Founded in 1988 as a chromatography supplier'

1
SEPARATIONS History

• Founded in 1988 as a chromatography supplier.
• Expanded into 4 divisions over the last 20 years.
• Current divisions are Chromtechniques,
  Biotechniques, Watertechniques, and
  Biopharmtechniques (latest addition).
• Sales staff comprise of Microbiologists,
  Biochemists, Geneticists and Chemists.
• Apart from PALL, SEPARATIONS are proud to
  represent companies such as Hyclone Machery
  Nagel, Phenomenex, Hirschmann
• www.separations.co.za

2
PALL History

• The PALL Corporation was initiated by Dr. David
  Pall 50 years ago, and has now expanded across 23
  countries, making PALL, the largest filtration,
  separation and purification company in the world.
• PALL is globally recognized for quality,
  technical support and superior product
  performance. The PALL corporation prides itself
  on breaking innovative barriers, developing
  integrated solutions and optimizing process
  efficiency.

3
GENERAL PRINCIPLES OF FILTRATION AND FILTRATION
PRODUCTS
4

• FILTRATION

5
Filtration

• What is it?
• Operation used to separate solids from
  liquids/gases.
• Numerous types of filters used for these
  processes.
• Many different types of filtration
• Where is it used?
• Every industry Aerospace, Fuels/chemicals,
  Marine, Graphic arts, Industrial manufacturing,
  Microelectronics, Power generation,
  Transportation, Water treatment, Food and
  beverage, Biopharmaceuticals, Laboratory, Medical

6
The Four Levels of Filtration
The Four levels of Filtration

• Macro Filtration
• Particle size range 10µm to 1,000µm
• Sand, Mist, Pollens
• Microfiltration
• Particle size range 0.1µm to 10µm
• Bacteria, Yeast, Fungi, Colloids
• Ultrafiltration
• Particle size range 0.001µm to 0.1µm or
  10,000 to 1,000,000 Mol. Wt.
• Proteins, Nucleic acids, Endotoxins, Colloids
• Reverse Osmosis
• Particle size range 50 to 10,000 Mol. Wt.
• Ions, Soluble salts

7
Direct Interception
Particles are removed within the structure when
the particle is larger than the flowpath
8
Inertial Impaction
Because of the momentum, the particles leave the
streamlines of fluid flow and come into contact
with the filter media
9
Surface Charge (Zeta Potential)
NegativelyCharged Contaminant
Flowing Aqueous(Ionisable Liquids)
When in contact with the medium, the particle
will be retained by absorptive forces
PostivelyCharged Filter Medium
10
Diffusional Interception (gases only)

• Gas molecules are in a state of random motion
• Particles much smaller than the pore size are
  retained
• Movement of particles ordroplets resulting
  frommolecular collisions is knownas Brownian
  Movement(Robert Brown 1773-1858)

11
Membrane Filtration

• A Membrane Filter typically traps contaminants
  larger than the pore size on the addressed
  surface of the membrane.

12
What is depth Media

• A Depth Filter is a filter consisting of either
  multiple layers or a single layer of a medium
  having depth, which captures contaminants within
  its structure, as opposed to on the surface.

13
Depth Membrane

• Particles may be trapped
• on the surface But
• Dirt holding capacity also
• increased by particles
• being retained throughout
• the thickness of the filter
• medium.

14
A Combination Filter

• A Combination Filter combines different membrane
  pore sizes, or combines depth media and a
  membrane filter to create self-contained serial
  filter units. They can offer an economical
  alternative to using individual prefilters and
  final filters.
• Sometimes two membranes are used in series e.g.
  0.8µm/0.2µm

15
What makes a Good Filter?
2. NO Unloading
1. NO Media migration
3. NO Channeling
4. Reproducible Performance 5. Economic to use
16
Pore Size Ratings

• Nominal Rated
• Specifies the pore size at which a challenge
  particle of a particular size will be retained
  with an efficiency of 60-98.
• Nominally rated filters vary significantly in the
  filtration industry from supplier to supplier.

17
Pore Size Ratings

• Absolute Rated
• Specifies the pore size at which a challenge
  organism of a particular size will be retained
  with 100 efficiency under specific test
  conditions
• Example 0.2µm rated membranes must retain 100
  of the microorganism Brevundimonas diminuta
  according to ASTM F838-83 methodology

18
Extractables

• Contaminants eluting from the filter media or
  device which may adversely effect effluent
  quality
• HPLC Analysis - Add extraneous peaks
• Cell Culture - Kills cells
• Micro Analysis - Inhibits growth / affects
  recovery
• Contaminants may be
• Wetting agents in filter media
• Sterilization residuals (EtO- Ethylene Oxide)
• Additives in polymer or housing components
  (colorants, mold release agents, etc..)
• Remember its not just about the filter,
  consider the housing

19

• CARTRIDGE CONSTRUCTION

20
Normal Direction of Flow

• Typical Pall cartridge showing normal flow -
  outside to inside

21
Typical Cartridge Construction
Welded locating fins
Melt-sealed end-caps
Reliable melt-sealed side-seam
Close pleating for optium area
22
Polyfine II Construction
End Cap
Core
Medium
Support
23
Pleating machine
24
Side Seams
25
Filter Area

• Pall filter cartridges offer a very large
  effective filtration area

Typical example - Emflon 0.81m2 of medium in a
single 254 mm module. Large area gives long life
26
Construction of a Module
Ends of pack sealed with polypropylene
End-cap melt sealed
27
Assembly of Core,Cage and Pack
28
Melt-Sealed Construction

• The media in Pall cartridges are melt-sealed into
  the end caps

Ends of media packs are also melt-sealed. No
adhesives are used
29
Module Assembly
Modules welded together
30
Profile filter cartridges
31
Batch Documentation
32
P Grade Filters
Are made to the following specification

• To USP biological standards.
• Comply with FDA and CGMP.
• Manufactured in a controlled environment.
• Traceability of individual filters.
• Forward Flow Tested.
• Batch tested for, Pyrogens, Oxidisables and pH
  shift.

32
33
P Grade Certificate
34
Seals

• Remember the filter can be no better than the
  seal
• Pall seals are offered to complement a high
  quality product
• carefully chosen
• quality controlled
• specific for Pall
• Wide range to cope with wide range of
  applications
• Consider Application and PRICING!

35

• FILTER HANDLING

36
Installation of Cartridges

• Warning. Before opening a housing make sure it
  is not under pressure.
• Drain any residual liquid from the housing.
• Prepare the housing in accordance with the
  Service Instructions
• First, refer to the instructions packed with the
  cartridges
• Verify, from the part number that the cartridge
  is of the type used at the location
• Open outer bag outside clean area if required

37
Storage and Care Instructions
Storage box
Service instructions
38
Service Instructions
Example SD1073 for Sealkleen cartridges
39
Fitting into Housing
Cut off bottom of bag, slide cartridge
out. Remove bag only when located in tube sheet.
40
Bayonet Lock Double O-ring style
Remember to wet O rings with a suitable non -
contaminating liquid.
Steaming or Autoclaving - do not use alcohol to
wet.
41
Cartridge Handling

• Warning. Before opening a housing make sure it
  is not under pressure. In clean area, cut open
  inner bag do not force cartridge through
  unopened bag
• Retain bag around cartridge while handling
  remove bag only when cartridge is in position in
  tube-sheet
• Remember, the objective should always be to
  minimize the generation inclusion of particles

42
Housing Closure and Venting

• Close secure housing in accordance with the
  Service Instructions
• Before service, the housing should be flushed
  vented
• Purpose of venting is to remove trapped air so as
  to utilise all available filtration area

43
Venting the Housing

• Ensure outlet valve is closed open vent valve
• Slowly open vent valve allow small flow through
  vent until bubble-free liquid emerges
• Remember any safety precautions for aggressive
  liquids
• Note An unvented housing could contain up to 1/3
  of its volume of air which could reduce the
  filter life to 1/2 !

