How real-time release (RTR) can transform pharmaceutical manufacturing

The RTR method has significant potential, but pharmaceutical manufacturers looking to adopt it must first meet several prerequisites.

In brief

• With the RTR approach, pharmaceutical manufacturing companies can boost their efficiency, lower costs and enhance product quality, among other benefits.
• The requirements for successful RTR implementation include advanced data integration and a mature digital plant model.
• RTR is building momentum in the pharmaceutical industry.

In the rapidly evolving pharmaceutical industry, digital transformation is essential to maintain competitiveness and drive compliance with stringent regulatory standards. One of the most promising advancements in this realm is the real-time release (RTR) method for drug manufacturing. Leveraging advanced data analytics, the Internet of Things and automation, RTR enables manufacturers to monitor and control production processes in real time. This innovative approach enhances product quality, reduces batch release times and minimizes the risk of errors, potentially leading to a reduction of over 30% in manufacturing cycle time.¹

Overall, RTR is transforming pharmaceutical manufacturing by improving quality, efficiency and cost-effectiveness.

RTR implementation prerequisites 

Despite its advantages, advancing pharmaceutical drug manufacturing to deploy RTR has some very high barriers to entry, which contributes to its limited adoption in the industry. To facilitate the initiation of RTR, the following enabling technologies and prerequisites must be considered. 

Digital Plant Maturity Model and Requirements

The Digital Plant Maturity Model (DPMM) defines a comprehensive set of characteristics of business and enabling capabilities that characterize a manufacturing site, ranging from the lowest level of automation to full end-to-end value chain integration from suppliers to patients. Achieving RTR necessitates a more advanced state within the DPMM (see below), particularly the characteristics of the Predictive and Adaptive Plant, which reflect the high-level requirements needed to adapt RTR. 

Figure 1: Digital Plant Maturity Model

Source: BioProcess International

Advanced data integration of systems

Making the leap to RTR requires an advanced level of data integration within the manufacturing execution system. Any release criteria required for in-process and post-process should relate to the MES. This could include, but is not limited to:

• Quality management system
• Enterprise computerized maintenance management system 
• Laboratory information management system 
• Warehouse management system
• Equipment calibration system

The integration of these systems with the MES is a critical steppingstone prior to considering the advancement into RTR. 

Process analytical technology (PAT)

Defined by the FDA, PAT is a methodology used to design, analyze and control pharmaceutical manufacturing processes by measuring critical process parameters (CPPs), which impact the critical quality attributes (CQAs). PAT can cover a broad range of capabilities, in-line sensors and analysis techniques. Ultimately, these devices should assist in providing analytical results that predict product quality to assist in the real-time release of the product. 

Product release criteria and process

The product and its manufacturing process must warrant the need to implement RTR. This entails having a high maturity of process understanding and data to support the evolution to real-time release. And the process should be predictable and repeatable concerning CPPs and CQAs. 

In addition, the process should have a cycle time that stands to benefit significantly from the implementation of real-time release. For example, if post-processing product release testing for Product A takes over 30 days and Product B takes 1 day, implementing RTR for Product A would yield much greater benefits in cycle time. Products should be prioritized with a value-based approach for cycle time improvements. 

Current trends in RTR adoption

Real-time release is gaining traction in the pharmaceutical industry because of its ability to enhance efficiency and product quality. Key trends driving this momentum include: