The IRmadillo for Monitoring Pharma and BioPharmaceutical Manufacturing Processes
The pharmaceutical sector has been an area of intense and rapid evolution in recent years, with the advent of Quality by Design (QbD), continuous manufacturing and aims of achieving Real-Time Release Testing (RTRT). Achieving this requires a fundamental shift in the mindset of manufacturing teams, and they need the tools that will allow them to better control their processes and ensure tightly controlled specifications are met.
Analytical experts are used to using high performance equipment in laboratory settings (such as NMR, HPLC and reaction control systems with integrated spectrometers), but these are simply not suitable for manufacturing environments. Moreover, many of these instruments are not stable enough for long-term manufacturing campaigns that are a key backbone of the continuous process. So how can QbD and RTRT be achieved if the tools are only suitable for laboratory settings?
The answer lies in industrial-grade spectrometers, providing real-time spectra that can be analysed to provide concentration traces, batch modelling and descriptive statistics of a campaign. They can be installed on both batch and continuous processes, and work with both classical small molecule chemistry and large molecule bioprocesses. The most important feature of spectroscopy is not whether it can work or not, but in choosing the right technique for the process.
The Keit IRmadillo family of spectrometers has been developed specifically to bring FTIR out of the laboratory and onto the manufacturing floor. The IRmadillo variants are:
- IRmadilloDiamond: the workhorse of the IRmadillo family, the IRmadilloDiamond comes with a diamond-ATR tipped probe. This gives it a wide range of chemical compatibility, and increased robustness and scratch resistance. It can be used for a wide range of chemical processes, as well as biochemical processes as it has been specifically designed to withstand both CIP and SIP.
- IRmadillo25H: this model has been specifically designed for high temperatures, and has a working range up to 220°C. The ATR tip is composed of a chalcogenide glass, which gives a full working spectral range of 800 – 3800 cm-1, with no “diamond dead zone” present in the majority of other commercial probes. It does only have a working pH range of 0 – 9, so is not suitable for alkali processes.
- IRmadillo25: The globally Ex-certified (C1D2, ATEX, IECEx) original model. The IRmadillo25 has infrared-glass ATR making it better suited for processes that don’t require caustic clean-in-place (CIP) & sterilise-in-place (SIP) processes.
Using the IRmadillo to Monitor Pharmaceutical Production
The choice of instrument for your process does depend on the process itself, as well as the sorts of information that you need to better control and optimise it. In practical terms, this often comes down to a choice between Raman, near infrared (NIR) and FTIR (mid-infrared).
There are an almost unlimited number of different small molecule reactions in organic chemistry, and the vast majority of those can be studied using FTIR. A representative list of processes that have strong features in the infrared spectrum are:
- Transition metal catalysed coupling reactions (i.e. Heck, Sonogashira, Suzuki, Stille)
- Addition, elimination and substitution chemical reactions
- Protection and deprotection steps
- Chemical rearrangements
- Hydorgenation and other catalysed reactions
- Purification, distillation and separations
Any process that has a change in the chemical functional groups present will have an infrared spectrum, and even slightly changes in chemical (for example reduction of a carbonyl to an alcohol) will have a clear feature that can be used to track reaction progress.
Biochemical processes fall into two main categories: fermentation and cell culture. These tend to occur in bioreactors with the addition of a feedstock that is consumed by biomass to generate the compound of interest. The IRmadilloDiamond has been demonstrated to operate in biopharmaceutical production and can easily monitor the following compounds:
- Organic acids (i.e. lactic, formic, pyruvic and acetic)
- Inorganic acids and salts (i.e. sulphate, nitrate, phosphate)
The IRmadilloDiamond can be used for controlling feedstock addition regardless of biomass growth rate, monitor production of the product (such as monoclonal antibodies), and track any contaminant presence all at the same time.
What about other instruments – Raman, NIR and other manufacturers of FTIR?
- Raman spectroscopy is similar to the FTIR that drives the IRmadillo’s process monitoring, but it can be very strongly and negatively affected by particles and bubbles in the solution, as well as showing strong fluorescence in many cases. Raman is a good tool for measuring the solids in a solution – for example monitoring crystal growth in crystallisation steps.
- Near infrared (NIR) technologies provides much less specific information than FTIR, but can be very cost-effective instruments. They can give a less specific and accurate results compared to an FTIR or Raman, but may be good enough for some situations.
- Other FTIR instruments are available and have been trialled by many pharmaceutical manfuacturers in recent years. These instruments rely on sensitive moving optics, which are not compatible with manufacturing environments. They then make use of fragile mid-infrared fibres, which further compound the problem, making the instruments unreliable and unstable – rendering them unsuitable for QbD and RTRT.
I need 21-CFR-11 capable instruments – are you?
The IRmadillo system is designed to communicate with a DCS or SCADA system using standard communications protocols such as Modbus and OPC-UA. This means the instrument can be installed as part of an existing 21-CFR-11 system.
For more standalone installations, Keit is currently working on a version of our control software that is 21-CFR-11 capable, with audit trails, electronic signatures and restricted access. Please contact us for more information.
My process is exposed to the weather, hot and cold temperatures – how does the IRmadillo cope?
The IRmadillo was originally developed for the petrochemicals and oil and gas industries – so it can take a beating. It has an ambient temperature range of -20°C to 55°C so temperature variations aren’t a problem. It also has an IP65 rating meaning it doesn’t mind whatever the weather throws at it.
The IRmadillo looks fairly large and bulky – can I have a small lightweight version for the lab?
The IRmadillo was designed for stability, robustness and trustworthiness on plant. This means it is a fairly large and heavy instrument, but has hazardous area certification with no need for sample or instrument conditioning systems. We have a range of accessories for the laboratory setting to facilitate calibration, but it’s real use and power comes from plant installations.
The IRmadillo for Pharmaceutical Manufacturing
If you purchase the IRmadillo for pharma and biopharmaceutical processing you will receive:
- IRmadillo process analyser
- Interface and mounting accessories to integrate with your process (following a consultation with your engineering team)
- IRmadillo controller PC
- Calibration services
- Ongoing technical and recalibration support (as per your warranty or maintenance contract)
If you like the sound of this, please contact us for more information. We can arrange a trial installation on your plant for several months so you can see you yourself just what the IRmadillo can do.