Quality by Design-Based Workflow To Develop and Transfer Analytical Methods PDF

Quality by Design (QbD) Solutions
for Analytical Method Development

A systematic approach to reducing
variability
Andreas Tei
Pharmaceutical Segment Manager
QbD Method Development & Method Transfer Workflow
From UHPLC to HPLC in a nutshell
1290 1260 1260

1290 Emulation
QA/QC
R&D R&D R&D
3
1 2
Method transfer
Target System
Method development Target Systems in
Emulation by ISET
System QA/QC labs
Use of 1.8 µ particles
Robustness study by
and QbD software
QbD software
2
Content
• Introduction
- Traditional approach of method development and transfer
- QbD approach for method development
• Agilent solutions for method development

-Agilent method development systems
-Intelligent system emulation technology (ISET)
-Method scouting wizard software
-Third party QbD software
• A practical approach of method development under QbD principles

- Screening
- Optimization
- Robustness study, Design of Experiments
- Transfer & Verification
Method Development & Transfer Workflows
A Classic Approach
Develop Validate Transfer

QA / QC
R&D
Parameters determined by trial-and error.

Robustness tests performed by the one
factor at the time approach (OFAT)
4
OFAT Approach: Method Transfer is a balancing act
Different results on different systems
Variability of critical method

attributes (resolution, tailing, etc)
Development Target QA/QC

Small changes in pH, temperature
System Systems or flow rate shows a large effect
Even buffer solutions from different

operators deliver different results
10% of analytical methods are discarded per year to avoid high revalidation costs
after the methdod showed instabilities on the QC system
Quality by Design - A systematic approach to obtain a
“consistent quality” output
System System
Variabilities Understand
variability Variabilities
Fixed Flexible
process Quality
by process
Design
Control Continuous
Variability improvement
Variable
Consistent
output
output
ICH Q8-Q11
http://www.fda.gov/downloads/Drugs/Guidances/ucm073507.pdf
6
More Robustness by Applying QbD Principles
Risk assessment process
Define Critical Method Attributes CMAs

(resolution, peak tailing, etc.)
Define critical method parameters CMPs

(flow, temp) which affects the CMAs
Perform a Design of Experiment (DoE) study by

modifying multiple CMAs in simultaneously
and create a Design Space
7
QbD Approach for Method Development
Key is the statistical „Design of Experiment“

(DoE) where multiple CMPs will be varied in
each experiment
A method is robust, as long all changes of CMAs

are within the determined Design Space
8
Creating a Design Space
Optimizing through One Variable at a Time vs. DoE
0.6 Injection Volume (µl) 3.0

One Variable at a Time
20
% Organic mobile
phase (methanol)
Variable 2
1.6 10
Flow Rate (ml/min)
0.8
Variable 1 30 Column Temp. (oC) 40
Impact of variables 1 and 2 (e.g. % organic mobile phase and column temperature)
on Critical Method Attributes (CMAs) e.g. peak resolution or %recovery
9
What Are The Advantages ?
The relationship between the different critical method

parameters (CMPs) will be described and visualized in surface
or contour plots
Increase of efficiency by avoiding unnecessary experiments

during the method development process (no trial an error!)
DoE is delivering robust methods compared to the classic

„one-factor-at-the-time“ (OFAT) robustness testing process
10
Content
• Introduction
- Traditional approach of method development and transfer
- QbD approach for method development

-Agilent method development systems
-Intelligent system emulation technology (ISET)
-Method scouting wizard software
-Third party QbD software
• A practical approach of method development under QbD principles

- Screening
- Optimization
- Robustness study, Design of Experiments
- Transfer & Verification
Agilent Solutions for QbD Method Development
Method Development
System & Method Scouting SW
ISET
Intelligent System Emulation Technology
Harmonized Qualification
ACE RA
Remote Advisor
Rapid Development of Robust New Methods
Agilent 1290 Infinity II Series Method Development Solution
Agilent 1290 Infinity II Method Development Solution

6100 Series MSD and 1290 ELSD are optional detectors to
ensure the most comprehensive compound detection
13
1290 Infinity II Series Method Development Solution
Schematics
1290 Infinity II
MCT 8
1290 Infinity II x = 1352

