Single Use technologies and their

impact in Biomanufacturing

Marcel Bassil, Ph.D, C.C.R.P.

Associate Director Biotech

During the past 10 years, single use systems and devices have

emerged as a key change agent in the biomanufacturing

landscape.

Acceptance in R&D and scale-up has been driven by their

effectiveness.

single use products (Disposables) have pushed beyond an

early-stage technology, and are poised to emerge into the

much larger, GMP commercial-scale operations.

Langer, ES. 2011.Eighth Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, BioPlan

Associates, Inc., Rockville.

Introduction

Some Examples

WuXi Biologics, CMO producing antibodies and proteins. Supplied

by Merck Millipore

Shire’s Lexington facility has installed a 2000 L commercial Single use Bioreactor.

Roche Diagnostics GmbH (Mannheim, Germany) recently implemented a single-use

assembly (pre-assembled, gamma-irradiated, ready-to-use, tank-to-needle concept)

In 2013, Catalent, a contract manufacturer, opened a 100,000 square foot clinical scale

manufacturing facility based on single-use technology

Merck Serono uses Millipore SUS for the production of the Biopharmaceutical

molecules

1)Paul Thomas ,On Shire, Pharmaceutical Manufacturing, Single-Use and Simplicity, Feb, 2012

2)Bioprocessing and Sterile Manufacturing, Advanstar Pharmaceutical, 2014

3) PharmTech, “Catalent Moves Forward With New Single-Use Biopharmaceutical Manufacturing Facility”, August 28, 2013

The market for single-use technologies is growing. In a recent survey by

Bioprocess International on behalf of BPSA (Bio-Process Systems Alliance),

the biggest market driver for switching to single-use technologies is the

elimination of cleaning and sterilization cycles.

According to BCC Research, the global SUT market was valued at just $1.7 billion for

2014. This market is forecast to grow to more than $3 billion by 2019, to register a

healthy 5-year compound annual growth rate (CAGR) of 11.7%.

The biggest increase will come in the disposable mixing systems segment.

This market is forecast to jump to $301.3 million by 2019.

Market

By adopting single-use technologies, companies can lower the

costs of turning a manufacturing operation around after campaigns

by reducing or eliminating the need for expensive stainless steel

equipment and the associated expenses of installation and cleaning.

Comparing single-use technologies with stainless steel for g/l cell

titers, a company can potentially realize savings of almost 50% in

total cost of goods (including amortized capital, labor, consumables,

water, utilities and other plant infrastructure requirements).

A 2008 and 2012 studies found that disposables required:

87% less water;

21% less labor (primarily by reducing CIP activities);

38% less space;

29% less energy to run.

1)The Environmental Impact of Disposable Technologies, Andrew Sinclair, Lindsay Leveen, Miriam Monge,

anice Lim, Stacey Cox, Biopharm International, November 2008.

2)Environmental Considerations for Biomanufacturing Processes, Industry Pharma, February 2008.

In terms of the environmental footprint of a stainless steel-based bioprocessing

facility to one based on disposables,

Comparison

Timeline: Applications of Single Use Bioprocess Equipment

The Shift in Materials

Antibodies, proteins, vaccines, cell therapy, and gene

therapy all fall into categories of molecules that can

benefit from being produced in SUS

Products that can be manufactured in

fully single-use, end to end processes.

Since single-use equipment can be pre-sterilized by the supplier prior to use,

there is the potential elimination of classified environments from the

manufacturing process.

single-use systems can connect two unit operations, thereby minimizing hold

time and enabling continuous processing.

single-use systems are shown to reduce overall operating costs by minimizing or

eliminating the need for clean in place (CIP)/sterilize in place (SIP).

Pros

analytical quality control costs, specifically for raw materials

and improving facility utilization time.

This will reduce the amount of time staff must spend on

preparation, set-up, validation and documentation, along with

the related costs.

Single-use systems also enable increased productivity and

reduced cost of goods.

Companies turn to single-use technologies because they

want more flexibility with varied batch sizes, faster

processing times and more efficient unit operations.

Reducing water consumption

Ability to run multi-molecules in the same facility

Small-scale commercial

production with low

numbers of batches per

year

Closed systems and reduced environmental constraints

clearly reduce capital cost of a facility and ongoing

HVAC/energy costs

reduced gowning

requirements

1)Paul Thomas ,On Shire, Pharmaceutical Manufacturing, Single-Use and Simplicity, Feb, 2012

support systems are

reduced

Single use Bioreactor, 50 Liters

Simplified,

1-Flexible Tubing

2-Integrated Filters

3-Choice of Probes/Sensors

4-Fast Turnaround

5-New Process = New Bag

Upstream

Trends that we see in the use of SUS in downstream

processing for the near future.

1-Chormatography columns (resins), Filtration, Formulation and filling

systems.

2-This standardization will also reduce the risk of unanticipated failures

related to untested designs or products.

3-Reduce risk of cross contamination and carryover due to inadequate

cleaning steps.

1) S.Haigney, "Using Single-Use Technologies in Downstream Processing," BioPharm International, 28 (7) 2015

2) A. Trotter .Single-Use and Disposable Systems and Devices in the Biopharm Industry, Trotter Biotech Solutions, 2012

Batch cross contamination through

inadequate CIP procedures or failure

to implement proper SOP can be

reduced or eliminated by SUS

The number and frequency of bacterial

contaminated lots has shown to be

reduced using SUS, (Media Fill Contamination PDA

2001 Aseptic Process Survey.)

In Demand: Prefilled Syringes (PFS)

Advantages of prefilled syringes A prefilled syringe is a single–dose packet of a parenteral drug attached to a

needle by the manufacturer,.

although traditionally used

for vaccines and blood

stimulants, they are now

used in a wide range of

therapeutic areas.

main advantage when

compared to single glass vials

is their ease of use. The user

does not need to withdraw the

required amount of vial from

a vial before using the

syringe.

PFS reduce human

error and administer

drugs with a higher

degree of accuracy

Dr Selma Khamassi, the head of the WHO team for injection safety will annouce a policy to introduce

the system for all injections by 2020

pre-use and post-use integrity testing

visible and non-visible particulates.

The long-term storage of solutions, such as buffers or cell-

culture media, in single-use systems can generate

extractables and leachables, which may cause impurities.

Solution : prepare buffer or media on an as-needed basis by using

solid materials that are customized for one single-use tank, rather

than concentrated buffer solutions that are already in liquid form

Challenges

Acceptance within the GMP community has grown, from 1% of the

biopharmaceutical industry in 2010 to 37% in 2015.

1)Langer E. 12th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production. Research and Markets: Dublin,

Ireland. 2015.

2) Single-use Technology in Biopharmaceutical Production, Dechema Biotechnologie, 2011

Regulatory and GMP aspects

All major suppliers of SUS follow the cGMP/regulatory requirements

(GE Healthcare, Merck Millipore, Sartorius Stedim Biotech, Pall Corporation,

Thermoscientific, etc…)

-EU GMP Guide Part II,

-21 CFR 211.65(a)

-ICH (Q7A)

Single Use Systems

To Resume

We should embrace the SUS and its technology and use to

our own interest to produce or develop new

biopharmaceutical products (Innovators or Biosimilars)

A learning period is

important in all new

activities: SUS are no

exception

General References:

1-Gerald Kierans, “Using disposable single-use systems for high volume manufacturing”, Pfizer Global Supply, May 22th, 2014

2-Disposable & Single Use Technology, Pharma IQ Sector Report & Resources 2011

Thank You !!!