ReactIR™ Product Introduction

Brian WittkampJanuary, 2008

2 Internal usage only

ReactIR™ - Reaction Analysis

ReactIR™ is Mettler-Toledo AutoChem’s brand name for a Mid Infrared, in-situ Reaction Analysis system.

ReactIR™ collects a “molecular” video of a chemical reaction. It “records” molecular bonds breaking and forming. The breaking and formation of bonds give rise to unique characteristics of the molecule that are “recorded” and displayed in the form of what’s called a “spectrum”.

3 Internal usage only

ReactIR™ - ATR Technology

The hardware key to successful reaction analysis is “robust & sensitive” sampling technology.

Mettler-Toledo AutoChem’s solution to reaction analysis sampling technology is their patented Comp™ ATR (Attenuated Total Reflectance) probe.- No brazed or o-ring type seals

- Impervious to nearly all chemical applications (special materials available for specific applications)

- Most sensitive sampling technology design on the market

4 Internal usage only

ReactIR™ - “Molecular Video”

The spectrum contains specific information related to each component in the reaction. It’s like a fingerprint of each reaction component, very distinct and very unique.

By monitoring the intensity of these signals (i.e. relative concentration) over time, the ReactIR™ can give the operator real time feedback on the progress (or lack thereof) of the reaction.

5 Internal usage only

Phase III – Clinical Trial Batch

Importance of this reaction step/ batch ?- Key API (Active Pharmaceutical Ingredient) for Lilly

- Phase III API set for clinical trial studies

- Only enough starting material (world wide) for a single run Cannot afford a mistake – “Right First Time”

- If run too long the entire batch will be lost due to impurities

- Never run before on pilot plant scale – only in laboratory

R1COH R1C=NR2 R1CH2NHR2 H2 - Pd/CTHF

50degCR2NH2+

50degC

(solvent)

(imine)(aldehyde) (amine) (amine)

Starting Material Intermediate Product

6 Internal usage only

ReactIR™ in-situ Reaction Analysis

- Interfaced the “production-hardened” ReactIR™ (MonARC) to the top-end of a glass lined reactor using state-of-the-art IR fiber optics.

- Fiber Optics, coupled with our field-proven Diamond probe (Comp™) technology made the interface to the reactor seamless and easy.

7 Internal usage only

ReactIR™ - Results

Real time end point detection prevented loss of entire (and only) clinical batch. If lost, it would have taken another 1yr before having enough material to run again and resulting in millions of lost potential revenue.

Real time reaction monitoring provided highest level of product yield and purity versus all laboratory trials.

Real time reaction monitoring showed that reaction initiation was near instantaneous upon “charging”, which was not known during laboratory studies.

Pea

k In

tens

ity (

A.U

)

End-point

Imine Peak

Amine Peak

8 Internal usage only

ReactIR™ - Reaction Analysis

With over 1000 highly versatile probes installed worldwide, 147+ years of dedicated reaction analysis experience and highly powerful automated data analysis software (ConcIRT), ReactIR™ and Mettler-Toledo AutoChem is the clear market leader in reaction analysis with an unmatched product, application base and support offering.

ReactIR™ has been an integral part of many well-known, high value products such as:- Droloxlifene (osteporosis prevention)

- Tamfilu® (flu prevention)

- Viagra ® (ED medication)

-…to name a few

ReactIR™ helps improve and save lives everyday by guiding scientists to develop more effective compounds faster and economically in a more environmentally friendly way.