ContinuousPlant® Software Suite

Continua Process Systems' ContinuousPlant® Software Suite is uniquely engineered for modular continuous manufacturing processes and skids enabling the seamless integration of in-process Process Analytical Technology (PAT) orchestrations with advanced process control, and real-time materials traceability and tracking systems. Through years of research and development, Continua created this innovative Process Orchestration Layer (POL) software to enable the life sciences industry, and their process equipment OEMs to consistently produce drug products more efficiently, faster, and of better quality than traditional batch manufacturing methods.

A strategic advantage of ContinuousPlant® Software Suite is its ability to allow users to easily integrate unit equipment such as feeders, blenders, and tablet presses from different suppliers into a single process automation system giving one the freedom to select the equipment best designed to handle the specific material characteristics of the drug products, APIs or biologics being manufactured.

The inherent modularity of ContinuousPlant® Software Suite's object-oriented programming architecture maximizes user flexibility by allowing for the interchangeability of unit operations while incorporating globally accepted S88 batch control standards and terminology to enhance its ease of use. The number, type, and order of the process units are simply determined by a single recipe without requiring additional programming or validation. This allows users to create a recipe quickly and easily in a drag-and-drop format similar to creating a Visio diagram, then configure the units within the recipe via simple drop-down menus.

ContinuousPlant® Software Suite can run multiple products with different processes on a single continuous manufacturing line through its recipe control feature. In the case of OSD manufacturing, this feature allows users to make a product using dry granulation one day and a different product using wet granulation the next. This unique modular, multi-product flexibility is built into ContinuousPlant® Software Suite and validated as a part of the system.

In addition to incorporating S88 software architecture to maximize its modularity, flexibility, and ease of use, ContinuousPlant® Software Suite offers two essential data management functions uniquely designed for controlling continuous processes – materials traceability and tracking. To accurately trace raw material concentrations and lot numbers in real-time throughout the process, each unit operation is assigned a Residence Time Distribution (RTD) model. The concentrations and lot numbers are recorded and stored to allow finished products to be traced back to lot material lots with a high degree of accuracy.

Each ContinuousPlant® Software Suite solution is configured by our expert systems engineers to meet your CM user requirements specification.

ContinuousPlant® Software Suite

ContinuousPlant® Flexible Batch

Built-In Flexibility Compliant with S88 & S95 Standards

  • ContinuousPlant® Flexible Batch enables a batch management system to be applied to continuous manufacturing. This is the core of the ContinuousPlant® Software Suite, which is built upon object-oriented design principles and established batch industry process control standards such as S88 and S95. Continua Process Systems developed the software to uniquely adapt the S88 batch standard to make continuous manufacturing more flexible, and easy to learn and use.
  • ContinuousPlant® Flexible Batch allows the user to build multiple product recipes and configure multiple continuous manufacturing processes through visually oriented software. The required units are dragged-and-dropped into a recipe window and the recipe parameters are added through drop-down menus. Once the recipe is created for the desired product and process, it is saved and downloaded. The recipe is then initiated and controlled by an operator through the Emerson DeltaV™ Batch Operator Interface.
  • Multiple recipes can be created by a recipe author to allow you to manufacture multiple products using multiple CM processes such as direct compression, dry granulation, wet granulation, and custom processes. ContinuousPlant® Flexible Batch is also ideal for running DOEs.
  • ContinuousPlant® Software Suite allows you to create operator interfaces from recipe parameters, working in conjunction with Flexible Batch to support multi-process, multi-product manufacturing lines. Using parameters embedded in each recipe, lists of active equipment and their subsequent equipment connections are generated. From this, a graphic is automatically generated in DeltaV™ Live with the desired configuration. Any process configuration can be generated, meaning that an operator interface can be created for every possible combination of equipment for use in any recipe thereby enabling the complete customization and modularization of your continuous manufacturing line.

Batch Reports - InfoBatch™

  • InfoBatch™ software from Informetric Systems provides comprehensive reporting by aggregating data from the Materials Traceability and Materials Tracking systems. InfoBatch incorporates ContinuousPlant® batch context based on a specified number of tablets, material quantity or run time. The batch context enables traceability from incoming materials through intermediate process steps to final product containers.
  • Batch reports can include active and excipient ingredient lot information, intermediate process conditions, alarms and events, and final tablet summary data and statistics. Reports can be generated automatically with InfoBatch AutoGen™ or interactively through the InfoBatch Web Server. InfoBatch can also print barcode labels in a configurable format.

ContinuousPlant® Materials Traceability

  • Unlike batch processes where raw material sources are known with certainty, raw material sources in continuous processes must be estimated with a statistical probability. The ContinuousPlant® Materials Traceability model utilizes a statistical equation called Residence Time Distribution (RTD) that estimates the time a particle will spend in a vessel to trace material from the tablet drum back to the raw material drum. Each RTD model is fit to the process or product being produced to optimize accuracy.
  • Based on RTDs, our mechanistic and semi-empirical based model is developed from first principles, then combined and validated with experimental data to accurately predict the states of individual unit operations in the process. Utilization of this model versus empirical methods alone has the advantage of dynamically modifying RTDs based on real-time process parameter data thus enabling automatic control adjustments in response to varying process conditions. The model can also be integrated with Process Analytical Technology (PAT) orchestrations to accurately associate the time when Critical Process Parameters (CPP) are predicted to the time tablets are produced downstream.
  • Each ContinuousPlant® unit contains a control module that runs an RTD model in real-time to provide both synchronized real-time materials traceability and process control. Each unit RTD can have up to thirty (30) inputs and predicts up to thirty (30) outputs. The inputs and outputs are objects that contain the mass flowrate, the composition, and the lot number of each component. The thirty (30) inputs and outputs can be comprised of up to ten (10) components with three (3) lots each.
  • The Materials Traceability model reduces transient off-spec production that could mean the difference between disposing of a few minutes versus several days of production. It also fulfills the FDA requirement for drug product traceability back to the original raw material sources.

ContinuousPlant® Materials Tracking

Continuous Manufacturing Execution System (C-MES)

  • The Materials Tracking system uses the data from the Materials Traceability model to provide several functions of a typical batch Manufacturing Execution System (MES). The Materials Tracking application constitutes a Continuous Manufacturing Execution System (C-MES).
  • Material is tracked from the time it enters the system through raw material drums to the time it exits the system as packages of tablets. The barcodes of the raw material drums are scanned into the Materials Tracking system as soon as they are loaded into the dispensing bay bins. The barcode is stored with the drum weight, material ID, and lot number. This lot and material data is propagated through the system of units via the RTDs.
  • The material compositions and lot numbers of the tablets are stored along with a barcode that is generated for each package of tablets. The barcode and the final package weight are printed onto a label that is attached to the final package of tablets.

ContinuousPlant® Nonlinear Process Optimizer

  • The Nonlinear Process Optimizer is an embedded advanced process control (APC) algorithm that either maximizes or minimizes a convex or concave parabolic process value in real-time for nonlinear applications. Unlike a linear process controller, there is no predetermined or fixed setpoint for a nonlinear controller because the process is designed to continuously control within its optimal minimum or maximum specified value limits, which are variable.
  • The Nonlinear Process Optimizer can be used in continuous manufacturing for optimizing blend uniformity of a continuous blender by varying its rotational speed to minimize the Relative Standard Deviation (RSD). The process controller running the Nonlinear Process Optimizer algorithm looks at the current RSD, then semi-continuously adjusts the blender speed in real-time to maintain the RSD at its minimum/optimum control point to prevent over-mixing and under-mixing. Each process or process point can have a different nonlinear curve associated with it and a different optimum blender speed. Process conditions can vary even within the same product run. The process controller for the blender must be able to dynamically adapt to various operating conditions to maintain the minimum RSD.

