A Technology Roadmapping Process to Transform the Biopharmaceutical … · A Technology Roadmapping...

© BioPhorum Operations Group Ltd

A Technology Roadmapping Process to Transform the Biopharmaceutical Manufacturing Industry

Stewart McNaull, PhD

KBI BioPharma Inc.

BPI West Conference. Mar 02, 2017


Agenda

Introduction to BPOG

How will a Technology Road Map help the industry ?

What does the Map entail? The Methodology

Overview of Key Roadmap Content

• Market Trends and Business Drivers

• Biomanufacturing Scenarios

• Workstream Outputs

• Scenario Modeling

Plans for publication and industry utilization

BPOG Introduction March 17 2


Our members manufacture >90% of US and European biotech drugs

March 17 BPOG Introduction 3

BPOG is a collaboration of the World’s top biopharma manufacturers and supply partners

Mission: To create an environment where the global biopharmaceutical industry can collaborate and accelerate their rate of progress, for the benefit of all


Agenda



What does the Map entail?: The Methodology





What is BPOG?

Unique global collaboration

Powerful vehicle for change

6 Phorums

>50 industry changing initiatives

Industry leaders and experts working in concert

Delivering results by pooling knowledge, practices and ideas



Why is a Technology Roadmap needed for the Biopharm Industry?

Complex global regulatory environment • Multiple jurisdictions

• Varying requirements

Biomanufacturers are risk averse • The penalties are severe for delays and setbacks in drug commercialization

• Uncertainty around product comparability between scales and process changes

• New technology may not be adapted because of perceived risks to program

• Everyone wants to be a Fast Second!

Biomanufacturers and Suppliers develop technologies in isolation

Technology standardisation usually only occurs after the technology is launched

Suppliers find it difficult to innovate • Have to guess end user requirements

• Risk-reward balance is poor

Technology Roadmapping 6

Complex industry has traditionally held back innovation….


What is the scope of the Technology Roadmapping process?

Technology Roadmapping

What it is

Process to engage and align industry stakeholders to define future needs of the industry, difficult challenges & potential solutions

Involves cross industry, supply partner, regulator, academia input

Communication of the needs, challenges and potential solutions to industry stakeholders to guide innovations

Process to monitor industry progress

What it is not

Actual implementation – that is the responsibility of the industry once the consensus on requirements is clear

Focused on short term tactical needs – the roadmap provides a long term, big picture view of industry requirements

Jan 2017 7


Agenda



What does the Map entail? The Methodology




Following the Lead from other Industries….. Using method from University of Cambridge’s Institute of Manufacturing

3/9/2017 9

Semiconductor Industry

NASA

10 March 17 BPOG Introduction

Technology Innovation

Overview of Methodology for Technology Roadmap Construction

11 3/9/2017

Evaluate Biopharmaceutical Market Trends

Identify Main Business Drivers & Metrics

Identify/prioritize Advantages / disadvantages

Develop Representative Scenarios

Identify/prioritize Opportunities for Improvement

Model Facility Types Fix: Process/Facility Type

Vary: Throughput, utilization, product mix

Identify Potential Solutions and Alternatives

Define Development Timelines and Pathways

Technology Roadmap

Define Scenario/Options Matrix and Objectives

Business Scenarios (Key Drivers)

vs.

Biomanufacturing Facility Type Scenarios (Options)

Define

Objectives

Model Business Scenarios Fix: Throughput, Product mix Vary: Process/facility design

