An LNP Innovator’s Journey – From Concept Through Commercialization

In the field of targeted drug delivery, nanoparticles offer many advantages — such as improved solubility, enhanced drug stability, and reduced toxicity. However, lipid nanoparticles (LNPs) have highly precise processing requirements and can be challenging to manufacture. Specifically, microfluidics-enabled batch processing, the conventional LNP manufacturing method, presents scaling difficulties, as well as high batch-to-batch variability that impacts the critical quality attributes of the final products.

Our customers come to us because they recognize that using a continuous manufacturing process incorporating DIANT^®’s jet mixing technology optimizes LNP formulation and manufacturing. This results in more uniformly sized nanoparticles that better encapsulate the active pharmaceutical ingredient (API), creating safer, more effective LNP drug products.

When pharma innovators first come to DIANT, they typically have an LNP product that has proven difficult to transition from microfluidic batch processes to GMP manufacturing for clinical production. Some customers also wish to find a much more efficient manufacturing alternative. Other scenarios involve having poor LNP encapsulation efficiency (which wastes expensive API), slow production due to subpar flow rates, or expensive dilation processes.

By the time they come to DIANT, most of our customers have already performed some in silico discovery using computer models or high-throughput screening testing on lipid structure and buffer selection.

DIANT takes it from there, evaluating the charge and the solubility of the customer’s payload to refine the initial lipid selection. It typically takes eight to ten runs on the DIANT^® LARU, a benchtop unit, to provide a formulation starting point. DIANT then proceeds with downstream processing on select formulations and analyzes the nanoparticle characteristics. This analysis includes size measurements, percent encapsulation and composition, and some studies on short-term and long-term stability under selected storage conditions and medium.

Once nanoparticle stability, suitable size range, and percent encapsulation have been locked in to create a baseline, DIANT creates a service contract for developing the process to meet the requirements of the client, such as bringing the nanoparticle formulation to commercial scales following cGMP. This process entails:

• Sourcing all materials
• Necessary equipment modifications
• Sensor modifications and integration
• Filtration approach customization
• PEGylation or other internal/external modification considerations
• Documentation and Support (e.g., IQ/OQ/PQ, material certs, user manuals)

 
We then transfer this process, together with the modified DIANT equipment, directly to the innovators or their chosen CDMOs. DIANT also offers direct training on formulations and system operation.

As the industry becomes increasingly familiar with DIANT’s technology, the DIANT LARU (benchtop unit) and the DIANT LiFT (GMP-ready, high-throughput unit) are being embraced by the CDMO community. Customers especially like our systems’ ability to process multiple products on the same equipment—a value proposition attractive to CDMOs producing various products for numerous clients. For example, a system set up for LNP production can be easily and rapidly converted to produce liposomes.

DIANT’s high-throughput production, payload delivery versatility, and ability to produce large amounts of drug product within a small footprint have led to a growing interest beyond Pharma.

DIANT’s core business is offering customizable solutions for our clients’ nanoparticle campaigns by acting as a contract research and development organization and also offering manufacturing equipment. DIANT routinely assists customers in the early stages of their therapeutic development process by determining which drug delivery mechanism would provide optimal yields.

Additionally, we’re helping some clients consider ways of delivering off-patent payloads using a nanoparticle delivery mechanism because reconsidering the delivery mechanism may help enhance the drug’s efficacy and present new patent protection opportunities.

As the pharmaceutical landscape continues to evolve, DIANT is committed to driving innovation and empowering our partners to realize the full potential of LNP-based drug delivery. DIANT is poised to help innovators with their entire LNP formulation journey—from initial concept to final commercialization. We provide close collaboration during contract development and manufacturing projects and training on our continuous nanoparticle manufacturing equipment.

The future is very bright for nanoparticle therapeutics, and we look forward to helping the industry advance by providing turnkey solutions using DIANT^® technology.