GE Healthcare

Validation guide
ULTA Prime GF
capsule and cartridge filters

28-9094-72 AA
Table of contents
Introduction 3
Quality policy 3
Quality assurance 3

Product traceability 4
Summary of test methods 5
Preparation of pharmaceutical grade filters 6
Pharmaceutical grade standard 6
Quality of purified water used in the preparation of pharmaceutical grade filters 6

Certificate of Quality 7
Product coding and range for ULTA Prime GF cartridges 8
Product coding and range for ULTA Prime GF capsule filters 8
Capsule dimensions 9
Product specifications 9
Application 9
Materials of construction for ULTA Prime GF cartridges and capsules 9
Filter media 9
Flow Characteristics 10
Operating temperatures and pressures 11
Steam sterilization 11
Autoclave 11
Steam in Place (SIP) 11
Tests for BioCompatibility 11

Determination of micron ratings 12

Chemical compatibility 13
Chemical compatibility summary chart for pharmaceutical products 13
Chemical compatibility user instructions and notes 15

2 Validation Guide 28-9094-72 AA

Introduction Quality policy
Clarification or pre-filters that come into contact with pharmaceu- Quality assurance
tical products, such as injectable or infusion liquids, must conform
Quality is of paramount importance to GE Healthcare. The filtration
to strictly defined quality standards.
products are manufactured under controlled environmental
By using filter technology that conforms to the standards laid conditions to the highest quality regimes and are subjected to
down by the various certifying bodies, the quality of the final a demanding program of Quality Assurance. Inspection and test
product can be assured. Contamination can also be prevented protocols are implemented from vendor assessment, specification
from entering the final product by its comprehensive removal at and receipt of raw materials, through every stage of the manu-
each stage of the primary and secondary process. facturing process culminating in a nondestructive integrity test
of the filter prior to packing and release.
When pharmaceutical grade filters are used in the manufacture
of products, the interactions between product, filter and process Every stage of the manufacturing process has well defined assembly
must be fully investigated and validated. protocols laid down, thus ensuring operational repeatability.

Guidelines for validation can be sourced from publications issued GE Healthcare’s responsibility as a manufacturer of quality
by the FDA, EMEA, USP, EP, BP, PDA1 etc. This Validation extends beyond the manufacturing site, through a world-wide
Document has been produced with these guidelines in mind to network of filter and separation specialists.
enable the end user to incorporate this information within their
The Quality Assurance Department operates with a well-equipped
own validation documentation or standard operating instructions
Laboratory Services Department, in which specialized personnel
for the process.
are employed to perform the essential quality inspections. The
This Validation Document shows that ULTA™ Prime GF surpasses manufacturing site has been assessed by the British Standards
the product specification requirements that have to be imposed Institution and is registered to BS EN ISO 9001:2000, which defines
on pharmaceutical grade filters. the standards for quality systems, model for quality assurance in
design, development, production, installation and servicing.

As a concerned environmentally aware manufacturer, the site

is also audited and certified to BS EN ISO 14001:1996 for its
Environmental Management System.

1
FDA, EMEA, USP, EP, BP, PDA – Food and Drug Administration, European Medicines Evaluation Agency, United States, European, and British
Pharmacopoeia, Parenteral Drug Association.

Validation Guide 28-9094-72 AA 3

Product traceability
To enable full traceability of all pharmaceutical grade filter prod-
ucts, each filter module is marked with an individual serial num-
ber. In addition, each filter product is marked with a lot number,
product code and general description which is also shown on
both the protective polyethylene bag in which the filter is sealed
and on the outer surface of the final product packaging.

4 Validation Guide 28-9094-72 AA

Summary of test methods
A number of the critical procedures used within this validation
document are based on external methods sourced from publica-
tions issued by the USP, EP, FDA, ISO2 and ASTM3. The remaining
procedures are in-house methods prepared using GE Healthcare’s
relevant experience and industry accepted standards in the fine
filtration field. The comprehensive nature of these procedures
ensures high batch to batch compliance to the specification.

2
ISO – International Organisation for Standardisation
3
ASTM – American Society for Testing and Materials
4
ACFTD – AC Fine Test Dust

Validation Guide 28-9094-72 AA 5

Preparation of pharmaceutical Quality of purified water used in the preparation of
pharmaceutical grade filters
grade filters
The current USP and EP standards for Purified Water and Highly
Pharmaceutical grade standard Purified Water specify a maximum conductivity of 1.1 ÌS/cm @
ULTA Prime GF filters must meet stringent standards to be 20°C (68°F) and a maximum TOC (Total Organic Carbon) content
certified P-grade product by GE Healthcare. The standards that of 0.5 mg (500ppb) of carbon per liter.
must be met are:
The water used in the flushing stages of pharmaceutical grade
• Effluent quality following a purified water flush must also be filters exceeds these Pharmacopoeial requirements.
met as determined by the following tests:
In addition, two other tests are carried out on samples taken from
– Test for oxidizable material per USP 23 Purified Water. point of use and from a number of points in the supply pipework:

– Test for bacterial endotoxins using a gel clot LAL • A Membrane Filtration Method Standard Plate Count Technique,
(Limulus Amoebocyte Lysate). to establish the microbial content.

