(189q) Optimizing the Pharmaceutical Cleaning Process: Challenges and Opportunities

Optimising the pharmaceutical
cleaning process: challenges and opportunities

Rabah
Mouras^1,2, Gavin Walker^1,2 and Ahmad
Albadarin^1,2

¹
Department of Chemical Sciences, Bernal Institute, University of Limerick,
Castletroy, Limerick, Ireland

² Pharmaceutical
Manufacturing Technology Centre (PMTC), Bernal Institute, University of
Limerick, Castletroy, Limerick, Ireland

Abstract:

Cleaning
validation and verification is a regulatory requirement within the
manufacturing of active pharmaceutical ingredients (APIs) and drug products.
Thus production equipment in pharmaceutical plants ((reactors, dryers, pipes…)
need to be periodically cleaned to eliminate cross-contamination between
different products due to the adhesion of APIs, intermediates, by-products and
raw materials. This process has been proven to be very difficult, time
consuming and result in undesirable effects such as staining, and the
manufacturers strive to improve the efficiency, cost, quality, and time
required to design, qualify, and monitor the cleaning process. There is an
urgent need to optimize the cleaning process that leads to a high
competitiveness through reduced batches rejection, reduced laboratory costs,
and improved process yields and reduced changeover time.   

Our
approach towards developing an efficient cleaning process is based on: (1)
selection of best cleaning agents with the help of modelling and solubility
predictions using conductor-like screening model for real solvents (COSMO-RS) that allows the
screening for innumerable solvents and mixtures, (2) APIs and
intermediates solubility  measurement in
selected cleaning fluids, (3) cleaning trials using metal or
glass coupons in a dipping test apparatus to mimic the cleaning in plants, (4)
ensuring the surfaces are clean by means of spectroscopic and analytical
techniques and (5) developing rinse solution analysis using process analytical
technology (PAT) methods.

Our approach allowed us to choose the most
efficient cleaning fluid resulting in a better cleaning with a considerable
reduction in time and usage of cleaning solvents.

In this presentation, theoretical and
experimental data will be presented and discussed and challenges in the
optimization and developing efficient cleaning process will be addressed.

Key
words: Pharmaceutical cleaning Process, Cleaning
validation, Active Pharmaceutical Ingredient
(API), COSMO-RS, process analytical technology (PAT)

Acknowledgment: The research leading to these
results has received funding from Enterprise Ireland Innovation Partnership
Programme (IP-2018-0727).