Flexible Pump
12 + 1
A1 A2 B1 B2
External Solvent
Selection Valves x = 169
SSV1 SSV2
12 + 1
Up to 12 solvents
per SSV!!!
1352 different combinations of column chemistries and eluents

A nearly infinite number of separation conditions is created by including
different temperature and flow rates as variable parameters
14
Agilent ChemStation Method Scouting Wizard
There is no easier way to set up even complex screening campaigns
• Define project
Choose scouting combinations and
base method.
• Select columns
All installed columns are shown
automatically.
• Select solvents
Pump types and valves are
automatically detected.
• Define gradients
Select between different gradients and
temperatures.
• Review and select screening
methods
Check for incompatible combinations.
• Set up samples
Define injection volumes and number of
repetitions. Easy and fast
setup of sequences !
15
Agilent ChemStation Method Scouting Wizard
Ease of Use: Screening Report
Fast screening of mobile and stationary phases with 1290 Infinity II LC –
Analysis of Degradation Products of Metoprolol
Max. Retention Time
Injections
Bubble size represents the number of integrated peaks and,

consequently, best mobile and stationary phase
combination.
https://www.agilent.com/cs/library/applications/5991-0989EN.pdf
16
Intelligent System Emulation Technology (ISET)
- Seamless transfer of methods between LCs, regardless of the brand
PO-Nr. G2197AA
Method Transfer Between Different LC Instruments
Method transfer from a UHPLC system with a minimized dwell
volume and optimized mixing behavior to any other LC system is
often challenging and affects rentention time and resolution
Example: Method Transfer from a 1290 UHPLC to a 1100 HPLC system

mAU
175
150
125
100 1290 Infinity LC

75
50
25 1100 Series Binary System
0
3 4 5 6 7 8 9 10 11 min
Practical aspects how to measure dwell volumes, transfer & optimize methods
19
How To Measure Dwell Volumes
Add a UV active tracer to solvent B (often acetone)
Remove the column, fit a restriction capillary
Run a step gradient from 10%B to 90%B
Calculate the dwell volume by the delay between
UV response and the step with respect to the flow rate
20
Gradient differences due to different dwell

mAU volumes and different mixing behavior
600
1290 Infinity LC
500
400 1100 Series Quaternary LC
300
200
100
Results from a tracer experiment

0
0 1 2 3 4 5 6 7 8 9 min
21
Approach # 1: Isocratic holding step to synchronize
1290 Infinity LC
mAU
Still gradient differences due to 1 min isocratic hold
different mixing behavior
400
1100 Series Quaternary LC
300
200
100

0
0 1 2 3 4 5 6 7 8 9 min
22
Approach # 1: Applying Isocratic Holding Steps
Results
1260 Infinity LC
1290 Infinity LC
+ 900 µl hold
• Results shows a low consitency

• Requires manual determination of the dwell volume/ isocratic hold
(in solvent delivery systems equipped with dampeners the dwell volume is pressure
dependent and variable)
• Requires modification of the methods
(should be avoided in validated environment,
but doesn’t require revalidation USP Chapter <621>)
23
Approach # 2: Adding a physical void volume
1290 Infinity LC
mAU
Almost consistency of both 1 mL loop installed
gradient curves
400
1100 Series Quaternary LC
300
200
100

0
0 1 2 3 4 5 6 7 8 9 min
24
Approach # 2: Adding a Physical Void Volume
Results
1290 + 1000 µL dwell vol.
1100/1200 Quat Pump
• Results shows a good consitency

• Manual determination of dwell volumes required (issues of a variable
dwell volume with systems containing damperners)
• All mechanical changes are laboriously not flexible
25
Agilent Solution:
Intelligent System Emulation Technology (ISET)
mAU
400
350
Injection
300
Software controlled compensation
250
of dwell volume differences and
synchronization of mixing
200 behaviors
150
100 Programmed gradient

