copyright @ b&w tek overview of the nanoram handheld raman for rapid material identification...

Copyright @ B&W TEK

Overview of the NanoRam Handheld Raman for

Rapid Material Identification

B&W Tek, IncNewark, DE

USASeptember 2013

www.bwtek.com 2Copyright @ B&W TEK

We are Your Spectroscopy PartnerGlobal leader with > 10,000 Portable and handheld Raman systems

B&W Tek, China

Ming Shen Commercial Plaza

400 CaoBao Rd., Suite 2206, Shanghai - 200233, China

Phone: +86 021-64515208

B&W Tek, Japan

2-3-2 7F, Kamiochiai, Chuo-ku, Saitama-city, Saitama - 338-0001, Japan

Phone: +81(0)48 851 3150

B&W Tek, Corporate Headquarters

19 Shea Way Newark, DE 19713, USA

Phone: +1-302-368-7824

Web: www.bwtek.com

B&W Tek, Europe

Seelandstraße 14-16, 23569 Lübeck, Germany

Phone: +49(0)45130803854

Over 15

years

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Copyright @ B&W TEK www.bwtek.com 4

Country NanoRam Distributor Country NanoRam Distributor

Abu Dhabi LabGulf fzc Japan Sanyo Trading Company

Argentina Carpe Scheider Korea Sunil-Ina Instruments

Australia Scitech Pty Ltd. Malaysia, Singapore Lab Science Solution

Benelux Vadeno Mexico Perkin Elmer Mexico

Brazil Erwing Mondragon Pakistan Chemtech

Canada Betatek Inc. Peru Cientifica Andina

Chile Perkin Elmer Chile Poland Bioanalytic

Czech Republic Nicolet Portugal STEC Instruments-Sistemas Tecnicos

Dominican Republic Amco Instruments Romania Ronexprim

Egypt Cairo Scientific Russia, Belarus, Kazakstan Promenerdolab, LLC

Finland Lab-dig Oy Spain Microbeam

France Opton Switzerland IG Instrumenten (IGZ)

Germany, Austria, Switzerland

Polytec Taiwan

Schmidt Scientific

Hungary Metalon Thailand Pondpol Analytical

India Spinco Biotech PVT ltd. Turkey Tetra Teknolojik Sistemler

Indonesia Mensa Group Ukraine Medtechnika-Dent

Ireland Brennan & Company United Kingdom & Ireland Pacer

Israel Lahat Technologies USA SciMark International

Italy Madatec 5

What is the need?• Pharmaceutical companies must meet worldwide PIC/S

initiatives, local Pharmacopeia and the US Food and Drug Administration’s regulations on Good Manufacturing Practice (GMP)

• There has been a trend of increasing product contamination incidents, product recalls and facility shutdowns

• Companies must develop and implement improved analytics to check the identity, integrity and quality of ingredients and products

• Implementation of 100% testing of raw materials is coming!www.bwtek.com 6Copyright @ B&W TEK

Regulatory Standards Compliance

• 21 CFR Part 11 Electronic Records; Electronic Signatures

• 21 CFR Part 1040.10 Laser and Laser Systems

• US Pharmacopeia <1120> Raman Spectroscopy

• European Pharmacopeia Ch.2.2.48 guidelines for Raman Spectroscopy- includes information on spectral library validation

• ASTM 1840-96(2007) Standard Guide for Raman Shift Standards for Wavelength Calibration


Incremental Regulatory Control for Incoming Material Identification

•PIC/S recommendations on complete traceability of incoming materials•GMP is expanding to new products

Global Supply Chain•Companies are moving toward a more delocalized supply chain•Problems associated with supplier quality assurance and transportation

Quality Assurance and Cost Reduction•Increase analytical capabilities to assure material quality•Reduce operational cost•Optimize operational efficiencies

Industry Trends and Requirements

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100% Raw Material Inspection

Why do we need to perform 100% container identity testing?

GMP for Raw Material Identification

US FDA 21 CFR requires testing of raw materials: 21 CFR 211.84 (d)- “At least one test shall be conducted to

verify the identity of each component of a drug product. Specific identity tests, if they exist, shall be used.”

