USP Workshop on Particle Size

Welcome to the

USP Workshop on Particle Size:Particle Detection and Measurement

Day 2

December 8-10, 2010

USP Headquarters, Rockville, MD

USP Workshop on Particle Size:

Particle Detection and Measurement

December 8-10, 2010; USP Headquarters

Desmond Hunt, Ph.D.

USP Senior Scientific Liaison

Welcome and Opening Remarks




Session III: USP General Chapters

Track 1: Parenterals

Spalding Auditorium

Track 2: Aerosols

Briggs/Parker/

Marshall/Wiley




Chair: Mr. Scott Aldrich

Ultramikro

Session III, Track 1: Parenterals - USP

General Chapters and

Quality Standards for Medicines, Supplements, and Food Ingredients throughout the World

8.1 Parenterals USP General Chapters /

Historical Perspective and Current Chapters ReviewScott Aldrich


Particle Detection & Measurement

Outline

Introduction

Background

History and Limits Evolution

History of liquid particle counting

Periods of Investigation

Harmonization of Aug 1 2007

Current chapters

Limits according to container volume and method used

informational chapter official USP 34, 2011

follows discussion

Chapter Crossover

What is Particulate Matter?

Test Methods

Light Obscuration Counting and Operations

Membrane Microscopic Counting and Operations

Comparison of LO and MM methods

Introduction

Parenteral injections and ophthalmic solutions are sterile

liquids, with expectations for physical appearance and

stability.

All released product must comply with two limit tests for

particle content:-

USP General Chapter Injections

See PF Stimuli Article Vol. 35(5) [Sept.-Oct. 2009], Visible

Particulates in Injections - A History and a Proposal to Revise USP

General Chapter Injections

Must contain low amounts of sub-visible particles

USP Injections

USP Ophthalmic solutions


History of liquid particle counting

Periods of Investigation1

Cognitive

Latent

Definitive

Evaluative

Harmonization

The Future

1Floyd Benjamin, IES conference 1990


Cognitive Period 1905-1948

1905 First USP reference to parenteral solution as a compendial drug. No references to particulate matter content or clarity.

1916 NF IV includes 6 monographs for parenterals; however, no mention of appearance.

aqueous solutions are to be clear, i.e., when observed over a bright light, they shall be substantially free from precipitate, cloudiness or turbidity. Specks or flecks; fibers or cotton hairs, or any undissolved

In 1942, USP XII and NF VII both attempt to further define the

published definition.


Latent Period 1949-1965 No changes in compendial requirements, although many reports in literature regarding medical events from particulate matter injection.

1949 USP revision committee eliminates the clarity test

should be exercised in the preparation of injections to

1965 - First Limit Standards (Canberra, Australia)In 1965, the National Biological Standards Laboratory, Canberra

-stimulated compendia and regulatory activities in the US, leading to the Definitive Period.

Definitive Period I 1966-19731966 FDA symposium on the safety of large volume parenterals1

1972 Australian comparison of Coulter and HIAC counts for parenteral products2

Australian and English standards for particulate matter in

Australia - ten containers must be less than 2x the following limits:

NMT 100 particles/mL 2m


British Std: mean of 5 containers and individual

1973 Turco and Davis review the clinical consequences of injected particulate matter3


1. FDA - National symposium on safety of large volume parenteral solutions. U.S. Dept. of Health, Education and Welfare,

Washington DC, 1966.

2. Kendall and Tilley, Comparison of Coulter counter and HIAC counts for parenteral products

3. Turco S. Davis NM. Hosp Pharm. 1973;8:137-40.


Definitive Period II 19741974 Revision of Foreign Particulate Standards

Great BritainNMT 1000 particles/mL 2m


AustraliaNMT 1000 particles/mL 2m

NMT 250 particles/mL 3.5m




PMA, USP, FDA meet to discuss further refinement of the standard for

In December 1974, USP proposed:NMT 50 particles/mL 10m


studies and collaboration with AMA, ASHP, PMA:Absence of particles 50m in a 10 sample mean

NMT 1 particle/mL 5m in a 10 sample mean


Definitive Period III 1975-19861975 USP XIX chapter used a membrane test to evaluate the particle

50 particles/ mL 10 m

5 particles/mL 25 m

electrical zone sensing (Coulter) or light extinction (HIAC) instruments.

