pda annual meeting orlando march 2010 mj

PDA Connecting People, Science and RegulationSM

Disposable Biopharmaceutical ProcessesAdvances & Benefits

March 15-19, 2010, Orlando, FL

Maik W. Jornitz & Thomas Paust, Sartorius Stedim Biotech


Agenda

Benefits of Disposability

Existing & Emerging Single-use Technology

Example Cases

Conclusion


Benefits of Disposability

4


Benefit – Risk Reduction

Risks (drug efficacy, approval)

CAPEX Motivation

5


MediaMedia Filtration

Media Bags

Upstream

BioReactors

HarvestingContaminant

Removal

Fermentation/Cell Culture

Concentration TargetPurification

Purification

Viral Removal

SterileFiltration

Form/Fill

Buffer Prep/Filtration

$ k $ M $ M $ k $ kPossible Investment Costs$ k - MPossible Validation Costs

Potential Costs for a Process per m²: $ 60 - 100

Source: S.J. Tarnowski, PhD, ImClone, San Diego, 2001

Benefit - Capital Investment Reduction

6


Benefit – Set-up Time ReductionExample: Cell Culture Media Hold

7


Benefit – Cleaning/Protection of the End-userIncreasing Potency of Drug Products

Fraction of Daily Dose Permitted

Topical products 1/10th-1/100th Oral products 1/100th-1/1000thInjections, 1/1000th-1/10,000thophthalmics

Research, 1/10,000th-1/100,000thinvestigationalproducts

Source: PDA Technical Report #29

Source: FDA CDER, Florida office, 2009

8


Benefit – Environmental Impact ?

Source: Sinclair; Leveen, et.al.; The Environmental Impact of Disposable Technologies, The Biopharm International Guide, 11.2008

9


Single-use LimitationsVolume [L]

Phases

104

103

102

101

100

10-1

Development Pilot Phase III/ProductionClinical Material (Phase I – II)Screening

Trends:Higher Expression Rates

Increasing Titers & Personalized Medicine

Reduction inProcess Volume10-2

hybri

d syst

ems

multi-u

se sys

tems

single

-use s

ystem

s

10


Existing Technology – Benefits vs. ShortcomingsBenefits

☺ Reduced CAPEX

☺ Reduced cleaning

☺ Minimal set-up

☺ Reduced down-time, i.e. increased equipment utilization

☺ Reduced foot-print needs

☺ Increased flexibility/multi-purpose use

☺ End-user protection

Shortcomings

Extractable/Leachable

Scalability (in instances)

Mechanical strength

Sensor stability

Performance comparability

“The great unknown”

Source: Aspen Brook Consulting, 2009


Existing & Emerging Single-use Technologies

12


Source: ATMI

Existing – Single-use Process Components

Source: Pall

Source: GE Healthcare

Source: Xcellerex

Source: Millipore

Source: Sartorius Stedim

Source: ThermoFisher

Source: Cuno

Source: NewAge Industries

13


Emerging – Single-use Unit Operations


Source: Millipore

Next Integration of SUUnit Operationsto a Process ?!

14


Single-use Technology Positions (comparison of SU technologies)

Low Level of Experience High

High

Levelof

Use

Low

Filter Capsules

PolymericTubing

RFID

UnitOps.

SUBags

SUMixing

Chroma-tography

Bio-reactor

Connector

SUValves

SUPumps

SUSensors

SUFilling

Technology & Experience Trend

SUTFF

Source: Aspen Brook Consulting, 2009

15


Validation/Qualification Requirements

γ Sterilization Validation

Extractables Analysis

Actual Product Contact & Duration

RP-HPLC, GC-MS, FTIR

USP Class VI

Chemical Compatibility Physical Testing

Burst TestLeak Test, Seal Strength Film Thickness

Endotoxin Testing

Permeation Analysis

Long-term Shelf Life

Unspecific Adsorption

Particle Release

1- Polyethylene Terephthalate (PET) 2- Polyamide (PA) 3- Ethylene Vinyl Alcohol (EVOH) 4- Ultra Low Density Polyethylene (ULDPE)


Example Cases

17


Single-use vs. Multi-use (water consumption w/o steam needs)

Source: BioPharm Services

60 % of the costsof a re-usable system

Major cost component:Water,also a common major bottleneck

18


Cleaning/Set-up Delay Impact (actual case)

Biotech facility produces max 4 batches, often only 3Each batch has an estimated market value of $ 30 Mio

It turned out the bottlenecks are holding tanks:Cleaning/Set-up/Sterilization Time > 8 hoursadditional rinse WFI availability limitations

A disposable holding and/or mixing systemwould be set-up in minutes

This improvement would mean:min 1 batch more/week $ 1.5 Bio additional revenue

19


Single-use vs. Multi-use (time to implementation)

Source: Stephen Brown, Vialis, PDA/EMEA Meeting 2009

The time to implement a single-use fermentation system is greatly reduce in comparison to a multi-use system:

2 - 3 years

4 - 7 months

Main reasons for the 5 fold reduction:

• Qualification of the equipment

• Cleaning validation

• Qualification of set-up

20


Costs of Polishing: Resin or Membrane ?Anion exchanger polishing step (flow through) for the removal ofDNA, HCP, Protein A and endotoxins

Source: Gottschalk, PhD

21


Cost Evaluation Tools

End-user Information

- Type of Process(e.g. mAb)

- Brief Process Description(e.g. Block schematic)

- Basic Process Data (# Batches, Titre, ...)

- other InformationsOutput for end-user

- Process Flow Diagram

- Equipment List

- Standard Layout Studies

- Total Investment Cost

- Capital investment

- Operational costs (disposables vs. re-usable)Vendor input

- Equipment Data

- Pricing Informations

- Process Know-how

- Process Pattern

- Other information

22


Possible Process Schematic

Source: Xcellerex

Benefits in this Scenario:• Lower HVAC ceiling area• Reduced energy costs• Contained system design• Lower risk by human intervention• High production flexibility

23


Possible...?Production Micro-Sites using single-use technology to produce,for example, a vaccine at the point-of-use

Source: GE Healthcare


24


Conclusion

Some disposable technology has been used successfully for decades

Some components and validation requirements still pose the „great unknown“

New technologies are developed to fill existing process gaps –a 90% disposable process might be possible

Disposability creates major advantages, by reducing costs, increasing production utilization and protect end-users


A pessimist sees the difficulty in every opportunity;

an optimist sees the opportunity in every difficulty.

Sir Winston Churchill

[email protected]@Sartorius-Stedim.com

Thank you

pda annual meeting orlando march 2010 mj

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