3M Purification

3M Emphaze™™

AEX Hybrid Purifier

Capsules
Regulatory Support File
 Table of Contents
I. Regulatory Support Information ............................................................................................................... 2 
II. Drug Master File Reference ..................................................................................................................... 3 
III. Product Descriptions .............................................................................................................................. 3 
IV. Product Design and Materials of Construction .......................................................................................... 4 
A. Media .......................................................................................................................................... 4 
B. Capsules ...................................................................................................................................... 4 
C. Materials of Construction and Design Characteristics ...................................................................... 7 
V. Product Specifications and Operation Parameters ..................................................................................... 9 
A. Product Release Specifications ...................................................................................................... 9 
B. Installation and Operation Instructions.......................................................................................... 10 
C. Minimum Required Preconditioning Flush ..................................................................................... 10 
D. Pre-Use Sterilization / Sanitization ............................................................................................... 12 
E. Post-Use Sterilization .................................................................................................................. 13 
VI. Performance Verification ....................................................................................................................... 13 
A. Permeability ............................................................................................................................... 13 
B. Charge Capacity - DBC As a Function of Flow Rate; pH and Conductivity ........................................ 14 
C. BSA and DNA Dynamic Binding Capacity ...................................................................................... 15 
VII. Effluent Quality ..................................................................................................................................... 16 
A. USP <643> Total Organic Carbon (TOC) and Total Nitrogen (TN) .................................................... 17 
B. USP <645> Conductivity ............................................................................................................. 19 
C. USP <791> pH ........................................................................................................................... 19 
D. USP <232>/<233> and ICH Q3D Elemental Impurities ................................................................. 21 
E. USP <788> Particulate Matter in Injections .................................................................................. 22 
F. USP <85> Bacterial Endotoxin .................................................................................................... 23 
VIII. Shelf Life ............................................................................................................................................. 23 
IX. Regulatory Compliance ......................................................................................................................... 25 
A. USP <87> Biological Reactivity Test, In Vitro ................................................................................ 25 
B. USP <88> Class VI Biological Reactivity Test, In Vivo .................................................................... 25 
C. BSE/TSE .................................................................................................................................... 26 
X. Quality Assurance................................................................................................................................. 26 

1 
I. Regulatory Support Information
3M Separation and Purification Sciences Division is a global supplier in advanced filtration and purification solutions, offering a
wide range of products and services for various stages of pharmaceutical and biologics manufacturing.
3M, a U.S. based multinational high technology company with over 91,000 employees worldwide, has operations in more than
65 countries. The manufacturing facility for 3M™ Emphaze™ AEX Hybrid Purifiers, is registered to ISO 13485.
Columbia, MO, USA
Registered
 
This Regulatory Support File provides information pertinent to 3M™ Emphaze™ AEX Hybrid Purifiers. Contained herein are
detailed test methods, product specifications, product performance information and regulatory compliance documentation
related to pharmaceutical and biologics manufacturing processes. 3M supplied documentation can be used to support risk
assessments and regulatory submissions, prepare standard operating procedures, and streamline testing requirements, all of
which save time and cost for the manufacturer. The manufacturer of a pharmaceutical or biologic product is ultimately
responsible for registration through regulatory authorities in each country or region where their product will be produced or used.
The U.S. Federal Food, Drug, and Cosmetics Act designated the United States Pharmacopeia (USP) and the National Formulary
(NF) as official compendia for drugs marketed in the United States. USP-NF is a combination of two public compendia of
pharmacopeia standards. The International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) brings together the regulatory authorities and pharmaceutical industry to discuss various
aspects of drug registration and to achieve greater international harmonization. These standards form the primary basis for
technical information provided in this product support document. 3M completes a thorough annual review of the USP and ICH
standards and this regulatory support file to ensure that the claims and data package are current.
The intended and prohibited uses for Emphaze AEX Hybrid Purifiers are stated below. Customers must evaluate and determine
the suitability of the product for their applications.
Intended uses: Single use processing of aqueous based biological pharmaceuticals (drugs) and vaccines strictly following the
product operating instructions and cGMP requirements, where applicable. Customers must determine whether the 3M product is
suitable for a specific application based on a risk assessment that considers the product leachable characteristics and its impact
on drug safety.
Prohibited uses: Do not use as a component in a medical device that is regulated by any agency, and/or globally exemplary
agencies, including but not limited to: a) FDA, b) European Medical Device Directive (MDD), c) Japan Pharmaceuticals and
Medical Devices Agency (PMDA). Do not use in applications involving permanent implantation into the body, life-sustaining
medical applications, or applications requiring global Food Contact compliance.
Complementary product information, use and operating instructions and guidelines, and technical data can be found in Emphaze
AEX Hybrid Purifier product literature and product quality certifications. Further information can be obtained by contacting your
local 3M representative.

2 
 
II. Drug Master File Reference
3M™ Emphaze™ AEX Hybrid Purifiers are listed in a Drug Master File (DMF) registered with the United States Food and Drug
Administration (FDA).
The information contained in the 3M Drug Master File may be utilized by regulatory reviewers to support a New Drug Application
(NDA), Investigational New Drug Application (INDA), Abbreviated New Drug Application (ANDA), another DMF, an Export
Application, or supplements to any of these.
Permission by 3M for review of a Drug Master File is granted only to appropriate United States Food and Drug Administration
(FDA) or similar regulatory agency personnel as the document contains 3M proprietary information. Following the FDA Code of
Federal Regulations (CFR) Title 21 Section 314.420, before FDA may review the DMF in support of an application, 3M must
provide a letter of authorization permitting FDA to reference the DMF. The applicant is required to include a copy of the 3M letter
of authorization in its application. 3M is required to maintain a complete list of each applicant authorized to incorporate by
reference any information in the 3M DMF. 3M will update this Regulatory Support File as a routine aspect of product
maintenance. Customer notification is not required in these updates. However, 3M will notify all formally registered applicants of
any changes made to the DMF in the course of the required annual review. Contact 3M to initiate this process.

III. Product Descriptions

The Emphaze AEX Hybrid Purifier is a fully encapsulated single-use product designed to remove impurities from
biopharmaceutical process streams. The Emphaze AEX Hybrid Purifier is an all-synthetic, multi-mechanism clarifying product
containing both a Q-functional anion exchange nonwoven, and a microporous membrane for fine particulate removal. The
quaternary amine functional nonwoven provides mechanical sieving of particles, as well as a high anion exchange capacity for
reduction of negatively charged cell debris and soluble anionic contaminants including DNA, host cell proteins (HCP) and viruses.
The anion exchange media in the Emphaze AEX Hybrid Purifier is extremely hydrophilic such that the only mode of interaction
between the proteins and the media is electrostatic. This allows the balance between binding and recovery of proteins to be
controlled by pH and conductivity.
The Emphaze AEX Hybrid Purifier can be either autoclaved or base sanitized prior to use. Legacy versions of this product use the
same media and have equivalent performance, but are not designed to be autoclaved or base sanitized. Refer to the part
numbers in Table 1 and product literature included with the filter capsule to confirm compatibility.

Table 1. 3M™ Emphaze™ AEX Hybrid Purifier Ordering Guide:

Lab Capsules
Product Name BV0.3R BV1R BV8R-Luer BV8R-Sanitary
Catalog Number EMP101AEX020R EMP201AEX020R EMP301AEX020R EMP303AEX020R
Current Part Number 70020346857 70020346865 70020346873 70020346881

Scale-Up / Production Capsules

Product Name BV60R BV120R BV360R BV800R BV5600R
Catalog Number EMP503AEX020R EMP513AEX020R EMP533AEX020R EMP710AEX020R EMP770AEX020R
Current Part Number 70020346899 70020346907 70020346915 70020346923 70020346931

AEX Hybrid Purifier / Zeta Plus™ Manifold

Catalog Number 6129001
Part Number 70020262369

3 
IV. Product Design and Materials of Construction
All components used in the manufacture of 3M™ Emphaze™ AEX Hybrid Purifier capsules are traceable. Intermediate products
are packaged and labeled throughout the manufacturing process to provide complete traceability from the raw materials to
media batch to finished product.

