What Does Remspec Do? Remspec provides fiber-optic reaction monitoring solutions for R&D and process development. Remspec develops reaction-monitoring software for both real-time interpretation and post processing. Remspec provides kinetic data interpretation support. Remspec provides spectroscopic surface contamination measurement systems for cleaning validation. Remspec assembles turnkey systems for particular analyses, including analytical development and software customization. © Remspec Corp. 2006

New FDA PAT (Process Analytical Technology) Guidelines call for:...design of effective and efficient manufacturing processes Continous real-time quality assurance Process knowledge...scientific understanding of how formulation and manufacturing process factors affect product quality and performance PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance, US FDA Guidance for Industry, September 2004 © Remspec Corp. 2006

Why Reaction Monitoring Improved Understanding Solve problems without guessing Avoid problems before they happen Cost Saving More Rapid process development Immediate detection of side reactions etc. Accurate end-point detection Safety No sample grabbing, no side-streams required © Remspec Corp. 2006

Why Fiber-Optics ? Flexibility –Probe can be repositioned easily without compromising calibrations Convenience –No need for laborious optical re-alignment for each experiment Vibration tolerance –Can be used with automated reactors and in process environments Small Size –Fits into most laboratory reactors Adaptability –Interchangeable sampling heads for a wide range of conditions © Remspec Corp. 2006

How Mature is Mid-IR Fiber Technology? Good-quality mid-IR optical fiber has been available for 14 years. Remspec has been in business making mid-IR fiber optic systems since 1993 (over 12 years). Remspec has sold well over 100 systems into laboratory and portable applications. The technology has been rapidly evolving but is now stable. Cable design is highly developed and effective solutions have been devised for –High pressures –High temperatures –Low temperatures © Remspec Corp. 2006

ReactionView® ● Compact FTIR, 35 lb, 1- ft 2 footprint ● Range cm -1 ● ATR and transmission heads fit wide range of reactors ● Full control and display software on a laptop ● No samples, the optical beam enters the reactor © Remspec Corp. 2006

ReactionView®-4 ● The four-channel version of ReactionView® allows four probes to be used at once on one spectrometer. ● Ideal for use with parallel reactor arrays. © Remspec Corp. 2006

Mid-IR Probes with interchangeable heads Fiber-optic probe with cables Liquid transmission head ATR head (with ZnSe crystal) © Remspec Corp. 2006

ATR Head A range of materials can be used (ZnSe is shown) Good, general-purpose probe Sensitive down to about 0.1 wt.% of most analytes Works in all solvents, including water Stainless steel* probe, shaft graphite-filled Teflon® seals, and inert crystal materials make the probe corrosion-resistant. *Hastelloy is available for extreme conditions © Remspec Corp. 2006

Sampling Heads: High Temperatures ● High Temperature Head ● Gas cooled (air or nitrogen) ● ATR or Transmission ● -100ºC to >200ºC ● 15mm OD © Remspec Corp. 2006

In-Situ Spectroscopy at High Pressures ● High Pressure Head ● 9/16” HIP or 1/2” Dynisco fittings ● P > 200 bar ● ATR or Transmission ● Gas cooled (air or nitrogen), -100ºC to >200ºC © Remspec Corp. 2006

Approximate penetration depth at each bounce is given by the expression: = wavelength of the radiation, n p = refractive index of the crystal,  = angle of incidence of the light beam, and n sp = ratio of refractive indices of sample and crystal. ATR Design: Variation of Penetration Depth with Incident Angle © Remspec Corp. 2006

ATR Design for Calibration © Remspec Corp. 2006

ATR Design for Calibration Bundle Fiberoptic ATR (Remspec) –Angular distribution of light entering the ATR crystal is always the same. Thin Film ATR (SensIR) –Incident angles change when framework is moved –Errors multiplied by multiple bounces –A sensitivity adjustment is required (Contrast adjustment) © Remspec Corp. 2006

Calibration: Mid-IR Spectrum of Phenyl Isocyanate in Acetone © Remspec Corp. 2006

Calibration: Curve Fitting of cm -1 Region in Mid-IR Spectrum of Phenyl Isocyanate 2283 cm cm -1 © Remspec Corp. 2006

Phenyl Isocyanate in Acetone © Remspec Corp. 2006

Phenyl Isocyanate in Acetone © Remspec Corp. 2006

VizIR™ Software ● VizIR™ includes a Control Panel for setting the resolution and timing of data collection during an experiment, as well as Start and Stop buttons. ● The display windows show a 3D picture of the spectra versus time, and window for most recent spectra or trend-lines. ● Display settings are controlled from the menus at the top of the screen. © Remspec Corp. 2006

VizIR™ Software ● Trend lines can be set up by eye using the Peak- Picker utility, by typing in a desired wavelength, or by using peak fitting (useful for resolving overlapping peaks). ● Both products and reactants can be followed. © Remspec Corp. 2006

VizIR-Remote™ Software ● When a VizIR™ experiment is running, the VizIR-Remote™ Java applet can be used to view the results in real time across a computer network using VizIR's internal data server. © Remspec Corp. 2006

In Summary ● Remspec manufactures and supplies mature well- supported systems with a wide choice of sampling options that are easy to use and provide repeatable data. ● Remspec systems are easily linked to automated reactor systems. ● Remspec provides specialized software that is specifically optimized for reaction monitoring. © Remspec Corp. 2006

Some Companies with Remspec Systems © Remspec Corp ● Air Products ● Dow chemical ● Mitsubishi Chemical ● Tosoh Fine Chemical ● Rohm and Haas ● Dupont ● DSM ● Boeing ● Lockheed Martin ● Astra Zenica ● Abbott Laboratories ● BMS ● GSK ● Johnson & Johnson ● Pfiser ● Wyeth ● Procter & Gamble ● Unilever