Small volume parenteral process.

Products. Services. Expertise.

Small Volume Parenterals (SVP) include a wide variety of traditional and

bioengineered drugs. SVPs are typically packaged as small vials (<100 mL),
pre-filled syringes, ampules or lyophilized powders. A careful selection of raw
materials and excipients is necessary to achieve the required quality of the final
product. With our EMPROVE® bio and EMPROVE® exp portfolio, you can select
ingredients as close as possible to the desired specification and purity of the
final product.

Many SVPs are heat labile, requiring aseptic processing. Sterile filtration is
performed after compounding or at the filling head. An extra measure of sterility
assurance can be achieved by using sterilizing grade filters at both locations.
Prefiltration reduces bioburden and particles that could prematurely clog final
filters. Final filtration provides a sterile filtrate per current regulatory guidelines.
A final, sterilizing grade filter should provide a sterile filtrate without altering the
efficacy or potency of the drug product. This is best accomplished by using filters
with low Active Pharmaceutical Ingredient (API) binding, low extractables, and
that are non-pyrogenic. In addition, sterilizing filters must be easily testable for
integrity, and either readily sterilizable or supplied pre-sterilized. Final filters used
in filling machines must have a rigid support structure to prevent media flexing
during pulsed flow fill operations in order to prevent particle release, after-drip or
other dispensing problems.

No guide will replace the need to conduct process development and optimization experiments. The unique
nature of every process stream combined with application and regulatory requirements play a part in
determining the optimum process solutions. Use this selection guide as a starting point for selecting and
sizing the most appropriate EMD Millipore solutions.

EMD Millipore is a division of Merck KGaA, Darmstadt, Germany

Small volume parenteral process. Products. Services. Expertise.

Lynx® S2S
Prefiltration/ connectors
Disposable formulation tank Sterile filtration Final fill
Gamma-irradiated single-use

Bioburden reduction

• EMPROVE® raw materials for pH and tonicity adjustment, buffers, stabilizers, surfactants, preservatives and solvents such • Durapore® 0.45 µm hydrophilic filters • Millipak® disposable filter with Durapore® 0.22µm membrane • Mobius® single-use fill finish
as for instance: • Opticap® XL capsule filters with • Opticap® XL capsule filters with Durapore® 0.22µm membrane assemblies
- D(+)-Glucose monohydrate suitable for use as excipient EMPROVE® exp Ph Eur, BP, USP Millipore Express® HPF membrane • Millipore Express® 0,2 µm small scale capsules • Millipore Express® SPG
- Glycine cryst. suitable for use as excipient EMPROVE® exp Ph Eur, BP, JP, USP • Mobius® 2D and 3D assemblies and • Integritest® 4 series automated filter integrity test instrument hydrophilic filters
- Parteck® SI 400 LEX (Sorbitol) suitable for use as excipient EMPROVE® exp Ph Eur, BP , NF, JP storage system • Mobius® 2D and 3D assemblies and storage systems • Mobius® 2D and 3D assemblies
- tri-Sodium citrate dihydrate suitable for use as excipient EMPROVE® exp Ph Eur, BP, JP, USP, E 331 • NovaSeptum® sampling systems and storage systems
- D(-)-Mannitol low in endotoxins, suitable for use as an active pharmaceutical ingredient EMPROVE® api Ph Eur, BP, USP, JP • Bacterial retention testing • Particle shedding validation
- Sucrose low in endotoxins suitable for use as excipient EMPROVE® exp Ph Eur, BP, JP, NF services
• Drug-product based integrity testing
- Sodium chloride low in endotoxins suitable for use as excipient EMPROVE® exp Ph Eur, BP, JP, USP • Filter and assemblies extractible analysis
• Mobius® single-use mixing solution • Chemical compatibility testing
• Mobius® powder delivery system
• NovaSeptum® sampling systems
• Mobius® 2D and 3D assemblies and storage systems

Lynx® ST connectors

Lynx® ST
Prefiltration/ connectors
Stainless-steel formulation tank Sterile filtration Final fill
Bioburden reduction
Steam-sterilized equipment

