Disposables TechnologyTrends, drivers & practices

Gordon Farquharson

July 2017

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Agenda

1. Business drivers

2. Technical trends

3. Systems in practice

4. Comparison with fixed systems & justifications

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The basic decision

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Basis for analysis

• Process Cost Models

• Analyse the impact of a specific technology within a given process

• Disposables vs. stainless

• Technology performance can be modelled in computer programmes like “BioSolve”

• Impact on Cost of Goods

• Process throughput

• Impact on facility: utilities, waste streams, etc.

Paper reference:

November 2008 BioPharm International paper "The environmental impact of

disposable technologies — Can disposables reduce your facility's

environmental footprint?“ (Sinclair, Leveen, Monge, Lim and Cox)

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Challenges in Bio-pharma

1. Compared to chemical pharmaceuticals

• Drugs are complex products.

• Sophisticated manufacturing facilities.

2. Product development is expensive & slow

3. Products are expensive to make (on a per treatment basis)

• Especially current generation MABs

4. Production facilities have traditionally been very expensive and inflexible

5. Rapid response is often required

• Biodefense

• Epidemics (Pandemic flu)

6. Competition from Bio-similars

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Manufacturing trends

Trends

• Success rates & yields increased

• Titres have greatly increased

• Titre improvements continue & will reduce the volume of bioreactor capacity.

• Titres and Yields of Licensed Antibodies will gradually increase over time'

• There will be more Antibodies with smaller market penetration/sales and lower Product Mass (50-500kg) requirements'.

Implications

• Plant size decreasing

• Need for more flexible facilities

• Disposable technologies will have greater application for commercial supply

• However

• Cost is an issue

• Maturity and supply chain security

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Facilities that can be rapidly expanded with minimum effort.

Key challenges

Impact on design logistics

Need for better understanding of the possibilities

Environmental impact of disposables.

Procurement and supply chain dependency.

Business analysis

When & where is it cost effective to implement disposable technologies into

a given process.

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Disposable – Risk/Benefit Assessment

Risks Nature Mitigation

Technology maturity Supplier and application dependent

Formal assessment

Economics Depends on degree of novelty and extent of available competition

Evaluate full life-cylecosts – capital & operation

Supplier dependency Available competition Design system to maximise choice.

Validation Dependent on the defined approach

Risk based approach to current industry practice

The environment Extent and method of waste treatment

Assess, mitigate impact, treat waste stream

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Disposable – Key positive effects

Feature Effect Outcome

Remove or reduce CIP & SIP requirements

Reduce complex pipework.Reduce automation systems requirements.

Reduced periodic qualification.De-couple building and process systems.Lass labour.Less water and energy.

Faster product/batch change-over

Reduced activity for washing, cleaning, and preparing reused equipment.

Less labour.Better utilisation.Supports lean manufacturing.

Ease of reconfiguration Can set up new process trails easily. Can be developed and validated off-line.

Easily reconfigured in response to new products and improved yield as process matures.

Note: Facility design has to be completely changed in concept = loose fit solution.

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Result = Less complexity, smaller (1000 L scale)

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Disposable examples –

Reactors & vessels

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Disposable examples – Connectors

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Layout of a CompleteDisposable Aseptic Processing

mixer

Pump

Disposable

formulation,

Filtration

system

Grade A

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Disposable Final Fill and FinishAcerta Dispensing System (Millipore)

Novel patented disposable liquid dispensing

• Volumetric Fill - Gravity Driven

Matches Conventional Filling Systems

• Fill Reproducibility: < 0.5% at 1.0 mL

• Set-up Time: 30 min.

• Fill Volume Range: 0.5 to 20 ml

• Fill Rates: up to 40 / minute per head at 1.0 ml

All product contact parts are disposable

The set-up is pre-assembled, integrity tested and gamma sterilized up to 45 kilograys

• Components are:

• Platinum-cured silicon and C-flex tubing

• LDPE reservoir

• Polycarbonate sight tubes and needles

• All materials are USP Class VI

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Conclusions

Pressure to reduce price of medicines to patients, and maintain margins for inventors and manufacturers

Biological medicines are very significant business going forward

• Driving out cost in biologics manufacturing

• Reducing complexity

• Rapid expansion & contraction of capacity

Disposables have a key role to play as a platform technology:

• Supply chain security

• Manufacturing standards and capacity

• Varying quality standards

• Disposable system standardization

Many challenges remain for disposables:

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Conclusions- a structured apprach

• Rapidly changing area need to keep current• Identify the added value technologies

Single-use technology analysis and feasibility assessments

Use the appropriate amount don't go fully disposable for disposables sake

“Fully" disposable manufacturing plant design

Use structured evaluation methodology

• Cost

• Technologies

• Design options

• Vendor Supply chain security

Integrated disposable and stainless steel manufacturing plant design

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Thank you for your time.Questions?

Gordon Farquharson

gordon.farquharson@pharmout.net

www.pharmout.net

Executive Consultant