1290 gradient
50
1200 gradient
0
0 0.5 1 1.5 2 2.5 3 3.5 min
26
Agilent Solution: Method Transfer by ISET
Results: 1260 Infinity Binary LC to 1290 Infinity LC
Paracetamol
mAU
• Consistency of results
40
Imp J
Imp H
30
Imp K
Imp F
20
Imp A
Imp B
10
1290 Infinity LC with ISET
1260 Infinity Binary LC
1 2 3 4 5 6 7 8 9 min
27
Agilent Application Notes
Method Transfer by ISET
• Fast screening of mobile and stationary phases with the Agilent 1290 Infinity LC
and seamless method transfer to an Agilent 1200 Series LC using ISET
Agilent Application Note 5991-0989EN
• Developing faster methods for generic drugs within USP <621>allowed limits
• Effective use of pharmacopeia guidelines to reduce cost of

chromatographic analysis
• Developing faster methods for generic drugs within EP 2.2.46E allowed limits
28
3rd Party Add-On QbD Software
Turn your LC into an automated
QbD method development system!
AutoChrom
ChromSwordAuto
Chemstation
Fusion QbD
Only Agilent‘s Method Development Solution is supported by all
three big manufactures of automated method optimization software!
29
Fusion QbD Software (S-Matrix)
Statistical approach identifying the best separation conditions
A graphic plot illustrates the position of the best conditions
15.0
Initial %
Organic 4.5
3.5
pH
5.0
2.5
30.0 60.0
Oven Temp
Sequence of Experiments 3 Dimensional Results Plot
30
Creating a Design Space
Simple DoE Example for HPLC Method
CMPs: Impact on Selectivity, Five Variables Two Levels

Run # % Org.Phase pH Col. Temp Column Flow Rate
1 -1 -1 +1 +1 +1
2 -1 +1 +1 -1 +1
3 -1 +1 -1 +1 +1
4 +1 -1 +1 -1 -1
5 +1 -1 -1 +1 -1
6 +1 +1 -1 -1 -1
40 % ACN
Level -1 = 4.0 25 ºC 10 cm 2.0 ml/min
-
60% ACN
Level +1 = 6.0 40 ºC 20 cm 2.5 ml/min
40% Water
FDA: Need sufficient statistical power to support analytical “Design Space”
31
Creating a Design Space (Fusion QbD Software)
Robustness Testing & Establishing a Design Space (MODR)
Design Space
List of CMPs and CMAs for robustness
testing
* The coded names are used in robustness model displays
32
Chromsword Software
• Method scouting • Interactive
• User defined • Find workable
• Statistical DOE method ASAP
Rapid
Screening
optimization
Robustness Fine
Studies Optimization
• Full factorial • Interactive

• Statistical DOE • Sample profiling
• Impurities search
33
Details of Chromsword Software
• Method development and optimization based on

the solvatic model of RP-LC
• Building retention models after processing results

by applying different variables as listed below
• Organic modifier concentration (C)
• Gradient time (Grad)
• Temperature (T)
• pH
• Multi variables: C+pH; Grad +T; C1 +C2
34
• Automated resolution optimization of critical peak pairs
3.232
Norm.
Norm.
3.070
100 600
80 500
60 400
300
40
1.136
1.384
200
20
1.970
2.820
2.049
100
0
0
1 2 3 4 5 6 7 8 9 min 0.5 1 1.5 2 2.5 3 3.5 4 4.5 min
35
Design space creation after robustness study is fundamental to the
Quality by Design approach
36
ACD/AutoChrom Software
1. Data Collection
Start
5. Next
Experiment Column, Buffer &
2. Peak Tracking
Solvent Screening
Select Best
Optimize Gradient
& Temperature
End
4. Modeling
3. Interpretation
Gradient
Temperature
Report
37
Content
•Introduction
– Traditional approach of method development and transfer
– QbD approach for method development

–Agilent method development systems
–Intelligent system emulation technology (ISET)
–Method scouting wizard software
–Third party QbD software
• A practical approach of method development under QbD

principles
– Screening
– Optimization
– Robustness study, Design of Experiments
– Transfer & Verification
QbD Method Development & Method Transfer Workflow
From UHPLC to HPLC in a nutshell
1290 1260 1260