44
Filter Life Dependant on Available Filter Area
Air
Water/ product
Available filter area
45
Surface Roughness

Ra The arithmetical average value of all
absolute distances of the roughness profile from
the centre line within the measuring length
Electropolishing gives a surface that is Smoother
,Cleaner, More corrosion resistant All Advanta
housings are electropolished Inner surfaces to Ra
lt 0.4 µm Outer surfaces to Ra lt 0.8 µm

46
Electropolishing
A method of polishing metal surfaces
electrolytically. The component is immersed in
an acidic electrolyte solution and a DC voltage
is applied using the component as the positive
electrode (anode). Microscopic irregularities
are dissolved away leaving a smooth, bright
surface

• Bacteria have diameters typically of 1 µm
• An Ra-value (roughness average) of 0.4 µm is
  economic and makes sense
• Bacteria are not trapped in crevices
• Bacteria in direct contact with cleaning fluid
  or sterilisation media

47
Sanitary Housings

• A housing designed to meet the needs of the
• pharmaceutical, food and beverage industries,
• Should have the following features
• Made from materials which do not corrode when in
  contact with the process fluids
• Easy-to-clean surfaces (mainly polished surfaces
  specified by these industries)
• Free from crevices and dead spaces in which
  organisms could lodge and survive
• Suitable for autoclaving or in situ steam
  sterilisation
• PALL supplies a complete range of housings
  suitable for all applications, with variety of
  inlet/outlet connections and styles.
• PALL also have a low cost Industrial Range with
  NO Ra claims

48
When to change Cartridges?
End of batch
System max ?p
End of calendar life
Cartridge max ?p
End of compatibility life
Flow rate too low
At servicing shut-down
49
Throughput not Achieved
Possible Reason
Solution

• Filterability change

Check up stream process.
Change filters.

• Wrong filters

• Housing not vented

Vent housing.

• Flow rate higher than designed

Revert to original flow rate.
50
Difficulty in Passing and Integrity Test
Possible Reason
Solution

• Filter not fully wetted.

Rewet and vent.

• Wrong test values used.

Check with SEPARATIONS

• Temperature changes during test.

Stabilise temperature.

• Water level too low in WIT.

Refill.
51
Filter Steaming
Damage caused by excess temperature. Note height
reduction, compared with normal 254mm cartridge.
52
Filter Steaming
Cartridge melted by the application of super
heated steam.
53

• MEMBRANE TECHNOLOGY

54
?-ratio
?x
2.7
55
?-ratio
Total of 10000 particles greater than 10um

• 10000 10 000

1
Efficiency (10 000 1) x 100 99.99 10 000
One particle greater than 10um that penetrated
membrane
10um membrane
56
?-ratio is more meaningful than Efficiency
Efficiency
Downstream Count
? Ratio
Filter
A 1 10,000
99.99
B 10 1,000
99.9
C 100 100
99.
Filter A is 100 times more efficient than Filter
C . . . although efficiencies differ by only
0.99 !
2.14
57
Variation in Permeability Dirt Capacity as a
Function of Fibre Diameter
Area A Area A Area A ?p Px ?p Px/4 ?p
Px/16 Dirt Capacity Y Dirt Capacity 4Y Dirt
Capacity 16Y
?p differential pressure
58
Profile Media Construction
Core
Outer pre-filter layer tapering to....
Inner pre-filter layer
Absolute-rated layer
59
Benefit of Graded Pore Structure
Uniform Pore Structure Graded Pore
Structure Contaminant Captured Contaminant
Captured in outer 15 of filter in outer 60 of
filter Up to 3 x dirt holding capacity
60
New Developments and TrendsThe Magic Combination
MachV technology
Ultipleat technology
Small core design
61
Membrane Structure

• Asymmetric membrane structure
• Many different V-grades possible
• High dirt load capability
• Superior flow rates