Raw materials are quarantined until identity is verified Raw materials must meet predetermined specifications US FDA Compliance Program Guidance Manual Program (Drug

Manufacturing Inspections-FDA CP7356.002) Material systems: at least one specific identity test is

conducted on each lot of each componentDietary Supplement GMPs US 21 CFR 11121 CFR 111.75(a)(1)(i)Conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient

GMP for Raw Material Identification

EU GMP and PIC/S GMP Guide

Chapter 5. Production

5.30 There should be appropriate procedures or measures to assure the identity of the contents of each container of starting material.

Annex 8 -Sampling of starting and packaging materials

2. Starting Materials

The identity of a complete batch of starting materials can normally only be ensured if individual samples are taken from all the containers and an identity test is performed on each sample.

This means: 100% container testing

US FDA Warning Letter Review- Identity Tests

• Xian Libang Pharmaceutical Co., Ltd., China. (Jan 28, 2010)1. Failure of your quality unit to ensure that materials are appropriately tested and the results are reported.

• Your firm used the IR spectra for one lot to approve and release two subsequent incoming lots. This practice is unacceptable and raises serious concerns regarding the integrity and reliability of the laboratory analyses conducted by your firm.

• It is essential that at least one test be conducted to verify the identity of each lot of incoming material.

• In addition, the laboratory control records should include complete documentation of all raw data generated during each test, including graphs, charts and spectra from laboratory instrumentation.

Requirement-development of methods/libraries with well-characterized materials


Copyright @ B&W TEK

Regulatory Expectations for Spectroscopic-based

Methods

Issues and Customer Concerns• Can Raman help my project?• What are the differences between Raman and NIR?• Should I really perform 100% container ID test? What are

my options? • Do I need to validate the Raman method? If yes, what are

the requirements for method validation?• What is next after the Raman ID becomes a routine

method?• Do I need to know the filing expectations from regulatory

agencies (JP/EMA/FDA..)?• Can vendors provide GMP support & related documents?

15

Applicability of Raman Spectroscopy

04/19/23 Confidential16

Raman Spectral Information• Raman spectroscopy is a form of

molecular spectroscopy based on the scattering of light by molecules.

• A Raman spectrum is a molecular ‘fingerprint’ that provides structural information– Can identify materials based on the

spectrum

• Changes in intensity, frequency and peak bandwidth provide valuable information for quantitative and qualitative analysis

www.bwtek.com 17

500 1000 1500 2000 2500 3000

Raman shift (cm-1)

(CH3)2C=O

CH3CH2OH

(CH3)2S=O

CH3CH2O2CCH3

C6H5CH3

C=O

C=O CH3

Ar-H

S=O

CH3CH2

C-O

CH3Aromatic

Raman Spectra Raman ShiftIndependent of laser outputExcitation wavelength is determined by analytical and sample needs (avoid fluorescence interference with longer wavelength)

Raman IntensityDepends on laser wavelength The longer the excitation wavelength the lower Raman peak counts (at same power output)


Components of a Raman Spectrometer

Laser Narrow Line width Small form factor Low power consumption Extremely Stable Power Output


SpectrometerHigh ResolutionLow Noise Small form factor Low power consumption

Probe Backscattered laser rejection filter

PC and analysis software

What can Raman do for you?

www.bwtek.com20

Strong Raman SignalActive Pharmaceutical IngredientsAlcohols AntibioticsAntioxidantsBuffersCoatingsDiluentsEmulsifiersExcipientsFlavorsFragrancesLubricantsMonomers and polymersPolyatomic inorganicsPreservativesSolventsVitamins

Weak Raman SignalMaterials that are dark in colorHighly fluorescing moleculesFillers/binding agentsGlassThin-walled plasticsWater

No Raman Signal•Black materials•Metals•Mono-atomic ions

Raman can measure through a broad class of packaging

Bottles Thickness

Amber Glass < 2 mm

Clear Glass < 3 mm

High Density Polyethylene (HDPE) < 1 mm

Teflon FEP < 1 mm

Polystyrene < 1 mm

Vials

Amber and Clear Glass < 1 mm

Bags

Polypropylene (PP) < 0.1mm

Polyethylene (PE), Low-Density Polyethylene (LDPE)

< 0.1mm

21

How does Raman compare?In comparison to other vibrational spectroscopy methods, such as FTIR and NIR, Raman has several major advantages


23

The Measurement Challenges- Measure Through Plastic

PackagingImplementation advantages of spectroscopic methods•No cross-contamination (the material inside the bag)•Safe and easy to implement•Can be implemented in warehouse, docking area or lab

But…challenges exist if using NIR technique•Spectral profiles include packaging absorptions •Packaging interferences may reduce the specificity of the method when identify similar materials•The library requires assessment or change if the bag changes, i.e., not suitable for multiple suppliers of same materials•Packaging could have multiple layers, with different colors or materials

24

No PE bag (pure sample).4

.6

.8

1

1.2

1.4

1.6

1.8

8500 8000 7500 7000 6500 6000 5500 5000 4500

.4

.6

.8

1

1.2

1.4

1.6

1.8

8500 8000 7500 7000 6500 6000 5500 5000 4500Wavenumber (cm-1)

Two layer PE bagOne layer PE bag

NIR Spectra of material –with plastic bag

Required to evaluate the method specificity in the presence of bag!

NIR Spectra of API (Plastic bag contribution)

25

Raman Spectra of API (Plastic bag effect)

0200400600800100012001400160018002000220024000

900

1800

2700

3600

4500

5400

6300

7200

8100

9000

9900

Raman shift [cm-1]

Inte

nsity

No bag

One layer bag

Two layer bag

No significant spectral absorption from PE bag

No significant spectral absorption from PE bag

Raman has greater specificity than NIR: same

pharmaceutical tablet

04/19/23 www.bwtek.com 26

Wavenumber (cm-1)

7398. 7544. 7691. 7838. 7984. 8131. 8277. 8424. 8570. 8717. 8864. 9010. 9157. 9303. 9450. 9596. 9743. 9890. 10044 10206 10368

NIR

Re

flect

an

ce

0

0.5

1

1.5

NIR Spectrum of tablet

Raman shift (cm-1)

3200 3078 2954 2830 2706 2582 2458 2334 2210 2086 1962 1838 1714 1590 1466 1342 1218 1094 976. 864. 752. 639. 527. 415. 303.

Ra

ma

n in

ten

sity

20

40

60

80

Raman Spectrum of tablet

Benefits of NanoRam for ID Testing

• Reduced material movement – directly implement in warehouse, loading dock, fewer accidents/reduced manpower

• Easy and simple operations- simple training & improves manpower usage

• Reduce chemical exposure and contamination– scan through packaging materials & maximize personnel safety

• Fewer lab delays reduce cycle time – on-time production & higher throughput

• Free up laboratory instruments – increases lab capacity• Reduced transcription – fewer errors; lower personnel and equipment overhead; control costs


Productivity (35-50% Up)

• 100% ID using HPLC or wet chemistry: 16.5 hrs

• Quarantine period 2 shifts or longer

• With NanoRam <1 minute per sample: 11 hrs total from receipt to acceptance

• Quarantine period within hours


NanoRam• Incoming non-destructive

testing of Raw Materials• Reducing Waste in the

Dispensing Suite• Plastic Packaging

Identification• At line identification of

intermediates• Final product

identification• Substandard, Adulterants,

and Counterfeit Deterrent

NanoRam Handheld Innovations


• Only handheld with high resolution touch screen interface

• Only handheld offering easy data management and reporting

• Best methodologies for robust analysis

• Fastest in adding Methods and Libraries

• Only handheld allowing editing Method

• Full method development and validation support

NanoRam ® specifications


NanoRamBWS456

Detector TE Cooled linear CCD Array

Laser Excitation 785nm

Laser power tunable from 0 mW to 300 mW

Laser Power Control0 to 100% in 10% increments

Range / Resolution

176cm-1 to 2900cm-1

~ 9.0 cm-1 @ 785nm

Display High Visibility OLED touch screen, 3.7" size

Barcode Reader 1D and 2D barcodes

Data Formats .txt, .csv, .spc, .pdf

DC Power 12V DC at 6.6 Amps

Battery Rechargeable Li-ion Battery, > 5 hours operation

PC Software NanoRam ID

Computer InterfaceUSB to Ethernet, Wifi

IP ProtectionClass

IP64- Protection from infiltration of dust and splashing water

Features of NanoRam®

• 2D/1D Bar Code Reader• IP64 Dust/Splash Proof• Easy Battery Replacement• TCP/IP and WiFi Interfaces