1290 Emulation
QA/QC
R&D R&D R&D
3
1 2
Method transfer
Target System
Method development Target Systems in
Emulation by ISET
System QA/QC labs
Use of 1.8 µ particles
Robustness study by
and QbD software
QbD software
39
QbD Based Method Development Workflow
Overall workflow which

consists of four main steps Screening
namely • Column Chemistry
Agilent Method • pH conditions
• Organic Solvent Selection
Scouting
• Gradients, temperatures
• Step # 1: Screening Wizard
Optimization
• Step # 2: Optimization • Optimize Gradient Profiles
• pH conditions
QbD Software • Flow rates, temperatures
40
Optimization
Results: peak purity and separation after optimization 99.8%
| |
| ' ' ' ' ' |
| |
| ' ' ' ' ' |
Set by User
998
Set by User 998
10.543
mAU
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
350 ++++++++++++++------+++++++++----------+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ 10 10.2 10.4 min
300 10.5 10.55 10.6 10.65 10.7 min
250
200 Purity< 90%
150 Before
100
50
Optimization
0
2.5 5 7.5 10 12.5 15 17.5 20 min
10.007
mAU
350
300
250 99.8 % purity After
200
150 Optimization
100
50
0
2.5 5 7.5 10 12.5 15 17.5 20 min
41
Overall workflow which Screening

consists of four main steps •
•
Column Chemistry
pH conditions
Agilent Method
namely Scouting •
•
Organic Solvent Selection
Gradients, temperatures
Wizard
Optimization
• Step #1: Screening •
•
Optimize Gradient Profiles
pH conditions
• Step #2: Optimization QbD Software • Flow rates, temperatures
Design of Experiments
• Step #3: DOE & Emulate
• Multivariate study
• Robust region
QbD Software • Design Space
42
Method Transfer & Verification
From UHPLC to HPLC
1290 Emulation 1260

R&D R&D
2
Method transfer
Target System
Emulation by ISET
Robustness study by
QbD software
43
Method Transfer From UHPLC To HPLC
HPLC Calculator University of Geneva
http://www.unige.ch/sciences/pharm/fanal/lcap/telechargement.htm
Crawford Scientific Calculator

http://www.crawfordscientific.com/
HPLC_Method_Transfer_On-line.htm
44
Robustness Study
Modeling a HPLC design space on an emulated 1260 system
HPLC design space parameters HPLC design space with new CMA
Critical Method Proven Critical Method
Parameters (CMPs) Acceptable Attributes (CMAs)
Range (PARs)
Column: Agilent ZORBAX No. of peaks (>40)
Eclipse Plus C8 4.6X150 API resolution (>4)
mm, 3.5 µm Peak purity (≥ 98%)
Peak tailing (<1.3)
Strong solvent: Methanol
% Strong solvent: 87.5.% ± 1.5%
Aqueous solvent pH: 7.7 ± 0.1
Gradient range: 5% to
87.5%
Oven Temperature: 37°C
Gradient time: 45 min
Flow rate: 1.4 mL/min

Wavelength: 292 nm
45
Proof Of Robustness
Conditions applied from center point and the four corner points of the Design Space
Critical Method Attributes remain within the limits
mAU
350
A
250 API Rs> 4 and API tailing = 1.2 for all runs
150 % B max: 86 %; pH: 7.6
50
0
10 20 30 40 50 min
mAU B
350
250
% B max: 89 %; pH: 7.6
150
50
0
10 20 30 40 50 min
mAU T
350
250
% B max: 87.5 %; pH: 7.7
150
50
0
10 20 30 40 50 min
mAU D
350
250 % B max: 89 %; pH: 7.8
150
50
0
10 20 30 40 50 min
mAU C
350 % B max: 86 %; pH: 7.8
250
150
50
0
10 20 30 40 50 min
46
Screening
• Column Chemistry
Overall workflow which has Agilent Method • pH conditions
• Organic Solvent Selection
four main steps namely Scouting
Wizard
• Gradients, temperatures
Optimization & DOE
• Optimize Gradient Profiles
•Step #1: Screening • DOE
QbD Software • Creating a Design Space
•Step #2: Optimization Emulate Target System
•Step #3: DOE & Emulate • Transfer gradient profile
•Step #4: Verify ISET •
•
Emulate target system
DOE
QbD Software
• Creating a Design Space
Verify on Target System
• Apply Method
Target System • Verify Results
• Validate Results
47
Verification Of The Final Method With The Target System
Results: 1260 Infinity data compared to 1290 Infinity data in emulation mode
Final gradient
Time %B
24.115
mAU
1260 target system 0.3 5
45.6 87.5
400
49.2 87.5
300 49.5 95
49.8 95
200
API Rs = 4.1
23.347
50.1 5
API tailing = 1.2 53.1 5
100
10 20 30 40 50 min
24.091
mAU
400 1290 emulated as 1260

