--S, LOD S, LOD
-------
--S S11
P=Precision; S=Specificity; L=Linearity; LOD=Limit of Detection; LOQ=Limit of Quantitation;
Verification process
There are no general Validation protocols There are no general Verification protocols
Verification
DEGREE OF VERIFICATION
Perform the test as written
Full validation12
Case study Sodium ChlorideAcidity or alkalinity To 20 mL of the solution prepared for the test for Appearance of solution, add 0.1 mL of bromothymol blue TS: not more than 0.5 mL of 0.01 N hydrochloric acid or 0.01 N sodium hydroxide is required to change the color of this solution. Loss on drying Dry the test material at 105 for 2 hours: it loses not more than 0.5% of its weight, determined on about 1.000 g of sample. Limit of bromides To 0.5 mL of the solution prepared for the test for Appearance of solution, add 4.0 mL of water, 2.0 mL of pH 4.7 phenol red TS, and 1.0 mL of chloramine T solution (0.1 mg per mL), and mix immediately. After 2 minutes, add 0.15 mL of 0.1 N sodium thiosulfate, mix, dilute with water to 10.0 mL, and mix. The absorbance of this solution measured at 590 nm, using water as the comparison liquid, is not greater than that of a Standard solution, concomitantly prepared, using 5.0 mL of a solution containing 3.0 mg of potassium bromide per L and proceeding as above, starting with the addition of 2.0 mL of pH 4.7 phenol red TS (0.010%). Heavy metals, Method I : 5 ppm13
Case study Sodium Chloride
AssayDissolve 50 mg of Sodium Chloride, accurately weighed, in water and dilute with water to 50 mL. Titrate with 0.1 N silver nitrate VS, determining the endpoint potentiometrically (see Titrimetry ). Each mL of 0.1 N silver nitrate is equivalent to 5.844 mg of NaCl.
Performance Characteristic Accuracy Precision Specificity LOD LOQ Linearity Range
Validation Yes Yes Yes No No Yes Yes
Verification No Maybe No No No No No
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Case study API
Identification IR, UV HPLC Purity test Loss on drying, residue on ignition, Heavy metals pH Related substances Assay Titrimetry HPLC
Performance Characteristic Accuracy Precision Specificity LOD LOQ Linearity Range
Validation No No Yes No No No No
Verification No No Maybe No No No No
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Case study API
Identification IR, UV HPLC Purity test Loss on drying, residue on ignition, Heavy metals pH Related substances Assay Titrimetry HPLC
Performance Characteristic Accuracy Precision Specificity LOD LOQ Linearity Range
Validation No No Yes Yes No No No
Verification No No No No No No No
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Case study API
Identification IR, UV HPLC Purity test Loss on drying, residue on ignition, Heavy metals pH Related substances Assay Titrimetry HPLC
Performance Characteristic Accuracy Precision Specificity LOD LOQ Linearity Range
Validation Verification Yes Yes Yes No Yes Yes Yes No Maybe Yes No Yes No No
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Case study API
Identification IR, UV HPLC Purity test Loss on drying, residue on ignition, Heavy metals pH Related substances Assay Titrimetry HPLC
Performance Characteristic Accuracy Precision Specificity LOD LOQ Linearity Range
Validation Verification Yes Yes Yes No No Yes Yes No Maybe Maybe No No No No
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Case study Dosage form
Identification HPLC Specific tests Particle in injections Uniformity Dissolution Impurities: related substances residual solvents Assay
Performance Characteristic Accuracy Precision Specificity LOD LOQ Linearity Range
Validation No No Yes No No No No
Verification No No Yes No No No No
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Case study Dosage form
Identification HPLC Specific tests Particle in injections Uniformity Dissolution Impurities: related substances residual solvents Assay
Performance Characteristic Accuracy Precision Specificity LOD LOQ Linearity Range
Validation Maybe Yes Maybe Maybe Maybe Maybe Maybe
Verification Maybe Yes Yes No Maybe No No
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Case study Dosage form
Identification HPLC Specific tests Particle in injections Uniformity Dissolution Impurities: related substances residual solvents Assay
Performance Characteristic Accuracy Precision Specificity LOD LOQ Linearity Range
Validation Yes Yes Yes No Yes Yes Yes
Verification Maybe Yes Yes No Yes No No
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Case study Dosage form
Identification HPLC Specific tests Particle in injections Uniformity Dissolution Impurities: related substances residual solvents Assay
Performance Characteristic Accuracy Precision Specificity LOD LOQ Linearity Range
Validation Yes Yes Yes No No Yes Yes
Verification Maybe Yes Yes No No No No
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Horacio N. Pappa [email protected]