ContinuousPlant® Process Solver

  • The Process Solver is an embedded advanced process control (APC) algorithm that continuously solves nonlinear differential equations in real-time using numerical methods for closed loop process control.
  • The Process Solver can be applied to a variety of continuous manufacturing applications to solve nonlinear equations such as tablet press feed rate to optimize tablet hardness and weight.

ContinuousPlant® Process Modeler

  • The Process Modeler is an embedded advanced process control (APC) algorithm that fits a nonlinear equation to real-time data that solves for multiple coefficients. The result can be used to predict the future trajectory of multiple time variant nonlinear processes such as bioreactors and chromatography systems.
  • This technique differs from traditional modeling techniques where the model is developed offline from first principles with model coefficients developed from regression of historical process data. Variations in process data may cause offline models to be inaccurate when run in real-time.
  • The Process Modeler uses the same model as one developed from first principles but calculates and recalculates the coefficients dynamically in real-time versus using theoretical coefficients. The algorithm runs continuously producing a new curve with every scan. It predicts a new set of coefficients based upon the new process data inputted from each scan that can be used for model prediction and/or process control. This technique fuses the theoretical model with real-time process data to predict the optimal state.
  • Use case examples for the Process Modeler include chromatography elution end point prediction and control, the modeling of extrusion and fluid bed processes, bioreactor glucose control, and the optimization of wet granulation processes for incorporating extruder and fluid bed dryers into continuous manufacturing processes.

ContinuousPlant® Kalman Filter

  • The Kalman Filter is the de facto standard in avionics and robotics where it is necessary to reduce noise and improve accuracy. It is particularly useful for applications such as GPS, weather forecasting, and missile guidance where both measurement and model data are available but neither one is sufficient by itself.
  • Continua Process Systems developed the ContinuousPlant® Kalman Filter, a powerful algorithm that combines measurement data and model prediction to find the statistically optimal estimate of the system state. The Kalman Filter is considered the optimal estimator for applications where there is statistical noise and a priori knowledge.

ContinuousPlant® Kalman Filter Feeder Algorithm

  • Feeder loss-in-weight (LOI) algorithms are known to be problematic. Since the feeder is mounted on top of a weigh scale, the rotation of the feeder and mixer shafts transmit a significant amount of noise to the weigh scale. The weigh scale needs to be highly sensitive to pick up the change in weight and accurately predict the mass feed rate out of the hopper. The combination of the sensitive signal and physical vibration creates noise in the weight signal.
  • To dampen the noise, the feeder weight data needs to be filtered. However, if the data is over-filtered the mass rate prediction is not representative of the true mass weight. The method in which the data is filtered is also critical to obtain an accurate representative of the mass rate.
  • Our ContinuousPlant® Kalman Filter Feeder Algorithm utilizes a feeder model that estimates the powder density to predict the expected mass rate. The Kalman filter then uses the expected mass rate along with the raw LOI data to statistically estimate the optimal mass rate.

ContinuousPlant® Nonlinear Kalman Filter

  • The Kalman Filter is the de facto standard in avionics and robotics where it is necessary to reduce noise and improve accuracy. It is particularly useful for applications such as GPS, weather forecasting, and missile guidance where both measurement and model data are available but neither one is sufficient by itself. The Kalman Filter algorithm combines measurement data and model prediction to find the statistically optimal estimate of the system state.
  • This technique can also be utilized with Process Analytical Technology (PAT) applications in the pharmaceutical and biotech industries where process measurements and predictions are typically noisy, and models can be developed.
  • The Nonlinear Kalman Filter developed by Continua Process Systems is a novel implementation of the filter that uses an adaptive nonlinear regression technique as the predictive model. This predictive model performs a regression of a nonlinear model in real-time for each new measurement. The model coefficients are updated with the adaptive regression for each iteration of the filter. The process model can be a mechanistic or empirical equation supplied by the user or a standard polynomial, log, or logistic equation built into this product.
  • The ContinuousPlant® Nonlinear Kalman Filter has many applications including chromatography elution endpoint detection, bioreactor glucose control, and API crystallization.

ContinuousPlant® Throughput Optimization

  • Continua Process Systems process control engineers and data management solutions architects have the expertise and technology to develop and implement integrated real-time model predictive control (MPC), in-process PAT software applications, and process data management solutions. Our fully integrated Throughput Optimization solutions are designed, orchestrated, and tuned to maximize your production flow/feed rate or throughput and product quality within a user defined design space.

Continua Process Systems Services

Continua Process Systems
Process Automation & Data Management Services

Continua Process Systems offers a full range of process automation, data management, and systems integration services to assist with the design and implementation of the solution best suited for your continuous manufacturing (CM) process.

We recommend utilizing an integrated project team model to architect, plan and manage the implementation. This approach minimizes chances for incurring unexpected budget overruns and schedule delays.

At a minimum, project team members should include a project manager and systems engineers from Continua plus the user’s process automation project team lead, OEM suppliers (i.e. feeders, blenders, and tablet presses, etc.) and engineering firm. The integrated team model encourages close collaboration and direct communication between project team members starting with the initial front end engineering and design (FEED) phase through project scoping, implementation, startup, and system commissioning.

At the front end, it is essential for the project team to mutually review the User Requirements Specification (URS) to agree upon the scope of work, the optimal process orchestration layer architecture, control network communication protocols, and process automation and data management strategy for monitoring and controlling the critical product quality attributes and process parameters defined in the URS.

Our experience shows that deploying an integrated project team model from project conception to completion enables key project stakeholders to stay focused on assuring the intent of the URS is clearly understood and met.

Each ContinuousPlant® Software Suite solution is configured, tested, and documented by our CM systems engineers. Our engineering team has the expertise and experience to develop and implement process control, Process Analytical Technology (PAT), materials traceability and tracking, manufacturing execution systems (MES), and other data management solutions.

This combination of process automation and data management expertise coupled with our extensive life sciences project implementation experience mitigates project risk by allowing us to take a more holistic view on how best to solve your CM process automation and data management challenges.

Continuous Manufacturing Partners

Emerson is the leading supplier of automation solutions to the Life Sciences industry, with automation expertise and technologies to solve your greatest cGMP manufacturing challenges. Emerson has effective technology solutions for improving your real-time product quality, reliability, and operating costs. From design to implementation, and start-up to on-going optimization, you can rely on Emerson to stay competitive in a global economy.

Emerson’s DeltaV distributed control system (DCS) is an easy-to-use automation system that simplifies operational complexity and lowers project risk. The state-of-the-art suite of products and services increases continuous manufacturing performance with intelligent control that is easy to operate and maintain. The DeltaV DCS adapts to meet your needs, scaling easily without adding complexity.

Founded in 2006, the Center for Structured Organic Particulate Systems (C-SOPS) brings together a cross-disciplinary team of researchers from major universities to work closely with industry leaders and regulatory authorities to improve the way pharmaceuticals, foods and agriculture products are manufactured. C-SOPS focuses on advancing the scientific foundation for the optimal design of SOPS with advanced functionality while developing the methodologies for their active control and manufacturing.

Headquartered at Rutgers University, C-SOPS partners include the New Jersey Institute of Technology, Purdue University, the University of Puerto Rico at Mayaguez, and more than 40 industrial consortium member companies including Continua Process Systems and Emerson.

Integra CMS is the leading provider of comprehensive scientific and technical support to manufacturers who seek to formulate, implement, or optimize continuously manufactured products. Their top network of global universities, industrial partners, and technology suppliers are here to deliver tailored, effective continuous manufacturing solutions. Integra applies a step-by-step approach to help pharmaceutical manufacturers create efficient systems through effective integration of multiple methods and tools to meet key objectives, including maximum process understanding and maximum product quality at minimal cost.

Informetric Systems Inc. develops software applications that enable manufacturers to improve quality and increase productivity. Informetric software provides data acquisition and reporting for critical product release activities in batch and continuous GMP manufacturing facilities.

If you would like to learn more about Continua Process Systems and how our ContinuousPlant® Software Suite of products and services can be applied to your continuous manufacturing process, please contact us to request more information.

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