300
200 API Rs = 4.2

23.344
100 API tailing = 1.2

0
10 20 30 40 50 min
Critical Method Attributes are within the defined limits
48
Conclusions
Agilent Method Scouting Wizard Software supports
automated method development workflows
Significant time saving has been achieved by using sub-2-

micron columns for method development workflows
ISET supports seamless method transfer processes to other

LC-systems
Additional 3rd Party QbD software is used to create more

reliable and robust methods
49
Agilent Application Note
Title: QbD Based Method Development on an

Agilent 1290 Infinity UHPLC system Combined
with a Seamless Method Transfer to HPLC
Using Intelligent System Emulation Technology
Type: Application Note
Publication Number: 5991-5701EN
Pages: 8
Target segments: Pharmaceutical QA/QC
Language: English
Author: Vinayak A.K.
LitStation Availability: May 5, 2015, CPOD
50
Agilent Application Notes
QbD based Method Development
• Quality-by-Design Approach to Stability Indicating Method

Development for Linagliptin Drug Product
– Agilent Application Note 5991-3834EN
• Automated QbD Based Method Development and Validation of

Oxidative Degraded Atorvastatin
• Development of an UHPLC Method for Azithromycin Tablets Using

ChromSword Auto Software
• QbD Based Method Development on an Agilent 1290 Infinity UHPLC

system Combined with a Seamless Method Transfer to HPLC Using
- Agilent Application Note 5991-5701EN
51
Agilent Instrument Control Framework (ICF)
Seamless Integration Of Innovative Technology
WATERS THERMO AB SCIEX SHIMADZU
Empower Chromeleon Analyst LabSolution
ICS/OIP Adapter DDK Adapter AB SCIEX I/F Shimadzu I/F
ICF
RC.NET
API
Driver
Agilent
Instrument
• One consistent driver set developed by Agilent

• Developer support provided by Agilent
• Significantly less effort / faster time to market
Waters Empower 3: Ready for Agilent 1290 Infinity II
Agilent LC and ICF Releases
1290 Multisampler 1290 Infinity II LC

LC Drivers 2.10 LC Drivers 2.11
Agilent LC Hardware
Time A ICF A.02.03 Time B ICF A.02.03 DU1
LC Drivers 2.10 LC Drivers 2.11
Agilent ICF Software

Time A Time B
+ 6 weeks + 6 weeks
Waters ICS 2.1 HF1 71600xxx
ICF A.02.03 DU1
LC Drivers 2.11
Waters Empower Software

Oct 16th 2015
Chromeleon 7.2 SRx
ICF A.02.02/3
Agilent LC 2.10/2.11
Work in Progress: Thermo Chromeleon Software

Agilent LC Instrument Control in Empower 3
Required software modules to support Agilent 1290 Infinity II
Waters Empower 3
CDS and CDS specific
adapter from Waters
Adapter: Waters ICS 2.1 HF1 (ICS= Instrument Control Software)
Agilent ICF A.02.03 DU 1 HF2
Agilent ICF Adapter

RC.NET
API
Core
Driver
A.02.11SP1
Agilent RC.Net Drivers
Agilent
1290 LC
Agilent 1290 Infinity II under Empower 3
How does it look like?
LC Status Interface
Method Interface
Agilent’s ICF Concept
Please download our Technical Notes
ICF website: www.agilent.com/chem/icf
ICF Release Notes on agilent.com ICF Publications / Technical Notes
• ICF Technical Overview, Pub. No.: 5990-6504EN

• Using the Agilent Instrument Control Framework to control the Agilent 1220 Infinity LC system through
Waters Empower software, Pub. No. 5990-9399EN
• Using the Agilent Instrument Control Framework to control the Agilent 1260 Infinity LC through Waters
Empower software, Pub. No 5990-9092EN
• Using the Agilent Instrument Control Framework to control the Agilent 1290 Infinity LC through Waters
Empower software, Pub. No 5990-9093EN
• Using the Agilent Instrument Control Framework to control the Agilent 1260 Infinity Bio-inert Quaternary LC
through Waters Empower software, Pub. No 5990-9354EN.pdf
• Agilent 1290 Infinity LC with ISET under Waters Empower Control - Emulation of Agilent 1100 Series LC
5991-2275EN
• Operating the Agilent 1260 Infinity LC with Dionex Chromeleon software using Instrument Control
Framework, Instrument control and performance, Pub. No 5990-7232EN
• Operating the Agilent 1290 Infinity LC with Dionex Chromeleon software using Instrument Control
Framework, Instrument set up and performance Pub. No 5990-7215EN
*SPRS: Skills & Resources Planning System
THANK YOU
57
QbD terminology in Method Development
Appendix
Analytical QbD Terminology
QbD process terminology Analytical QbD Examples