A. Media
The composite purification media comprises three primary components: anion exchange nonwoven, microporous
membrane, and membrane support. The anion exchange media is composed of four layers of polypropylene nonwoven that
have been surface functionalized with a covalently attached quaternary ammonium polymer. The membrane is a highly
asymmetric polyamide with six zones of decreasing pore size, spanning approximately a 20X range, and terminating with a
nominal 0.2 μm rated qualifying layer. This is followed by a polypropylene nonwoven used as a support layer in the capsule.
               Functionalized Non‐Woven Media   

             Anion Exchange 

            
             Polyamide  membrane 

     
Figure 1. 3M™ Emphaze™ AEX Hybrid Purifier Media Design

B. Capsules
There are three capsule categories of 3M Emphaze AEX Hybrid Purifier based on size, intended use, and connector type:
Laboratory, Scale-up and Production capsules.
Capsule sizes across all three categories are designated by media Bed Volume (BV). For example, a BV120R capsule has a
bed volume of 120 mL. The media bed volume in a capsule is calculated using the total media thickness multiplied by the
accessible surface area. For the Emphaze AEX Hybrid Purifier, BV (in mL) = 0.35 x Surface Area (in cm²).
The Laboratory capsules (BV0.3R, BV1R, and BV8R) are constructed by compressing the composite purification media
between the inlet and outlet capsule components, and overmolding the entire unit with polypropylene. The BV0.3R and
BV1R (Figures 2a and 2b) laboratory capsules are available with luer lock connectors. The BV8R capsule (Figure 2c) has
matched inlet and outlet connections, available with either luer locks or mini sanitary fittings that accommodate both 1/2"
and 3/4" sanitary connectors.
Scale-up capsules are constructed from an 8-inch diameter lenticular media cell design (Figures 3a and 3b). The lenticle is
either one-sided (BV60R) or two-sided (BV120R and BV360R), with opposing layers of the composite purification media and
an inner separator. This unit is compressed and held together by injection molding at the outer and inner diameter with
glass-filled polypropylene, which simultaneously seals all edges and forms the inner fluid outlet manifold. The lenticles have
an outside-to-in flow path (Figure 3c). The flow passes through the composite media and is directed to a central exit flow
4 
 
 channel by the separator. For the BV60R lenticle, one of the composite media layers is replaced with an injection molded
polypropylene disk, reducing the accessible surface area by a factor of two. The BV360R capsules contain three stacked
and sealed lenticles. The lenticles, or lenticle stack, are sealed to the outlet side of the capsule with a polypropylene support
ring and fluoropolymer o-ring. The top and bottom pieces of the polysulfone capsule are sealed together by a thermal bond.
Scale-up capsules have matched inlet and outlet connections with mini sanitary fittings that accommodate both 1/2" and
3/4" connectors.
Production capsules have a similar lenticular cell design to that of scale-up capsules, but with a 16-inch diameter (Figure
4). Each lenticle has two opposing layers of filter media and an inner separator with a polymeric molded edge seal. The
lenticle is compressed, held together by injection molding at the outer and inner diameter with glass-filled polypropylene.
This simultaneously seals all edges and forms the inner fluid outlet manifold. A polypropylene spacer is placed between the
lenticles in 7-cell capsules. Two Production capsule configurations are available, both using glass-filled polyphenylene
oxide / polystyrene shells: the BV800R contains a single double-sided lenticle (Figure 4a); the BV5600R contains a stack of
seven double-sided lenticles (Figure 4b).
Male and female connectors are thermally attached to the outermost lenticles of the lenticle stack. The connectors use
silicone o-rings to seal adjacent capsules or manifolds. The top and bottom halves of the capsule shell are sealed together
by a thermal bond. The multicell Production capsule has a self-guiding locking mechanism for a robust capsule-to-capsule
connection, and two handles for convenient loading and unloading.
A set of manifolds is required for connecting the production capsules to external components of the purification train (Figure
4c). The Production capsule manifolds have 1.5" sanitary connections on the inlet and outlet.
The Production capsules may be used in a multi-stage filtration or purification train with a single 3M Encapsulated System
holder (Figure 4e). As many as seven BV5600R Production capsules can be installed in a single holder. An extra pair of
manifolds is required between each stage of the multi-stage train within the 3M Encapsulated System holder.

Figure 2. Laboratory Capsules

Inlet
Inlet
Inlet Inlet
Vent

Vent

Outlet Outlet Outlet Outlet

Figure 2a. BV0.3R Capsule Figure 2b. BV1R Capsule

Inlet Inlet

Inlet Vent Inlet Vent

Vent
Vent

Outlet Outlet
Outlet
Outlet
 
Figure 2c. BV8R Capsule – Luer Style Figure 2d. BV8R Capsule – Sanitary Style

5 
 
Figure 3. Scale-Up Capsules

Vent

Vent

Inlet Inlet

Outlet Outlet
   
Inlet
(not shown)
Inlet

Vent Outlet Vent Outlet

 

  Figure 3a. BV60R and BV120R Capsules Figure 3b. BV360R Capsules 

Luer Cap Scale-up Capsule Shell

Top

Lenticle
Edge Seal

Fluid
Fluid Inlet
Outlet

Downstream
Scale-up Capsule Shell
Bottom
Separator Media-Top
Upstream
 
Figure 3c. Scale-up capsules cross-section

Figure 4. Production Capsules

Upstream Vent Female Connector

Female Female Connector Straight Handle Downstream Vent
Connector

Manifold Stop

T-Handle
O-rings

Capsule Stop
Outlet
Male Connector Manifold
Inlet Stop
 
Figure 4a. BV800R Figure 4b. BV5600R Top Manifold Bottom Manifold
Figure 4c. Production Capsule Manifolds
6 
 
 Capsule Shell

Female
Connector Handles

Lenticle Edge
Seal

Capsule Stop

Figure 4d. BV5600R Production capsule cross-section

Figure 4e. Production capsules installed in 3M™ Encapsulated System holders

C. Materials of Construction and Design Characteristics

Table 2a. Materials of Construction - Laboratory Capsules

Part Type Materials
BV0.3R BV1R BV8R
Filter Surface Area (cm2) 0.7 3.8 25
Filter Media Quaternary Amine Terpolymer Grafted to a Polypropylene Nonwoven
Membrane Polyamide
Membrane Support Polypropylene Nonwoven
Capsule Shell Glass-Filled Polypropylene Polypropylene

Edge Seal Polypropylene Glass-Filled Polypropylene

Luer cap & luer-barb connector Polypropylene

7 
 Table 2b. Materials of Construction - Scale-Up Capsules
Part Type Materials
BV60R BV120R BV360R
Filter Surface Area (cm2) 170 340 1020
Filter Media Quaternary Amine Terpolymer Grafted to a Polypropylene Nonwoven
Membrane Polyamide
Membrane Support Polypropylene Nonwoven
Separator Polypropylene Glass-Filled Polypropylene
Flow Inhibitor Disc Polypropylene N/A
Edge Seal Glass-Filled Polypropylene
Capsule Shell / Connectors Polysulfone
O-ring Fluorocarbon (FKM)

Table2c. Materials of Construction - Production Capsules

Part Type Materials
BV800R BV5600R
2
Filter Surface Area (m ) 0.23 1.6
Filter Media Quaternary Amine Terpolymer Grafted to a Polypropylene Nonwoven
Membrane Polyamide
Membrane Support Polypropylene Nonwoven
Separators Glass-Filled Polypropylene
Edge Seal Glass Filled Polypropylene
Capsule Shell / Connectors Glass-Filled Polyphenylene Oxide / Polystyrene
O-rings Silicone

Table 2d. Capsule Design Characteristics – Laboratory Capsules

Product Name BV0.3R BV1R BV8R
½” - ¾” Sanitary
Inlet/Outlet Luer
Style
Dimensions (cm) 3.0 x 2.2 4.8 x 3.7 4.5 x 7.7 8.8 x 7.7
(ht x diam) (inches) (1.2" x 0.9") (1.9" x 1.5") (1.7" x 3.0") (3.5" x 3.0")
Weight
Dry 4.1 g 10.3 g 71 g 77 g
Wet, post blow-down 4.5 g 12.1 g 80 g 85 g
Volume
Capsule Fill Volume1 0.8 mL 4.1 mL 13 mL 16 mL
Post blow-down
0.4 mL 1.8 mL 9 mL 9 mL
Hold-up volume2
 
Table 2e. Capsule Design Characteristics – Scale-up and Production Capsules
Product Name BV60R BV120R BV360R BV800R BV5600R
Inlet/Outlet ½” - ¾” Sanitary Style 1 ½” Sanitary Style
Dimensions (cm) 10.3 x 21.6 15.2 x 21.6 5.7 x 45.2 20.3 x 45.2
(ht x diam) (inches) (4.1" x 6.5") (6.0" x 6.5") (2.2" x 17.8") (8.0" x 17.8")
Weight
Dry 1.0 kg 1.1 kg 1.6 kg 3.4 kg 9.5 kg
Wet, post blow-down 1.1 kg 1.2 kg 2.1 kg 4.1 kg 14.2 kg
Volume
Capsule Fill Volume1 0.55 L 0.55 L 1.4 L 3.4 L 10.6 L
Post blow-down
0.10 L 0.15 L 0.46 L 0.70 L 4.7 L
Hold-up volume2
1 Capsule Fill Volume is defined as the volume of liquid required to fill the capsule (experimentally measured).
2 Post blow-down hold-up volume is defined as the volume of the residual flush liquid after air/gas blow-down (calculated by post-blow-down weight and flush fluid density)

8 
 
 Table 2f Encapsulated Systems Manifold Design Characteristics (for BV800R
and BV5600R)
Component Top or Bottom Manifold
Dimensions (cm) 5.2 x 45.2
(height x diameter) (2.0" x 17.8")
Connector 1½” Sanitary Style
Material of Construction Glass-filled Polyphenylene Oxide / Polystyrene
Weight 4.5 kg
Hold-up Volume <250 mL

The wetted surface areas of various components in 3M™ Emphaze™ AEX Hybrid Purifier capsules are listed in Tables 3a
through 3c. For O-rings, it is estimated that 50% of the surface area is wetted. Media surface areas are listed in Tables 2a
through 2c.