10,000 particles/container 10m

1000 particles/container 25m

Throughout 1985, many meetings between PDA, PMA, FDA, industry and USP reviewed the limits and methods for all volumes

A new method, light extinction (obscuration), was added in 1985, in USP XXI chapter for small volume parenterals (SVP, 100mL and lower volume).

Thus, LVP standards were established in the US as well, and initiated the

Problems meeting particle standards for terminally sterilized dextrose-containing solutions were due to 5-hydroxymethylfurfural

USP and FDA to insert a disclaimer into the definition of valid particulate matter. do not attempt to size or enumerate amorphous, semi-liquid, or otherwise morphologically indistinct materials, that is, material that has the appearance of a stain or discoloration on the membrane surface.

January 1, 1986, the SVP standard and test method become official.


Evaluative Period 1986 1995The test methods for counting particles were continually improved through collaborative investigation and method revision.

1990 USP XXII defined new limits by membrane

for large-volume injections (>100mL):

for small-volume injections ( 100mL):

1995 USP 23 provided the most dramatic change. The light obscuration method became the preferred or Method 1 approach.

Ease of method control, objectivity, and efficiency

History of product experience and regulatory filing

for large-volume injections (>100mL):

for small-volume injections ( 100mL):


Evaluative Period 1995 2006In 2004, a new chapter for ophthalmic solutions was published in USP 27 for particulate matter in three size categories:

LO and MM50 particles/mL 10 m

5 particles/mL 25 m

MM testing by membrane methodologyThe same 10 m and 25 m limits and 2 particles/mL 50 m

Two important non-U.S. compendial organizations, European Pharmacopoeia (Ph. Eur.) and Japan Pharmacopoeia (JP) included the USP change to include the SVI products in particle limits.

Ph. Eur. changed to include SVI products in 2005

JP updated to include them in 2006.


Harmonization Period 2007 2010

2007 all three organizations, through the Pharmacopeial Discussion

Group, have harmonized the methods, definitions and limits.

This chapter is seen in the respective pharmacopeia as USP ,

EP 5.5 and JP XIV, XV, and is the current standard.

These standards monitor injectable solutions for the content of

particulate matter undetected by visual inspection. However, the

harmonized USP chapter provides much less method direction than in

previous USP versions, and is addressed by the planned

publication of chapter in 2011.

Harmonization - Current USP Guideline

USP 33 --InjectionsStipulates the expectations and tests for all injectable dose forms

Foreign and Particulate Matter

Test methods concern quantification of particulate matter in:

Pharmaceutical injectable products

Ophthalmic solutions

USP 33 --Particulate Matter in Injections2 methods: LO and MM

Limits depend upon product volume

USP 33 --Particulate Matter in Ophthalmic Solutions2 methods: LO and MM

Limits are per mL

Exempt from limits:

Radiopharmaceuticals

Parenteral products for which labeling specified use of a final filter (provided

available scientific data justify the exemption)

Irrigating solutions

Current Limits

The use of two methods is a "two -LO results are suspicious or fail limits, the microscope method is run

Method 1 LO Method 2 - Microscope

Parenteral Volume

10 m 25 m 10 m 25 m

SVI 100 mL and lower

6000 per container

600 per container

3000 per container

300 per container

LVI above 100 mL

25 per mL 3 per mL 12 per mL 2 per mL

Current Limits

Since 2004 Chapter --Particulate Matter in Ophthalmic

SolutionsOfficial for the sub-visible particle limits of Ophthalmic products

All limits on a per mL basis.

Methods are essentially and Limits are tight

Method 1 - LO Method 2 - Microscope

10 m 25 m 10 m 25 m 50 m

50 per mL 5 per mL 50 per mL 5 per mL 2 per mL

Comparison of Injectable & Ophthalmic Solution

Product Particulate Load Limits As 5mL Fill Volumes. Particle Size

by Membrane

Assay

USP Limits

5mL Injectable

Volume

USP Limits

5mL Ophthalmic Volume

10 m 3000 part./container 250 particles in a 5mL

container or 50 particles/mL

25 m 300 part./container 25 particles in a 5mL


50 m No specification 10 particles in a 5mL


Particle Count by Membrane Microscopy

Limits for Liquid Products


How will we characterize the next period of work?

USP Chapter Crossover

Two Particle Count Tests in USP Guideline Chapter

Light obscuration

Microscopic

Represent the baseline and standardized approach for particle

measurement, with which many companies have compiled deep

historical data.

Provide a snapshot of particle load in final product form

Are not necessarily optimal for every formula or dose form

Visual Inspection detects particles there is crossover

Note that

Analytical methods and limits evolve with technical improvements

Changes to methods and limits are influenced by regulatory,

commercial and harmonization efforts

Visible Sub-visible Sub-micrometer

1m25m 10m150m

Increasing Probability of Detection

Visible

Gray zone

Compendial Threshold

Size Domains

Where do the visible and sub-visible domains crossover?

Visual Inspection

Product development and release must include both visual

inspection and particle counting

Commercial products must comply with Chapters and

or

Size Crossover: Material may be visible down to ~50m

Particles are visible in the upper end of the detectable size

range by the primary sub-visible count method, light

obscuration

The microscopic method retains solids (some semi-solids) at

into the visible zone

Size domain intersection for Chapter visual

inspection and Chapter / sub-visible

methods

LO results are truly sub-visible

Membrane results span a wide size range, into the

visible

Product must meet all requirements from time of

release to end of shelf life

What is Particulate Matter?

Particulate matter in injections and parenteral infusions is

defined as extraneous, mobile, undissolved particles, other

than gas bubbles, unintentionally present in the solution.

Practically, any semi-solid to solid material, soft to hard,

transparent to opaque may be counted as a particle and may

be considered objectionable dependant upon the identity.Such as air, liquid, gel, singular solid, aggregate, agglomerate, drug

solid, salt, polymorph, lubricant, plasticizer

Particulate Matter Details

What forms do we see?Insoluble, mobile solids/semi-solids

Single entity alone or in aggregates

one specie or multiple species

chemical interactions yielding solids

Formulation change yielding solids

OriginsForeign to the Process: Presence due to Extrinsic Source

Part of the Process/Product: Formation due to Intrinsic Source

Process function failure

Formulation/Package origin

Inherent to the formulation Presence in biologic products

Studying the Particle Load aids Refinement of the Final

Product

Test Methods

Light Obscuration

Membrane Microscopy

Current Test Methods

Two procedures are specified in both Chapters and

has particle limits according to test article volume:Method 1 (Light Obscuration Particle Count Test)

1a. > 100mL per mL

1b. = 100mL per container

1b. < 100mL per container

Method 2 (Microscopic Particle Count Test) 2a. > 100mL per mL

2b. = 100mL per container

2b. < 100mL per container

has limits per mL regardless of product volume.

Method 1 is preferred when examining injections, parenteral infusions and ophthalmic solutions

It may be necessary to test some preparations by the light obscuration particle count test followed by the microscopic particle count test to reach a conclusion on conformance to the requirements.

It may be necessary to utilize membrane microscopic alone, based upon the nature of the formulation or package.

LO Particle Count Test

Equipment: an apparatus that sizes particles and counts

by size using light obscuration (extinction) principle

Not Included:Instrument Standardization TestsCalibration Options

Typical CalibrationMono-disperse spherical solids between 10m and 25m

System Suitability verified with USP Particle Count

Reference Standard

Blank ControlParticle-free water

Particle-free water is water that has been passed through a

0.22m filter

5 x 5ml aliquots, total load 25 particles

Product Samples

Volume 25mL

Pool 10 or more containers to allow sufficient aliquot

Necessary for LO/Unnecessary for MM

Volume 25-100mL

One container, minimally

Volume >100mL

One container, minimally

What is your statistical sampling consideration?

Light Obscuration Method

The product particulate matter content

is determined by counting particles in

pre-determined size bins, from small

portions of product liquid

Pools of sample are required for

products


Voltage response is recorded

for a sphere of equivalent

circular diameter

The resultant particle size is

generated from a size-

voltage response calibration

curve constructed using

spherical mono-disperse

certified size standards

33

Per HachUltra


Enumerates sub-visible

solids, but also liquid and gas

Samples test fluid via a

metered system

Vendor-specific analysis

routines for calibration and

daily sampling

LO method has few operator-

induced effects

Some articles cannot be

tested meaningfully by light

obscuration

34


Blank Control

Degas the open container, by

Sonication at 80 to 120 watts for

approximately 30 seconds, or

allowing the sample to stand to

dissipate gas bubbles, or

evacuate the sample to outgas

(new in USP

LO Instrument Standardization

Instrument qualification is essential to test performance

Light Obscuration sections emphasize criteria rather

than specific determination method:Calibrate with spheres 10-25m

System Suitability can be verified with USP PCRS

User is responsible for

Ensuring that the counter is used and operated according to the

manufacturer's instructions

Ensuring proper standardization methods are applied to instrument

see Chapter Instrument Standardization Tests

Calibration

Interim checks

Daily

Weekly

3 month

These principles must be followed ensure that instruments operate

accurately within defined ranges36

LO Test Particle Limits

Reporting: average of 3 aliquots not to exceed particle limit

General Chapter

Test 1.A. Large-Volume Injections

(more than 100mL)

