analytikLtd Whitepaper

Estimating the Return on Investment for Raw Materials Identification

Testing of Pharmaceuticals using Handheld Raman Analysers
Moving raw material ID testing out of the laboratory and into the warehouse can improve
product quality and save time and money

By Dr Heather Murray, Analytik

Introduction

Raw material ID is commonly performed in many industries to ensure end-product quality and safety. Within
the pharmaceutical industry there is a great emphasis on designing quality into a product by monitoring and
controlling manufacturing processes rather than relying on end-product testing. As part of this process the
identity and quality of raw materials should be verified. Potentially this places a great strain on pharmaceutical
manufacturers as their QA departments struggle to cope with the increased testing burden. However, by
moving analysis out of the laboratory to the point of need - the warehouse - raw material testing costs can be
greatly reduced, 100% inspection becomes possible and ultimately product quality assured.

Current Practices in Raw Material Testing

Traditional raw material testing requires extensive

handling of material containers and lengthy delays
as they are transported from loading bays to
warehouses, receiving areas, quarantine storage,
isolation rooms, laboratories, and finally into the
manufacturing areas. Typically, materials are
received at a loading bay where they are stored in a
quarantine area until they are ready to be tested
and released. In order to test the contents of the
container they must first be moved from quarantine
to a safe sampling area or containment room to
avoid contamination of the material and to reduce
risk associated with operator exposure. Once in the
sampling area the container may be opened. In the
case of materials arriving in drums, the inner bag
liner is opened; some material is extracted, placed
in a suitable container and logged into the
information management system. Only then is it
transported to the testing laboratory. Once
received in the laboratory, the sub-samples are
queued awaiting analysis.

Meanwhile, the original containers are placed in a holding area, while their respective sub-samples await
analysis. Once positive identification results are received, the containers are finally released to manufacturing.
While this process is operational, it is not efficient. Handheld analysers for materials identification, used in the
warehouse as the containers are received can greatly simplify sample handling and streamline the
manufacturing process.

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The Benefits of 100% Testing

Depending on the relevant regulatory requirements for each active and excipient material; a company will
follow their own protocol for analysis from incoming containers varying from statistical sampling of √ (N+1) to
100% of containers, or sub-sampling from multiple areas within a container. Although it is extremely difficult
to estimate the total cost of a failed production batch caused by a limitation in raw materials testing if a re-call
of shipped product is required, the final costs may easily run into millions of Euros.

Pharmaceutical manufacturers are facing continual customer pressure to reduce the price of their products.
Shareholders are demanding more efficient manufacturing, quality systems and initiatives for improving real-
time control now abound. However, there have been multiple instances of non-compliant raw materials
entering the pharmaceutical supply chain. Public safety is paramount and product quality cannot be
compromised in efficiency savings. Faced with this daily demand for improved efficiency a new approach for
raw material ID testing, the adoption of portable analysers used in the warehouse is required. Simply put -
100% testing is desirable, but not achievable via current practices.

Raman Spectroscopy for Raw Materials Identification

Raman Spectroscopy is a very well established technique in the pharmaceutical industry, it is used mainly for
research and development applications such as rapid analysis of microplate arrays in discovery, tracking
polymorphs through development and scale up or spatial distribution mapping; or in product manufacturing
for monitoring of granulation, blending or drying processes. Raman instruments for these applications range
from laboratory-based automated microscope systems to dedicated process analysers equipped with fiber
probes. However, moving away from these more specialised applications and considering bulk materials
identification only – how suited is Raman spectroscopy to this task? Requirements and suitability are
summarised in table A below.

Requirements and suitability of Raman Spectroscopy for Raw Material Identification

Raman has excellent chemical specificity - similar to mid-IR
Operates in the visible region - does not require sample purging or specialised accessories – simply point-and-
shoot, results available in seconds
Non-destructive analysis technique - original packaging and bottles can often be used, no contamination or
waste, no sampling induced errors
Raman is sensitive to the sample chemistry not the physical properties – a single spectrum is often all that is
required for a representative library entry* (explained below)
Water has a weak Raman spectrum - wet samples can be analysed without pre-drying, the presence of water
will not obscure the sample spectrum
Raman spectra are generally well defined (see Figure B); data is understandable and does not automatically
require complicated pre-processing
Raman is suitable for the analysis of the vast majority of pharmaceutical raw materials whether excipient or
active, solid or liquid
Table A

Fig. B: Typical Raman Spectrum

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*When building an NIR library, often a number of samples/spectra are required for each entry to fully
represent allowable physical differences between lots (such as variation in particle size distribution).
Advanced spectral pre-processing and chemometric techniques are generally required for NIR library building
requiring considerable time and expertise. However, Raman spectroscopy is much less sensitive to the physical
characteristics of a sample than NIR and as a consequence a single Raman sample is very likely to be all that is
required for a Raman library in a similar way to FT-IR. This is evidenced by the widespread availability of
commercial Raman and FT-IR libraries. Raman is however very sensitive to changes in chemical form;
individual polymorphs, isomers and amorphous compounds and hydrates can all be differentiated.

