Return on Investment of Mass Spectrometry in Method ... · ©2017 Waters Corporation 1COMPANY...

©2017 Waters Corporation 1 COMPANY CONFIDENTIAL

Return on Investment of Mass Spectrometry in Method Development and QC

Patrick Boyce Customer Experience Manager

Waters Corporation, Manchester, UK


Example: using UPLC with mass detection to develop identity & impurity profile methods for a combination therapy with two active ingredients

Method development return on investment – ACQUITY H-Class UPLC with PDA & QDA, Empower Software – Including Fusion software to assist with ‘Quality by Design’ method development – Compared to using an existing HPLC PDA system in your laboratory

QC return on investment – ACQUITY H-Class UPLC with PDA & QDA, Empower Software – Compared to a new HPLC PDA system

Overview


ACQUITY H-Class UPLC with PDA and QDa detectors, Empower Software & Fusion Software

in Method Development


Instrumentation & chemistry

Business Impacts

High quality robust methods, reduced OOS, faster batch

release

Informatics

Compliant-ready with method development, validation and

transfer tools

Service & support

Experienced highly trained local Waters teams to maximize

uptime


Make selections & inputs based on the customers interests.

Scenario

Selection Scenario

New LC UPLC Select scenario

Comparison HPLC

Service Service & Qualification

Years ROI 5

Currency Euro

Cost per project per day 1,000

118.853

64.382

28.349

42.698

18.200

Competitor service price

Competitor system price

Waters system price

Waters service price

Waters training price


Method creation, testing and data review work without Fusion, using HPLC – # methods to create

o 96 screening methods (2 solvents, 2 pH, 2 temperatures, 2 gradients, 6 columns) for full factorial design o 10 optimization methods

– 1.2 minute for each method creation – 1.2 minute per method in creating sample set – 1.2 minute per method error checking to avoid human errors – 30 minutes cycle time, triplicate injections – 1.2 minute per injection ensuring that peaks of interest have been integrated – 5 mins to export each screening condition into a statistical package

Fusion & QbD


Method creation, testing and data review work with Fusion – # methods to create

o 32 screening methods (2 solvents, 2 pH, 2 temperatures, 2 gradients, 6 columns) partial factorial design o 10 optimization methods

– 40 mins set-up work in Fusion – 7.5 minutes cycle time, triplicate injections – 1.2 minute per injection ensuring that peaks of interest have been integrated

Fusion & QbD


Fusion & QbD

Value per Year: 16,600

Fusion integration with Empower means a QbD approach can be utilized to ensure the the most robust method and highest quality product.

# Conditions - full factorial screen QbD 96

Labour & instrument time - manual (days) 9.2

Labour & instrument time - Fusion (days) 0.9

Value of quality gain with Fusion in days 8.3

Average cost per project per day 1,000

# Method development projects per year 2

- - - - - - -

29.850

33 -

16.600

- - - - -


Sample testing and data review time to do a high quality job HPLC without mass detection and without standards – 32 screening injections – 11 optimization injections – 30 mins cycle time – About 1.5 hour preparing tables of peak area, retention time, and UV spectra per chromatogram – Total for 1 method development: about 86 hours work

Plus about 50% chance that all this work will have to be repeated – Total work on average = 86 hours + 50% * 86 hours = 129 hours

Method development - peak tracking


Sample testing and data review time to do a high quality job with UPLC and mass detection without standards – 32 screening injections – 11 optimization injections – 7.5 mins cycle time – Mass data and PDA spectra review per chromatogram

o 6 mins per chromatogram – About 9.6 hours work

Time saving about 119 hours, or 14.9 days Approximate cost of development project per day

– €1000

Value per project about €14900



Impurity standards? No

# Impurities 4

# Conditions – screening & optimization 43

Risk of repeat method dev? 50%

Peak tracking hours with no QDa 86.0

Peak tracking hours with QDa 9.6

Method dev. projects per year 2


Value per Year: 29,850

With mass data, the higher quality methods can be developed without peak tracking injections.

- - - - - - -

29.850

33 -

20.800

- - - - -


Total Econimic Value: 58,630

Our Price: 42,317

Comparison LC

HPLC

Service

Service & Qualification

Waters LC

UPLC

Value to You

Value Summary Pharma Development

Value to Customer: 16,313

per Year

Our Price; 42.317

Additional Value; 16.313

Competitor Price;

12.180


Total Econimic Value: 293,148

Our Price: 211,585

Comparison LC

HPLC

Service

Service & Qualification

Waters LC

UPLC

Value to You

Value Summary Pharma Development


per System over 5 years

Our Price; 211.585

Additional Value; 81.564

Competitor Price;

60.898


ACQUITY H-Class UPLC with PDA and QDa detectors, Empower Software

in Quality Control


Out of Specification and Test Failures

Reduce the impact Out of Specification & test failures

Business Impacts

Inventory Improve your inventory

holding period and working capital efficiency with faster

batch release

Business Growth & Capacity Increase the analytical testing capacity in your laboratory to

support increasing production or short-term fluctuations in

demand

ACQUITY method Choose between a simple transfer or new method development using QbD

principles

Solvents Reduce solvent

consumption by up to 90%, lowering your costs

and exposure


Input an example method to cover all analysis, sample numbers and financial requirements.