25 per mL 3 per mL

Test 1.B. Small-Volume Injections (less

than and equal to 100mL)

6000 per

container

600 per container

Ophthalmic Solutions 50 per mL 5 per mL

1.A. > 100mL 1.B. 100mL 1.B.

Membrane Assay Method

Harmonized Compendial Methods USP/EP/JP

100 x 2% with graticule

Two illumination paths

USP Graticule verified at installation

Not included:Calibration day-of-use

Blank control considerations

QualificationTraining and Inter-Lab Certification

Mono-disperse spherical solids from 10m and upUSP Particle Count RS

Microscopic Particle Count Test

Blank Control for Particle-free water

USP Particle-0.22-

Considerations for ?

Sampling LVP: may use single containers

SVP: may use single containers

Unless volume 25mL use 10 fills, pooled

Dilution and Recon with particle-free water or suitable solvent

20x inversion to mix

Entire volume is sampled

Use wetted, full particle-free water rinses

Membrane Microscopy Method

Captures solid matter from liquid of one or more product containers

onto a filter membrane

Enumerates sub-visible to visible, solid to soft or semi-solid

particulate matter on the membrane surface

Retained particles are counted by scanning the retention surface at

100 with a compound binocular light microscope

Method is highly operator-dependent

Operator makes decisions regarding

-the-

40

Membrane Microscopy Lab

Minimize traffic

Separate HEPA areas for wet

filtration and dry counting

steps

Dedicated glassware

Dilution and pooling systems

developed for product

volumes, product types

Establish lab controls

Operator training essential

Operator performance

evaluation recommended

Microscopic Particle Count Test

Full

Count particles in entire effective filtration area

Wet zone of liquid passage

Inner diameter of funnel

undefined

defined

If 1000 or less particles are present, the membrane should be fully counted

If the count difference between a GFOV at center and one at the

Count 20 GFOV for 25mm (16mm EFA) membranes

Count 100 GFOV for 47mm (37mm EFA) membranes

General Chapter

Test 2.A. Large-Volume

Injections (more than 100 mL)

12 per mL 2 per mL Not applicable

Test 2.B. Small-Volume

Injections (less than and equal

to 100 mL)

3000 per

container

300 per

container

Not applicable

Ophthalmic Solutions 50 per mL 5 per mL 2 per mL

MM Test Particle Limits

Reporting: average count from units tested not to exceed

particle limit

2.A. > 100mL 2.B. 100mL 2.B.

Informational Chapter

Provides LO calibration and control guidance removed from

after harmonizationInstrument Standardization Tests

Flow Rate

Volume Accuracy

Calibration

Sensor Resolution

Particle Counting Accuracy

Provides microscopy setup and counting guidance

Provides discussion regarding pharmaceutical development

practices

Previewed in Pharm Forum 35(6) Nov.-Dec. 2009

Official USP34, 2011

LO and MM: Compare and Contrast

Light Obscuration

Provides a robust, vendor-supported, precise and accurate

electronic particle count methodology

It counts suspended particles that are solid and others that may

be semi-solid, liquid or gas

Membrane Microscopy

Provides a count of particles by a 100 microscopic scan of a

membrane surface

Provides an orthogonal means of counting

As a second-pass, is it a Referee method ?

The two methods yield different perspectives of the particle

population

45


Light Obscuration

Effectively counts all particles as equivalent circular diameters,

over a wide range of concentration

Skews resultant sizes relative to shape when deviating from the

ideal spherical, or 1:1:1, axial ratio

Counts air bubbles and immiscible oil droplets

46


Membrane Microscopy

Directly compares isolates to

calibrated 10m and 25m circles and

includes a linear scale

equivalent 10m and 25m circles

while counting the membrane isolates

Many users attempt to correlate the

membrane count to that obtained by

LO

47

Ongoing Revision Process

Current methods and reliability are continually reviewed and

improved by USP staffContribution from industry

Assistance by industry specialists

Contributions from industry and by industry specialists

are overseen by the USP-DF (Parenteral Products: Industry)