Wetted surface area calculations are based on 3D models where all geometries are represented by a finely spaced discrete
set of points; curves are approximated by linear interpolation between these points. A numerical quadrature algorithm is
used to estimate the surface area and volume. The listed wetted surface areas represent the nominal values with tolerances
allowed in component dimensions.

Table 3a. Wetted Surface Areas of Laboratory Capsules

Capsule Components Wetted Surface Area [cm2]
BV0.3R BV1R BV8R (luer) BV8R (sanitary)
Shell (inlet) 8 12 41 54
Shell (outlet) 10 14 48 58

Table 3b. Wetted Surface Areas -Scale-Up Capsules Table 3c. Wetted Surface Areas – Production Capsules
Wetted Surface Area Wetted Surface Area
Components Components
[cm2] [cm2]
BV60R BV120R BV360R BV800R BV5600R
Separator Separator (per lenticle) 2,178
480 560
(per lenticle)
Edge Seal, (per lenticle) 592
Membrane Support (per
439 878 Inner Seal (per lenticle) 68
lenticle)
Flow Inhibitor Disk 439 NA Connectors
377
(Male and Female)
Edge Seal (per lenticle) 250 208
Capsule shells
Inner Seal (per lenticle) 47 3,554 5,477
(top and bottom
Shell Top 388 679 O-ring large retainer 28
Shell Bottom 420 O-ring large 14
EndCap 14.7 O-ring small 4
Back-up O-ring 2.5 Manifold (Total Top and
1,047
O-ring 1.4 Bottom)

V. Product Specifications and Operation Parameters

A. Product Release Specifications

Product specifications verified during filter manufacturing and prior to the release of media lots include but are not limited to
the following:
1) Capsule Integrity: Capsules BV8R and larger are 100% tested using pressurized air.
2) Total Nitrogen Extraction: Media extracted to show consistency of functionalized media and to confirm compliance with
USP <88>.
3) Endotoxin Extraction: Media effluent is tested for extractable endotoxin using the Limulus Amebocyte Lysate (LAL)
bacterial endotoxin reactivity assay.

9 
 4) Dynamic Binding Capacity (DBC): Charge capacity is measured by challenging the media with a solution of the negatively
charged Metanil Yellow dye and measuring the volume required for dye breakthrough.

Table 4. Product Release Properties for 3M™ Emphaze™ AEX Hybrid Purifiers 
Specifications
Product Release Properties BV0.3
BV1R BV8R BV60R BV120R BV360R BV800R BV5600R
R
1
Capsule Integrity NA NA 8.0 sccm 9.0 sccm 0.010 psi
Media 
Total Nitrogen Extraction (ppm)2 ≤ 6.6
Endotoxin Extraction (EU/mL)3 ≤ 0.12
Metanil Yellow Dynamic Binding
≥ 28
Capacity (mg MY/cm2 media)4

1 BV8R and scale-up capsule integrity are confirmed using leak test; BV8R’s is tested at 40 psi; BV60R, BV120R, and BV360R are tested at 45 psi. BV800R and BV5600R are tested using pressure decay at
50 psi.
2 Four layers of media flushed with 25mM NaCl (aq) solution to recommended preconditioning flush volume; 45mm discs are extracted in 50 mL 25mM salt solution for 1 hour at 121C, and the extract tested
for Total Nitrogen (TN) on instrumentation using catalytic thermal decomposition/chemiluminescence methods.
3 Determined by flushing a 47 mm disc of media at a flow rate of 8 mL/min with 200 mM NaCl then collecting a 2 mL effluent sample after 80 mL flush. Samples are tested according to USP <85> using a
LAL turbidimetric assay.
4 A solution of 0.160 mg/mL Metanil Yellow dye (CAS#: 587-98-4) prepared in 50 mM phosphate buffer / 140 mM NaCl at pH 7.2 is passed through the media at a flow rate of 1 mL/min per cm2 of effective
area. The DBC is determined by volume of solution required to reach 5% optical absorbance breakthrough at 414nm in the effluent.

B. Installation and Operation Instructions

The installation and operation of 3M™ Emphaze™ AEX Hybrid Purifier products should follow the appropriate instruction for
each filter configuration. Always operate within the pressure and temperature design limits of the filter product.
Prior to filtration operation, the end-user should verify that capsules have been properly installed and sealed. Therefore, a
qualification test should be performed per the recommended test procedure contained in 3M's Installation and Operating
Procedures manuals. Installation and Operation Instructions are available upon request from your local representative.

C. Minimum Required Preconditioning Flush

Emphaze AEX Hybrid Purifier capsules are comprised of all synthetic components. Sodium chloride (NaCl, USP37 Monograph
Compliant, CAS 8028-77-1) is used as a production processing aid and remains in the media as packaged. Glycerin (C3H8O3,
USP37 Monograph Compliant, CAS 56-81-5) is added as a humectant to help maintain the purification media at a controlled
moisture content. This acts to stabilize the media against performance degradation due to moderate temperature and
humidity fluctuations.
3M specifies a preconditioning flush of the Emphaze AEX Hybrid Purifier by the customer prior to contact with customer
process fluids to be consistent with the USP <87> and <88> Class VI compliance claims. This specified preconditioned
flush is termed "Required Preconditioning Flush" in this and related Emphaze AEX Hybrid Purifier documents. The
preconditioning flush is sufficient to be compliant with USP<88> Class VI and to remove glycerin from the media. Emphaze
AEX Hybrid Purifiers may also be autoclave sterilized or base sanitized by the customer prior to use. To reduce the risk of
product loss associated with nullification of Supplier's USP<88> Class VI compliance of filter capsule components, the
capsule must be subjected to a preconditioning flush prior to use. The required preconditioning flush volumes for autoclaved
capsules is equivalent to that of untreated capsules. For base sanitized capsules, the preconditioning flush necessary to
return treated capsule effluent to satisfactory pH and conductivity levels may differ from untreated capsules, depending on
the buffer selection and capsule configuration.

10 
 The preconditioning flush is performed at room temperature with aqueous buffer or a minimum 25 mM sodium chloride
solution (2.9 mS/cm in H2O). The product can be flushed with appropriate solutions that are compatible with the process
stream, as long as minimum solution conductivity is maintained. Water alone cannot be used because the strong cationic
functionality of the media causes it to become highly swollen and effectively impermeable without the presence of aqueous
counter ions.

Detailed Preconditioning Flush Protocols are provided in the product installation and operating Instructions. The required
preconditioning flush volume for each capsule size is provided in Tables 5a and 5b. The recommended maximum flux for
the preconditioning flush is 210 L/m2/hour (LMH). Pressure drop across the filter should not exceed 2.4 bar [35 psid]. The
data package of effluent quality presented in this Regulatory Support File uses this recommended flux for the required
preconditioning flush.

Table 5a. Minimum Required Preconditioning Flush Volume and Operating Conditions – Laboratory
Capsules
Product Name BV0.3R BV1R BV8R
Liquid Operating Conditions
Recommended Maximum Flux 210 LMH (L/me/hour)
Maximum Inlet Pressure 2.8 bar (40 psig)
Maximum Differential Pressure 2.4 bar (35 psid)
Maximum Operating Temperature 40°C (104°F)

Post-Use Compressed Gas for Blow Down Only¹

Maximum Inlet Pressure 1.4 bar (20 psig)
Maximum Operating Temperature 25°C (77°F)

Required Preconditioning Flush Volumes²

No Treatment 5 mL 16 mL 0.13 L

Post-autoclave3 5 mL 16 mL 0.13 L
3
Post-Base-sanitization
5 mL 16 mL 0.13 L
50mM Phosphate Buffer4
Post-Base-sanitization3
5 mL 16 mL 0.13 L
100mM Phosphate Buffer4
Post-Base-sanitization3
5 mL 16 mL 0.13 L
Acetate Buffer5

Recommended Flush/Use Flow Rate 0.3 mL/min 1 mL/min 8 mL/min

Maximum Flow Rate 1.2 mL/min 5 mL/min 24 mL/min

Controlled indoor temperature: 0 - 30°C (32 - 86°F) in original sealed
Storage Conditions6
packaging
Shelf-Life7 2 years from date of manufacture @ 30°C maximum storage