– Test for particulates. • A gel clot LAL (Limulus Amoebocyte Lysate) test, for detection
of bacterial endotoxins at 0.125 EU/ml sensitivity.
– Test for TOC (Total Organic Carbon).

– Test for Conductivity.

• All components conform to the Biological Safety Standards

identified in USP <88> to Class VI-121°C levels.

• All P-grade filters are flushed with a high flux of purified water
prior to despatch, as a guarantee of product cleanliness.

6 Validation Guide 28-9094-72 AA

Certificate of Quality
To certify that GE Healthcare’s ULTA Prime GF filter products
meet the highest pharmaceutical quality and performance
requirements, a Certificate of Quality is issued.

A specific Certificate of Quality is issued for ULTA Prime GF capsules.

Validation Guide 28-9094-72 AA 7

Product coding and range for
ULTA Prime GF cartridges
Represented below are details of the product code structure for
ULTA Prime GF cartridges. This product code structure indicates
cartridge sizes, micron ratings, end-cap configurations and ‘O’ ring
materials that are available within the product range.

Device Type Media Type Special Detail Special Micron Rating Size Code Cartridge O-ring

Digit 1 2 3 4 5 6 7 8 9 10 11 12

C = Cartridge G F Hyphen - A Hyphen 9 6 H = 5” 0 = Code 0, 222 Double O-ring 0 E = EPDM

D = Disc 0 1 7 = Code 7, 226 Locking Tab, S = Silicone
0 2 Double O-ring/ Fin* (Flat Top
0 5 1 = 10” 5” Only)
0 7 2 = 20”
1 0 3 = 30”

Example: ULTA™ Prime GF, 0.6 µm, 10” 226, Silicone O-ring
CGF-A-96170S Hyphen 4 7 0 Disc

Product coding and range for

ULTA Prime GF capsule filters
Represented below are details of the product code structure for
ULTA Prime GF capsules. This product code structure indicates
capsule sizes, micron ratings, connection configurations, sterility and
material options that are available within the product range.

Device Type Media Type Special Detail Special Micron Rating Size Size End Fittings
Inlet Outlet
Digit 1 2 3 4 5 6 7 8 9 10 11 12

K = Capsule G F Hyphen - A Hyphen 9 6 T = 1.5” TC T = 1.5” TC

0 1 G = SHB*
G = SHB*
0 2 H = 1/2” HB
H = 1/2” HB
0 5 02 = 2”
0 7 04 = 4”
1 0 06 = 6”

Example: ULTA™ Cap PP, 1.0 µm, 4”, 1/2 Hosebarb inlet, 1.5 inch TC outlet * Stepped Hose Barb 1/4”
KGF-A-0104HT

8 Validation Guide 28-9094-72 AA

Capsule dimensions

Product specification Component Material of construction

Filtration Media Borosilicate Glass Microfiber
Application with Acrylic Binder5
All products within the ULTA Prime GF range, cartridge, capsule Upstream Support Polypropylene
and disc have been designed for use in pharmaceutical applica-
Downstream Support Polypropylene
tions for prefiltration and clarification duties. Whilst these prod-
ucts present minimal fiber shedding potential as required by Inner Support Core Polypropylene
cGMP guidelines, when they are used with 0.20um or 0.45um Outer Protection Cage Polypropylene
membrane based products downstream in the process, the ULTA Endcaps Polypropylene
Prime GF products are seen to meet the FDA guideline
Endcap Insert 316 Stainless Steel
21CFR211.72 for non fiber-shedding filters.
Standard O’rings Silicone
Materials of construction for ULTA Prime GF Capsule Body Polypropylene
cartridges and capsules Capsule Vent Seals Silicone
All materials used in the construction of ULTA Prime GF products Filling Bell Polycarbonate
that have product contact have met the requirements of the cur-
rent USP Biological Reactivity Tests, In Vivo to Plastics Class VI-
121°C. Filter Media
The high efficiency of each ULTA Prime GF filter cartridge and cap-
All jointed surfaces are assembled by the use of heat sealing tech-
sule is achieved using a composite structure offering high voids
nology. No resins or binders are used in the manufacture of the fil-
volume. High dirt holding capacity results from the depth of filtra-
ter and no surfactants are added to aid wetting.
tion within each composite layer giving the extended life of ULTA
Prime GF from coarse particulate prefiltration to very fine ultimate
retention at the filters quoted micron rating.

5
0.6μm Grade includes a dioctyl sodium sulfosuccinate surfactant.

Validation Guide 28-9094-72 AA 9

Flow characteristics
The effective filtration area of a standard 250mm (10”) module is
up to 0.57 m2 (6.4 ft2), dependent on the grade selected.

10 Validation Guide 28-9094-72 AA

Operating temperatures and pressures
Below are the recommended maximum differential operating
pressures at various temperatures:

Differential pressure Operating pressure capsules

Temperature Cartridges Liquids (gases)
°C °F bar psi barg psig
20 68 5.00 72.5 5.00 (4.00) 72.5 (58.0)
40 104 4.00 58.0 5.00 (4.00) 72.5 (58.0)
50 122 3.00 43.5 3.00 (3.00) 43.5 (43.5)
70 158 2.00 29.0 Not Recommended

Steam sterilization
Autoclave
Autoclave temperature Number of Cycle time
Product format °C °F cycles Minutes at temp.
Cartridges 121 250 10 30
Capsules 121 250 10 30

To maximize cartridge and capsule life, a slow exhaust cycle

is recommended.

Steam in Place (SIP)

SIP temperature Number of Cycle time
Product format °C °F cycles Minutes at temp.
Cartridges 121 250 10 30
Capsules Do not Steam in Place

To maximize the life of the cartridge, the differential pressure across the cartridge should
not exceed 0.30 bar (4.4 psi) at 121°C (250°F). For new applications it is recommended
that GE Healthcare guidance for the method of steam sterilization be followed.

Tests for biocompatibility

An independent research establishment has assessed the biological
safety associated with the use of ULTA Prime GF filters designed
for processing pharmaceutical products. The materials used in the
construction of ULTA Prime CG products meet the requirements of
the current USP <88> Biological Reactivity tests at Plastics Class
VI – 121°C.

Validation Guide 28-9094-72 AA 11

Determination of micron ratings
Particle removal efficiencies of ULTA Prime GF filter cartridges
have been determined by challenging with a standard aqueous
suspension of ACFTD (AC Fine Test Dust) with particle size as
defined in table 1, using in-line laser particle counters.

Ratings are based on Beta ratio of 5000 or >99.98% efficiency at

the micron size specified.

Testing is carried out in accordance with ASTM F795-88 Standard

Practice for Determining the Performance of the Filter Medium
Employing a Single-Pass, Constant-Rate, Liquid Test.

Table 1. ACFTD Specification (SAE J 726 Fine ISO 12103 Pt 1 A2 Fine) s.g. 2.6 – 2.7 g/cm3

Particle size Volume % smaller than Approximate number of particles per gram in band
10
1 2.5 - 3.5 5 x 1010
2 10.5 - 12.5 3 x 1010
3 18.5 - 22.0 1 x 109
4 25.5 - 29.5 4 x 109
5 31.0 - 36.0 1 x 108
7 41.0 - 46.0 8 x 108
10 50.0 - 54.0 1 x 107
20 70.0 - 74.0 4 x 106
40 88.0 - 91.0 4 x 106
80 95.5 - 100 7 x 10

12 Validation Guide 28-9094-72 AA

Chemical compatibility
Testing has been carried out that shows ULTA Prime GF filters and
capsules have a broad range of chemical compatibility with
chemicals commonly used in the pharmaceutical industry.

Chemical compatibility summary chart for

pharmaceutical products
ULTA Pure SG ULTA Pure HC ULTA Prime CG ULTA Prime PP ULTA Prime GF
Acetic Acid 3.5N C C C C C
Acetic Acid 8.75N - - - C C
Acetic Acid Conc. 17.5N - - - C C
Acetone NC NC NC C C
Acetonitrile - - - C LC
Acidbrite 4 (Diversey) 3.0% v/v - - - C C
Ammonium Hydroxide 8N LC LC LC C C
Ammonium Oxalate 0.07N - - - C C
Amyl Acetate LC LC LC C LC
Aqueous Ammonia 15.5N LC LC LC C LC
Benzyl Alcohol - - - NC NC
Benzyalkonium Chloride 0.1% - - - C C
Boric Acid, Saturated - - - C C
Butan-1-ol C C C C C
Butan-2-ol C C C C C
Carbon Tetrachloride - - - NC NC
Chloroform NC NC NC NC NC
Cyclohexane - - - NC NC
1,4 - Dioxane - - - C LC
Diverflow (Diversey) 3% v/v C C C C NC
Diversey 212G 0.6% v/v - - - C
Divosan Forte 0.5% v/v C C C C C
Divosan XT 1% v/v - - - C C
Ethanol C C C C C
Ethanol 45% C C C C C
Ethyl Acetate NC NC NC LC LC
Formaldehyde 0.3% C C C C C
Formaldehyde 37% - - - C C
Formic Acid Conc. - - - C NC
Glycerol C C C C C
Hexane - - - NC -
Hydrochloric Acid 1N C C C C
Hydrochloric Acid Conc. - - - C NC
Hydrochloric Acid Conc. 13% - - - - -
Hydrogen Peroxide - - - C -
Hydrogen Peroxide 10 Vol C C C C C
Hydrogen Peroxide 100 Vol - - - C C

