How Neuland Expanded Esperion’s Bempedoic Acid Amid Pandemic Lockdowns and Supply Chain Interruptions
Just as COVID was making itself known in February 2020, the FDA was approving Esperion Therapeutics’ new first-in-class medication for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C.
The emerging coronavirus and the FDA approval would converge as Esperion planned on expanding Bempedoic Acid supply at Neuland in 2020, setting up a challenging manufacturing environment for this potentially ground-breaking drug.
Esperion Therapeutics’ NEXLETOL® & NEXLIZET®
Esperion Therapeutics began working with Neuland Labs prior to the pandemic to support expansion of Bempedoic Acid, the major active ingredient in NEXLETOL® and NEXLIZET®. In 2019, we entered into a technology transfer and supply agreement for the subsequent commercial API production of Esperion’s New Chemical Entity (NCE), bempedoic acid.
Overcoming a Challenging Pandemic Manufacturing Environment
The Esperion project encompassed technology transfer, pilot batch production, scale-up studies, process validation and production of commercial quantities of the Bempedoic acid API.
Neuland and Esperion worked together to put supporting processes in place. This ensured Esperion’s Process, Analytical, Engineering and Supply Chain teams possessed remote monitoring capabilities and could provide virtual guidance in real-time.
Developing and implementing this level of communication and access proved critical to every facet of the project, from technology transfer and production of pilot batches, to process validation (PPQ), global regulatory filings and – ultimately – commercial production. All documentation was reviewed and approved online by Esperion. The intercompany team reviewed the project twice weekly, with technical meetings focusing on scale-up of both the intermediate as well as bempedoic acid API.
Managing Through an Operational Slowdown
In terms of manpower management, lockdowns and strict safety protocols meant that our staff strength was, by necessity, reduced to 50% of pre-pandemic levels. To account for these manpower constraints, we prioritized the team working on Esperion’s bempedoic acid.
Facility and equipment readiness during the lockdown also posed additional challenges. Systems which were idled for extended periods needed to be prepared and brought back online.
Managing Difficult Supply Chains
COVID caused a slow-moving (and still – to some degree – ongoing) supply chain challenge. As the pandemic progressed through early- and mid-2020, two supply chain complications became all-too-common: uncertainty and interruptions.
While unsurprisingly, supply chain logistics did cause challenges in import/export, shipping of reference standards, impurity standards and samples, they were generally minimized.
We had already taken steps to ensure alternative supplier readiness in the event of supply chain delays or disruptions. In this particular case, however, the client’s vendors were already qualified. This meant that the project could rapidly shift to validation and commercialization work.
Outcome: Project Success
Our team was tasked with implementing the process outlined during technology transfer. The process and specifications were therefore in-line with the expectations set by Esperion. Consistent and regular remote collaborative work with the various in-house teams at Esperion allowed us to complete technology transfer, process validation and approval of Neuland in the global regulatory filings on-time.
We’re proud to say that the story does not end there. After successful scale-up, commercial production of the bempedoic acid was shifted from Neuland’s R&D Centre to one of the manufacturing units in Hyderabad, India for continued commercial production of global supply.
In late 2022, Esperion announced that their Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial met its primary endpoint, demonstrating statistically significant risk reduction in MACE-4 in patients treated with 180 mg/day NEXLETOL® compared to placebo.
Neuland is honoured to play a critical role with Esperion, providing prescribers innovative options to reduce LDL-cholesterol and overall potential cardiovascular risk for patients.
We continue investing in agile development and manufacturing capabilities to quickly respond to our customer’s needs. With the experience of working with Esperion, we have been able to successfully place processes to manage projects effectively minimising the need for on-site or in-person interactions.
While the pandemic may be behind us, we are seeing an increasing need for a CDMO to be self-reliant and self-driven to execute API expansion projects. In that context, working with Esperion has been a highly enriching experience for Neuland.