Cell and gene therapies (C>s) are swiftly developing within the biopharmaceutical sector. The expanding C> space is exerting substantial influence on the trajectory of healthcare and the management of genetic disorders. C>s provide a long-awaited solution for patients affected by rare diseases, creating a lasting impact by moving away from the treatment of symptoms to providing life-changing cures. However, despite recent advancements, numerous obstacles need attention to help establish C>s as a feasible and extensively adopted therapeutic choice.
In this article, Dr. Samir Acharya, Dr. Rajiv Vaidya and Cyrill Kellerhals from Andelyn Biosciences discuss the trends in the field of C> and explore the current and future challenges facing C> developers and manufacturers as well as solutions to overcome these challenges.
Recent Developments in the C> Space
Advances in gene-altering techniques have been key drivers in transforming C> research. As integral tools in C>s, viral victors are adept at transporting genetic modifications into cells. Confirming their importance, the global viral vector market is expected to grow from $0.69 billion in 2021 to $1.38 billion in 2026.
Progress in the C> field relies on enhancing treatment safety and efficacy of viral vector therapies. Future breakthroughs are likely to happen in process development, technology and quality standards, ensuring that viable and potent therapeutics are being produced to drive healthcare innovation.
C> Development Challenges
The biopharma sector’s increasing demand for high-quality viral vectors such as adeno-associated viruses (AAVs) brings about a series of intricate challenges in the development of C>s. As they play a pivotal role in delivering therapeutic genes into target cells, ensuring viral vector quality and consistency is critical for the success and safety of these advanced therapies. To meet the rising demand for viral vectors, it’s important to find solutions to the main challenges in C> development, including:
Regulatory Compliance
Viral vectors should adhere to rigorous standards of quality, yield and potency to be safe for patient use. The C> space is relatively new and advances have been rapid. This has meant regulations and guidelines must change with new understanding, and developers must be flexible to keep up with these. Regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) establish strict guidelines to ensure the safety of the novel viral vector therapies. Adhering to these guidelines is essential to prevent potential risks to patients and minimise adverse events associated with viral-vector-based C>s. Ensuring quality throughout the process development phase is paramount to maintaining these standards.
Keeping up with Advancements in Platform Processes and Purification Methods
During the production of C>s, it is essential to keep up to date with advancements in processes to support viral vectors with novel serotypes and delivery vehicles like lipid nanoparticles. Technological progression in the AAV field can impact viral attributes such as potency and tropism by enhancing transgene expression efficiency, tissue targeting and immune evasion for more effective and targeted gene therapy treatments. As more advanced measures of these attributes become available, it is essential to have flexibility ing process development to ensure effective production and purification for final product quality and stability.
Testing for Viral Vector Quality
At both small and large scales, there are challenges with testing for viral vector quality. This can be due to the complexity of viral vectors, which can make establishing testing methods difficult, and also variability in viral production. Common quality control (QC) issues occur when scaling up or down. Maintaining quality at both ends of the scale is essential to meet regulatory requirements.
Targeting Therapeutic Delivery to the Right Location
One of the major challenges facing C> developers is targeting therapeutic delivery to the right location in the body while ensuring the immune response is minimal to avoid adverse reactions. Achieving high specificity and selectivity is difficult as many cells and tissues share similar surface markers and there are biological barriers to consider within the body that can restrict the entry of molecules.
Overcoming Development Challenges
A lack of effective treatments for rare diseases has driven many of the advancements in C> technologies. One such advancement is the development of novel serotypes and delivery vehicles like lipid nanoparticles (LNPs) that has allowed for tissue-specific and targeted delivery of C>s, reducing the risk of adverse immune response reactions and targeting the correct area in the body.
Successfully navigating development challenges accelerates the translation of scientific breakthroughs into clinical applications and improves the global healthcare space. To overcome these challenges, it is crucial to consider the following strategies that could ensure the successful development of C>s:
- Integrating quality-by-design (QbD)
This concept tailors product attributes to meet customer demands and ensures dependable manufacturing processes are created. Robust QbD processes accelerate timelines to market and trim costs, offering a cohesive approach to rapid operations and budget efficiency. They can also help with addressing rapidly changing regulatory requirements, ensuring the product is safe for patient use.
- Applying expert knowledge and adopting innovative technologies
To meet rising demand and deliver critical therapies to patients worldwide, process development must aim to deliver cost-effective and timely C> production. Drug developers should apply expert knowledge to techniques and technologies aimed at achieving this while considering implementing innovative technologies such as viral vectors, artificial intelligence (AI) and gene editing. Additional factors include having a manufacturing team that works closely with the analytical process development team to help streamline process timelines through effective collaboration and coordination between departments.
- Implementing innovative technologies
Process developers should consistently explore novel technologies and generate new assets for efficient production, purification and quality evaluation of C>s. This includes utilising diverse technologies and techniques to assess product attributes during the process, such as adopting rapid production platforms, employing combinational chemistry, embracing light or mass spectrometry for quality assessments and incorporating innovative chromatography methods for seamless purification of high-quality products.
- Keeping up to date with advances in the space
With 3,649 C>s in the pipeline, there is a strong need for developers to keep up with the most recent innovations as well as for manufacturing support and state-of-the-art facilities and equipment.
The development of a C> involves examining regulatory compliance, working alongside regulatory agencies, as well as developing the best possible clinical trial design and meeting numerous analytical requirements. Implementation of innovative strategies into C> development and manufacture will help to effectively meet increasing demand in the space. In addition, it will allow for timely adjustment to industry structure in response to new technologies or advancements.
Aligning with an Industry Expert in the C> Space
There is a large amount of pressure on C> companies to make the most of investment resources and bring high-quality products to market quickly to avoid costly delays in development and manufacturing. Achieving this requires expertise in adherent and suspension cell culture. Being proficient in both areas allows for flexibility to accommodate different C> products and industry demands. The processes involved in C> production can be challenging, and partnering with external innovators can help to ease the burden and facilitate successful product delivery.
In addition, the focus in the C> field is moving toward generating stable cell lines to achieve consistent viral vector quality, scalability, cost-effectiveness and time efficiency. Aligning with an expert in C> ensures these challenges can be overcome and strategies implemented to allow companies to thrive in the competitive C> industry, producing potentially life-saving treatments for patients worldwide.