1

3

5

2

4

Identify Potential Solutions and Alternatives

Define Development Timelines and Pathways

Model

Analyze

Plan

6

7

8


Building the industry technology roadmap



Agenda











Evaluating Biopharmaceutical Market Trends

14 Feb 2016 Technology Roadmapping

Robust

Pipelines

Biosimilars

Competition

Diversification

of product

groups

Payer

pressure on

cost of drugs In-region

manufacturing

requirements

Personalised

medicine

Complex Global

regulatory

environment

Strength of

Sales (Biologics) New

Treatment

Modalities

Emerging

Markets

Social / Political

Perceptions

Clinical Failures Dose

Requirements

Market

Share

Demand

Forecasts

Rising Costs

of Drug

Development

Advances

in Systems

Biology

Business Drivers



High level Technology Roadmap structure

Speed Cost Flexibility Quality

Uncertainty Cost pressure Market Growth New Product

Classes

Inline

Monitoring &

Real time

Release

Industry Trends

Business Drivers

Biomanufacturing

scenarios

Enabling

Technologies

16

Process

Technology

Modular &

mobile

Automated

Facility

Knowledge

Management

Supply

Partnership

Management

March 17 BPOG Introduction

Drug

Product

High volume

Drug

Product

Low volume

Scale Distributed

1. Large-scale Stainless Steel Fed Batch

2. Intermediate-scale Single-use Perfusion

3. Intermediate-scale Multi-product Single-use Fed Batch

4. Small-scale <500L Portable Facility

5. Small-scale <50L for Personalized Medicine


Expert teams developed roadmaps for six key enabling technology areas

17

Roadmap Team Vision / Key Themes

Process Technology

• Process Intensification - combining multiple USP/DSP unit operations • Continuous Processing: New separation and media technologies,

coupled with advanced automation and process control • Disruptive technologies and streamlined implementation/validation

Modular and Mobile

• Quick to configure manufacturing w/ ‘plug and play’ standard designs • Facility as Equipment – modular and rapid expansion. • Flexibility- expand on demand, regional deployment

In-line Monitoring & Real-time release

• Process control and product quality through advanced monitoring devices, indirect or multi-attribute sensors and PAT

• Global regulatory testing standards, advanced process control strategies and raw material characterization

Fully Automated Facility

• Scale up with a focus on automation, equipment and biology results in a fully automated facility

Supplier Management

• Suppliers become technology development partners for our industry, collaborating to solve problems

Knowledge Management

• Integrated knowledge of product and process technology across development, manufacturing and commercial value streams

March 17 BPOG Introduction


Example of Technology Opportunities: Process Technology Workstream

Production cell lines • Cell specific productivity • Impurities and product quality features (glycans) • Harmonized expression system

Upstream batch titer • Cell line specific productivity • Perfusion applications to batch culture • Culture duration

High downstream step yields • Purity and impurity profiles (simple and robust product modalities) • Resin features (capacity and impurity clearance)

Perfusion media costs and specific perfusion rate • Media design and waste product formation • Highly concentrated and balanced media of low cost

Consumables cost • Improved filter capacity and production processes

Buffer production strategy • Buffer concentrates and in-line dilution

18 3/9/2017


Agenda











Manufacturing Scenarios and Linkage to Business Drivers


Scenario Manufacturing Description Facility Type

1 Large-scale Stainless Steel 6 x 15kL SS

2 Single-use (SU) Perfusion 2 x 2kL SU

3 SU fed-batch/intensified fed-batch 6 x 2kL SU

4 Small scale SU perfusion <500L


Defining Objectives and Options for Modeling (Step 4)

Purpose of Modeling

• Identify areas of opportunity for improvement within a given scenario / facility type.

• Compare performance between options within a scenario or between scenarios relative to a given metric

o e.g. compare estimated Cost of Goods using different process formats

• Process parameter sensitivity analysis

• Identify bottlenecks in throughput and breakpoints in technology strategy/selection.

• To evaluate the technology improvements proposed by the roadmap teams

21 3/9/2017

Modeling Approach

• Modeling approach used the manufacturing facility scenarios as a basis to ground the modeling work to industry needs.

• Biosolve software was used along with current and future state parameter inputs to calculate the COGs for each scenario.

• Mfg throughput ranges were varied to represent quantities required for clinical trials or launch stages of development.

• COGs analysis does not provide the full cost of manufacture due to differences in the upfront capital investment. Future modeling efforts may incorporate NPV based analysis to allow more comparisons across the scenarios.


Scenarios Used for Modelling COGs

22

Scenario number

Reactor volumes

Production methods 250kg/yr 500kg/yr 3.5t/yr*

1 a 6x15kL SS Batch / Batch x x x

b Batch / Continuous x x x

2 a 2 x 2kL SU Perfusion / Batch x x x

b Perfusion / Continuous x x x

3 a 6 x 2kL Batch / Batch x x x

b Batch / Continuous x x x

4 a 2x200L Continuous / Continuous x x x

b Batch / Batch x x x

Sensitivities run at 80% utilization *Model multi products at 3.5t/yr - 1, 3, 5

October 2016


Manufacturing Scenarios COGs Summary and Throughput Impact


Table 3 Comparison of Scenarios COGs at 80% plant utilization

Scenario

(batch or continuous DSP)

Cost per gram

($/g)

Annual Facility Output

(kg)

6x15KL fed-batch $43-46 2974

6x2KL fed-batch $71-79 405

6x2KL conc. fed-batch $55-59 1805

2x2KL perfusion $73-88 452


Manufacturing Scenarios COGs Summary and Throughput Impact

Scenario

(batch or continuous DSP)

