process<br />development

process
development

Continuous Manufacturing can involve each individual unit operation in the production of drug substances and drug products.  In addition, it can encompass the integration of several unit operations into an economically and operationally efficient process. CONTINUUS can provide clients with significant advantages across the manufacturing spectrum, while targeted ones can offer quick improvements over existing methods.

Different Solutions for different challenges

Over the past decade, many pharmaceutical companies have developed and implemented continuous manufacturing technologies. However, these efforts are very different in nature and scope (see figure below), with varying degrees of risks and benefits.

Many companies are using single continuous unit operations to overcome technical bottlenecks amongst a series of batch processing (A).  Others have developed the technical ability to integrate solutions for part of the manufacturing process (B). CONTINUUS can support the development for these solutions, as well as leverage end-to-end  Integrated Continuous Manufacturing (ICM), which integrates both the upstream production of API and the downstream formulation steps into a single seamless continuous process (C).  Critical components include:

Novel Continuous Unit Operations: New unit operations that are continuous in nature allow integration and enhance system performance. Currently, many “continuous processes” are utilizing batch-based technologies.
Plug-and-Play Strategy: Continuous unit operations need to be flexible to be used to process many different drugs/drug classes. In addition, for each step, different units may be needed (e.g., plug flow reactor vs. continuous stirred tank reactor), depending on the compound’s properties and process conditions.
Integration Strategy: This requires a deep process understanding to identify all the Critical Process Parameters (CPPs) that impact the final product’s Critical Quality Attributes (CQAs). Control loops based on real-time monitoring of CPPs maintain the CQAs within their required specifications.
Integrated Control Strategy: The control system is critical, as ICM processes run fully automated. The control system continuously receives information from PATs and sensors, issuing immediate precise corrective actions that maintain the process in a state of control (see Control Systems)

By leveraging different aspects of ICM, CONTINUUS Pharmaceuticals is able to offer clients a range of advantageous solutions (see CONTINUUS ADVANTAGE), based on the specific requirements.

Targeted solutions

The unit operations that comprise our Integrated Continuous Manufacturing lines are novel, and provide advantages over existing conventional batch technologies. They permit reactions and formulation steps that are not possible in batch.

Flow Chemistry

Our team has experience converting batch reactions to continuous ones, using a variety of reactors, which include plug flow reactors, continuously-stirred tank reactors (CSTRs), packed-bed reactors and trickle-bed reactors.

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Continuous Crystallization

We have significant expertise converting batch crystallizations to continuous ones. Through the use of in-line PATs, including ReactIR, FBRM, and Raman spectroscopy, we can determine the rates of nucleation and crystal-growth to create robust and reliable crystallizations systems.

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Continuous Filtration

Our proprietary continuous, small scale rotary filtration and washing system purifies concentrated suspensions containing active pharmaceutical ingredients (APIs) or API intermediates.

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Continuous Drying

Our proprietary rapid, continuous, small-scale device forms dry powder from a concentrated or diluted suspension that contains active pharmaceutical ingredients (APIs).

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Continuous Formulation and Product Formation

We have developed proprietary continuous technologies for the manufacturing of pharmaceutical drug products, which are able to be integrated with our upstream continuous processes, as well as the appropriate in-line PATs.

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Control Systems

Integrated control systems are paramount for ICM lines, as they allow for real-time responses to process disturbances. They enable operators to visualize the entire process and respond accordingly.

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PAT

At CONTINUUS, PAT tools are systematically deployed for various unit operations after demonstrating feasibility during the process characterization activities with the aim to implement and ensure the quality and safety of our products

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Continuous Polish Filtration

An automated continuous polish filtration system was developed at CONTINUUS to remove the suspended particulate matter from solutions. They system features two filters working in tandem for uninterrupted operation.

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Continuous Solvent Recovery

A continuous Solvent Recovery system for was designed for our end-to-end ICM Line. The recovered purified solvents can then be reused in the manufacturing process, reducing overall solvent consumption and significantly reducing waste.

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END-TO-END SOLUTIONS

ICM enables seamless end-to-end continuous manufacturing processes that incorporate API formation steps with final drug product formulation. More specifically, by eliminating all the stops-and-starts that make current manufacturing processes time- and cost-inefficient, we are able to attain all the benefits associated with continuous manufacturing. Important underlying principles include continuous flow, an end-to-end strategy, a systems approach, and an integrated control system.

Watch below for the video of our pilot plant in action and the results of our case study