In today’s rapidly evolving biopharmaceutical landscape, the production of RNA-LNP (Lipid nanoparticle) formulations has gained immense prominence as a revolutionary technology. The rapid development of mRNA vaccines by Moderna and BioNTech/Pfizer during the COVID-19 pandemic significantly increased academic and industrial interests.

As the demand for these innovative therapies continues to surge. Companies are increasingly exploring the strategic advantage of outsourcing RNA-LNP production which holds the promise of streamlining the manufacturing process, significantly reducing operational complexities, and enhancing cost-efficiency. In RNA-LNP production, the LNPs encapsulate RNA, protect it from degradation, facilitate cellular entry, and release the RNA payload into the cytoplasm for ribosomal protein synthesis.  A lack of expertise, operational infrastructure, and the inability to produce consistent quality RNA-LNP drug products can lead to unsuccessful projects and commercial losses. Specialized and experienced outsourcing partners with dedicated expertise in the intricate production of these complex nanoparticles can offer a level of precision and scalability that is challenging to achieve in-house. This approach enables companies to channel their resources towards, innovation and ground-breaking research. The decision to outsource RNA-LNP production represents a strategic move that can position biopharmaceutical companies at the forefront of innovation and competitiveness.

Manufacturing the RNA-containing LNPs is a complex process and requires specialized proficiency and experience. Its time-consuming, multi-faceted nature requires substantial investments and the dedication of extensive resources. In addition, there are many challenges and inherent risks that can lead to hurdles in the manufacturing process. Some of the challenges are listed below:

RNA–LNP Drug Manufacturing Challenges

1. Drug Product Quality – Inadequate capability to produce the required quality of RNA-LNP drug product to meet regulatory milestones.
2. Drug substance and lipid Quality -High-grade drug substances (RNA) and lipids are crucial to ensure drug quality, therapeutic effects, storage conditions, and safety profiles.
3. Infrastructure – Lack of facilities with appropriate cleanrooms and cGMP space.
4. Scalability – Lack of cGMP expertise, instrumentation, scalable clinical lipids, and analytical and bioassay expertise can be a barrier to scaling RNA-LNP production. 
5. Cost – Manufacturing costs increase the financial pressure to invest in CAPEX equipment due to time-consuming and labor-intensive late-stage production.
6. Time – The development time from bench to clinic impacts patient outcomes and the financial return that will fund future research.
7. Regulatory Obligations – As the field evolves, deep knowledge of regulatory guidelines is required to understand the documentation and clinical/regulatory processes. 

Outsourcing RNA–LNP drug manufacturingaccelerates drug development by providing biopharma companies access to high-quality, value-added services. According to InsightAce Analytic, the Lipid Nanoparticles (LNPs) CDMO Market will grow at a CAGR of 13.8% between 2022 and 2030. End-to-end solution providers who have been leaders in the LNP space for over a decade are addressing the common process pain points and offering winning value propositions at a faster timeline to help clients meet data and quality milestones.

Advantages of Outsourcing RNA-LNP Formulations

Best Practice

Drug development is a complex process, and it is crucial to achieving a high-quality drug product for human safety. When looking for a service provider, identify, assess, and audit core competencies to reduce burn rate and project timelines by investing in a partner that delivers scientific expertise and advanced cGMP technologies. Access to an experienced and efficient service provider can avoid unpredictable delays that cost time and money.

Gap Analysis – While developing a drug targeted to treat disease is fundamental, having too many initiatives and broad strategies could impede the project if the risks involved are not mapped and prioritized correctly. Target product profile (TPP) is a rational and practical consideration in the drug formulation development process that helps identify a product's critical attributes before development and serves as a planning tool to facilitate discussions with regulatory agencies. However, efficient screening while protecting precious research samples can be tricky as scientists define an optimal TPP. A service provider can help develop the TPP, gather requirements, identify gaps, develop the process, and establish a detailed action plan with due diligence to de-risk and accelerate the RNA drug to the clinic. Some service providers also offer nanomedicine education and training as a bundled package, such as NanoMedU courses that provide hands-on learning for scientists in the industry to help advance nanomedicine development to build in-house knowledge.

Effective Formulation – At the discovery stage, high throughput screening of nanoparticle formulations for optimal payloads can maximize the probability of developing a high-performing formulation. However, since the raw materials, such as genetic payload, are costly to manufacture, biopharma companies can sometimes select the first lead formulation without optimization to save time but end up paying the price later when optimization is required and delays the project timeline. Therefore, an ideal biopharma service provider should have the deep technology expertise to help select the right lipid delivery compositions for effective lead formulation selection to improve safety, efficacy, stability, and process scalability. 