Expert Committee

USP publishes Stimuli Articles in Pharmacopeial Forum to

allow perspectives, dissension, and initiatives from

participants

Certain formulations cannot be tested directly by either

method:Examples: sterile suspensions, nano/micro-suspensions, some

emulsions, low-volume and special device products

USP Workshop ParticlesDecember 8 - 10, 2010

USP Chapters and Methods

- VS -

Alternative Methods for Investigation and Compliance

49

Biotech products

Vacines

Novel treatments for Cancer

Nanoparticles (overcoming insolubility)

Controlled release microspheres

Polymers

Crystalline nanoparticles

Liposomal formulations

50USP Workshop on Particles

Extrinsic

Glass/stopper fragments

Metals

Silicon oil

Filter/process particles

Skin flakes

Ordinary dirt particles

Insect parts

Fibers: clothing/hair/etc.

51

Intrinsic

Ingredient degradation

API / Excipient changes

Active ingredients

Protein aggregation

Aggregation/foreign matter

Silicon interaction

Process related

Ingredient anomalies

Immiscible droplets

USP Workshop on Particles

Leachables

Extractables

Foreign particles

Protein aggregation

Glass delamination

Increased use of plastics

Pre- filled syringes

New stopper materials/coatings


ComplianceDetect manufacturing problems

USP Particulate Matter, Lot release

Formulation degradation over time/stress/ stabil .

Research Particle Size Analysis (especially sub - micron)

Evaluation of processing methods

Evaluation of ingredients

New drug products are more complex and often require more characterization.

Investigational (methods, understanding)


Provides 100% inspection of the batch.

Provides a pass/fail from brief observation.

Over 12 variables affect results.

Particles in rejects may not be identified.

Plays vital role with complex formulations


What is the smallest particle size our inspectors see reliably ?

What factors in sub - visible results, show correlation with V.I. results?

What is the variability between our inspectors at this plant, and those in our other plants ? Same with results ?

How much does this variability affect our product reject and acceptance levels ? (cost ) ?

Do we understand the relations between Vis. Inspector Training, our actual inspection process, our rejection levels and USP with each of our products ?

What are the critical issues for our products when comparing human and automated inspection with Sub - Visible (USP) results ?

Attend the annual PDA Visual Inspection Forum in Fall/2011 .


METHOD I

Light Obscuration (LO) Laser (usually) light extinction (blockage).

METHOD II

Microscopic Membrane (MM) Sample is

membrane and examined by optical microscopy.


particle size.Different methods or instruments used to measure particle size (or count), produce different results.The current Compendial methods are LO and MM

Current (laser base) instruments for particle countingInvestigational (orthogonal) methodOther (analytical) complimentary principles


59

Formulation

Immiscib

droplets

Gels

Fibers &

discrete

particles


USP Particulate Matter Methods I and II

Single Particle Optical Sensing Test Results (Summation Mode)

Particles per mL size (in microns)

Microscopic Membrane

Method

Sample

>0.5m > 0.7m > 0.8m > 1m > 2m > 5m > 10m > 25m > 10m > 25m

A

737995 562576 523208 460241 153786 36004 4441 0 4.7 2.6

B

1020601 768623 707751 603883 171300 41064 7145 203 2.3 0.7

C

1732076 1449868 1376814 1242247 497642 148685 22078 128 2.7 1.3


SAMPLER

Ensures consistent flow rate Low flow rates are advantageous for investigations/etc.

Volume precision

Commonly syringe based (1, 5, 10, 25 ml)Flow rates are usually limited to syringe size

(may not achieve 30ml/min with 1ml syringe)

Accepts large or small containers


USP Workshop on Particles 64

SENSOR Single detector for USP

Minimum size sensitivity: 2 microns (or less)

Flow rate range from 10ml/min

Large cell opening (400 m) preferable

Know coincidence values for 2 to 25 microns

Remote sensor mounting may be helpful for Use in a small Biosafety cabinet or clean hood

Accommodates very large containers

Allow sampling directly from experiment

Easier to accommodate stirring boxes


Software (must be part 11)

Includes recipe structure

Includes particle size distribution capability

Export data to Excel

Includes custom alarms for size

Built - in PQ Check routine with trend monitor

Converts output report to per/ml or other

Graphic sample overlays for comparisons


LO instruments with < 15 channels of size resolution.