Inputs

Column length (mm)

Column diameter

(mm)

Particle size (µm)

Flow rate (mL/min)

Cycle time (mins)

Solvent cost per

liter

Annual samples

Samples per batch

HPLC instruments

required

Method 150 4.6 5 1.0 120.0 20 3,000 26 1

New LC UPLC

New methods

New QbD method

(✔)

Purchase 100% upfront Euro

Holding time

Include holding

time

Capacity Include capacity


Here are the calculated ACQUITY® methods.

ACQUITY® methods

Col. length

(mm)

Col. diam. (mm)

Flow (mL/min) Dp (µm) Cycle time

(mins) Annual solvent

volumes Instruments

required

UHPLC 100 2.1 0.417 2.500 40.0 50 1

UPLC® 50 2.1 0.613 1.700 13.6 25 1

APC 0 0 0.000 0.000 0.0 0 0

UPC2® 0 0 0.000 0.000 0.0 0 0


This shows how the key figure of 'LC & labour cost per downtime event' is calculated.

Cost Calcs.

#

Annual solvent costs

Annual instrument

costs

Annual total costs

Cost per sample

HPLC 1 7,200 127,605 172,605 11.51

UHPLC 1 1,000 168,894 175,144 11.68

UPLC 1 500 177,587 180,713 11.84

APC 0 0 0 0 0.00

UPC2 0 0 0 0 0.00

6.000

2.000

680 0 0

HPLC UHPLC UPLC APC UPC2


Solvent Use and Costs

REDUCE SOLVENT USAGE

ACQUITY® methods are

faster and often use lower flow rates. Solvent consumption is reduced which lowers costs and

helps reach environmental targets.

Solvent saving factor 93%

Solvent cost savings 8,375

Solvents annual volume - reference (L)

Solvents annual volume - ACQUITY® (L)

Solvents purchase & disposal cost per liter

360

25

25.0

Per year

Euro


Out Of Specification (OOS) & Test Failures

REDUCE THE IMPACT AND FREQUENCY OF OOS & FAILURES

Validating a faulty method and poor training will lock extra costs into your business for years. If 1-2 re-tests are performed per

failure, then 3-6% of instrument time may be spent on repeat

work & investigations.

6%

'The assignment of a cause for OOS results will be greatly facilitated if the retained sample preparations are examined promptly.' (https://www.fda.gov/downloads/drugs/guidances/ucm070287.pdf).

2% 1%

Example of OOS failure rate due to faulty method:

Example of OOS failure rate due to human error:

https://www.fda.gov/downloads/drugs/guidances/ucm070287.pdf


Out of Specification (OOS) & Test Failures

REDUCING THE FREQUENCY AND IMPACT

OF TEST FAILURES

Faster methods allow prompt re-testing and also

reduce the time for retesting and investigations.

Methods designed using QbD can cut the rate of

OOS & failures.

Improved OOS & failure rate - QbD

1%

Out of Specification & Failure Savings

17,933

OOS & failure rate - average HPLC

Re-test time saved (days)

Cost of delay per day

3%

17.9

1,000

Per year

Euro


Holding Period

INVENTORY MANAGEMENT IN PHARMA

‘The pharmaceutical sector has both the highest weighted average and the highest spread in DIO’

(days inventory outstanding) with its average being over 100 days.

Link to PWC report

100 days

Improving inventory management and improving working capital efficiency represents a cash opportunity and strategic for many pharma companies. Link to pharmaexec.com report

https://apps.leveragepoint.com/1/VM/client/ValueProposition/view.html?id=17344&from=fs

https://apps.leveragepoint.com/1/VM/client/ValueProposition/view.html?id=17344&from=fs


Holding Period

INVENTORY HOLDING PERIOD

Inventory held during

batch release testing incurs costs for manufacturing,

such as warehousing. Longer inventory holding periods incur more costs,

impact lead times and also affect competiveness.

Speed improvement factor 8.8

Holding time savings 20,905%

Deliverables (e.g. batches) per year

Time saving per deliverable (days)

Other holding costs per day

109

1.92

100

Per year

Euro


Waters Professional Services

ABILITY TO DELIVER

Waters Professional Services is the key for many labs to make the maxiumum efficiency gains

with ACQUITY systems and methods.

The impact of an extra 20% efficiency improvement with our team's support - perhaps going from 80% to 100% of the expected efficiency gain -

is shown here.

Solvents impact per year (L) - 20% efficiency gain

Analysis time impact per year (hrs) - 20% efficiency gain

Annual savings with 20% efficiency gain

67

136

7,335

Euro


Competitor Price

60.899

Our Price 183.235

Competitor Additional

Cost 236.064

Value to You

Value Summary Analytical laboratories

Competitor Total Cost: 296,963

Our Total Cost: 183,235


per 5 years

# samples per year

3,000

ACQUITY® method

New QbD method (✔)

OOS & failure rate - human error

1%

OOS & failure rate - faulty methods

2%

OOS & failure rate - human error

1%


Value by year

(250.000)

(200.000)

(150.000)

(100.000)

(50.000)

0

50.000

100.000

150.000

200.000

250.000

300.000

Initial Year 1 Year 2 Year 3 Year 4 Year 5 Total

Val

ue

Payback at 1.81 years, NPV at 7.400% = 79,286

HPLC System & Service ACQUITY UPLC & QDA System & Service Our Differentiated ValueNet Value to Customer Cumulative Value

Return on Investment of Mass Spectrometry in Method ... · ©2017 Waters Corporation 1COMPANY...

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