So you’ve completed the R&D phase of your Active Pharmaceutical Ingredient (API) or New Chemical Entity (NCE). You’ve successfully produced small batches with good yield and you’re ready to take it to the next level – scale-up.
The successful transition of technology from the lab to current Good Manufacturing Processes (cGMP) suites or the plant for scale-up within a commercial production environment can be a daunting task. After all, during the R&D phase, you can keep costs lower, by producing smaller quantities, without the need for cGMP manufacturing (which can cost upwards of $80K per week). Yet, changing small-scale processes to meet regulatory requirements for commercial production is a whole new ballgame.
When you scale up, cGMP guidance requires that you meet stringent assay, quality, and purity requirements. The plant where scale-up occurs must have appropriate quality management systems in place that can detect and address any deviations to quality. Not adhering to these guidelines, or not having sufficient data can cause your Investigational new drug (IND) submission to be delayed.
Despite the most thorough method development and testing, experienced scientists and meticulous attention to every detail, when a molecule moves to the scale-up stage, Murphy’s Law often kicks in and anything that can go wrong, will. Sometimes it’s because of the sheer fact that operating under cGMP can be slower and more painstaking and the longer time may cause different reactions. Other times, producing larger quantities throws everything off kilter and allows new impurities to enter. In addition, the geometry of the various vessels or agitation can have impact on GMP batches. Molecules are comprised of naturally occurring materials, and often nature has a mind of its own.
Despite its common occurrence through no fault of anyone, when problems occur in scale-up it can translate to hundreds of thousands of dollars, delayed commercialization, loss of funding or the halt of your project.
So how can you do everything in your power to ensure successful scale-up? It begin with robust method development and thorough testing in the R&D lab, and then effective technology transfer for scale-up.
Below are three key steps for ensuring a smooth and effective technology transfer:
Other considerations to ensure that problems in scale-up are minimized include the following:
Scale up can be the most expensive phase in your journey to product commercialization and requires expertise, experience and meticulous collaboration across departments, CROs and CMOs. While it’s impossible to predict how molecules will react when they are produced in larger quantities, implementing rigid protocols and best practices can go a long way to minimizing them.
For additional insights and observations, please check out: API Manufacturing Technology Transfer; Shattering 5 Myths About CDMOS; or Analytical Method Development in API Manufacturing.