technology roadmapping collaborating to … roadmapping – collaborating to accelerate innovation...

© BioPhorum Operations Group Ltd

Technology Roadmapping –Collaborating to accelerate innovation in biopharmaceutical manufacturing

Paul Ilott

March 2017


Agenda

▪ Introduction to BPOG

▪Ambition, process and structure

▪Content of the Technology Roadmap

▪How to get involved

Technology Roadmapping March 2017 2


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

March 2017Technology Roadmapping 3

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


Drug Substance

Development Group

FillFinish

Information Technology

TechnologyRoadmapping

Supply Partner

BPOG has 6 Phorums covering all aspects of biopharma operations

Technology Roadmapping 4

Drug Substance, Fill Finish, Development, Information Technology

Accelerating the way the industry delivers near term results, making best practice development and implementation faster, cheaper and smarter

Supply Partner Phorum

Creating the supply chains the industry needs; defining, developing and implementing solutions for business processes, systems and culture

Technology Roadmapping

Revolutionising the way the industry develops longer term transformational manufacturing and technology capabilities

Focusing on strategy and 10yr time horizon, defining needs, difficult challenges and potential solutions

Regulatory Interaction

Ensure efforts to design and adopt advances in manufacturing are aligned through engagement with Health Agencies

BPOG Facilitation

Decisions are made at the right time, at the right place by the right people

Linkages are made visible to avoid redundancy

Synergies are leveraged through effective coordination

March 2017


Agenda







Audacious goal: To agree an industry technology strategy

An industry technology roadmap is a dynamic and evolving collaborative technology management process for

▪ determining precompetitive critical needs and drivers,

▪ identifying technology and/or manufacturing targets, and

▪ assessing/modeling potential solutions

to

▪ focus an industry community,

▪ provide direction, and

▪ resolve those critical needs for a specific timeframe by consensus



A strong collaboration, bringing the industry’s top people together to contribute to & benefit from the technology roadmap

▪ Developed a strong Steering Committee

• Required decision making

• Driving roadmap

• Subject matter experts access

▪ Diverse participants

• 32 member companies from across biomanufacturers and supply partners

• Academics & regional centres, e.g. MIT, AMBIC, CPI, SEDB, NIIMBL

▪ Over 170 people involved globally

7March 2017Technology Roadmapping


Agenda







High level Technology Roadmap structure

Speed Cost Flexibility Quality

UncertaintyCost pressure Market GrowthNew Product

Classes

Inline

Monitoring &

Real time

Release

Industry Trends

Business Drivers

Biomanufacturing

Scenarios

Enabling

Technologies &

Capabilities

9

Process

Technology

Modular &

Mobile

Automated

Facility

Knowledge

Management

Supply

Partnership

Management

March 2017Technology Roadmapping

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

Evaluating Biopharmaceutical Market Trends

10

Robust

Pipelines

Biosimilars

Competition

Diversification

of product

groups

Payer

pressure on

price

In-region

manufacturing

requirements

Personalised

medicine

Complex Global

regulatory

environment

Strength of

Sales (Biologics)

New

Treatment

Modalities

Emerging

Markets

Social / Political

Perceptions

Clinical FailuresDose

Requirements

Market

Share

Demand

Forecasts

Rising Costs

of Drug

Development

Advances

in Systems

Biology



Collective Brainstorming by Industry Experts



High level Technology Roadmap structure

Speed Cost Flexibility Quality

UncertaintyCost pressure Market GrowthNew Product

Classes

Inline

Monitoring &

Real time

Release

Industry Trends

Business Drivers

Biomanufacturing

Scenarios

Enabling

Technologies &

Capabilities

12

Process

Technology

Modular &

Mobile

Automated

Facility

Knowledge

Management

Supply

Partnership

Management


Drug

Product

High volume

Drug

Product

Low volume

Scale Distributed







The team agreed a range of biomanufacturing scenarios that would be important over the next 10 years

13


• Figure shows an approximate range of production rates typical for a given scenario and facility type.• A technology determined to have high impact across multiple scenarios would reinforce importance

to the industry.• Quantitative computational models provide valuable insight in estimating the value of a technology

or process innovation that would otherwise be difficult to predict.


