1Digital Integration & Predictive Technologies2Drug Substance Technology

Xiaoxiang Zhu1,Rahul Sangodkar2, Ahsan Munir1, Elcin Icten2

COMSOL: A Single-Platform Approach for Kinetics Identification, Reaction Engineering, and Model Deployment

COMSOL

CONFERENCE

2017 Boston

2

Modeling at Amgen Process Development

Reactors Separation Formulation Manufacturing Devices

Activities In Both Biologics and Synthetics

3

Synthetics Modeling

Component and System-Wide Models

• Unit Ops

– Reactors

– Separators

– Crystallizers

– Etc.

• Continuous Manufacturing

Reactions Separation Crystallization Filtration/Dissolution

4

A Reaction System of Interest

𝑟𝑎𝑡𝑒1 = 𝒌𝒓𝒆𝒇,𝟏𝑒−𝑬𝟏𝑅𝑇

1𝑇−

1𝑇𝑟𝑒𝑓 [𝑐𝑎𝑡]𝒙 𝐴 [𝐻2𝑂2]

𝑟𝑎𝑡𝑒2 = 𝒌𝒓𝒆𝒇,𝟐𝑒−𝑬𝟐𝑅𝑇

1𝑇−

1𝑇𝑟𝑒𝑓 [𝑐𝑎𝑡]𝒙 𝐴 [𝐻2𝑂2]

Rate LawReaction Pathway

A

B

C

+ H2O

+ H2O

H2O2 +

Kinetic model & regression

Experimental design & execution

In Silico predictive design

Continuous/batch implementation

Objectives

5

Step 1. Catalyst dependency

Kinetics Identification: Previously a two-step process

Catalyst exponent x_cat = 1.33

0.0000 0.0001 0.0002

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

D-P

R-0

15

(m

mo

le)

t .[cat]1.33

(min.mmole1.33

)

0.1 mole%

0.05 mole%

0.01 mole%

[A]

(mm

ole

)

Four parameters (kref,1, kref,2, E1, and E2)

Step 2. Rate constants

A

B

C

6

Scenario 1. Two step approach*(4 parameters)

Kinetics Identification: Flexibility in COMSOL

*Uses catalyst exponent from regression

Scenario 2. One step approach (5 Parameters)

AB

C

AB

C

7

Estimation Results Comparison

*Obtained via separate regression.

Previous Tool COMSOL

(4 Params)COMSOL

(5 Params)

kref,1 (m3/mol)(1+x_cat)/s 4.7 x 10-5 (± 6%) 4.66 x 10-5 5.94 x 10-5

Ea,1 (kJ/mol) 14 (± 52%) 13.91 19.71

kref,2 (m3/mol)(1+x_cat)/s 5.3 x 10-6 (± 5%) 5.25 x 10-6 6.63 x 10-6

Ea,2 (kJ/mol) 29 (± 22%) 29.56 36.12

x_cat 1.33* 1.33* 1.42

8

Plug Flow Reactor Design

• Non-isothermal condition

• Straightforward extension from batch kinetics model to PFR

Conversion Selectivity

9

Reaction engineering modeling with non-idealities

1-D Ideal PFR Model

Full scale CFD studyCFD Integration

• Trouble shooting non-idealities in reactor (hot spot, mixing, etc.)

V (m/s)

T (K)extend

10

MODEL DEPLOYMENT AS WEB APPLICATION

Enables

• Online access

• Non-modelers

menu bar (model documentation, automatic report, etc.)

inputs results plotting

11

Summary

COMSOL as a Modeling Platform:

• Flexible parameter estimations for kinetic identification

• Straightforward extension from kinetics model to reactor modeling

• Integrated platform for non-ideal reactors using CFD simulation

• Accessible web deployment for non-modelers

12

END

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Supplementary Slide – 4 Parameter Estimation in COMSOLExperiment 3

Experiment 1

Experiment 2

Experiment 4