Dynamic Process Control: Implementation

of Feedback/Feedforward Control for

Continuous Systems

Mojgan Moshgbar (PhD)

Director of Advanced Manufacturing Technology Group Director of Pfizer Intellicentic® Partnership

Overview

• Introduction to Static & Dynamic System Analysis

• Continuous Processes – Examples of Process Dynamics

• Advanced Process Control in Continuous Pharmaceutical Processes

• Example Results from Continuous SOD processing

• New Platform Technology

Statics

• “Steady State” Conditions

• Initial vs Final States

Dynamics • Transition Between States

• Change over Timer

Reality • Superimposed dynamics & Statics

• Analysis must consider both

System Behavior

Introduction & Terminology

Static & Dynamic Response

0 10 20 30 40 50 60 20.8

21

21.2

21.4

21.6

Time

Te

mp

era

ture

0 10 20 30 40 50 60 20.8

21

21.2

21.4

21.6

Te

mp

era

ture

Response to Setpoint Change

Dynamic Response

0 50 100 15018

20

22

24

26

Ro

om

Te

mp

era

ture

0 50 100 1501.5

2

2.5

3

Time (mins)

Po

we

r (k

W)

time delay time constant

Process Gain = output

input

1)(

Ts

KesG

std

First Order System

Dynamic Response

First Order Systems Response to Input Change

0 10 20 30 40 50 60 70 80 90 1000

2

4

6

8

10

12

14

16

18

20

Time

Out

put

Oscillatory response for under-damped systems

Over-damped Response

Many continuous processes exhibit first order system dynamics

Stopping Starting

Continuous Processes Dynamics

Startup API Concentration (NIR) 28.7% 30.2% 31.7%

Stopping Starting

85

90

95

100

105

110

115

0 200 400 600 800 1000 1200 1400 1600 1800 2000 2200 2400

Pred

icted

Pote

ncy %

LC (N

omina

l Weig

ht)

Sample NumberSIMCA-P+ 11.5 - 6/13/2008 12:53:18 PM

88%LC

100%LC

Typical Dynamic Responses of Continuous Solid Formulation Processes Response Time: dependent on mixing/throughput parameters

Steady state fluctuations partially due to measurement errors caused by moving powder

APC in Continuous Processing

Continuous processes are time dependent & may experience transient process upsets

Fast PAT systems are essential to monitor real-time performance, and divert OOS material

Simulated Transient Disturbance

A transient ½ minute process

upset, in a high throughput

continuous Process can result in

high volume of rejected OOS (eg.

5000 OOS units with throughput

of 120 kg/hour

(assumes 200mg dosage weight)

APC Architecture for

Continuous Blending Applications

Model Predictive

APC

Raw Materials Concentration

Setpoints

Feeders Ratios

Impeller Speed

Retention Mass

Continuous Formulation

System

Blend Composition Fast NIR System

Retained Mass

Blend

Initial Process Setpoints

Throughput Setpoint

Static Setpoints

Dynamic Setpoints

Multiple Feeders

Load Cells

Load Cells Readings

Feedback Loops

Feedforward Loops

Feedback vs Feedforward

Feedback Loops provide dynamic information on the process outputs error

Feedback Loop Measurement Point (location) is critical for stability of control loops

Large separation between measurement & Actuation points increases the response delay (dead-time)

Feedforward loops are used to preemptively reduce the impact of dead-time and delay in system response to feeder excursions

Pfizer’s New Continuous SOD Portable, Continuous, Miniature & Modular

Continuous Mixing Direct Compression

ConsigmaTM -25 TSWG

Raw Material Dispensing

Slide Curtsey: Dan Blackwood et al. AIChE 2013

APC Turned ON 2. Feeder performance adjusted to achieve target API

Concentration

3. API Concentration by on-line NIR is centered at Target

1. API Concentration is above target

Slide Curtsey: Dan Blackwood et al. AIChE 2013

5. Potency setpoint change from 14 to 10%.

2. Production has been

increased from 3 to 3.5 kg/hr

3. Feeder Performance is adjusted

6. The APC implements the

potency change while controlling

production and hold-up mass to setpoint.

1. API Potency is at target

4. Hold Up Mass is held

Constant

Slide Curtsey: Dan Blackwood et al. AIChE 2013

Real-time Material Characterization Platform Capturing Process Signature

Real-time NIR Imaging System

Dynamic Process Signature

Hidden Process Fingerprint

Beginning Middle End

Visualization of MgSt dispersion and lubrication film in SOD Matrix

Advanced Image Processing Algorithm for Visualization of Blend Lubrication, Micro Temp Variations & Environmental Impacts on

Blend Performance

Color Key: Relative Lubricant Concentration Distribution

APC in Continuous Processing

APC system can reduce the frequency and severity of transient excursions and associated cost impact

In Pfizer, APC is rapidly gaining acceptance as a key enabling and transformational technology for both continuous and batch processes

New platform technologies for real-time material characterization provide new capabilities for validation

Acknowledgement

Pfizer PCMM Team

Pfizer GTS Colleagues

Pfizer AMT Colleagues