11 
 
 Table 5b. Minimum Required Preconditioning Flush Volume and Operating Conditions –
Scale-up and Production Capsules
Product Name BV60R BV120R BV360R BV800R BV5600R
Liquid Operating Conditions
Maximum Inlet Pressure 3.1 bar (45 psig) 3.4 bar (50 psig)
Maximum Differential Pressure 2.4 bar (35 psid) 2.4 bar (35 psid)
Maximum Operating Temperature 40°C (104°F)
Post-Use Compressed Gas for Blow Down Only¹
Maximum Inlet Pressure 2.0 bar (30 psig)
Maximum Operating Temperature 25°C (77°F)

Required Preconditioning Flush Volumes²

No Treatment² 0.9 L 1.8 L 5.5 L 12 L 85 L

Post-autoclave3 0.9 L 1.8 L 5.5 L 12 L 85 L

3
Post-Base-sanitization
4.5 L 5.4 L 10.2 L 24 L 85 L
50mM Phosphate Buffer4
Post-Base-sanitization3
3.0 L 3.6 L 7.3 L 16 L 85 L
100mM Phosphate Buffer4
Post-Base-sanitization3
4.5 L 5.4 L 10.2 L 24 L 85 L
100mM Acetate buffer5

Recommended Flush/Use Flow Rate 60 mL/min 120 mL/min 360 mL/min 800 mL/min 5.6 L/min

Maximum Flow Rate 180 mL/min 360 mL/min 1.1 L/min 2.4 L/min 16.8 L/min

Controlled indoor temperature: 0 - 30°C (32 - 86°F)

Storage Conditions6
in original sealed packaging
Shelf-Life7 2 years from date of manufacture @ 30°C maximum storage
1 Do not use this product for continuous service with compressed gasses. Use of compressed gas is permissible for post-use integrity testing and blow-down purposes only. Limit post-use integrity test
and blow-down gas pressures to less than 1.4 bar (20 psig) and temperature less than 25°C for no longer than 30 minutes.
2 Required Preconditioning Flush is a saline solution with conductivity comparable to 25 to 150 mM NaCl (typical 3-16 mS/cm). DO NOT use water to flush the capsule.
3 The capsules were pre-use sterilized/sanitized as per Section V.D protocols and flushed as per non-treated capsule.
4 The Required Preconditioning Flush following base-sanitization using a phosphate buffer in 25mM NaCl solution; (10mM Na2HPO4: 1.8mM KH2PO4) scaled to appropriate phosphate buffer molarity for
50mM and 100mM flush solutions; buffer pH 7.4±0.2, with capsule flushed to achieve pH 7.6. Subsequent flushing with 25 to 150 mM NaCl (3-16 mS/cm in H2O) may be used to clear the system of
buffer. DO NOT use water to flush the capsule.
5 The Required Preconditioning Flush following base-sanitization using an acetate buffer solution (0.1M HOAc and 0.1M NaOAc) at pH 6.0±0.2, with capsule flushed to achieve pH 6.2. Subsequent
flushing with 25 to 150 mM NaCl (3-16 mS/cm in H2O) may be used to clear the system of buffer. DO NOT use water to flush the capsule.
6 Do not allow product to be exposed to freezing or extreme heat conditions.
7 USP <88> Class VI compliance and high adsorption capacity for up to 2 years from date of manufactured if stored as indicated. Product labeling includes the expiration date.

D. Pre-Use Sterilization / Sanitization

3M™ Emphaze™ AEX Hybrid Purifier products are not bioburden controlled. They can be autoclaved or in-situ base
sanitized per recommended conditions listed in Table 6.  Studies were conducted to ensure sterility after autoclave or in situ
base sanitization. If the filter is autoclaved or in-situ base sanitized, 3M requires that it be flushed after treatment using the
required preconditioning flush.

Table 6. Pre-use Sterilization Conditions

Capsule Class Laboratory Scale-up BV800R BV5600R
1
Autoclave sterilization Autoclave cycle at 121°C for 30 minutes 121°C for 40 minutes
1M NaOH soak for 1 hour at ambient temperatures followed by gravity drain to remove excess base Do
Base-Sanitization2
Not Blow Down
1 Samples tested with steam autoclave with pre-vacuum cycle.
2 Capsules tested to confirm safety and performance after 1M NaOH sanitization. Do not exceed 1M NaOH concentration. Concentrations lower than 1M NaOH may be used as qualified
by the end user.

References:
3M SOP: 10L.600.129 (ORIG)
Laboratory Report: SASS – 2460

12 
 
 E. Post-Use Sterilization
3M™ Emphaze™ AEX Hybrid Purifier products may be sterilized by the procedure in Table 7 prior to disposal if necessary
to comply with local regulations or customer requirements.

Table 7. Post-Use Sterilization Conditions1

Product Class Laboratory Scale-up Capsules Production Capsules
Capsules
Autoclave cycle at 121°C for 40 minutes
Autoclave sterilization

Caustic Sanitization Capsule soak for 1 hour with 1M NaOH or 5% NaClO (bleach)2
1 Do not exceed maximum pressure and temperature ratings during sanitization.
2 Do not use NaClO (bleach) for pre-use sterilization

VI. Performance Verification

All data sets provided in this Regulatory Support File are based on testing of media and product close to the manufacturing date.
The exception is that which is reported in the Shelf Life section. The performance characteristics reported in this Regulatory
Support File have been derived from a statistical analysis of multiple production qualification lots.

A. Permeability
The cationic polymer chains of the Emphaze AEX Hybrid Purifier media are highly extended in deionized water due to
repulsion between neighboring positive charges on the chains. The addition of a small concentration of salt (equivalent to at
least 25 mM NaCl, 2.9 mS/cm) effectively reduces the repulsion of the neighboring charged groups of the polymer. This
phenomenon causes polymer chains to adopt a less extended conformation thereby increasing the permeability. Deionized
water should never be used with Emphaze AEX Hybrid Purifier capsules as it will result in the media becoming
impermeable.

The permeability was characterized by measuring the pressure drop across the respective capsule sizes using a saline
solution (35 mM NaCl, 3.9 mS/cm) at a flow rate of 210 L/m²/hr (LMH).

Permeability for capsules that were pre-use autoclaved or base-sanitized was also measured. No difference in permeability
between untreated, autoclaved, and base-sanitized capsules after preconditioning flush was observed.

Table 8. Permeability   Differential Pressure (bar [psid])

Product Number of Manufacturing Total number of Average STD DEV
Lots Samples
BV0.3R 2 12 0.17 (2.5) 0.03 (0.5)
BV1R 1 16 0.05 (0.66) 0.007(0.1)
BV8R 4 13 0.06 (0.87) 0.04 (0.7)
BV60R 4 12 0.07 (0.98) 0.04 (0.6)
BV120R 4 12 0.04 (0.54) 0.01 (0.2)
BV360R 4 13 0.02 (0.26) 0.02 (0.3)
BV800R 3 3 0.02 (0.30) 0.02 (0.3)
BV5600R 1 1 0.01 (0.10) -
Minimum Qualification Specification: 35 LMH/psi with 35 mM NaCl

References:
3M SOP: 10L.600.102(ORIG)
Laboratory Reports: LAB-12349, LAB-12398 & LAB-12626

13 
 
B. Charge Capacity - DBC As a Function of Flow Rate; pH and Conductivity
A metric of media charge is the dynamic binding capacity (DBC) of the anionic, negatively charged dye Metanil Yellow (MY).
Emphaze AEX Hybrid Purifier is challenged after pre-conditioning flush with a MY solution, and DBC is defined as the 5%
optical absorbance breakthrough of MY in the effluent.
Scalability between capsule sizes is shown using DBC measurements in capsules, normalized using the measured DBC of
the media alone. Results are shown in Table 9a and Figure 5. Insensitivity of DBC to autoclaving or base sanitization is
shown in Table 9b.

Table 9a. 3M™ Emphaze™ AEX Hybrid Purifier Capsule Normalized Dynamic Binding Capacity
Scalability  (Capsule DBC/Media DBC

Capsule Number of Lots Total Samples Average STD DEV

BV0.3R 1 9 0.84 0.04

BV1R 1 8 0.99 0.01785
BV8R 4 14 0.95 0.177
BV60R 4 12 1.13 0.12672
BV120R 4 12 1.24 0.20954
BV360R 4 13 1.18 0.12381
BV800R 3 3 1.00 0.0978
BV5600R 1 1 1.02 -
Metanil Yellow dye (3-(4-Anilinophenylazo)benzenesulfonic acid sodium salt; C18H14N3NaO3S; CAS#: 587-98-4; 50 mM phosphate buffer containing 140 mM NaCl and 0.160
mg/mL of Metanil Yellow at pH 7.2 at a flow rate of 600 L/m2/h (1 mL/min per cm²effective area).