It is clear from table A above that the Raman technique is well matched to the requirements
for building a materials identification library. The next step is to determine how suited the
instrumentation is to the hostile environment of the warehouse.

Streamlining Testing with the PHARMA•IDTM

Handheld Raman devices are now available due to recent advances in

both laser and filter technology. An example is shown in figures C
TM
and D, the PHARMA•ID from DeltaNu. Weighing just over 300g,
with dimensions of 13.5 x 6.5 x 4 cm, with a ruggedised case, and no
fibers the analyser is operated via a simple push button, with ID
results displayed on an LED screen. Point and shoot analysis and
identification are complete in a matter of seconds, all data is
saved and downloadable via USB for backup at end of shift.
Detailed IQ/OQ procedures are available, and the
TM
PHARMA•ID complies with USP <1120> and
EP Ch.2.2.48 guidelines for Raman.

Fig. C

Replacing current laboratory based raw materials

testing methods such as FTIR, Raman or NIR with
handheld Raman analysis greatly simplifies sample
handling – many materials can be analysed directly
through their packaging, samples are analysed as
they are received and can be sent for immediate
processing. A case study showing the return on
investment (ROI) for the implementation of
TM
PHARMA•ID is shown below.
Fig. D: PHARMA•IDTM

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Understanding the Return on Investment

There are many factors to consider when evaluating the benefits of changing from current lab-based materials
testing protocols to a handheld Raman-based testing regime and calculating the potential ROI. In this first
TM
example we will estimate the cost of a single analysis using the PHARMA•ID against an existing lab based
method, differentiating only the sample transport and lab-based sample preparation and clean up time.

Cost comparison of conventional lab based spectroscopic analysis and warehouse based analysis

TM
FT-IR Lab NIR PHARMA•ID

Sample transport and subsampling* 15 min 15 min 2 min

Sample preparation/presentation 5 min 1 min 2 min

Lab analysis time 2 min 1 min 0.5 min

Clean up time 3 min 1 min 0.5 min

Total 25 min 18 min 5 min

Cost per sample €14.57 €10.49 €2.91

Monthly labour cost for 500 samples €7 285 €5 245 €1 455

*Typical time for sample transport to central lab from receipt in warehouse

From this simple cost comparison laboratory based spectroscopic techniques show a cost per analysis of
approximately €10.49 to €14.57, whereas a warehouse based Raman analyser has a much reduced figure, at
€2.91. By expanding the calculation to consider low, medium and high sample analysis costs below, the
potential cost savings of warehouse based analysers based on labour costs only is remarkable.

Labour cost comparison

Usage Samples per year Labour costs per year for analysis
TM
FT-IR Lab NIR PHARMA•ID

Low 2500 €36 425 €26 225 €7 275

Medium 6000 €87 420 €62 940 €17 460

High 12000 €174 840 €125 880 €34 920

In the example below a comparison is made between the ongoing cost of continuing analysis with an existing
TM
FT-IR or existing lab based NIR and purchasing and commissioning a PHARMA•ID to be used in the
warehouse. This example also includes the development and comparability protocol costs associated with the
TM
creation of a new PHARMA•ID Raman library containing 30 materials and the subsequent annual costs of
analysing 6000 samples in the first year.

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Initial purchase, development and analysis costs

TM
FT-IR Lab NIR PHARMA•ID

Library build and validation / days Already established Already established 15

Comparability protocol with FTIR / days Not required Already established 10

Annual library maintenance / days 1 6 3

Total / days 1 6 28

Combined labour cost €260 €1 570 €7 340

Approx capital cost dependant on application €23 600

Yearly analysis costs €87 420 €62 940 €17 460

Total €87 680 €64 510 €48 400

It is evident that the combined initial purchase cost and subsequent development cost of implementing the
TM
PHARMA•ID are quickly outweighed by the labour costs of laboratory analysis be it FT-IR or NIR.

Calculating the Return on Investment and Payback

In this case the ROI is based on cost savings rather than income generated and it is possible to calculate a
TM
simple ROI for the PHARMA•ID for the first year versus the same analysis by FTIR at medium usage levels as
130% with a payback of less than 6 months.

Assumptions used in the above calculations

A single averaged operator rate (fully loaded to include overheads) was calculated at €59 000 p.a.
TM
Investment in PHARMA•ID includes purchase and development costs of producing and validating a
30 component library then carrying out the comparability protocol
TM
Cost savings = difference in analysis and running costs between FT-IR and PHARMA•ID for the first
year at medium usage levels (600 samples per month)
ROI = (Cost savings – investment)/ investment * 100

Conclusion

From the standpoint of sample analysis only there are remarkable efficiencies to be made by utilising the
TM
PHARMA•ID for materials identification in the warehouse as the ROI of 130% and payback of less than 6
TM
months shows. However, there are also operational benefits from employing PHARMA•ID and removing the
bottleneck at the QC laboratory - reducing inventory and increasing material turnover. Ultimately, the
greatest benefit comes from the potential improvements in product quality possible from 100% inspection.

TM
To learn more about PHARMA•ID please visit www.analytik.co.uk (UK and Ireland) or alternatively visit
www.intevac.com/deltanu

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