PHARMACEUTICAL CLEANING: A RESEARCH AND METHODOLY APPROACH Adeyinka Aina 1#, Chris Edlin 1 and Charles Gordon 2 1. Pharmaceutical Manufacturing and Technology Centre, University of Limerick, Ireland. 2. Britest Limited, The Innovation Centre, Daresbury, Cheshire, WA4 4FS, United Kingdom. Introduction: The Pharmaceutical Manufacturing Technology Centre (PMTC) was established in December 2013 and funded both by Enterprise Ireland and IDA Ireland, supplemented with co-funding from industry and other public sources, its mission is to make Ireland the global hub of pharmaceutical process innovation and advanced manufacturing. It also shares a common vision with other centres by helping to support and develop the Irish pharmaceutical industry (small and large molecule). Companies access PMTC to create projects and execute world-beating industry-relevant research in advanced technology solutions to address contemporary manufacturing issues. In collaboration with leading pharmaceutical companies, PMTC currently has six main themes of research; Cleaning, validation and verification, enabling and control of continuous processing, soft sensor modelling tools, API (Active Pharmaceutical Ingredient) real time release PAT (Process Analytical Technology), powder processing and advanced rapid micro-analytical techniques. In response to developments in the regulatory environment relating to cleaning validation, PMTC commissioned the ‘compliance group’ to deliver a Good Cleaning Validation Practice (GCVP) document. This document was produced based on a review of current guidelines and input from the Health Products Regulatory Agency (HPRA) and industry, it is available online ( Dr. Chris Edlin is the current director of the centre. Vision: To develop the reputation of the PMTC as a world class centre of excellence for pharmaceutical manufacturing issues, with the ability to attract significant future R&D funding from both industrial and EU/National funding agencies. -Collaborative -Inclusive -Shared infrastructure -Connected Ecosystem Project aim: To use an already existing collaboration between Britest, UK and the Pharmaceutical Manufacturing and Technology Centre (PMTC), Ireland, to scope pharmaceutical cleaning research methodologies, using gap analysis, Process Analytical Technology (PAT) and modeling technologies with the aid of proprietary tools (provided by Britest UK). These tools defines, structure and translate process knowledge and information into process understanding. To achieve the above, multiple studies would be carried out at various Irish pharmaceutical companies by both Britest, UK and PMTC. Output from these studies would be made available to participating companies and other generic industry sectors. PMTC will also benefit from these studies in its endeavour to assist local Irish companies improve their competitiveness. Plant cleaning challenges: Low volume High volume cleaning active Drawbacks: - Average cleaning cycle can take up to 15 days Clean-out can require: - 8 tonnes of solvent* -total number of changeovers ~ 53 (2013)* -500 person hours* -~£1mn lost production / cycle* - Decreasing volume requirements result in even greater impact of cleaning on the environment Approach A better understanding of the manufacturing process will help develop a robust cleaning protocol tailored-made for every specific processes. These protocols will then facilitate: - Greener, quicker and cheaper cleaning - Clean General Manufacturing Practice (cGMP) - Help choose appropriate sampling and validation techniques Work plan: Activity Sep/ Oct-15 Nov-15Dec-15Jan-16Jan/ Feb- 16Mar-16Apr-16May-16Jun-16 Training and background Case study 1 Case study 2 Case study 3 Case study analysis Case study 4 Methodology development Case study validation Assessment and future planning Validation: -Visual inspection -Total Organic Carbon (TOC) -Conductivity measurements -High Performance Liquid Chromatography (HPLC) -Ultra Performance Liquid Chromatography (UPLC) -Ultra Violet spectroscopy -Raman spectroscopy Expected outcomes: -Be able to set visual acceptance criteria -Come up versatile approach for detergent removal -Estimate microbiological limits -Merge worst case approach with toxicological limit * Figures presented at the PMTC meeting in May 2015