Uncertainty

▪ Regulatory approvals

▪ Demand variability

▪ Competition

Cost pressure

▪ Payer pressure

▪ Biosimilars

▪ Development

Market Growth

▪ Emerging markets

▪ Global reach

▪ In region manufacture

New Product Classes

▪ Non-mAbs, ADCs

▪ Gene therapy

▪ Cell therapy

Inline Monitoring and

Real time Release- Product Release

1-2 day

+ ↑ Quality, Efficiency &

Supply

▪ Enhanced In-Line

Monitoring

▪ Indirect and

Multivariate Sensors

▪ Multivariate Analysis

and Predictive

Modeling

Process Technologies- 90% CoGs

- 90% process

investment

▪ Process Intensification

& combination of unit

operations

▪ Continuous processing

technologies coupled

with advanced process

control

Modular and Mobile- 70% build time

- 75% CAPEX

▪ Quick to configure &

scale

▪ Standard designs

▪ Streamlined validation

Automated Facility− 50% Facility Build

Speed

− 50% OPEX costs

from current

▪ Agile, high quality, and

robust

biomanufacturing

▪ Plug and Play

▪ Open data standards

▪ Interoperability

Knowledge

Management‒ Cost of process

development

– Time to introduce a

change to an existing

process to 1 Month– Cost of Non-Quality

to 2% of operating costs

• Efficient tech. transfer

• Integrated knowledge

• Quality throughout

lifecycle

Supply Partnership

ManagementSafe, innovative supply

chains:

− Cost of quality− Time

▪ Partnerships with

quality built in

▪ Standard working,

integration and real

time Electronic Data

Exchange

▪ Shared Planning

Market Trends & Business Drivers – The Why

Enabling Technologies & Capabilities – The How

Speed

-70% build time

-80% lead time

Cost

-90% manufacturing cost

-90% CAPEX

Flexibility

-90% changeover

Demand response

Quality

10x robustness

-90% cost of quality

Drug Product

High volume

Drug Product

Low volume

Scale Distributed





Biomanufacturing scenarios – The What

(Facility types)


Roadmap Vision



Process Technologies example - Process technology developments are at the heart of any

efforts to increase the productivity and robustness of biopharmaceutical manufacturing. While incremental improvements to current processes will make a difference, real breakthroughs in effectiveness will come from disruptive process changes

Priority technologies & capabilities:▪ Media performance - Richer, chemically defined medias, feeds and

supplements that enable higher cell densities, higher titers, simplified media make-up, and longer media stability.

▪ Robust harvesting - Scalable harvest technologies and cell retention devices that minimize large capital investments and can handle ever increasing cell densities.

▪ Viral clearance - Standardized modular claims that provide streamlined regulatory processes and ease process development.

▪ Buffer management approaches that reduce operational constraints and space requirements for buffer preparation.

▪ Single use technologies to increase flexibility and improve closed systems, resulting in decreased capital cost, and decreased total cost of goods over the lifetime of a product.


Process

TechnologiesBenefits:

90% CoGs

90% process

investment

Key themes:

▪ Process

Intensification -

Intensifying production

through highly

concentrated reactants

& products, combining

unit operations into

single units

▪ Continuous

Processing - New

separation & media

technologies, coupled

with advanced

automation & process

control


The collaboration can explore options for biomanufacturing in more detail (eg Net Present Cost: Scaling up vs. Scaling Out )

16March 2017

Conventional

“Six-pack”

Facility

6 x 15,000L Stainless Steel

Bioreactors

Expanded or

Multi-Facility

6 x 2,000L Single-use

Bioreactors

Total Facility Output (kg/yr)

Technology Roadmapping


Agenda







Roadmap edition 1 will be published on the BPOG Technology Roadmapping website and available to anyone who registers

▪Edition 1 will be published ~June’17, and can be accessed by registering on the BPOG website

• The edition 1 document will be free of charge

▪Published material (egarticles, conference presentations) can be accessed from the website

www.biophorum.com


http://www.biophorum.com/


Strategic cycle of Technology RoadmappingValue continues to grow through 2017

2017 provides an opportunity to exploit a strong position and accelerate change in the industry.

