Analytical method validation as per US-FDA

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Analytical method validation as per US-FDA

by Amrita Shetty, 02/04/2021

       I.            INTRODUCTION

1.      Analytical method required during product and process development activities are discussed in FDA guidance for industry on Process validation:

2.      Analytical procedure verification or validation data should be submitted in the corresponding section of the application in the ICH M2 eCTD: Electronic Common Technical Document Specification

3.      United States Pharmacopeias/National Formulator (USP/NF) or a validated procedure submitted that was determined to be acceptable by FDA.

4.      To apply an analytical method to a different drug product, appropriate validation or verification studies for compendial procedure with the matrix of the new product should be considered.

5.      parameter that may be evaluated during method development are specificity, linearity, Limit of detection (LOD), Limits of qualification (LOQ), range, accuracy and Precision.

6.      To understand the changes effect in method parameter on an analytical procedure should adopt a systematic approach for a method robustness study (e.g., experiment design with method parameters)

 

        i.            Begin with Initial risk assessment along with multivariate experiments.

      ii.            Factorial parameter effects on method performance.

    iii.            Evaluation of method performance include: -

 

a.       Sample analyses obtained from various stage of the manufacturing process from in-process to the finished product.

b.      Method variation is helpful while method performance.

 

    II.            ANALYTICAL PROCEDURE CONTENTFD

 

1.      A recognized source e.g., USP/NF, Association of Analytical Communities (AOAC) if the referenced analytical procedure is not modified beyond is allowed in the published method.

a.       Principle/Scope

b.      Apparatus/Equipment

c.       Operating Parameters

d.      Reagents/Standards

e.       Sample Preparation

f.        Standard Control Solution Preparation

g.      Procedure

h.      System Suitability

i.        Calculation

j.        Data Reporting

a.       Principal/Scope

·         Analytical test principle (Separation, detection).

·         Target analyte

·         Sample

·         Drug type: Drug substance, drug product, impurities & compound in biological fluids).

 

b.      Apparatus/equipment

·         Qualified equipment and components

§  Instruments type

§  Detector

§  Column type

§  Dimensions

§  Alternative column

§  Filter type

 

c.       Operating Parameters

·         Qualified optimal setting and range (include allowed adjustment supported by compendial source or development and or validation studies) critical to the analysis

§  Flow rate

§  Components temperatures

§  Run time

§   Detector settings

§   Gradient

§   Head space sampler.

 

d.       Reagents/Standard

·         Reagent or standard description

·         Chemical grade

§  USP/NF

§  American Chemical Society (ACS)

§  HPLC

§  GC

§  Preservative-free

·         Reference source

§  USP reference

§  Qualified in-house reference material

§  WHO International Standard/ Reference Material

§  CBER Standard

·         Purity for pure chemical only

·         Dried and undried state

·         Concentration

·         Potencies by CFR, USP

·         Storage condition

·         Safety data sheet

·         Validation or documented shelf life

 

 

e.       Sample preparation

·         Procedure

§  Extraction method

§  Dilution

§  Concentration

§  Desalting

§  Mixing

§  Sonication

 

f.        Standard Control Solution Preparation

·         Preparation of control standard & control solution

§  Concentration

§  Standard stability

§  Storage condition

§  Calibration standard

§  Internal standard

§   System suitability standard

g.      Procedure

·         Equilibrium times

·         Scan/injection sequence

§  Blanks

§  Placeboes

§  Samples

§  Control

§  Sensitivity solution for impurity method

§  Standard to maintain validity of system suitability during span of analysis

§  Allowable operating ranges

 

h.      System Suitability

·         Procedure & parameters to ensure that the system will be function correctly as an integrated system at time of use such system as.

§  Equipment

§  Electronics

§  Analytical operations

§  Control

·         System suitability acceptance applied to standard controls & sample

§  Peak tailing

§  Precision

§  Resolution acceptance criteria

 

i.        Calculation

·         Integration method & representative calculation formulas for data analysis

§  Assay

§  Specified & Non-specified impurities

§  Relative response factor

j.        Data Reporting

·         Report results

§  Percentage label

§  Weight/Weight

§  Weight/Volume

·         Chromatographic method

§  Retention time (RT) for identification with reference standard comparison basis.

§  Relative Retention Time (RRT) for known and unknown impurities

§  Acceptable range

§  Sample result reporting criteria.


 Reference.: Analytical Procedures and Methods Validation for Drugs and Biologics Guidance for Industry by U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) July 2015 Pharmaceutical Quality/CMC.

 

 

 

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