PMTC

PMTC Projects

PMTC Core funded Project 1 

Plant Cleaning and Changeover:  Is the most recent program to be initiated and includes methodology development, applied mathematical models and development of novel spectroscopic techniques, the work is resourced across Bernal Institute and CIT.  Cleaning and subsequent verification and validation has always been a time consuming and costly operation in multipurpose Pharmaceutical plants.  This has become even more problematic in recent years with an increasing focus on smaller production volumes resulting in increased numbers of changeovers and more time spent devoted to cleaning.  In many plants average cleaning changeover cycles can take ~15 days, which represents a significant proportion of plant utilisation time in a yearly cycle, more than 50% in some cases.  

PMTC designed and published A best practice guideline document detailing good practice for cleaning, validation and verification.  The document contains, cleaning methodologies and presents calculations in a structured, common format.  It also makes clear distinctions for handling small molecules, large molecules and investigational new products where appropriate.   

A third workstream initiated in early 2017 is developing a point-and-shoot device to replace swabbing for cleaning verification which will enable at-line detection thus reducing wait time and allowing access to difficult to reach places in the equipment train.  The aim is to build a bench top prototype to determine the detection/sensitivity of DUVRRS for use with pharmaceutical excipients, APIs and cleaning agents. 

A fourth workstream also initiated in 2017 aims to support the improvement of new cleaning methodologies by developing, validating and analysing mathematical models of the interactions of adherents and cleansers on different surfaces. The program will develop and analyse mathematical models of the key physical processes of cleaning. These models will be informed and validated by discussions with industry partners and by comparison with data from an experimental rig that will be constructed at the PMTC. The rig will simulate various aspects of cleaning processes (on a smaller scale) from the pharmaceutical industry. 

Partnerships with GSK, MSD, Pfizer, Janssen, Helsinn Birex, Roche, Avara, Lilly, Novartis, Ecolabs, Carbon Group, Steris, have been established.   

PMTC Core funded Project 2 

Enabling Continuous Processing: This project, based between the Bernal Institute and UCC, aims to develop and advance the capability and knowledge to enable continuous processing of pharmaceutical materials.  The work has focussed on the initial continuous feeding step, which is a critical manufacturing step to any continuous solids process and any variability in this first step will be passed on downstream to the final product; on assessing the suitability of API and tablet blends for various processing routes based on literature sources; dry granulation (roller compaction and twin screw) for continuous processing, including integration of existing and novel PAT technologies (NIR, Raman and Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) to monitor blend wetting and tablet dissolution performance at-line).  Additionally, this program has combined direct compression / dry granulation strategies along with continuous processing together with model predictive control to monitor various pharmaceutical unit operations as individual separate units or a single unit operation which has included blending and direct compression, freeze drying, tablet manufacturing and coating.  Partnerships with Hovione, JRS, Chanelle Pharma, Eirgen, McKesson-Northstar Healthcare Ltd, Glatt, Colorcon, Pfizer, MSD, Helsinn Birex, GSK, Novartis, Alkermes, Innopharma Labs, GEA, Servier, Janssen and Astellas have been established.  Deliverables have included: 

• Developed fully PAT enabled unit operations including blending, roller compaction, freeze drying, twin screw, tabletting 
• Established PLS models for control of unit operations 
• Broadband Acoustic Resonance Spectroscopy (BARDS) application to direct compression tableting as a rapid analysis/PAT tool 
• Developed basic decision software to inform processing route selection. 

PMTC Core funded Project 3 

Soft Sensors and Chemometrics: Resourced at Bernal Institute this project uses Chemometrics (a branch of statistics involved with dealing with chemical data) to develop Soft Sensor (the inference of an attribute from measurement of another, more accessible one) methodologies to allow process control and real-time decision making.  By utilising existing infrastructure, the utility of advanced data analysis with chemometric methods has been demonstrated. A range of exemplar systems have been developed which allow the utility of chemometric analysis to be demonstrated in a “something for everyone” way. This approach has led to increased engagement from multiple industry partners.  A selection of the examples developed to date include: 

Partnerships with Rottapharm, Mylan, Eirgen, Teva, EviView, Croom Precision, GSK, Innopharma Labs, Janssen, Ballina Beverages, Valitacell, and Astellas have been established.   

The outcomes from this program of research has delivered a significant number of soft-sensors underpinned by chemometric analysis addressing contemporary industry problems.  Examples of the outcomes generated to date include: 

• Image Analysis for determination of drying progress 
• Inference of Ribbon Density from in-line NIR measurements During Roller Compaction 
• MVDA of in-line NIR measurements for End-Point Detection 
• MVDA of Visible spectroscopic data for measurement of evolution of emulsification reaction 
• Inline Raman spectroscopy applied to pseudo-polymorphic conversion 
• Extended Raman Mapping for tablet content uniformity 
• PAT for KQA control during twin screw wet granulation 
• Classification analysis for Predictive maintenance scheme of grinding process from power draw measurements.