• EMPROVE® raw materials for pH and tonicity adjustment, buffers, stabilizers, surfactants, preservatives and solvents such • Milligard® cartridge filters with • Millidisk® and Millipak® cartridge filters with Durapore® • Sterilizing-grade Aervent® filters
as for instance: 0.5/0.2 µm membrane 0.22µm membrane • GMP manufactured solutions for
- D(+)-Glucose monohydrate suitable for use as excipient EMPROVE® exp Ph Eur, BP, USP • Series 3000™ single-round housings • Opticap® XL capsules and cartridges with Millipore Express® cleaning in place and storage1
- Glycine cryst. suitable for use as excipient EMPROVE® exp Ph Eur, BP, JP, USP • Millipore Express® HPF hydrophilic 0,2 µm membrane • Particle shedding validation
- Parteck® SI 400 LEX (Sorbitol) suitable for use as excipient EMPROVE® exp Ph Eur, BP , NF, JP filters • Series 2000™ sanitary Millidisk® cartridge housings services
- tri-Sodium citrate dihydrate suitable for use as excipient EMPROVE® exp Ph Eur, BP, JP, USP, E 331 • Custom filtration skids • Optiseal® cartridge filters with Durapore® 0.22µm membrane
- D(-)-Mannitol low in endotoxins, suitable for use as an active pharmaceutical ingredient EMPROVE® api Ph Eur, BP, USP, JP • GMP manufactured solutions for • Optiseal® sanitary cartridge housings
- Sucrose low in endotoxins suitable for use as excipient EMPROVE® exp Ph Eur, BP, JP, NF cleaning in place and storage1 • NovaSeptum® sampling systems
- Sodium chloride low in endotoxins suitable for use as excipient EMPROVE® exp Ph Eur, BP, JP, USP • Integritest® 4 series automated filter integrity test instrument
• NovAseptic® mixer • Custom filtration skids
• NovaSeptum® sampling systems • GMP manufactured solutions for cleaning in place and
• Sterilizing-grade Aervent® filters storage1
• GMP manufactured solutions for cleaning in place and storage1 • Bacterial retention testing
• Drug-product based integrity testing
• Filter extractible analysis
• Chemical compatibility testing

Provantage® services include process development, process validation, equipment qualification, and GMP drug production | EMD Millipore biopharmaceutical courses
We provide information and advice to our customers on application technologies and regulatory matters to the best of our
knowledge and ability, but without obligation or liability. Existing laws and regulations are to be observed in all cases by our
customers. This also applies in respect to any rights of third parties. Our information and advice do not relieve our customers of
their own responsibility for checking the suitability of our products for the envisaged purpose.

The holder of the manufacturing authorization shall ensure that the excipients are suitable for use in medicinal products by
ascertaining the appropriate good manufacturing practice.
This is particularly true if the material in a certain application is regarded as high risk excipient, for example in parenteral
dosage forms.

To place an order or receive technical assistance

In the U.S. and Canada, call toll-free 1-800-645-5476

For other countries across Europe and the world,

please visit www.emdmillipore.com/offices

For Technical Service, please visit:

www.emdmillipore.com/techservice

For other countries across Europe,

please call: +44 (0) 115 943 0840

www.emdmillipore.com

1
based on IPEC - PQG GMP guide for pharmaceutical excipients 2006.
Aervent, Durapore, EMPROVE, Integritest, Lynx, Millidisk, Milligard, Millipak, Millipore Express, Mobius, Opticap,
Optiseal, Parteck, and Provantage are registered trademarks of Merck KGaA, Darmstadt, Germany.
NovAseptic and NovaSeptum are registered trademarks of Millipore AB.
EMD Millipore, the M mark, Series 2000, and Series 3000 are trademarks of Merck KGaA, Darmstadt, Germany.
Lit No: PS5263EN00 Rev. B. © 2014 EMD Millipore Corporation, Billerica, MA, USA. All rights reserved.