High Throughput

(1805-2974 kg/yr)

Low Throughput

(250-450 kg/yr)

Cost per gram ($/g)

6x15KL fed-batch $43-62 $199-362

2x2KL perfusion $72-92 $73-120

6x2KL fed-batch $75-83 $71-109

6x2KL conc. fed-batch $55-59 $105-168


Table 4 Comparison of Scenarios COGs at High and Low Product Throughput


Sensitivity parameters

25 October 2016

Sensitivity Range

Base - Base Base + 5 Years 10 Years

Cell line productivity (pcd) 15 20 25 30 60

Fed-batch titer (g/L) 1.5 3 5 10 20

Fed-batch media cost ($/L) 30 15 10 7.5 5

Fed batch culture duration (days) 12 14 16 10 7 Perfusion steady state cell mass (million/mL) 30 60 80 100 120

Perfusion media cost ($/L) 15 10 7.5 5 2.5 Concentrated Fed-batch (CFB) perfusion rate over last 10 days (reactor volumes per day) 2 1

Concentrated fed-batch peak cell mass (E06 per mL) 80 120

Concentrated fed-batch specific productivity (PCD) 20 60

Conc’d fed-batch titer (g/L normalized for cell mass) 12 36 ProA resin capacity 30 35 45 60 80 CEX resin capacity 60 90 120 AEX resin capacity (FT) 200 500 800 Chrom cycles number ProA 2 4 6 8 16 Chrom cycles number Polishing steps 1 2 3 4 8 Viral filter loading (kg/m2) 5 20 50 UF/DF loading (L/m2) 400 1000 5000 Chrom Cycle Time, ProA (hours) 12 24 36 32 48 Chrom Cycle Time, Polishing (hours) 3 6 9 12 18


Scenario 1a & 1b – all unit operations

26 November 2016

6X15kL Batch USP & Continuous DSP Facility Annual Thoughput: 2974 Kg/yr

6X15kL Batch USP & Batch DSP Facility Annual Throughput: 2974 Kg/yr


Scenario 1e & 1f – all unit operations

27 November 2016

2X2kL Perfusion USP & Continuous DSP Facility Annual Thoughput: 451 Kg/yr

2X2kL Perfusion USP & Batch DSP Facility Annual Thoughput: 451 Kg/yr


Scenario 1c & 1d – all unit operations

28 November 2016

6X2kL Batch USP & Continuous DSP Facility Annual Thoughput: 405 Kg/yr

6X2kL Batch USP & Batch DSP Facility Annual Thoughput: 405 Kg/yr


Scenario 1g &1h – all unit operations

29 November 2016

6X2kL Conc. Fed-Batch USP & Batch DSP Facility Annual Thoughput: 1805 Kg/yr

6X2kL Conc. Fed-Batch USP & Continuous DSP Facility Annual Thoughput: 1805 Kg/yr


Agenda







Example technology roadmap report

Contents

• Summary

• Introduction; vision, scope & benefits

• Needs, challenges & potential solutions

• Disruptive technologies

• Regulatory considerations

• Conclusions and recommendations


Selected pages from the Modular and Mobile roadmap


Timing of publication, communications & feedback mechanism

1st edition published in May 2017, freely available on BPOG website • http://www.biophorum.com/category/resources/technology-roadmapping-

resources/roadmap/

Complemented by broad communications mix • Webinars, conference presentations, articles, newsletters

Request input on roadmap’s content & scope of future editions • Individual comments or formal response from your organisation • Your organisation becoming active members of the

collaboration

Roadmapping is about stimulating an industry response, encouraging required innovation to happen

What solutions can you bring to overcome difficult challenges facing the industry?


Communications

2016 2017 2018

Articles Articles & conferences

CASSS Publish 1st Edition

May’17 CASSS BIO

Engagement & feedback

Publish 2nd Edition

BPOG Website

Conference presentations

http://www.biophorum.com/category/resources/technology-roadmapping-resources/roadmap/






Acknowledgements: The Technology Roadmapping teams

Jan 2017 Technology Roadmapping 33


Disclaimer

This presentation was prepared by the BPOG Consortium. The opinions and views expressed are from the BPOG Consortium and do not reflect the views of individual member companies

34 3/9/2017

Thank You!

Date post:	28-May-2020
Category:	Documents
Upload:	others
View:	8 times
Download:	0 times

A Technology Roadmapping Process to Transform the Biopharmaceutical … · A Technology Roadmapping...

Documents