Minakem: CM reaps time-saving, quality-boosting benefits
Outsourcing-Pharma (OSP) recently spoke with two leaders from Minakem—Jean-Louis Brayer, research director, and Olivier Jentzer, R&D director at Minakem—about how an increasing number of companies are turning to continuous manufacturing (CM), and how the practice can transform operations.
OSP: Please tell us about Minakem—who you are, what you do, key capabilities/specialties and what sets you apart from the competition.
M: Minakem is a leading European contract development and manufacturing organization (CDMO)for active ingredients in the pharmaceutical industry. It offers an extensive range of advanced technologies and full pharma services to ensure global customers a robust global supply chain and high-quality product delivery.
The company provides expertise in custom process development and cGMP manufacturing. With patient needs placed at the center of its operations, Minakem assures that the drug products it manufactures meet the highest health and environmental safety standards.
Capacity and on-time delivery of high-potent, non-high-potent, advanced intermediates, building blocks, purification by HPLC and solid form studies are carried out at Minakem’s three FDA-approved industrial manufacturing sites located in Louvain-la-Neuve (BE), Dunkirk (FR) and Beuvry-la-Forêt (FR), totaling 290m³.
What sets Minakem apart from the competition are the significant ongoing investments it devotes to its two R&D centers, where highly skilled scientific teams are dedicated to bringing innovation to process chemistry and analytical technologies. Each year sees successful improvements in chemical processes: continuous flow reactions, flow photochemistry or flow electrochemistry.
OSP: From your perspective, how have industry attitudes and the adoption of CM changed in recent years?
M: CM is an established process in many fields, but continuous chemical manufacturing is relatively recent. Without the US Food and Drug Administration's (FDA) policy towards continuous manufacturing, it is very likely that flow chemistry would have remained a good research tool.
In the field of continuous process development, there are two main classes of companies.
The first is the pharmaceutical laboratories themselves and the second is made up of CROs and CDMOs. The financial firepower of pharmaceutical labs has enabled them to invest very quickly in new continuous process technologies and accelerate in this area because they know and work on their own products; they have been able to very quickly develop their own continuous processes.
The second class of company faces a different problem is different. CROs and CDMOs have industrial tools that aim to be permanently in operation; they are dependent on the big pharmaceutical laboratories; in addition, they have to produce APIs on the basis of validated and registered batch processes.
Any change from a batch process to a continuous process is accompanied by a modification and a new regulatory registration which remains very expensive.
It is equally important to mention the evolution of the chemical engineering tools that are made available for process development. In addition to the continuous reactor core, new tools must also be taken into account in terms of the treatment of reactions, extractions and concentrations. For a long time, the technology was centered on the reactor. But now it is the whole chain that must be designed continuously.
When scaling up, even if continuous chemistry saves time in terms of development, it does not completely replace classical batch chemistry and is limited for the moment to particular operating conditions (low temperatures, high dilution, exothermic reactions, dangerous reactions, etc.). This has been highlighted in recent articles published in the OPRD 2020 (Organic Process Research & Development).
OSP: What benefits have companies that have adopted CM realized?
M: The benefits that have been achieved by CMOs that have adopted continuous flow chemistry are fairly well summarized in the article published by Marcus Baumann, Thomas S. Moody, Megan Smyth, and Scott Wharry in the January 2020 OPRD. (DOI: 10.1021/acs.oprd.9b00524):
- Saving time in development and production
- Greater process safety
- Carrying out delicate chemical reactions
- Quality of the products obtained thanks to the greater reproducibility of the processes, and
- A reduced ecological footprint.
This ecological footprint translates into lower energy consumption and lower solvent consumption as well. Personally, we would emphasize process safety and reproducibility.
OSP: What technologies and practices have emerged in recent years that have streamlined the process?
M: It is difficult today to draw a complete panorama of all the reactors that have been made available to the development chemists, from Corning's G1 to G3 to De Dietrich's low-temperature reactor. In terms of reactors, we must not forget the arrival of photochemical reactors combined with the use of diodes or excimer lamps with spectra more adapted than the traditional mercury vapor lamps (low or medium pressure).
As previously mentioned, the arrival of new continuous separation systems are also indispensable tools for successful integration.
OSP: What are the important elements that professionals should keep in mind before embarking on CM?
M: These are essentially regulatory concerns; aside from these, one must be aware that a shop designed for continuous production will be less versatile than a batch shop. This is the difficulty we have had to overcome in the design of our continuous technology platform.
So we can see that the choice is not simple: all batch or all continuous. I sincerely believe that for the moment it's the right use of these two technologies that will develop.
OSP: Do you have success stories of organizations that have adopted CM?
M: The market leaders in fine chemicals for pharmaceutical use have pioneered adoption of continuous manufacturing, not only by producing continuously but also by partnering with continuous equipment manufacturers.
OSP: How might the COVID-19 pandemic have impacted the process?
M: One of the consequences of the COVID-19 pandemic could be a return of the manufacture of some APIs in Europe; in this case, as there will be a change of production site, there will necessarily be regulatory issues to review. Undoubtedly, there is an opportunity to integrate certain challenging steps into continuous processes.
OSP: Do you have anything to add?
Minakem is positioning to be a strong player in continuous process chemistry for the pharmaceutical industry. We already have all the required tools in place to define the critical parameters of the continuous process developments clients submit to us.
Shortly, customers will have access to the complete continuous process development technology platform that has been built upon the in-house expertise our US affiliate Pennakem has developed in continuous processes over the last decade.