assessment of process modeling tools for innovative technologies€¦ · · 2017-09-06process...

© BioPharm Services Ltd

Assessment of Process Modeling Tools for Innovative Technologies

BioProcess International Conference

October 9, 2012

Miriam Monge - VP Biopharm Services

Jim Velez – Merck Global Engineering Services

© BioPharm Services Ltd 2 CONFIDENTIAL

Agenda

Introduction to Biopharm Services

Industry challenges

Why use Process modelling?

User case study: Merck Global Engineering Services

Questions


Biopharm Services

Biopharm Services’ helps clients make well informed decisions quickly, saving

time & resources during the development and manufacture of cost

effective medicines

Driving development & manufacturing

innovation through bioprocess modelling

Biopharm Services

Software

Products

Support Consultancy


Biopharmaceuticals Today & Tomorrow

Manufacturing is a key requirement for the industrialization of the biosciences

Insights into the cost implications of decisions made in development are critical to successful commercialization

Traditional biopharmaceuticals have been vaccines and recombinant proteins

Flu vaccine

Monoclonal antibodies

New products based on new science, these pose challenges in terms of industrialization and cost effectiveness

Tissue engineering

Cell therapies - autologous & allogeneic

Gene therapy

Novel vaccines


Manufacturing cost is

single variable cost

(14% of sales)

Development costs

are fixed and include

losses around failed

drugs (21%)

Data source: GE Healthcare webinar

Manufacturing Costs are Important


Why Use Models?

Get the big picture – what are the variables?

Make predictions – what will happen if…

Evaluate alternatives which one is best?

Communication a simple picture or chart is better than a thousand words

Make better business decisions

Cost breakdown by unit operation

1000$/batch for a Mab process


Building a Good Cost Model

Understand the manufacturing process

Resource requirements

Timing

Understand the cost structure

Fixed/variable – not always obvious

Beware of hidden costs

Activity-based costing (ABC) can help with this

Understand where to make assumptions

Impossible to model all variables

Can introduce more error by false confidence


Models Realizing Value Education, Suppliers, Manufacturers

Integrating

technologies in

BioSolve: Pall Cadence

single-pass TFF

Total cost in use analysis

of a chemically defined

media supplement as

compared to a legacy

process using peptone

supplementation

Developing business cases for

new products & new

technologies

Upskilling the next

generation of bioprocess

engineers, linking BioSolve

to USD

Environmental life-cycle

assessment of single-use

versus conventional process

technology for mAb production

Process models guiding

process development

Process cost & facility considerations

when selecting cell culture clarification

technology

and

User Case Study: Assessment of

Process Modeling Tools for Innovative Technologies

BioProcess International Conference October 9, 2012

Jim Velez - Merck Global Engineering Services

Merck Manufacturing Division

• To be the most trusted and competitive supplier of pharmaceuticals, animal health and consumer healthcare products, vaccines and biologics to the world’s patients and customers, enabling Merck’s growth

– Capability to Serve 80% of the World’s Population

– Become a World Class Supply Organization

– Lead in New Technologies for New Business Growth

– High Performance Organization

Focus on Key Terms

Competitive

World (Global)

New (Innovative) Technologies

High Performance

Low Cost

Anywhere & Everywhere

Same Quality / Efficacy / Safety & Security

Very Fast

How?

Understand & incorporate into everyday job:

• Sales forecasts

• Total costs of ownership

• Innovative technologies

• Regulatory requirements

• Safety / industrial hygiene / environmental

• Etc.

Scientists and engineers are being asked to wear many hats

Process

Modeling

What?

• Find the “right tool for the right job”

• Assemble a team with the required skills

– Partner with BioPharm as part of the extended team

• Establish a reference point and bookends

• Perform “calibration” with BioPharm

• Establish a common template

• Build scenarios and run sensitivities

• Analyze the results and make recommendations

Challenges / Opportunities

• Names & nomenclature are different

• Greenfield vs. Brownfield

• Unit costs were different

• Utilities & infrastructure methodology are scaled to fit scenario / sensitivity; does not “overbuild”

• Default values vary from operation to operation, site to site, company to company

• NPV Add-On needed customization

Case Study: Reference Point

• New “Greenfield” Monoclonal Antibodies Facility in US

• 6 x 15,000L Stainless Steel Bioreactors

• Traditional Upstream / Downstream Stainless Steel Equipment

• Stainless Steel Media & Buffer Prep / Hold

• Stainless Steel CIP / SIP Infrastructure and Utilities

• Support Infrastructure, Utilities, Warehouse, Labs & Offices

• 120 lots per year

• Titer = 3 grams / L

Case Study: Bookend #1

• New “Brownfield” Monoclonal Antibodies Facility in US

• 6 x 2,000L Stainless Steel Bioreactors

• Traditional Upstream / Downstream Stainless Steel Equipment

• Stainless Steel Media & Buffer Prep / Hold with 500L Single Use Threshold

• Stainless Steel CIP / SIP Infrastructure and Utilities



Case Study: Bookend #2

• New “Brownfield” Monoclonal Antibodies Facility in US

• 6 x 2,000L Single Use Bioreactors

• Non-Traditional Upstream / Downstream Single Use Equipment

• Single Use Media & Buffer Prep / Hold with 3000L Max Threshold

• Minimal “Clean” Infrastructure and Utilities



Case Study: Calibration

Facility Sq Ft Capital Cost

6 x 15kL SS Merck 200,000 $575 MM

6 x 15kL SS BioSolve 300,000 $550 MM

6 x 2kL SS Merck 70,000 $180 MM

6 x 2kL SS BioSolve 50,000 $195 MM

6 x 2kL SU Merck 50,000 $70 MM

6 x 2kL SU Biosolve 50,000 $60 MM

Case Study: BioSolve Results

Platform Bioreactor Size COGS % Utilization Batches/yr $ per Gram

SS 15,000 L $160,041,878 97 120 $52

SS 2,000 L $57,533,910 100 120 $129

SU 2,000 L $46,151,637 94 120 $102

Case Study: BioSolve Results

Platform Bioreactor Size COGS % Utilization Batches/yr $ per Gram

SS 15,000 L $160,041,878 97 120 $52

SS 15,000 L $71,166,987 14 17 $174

SS 2,000 L $57,533,910 100 120 $129

SU 2,000 L $46,151,637 94 120 $102

Case Study: Data Analysis

Bioreactors: 6 x 15,000L vs 6 x 2,000L (3g/L Titer)

Kg per Year

NP

C

15kL SS

One 6 x 15,000L SS

facility @ 14%

utilization

One 6 x 15,000L SS

facility @ 49%

utilization



Kg per Year

NP

C

15kL SS 2kL SS

One 6 x 15,000L SS

facility @ 14%

utilization

Two 6 x 2,000L SS

facilities @ 97%

utilization each

One 6 x 15,000L SS

facility @ 49%

utilization



Kg per Year

NP

C

15kL SS 2kL SU 2kL SS

One 6 x 15,000L SS

facility @ 14%

utilization

Two 6 x 2,000L SS

facilities @ 97%

utilization each

Three 6 x 2,000L SU

facility @ 97% utilization

each

One 6 x 15,000L SS

facility @ 49%

utilization

Innovative Technologies

• Single Use Bioreactors

• Single Use Centrifuge

• Single Use Depth Filtration

• Single Use Ultra Filtration

• Natrix

• Single Use Chromatography Columns

• >500L Single Use Mixing & Storage

• Modular facilities

Conclusions

• Use the right tool – for this case BioSolve was the right tool

• Set Up Work Required - Training, calibration, verification, templates, unit costs, labor rates, indirect costs, assumptions and documentation / notes

• Multiple scenarios and multiple sensitivities rapidly

• Business decisions based on “virtual” data

Acknowledgements BioPharm Services Ltd.

– Claire Burden

– Andrew Brown

– Andrea Rayat

Sponsors: Andrew Sinclair & Miriam Monge

Merck

– Mark Brower

– Alexandra Buttke

– Daniel Caparoni

– Stephen Blume

Sponsors: Dave Pollard & Jeff Johnson

Questions

Thank You

assessment of process modeling tools for innovative technologies€¦ · · 2017-09-06process...

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