62
Optimised Filter AreaPleating Technology
Up to twice the area
63
Optimised Filter AreaPleating Technology
Crescent shaped pleats Higher membrane area per
cartridge ? Higher flow rates ? Increased service
life Tight filter pack ? Greater mechanical
strength of filter pack ? Allows higher Dp during
steaming
Pall patented Ultipleat technology
64
Filtration Area

• Pleating of membranes necessary to achieve high
  surface area

• Typical area - 0.5 to 1.5m2 in a 10 module
• Large area gives high flow, low ?p and long life

65
Optimised Filter AreaOrifice Organization
Pall Small Core Design

• More membrane area
• Longer service life
• Whole filter area accessible
• Very stable in Ultipleat design

66
PALL Membrane Materials

• Emflon PTFE membrane, vent/air filtration
• Flourodyne II PVDF, for sterile liquid
  filtration
• Ultipor Nylon 6,6, sterile filtration
• Posidyne covalent charged Nylon 6,6.
• Supor Polyethersulphone membrane for sterile
  filtration
• HDC II Polypropylene high dirt capacity
  membrane
• GF plus filters Glass fibre with positive Zeta
  potential
• Stainless steel filters Sintered Metal Mesh
  Filter Cartridges

66
67
Posidyne
Posidyne
Negatively Charged Contaminant


POSIDYNE Positively charged membranes to atrract
negatively charged particles e.g. endotoxins
68
Disposable Technology

• Novasip patented Technology
• Can be Steamed in Place up to 142degrees celcius.
• No stainless steel housing required Low
  installation and cleaning costs
• Operating pressures up to 6.5bar

69
Disposable Technology
70
New developments allow

• Much smaller sizing
• Higher speed
• Longer service life
• Lower total filtration costs
• User friendly filter handling
• New options for disposable solutions with higher
  performance in smaller units

71
Filter A ? Filter B
B
A
Processes 10 000 Litres. High Extractables 10
um Nominal Rated OR Abs rated with B-ratio of
1000 Use of adhesives to join endcaps
Processes 20 000 Litres. Low Extractables 10um
Absolute Rated with B-ratio of 5000 Melt sealed
endcaps
?
Cost R80
Cost R100
Which one is more expensive ?
72
When selecting or validating a filter

• Check the membrane material (e.g. Nylon 66, FDA
  listed, positively charged, pre-filter layers)
• Check the claim on extractables
• For 0.2um filters, check if it is STERILIZING
  grade or MICROBIAL grade only
• Make sure the ends are melt sealed so that
  contamination from adhesives does not occur
• Ensure the seal material is compatible with your
  process fluid
• Check if the filter is absolute or nominal rated
• If it is absolute rated, check the B-ratio, NOT
  efficiency.
• Check the flow-rates the filter is able to
  provide (can it process
• 10 000L per hour or 20 000L/hour?)
• Check the operating conditions (Highest operating
  temp, highest Differential Pressure)
• Check the No. of Autoclave cycles
• Check the filter cage and support material

73
What PALL has to offer

• Entire Range of disposable solutions to minimize
  start up costs, cleaning costs, standard costs.
• Range of filters for low cost /non-critical/
  non-pharmaceutical applications e.g. CLARIS from
  Filterite Range R30/filter
• Highest quality, absolute rated filters with
  B-ratios gt 5000 for all pharmaceutical and
  biotech applications
• TFF/UF casettes and modules for Biotech
• Complete Chromatography solutions
• Automated Large Scale Systems
• Resins in various formats

74
SEPARATIONS and PALL Services to YOU

• Filterability trials on new products
• Product/Process validation (Pall UK)
• Filter Integrity Testing
• Water Plants
• Filtration Training

75
Contact Details

• René Moodley
• Tel [phone]
• Mobile [phone]
• Fax [phone]
• rene_at_separations.co.za

76
Important Note !
The handling notes in this presentation are
intended only as an introduction to the
subject.Equipment should be operated strictly in
accordance with the Service Instructions included
with cartridges housings in accordance with
SOPs