Figure 5. Normalized Dynamic Binding Capacity with differing capsule size 

Table 9b. 3M™ Emphaze™ AEX Hybrid Purifier Metanil Yellow Dynamic Binding Capacity1
Dynamic Binding Capacity - Post Pre-Use Sanitization (mg/cm²)
Number of Total number of
Product Minimum Average STD DEV
Manufacturing Lots* Samples
BV8R
3 9 44.0 44.9 1.4
Untreated
BV8R
3 9 41.4 45.2 2.7
Autoclaved2
BV8R
3 9 40.3 43.1 1.4
Base-sanitized2
1 Minimum Qualification Specification: 28 mg/cm²
2 Autoclaved at 121C for 30 minutes, Base Sanitized using 1M NaOH for 1 hour, both followed by specified pre-conditioning flush

References:
3M SOP: 10L.600.120
Laboratory Reports: LAB-12349, LAB-12398, LAB-12626, & LAB-13204

14 
 C. BSA and DNA Dynamic Binding Capacity
The BSA and DNA dynamic binding capacities (DBC) of the 3M™ Emphaze™ AEX Hybrid Purifier media composite were
determined based on testing of multiple manufacturing qualification lots that met all release specifications.
Reference solutions with a known concentration of BSA or Calf Thymus DNA were prepared in the appropriate loading
buffer. The UV maximum absorbance of the reference solution was measured at 280 nm for BSA and 260 nm for DNA. The
DBC test was performed using an automated liquid chromatography system that continuously monitors the UV absorbance.
The DBC was determined at 10% breakthrough of UV maximum absorbance.

The samples were flushed with equilibration buffer at 5 BV/min until a constant UV baseline was achieved. Equilibration
buffer had the same composition of the reference solution but contained neither BSA nor DNA. The Emphaze AEX Hybrid
Purifier media composite was then challenged with the BSA or DNA solution at 5 BV/min. The conditions tested included
various buffers, pH levels, and conductivities. Each lot was tested in quintuplicate per condition. The data presented are for
information purpose only based on performance of product meeting all release criteria, and should not be regarded as
product specification. Results using low conductivity solutions (1.5 mS/cm) are for comparison only, and are outside the
recommended use conductivity range.

Table 10a. BSA and DNA Dynamic Binding Capacity at 10% Breakthrough for Various Buffers
BSA at 10% Breakthrough DNA at 10% Breakthrough
mg/cm² mg/mL mg/cm² mg/mL
Buffer Condition
Avg STDEV Avg STDEV Avg STDEV Avg STDEV
20 mM Tris-HCl
9.6 2.8 27.4 8.1 3.6 0.5 10.4 1.5
pH 7.0
20 mM Na-Phosphate
9.4 0.6 27.0 1.7 4.3 0.3 12.4 0.7
pH 7.0
20 mM HEPES
9.9 2.9 28.3 8.3 4.1 0.3 11.8 0.8
pH 7.0

Table 10b. DNA Dynamic Binding Capacity at 10% Breakthrough as a Function of pH and Conductivity
1.5 mS/cm (10 mM NaCl) 11.4 mS/cm (100 mM NaCl) 20.6 mS/cm (200 mM NaCl)
pH mg/cm² mg/mL mg/cm² mg/mL mg/cm² mg/mL
Avg STDEV Avg STDEV Avg STDEV Avg STDEV Avg STDEV Avg STDEV
5.0a 3.5 0.3 9.8 0.9 6.9 0.7 19.7 2.0 9.5 1.2 27.3 3.3
a
6.0 3.4 0.3 9.6 0.8 6.7 0.7 19.0 1.9 9.5 1.1 27.0 3.1
7.0b 3.6 0.5 10.4 1.5 6.9 0.6 19.6 1.7 10.0 1.0 28.6 2.8
8.0b 2.5 0.6 7.1 1.7 6.9 0.8 19.6 2.3 9.5 1.2 27.1 3.5
a Measured using 20mM Bis-Tris buffer
b Measured using 20 mM Tris-HCL

Table 10c. BSA Dynamic Binding Capacity at 10% Breakthrough as a Function of pH and Conductivity
1.5 mS/cm (10 mM NaCl) 6.6 mS/cm (50 mM NaCl)
pH mg/cm² mg/mL mg/cm² mg/mL
Avg STDEV Avg STDEV Avg STDEV Avg STDEV
6.0a 10.0 2.8 28.6 8.0 1.9 0.4 5.3 1.0
7.0b 9.6 2.8 27.4 8.1 6.1 0.8 17.6 2.2
8.0b 8.3 3.6 23.7 10.2 7.7 1.1 21.9 3.2
a Measured using 20mM Bis-Tris buffer
b Measured using 20 mM Tris-HCL

15 
 Figure 6a. 3M™ Emphaze™ AEX Hybrid Purifier media DNA Dynamic Binding Capacity

Figure 6b. 3M™ Emphaze™ AEX Hybrid Purifier media BSA Dynamic Binding Capacity

VII. Effluent Quality

Various regulatory organizations require that equipment used in pharmaceutical manufacturing that is in direct contact with the
drug product should not add to or change the drug in any way other than what is intended by the manufacturer.

Distribution of Responsibility
3M Separation and Purification Sciences Division has adopted the following supplier collaborative model (D. Jenke, Pharma Ed
Conference on Extractables & Leachables, keynote address Oct 2011) relative to Extractable and Leachable evaluation.

Shared Responsibility of Supplier and Producer

1. It is the responsibility of suppliers of plastic materials or systems to provide users with a full and complete composition of their
material or system.
2. It is the responsibility of the producer to supply regulators with a full and complete leachables assessment for their finished
therapeutic product.
3. It is the shared responsibility of the producer and supplier to collaborate on obtaining extractables information and in so doing
increases the effectiveness and efficiency of extractables studies.
In this Regulatory Support File 3M provides effluent quality data relating to the required preconditioning flush based on the
requirements listed in Table 11. As of August 2018, the USP <665> monograph outlining guidance for extractables/leachables of
polymers in pharmaceutical manufacturing is still in draft form. It is 3M’s commitment to comply with all regulatory
16 
 requirements, as well as provide data for our customers to make appropriate risk assessments. To this end, a separate data
package is available upon request as an addendum to the RSF that follows current USP draft guidance for reporting
extractables/leachables.

Table 11. Reference Industry Standards

USP Standards Applicable Methods
<643> Total Organic Carbon
<645> Conductivity
<791> pH
<232>, <233>, ICH* Q3D Elemental Impurities
<788> Particulate Matter in Injections
<85> Bacterial Endotoxin
<87>, <88>, BSE/TSE Biological Reactivity
* ICH – International Conference for Harmonization, Guideline for Elemental Impurities, Q3D, Dec. 16, 2014

A. USP <643> Total Organic Carbon (TOC) and Total Nitrogen (TN)
A preconditioning flush was performed on Emphaze AEX Hybrid Purifiers at a flux of 210 L/m²/hr (LMH) (0.29 mL/min/cm²)
using the conditions specified under Preconditioning Flush Section V.C. Sample aliquots from each flush condition were
analyzed for non-purgeable organic carbon content and total nitrogen content. Acetate buffer was not analyzed because of
its inherent carbon content. Extractions on the small laboratory capsules (BV0.3R and BV1R) were not performed due to
limitations in effluent volume.

The primary source of carbon is release of the glycerin stabilizer. TN is measured to confirm media stability, and that the
functionalized quaternary amine is not being released into the effluent.

Table 12a. Total Organic Carbon and Total Preconditioning Flush – 25mM NaCl
Nitrogen – Non-sterilized Total Organic Carbon Total Nitrogen
Number of
Product Manufacturing Total Number of AVG STD DEV AVG
Lots Samples

BV8R 3 15 114 40 ND
BV60R 3 9 96 37 ND
BV120R 3 9 63 13 ND
BV360R 3 4 58 19 ND
BV800R 3 3 51 3 ND
BV5600R 1 1 30 N/A ND

Table 12b. Total Organic Carbon and Total Preconditioning Flush – 25mM NaCl
Nitrogen – Autoclaved 
Total Organic Carbon Total Nitrogen
Number of
Product Manufacturing Total Number of AVG STD DEV AVG
Lots Samples
BV8R 3 3(3) 83 17 ND
BV60R 3 9 65 17 ND
BV120R 3 9 24 5 ND
BV360R 1 1 14 N/A ND
BV800R 3 3 10 2 ND
BV5600R 1 1 9 N/A ND
 
   

17 
 
 Table 12c. Total Organic Carbon and Total Preconditioning Flush 50mM Phosphate Buffer
Nitrogen – Base Sanitized Total Organic Carbon Total Nitrogen
Number of
Product Manufacturing Total Number of AVG STD DEV AVG
Lots Samples
BV8R 3 3(3) 42 2 ND
BV60R 3 3 21 4 ND
BV120R 3 3 20 4 ND
BV360R 3 3 11 1 ND
BV800R 3 3 7 1 ND
BV5600R 1 1 9 N/A ND
Flushed with 50mM Phosphate Buffer
 
