Workstreams

The current workstreams for PIPS include Biocatalysis, Continuous Manufacturing, Digital Factory, Particle Engineering and Plant Operations.

Biocatalysis

Biocatalysis has numerous benefits for pharmaceutical manufacturing, i.e. high chemo-, regio-, and stereo-selectivity; sustainable, safer materials; mild/safer reaction conditions; and multiple, cascaded reactions in one pot. However, its applicability in the pharmaceutical industry has been impeded. The limitation is due to the narrow range of chemistries with industry-ready enzymes, slow enzyme/process development which requires years of investment, low participation in early development route screening, lack of telescoped, multi-enzymatic reactions and little support for continuous operations.

Through partnership with stakeholders within PIPS, we see a future where:

Industry-ready enzymes cover all chemistries of pharmaceutical significance
Enzyme evolution/process development takes just weeks or months and allows enzymes to be evaluated in early development stages
Cascaded reactions open up new and low cost routes to pharmaceutically important intermediates and APIs
Enzymes are in frequent use in continuous operations
Significant opportunities in enzyme manufacturing, new enzyme class development, reaction and separation systems and enzyme evolution

Initial research in the workstream has focused on speeding enzyme evolution through in silico predictive methods and microfluidics-based enzyme screening and on novel enzyme immobilisation methods to increase enzyme stability and reactivity.

Current projects in the workstream include:

An Integrative Computational/Experimental Workflow for Enzyme Development
Microfluidics-based Rapid Evolution of Enzymes for Green Oxidation in Pharmaceutical Manufacturing

Continuous Manufacturing

A confluence of compelling economic and regulatory factors is driving a paradigm shift in pharmaceutical manufacturing. From batch manufacturing processes, which have held sway for well over a century, to modular, highly controlled and automated continuous manufacturing processes, the industry has moved to embrace manufacturing efficiency through automation.

The main objective of this workstream is focused on developing novel, scalable, single- and multi-stage continuous manufacturing processes, especially at the intersection of novel chemistries and unconventional reactors, and to accelerate their industrial implementation via strategic development of state-of-the-art model-based control methods.

Projects in this workstream tackle open multi-scale challenges in the development of continuous processes involving heterogeneous precious metal-based catalysis or photocatalysis all the way from the understanding and design of catalysts to the scaling up of novel flow reactor modalities. The formulation of mathematical models and their use in predictive control is also an overarching theme in this workstream.

Current projects in the workstream include:

Atomically Dispersed Single Site Heterogeneous Catalysis (completed in September 2020)
Development of Multi-step Processes in Pharma
Gas Liquid Solid Heterogeneous Catalysis
Heterogeneous Catalysis for Cross-coupling Reactions in Batch and Continuous Flow
Scalable Photochemistry - From Deep Chemical and Process Understanding to Manufacturing Scale Reactor Systems
Developing Efficient Electrochemical Trifluoroalkylation for Pharmaceutical Derivatisation
Model-based Design, Scale-up and Optimisation of Electrochemical Reactors for Pharmaceutical Production
3D Printing of Electrodes for Electrochemistry Processes
Development of an Adaptive Flow Electrosynthesis Platform with In-line Detection and Electrode Fouling Assessment for Electrofluorination Reactions

Digital Factory

With the advent of Industry 4.0 and the accompanying waves of technological advances, such as artificial intelligence, machine learning, IIoT, sensors, big data, automation, data mining and analytics, there are many tools which the pharmaceutical industry can leverage to revolutionise the next quantum leap in performance. In the context of quality control, business decision making, enhanced operations, just to name a few, digitalisation is an integral and inevitable pathway which the pharmaceutical industry has to adopt.

In addition, under the current landscape of uncertainty and disruptions, it is critical to apply digitalisation to stay relevant by delivering higher operational efficiency by mitigating human errors, enhancing system and modular connectivity and understanding trends to predict the future.

Although this proposition is widely accepted, the uptake rate by pharmaceutical companies is low due to various factors, such as lack of expertise and high investment. To address this gap, the Digital Factory workstream aims to partner thought leaders to innovate and adopt new applicable and transferable technologies which can be piloted and subsequently used in the pharmaceutical plants to drive operational excellence.

Current projects in the workstream include:

Data2Knowledge in the Digital Manufacture of Pharmaceuticals
Novel PAT Sensors
Visioning the Digital Future of PIPS

Particle Engineering

With product portfolios becoming more diverse, novel routes of delivery have to be sought to enable differentiation. In addition, combination products must continue to increase in prevalence with sustained exertion of pressure to drive down costs. Flexible engineering technologies allow the pharmaceutical industry to deliver on target product profiles through streamlined production platforms.

The main objective of this workstream is to develop and demonstrate novel platforms for rational drug product manufacturing via particle engineering. The platforms will move beyond traditional crystal engineering approaches by combining scalable and continuous generation methods with rationally chosen mixtures of APIs and excipients to enable the creation of novel 'designer' particulate drug products with enhanced downstream processing properties and tunable drug release profiles.

These platforms are envisioned to ultimately extend beyond conventional direct compression/tableting methods and enable diverse modalities, such as long-acting injectables and the delivery of macromolecules.

The current project in the workstream is:

Particle Engineering to Enable Drug Product Performance

Plant Operations

The manufacturing sector contributes to approximately 22% of Singapore's GDP. Of this percentage, 40% of activities is attributed to chemical and biomedical processes. With the ultimate goal of better responding to a VUCAH (Volatile, Uncertain, Complex, Ambiguous, Hyper-connected) world and to boost competitiveness on existing and future manufacturing processes, companies from the same, or related industries, must endeavour to join forces to revisit and address gaps in current plant operations in the pre-competitive space.

With a right mix of short term, implementable solutions to current challenges ("quick wins") and long term, more speculative ideas to address opportunities ("high risk-high reward"), the workstream targets research areas which are typically underserved by academia. However, it should be noted that the identified solutions could solve real world problems.

Topics under this workstream include:

Alternative REACH compliant scrubbing solutions for hazardous gases
Cleaning and changeover in batch multipurpose plants
Enhanced crystallisation and second cropping
Enhanced inspection of areas inaccessible to humans
Membrane technologies for aqueous waste treatment
(Re)design of equipment and/or chemical plant
Solvent recovery/recycling/reuse technologies

Current projects in the workstream include:

Automated Calibration and Model Maintenance of Probe-based Spectroscopy in the Plant Environment
Cleaning Project: Fundamental Understanding and Laboratory Protocol
FBG Sensors for Condition Monitoring of Glass-lined Equipment used in Pharmaceutical Manufacturing Integrity Monitoring
Feasibility Study on Automatic Detection of Anomalies in Captured Images with Limited Training Data
Feasibility Study on the Use of Single Use Technology (SUT) in High Potency/Low Volume API Manufacture
Membrane Separation Technologies
Sharing and Identification of Best Cleaning Practices for Filter Dryers
Understanding and Mitigating Membrane Fouling to Exploit the Benefits of Membrane-based Filtration for the Separation of Biocatalysts in the Manufacturing of Small-Molecule API

Workstreams

Biocatalysis

Biocatalysis

Continuous Manufacturing

Continuous Manufacturing

Digital Factory

Digital Factory

Particle Engineering

Particle Engineering

Plant Operations

Plant Operations

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