▪ Publish roadmap edition 1 and plan / track industry response• Receive feedback and challenge from across the industry to further improve

the roadmap document• Work closely with supply partners, academia and regional hubs for rapid

demonstration of innovations and development of new technologies to address fundamental challenges

• Influence fundamental R&D that is required to deliver vision• Together use combined knowledge and experience to address the regulatory

challenges identified

▪ Roadmap edition 2• Continue to build a valuable coalition for change in the industry• Leverage the roadmapping structure and capability into adjacent squares and

deeper into critical areas



QUESTIONS


Anti-Trust Compliance Statement v4.0

▪ It is the clear policy of BioPhorum that Biophorum and its members will comply with all relevant anti-trust laws in all relevant jurisdictions

▪ All BioPhorum meetings and activities shall be conducted to strictly abide by all applicable antitrust laws. Meetings attended by BioPhorum members are not to be used to discuss prices, promotions, refusals to deal, boycotts, terms and conditions of sale, market assignments, confidential business plans or other subjects that could restrain competition.

▪ Anti-trust violations may be alleged on the basis of the mere appearance of unlawful activity. For example, discussion of a sensitive topic, such as price, followed by parallel action by those involved or present at the discussion, may be sufficient to infer price-fixing activity and thus lead to investigations by the relevant authorities..

▪ Criminal prosecution by federal or state authorities is a very real possibility for violations of the antitrust laws. Imprisonment, fines or treble damages may ensue. BioPhorum, its members and guests must conduct themselves in a manner that avoids even the perception or slightest suspicion that antitrust laws are being violated. Whenever uncertainty exists as to the legality of conduct, obtain legal advice. If, during any meeting, you are uncomfortable with or questions arise regarding the direction of a discussion, stop the discussion, excuse yourself and then promptly consult with counsel..

▪ The antitrust laws do not prohibit all meetings and discussions between competitors, especially when the purpose is to strengthen competition and improve the working and efficiency of the marketplace. It is in this spirit that the BioPhorum conducts its meetings and conferences.



Back-up slides



Six Enabling Technologies & Capabilities have been mapped in detail


Enabling Technologies & Capabilities

Vision Benefit

Process Technology

Process Intensification - Intensifying production through highly concentrated reactants and products and combining unit operations into single units

• Minimalized capital investment• Streamlined validation processes• Decreased total cost of goods

Continuous Processing - New separation and media technologies, coupled with advanced automation and process control

• Flexibility for smaller patient populations• Speed• Reduced cost and reduced facility size

In-line Monitoring and Real-time release

Enhanced in-line monitoring unlocks potential for robust material characterisation, process control and assurance of product quality

• Enabler of Real Time Release; Product Released in 1-2 Days• Improved Product Quality, Operational Efficiency and

Reliable SupplyHardware for advanced in-line monitoring devices including indirect and multi-attribute sensors

Software to enable multivariate analysis, predictive models and closed feedback control loops

Modular and Mobile

Manufacturing systems that are quick to configure, assemble, scale and relocate, using ‘plug and play’ standard designs and standard validation approaches

• Rapid tailoring of capacity to meet demand• Manufacturing process available in weeks • Mobility of facilities through lifecycle• Reduction in capital expenditure

Fully Automated Facility

Plug and play for fast response to capacity demands, with minimal staff, time to change over, and regulatory observations, that delivers products of lowest cost and highest quality, from receipt of raw materials to final drug product.

• Quicker and cheaper facility builds and lower lifecycle costs• Readily available and usable data• Reduced mfg. deviations and non-conformances• Streamlined real-time release• OPEX reduction

Supply Partnership Management

Supply Partnership Management undertaken in a spirit of openness and trust to drive successful collaboration making best use of technology and integration of systems and processes

• Lower cost/quality ratio for raw materials, services and capex investment

• Faster to develop, produce and make changes• Safe, innovative supply chains

Knowledge Management

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

• Accessible and applicable biomanufacturing information and knowledge, driving down development costs

• Efficiency and quality throughout product lifecycle.

Example “Enabling Technologies and Capabilities” 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 report


In-Line Monitoring and Real Time ReleaseEnhanced in line monitoring is a fundamental enabler of Real Time release and unlocks the potential for robust process control while improving operational efficiency, product quality and reliable supply to patients. Goals include a step change in lead-times for batch release from weeks to days.

Priority technologies & capabilities:• Raw Materials: Characterisation and Control

• Hardware: Advanced in-line monitoring devices including indirect and multi-attribute sensors

• Software: Enable multivariate analysis, predictive models and closed feedback control loops

• Technology: Advancements in rapid analytical testing for biological assays

• Quality and Business Systems: Integrated and streamlined to enable batch review by exception

• Regulatory: Contemporary and enabling Strategies


In-Line Monitoring

and Real Time

Release

Benefits

- Reduce Product Release

time from weeks to 1-2 day

+ ↑ Improved product Quality,

process efficiency and

reliability of supply

Key Themes

▪ Enhanced In-Line

Monitoring

▪ Indirect and Multivariate

Sensors

▪ Multivariate Analysis and

Predictive Modeling


Modular & MobileBiopharmaceutical products are currently produced in fixed facilities that require significant upfront, at-risk capital investment. Modular and Mobile concepts offer an opportunity to shift to networks of smaller, standardized manufacturing facilities that can be built in less than half the time.