Table 12d. Total Organic Carbon and Total At Required Preconditioning Flush
Nitrogen – Base Sanitized BV120R varying buffer Total Organic Carbon Total Nitrogen
composition 

Number of MFR Total Number of

Flush Condition AVG STD DEV AVG
Lots Samples

10mM Phosphate 3 3 67.6 7.1 ND

Buffer
50mM Phosphate 3 3 35 10 ND
Buffer
100mM Phosphate 3 3 45 11 ND
Buffer
Autoclaved 3 3 24 5 ND
Untreated 3 9 63 13 Not Measured
 

10000
BV8
BV60
BV120
BV360
BV800
1000 BV5600
TOC (ppm)

100

10

0 50 100 150 200

% Nominal Pre-conditioning Flush
 
Figure 7a. TOC vs. Flush volume: Non-sterilized capsules Figure 7b. TOC vs. Flush volume: Autoclaved capsules

18 
 
 10000
10,000 10mMPhosphate
50mM Phosphate
BV8 100mM Phosphate
BV60 Autoclaved
BV120 Untreated
BV360
1,000 BV800
BV5600 1000

TOC (ppm)
TOC (ppm)

100
100

10

10

0 100 200 0 100 200

% Nominal Pre-conditioning Flush % Nonminal Pre-Conditioning Flush

Figure 7c. TOC vs. Flush volume: base-sanitized capsules, Figure 7d. TOC vs. Preconditioning Flush volume in BV120R
50mM phosphate buffer flush capsules for varying treatment and flush solution

For reference, the results provided in Figures 7a-d demonstrate that the saline extraction is not compliant with USP <1231>
Sterile Water for Injection, which has a maximum TOC specification of 0.5 ppm.
References:
3M SOPs: 10L.600.118(A), 10L.600.116(ORIG) & 10L.600.124(A)
Industry Standards: USP <643> Total Organic Carbon & USP <1231> Sterile Water for Injection
Laboratory Report: 12322 & 12626

B. USP <645> Conductivity

A preconditioning flush was performed on Emphaze AEX Hybrid Purifiers at a flux of 210 L/m²/hr to 2X the required volume
(i.e., 108 L/m²) as indicated in Section V.C. Sample aliquots of flush solution were analyzed for a change in conductivity
compared to the blank solution used for the preconditioning flush. After 50% of the required preconditioning flush the
conductivity was equivalent to the flush solution conductivity in all cases, except for Base Sanitization in which the residual
NaOH requires the full preconditioning flush to reach baseline. This indicates that the media contributes a negligible
amount of conductivity to the effluent compared to the required conductivity of the flush solutions.
References:
3M SOPs: 10L.600.118(A) & 10L.200.059(ORIG)
Industry Standard: USP <645> Water Conductivity
Laboratory Reports: 12322 & 12626

C. USP <791> pH
A preconditioning flush was performed on Emphaze AEX Hybrid Purifiers at a flux of 210 L/m²/hr. A solution of 25 mM
sodium chloride in reagent water was used for flushing non-treated and autoclaved samples (2.9 mS/cm, 5.5-7.0 pH).
Phosphate buffer concentrations of 10mM, 50mM, and 100mM, as well as 100mM acetate buffer, were used to flush
capsules base-sanitized with 1M NaOH. Sample aliquots of flush solution were analyzed for a change in pH compared to
the blank flush solution. Laboratory capsules BV0.3R and BV1R were not tested because of effluent volume limitations.

Because of the large flush volume required to return the capsule to baseline pH using 10mM phosphate buffer, this buffer
concentration is not recommended to flush base-sanitized capsules. As indicated in Section V.C, 50mM phosphate buffer is
the minimum recommended concentration for base-sanitized capsules flush.

Table 13a. Effluent pH vs. preconditioning flush volume % – Non-treated

Capsule BV8R BV60R BV120R BV360R BV800R BV5600R
25mM NaCl 61 58 65 69 61 61
Initial 9.0 8.7 8.7 8.9 8.3 9.2
50% 8.1 7.9 7.9 8.2 8.1 7.3
100% 7.8 7.5 7.8 8.4 7.3 7.3
150% 7.8 7.4 7.9 8.5 6.6 6.6
200% 7.6 7.1 7.5 8.1 6.4 6.5

19 
 Table 13b. Effluent pH vs. preconditioning flush volume % – Autoclaved 
Capsule BV8R BV60R BV120R BV360R BV800R BV5600R
25mM NaCl 7.9 6.2 7.1 6.7 5.8 5.0
Initial 8.1 6.1 7.6 9.6 8.6 9.9
50% 7.9 7.6 7.7 8.4 8.6 6.0
100% 8.2 7.3 7.6 8.1 8.6 5.1
150% 8.2 7.5 7.0 7.3 8.4 4.9
200% 7.8 7.4 6.9 7.0 8.2 5.0

Table 13c. Effluent pH vs. preconditioning flush volume % – Base Sanitized 

Capsule BV8R BV60R BV120R BV360R BV800R BV5600R
50mM Phosphate 7.4 7.5 7.3 7.4 7.6 7.6
Initial 13.3 13.4 13.3 13.4 13.3 13.4
50% 7.8 12.9 12.3 12.6 11.2 8.0
100% 7.5 12.2 10.7 7.8 8.8 7.7
150% 7.4 11.6 9.5 7.5 8.1 7.6
200% 7.4 11.2 8.6 7.4 7.9 7.6
300% 7.4 9.3 7.6 7.4 7.7 7.6
400% 7.4 7.8 7.5 7.4 7.7 7.6
50 mM Phosphate Buffer flush, pH 7.3
Table 13d. Effluent pH vs. Preconditioning Flush Volume % -
Base Sanitized BV120R with differing Buffer Composition
10mM 50mM 100mM 50mM
Buffer
Phosphate Phosphate Phosphate Acetate
Buffer pH 7.8 7.3 7.4 5.9
Initial 13.3 13.3 13.3 13.1
50% 12.7 12.3 11.8 12.8
100% 12.7 10.7 10.3 12.2
200% 10.9 8.6 7.6 8.9
300% 9.2 7.6 7.5 6.1
400% 8.0 7.5 7.5 6.0
500% 7.6 7.4 7.5 5.9

13 10mM Phosphate
13 50mM Phosphate
BV8 100mM Phosphate
BV60 50mMAcetate
BV120 12
12 BV360
BV800
BV5600 11

11
10
pH
pH

10 9

9 8
Phosphate buffer 
7
8

6 Acetate buffer 
7
0 100 200 300 400 500 600
0 100 200 300 400 500 600
% Nominal Pre-conditioning Flush
% Nominal Pre-conditioning Flush
Figure 8a. pH vs. Flush volume % for base-sanitized capsules Figure 8b. pH vs. Flush volume of base-sanitized using
50mM phosphate buffer BV120R capsules for various buffer

Reference:
3M SOP: 10L.200.059 (ORIG)
Industry Standards: USP <791> Water pH
Laboratory Report: Lab-13089, Lab-13204

20 
 D. USP <232>/<233> and ICH Q3D Elemental Impurities
Preconditioning flush effluent was captured under conditions described above at 10% and 100% of the required
preconditioning flush volumes for BV120R and BV800R capsules, respectively. These capsules were chosen to be
representative of Scale-up and Production sizes of AEX Hybrid Purifier. Samples were then tested for ICH Q3D class 1-3
elements, as well as selected others indicated in Tables 14a and 14b, by ICP-AES, under the indicated pre-sterilization
treatment and flush conditions.

Table 14a – Flush Effluent Elemental Impurities for Emphaze AEX Hybrid Purifier Capsules (ppb) 

ICH LOD BV120R – untreated BV120R – Autoclaved BV120R – Base Sanitized

Element
Class [ppb] 25mM NaCl Flush 25mM NaCl Flush 50mM Phosphate Buffer Flush
Flush Flush Flush
At % of Flush Volume 10% 100% 10% 100% 10% 100%
Control Control Control
As 100 - - - - - - - - -
Pb 70 - - - - - - - - -
1
Cd 6 - - - - - - - - -
Hg 40 - - - - - - - - -
V 7 - - - - - - - - -
2A Ni 40 - - - - - - - - -
Co 20 - - - - - - - - -
Ag 40 - - - - - - - - -
Au 40 - - - - - - - - -
Tl 100 - - - - - - - - -
Pd 30 - - - - - - - - -
Pt 80 - - - - - - - - -
2B
Ir 50 - - - - - - - - -
Os 1000 - - - - - - - - -
Rh 20 - - - - - - - - -
Ru 20 - - - - - - - - -
Se 700 - - - - - - - - -
Sb 60 - - - - - - - - -
Ba 3 - 3 - - - - 4 - 4
Li 2 - 21 - - - - 5 12 5
3 Cr 3 - 2 7 - - - 41 16 40
Cu 3 - 18 - - - - 12 14 12
Mo 60 - - - - - - - - -
Sn 100 - - - - - - - - -
Al 4 - 12 - - 10 - 20 67 21
Ca 10 - 323 - - 90 - 240 120 240
Other Elements

