Cross-site collaboration in action
Mitigating impurities for commercial-scale manufacture
INTRODUCTION
In active pharmaceutical ingredient (API) development, complex chemical structures, low impurity concentration requirements, and situations in which a new process is set to go straight to commercial-scale manufacturing can all make impurity identification and removal even more challenging.
In a recent project, Sterling set about developing a new synthetic route for a generic API that had already been commercially approved. When dealing with generic APIs, existing competition in the market makes speed and cost containment especially critical. With limited time for multiple campaigns ahead of commercial-scale manufacturing, Sterling had to focus on careful proof of concept, comprehensive process understanding, and comprehensive impurity control from the very start.
To effectively carry out commercial-scale synthesis while simultaneously avoiding potentially harmful impurities, Sterling harnessed the combined expertise of our multiple global facilities. Read on to discover how our North Carolina, Newcastle Biosphere, and Cramlington sites came together to successfully navigate commercial-scale synthesis while ensuring quality, safety, and compliance.
North Carolina
Specialty spotlight
Early phase proof of concept and process development expertise to prepare for commercial-scale manufacture; deep experience in identifying and isolating challenging impurities
Cramlington
Specialty spotlight
Process development work, large and commercial-scale GMP manufacturing, and regulatory guidance
Newcastle Biosphere
Specialty spotlight
Expertise in impurity synthesis and isolation and specialised analytical methods, such as nuclear magnetic resonance (NMR) spectroscopy, for challenging analyses
North Carolina
Specialty spotlight
Early phase proof of concept and process development expertise to prepare for commercial-scale manufacture; deep experience in identifying and isolating challenging impurities.
While Sterling’s North Carolina site most often supports early phase development, the team inherently considers later phase implications in every project. The site’s expertise in designing and optimising processes for a variety of chemical syntheses, enabled process excellence without the benefit of typical early phase testing.
Defining specifications
Identifying and measuring impurities
Optimising the process
Newcastle Biosphere
Specialty spotlight
Expertise in impurity synthesis and isolation and specialised analytical methods, such as nuclear magnetic resonance (NMR) spectroscopy, for challenging analyses.
After the North Carolina team worked on initial proof of concept and impurity analysis, the Newcastle team applied its expertise in analytical method development and application to identify and synthesise particularly challenging impurities that surfaced.
Isolating impurities
for analysis
Isolating impurities for analysis
The Newcastle Biosphere team’s expertise in several complex analytical techniques aided in compiling precise structural information to determine impurity identities. To start, the team used semi-preparative HPLC and other chromatographic methods to isolate impurities and ensure an ample volume of pure material.
Obtaining precise
structural information
Obtaining precise structural information
LC-MS was used to determine the exact molecular weight of impurities for more accurate quantification. Then, NMR spectroscopy was used to find precise structural information, particularly for impurities that had a known mass but required pure material to correctly identify structures, or those where LC-MS data was inconclusive.
After carefully evaluating results, the team shared their findings with the Cramlington team to support their additional work in impurity identification and isolation.
Cramlington
Specialty spotlight
Process development work, large and commercial-scale GMP manufacturing, and regulatory guidance.
The Cramlington site’s expertise in commercial-scale process development and GMP manufacturing, including for complex and hazardous substances, enabled the team to get the process to plant as quickly and efficiently as possible while carefully accounting for time, budget, and safety considerations.
Preparing the process for commercial manufacture
Identifying and controlling impurities
Mitigating process hazards
Ensuring precision and purity, together
While for most projects, impurity work is completed well in advance of commercial-scale manufacture, the combined expertise of Sterling’s global facilities enabled us to adapt with ease when faced with accelerated project timelines, constrained product margins, and challenging requirements.
By leveraging the strengths of our expert teams, we ensured that impurities and other critical project considerations were carefully addressed, while supporting commercial-scale manufacture with the highest quality and safety standards.
