Shifting pharmaceutical production to continuous manufacturing is a decision that an increasing number of operations are making. Manufacturing drug products on a single, uninterrupted production line offers a wealth of potential benefits, but the process is not without its challenges.
One on-demand session during the hybrid CPhI Worldwide event this year (in-person in Milan, Italy, November 9-11, and digital content available October 25 to November 19), Developments and Opportunities in Continuous Manufacturing, participants will hear about CM trends, challenges, and benefits from two industry experts:
- Doug Hausner, senior manager of continuous manufacturing with Thermo Fisher Scientific
- Perrer Tosso, senior manager of advanced manufacturing technologies for US Pharmacopeia
Hausner spoke with Outsourcing-Pharma about the accelerated adoption of CM throughout pharma, why it appeals, and considerations for those yet to make the jump.
OSP: Could you please tell us about the recent evolution of CM in the pharma manufacturing realm—are more operations becoming savvy and adopting CM in their businesses?
DH: We continue to see evolution in the adoption of CM within the industry. The move is slower than many expected years ago but both branded and generic companies continue to move in that direction with their OSD products.
Some companies have fully integrated CM into their early-stage development, some are working through their first programs, some are saying that they will be doing CM in the future but just aren’t ready today.
OSP: Please share an overview of the benefits of adopting CM.
DH: The benefits of CM have been listed often and include increased quality/quality control, rapid process development, manufacturing volume flexibility, and of course cost. The challenge is that a lot of these benefits come into full effect with full adoption of the technology and coupling it with greater utilization of electronic data and batch systems, along with real-time analytical testing and even release. Much more benefit can be realized if CM is integrated properly within the organization and quality system.
OSP: What characteristics of an operation, its leadership, and corporate culture might make an operation more ready and willing to go with CM?
DH: I previously stated that much more benefit can be realized if CM is integrated properly within the organization and quality system. This takes support from leadership and a corporate culture that can embrace disruptive change for the long-term benefit of the organization. The folks that need to operationalize CM can do so if there is support for the business both in the short term with an eye on the long term.
OSP: Similarly, what might be some of the barriers to adopting CM?
DH: The main barrier for adoptions CM at this point given that it can be now accessed through CDMOs, which removes the capital barrier, is apprehension due to lack of organization experience or exposure to the technology. Today, we see both small and emerging companies, as well as generics, adopting CM, whereas it was really only large pharma a few years ago still. In many of those instances of small and emerging or generics there are people who had joined the organization after working on CM at a previous employer.
Another factor that should be mentioned is regulatory uncertainty, which is often a major factor in the apprehension to adopt CM, though with the recent release of ICH Q13, that should be a lesser hurdle moving forward.
OSP: In your session, you plan on sharing an overview of the state of CM regarding API, FDF, and biologics. Could you please share some of the commonalities, as well as key differences?
DH: The commonalities between different forms of continuous processing whether they be ‘for small molecules, biologics, or any other CM process are:
- continuous processes are inherently operating at or near a steady state, which allows for better monitoring and control which then leads to
- utilization of advanced process control with real-time analytical monitoring and data collection.
In general, CM brings in a number of elements that can be thought of as aspects of Industry 4.0.
OSP: Please tell us of the catalytic role of national regulatory agencies and pharmacopeias.
DH: National regulatory agencies have been helping to drive CM adoption for a number of years. National regulatory agencies have clearly articulated a desire for the industry to move towards adoption and have worked together in many instances to ease the pathway.
Even before ICH took up CM as a topic, the FDA, EMA, and PDMA were working collaboratively to provide harmonized guidance to the industry. Additionally, the FDA even established new processes where those interested in adopting the technology could engage and get feedback prior to submission.
With regard to pharmacopeias, the USP, in particular, has been active in convening experts, supporting research, and developing services that can support the industry with CM implementation.
OSP: How can companies like Thermo Fisher help their clients adopt and operate a CM environment?
DH: Our goal in helping clients is to be able to support them every step of the way. To this end, it is not just about installing commercial manufacturing capacity. We provide early-stage feasibility and development services for CM which can be easily integrated into a traditional early-stage development program.
Talking about CM early on and understanding the process and how we can guide you throughout allows you to be prepared from a business case perspective to take a product into CM for a Phase III clinical program. At this stage, we have multiple development teams to support the process development along with SMEs in real-time analytics, process control, ad regulatory aspects of CM. We then provide a full-service offering including full regulatory support through development, Phase III clinical supply, and into commercial.
Clients that don’t need full-service support can contract us for whatever they do need but having that full-service offering is key to helping clients without internal CM programs adopt the technology.
CPhI Worldwide 2021 is a hybrid event; the in-person component (expected to host up to 30,000 industry professionals with 1,400 exhibitors) takes place November 9-11 in Milan, and the digital content will be available until November 19. Read here to register or to see a list of sessions, events, and other features.