Fe 3 - - - - - - 31 5 28
Mn 2 - 10 5 - - - - - -
Si 30 - 125 - 300 420 300 260 430 200
W 30 - - - - - - - - -
Zn 40 - 610 536 - - - - - -
In this table, "-" indicates measurement below Limit of Detection "LOD"
 
   

21 
 
 
Table 14b – Flush Effluent Elemental Impurities for Emphaze AEX Hybrid Purifier Capsules (ppb) 

ICH LOD BV120R – Base Sanitized BV800R – Autoclaved BV800R – Base Sanitized
Element
Class [ppb] 100mM Acetated Buffer Flush 25mM NaCl Flush 50mM Phosphate Buffer Flush
Flush Flush Flush Control
At % of Flush Volume 10% 100% 10% 100% 10% 100%
Control Control
As 100 - - - - - - - - -
Pb 70 - - - - - - - - -
1
Cd 6 - - - - - - - - -
Hg 40 - - - - - - - - -
V 7 - - - - - - - - -
2A Ni 40 - - - - - - - - -
Co 20 - - - - - - - - -
Ag 40 - - - - - - - - -
Au 40 - - - - - - - - -
Tl 100 - - - - - - - - -
Pd 30 - - - - - - - - -
Pt 80 - - - - - - - - -
2B
Ir 50 - - - - - - - - -
Os 1000 - - - - - - - - -
Rh 20 - - - - - - - - -
Ru 20 - - - - - - - - -
Se 700 - - - - - - - - -
Sb 60 - - - - - - - - -
Ba 3 - - - - - 1 4
Li 2 5 11 5 - - - 35 13
3 Cr 3 - 5 - - -
Cu 3 7 16 10 - - - 11
Mo 60 - - - - - - - - -
Sn 100 - - - - - - - - -
Al 4 7 34 - - 20 - 20 40
Ca 10 90 100 100 - 50 - 150 90 160
Other Elements

Fe 3 - 4 - - - -
Mn 2 10 - 10 - - - - - -
Si 30 110 470 130 130 180 130 17000 5800 18000
W 30 - - - - - - - - -
Zn 40 - 800 - - - - - -
In this table, "-" indicates measurement below Limit of Detection "LOD"
 
Reference:
Industry Standard: USP <232> Elemental Impurities – Limits; USP <233> Elemental Impurities – Procedure; ICH Guideline for Elemental Impurities Q3D,
Dec 2014
Laboratory Report: Lab-13089, Lab-13204

E. USP <788> Particulate Matter in Injections

During preconditioning flush, effluent was captured under conditions described above at 10% and 100% of the required
flush volumes for BV120R and BV800R capsules, respectively. These were chosen to be representative of Scale-up and
Production sizes of AEX Hybrid Purifier. Sample aliquots of effluent were analyzed for the presence and concentration of the
particulates and fibers.
Samples were analyzed following USP <788> Method 1 (Light Obscuration Particle Count Test) for particulate release. Five
aliquots of 5 mL each were measured from each sample, with particles counted and measured at the size ranges specified
in the USP chapter: particles greater than 10 μm but less than 25 μm; and particles > 25 μm. The solution meets the
USP<788> requirement if it contains less than 25 particles/mL >10 μm and less than 3 particles/mL >25 μm.
All effluent samples meet the limits for particulates given in USP <1231> Sterile Water for Injection.

22 
 
 Table 15a – Particulate Matter Emphaze AEX Hybrid Purifier Capsules [ppb] - BV120R 

Particulate
BV120R – untreated BV120R - Autoclaved BV120R – Base Sanitized
Size
25mM NaCl 50mM
10% 100% 10% 100% 10% 100%
Phosphate
>10 μm 69.3 16.1 11.0 22.5 6.8 46.7 13.0 13.9
>25 μm 11.3 1.3 0.3 2.4 0.7 3.0 2.4 1.9

Table 15b – Particulate Matter Emphaze AEX Hybrid Purifier Capsules [ppb] - BV800R 

Particulate
BV800R – untreated BV800R - Autoclaved BV800R – Base Sanitized
Size
  25mM NaCl 50mM
10% 100% 10% 100% 10% 100%
Phosphate
>10 μm 107 14.0 12.0 24.7 10.7 48.7 10.2 12.2
>25 μm 0.3 1.3 1 1.3 0.6 1.7 0.9 0.6

References:
3M SOPs: 10L.600.118(A), 10L.300.007(D) & 10L.500.036(ORIG)
Industry Standards: USP37 <788> Particulate Matter in Injections, USP37 <1231> Sterile Water for Injection &
US FDA 21 CFR 211.72 and 210.3(5)
Laboratory Reports: Lab-12369, Lab-13204

F. USP <85> Bacterial Endotoxin

As part of the product release tests for every Emphaze AEX Hybrid Purifier media lot produced, 47-mm discs of media are
challenged individually with a 200mM aqueous NaCl solution at a flow rate of 8 mL/min (effective flux of 350 LMH) to a total
volume of 80 mL (equivalent to the required preconditioning flush volume of 54 L/m2). A 2 mL filtrate sample collected at
the end of flush is analyzed per USP <85> for extractable endotoxin concentration by a Limulus Amebocyte Lysate (LAL)
reactivity method. The extractable endotoxin release specification for AEX Hybrid Purifier media is ≤0.12 EU/mL.

Table 16. 3M™ Emphaze™ AEX Hybrid Purifier Extractable Endotoxin Post Required Preconditioning Flush
Number of Manufacturing Total number of
Product Endotoxin Concentration (EU/mL) STD DEV
Lots Samples

Emphaze AEX Hybrid Purifier Media 4 12 ≤ 0.12 0.006

Note the release specification is based on a dynamic flush protocol that does not necessarily reflect the total endotoxin
amount in the media. Therefore, the extractable endotoxin amount may be impacted if using a different challenge fluid (i.e.,
pH, conductivity, protein, etc.) under different test conditions.

Reference:
3M SOPs: 10L.500.041(ORIG); 10L.500.012(ORIG)
Industry Standards: USP <85> Bacterial Endotoxin

VIII. Shelf Life

Emphaze AEX Hybrid Purifier media: 2 years at recommended storage temperature: 5⁰C - 30⁰C

The shelf life/expiration date of the Emphaze AEX Hybrid Purifier is determined in accordance with ASTM: F1980-07 (Standard
Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices). An accelerated aging protocol is utilized to
determine the shelf life of new products within a shorter period of time by intensifying the temperature and in turn accelerating
the normal aging processes. Using an Arrhenius equation, accelerated aging period, temperature and a rate coefficient are used
23 
 
 to model the shelf life of the products. A rate coefficient equal to 2 is used initially for new products as it is generally accepted as
a conservative estimate for accelerated aging of medical devices. As both accelerated and real-time aging data become
available, the value of the rate coefficient for the product is refined to provide a more accurate estimate of shelf life.

Accelerated aging studies of the 3M™ Emphaze™ AEX Hybrid Purifier were carried out at 70°C in an environmental chamber.
After aging, performance metrics that form the basis for determining the shelf life are extractable TN and charged dye dynamic
binding capacity as described in the Product Specifications section.

All Emphaze AEX Hybrid Purifier products should be stored in the original package and in a controlled environment. To maintain
product stability the long-term storage temperature should be between 5 and 30°C. Brief excursions outside this temperature
range during storage or transport should have minimal impact on performance. All Emphaze AEX Hybrid Purifier capsules and
manifolds should be inspected before use to determine if any unanticipated damage has occurred during shipping and storage.
This includes an inspection of the O-rings to confirm that they have no nicks or cuts, are cracked or exhibit a loss of elasticity
that would prevent normal sealing operation.

Table 17. Emphaze AEX Hybrid Purifier Accelerated Aging Performance 

Metanil Yellow DBC²
Number of Accelerated Aging Accelerated Aging Modeled Shelf Life Total Nitrogen (ppm)
Product (mg/cm²)
Samples Temperature Time (days) @ 30°C (years)
Average STD DEV Average STD DEV
11 NA 0 0.0 3.6 0.9 30.5 1.0
8 0.4 2.6 0.7 31.9 2.7
15 0.7 4.9 0.8 28.7 0.6
BV120R 6 per time 22 1.0 5.2 0.5 31.5 0.6
70°C
point 28 1.2 6.0 1.1 35.6 2.3
56 2.5 10.5 3.3 33.5 1.9
68 3.0 14.7 2.8 35.1 0.3
Specification: 11.3* 28.0
* The level of TN shown to pass USP <88> is 18.9 as shown in Graph 9. The media release specification is 6.6 ppm. Based on these factors the maximum acceptance level for extractable TN
after aging is 11.3 ppm, providing a significant margin for compliance with USP <88>.