C= Compatible LC= Limited Compatibility NC=Not Compatible

Validation Guide 28-9094-72 AA 13

 ULTA Pure SG ULTA Pure HC ULTA Prime CG ULTA Prime PP ULTA Prime GF
Methanol C C C C C
Methyl-iso-Butylketone NC NC NC C C
Methylene Chloride @ 40C - - - LC L
Nitric Acid 2N 14.4% C C C C C
Nitric Acid 15.8N - - - C NC
Ozone NC NC NC - -
Paraffin Yellow - - - C LC
Pentane - - - LC LC
Peracetic Acid 0.5% - - - - -
Peracetic Acid 4% C C C C C
Perchloroethylene NC NC NC - -
Petroleum Spirits - - - NC NC
Phenol (aq) 0.5N - - - - -
Phenol 5% - - - C
Phenol 0.25% - - - C
Polyethylene Glycol 600 NC NC NC LC NC
Polyglycol 2000-E - - - - -
Potassium Dichromate 0.1N - - - C C
Potassium Iodine 0.6N - - - C C
Potassium Hydroxide 10N LC LC LC C NC
Potassium Permanganate 0.1N C C C C NC
Propan-1-ol C C C C NC
Propan-2-ol C C C C N
Propan-2-ol, 60:40 H2O C C C C N
Pyridine NC NC NC C NC
Sodium Chloride 0.5N C C C C C
Saline Lactose Broth C C C C C
Sodium Hydroxide 2N 8% C C C C C
Sodium Hydroxide 7N 28% NC NC NC C N
Sodium Hypochlorite (14% Free Cl2) C C C C C
Sodium Thiosulphate 0.1N - - - C C
Sulphuric Acid 1N C C C C LC
Sulphuric Acid Conc. NC NC NC LC LC
Sulphurous Acid NC NC NC - -
Toluene NC NC NC NC -
1,1,1 Trichloroethane - - - - -
1,1,2 Trichloroethane NC NC NC LC LC
Trichloracetic Acid 80% - - - C LC
Trichloracetic Acid 5N - - - - -
Xylene LC LC LC NC NC

This chemical compatibility chart is intended for use as a guide only. Factors such as temperature, pH, concentration, system pressures and exposure times can all have an effect on
the chemical compatibility of our filter products. Though we believe this information to be current and of value in screening the filter media against liquid solutions for general com-
patibility, no warranty is given or implied with respect to this information.
Note that the temperature at which these recommendations were given is 25C. For compatibilities at higher temperatures please contact GE Healthcare technical services.
Note that compatibility recommendations for each cartridge apply only to the filter media of that cartridge. Liquid compatibility for core and o-ring materials must be determined by
following the compatibility for those core and o-ring materials.
C= Compatible
LC= Limited Compatibility
NC=Not Compatible

14 Validation Guide 28-9094-72 AA

Validation Guide 28-9094-72 AA 15
GE, imagination at work and GE monogram are
trademarks of General Electric Company.
ULTA™ is a trademark of GE Healthcare companies.
© 2007 General Electric Company–All rights reserved.
First published Feb. 2007
All goods and services are sold subject to the terms and
conditions of sale of the company within GE Healthcare
which supplies them. A copy of these terms and
conditions is available on request.
Contact your local GE Healthcare representative for the
most current information.
GE Healthcare Bio-Sciences AB
Björkgatan 30, 751 84 Uppsala
Sweden
GE Healthcare Europe, GmbH
Munzinger Strasse 5, D-79111 Freiburg
Germany
GE Healthcare Bio-Sciences Corp.
800 Centennial Avenue, P.O. Box 1327
Piscataway, NJ 08855-1327
USA
GE Healthcare Bio-Sciences KK
Sanken Bldg., 3-25-1, Hyakunincho
Shinjuku-ku, Tokyo 169-0073
Japan

For contact information for your local offi ce,

please visit: www.gelifesciences.com/contact

GE Healthcare Bio-Sciences AB
Björkgatan 30
751 84 Uppsala
Sweden
www.gelifesciences.com

28-9094-72 AA 06/2007