Provide essential reporting

Easier to calibrate since fewer sphere sizes used

Data generally reported in a table

Reports should provide easy to see

Individual runs, displayed to observe run - run informity

Display all sizes reported in Cummulative mode

Provide additional reports to graphically compare sample counts (per ml or per container) vs size


Verify volume accuracy

Verify flow rate

Verify size accuracy

Verify count accuracy

Measure system drift

Perform routinely

Verification tests can overlap

Use Polystyrene latex particles (PSL)

Use standards certified for Size AND Count


73

Particle Std Size (m)

Previous Method New Method Size

Total Count >

10mRatio

10/15 Mean Size Std Dev

Counts Error

Date Initials

Within in PQ Check

Dil Fac Peak percent Lot #

3/2/2009 AP 15.02 4092 1.54 15.12 0.42 3285 0.6658 JB16A

3/3/2009 AP 15.02 4041 1.48 15.10 0.42 3147 0.5326 JB16A

3/4/2009 AP 15.02 4049 1.51 15.13 0.42 3361 0.7324 JB16A

3/5/2009 AP 15.02 4028 1.68 15.07 0.41 3318 0.3329 JB16A

3/6/2009 AP 15.02 4169 1.73 15.04 0.42 3215 0.1332 JB16A

3/9/2009 AP 15.02 5083 1.33 15.22 0.42 2993 1.3316 JB16A

3/10/2009 AP 15.02 3925 15.28 0.52 3.68 4166 1.7310 JB16A

3/11/2009 AP 15.02 5359 1.33 15.38 0.55 3.67 4106 2.3968 JB16A

3/12/2009 AP 15.02 4383 1.43 15.34 0.50 3.69 3924 2.1305 JB16A

3/13/2009 AP 15.02 4028 1.63 15.19 0.55 3.95 4299 1.1318 JB16A

3/16/2009 AP 15.02 3885 1.65 15.20 0.52 4.01 4202 1.1984 JB16B

3/17/2009 AP 15.02 3865 1.64 15.19 0.50 3.68 2923 1.1318 JB16B

3/18/2009 AP 15.02 3867 1.81 15.10 0.51 3.94 4076 0.5326 JB16B

3/19/2009 AP 15.02 3921 1.79 15.10 0.53 3.94 4360 0.5326 JB16B

3/20/2009 AP 15.02 4011 1.79 15.11 0.53 3.81 3884 0.5992 JB16B

3/23/2009 AP 15.02 4199 1.58 15.36 0.52 3.57 4083 2.2636 JB16B

3/27/2009 AP 15.02 4356 1.36 15.35 0.53 3.68 4331 2.1971 JB16B

3/30/2009 AP 15.02 3928 1.15 15.35 0.52 3.73 4562 2.1971 JB16B

Electrozone Sensing (EZS)

Optical Microscopy (human observation)

Image Analysis (camera w/software analysis)Static

Dynamic

Single Particle Optical Sensing (SPOS)

Nano Particle Tracking (NTA)

Fluorescence NTA (FNTA)

Archimedes, mass of individual particles

Spectrex


75

Syringes1 ml, 10 ml, 25 ml

Flow rate settings10 100 ml

Sensors (MC05 is added)

Sampling Probes(added short - small bore probe)


Interchangeable sampling probes, syringes, and sensors

Ensure you have one instrument to manage all applicationsNew MC05 sub - micron sensorChange configuration with no impact to instrument validation

Customized reporting

reportsAdd company logo, user defined descriptors

Customized test recipesProcedure Builder enables the development of unique test recipes for your applicationCopy a recipe and make the changes!


77

www.hachultra.comUSP Workshop on Particles


USP LO

HACH HRLD150 2.0 to 400mPMS APSS 200 2.0 to 120mHACH HRLD150 1.0 to 150mAccusizer LE400 - 1 1.0 to 400mAccusizer Fx 0.7 to 400m *Accusizer 780 0.5 to 400mHACH MicroCount 05 0.5 to 400mPMS S05 0.5 to 20mPMS S03 0.3 to 20mPMS S02 0.2 to 2mAccusizer FxNano 0.15 to 10m *Nanosight LM20 0.03 to 1m *Coulter Counter 0.4 to 1,000mDynamic Image Analyzers (next section )*Count determined via algorithm Contact Mfr for details


94

http://www.malvern.com/common/downloads/MRK652.pdf


www.nanosight.com 98USP Workshop on Particles

USP Workshop on Particle Size

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