From Glassware to Fixed Reactors in API Manufacturing
What’s the secret to successful drug substance manufacturing? Eliminating as many surprises as possible. By doing thorough discovery, research and testing at small scale, many companies can avoid those surprises that can cause large-scale headaches.
Unfortunately, some Contract Manufacturer Organizations (CMOs) and some sponsors don’t realize that factors like the glassware a CMO uses is important. This article provides an overview of why you should ask about the type of glassware your CMO uses.
A perfect example of this is in the use of jacketed glassware during the Familiarization and Optimization phases of API development when you are seeing exactly how the chemistry will work. The traditional way to develop a manufacturing process is to do the initial development in round bottom glassware and then make the transition to small-scale production-level reactors when you move to the pilot plant.
However, this phase can also be carried out in jacketed glassware to more closely simulate what will happen in scale-up, when fixed reactors are used in the plant and the process must fit the equipment instead of the other way around.
The Advantages of Jacketed Glassware
Better testing: The chief advantage of using a jacketed lab reactor is to get a better idea of how a process will work in production, at much smaller scale (usually up to 100 liters). Identifying problems that could occur in the plant is important to prevent wasting much larger scales of raw materials and other costly resources. Additionally, getting it right before moving into production can mean faster time-to-market without costly delays.
Closely simulates fixed reactors in the plant. At PCI Synthesis, we’re committed to using jacketed vessels, which are more expensive, but well worth the cost to ensure consistent, quality and results.
In the past, when we used round bottom vessels, we had some unpleasant surprises the first time we tested a process in a pilot reactor, and many times we had to go back and redevelop a process. We’ve had far less of these problems since we adopted jacketed lab scale glassware, and we can identify problems early and solve them before we get to the manufacturing plant.
Safety: Another advantage of using a jacketed lab reactor is safety. Chemicals are removed from a jacketed glassware reactor through a valve in the bottom of the vessel, whereas a glass vessel is usually sometimes emptied by picking it up. It can be dangerous to pick up a vessel, and if you heat one using a traditional mantle and the reaction starts to run out of control, there’s no way to cool it.
Adherence to GMP: The use of jacketed lab reactors also is another step in ensuring commitment to GMP (Good Manufacturing Practice), clean-in-place and cleaning verification procedures as a process is scaled up.
Higher Glassware Costs Means Better Quality Production
As I mentioned above, jacketed glassware can be very expensive, and it doesn’t involve only the glass vessels, but also the ancillary equipment, such as chillers, agitators, utilities and other equipment.
Yet, this extra effort is part of our commitment to quality at PCI Synthesis. Today, every process that goes through the Kilo lab is done using jacketed glassware and every process is run three times. In the end, this extra effort of time and investment ensures smooth operations when moving to the plant.
To learn about other ways PCI Synthesis is committed to quality, check out other articles on our blog, including: