The knowledge and means are in place to implement real-time release (RTR), a PAT pioneer said at AAPS, but questions remain about whether pharma has the will and desire.
Adopting RTR eliminates the need for conventional, end-of-line analytical testing of drug products and, in doing so, can reduce cycle time while offering more effective process control. By enhancing process understanding and control RTR can also improve quality assurance.
Interest in RTR has grown as implementation of quality-by-design (QbD) and process analytical technologies (PAT) has given manufacturers real-time data. Through continuous monitoring of critical product quality attributes (CQAs) end product quality can be assured without final testing.
Speaking at a Hot Topic session at AAPS 2010, Ali Afnan, president of Step Change Pharma, said manufacturers now have the knowledge and capabilities needed to implement RTR. However, Afnan questioned if the industry has the desire and will needed to adopt the change.
Afnan was part of the PAT team at the US Food and Drug Administration (FDA) and in this capacity was involved in drafting guidance on the topic. This guidance, the final version of which was published in September 2004, defines RTR testing, as does ICH Q8.
To implement RTR, which is used in most other industries, pharma manufacturers must be willing to engage with regulators based on science. Afnan said adopting an open, science-based approach will help pharma work alongside regulators to implement RTR.
Erik Skibsted, principal scientist at Novo Nordisk, and second speaker at the Hot Topic, also said manufacturers must work with regulators. In addition, manufacturers must work with their internal quality assurance teams to ensure everyone is comfortable with the shift to RTR, said Skibsted.
Successful implementation of RTR would be underpinned by technologies capable of effectively monitoring production processes and delivering real-time data. Furthermore, systems must be in place to handle the real-time data gathered by the monitoring tools, said Skibsted.
Technologies that can be used in monitoring for RTR include: near-infrared (NIR) spectroscopy; focused beam reflectance measurement (FBRM); acoustics; and terahertz time-domain spectroscopy.
In his presentation Skibsted primarily addressed NIR and, specifically, research Novo has performed into using it to underpin RTR. NIR can be used to monitor processes, and therefore control them, as well as detect quality defects.
For instance, NIR can be used to assess granule quality of starting materials, which, Skibsted has found, can be indicative of finished product quality. Consequently, monitoring starting materials with NIR and correlating intermediates with end product quality can support adoption of RTR.