Modular and Mobile

Benefits:

- 70% build time

- 75% CAPEX

Key themes

▪ Flexibility:

Manufacturing systems

that are quick to

configure, assemble,

scale and relocate,

using ‘plug and play’

configurations

▪ Standard designs:

Interchangeability and

multi-supplier market

▪ Standard validation

approaches:

Harmonized approach

to validation of facilities

Priority technologies & capabilities:▪ Standardisation

• Creation of equipment standards• Enable multi-supplier

environment• Regulatory harmonisation

▪ ‘Facility as Equipment’• Management of validation, capital

& speed to install• Eliminate non-value add activity

(manufacturers & regulators)▪ Standardisation

• Quick, easy scale up of processes & facilities

• Bring production to where mostneeded – closer to patients

• Speed to market

‘Russian Doll’ model of a modular and

mobile facility, showing different layers of

facility and kit management

© BioPhorum Operations Group LtdMarch 2017Technology Roadmapping 27

Automated Facility Plug and play for fast response to capacity demands, with minimal staff, time to change over, and regulatory observations, that delivers products of lowest cost and highest quality, from receipt of raw materials to final drug product.

Automated Facility− 50% Facility Build

Speed

− 50% OPEX costs

from current

Key themes

▪ Agile, high quality, and

robust

biomanufacturing

▪ Plug and Play

▪ Open data standards

▪ Interoperability

Priority Technologies and Capabilities• Full integration across all

systems (manufacturing execution system (MES), process control system (PCS), laboratory information management system (LIMS)) results in quicker and cheaper facility builds and lower lifecycle costs

• High availability of automation depends on automation IT systems and databases. Work with supply partners is critical in this space.

• Data management for readily available and usable data

• Robotics and Mechanization toreduce manufacturing deviations and non-conformances and OPEX reduction

S95 System Levels

© BioPhorum Operations Group LtdMarch 2017Technology Roadmapping 28

Knowledge ManagementIntegrated knowledge of product and process technology across the development, manufacturing and commercial value streams

Knowledge

Management‒ Cost of process

development

– Time to introduce a

change to an existing

process to 1 Month– Cost of Non-Quality to 2% of operating costs

Key themes• Knowledge as an asset

• People, process,

content, and technology

• Efficient technology

transfer

• Integrated knowledge

• Quality throughout

lifecycle

Priority Technologies and Capabilities• Cost: The embedded use of knowledge management tools for product and

process knowledge and structured lessons learned results in efficient manufacturing processes, less errors, and reduced cost of supply/development.

• Speed: Well-structured and coordinated product/process information management (findability of information) can significantly impact time to release product and time to introduce changes to an existing process.

• Quality: Improved management of multiple knowledge formats and easy access to information increases capability to understand how critical process parameters impact critical quality attributes, improves control, and reduces the occurrence of manufacturing out of specification product.


Supply Partnership ManagementThe supply chains to support the Technology Road map need to be safe and innovative and based on supply partnerships undertaken in a spirit of openness and trust to drive successful collaboration making best use of technology and integration of systems and processes


Supply Partnership

Management

Safe, innovative supply

chains:

− Cost of quality− Time

Key Themes:

▪ Partnerships with

quality built in

▪ Standard working,

integration and real

time Electronic Data

Exchange

▪ Shared Planning

29

Priority technologies & capabilities:

▪ Openness & Trust – Information sharing for mutual benefit

▪ Quality Built-In – ‘Right first time’ and removal of duplication

▪ Forecasting & Demand Planning – Consolidated industry plans

▪ Standardisation – ‘Plug and Play’ and simplification

▪ Electronic Data Exchange & Supplier Integration – Speed & time


▪ Approach to modeling (using the BioSolve Software)

• 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.

• Evaluate the technology improvements proposed by the roadmap

Modeling the bio-manufacturing scenarios can identify areas for technology innovation


technology roadmapping collaborating to … roadmapping – collaborating to accelerate innovation...

Documents