The first time an API is produced at a production scale is an exciting and critical period in the drug development process. There is often significant pressure on a company to produce the needed quantity and quality of material within a specific time window. Downstream toxicology studies or drug formulation production that have already been scheduled depends on the first production scale-up campaign to produce the needed material at the right quality within the needed time window. The first time a production process is run at scale is the most likely time for an unforeseen problem to arise. When looking at the drug development process as a whole, this is also one of the times that delays are most impactful to clients as they are under significant pressure to provide positive results from their toxicology or clinical trials in a timely manner with minimal investment.
What Are First-Time Scale-Ups?
First-time scale-ups occur in some of the very early phases of drug development. Clients have screened their compounds and selected the one, or few, that they’re interested in developing, and now need additional drug material to conduct toxicology testing, which requires a lot of chemistry optimization, or to run their initial clinical trials. These situations where the quantities of compound needed shift from grams to kilograms are exactly where these first-time scale-up services become needed.
Optimizing Production for a Successful Scale-up
For a successful production scale-up, extensive consideration of potential challenges is needed in the preparation process. During the drug discovery phase, clients may have impurities in their product that are left over from the various processes used, or there may be residual solvents in the product that may not affect the discovery, but will affect the development phase. There is an optimization component required in the scale-up processes, before ever moving into the production facilities.
Diverse Challenges Driving Production
A wide range of things can go wrong during a first-time scale-up. One challenge that may be encountered is the affect scaling-up can have on reaction kinetics. Difficult to remove impurities can form very quickly if safe operating time windows or ranges are not known beforehand. Larger scale production can affect the time it takes to heat up or cool down, and different polymorphs might come out of solution presenting challenges to drug formulation work or changing the expected impurity profile. Filtrations or phase splits that were able to be accomplished in the lab within 30 minutes can quickly become problematic at scale and take days or even weeks to finish becoming ineffective at the removing impurities or sometimes even creating new impurities.
Collaborating for Success
To mitigate some of the potential issues that might arise, the team at Olon USA interact closely to ensure the production process runs smoothly. The chemistry and engineering teams must work together in the process development for manufacturing in order to identify potential issues before production even takes place. This includes identifying parameters that may be a concern during scale up and testing safe operating windows in the lab before scaling the process up. Taking time to evaluate a process before starting production is well worth the effort as it helps ensure that processes are designed to be scalable in a reproducible, consistent fashion.
30 Years of Experience in Streamlining the Process
With over 30 years of experience and client satisfaction, Olon USA specializes in navigating the first-time scale-up process for their clients. The optimization and scale-up process may not always be simple, but they work diligently with the client to provide solutions when challenges do arise. Ultimately, Olon USA understands that the early drug development phase is very resource intensive, and they work to minimize the cost while maximizing the gain to the client. They provide phase-appropriate validation to provide clients with the information they need to successfully proceed down the development pipeline.
Flexibility is Key
Flexibility is key during the first-time scale-up process. At such an early phase in development, clients often don’t have much information on their product, and yet they need their drug material made in larger quantities. It is critical for a CDMO to be able to assess what parameters are essential to the production process and focus on optimizing those parameters so that scaling up can be completed successfully. When things don’t go as planned, being able to pivot and provide quick solutions to the problem is critical to prevent the loss of a batch. In addition, the overall production strategy is adapted to the client’s clinical phase which maximizes the speed and agility in how to respond to situations. The ability to adapt from early phase production through commercial production prevents the need for any external technology transfer to other companies, a costly and time-consuming process.
Not Just Technical Expertise
Beyond their technical expertise in process development and production, Olon USA also has access to regulatory experts within the Olon SPA network to help advise clients if something is necessary for the current developmental phase.
Tailored Solutions for Unique Needs
When working on drug discovery and development, there can be chemicals and reagents used in the initial discovery process that aren’t able to be handled in most scale-up facilities. These chemicals may be highly toxic, or very unique or dangerous, and many stand-alone CROs will not be willing, or able, to work with them. Olon USA’s chemistry group can handle these production challenges and can optimize the processes by removing or mitigating the hindrances with these types of chemicals to prepare clients for success at larger-scale production as well.
Prioritizing the Client Relationship
Clients are heavily invested in their product and its success, and Olon USA ensures they’re kept up to date on their project status. They can expect to be involved throughout the first-time scale-up process whether the project is running smoothly, or problems do arise so that timelines and potential solutions can be discussed. Clients are welcome to visit the facility during production runs and are given the opportunity to be highly involved in the project. Olon USA will continue to fine-tune a solution to a problem until our clients are comfortable with the action plan and are in agreement with moving forward.
Reach out to Olon USA Today
Still unsure if Olon USA is the right company for your first-time scale-up needs? To hear more about how Olon USA works with each client as an individual, read one of our case studies here.
Clients who are searching for a company to work with on their first-time scale-up processes should reach out to Olon USA today to learn how they can help find success. If you’re looking to get a product produced for tox studies, clinical trials, or even just investigating compounds for development, Olon USA will work with you to deliver exceptional results with their small and large-scale production capabilities.