# Risk-based process synthesis and Industry 4.0 framework for pharmaceutical manufacturing processes

> **NIH FDA U01** · PURDUE UNIVERSITY · 2020 · $975,988

## Abstract

Project Summary / Abstract
 Over the past five years, this Purdue University team has been collaborating with colleagues at Rutgers
University to investigate the computational and experimental infrastructure for continuous manufacturing (CM)
of solid oral dosage products. This work has built on a decade of research under the NSF supported Center for
Structured Organic Particulate Systems. In parallel, the PI and Purdue co-workers have investigated CM
approaches to small molecule API manufacture at micro and intermediate scales. This work has demonstrated
the essential roles of process modeling, process analytical technology, active process control, intelligent process
monitoring, material tracking and real time risk assessment. Moreover, current work is showing how these
components must be linked through an integrated data management and informatics infrastructure in order to
achieve the desired Industry 4.0 functionalities.
 While CM is an important development for the pharmaceutical industry, it is not a universal solution that
meets all manufacturing needs, either technically or economically: often hybrid batch-continuous or fully batch
modes can be advantageous. Moreover, given the major investment in existing batch facilities in the generic
\manufacturing sector, there is an unmet need to bring Industry 4.0 functionalities to those manufacturers and
thus significantly improve quality and reduce cost of medicines. The goal of this proposal is to expand the
research on CM to develop and demonstrate a framework for the design and operation of batch and hybrid small
molecule manufacturing systems. This will be achieved through five aims:
Aim 1: Development of Pharmaceutical Model Library for small molecule and oral drug product manufacture
Aim 2: General framework for the optimal synthesis of processes for small molecule-based API and product
manufacture, encompassing the spectrum from batch to fully continuous processes
Aim 3: Development of an Industry 4.0 real-time process management framework (RTPM).
Aim 4: Demonstration of these technologies using several case-studies including high cost/low volume and high
volume/low cost generic drugs at three different scales (lab, pilot and industrial)
Aim 5: Development of instructional modules for conducting training programs for both FDA staff and industry
as well as web-based access to tools and cases studies via pharmaHUB.
 This work will result in the development of the tool set necessary to implement Industry 4.0 across the
pharmaceutical sector as well as the demonstration of the framework for systematic design and operation of
processes for several specific drugs, including the effects of scale. The case studies will serve to inform and
promote innovative manufacturing practices across the numerous batch and hybrid batch-continuous facilities
existing worldwide. Moreover, by complementing the progress made in CM, it will enable the FDA to develop
effective guidelines on the application of Indus...

## Key facts

- **NIH application ID:** 9995462
- **Project number:** 5U01FD006738-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Zoltan Kalman Nagy
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $975,988
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995462

## Citation

> US National Institutes of Health, RePORTER application 9995462, Risk-based process synthesis and Industry 4.0 framework for pharmaceutical manufacturing processes (5U01FD006738-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9995462. Licensed CC0.

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