Comprehensive Analytical Testing and Bioassays – For a successful drug product, advanced analytical methodologies must support the characterization of the drug substance, raw materials, and nanoparticle formulation across the preclinical, clinical, process development, manufacturing, and quality teams. It is critical to ensure that the drug product's critical attributes remain consistent and within acceptable ranges during process development and scale-up. Outsourcing analytics help you access instrumentation, technologies, and analytical capabilities to perform In vitro potency assays, including lipid and nucleic acid-specific analytics to generate accurate data insights for proof of concept (POC), preclinical or clinical milestones, for accelerated clinical trials. Expert analytical teams help identify impurities that may be overlooked and can educate clients on raw material quality, such as selecting high-quality application-specific lipids appropriate to their process. Expertise in downstream processing and in-house bioassay saves time and accelerates the project.

Regulatory Support - The regulatory process for RNA-LNP drug products is still developing. Although the COVID-19 vaccine was approved in less than a year, regulatory agencies made accelerated approval decisions, with limited datasets, to serve patients quickly during a global pandemic. The regulatory guidelines continue to evolve for this new class of medicines. A strong understanding of Chemistry, Manufacturing, and Controls (CMC) information is needed to properly document manufacturing processes to be safe, reproducible, and robust. This requires deep knowledge of cGMP manufacturing, developing critical production protocols, and deep expertise at every step. The risks, including patient safety and costs of non-compliance, are high and impact the commercial approval of the drug product. Accessing regulatory savvy service partners with deep biopharma industry knowledge and experience in regulatory risk management and compliance is helpful to ensure success.

Expanded Portfolio of Services - Outsourcing provides access to facilities with an end-to-end suite of solutions offering bundled services. Technical support is provided across various stages of the drug development process, from formulation development, analytics, testing, and quality assurance to GMP and clinical manufacturing. It presents the opportunity to access a broader portfolio of support services while keeping a check on expenses and meeting timelines. Recently, Replicate Bioscience signed a licensing deal with Precision NanoSystems to access its end-to-end lipid nanoparticle solutions for scale-up and manufacture of up to 15 self-replicating RNA (srRNA) therapeutics to enable, de-risk, and accelerate their drug development program. As a result, the company is moving quickly and efficiently through the drug development process, and it frees up internal resources giving an opportunity to focus on other programs. Outsourcing also helps them quickly accelerate their portfolio of srRNA therapeutics from lead candidates to the clinic and these are slated to enter human trials next year. 

Cost Savings - Drug development requires high capital investment. For emerging biotech companies, the cost of buying instruments, hiring expertise, and managing cleanrooms can lead to regulatory and financial pressure. At the same time, there is the constant potential risk of failed experiments and not meeting milestones. Outsourcing can reduce this initial pressure and avoid the need to invest in facility infrastructure by sharing the operational responsibilities with a contract services team that can provide a greater probability of success and lower the business risk until such time that the therapeutic has gained clinical success, and the company has more investors.

Operation Management and Global Presence - A drug development company must deal with the many challenging stumbling blocks, including managing the process; procuring costly raw materials; conducting analytical tests, and tech transfer. These processes require comprehensive planning and project management, including logistics, which can be overwhelming for many companies doing this for the first time. Service providers act as a backbone, providing an integrated approach to managing the drug development process while also providing other advantages, such as expanding a company’s reach into new geographies.

Return on Investment - Limited resources and associated drug development costs can slow the product development pipeline. However, outsourcing provides access to advanced technology and expertise that can help eliminate bottlenecks, accelerating the drug development time that can significantly benefit a company's financial outcome. 

Potential Strategic Partnership - It can be incredibly challenging and cumbersome to outsource drug development; however, if the outsourcing partner offers the flexibility, collaboration, and innovation you are looking for, it can become a potential business partnership. This might help expand the resources and reduce the overall risk associated with the project. There is also knowledge sharing during the partnership that enables your in-house team to learn and be more successful with the expertise gained from external collaborations that can be applied to future projects.

Thus, outsourcing to a service provider with an end-to-end suite of solutions and services helps companies reduce resources, infrastructure costs, and other operating expenses to maximize their ROI (return on investment). 

About Precision NanoSystems

Precision NanoSystems is a Danaher company. Together with our partners Pall and Cytiva, we offer an end-to-end manufacturing workflow for clinical and commercial nanomedicine production. Our versatile solution for commercial manufacturing provides the ability to scale up and scale out a range of facilities. We are committed to a flexible, individualized approach with a global team of field application scientists for your support. Partner with Precision NanoSystems' BioPharma Services team and get started with a well-defined project plan, milestones, deliverables, and timeline customized to your needs. 

Learn more about Precision NanoSystems’ BioPharma Services