terminology
Analytical Target Profile Accurate quantitation of API
without interferences from
(ATP) degradants
Quality Target Product Quality Target Method Profile pKa, Log P, Solubility
Profile (QTPP) (QTMP)
Critical Process Parameters Critical Method Parameters Flow rate,
(CPP) (CMP) Temperature, pH
Critical Quality Attributes Critical Method Attributes Resolution, Peak
(CQA) (CMA) Tailing, Peak Capacity
Control Strategy pH ± 0.1; Wavelength
± 2 nm
Appendix: Agilent Application Notes
Method Transfer by ISET
• Fast screening of mobile and stationary phases with the Agilent 1290 Infinity LC
and seamless method transfer to an Agilent 1200 Series LC using ISET
• Developing faster methods for generic drugs within USP <621>allowed limits
• Effective use of pharmacopeia guidelines to reduce cost of

chromatographic analysis
• Developing faster methods for generic drugs within EP 2.2.46E allowed limits
59
Appendix : Agilent Application Notes
QbD based Method Development
• Quality-by-Design Approach to Stability Indicating Method

Development for Linagliptin Drug Product
• Automated QbD Based Method Development and Validation of

Oxidative Degraded Atorvastatin
• Development of an UHPLC Method for Azithromycin Tablets Using

ChromSword Auto Software
• QbD Based Method Development on an Agilent 1290 Infinity UHPLC

system Combined with a Seamless Method Transfer to HPLC Using
- Agilent Application Note 5991-5701EN
60

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Quality by Design (QbD) Solutions

for Analytical Method Development

1290 1260 1260

• Agilent solutions for method development

• A practical approach of method development under QbD principles

Develop Validate Transfer

Parameters determined by trial-and error.

Different results on different systems

Variability of critical method

Development Target QA/QC

Even buffer solutions from different

Risk assessment process

Define Critical Method Attributes CMAs

Define critical method parameters CMPs

Perform a Design of Experiment (DoE) study by

Key is the statistical „Design of Experiment“

A method is robust, as long all changes of CMAs

0.6 Injection Volume (µl) 3.0

The relationship between the different critical method

Increase of efficiency by avoiding unnecessary experiments

DoE is delivering robust methods compared to the classic

• Agilent solutions for method development

• A practical approach of method development under QbD principles

Intelligent System Emulation Technology

Agilent 1290 Infinity II Method Development Solution

1290 Infinity II x = 1352

1352 different combinations of column chemistries and eluents

Max. Retention Time

Bubble size represents the number of integrated peaks and,

Example: Method Transfer from a 1290 UHPLC to a 1100 HPLC system

100 1290 Infinity LC

25 1100 Series Binary System

Gradient differences due to different dwell

400 1100 Series Quaternary LC

Results from a tracer experiment

Results from a tracer experiment

• Results shows a low consitency

Results from a tracer experiment

1290 + 1000 µL dwell vol.

1100/1200 Quat Pump

• Results shows a good consitency

100 Programmed gradient

1290 Infinity LC with ISET

1260 Infinity Binary LC

Agilent Application Note 5991-0989EN

Agilent Application Note 5991-0278EN

• Effective use of pharmacopeia guidelines to reduce cost of

Agilent Application Note 5991-1053EN

Agilent Application Note 5991-0394EN

A graphic plot illustrates the position of the best conditions

Sequence of Experiments 3 Dimensional Results Plot

CMPs: Impact on Selectivity, Five Variables Two Levels

FDA: Need sufficient statistical power to support analytical “Design Space”

* The coded names are used in robustness model displays

• Full factorial • Interactive

• Method development and optimization based on

• Building retention models after processing results

• Automated resolution optimization of critical peak pairs

• Agilent solutions for method development

• A practical approach of method development under QbD

1290 1260 1260

Overall workflow which

Overall workflow which Screening