CordenPharma Expands Into GMP Lipid NanoParticle Formulation in Caponago

Edition 1 / February 2023

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Author
Umberto Romeo,
R&D Manager
CordenPharma Caponago

CordenPharma Expands Into GMP Lipid NanoParticle Formulation

CordenPharma Lipid NanoParticle with its payload.

Lipid NanoParticles (LNPs) have emerged as promising non-viral nanocarriers to deliver a variety of therapeutics. Specifically, they are considered ideal delivery systems for DNA, mRNA and synthetic RNAs (siRNA, microRNA, saRNA) due to their outstanding biocompatibility, biodegradability, and entrapment efficiency. Currently in the spotlight as core components of the COVID-19 mRNA vaccines, LNPs play a key role in the development of novel xRNA therapeutics under preclinical and clinical investigation as the main delivery platform of choice.

CordenPharma played an important role during the Covid-19 pandemic response, ramping up its lipid manufacturing capacity across multiple sites to support the global demand of GMP grade lipids needed for the manufacture of Moderna’s Spikevax™ vaccine.

Acknowledging the importance of LNPs as a key delivery platform for the therapeutics of the future, CordenPharma initiated in late 2020 a strategic investment program at our Sterile Injectable site CordenPharma Caponago (Italy) to establish LNP formulation development and manufacturing capabilities, supported by dedicated in-house analytical characterization and QC capacity. Today the investment fully integrates with existing Fill & Finish clinical and commercial operations capabilities, and with CordenPharma’s broad Lipid Excipients offering, including custom synthesis services, supported across our global facility network.

In Q2 2022, the CordenPharma R&D organization started supporting customers with the development of LNPs, Liposomes and Lipoplexes-based formulations using the most advanced technologies, along with highly qualified scientists, in our state of the art R&D laboratory. As a result, several compounds have been pushed through CMC development key milestones, reaching clinical manufacture readiness.

To support the clinical and potential commercial demand of LNP-based therapeutics that would logically follow these R&D milestones, CordenPharma additionally started building in Q3 2022 a new GMP LNP manufacturing suite through the expansion of an existing GMP area. The new facility is strategically placed adjacent to the clinical-scale Fill & Finish facility to streamline end-to-end manufacturing operations from cargo molecule encapsulation to Fill & Finish in the final primary packaging container.

The GMP LNP suite will be fully operational beginning Q3 2023, and will be equipped with the very same technologies available in the R&D area for process development purposes, to enable a smooth geometrical scaling to the relevant GMP scale.

The new suite will include 16 Class C (ISO 7) rooms designed to host processes from clinical scale (early to late-stage) up to rapidly-scalable large quantities if needed.

The facility includes the following features:

• >> Dedicated Warehouse
• >> Raw materials dispensing room
• >> One ATEX Class C room for the compounding of the organic phase containing lipids, equipped with 4 Stainless Steel (SS) vessels up to 30 L of capacity utilizing CIP/SIP technology.
• >> One Buffer preparation room
• >> Single-use compounding systems, temperature controlled (5-25 °C) for the preparation of the aqueous phase (containing the cargo) and process buffers

In terms of the main GMP LNP processing equipment, the following systems have been ordered:

• >> Knauer Core Duo^® Impingement jet mixing system for LNP encapsulation:
  The Impingement Jets Mixing (IJM) Core Duo Unit is designed for high flow production of NanoParticles (LNP, microemulsions, etc.) and is equipped with two parallel mixing units. Each unit consists of four pumps enabling all steps from predilution of the aqueous phase containing the cargo and NanoParticle assembly, through to Impingement Jets Mixing, and in-line dilution of the NanoParticle solution. Furthermore, each unit is equipped with four flowmeters for flow monitoring, one jets mixer, and two mixers for predilution and in-line dilution.
• >> PNI NanoAssemblr^® GMP Nextgen Microfluidic system for LNP encapsulation:
  This system is built upon the innovative NxGen™ microfluidic technology, that enables scalability from bench to clinical scale. NanoParticle assembly occurs under non-turbulent conditions across the microfluidic cartridges that are the core of the technology.
• >> Repligen KTM1600^® Tangential Flow Filtration system (TFF) unit that enables UltraFiltration (UF) and DiaFiltration (DF) processing large and small-scale batches, equipped with fully disposable flow-paths and disposable recirculation vessel temperature control (5-25 °C).

The GMP LNP suite is designed and equipped to support the manufacture of a wide range of batch sizes, and can be easily upgraded to ramp up LNP production to very large scale.