www.bwtek.comCopyright @ B&W TEK

Easily changed accessories


Push in

Liquid vial holder

Point & shoot adaptor

NanoRamInstrument Menu OperationTouch screen with on-screen keyboardLightweight: about 1 kg and able to be used with either handEasy to read screen for quick menu usageManagerial access levels allow for secure areas of the softwareUsers are designated with passwordsTraceability of all activity with the instrument and the users


Clear Results


User accounts

• ADMIN user can create other accounts

• Three levels of users:– Operator– Developer – Administrator

• Plus a Device Manager for administrative tasks


Device Manager• Device manager for

administrative tasks• Sets overall system clock and

password expiration period (6 months default)

• Can create Calibration files (as can ADMIN)

• Cannot do any analysis or data transfer

• Unique password tied to unit serial number


Operation Modes

• Identification method for statistical validation of incoming materials

• Investigation of unknown materials using correlation with a reference library

• Administrative functions such as operation presets, user accounts, calibration validation and data transfer setup


Easy administration

Administration


NanoRam: Operation Preset


• Managerial level access to set Operation Preset

• ADMIN can also – create user accounts:

Developer and Operator level users

– Create calibration files

Self check: by performing calibration validation using ASTM 1840 ref material: Polystyrene

Calibration Validation: part of the PQ

41Copyright @ B&W TEK

http://www.chem.ualberta.ca/~mccreery/ramanmaterials.html

Tools for different verification modes

• Identification using a defined method with p-value (significance level) to verify material identification

• Investigation for unknown samples: HQI

• In general, we recommend the use of p-value for ID (identification mode).

• The HQI (Investigation mode) may be used for identifying unknowns and as an additional tool for validation.


What to use?

p-value is ideal for verifying and/or qualifying the identity of a ‘known’ material. It provides more robust methodology and has can discriminate between molecules which have structural similarities.

HQI allows for the rapid comparison of a spectrum against a large library of spectra, making it ideal for analysis of unknown materials.

43

Built-in processing algorithms to automatically perform complex analysis, making these tools much more accessible to the general user. However, not clearly understanding the advantages and disadvantages of the various algorithms can lead to a misuse of the technology. Therefore, it is important to understand that both correlation and classification approaches have advantages and disadvantages depending on the goal of the measurement.

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Describe ID vs Investigation


Creating a Method• Create method for each material• Use barcode or user-entered

name for Method name• Will collect 20 sample spectra

per method- preferably of different lots of material


katherineb

add more screen shots

Developer/Admin can Create Method

• Easy steps to create methods

www.bwtek.com46

Method development: Data check

• Scan samples and view each scan as collected• Scans compared with previous ones, and if HQI < 85, it is shown in RED suggesting that may want to delete from method• Can view overlay of scans with average in method


Methods can be updated

• More sample spectra can be added• p-value threshold (significance level) can be changed• Note must be added to make change: TRACEABILITY


USING IDENTIFICATION MODE


Identification• Measure in batch or single mode• Load method to use• Enter sample information• Scan sample and get Pass/Fail

result


Identification• When running IDENTIFICATION get Pass or Fail.


If an identification fails, the system will automatically run an investigation to suggest potential matches.

Batch Mode• Batch mode allows user to

run many samples without having to enter information for each sample

• Batch summary report available in NID


Library Investigation approach• This mode allows the testing of unknowns• Will search libraries/methods selected in

Operation Presets• Number of matches (hits) and match threshold

also defined in presets• Gives Match/no Match result(s)


US FDA Warning Letter Review- Identity Tests

• Xian Libang Pharmaceutical Co., Ltd., China. (Jan 28, 2010)1. Failure of your quality unit to ensure that materials are appropriately tested and the results are reported.