18.9
Dynamic Binding Capacity (DBC) (mg/cm )

30
Total Nitrogen (TN) (ppm)

10

20

10
2

2
0
0 1 2 3
Modelled Shelf Life (years) at 30C Storage Temperature
Extractable Nitrogen Dynamic Binding Capacity
Figure 9. Emphaze AEX Hybrid Purifier Accelerated Aging Performance

References:
3M SOP: 10L.100.008 v1.0
Industry Standard: ASTM: F1980-07 (Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices)
Laboratory Reports: LAB-12386, TCG-1157
24 
IX. Regulatory Compliance

A. USP <87> Biological Reactivity Test, In Vitro

USP <87> Biological Reactivity Tests, In Vitro were performed on the anion exchange nonwoven in the 3M™ Emphaze™
AEX Hybrid Purifier Capsules following performance of the specified required preconditioning flush. The ISO 10993-5
standard is an equivalent test method referenced in both United States and the European Union. The tests were performed
by an accredited, independent laboratory following Good Laboratory Practices.
All wetted components are in compliance with the USP <87> requirements established in the reported USP revision. All USP
compliance reports are included in the Drug Master File and can be made available upon request.

B. USP <88> Class VI Biological Reactivity Test, In Vivo

The USP <88> VI Biological Reactivity Tests, In Vivo were performed on the anion exchange nonwoven in the Emphaze AEX
Hybrid Purifier (Table 2). The tests were performed by an accredited, independent laboratory following Good Laboratory
Practices (GLP). The test sample is based on 0.2 grams of media, excised from the product following the required
preconditioning flush, per 1 mL of extracting fluid.

All wetted components of the Emphaze AEX Hybrid Purifier products are in compliance with the USP <88> Class VI-70°C
requirements established in the reported USP revision. All USP compliance reports are included in the Drug Master File and
can be made available upon request.
The USP Biological Reactivity Test is performed on a single unit from a single production lot. Verification of manufacturing
control correlated to this claim is obtained by extracting the Emphaze AEX purification media prior to final capsule
assembly. The media is extracted at conditions described in the USP <88> Biological Reactivity Tests, In Vivo for Systemic
Injection. For efficiency in quality control, the extraction protocol for media release was chosen to be 121ºC for 1 hour using
0.9% sodium chloride in water (w/v). It is recognized that this 121°C, 1-hour protocol is more extreme than the 70°C, 24-
hour USP <88> VI compliance test for the Emphaze AEX Hybrid Purifier media, and likely provides more conservative
results.
To demonstrate consistency between the quality control sample media extraction and the testing done in the final product
configuration, a preconditioning flush was performed on a Emphaze AEX Hybrid Purifier in a capsule format at a flux of 210
L/m²/hr to the required volume. A solution of 25 mM sodium chloride in reagent water was used for the flush (2.9 mS/cm,
5.5-7.0 pH). Samples of the media were excised from the lenticle and extracted at either 70ºC for 24 hours or 121ºC for 1
hour, using 0.9% sodium chloride in water (w/v). Comparative results of the quality control samples and those tested by the
independent laboratory are provided in Table 18a and 18b.
Under all recommended conditions, the Emphaze AEX Hybrid Purifier is in compliance with the USP <87> and <88>
requirements established in the reported USP revision.

Table 18a. Emphaze AEX Hybrid Purifier Extractable Nitrogen

Total Number of Extraction Total Nitrogen (ppm)
Product Number of Lots
Samples Conditions Average STD DEV

BV60R 1 6 121° C, 1hr 5.1 0.9

1 12 121° C, 1hr 4.7 0.4
BV120R
USP <88> Compliance Lot 70° C, 24hr 3.8
121° C, 1hr 3.4 0.8
BV360R 1 1
70° C, 24hr 5.1 0.4
11 121° C, 1hr 1.5 0.8
BV800R 2
35 70° C, 24hr 3.2 0.9
BV5600R 1 53 121° C, 24hr 2.6 1.3

Flat Sheet Media 10 40 121° C, 1hr 3.7 0.9

Specification: 6.6

25 
 Table 18b. 3M™ Emphaze™ AEX Hybrid Purifier Extractable Nitrogen – Post-Sanitization
Number of Total Nitrogen (ppm)
Product Sanitization Flush Conditions
samples Average STD DEV

None 25mM NaCl 12 4.7 0.4

Autoclave 25mM NaCl 9 2.8 1.3

BV120R Base 100 mM Acetate Buffer 9 6.6 0.8

Base 50mM Phosphate Buffer 9 3.9 0.3

100mM Phosphate
Base 9 3.9 0.4
Buffer
Specification: 6.6

C. BSE/TSE
3M understands the continued public interest and the increased regulatory scrutiny concerning the transmission of bovine
spongiform encephalopathy (BSE) and other transmissible spongiform encephalopathies (TSE).

In order to address these issues, the following statement is offered: In order to assess the BSE/TSE risk associated with the
above products, we have contacted our suppliers of raw materials and performed an evaluation of our production processes
to determine if any of the materials used are of animal origin.

The result of our survey and inquiries of our raw material suppliers has revealed that the polypropylene resins used in the
nonwovens and the glass-filled polyphenylene oxide / polystyrene resin used in molded parts may contain tallow. We can
state, however, that our suppliers have indicated that these parts which use tallow derivatives and stearic acid are
processed at conditions conforming to the requirements of the European Medicines Agency note for guidance EMEA/410/01
rev.3.

X. Quality Assurance
Pharmaceutical and Biological products manufacturers routinely visit 3M manufacturing sites to audit production quality
management systems and documentation. The full ISO 9001:2008 certifications for 3M Separation and Purification Sciences
Division global plants are available on request.

The Emphaze AEX Hybrid Purifier products are released with Certificate of Quality (CoQ).

The Emphaze AEX Hybrid Purifier products are defined as non-hazardous articles under REACH and do not require a Safety Data
Sheet under Article 31 of Regulation (EC) No. 1907/2006.

These products are not regulated under the OSHA Hazard Communication Standard (CFR Title 29 1910.1200). An Article
Information Sheet is not required for these products. Article Information Sheets are available in the US as a courtesy.

26 
 Product Use
Intended uses: Single use processing of aqueous based biological pharmaceuticals (drugs) and vaccines strictly following the product operating instructions and cGMP
requirements, where applicable. Customers must determine whether the 3M product is suitable for a specific application based on a risk assessment that considers the product
leachable characteristics and its impact on drug safety.
Prohibited uses: Do not use as a component in a medical device that is regulated by any agency, and/or globally exemplary agencies, including but not limited to: a) FDA, b)
European Medical Device Directive (MDD), c) Japan Pharmaceuticals and Medical Devices Agency (PMDA). Do not use in applications involving permanent implantation into the
body, life-sustaining medical applications, or applications requiring global Food Contact compliance.

Technical Information
The technical information, guidance, and other statements contained in this document or otherwise provided by 3M are based upon records, tests, or experience that 3M believes
to be reliable, but the accuracy, completeness, and representative nature of such information is not guaranteed. Such information is intended for people with knowledge and
technical skills sufficient to assess and apply their own informed judgment to the information. No license under any 3M or third party intellectual property rights is granted or
implied with this information.

Product Selection
Many factors beyond 3M’s control and uniquely within user’s knowledge and control can affect the use and performance of a 3M product in a particular application. As a result,
customer is solely responsible for evaluating the product and determining whether it is appropriate and suitable for customer’s application, including conducting a workplace
hazard assessment and reviewing all applicable regulations and standards (e.g., OSHA, ANSI, etc.). Failure to properly evaluate, select, and use a 3M product and appropriate
safety products, or to meet all applicable safety regulations, may result in injury, sickness, death, and/or harm to property.

Warranty, Limited Remedy and Disclaimer

Unless a different warranty is specifically stated on the applicable 3M product packaging or product literature (in which case such warranty governs), 3M warrants that each
3M product meets the applicable 3M product specification at the time 3M ships the product. 3M MAKES NO OTHER WARRANTIES OR CONDITIONS, EXPRESS OR IMPLIED,
INCLUDING, BUT NOT LIMITED TO, ANY IMPLIED WARRANTY OR CONDITION OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, OR ARISING OUT OF A COURSE OF
DEALING, CUSTOM, OR USAGE OF TRADE. If a 3M product does not conform to this warranty, then the sole and exclusive remedy is, at 3M’s option, replacement of the 3M
product or refund of the purchase price.

Limitation of Liability
Except for the limited remedy stated above, and except to the extent prohibited by law, 3M will not be liable for any loss or damage arising from or related to the 3M product,
whether direct, indirect, special, incidental, or consequential (including, but not limited to, lost profits or business opportunity), regardless of the legal or equitable theory
asserted, including, but not limited to, warranty, contract, negligence, or strict liability.

3M Purification Inc.
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