validation presentation

8/7/2019 VALIDATION PRESENTATION

1/28

Module 1,, Part 4: QC-related validation Slide 1 of 28 WHO EDM 1/2002

Validation Part 4:

QC-related validation

Supplementary Training Modules onGood Manufacturing Practice


2/28


Validation

Introduction

Why is analytical monitoring necessary?

What is the purpose of analytical validation?


3/28


Validation

Objectives

To introduce the concepts of :

Protocol development Instrument qualification

Analytical procedure

Extent of validation

Method transfer

Chemical and physical, biological, andmicrobiological test validation


4/28


Validation of analytical procedures

requires:

Qualified and calibrated instruments

Documented methods

Reliable reference standards

Qualified analysts

Sample integrity

Validation


5/28


Validation protocol for analytical method

Statement of purpose and scope

Responsibilities

Documented test method

List of materials and equipment

Procedure for the experiments for each parameter

Statistical analysis Acceptance criteria for each performance parameter

Validation


6/28


Qualification of the instrument

Make, model and makers manual

Modifications

Installation and operational qualification

Calibration programs

Maintenance schedules

Validation


7/28


Characteristics of analytical

procedures (1)

Accuracy

Precision

Repeatability

Reproducibility

Validation


8/28


Inaccurate &

imprecise

Inaccurate but

precise

Accurate but

imprecise

Validation

Relationship between accuracy andprecision

Accurate AND Precise


9/28


Characteristics of analytical procedures (2)

Ruggedness

Robustness

Variability caused by:

Day-to-day variations

Analyst-to-analyst

Laboratory-to-laboratory

Instrument-to-instrument Chromatographic column-to-column

Reagent kit-to-kit

Instability of analytical reagents

Validation


10/28


Characteristics of analytical procedures (3)

Linearity and range

Specificity

Sensitivity

Limit of detection

Limit of quantitation

Validation


11/28


Lin ity

of an analyte in a material

0.010

0.015

0.020

0.025

0.030

0.035

0.040

0.01 0.015 0.02 0.025 0.03 0.035 0.04

Reference material mg/mlCalculatedanalytein

mg/mL

Table of values (x,y)

x y

#Reference

aterial g/ l

Calculated

g/ l

1 0.0100 0.0101

2 0.0150 0.0145

3 0.0200 0.0210

4 0.0250 0.0260

5 0.0300 0.0294

6 0.0400 0.0410

Validation


12/28


Linearity Statistics

Intercept -0.0002

Limit of Linearity and Range 0.005 0.040 mg/mL Slope 1.0237

Correlation coefficient

Pearson 0.9978

Olkin and Pratt 0.9985

Relative procedure standarddeviation 3.4%

Validation


13/28


LOQ, LOD and SNR

Limit of Quantitation

Limit of Detection

Signal to Noise Ratio

noise

Peak A

LOD

Peak BLOQ

Baseline

Validation


14/28


Different classes of analytical tests

Class A: To establish identity

Class B: To detect and quantitate impurities

Class C: To determine quantitatively the

concentration

Class D: To assess the characteristics

Validation


15/28


* A degree of bias may be allowed

Characteristic A Bquant.

BLimittest

C D

Accuracy X X X*

Precision X X X

Robustness X X X X X

Linearity and range X X X

Specificity X X X X XLimit of detection X

Limit of quantitation X

Validation


16/28


Extent of validation

New methods require complete validation

Pharmacopoeial methods require partialvalidation (or verification)

Significant changes mean partial revalidation

equipment changes

formula changed changed suppliers of critical reagents

Validation


17/28


Analytical method transfer

Method transfer protocol and procedure

precision accuracy

ruggedness

Written and approved specific test method

Proficiency check

Formal acceptance by new laboratory

Validation


18/28


Chemical laboratory validation requirements (1)

Balances

Chromatography

HPLC, HPTLC, GC, TLC

Dissolution or disintegration apparatus

Karl Fischer moisture determination

Melting, softening or freezing point apparatus

Ovens, refrigerators, incubators

Validation


19/28


Chemical laboratory validation requirements (2)

pH meter

Polarimeter - optical rotation Refractometer

Spectrophotometer UV/Vis, IR, FTIR, Raman, AA

Timers

Viscometer

Volumetric equipment

Validation


20/28


Validation

Typical validation of HPCL assay (1)

System suitability (performance check)

system precision column efficiency

symmetry factor

capacity factor


21/28


Validation

Typical validation of HPLC assay (2)

Method validation

specificity accuracy

precision

linearity

robustness


22/28


Biological assays

Can be difficult to "validate"

"Validity" on a case by case basis

Strictly adhere to the Biological Testing

monographs in pharmacopoeias

Validation


23/28


Microbiological testing requiring validation

Microbial limit testing

Microbial count

Sterility testing

Preservative effectiveness testing

Environmental monitoring program

Biological testing

Validation


24/28


Validation of microbial test procedures (1)

Virtually impossible to completely validate testprocedures for every microorganism

Neutralize /inactivate inhibitory substances, ordilute

Periodic media challenge

Media QC

Reliable methods

Validation


25/28


Validation of microbial test procedures (2)

Incubation temperature and time

Media may not grow all microorganisms

Variations in media may affect recovery

Inhibitory disinfectants or preservatives

Sample

procedures

handling, storage, transport

Validation


26/28


Microbiological viable count methodvalidation (1)

Methods

pour plate / spread plate

membrane filtration

Most Probable Number

Sample size

Test dilution

Inoculation size

Validation


27/28


Microbiological viable count methodvalidation (2)

Membrane filtration conditions Incubation conditions

Acceptance criteria

Validation


28/28


Sterility testing validation requirements

Media growth promotion, sterility, pH

Product validation

Stasis testing

Environmental monitoring

Negative controls

Challenge organisms

Validation

validation presentation

Documents