China is the world’s largest producer and exporter of active pharmaceutical ingredients (APIs) and a major supplier to the U.S. But recent history has seen several Chinese API producers thrust into the media hot seat for various offenses, including quality issues, improper waste management and the release of hazardous chemicals.
The Chinese government has tried to crack down, hitting API manufacturers with new environmental and regulatory restrictions, as well as an environmental protection tax. While many facilities across China ended up closing their doors, Chongqing-based Porton Pharma Solutions, a CDMO specializing in API development and manufacturing, found ways to continue its already impeccable reputation for quality and environmental safety.
Porton’s recent partnership with Codexis, a California-based protein engineering company, promises to accelerate the creation and commercialization of new, low-cost, sustainable API manufacturing processes, enabling Porton to offer a powerful new technology to its pharma clients.
BENEFITS OF BIOCATALYSTS
Traditionally, APIs are manufactured using a variety of chemical catalysts. But processes using these catalysts are often inefficient, labor-intensive, imprecise and require specialized manufacturing facilities. Disposing of hazardous byproducts created by these processes can also be dangerous and expensive.
Technical advances have enabled biocatalysts to be employed as an alternative to chemical catalysts, which results in a less cumbersome and environmentally safer process. Today, over a dozen different chemical transformations have been proven at commercial scale using biocatalysts, says John Nicols, president and CEO of Codexis, many of which are highly prevalent in today’s small molecule drug chemistry. But in order to get there, each biocatalyst must be engineered to fit with the corresponding substrate.
“Fundamentally, every intermediate or drug manufacturing process step that could benefit from biocatalysis needs its own biocatalyst — it’s very bespoke,” says Nicols.
Codexis’ CodeEvolver platform utilizes sophisticated processes to generate and screen large numbers of protein libraries. This ultimately produces an engineered protein with the properties needed to optimize the application.
Porton’s partnership gives the CDMO preferential access to Codexis’ proprietary technology, which combines DNA library synthesis and sequencing, advanced high-throughput screening and machine learning with scientific expertise. The technology is based on the concept that natural genetic mutation and selection can be accelerated in order to improve the function of protein pathways.
“Our platform technology sifts through the myriad of enzyme optionality to cost-effectively come up with the customized enzyme for each chemical transformation,” explains Nicols.
As a result, Porton is able to pass this cost- and time-savings on to its small molecule clients.
BIG WINS ALL AROUND
For Porton, technological leadership is central to its growth strategy — the company strives to progressively access leading-edge technology that enables them to differentiate themselves in a crowded contract market. The CDMO is currently in the process of equipping its China and U.S. facilities (J-STAR Research) for more cost-efficient screening of enzymes, while also marketing its new capabilities to the pharma industry.
The adoption of protein engineering by a growing and reputable CDMO may have broader implications for the pharma industry. Porton’s leadership is vocal in its view that biocatalysis is a highly impactful technology that will improve the future of pharmaceutical manufacturing.
In fact, Codexis estimates that at least one out of every three small molecules in development and/or on the market could be made at lower cost if a customized biocatalyst were designed and installed for each process.
Expanding the use of biocatalysis in drug manufacturing can lead to more cost-effective manufacturing: higher yields of expensive intermediates, less waste, and a greener alternative for API manufacturers.