• Your firm used the IR spectra for one lot to approve and release two subsequent incoming lots. This practice is unacceptable and raises serious concerns regarding the integrity and reliability of the laboratory analyses conducted by your firm.

• It is essential that at least one test be conducted to verify the identity of each lot of incoming material.

• In addition, the laboratory control records should include complete documentation of all raw data generated during each test, including graphs, charts and spectra from laboratory instrumentation.



Adding samples to library• Create library : enter library name• Add New sample: scan sample• Enter sample details and Add to library


Selecting libraries to use in Investigation

• The libraries against which the search and match is performed can be modified.

• Multiple libraries can be selected.

• The Methods also can be searched to establish a match of materials using an HQI against every Method.


Results from NanoRam


• Identification: Pass/Fail– sample identity verified by

comparison to defined method; p-value used as pass criterion

• Investigation: Match/No Match– sample matched by correlation

(HQI) to materials that are in the libraries available on the system

NANORAM EXAMPLES


Identification of Amino Acids

– L-alanine

– L-aspartic acid

– L-cysteine hydrochloride


Identification of Amino Acids• Create methods on

NanoRam for the following materials:– L-alanine– L-aspartic acid– L-cysteine hydrochloride

• 20 scans per method• 90% laser power (270 mW)• Point and shoot adaptor to

measure sample in direct contact

aspartic acid alanine cysteine HCl

Raman shift (cm-1)

176 260 348 436 524 608 696 784 868 956 1056 1168 1280 1392 1504 1616 1728 1840 1952 2064 2176 2288 2400

Nor

ma

lized

Ra

man

inte

nsity

0

0.1

0.2

0.3


Using Investigation Mode and HQI

Library Spectrum

SampleL-Alanine L-Aspartic Acid

L-Cysteine Hydrochloride

L-Alanine HQI=100 HQI=1.63 HQI=0.66

L-Aspartic Acid HQI=1.63 HQI=98.88 HQI=1.71

L-Cysteine Hydrochloride HQI=0.52 HQI=2.22 HQI=99.19


Multivariate PCA Scores Plot of Spectra of All 3 Methods

aspartic acid alanine cysteine HCl

PC-1 (69%)

-0.1 0 0.1

PC

-2 (

30%

)

-0.04

-0.03

-0.02

-0.01

0

0.01

0.02

0.03

0.04

0.05

PCA Scores for Raman Method Data


Identification Mode: Project Sample on Method Model

• 95% Confidence Ellipse (5% significance) Defines Sample Identification

• Blue Samples –Define the Method (20 Scans)

• Green Samples- Test the Method Calibration Projection

-0.05 -0.04 -0.03 -0.02 -0.01 0 0.01

-0.01

0

0.01

0.02

Scores

cyst. HCl

cyst. HClcyst. HCl

cyst. HClcyst. HCl

cyst. HClcyst. HCl

cyst. HCl cyst. HCl

cyst. HClcyst. HCl

cyst. HCl

cyst. HCl

cyst. HClcyst. HCl

cyst. HCl

cyst. HCl cyst. HCl

cyst. HCl

cyst. HCl

cyst. HClcyst. HCl

cyst. HCl

alaninealaninealaninealanine

aspartic acidaspartic acidaspartic acid

PC-1 (74%, 31%)

PC

-2 (

20%

, 2%

)


Specificity (or Proximity) Matrix

Proximity Matrix: Testing of all the materials in Identification Mode using specific methods generated by each of the materials Method Materials

L-alanine L-aspartic acid L-cysteine HCl

L-alanine PASS

p=0.7945

Fail

p=7.772 x 10-16

Fail

p=1.776 x10-15

L-aspartic acid Fail

p=7.661 x 10-

15

PASS

p=0.8915

Fail

p=7.25 x10-14

L-cysteine HCl Fail

p=8.436 x 10-

11

Fail

p=2.26 x 10-11

PASS

p=0.9995

p-value> 0.05

0.001 < p ≤ 0.05

10-6 < p ≤ 10-3 0 < p ≤ 10-6


Comparing Chemically Similar Materials

• Potassium Carbonate

• Potassium Carbonate Sesquihydrate

potassium carbonate sesquihydrate potassium carbonate

Raman shift (cm-1)

176. 276. 376. 476. 576. 676. 776. 876. 976. 1080 1192 1308 1420 1536 1652 1764 1880 1996 2108 2224 2340 2452

Nor

mal

ized

Ram

an in

tesi

ty

0

0.1

0.2

0.3

0.4

0.5

0.6

Raman spectra of potassium carbonate (red) and potassium carbonate sesquihydrate (blue).


HQI : Library Searching

Library Spectrum

SamplePotassium Carbonate

Potassium Carbonate Sesquihydrate

Potassium Carbonate HQI=99.5590 HQI=96.9013

Potassium Carbonate Sesquihydrate

HQI=97.5834 HQI=99.5908

Difficult to get unambiguous results as the HQI is >95 for both samples against library spectra


Identification Method Using p-value

Method

Sample

Potassium Carbonate

Potassium Carbonate

Sesquihydrate

Potassium Carbonate

p-value = 0.96390.97550.98250.99980.9262

p-value = 6.415 x 10-4

2.990 x 10-4

2.597 x 10-4

6.153 x 10-5

4.077 x 10-5

Potassium Carbonate

Sesquihydrate

p-value = 1.258 x 10-5

1.979 x 10-5

4.132 x 10-5

3.245 x 10-5

3.106 x 10-5

p-value = 0.99970.95340.99020.99190.9942p-value >

0.050.001 <p-

value≤ 0.0510-6 <p-

value≤ 10-3

0 <p-value≤ 10-6


NanoRam Flexible Sampling• Separate methods were created for

Ethanol with the vial holder, and with the immersion probe

• Test samples across these two and get passing results

• Can develop a single method including sampling variability to give more robustness

www.bwtek.com Slide 69

Testing with Different Accessories

www.bwtek.com Slide 70

Sample

Method

Ethanol via immersion

probe

Ethanol via vial holder

Ethanol via immersion

probe

0.94580.98510.9840.9790.9876

0.74260.71770.85880.81050.7318

Ethanol via vial holder

0.84570.77580.71750.63910.7317

0.53170.490.51910.620.6093

The ID test gives “Pass” result for samples in vial holders and samples directly measured using immersion probe

Sampling of solids• Solids can be measured with the point and shoot adaptor as

is directly or through transparent packaging.• Tablet holder has a larger beam size and samples a larger

area of a sample than does the point and shoot adaptor. It is recommended for use with tablets and samples that exhibit nonhomogeneity

• Right angle adaptor and immersion probe can also be used for solids


Tylenol tablet testing with different accessories

Samples

Method

Tylenol in whirl pak

Tylenol in tablet holder

Tylenol with point & shoot

Tylenol in whirl pak

0.99900.99570.99650.99370.9304

0.89620.78330.74790.91100.6893

0.38660.42150.40780.49170.6353

Tylenol in tablet holder

0.86490.98300.75160.94060.9975

0.95900.98260.99660.96990.9984

0.97930.85440.82480.96760.8172

Tylenol with point & shoot

0.24210.23610.83610.61190.43500.6930

0.93070.73770.95430.83360.62090.8901

0.58280.76300.69810.52420.6488

Tylenol with all 3

accessories/packaging

0.99970.99810.98940.9966

0.98590.99670.99240.9958

0.99750.97040.99860.9846


Data Management and reporting with NID


NID Software interface• Synchronization with

up to 8 units• Data archival and

retrieval• Records reporting• Audit trail• Methods review• Calibration validation

reports• Account

management


Data Synchronization with NID


Method Management via NID


Method information in NID


Reports in NID


Data exporting


Library viewing


Audit trail


Calibration validation report


How can we help?We can provide:• IQ & OQ• PQ and DQ• Method Validation Protocol• Method Development Guidelines • Libraries development service• Method development service• We can provide full validation

support • Certification of distributors for

IQ/OQ• Instrument Annual Certification


Method Validation for Qualitative Analysis (ID)

• It is important to test methods to ensure correct PASS of known good materials and correct FAIL of materials known to not be what the method was developed for

• OQ/PQ procedures and Method Validation protocols include tests for this – ensuring that there are not false positives or false negatives from the methods with test cases of aspirin and tylenol

• Validation requires risk assessment and should be done at a level commensurate with the risk that an incorrect result carries– Focus on minimizing possible harm to patient.


