Most biotech firms know that bringing a new drug into the marketplace — from discovery through clinical trials to approval – can take at least 10 years, with costs that can reach into the billions, so it’s no surprise that companies must look closely at where their money is being spent each step of the way.
As a continuation of the Familiarization stage, the Process Optimization stage fully establishes and tests the process that will form the basis for the whole program.
During Familiarization, tech transfer took place between the sponsor and the CMO. The Process Optimization stage is really the investigative phase when it is determined what will be required to scale up the molecule and turn the chemical into a drug substance that is free of impurities. During this stage, the team will determine the quantity and quality of the raw materials required, the chemistry and analytical requirements.
During this stage, you can expect to pay about $6,000 to $10,000 per week, which should include doctorate-level scientists conducting research and scale-up studies, documenting results, testing assumptions, and steadily improving the process.
The work resulting from this stage will ensure that yields are reasonable and that the end-synthesis can eliminate impurities to meet FDA requirements and ICH guidelines.
While typical costs fluctuate from CMO to CMO, to ensure that unnecessary overages don’t occur, below are some things to ask your CMO:
During this stage, the scientists need to understand as much as possible about the process. This includes the Critical Process Parameters (CPPs), or the key variables affecting the production process.
CPPs are attributes that are monitored to detect deviations in standardized production operations and product output quality or changes in Critical Quality Attributes.
Parameters usually include:
Other activities that ensure thorough research, is the Design of Experiments (DOE), or a systematic method to determine the relationship between factors affecting a process and the output of that process. In other words, it is used to find cause-and-effect relationships. This information is needed to manage process inputs in order to optimize the output, and to determine where there might be cliffs in the manufacturing process.
Lastly, thorough research affects the purification and the ultimate level of quality that can be achieved. It is essential that the scientist optimizes the chemistry to minimize any side products.
When developing a new chemical entity for clinical supply and eventual commercialization, hourly rate should be irrelevant. What should be more important is expertise and experience, since that will help you avoid greater costs in the long run.
Less experienced CMOs may have lower rates but can they complete the project on time and with few mistakes? Do they have the expertise to design processes that are efficient, safe, and deliver the right level of quality? Can they acquire the necessary raw materials, and do so at the volumes needed? Many a project has been scratched and started up all over again by a new CMO because of these problems – and that’s not only lost money but often more importantly–lost time.
The key to a successful Process Optimization project lies in the expertise of the scientists doing the investigative work. This phase can often last several months and continuity is crucial to meet timelines and budgets. As mentioned above, experience helps you get it right the first time, which saves money and helps you get to the Kilo lab faster, with the right process, so it’s important to ask about the credentials and experience of the scientists involved in your project. The Process Optimization phase is an iterative process and it takes experienced scientists to understand it. Too much turnover in an organization will slow down progress during this phase, since a new team member would need to be trained and brought up-to-speed on the project. Finding out the turnover rate or retention rate is an important piece of information.
On the journey to drug substance supply and commercialization, one of the most critical stages is the Process Optimization stage since it lays the groundwork for scale-up. This stage is not the time to haggle over hourly rates, or cut corners, but to ensure that the best and brightest are laying this groundwork, helping you avoid any set-backs so you get it right the first time when you move into GMP.
At PCI Synthesis, our tried-and-tested teams work on more process optimization stage projects in a year than many in-house teams work on in their careers. In these blog articles, we provide step-by-step suggestions and best practices to save time and money and to ensure you get what you need from your CMO. We’re happy to answer questions; just click on the link below.
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