12.03.

2023, 20:11 How Outsourcing RNA-LNP Production Can Have A Competitive Advantage

Article | February 23, 2023

How Outsourcing RNA-LNP Production Can Have A Competitive Advantage

Source: Precision NanoSystems

Lipid nanoparticles (LNPs) are used in nanomedicines, vaccines, nutritional

supplements, and diagnostics by different routes of administration, including
oral, topical, pulmonary, and IV/IM injection. The rapid development of mRNA
vaccines by Moderna and BioNTech/Pfizer for COVID brought the limelight to
RNA-LNP therapeutics, thereby increasing academic and industrial interest in
RNA-LNP formulations. As a result, several large pharmaceutical companies and
emerging biotechs are using lipid nanoparticles for nucleic acid drug
development, which is expected to capture tremendous market growth in the
future. In RNA-LNP therapeutics, the RNA is encapsulated in LNPs that protect
it from degradation, allowing it to enter cells, then release the contents into the
cytoplasm so ribosomes can use the RNA to synthesize the desired protein.
However, a lack of expertise, low operational infrastructure, and the inability to produce consistent quality RNA-LNP drug products can
lead to failed projects and financial losses.

Manufacturing the RNA-containing LNPs is a complex process and demands specialized expertise and experience. Developing a drug is
time-consuming, complex, and multi-faceted, requiring enormous investment and extensive resources. In addition, it has many
associated risks before achieving success. 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 substance (RNA) and lipids are crucial to ensure drug quality, therapeutic
effects, storage conditions, and safety profiles.
3. Scalability – Lack of cGMP expertise, instrumentation, scalable clinical lipids, and analytical and bioassay expertise can be a
barrier to scaling RNA-LNP production.
4. Time – The development time from bench to clinic impacts patient outcomes and the financial return that will fund future
research.
5. Cost – Manufacturing costs increase the financial pressure to invest in CAPEX equipment due to time-consuming and labor-
intensive late-stage production.
6. Infrastructure – Lack of facilities with appropriate cleanrooms and cGMP space.
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 manufacturing accelerates 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.

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12.03.2023, 20:11 How Outsourcing RNA-LNP Production Can Have A Competitive Advantage

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 strategy 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 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 biopharmaceutical industry knowledge and experience in
regulatory risk management and compliance is helpful to ensure success.
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12.03.2023, 20:11 How Outsourcing RNA-LNP Production Can Have A Competitive Advantage

Expanded Portfolio of Services - Outsourcing provides access to facilities that have an end-to-end suite of solutions and offer
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 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 who 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

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