Documentation

• User Manual• Quick Start Manual – for Operator-

level users• DQ/IQ/OQ/PQ• Software release notes

• Identification Method Development Guidelines for the NanoRam

• Method Validation Report• SOP for Operation of NanoRam

www.bwtek.com | www.nanoram.com85

http://www.bwtek.com/

http://www.nanoram.com/

DQ/IQ/OQ and PQ Documents for NanoRam-

Copyright @ B&W TEK

Raman has proven to be a promising tool to increase operational capabilities and reduce cost while providing rapid material identification.

87

Summary

Copyright @ B&W TEK

Thank you for your attention

www.bwtek.com 88

B&W Tek, Inc.302-368-7824

[email protected]

http://www.bwtek.com/

BACK UP SLIDES

89

Spectroscopic-based Identity Method

Method development

www.bwtek.com 90

• The methods/libraries must be developed and can then be run on a routine basis

Developer/Administrator

Measure 20 representative spectra Build method based on PCA and establish threshold p-value (typically 0.05)

Test Method

500060007000800090001000011000

Wavenumber cm-1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

Abs

orba

nce

Uni

ts

PC1

PC

2

PC1

PC

2

91

Spectroscopic-based Identity Method

Sample analysis

1. Access method 2. Scan sample 3. Identify material

Operator

Raman Related Documents (1)Pharmacopeia•United States Pharmacopeia (USP34/NF29) General Chapter <1120> Raman Spectroscopy•European Pharmacopeia (Ph Eur 7.0) 2.2.48 Raman Spectroscopy•Pharmacopeia of the People‘s Republic of China (2010)- Raman Spectroscopy 拉曼光谱法指导原则

EMA Guidance – effective Oct 1, 2012•EMA/CHMP/QWP/811210/2009-Final Guideline on Real Time Release Testing (formerly Guideline on Parametric Release) 2012- …may utilize process analytical technology (PAT) tools e.g. near infrared spectroscopy (NIR) and Raman spectroscopy

Raman Related Documents (2)• ASTM E1840 - 96(2007) Standard Guide for Raman Shift Standards

for Spectrometer Calibration• ASTM E1683 - 02(2007) Standard Practice for Testing the

Performance of Scanning Raman Spectrometers• ASTM E2529 - 06 Standard Guide for Testing the Resolution of a

Raman Spectrometer

• US FDA Advancing Regulatory Science at FDA: A Strategic Plan (August 2011): Section 2. Develop new analytical methods:a) Investigate feasibility and value of using emerging and improved analytical technologies like Nuclear Magnetic Resonance (NMR), mass spectrometry, or near infrared or Raman spectroscopy for evaluating product quality of pharmaceutical agents, and evaluate whether these technologies should replace existing methods;

Raman Applications in Pharma• ID

– Identification Verification of and Identification of unknown raw materials This is the application for NanoRam

• Quantitative analysis – Quantitative determination of active substances in different

formulations;

• Polymorphism – Supporting polymorphic screenings (polymorphs have different

solubility rates, thereby impacting the effective dosing);

• Process – Real time quantitative analysis for process analytical

technology (PAT) such as blending, titration, reaction monitoring and polymorphic transition monitoring.

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Analytical Instrument Qualification

USP <1058> Analytical Instrument QualificationCopyright @ B&W TEK

NanoRam User Levels

96Copyright @ B&W TEK

User Type User Type Symbol

User Privileges

Operator Select MethodPerform Material IdentificationSelect Operation PresetData Transfer

Developer All above, plus:Create /Edit MethodCreate/Modify Operation PresetCreate/Modify Data Library

Administrator All above, plus:Manage User Accounts Create calibration files

Device Manager Set system clockSet password expirationCreate calibration fileReset ADMIN password

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