Recent Regulatory Updates and Trends in Analytical Method Validation
Recent Regulatory Updates and Trends in Analytical Method Validation
Recent Regulatory Updates and Trends in Analytical Method Validation
Ludwig_huber@labcompliance.com
Overview
• Limitations of the current regulations and guidelines
• General trends in method validation, method transfer and verification
• Going through the new guidelines
– EU GMP Chapter 6, Quality Control: Analytical method transfer
– FDA guidance: Bioanalytical method validation
– USP Chapter <1200>: Requirements for compendial validation
– USP Chapter <1210>: Statistical tools for procedure validation
– USP PF Stimuli paper: Lifecycle management of analytical procedures
– PDA Technical Report 57 and 57-2: Analytical method development
and qualification for biotechnology products
– FDA Guidance: Analytical procedures and methods from 2015
• Six step QbD process
• Benefits vs. ICH Q2 and USP 1225
Precision
Repeatability No Yes No Yes
Intermediate No Yes No Yes
Reproducibility No Yes No Yes
Define performance
Define Validation Criteria characteristics
Acceptance criteria
Develop test cases
Test Test for performance
characteristics
SOPs
Define Routine Tests
System Suitability tests
Analytical quality control
Handle all changes through change control procedures
Precision
Repeatability Minimum of 9 determinations over the specified range
Intermediate Over 3 days, 2 operators, 2 instruments,
Reproducibility Only required if testing is done in different laboratories
Specificity Prove with specific methods: HPLC, DAD, MS, dif. columns
• Lifecycle approach
• Analytical target profile
• Risk management
• Analytical control strategy
– Ensures that ATP is realized throughout the lifecycle
• Knowledge management through robustness studies
– Acquiring, analyzing, and disseminating information
– Ensures ongoing effectiveness of control strategy
6
Continuous
3
Design Space,
Monitoring and Method
Improvements Operational
QC Tracking Ranges
5 4
Control Strategy
Method Validation/
for CMAs
Qualification
System Suitability
(ICH Q2)
% org Column
Flow rate
mobile phase type
Critical
Method
Attributes
CMAs)
pH Inj. Column
Volume temp
Method UV
col. %organic
variables flow rate pH Wave-
temp. phase
Method attributes length
LOQ 1 2 3 3 2
Linearity 2 1 2 3 2
Repeatability 2 1 2 2 1
Accuracy 2 3 1 3 1
Specificity 3 1 2 3 1
Risk Priority
10 8 10 14 8
Number (RPN)
Variable 2
Variable 1 Variable 1
Impact of variables 1 and 2 (e.g., %org phase, col temp) on
critical method attributes e.g. peak resolution or %recovery
© Copyright Ludwig Huber - LabCompliance Slide 32
Include different columns in Experiments
Column C
Column B
Column A
Variable 2
Variable 1
Repeat experiments on column 2 and 3.
1 -1 -1 +1
2 -1 +1 +1
3 -1 +1 -1
4 +1 -1 +1
5 +1 -1 -1
6 +1 +1 -1