Stacey Treichler- Director, Head of Marketing & Strategy, BioModalities, Catalent; Kaitlyn Vap- Life Sciences Lead Product Application Specialist, Sievers; Briana Nunez- Lead Researcher, Sievers Instruments’ Microbiology Center of Excellence; Hayden Skalski- Life Sciences Product Application Specialist for the Sievers Instruments product line at Veolia Water Technologies & Solutions
Over the last year, other than the pandemic, what do you feel has been the major industry issue with respect to biopharmaceutical product development and manufacture?
Stacey Treichler, Director, Head of Marketing & Strategy, BioModalities, Catalent: We are seeing continued growth in multi-specific antibodies, for example by-specific cs, tri-specifics, and T-cell engagers. Results from multi-specifics in the clinic look promising, but there can be unique challenges associated with their development and manufacture. Those challenges range from upstream development (e.g., optimizing the cell culture conditions for high titer) to downstream development (e.g., ensuring purification of products with the correct chain pairing), and analytical development (e.g., developing potency assays that properly measure activity). As more of these molecules advance through the clinic, the industry is working on solutions around cell line development, purification, process, and analytical development to improve manufacturing efficiencies.
Kaitlyn Vap, Life Sciences Lead Product Application Specialist, Sievers: The pandemic has contributed to many industry issues around supply chain, time-to-market, regulatory scrutiny, etc.; however, outside of the pandemic, the data-insight gap continues to develop as a major industry issue for biopharmaceutical product development and manufacturing. This issue has evolved as the volume of data being collected in product development, manufacturing, and clinical settings continues to grow exponentially, but the capabilities of leveraging that data to make decisions, predict, diagnose, and optimize do not match that level of growth. Companies continue to operate with manual and siloed processes, which ultimately leads to isolated data that does not provide insight into process performance characteristics. With tools like machine learning, predictive analytics, and artificial intelligence continuing to emerge, it will be pertinent for the biopharmaceutical industry to adopt software platforms that allow for the integration of these tools for the purpose of optimizing drug development, manufacturing, distribution, and clinical trial analysis. In doing so, the intent is to improve the time-to-market for life saving therapeutics without compromising patient safety or drug efficacy.
Looking at biosimilars - has their growth/approval rate met your expectations? If not, what has been holding them back?
Treichler: Various biosimilars continue to advance through the development pipeline in anticipation of innovators’ products coming off patent. The uptake in the market has been variable and depends on the indication, and the policies that regulatory bodies have put into place regarding interchangeability and substitutions. One key challenge to a biosimilar gaining approval is proving its biosimilarity to the reference product (the innovator product). Another challenge for companies advancing biosimilar products is that upon launch, they are likely to need to compete for market share not only with both the innovator’s product, but also with other biosimilars.
Vap: To date, 25 cell and gene therapies (CGT) have been approved by the FDA. Looking at the growth/approval rate in 2022, bluebird bio had two gene therapies approved – Zynteglo for treatment of patients with beta-thalassemia and Skysona for treatment of patients with cerebral adrenoleukodystrophy. Janssen also had a cell therapy approved in 2022 – Carvykti for treatment of patients with relapsed or refractory multiple myeloma. While three CGT approvals in 2022 is a small fraction of the 25 total CGTs approved, the industry is trending steadily and preparing to grow rapidly over the coming years. In the 2022 Prescription Drug User Fee Act (PDUFA) VII commitment letter, the FDA’s Center for Biologics Evaluation and Research (CBER) calls for additional resources to support the increasing volume of CGT programs in the Office of Therapeutic Products (OTP). In 2023 they plan to hire 132 additional resources and another 48 in 2024. This level of resource recruitment comes in light of bluebird bio’s two 2022 approved gene therapies and in preparation for an increasing amount in 2023, one of which may be Vertex and CRISPR Therapeutics’ ex vivo CRISPR/Cas9 gene-edited therapy, exagamglogene autotemcel, for the treatment of sickle cell disease and transfusion-dependent beta-thalassemia.
Supply chain issues have affected every industry. Specifically, how has this issue impacted the biopharmaceutical market?
Treichler: The supply chain issues caused by the pandemic and other factors have led to inconsistency in the ability to source key raw materials and consumables, for example purification resins. Long lead times and stock outs can impact the ability to schedule manufacturing slots, which can delay production. To mitigate this risk, many companies have secured secondary supply sources, extended their buying horizons, and increased their inventory of critical materials. Some have also developed improved business analytics to identify and track potential supply risks earlier, giving them more time to respond to potential issues.
Vap: While supply chain issues have influenced drug development and manufacturing timelines, there have also been other ways in which the biopharmaceutical industry has been affected. Novel techniques to reduce the need for more starting material have been more widely adopted. Examples include plasmid amplification and polymerase chain reaction (PCR) based mRNA manufacturing. The latter of the two replaces a pDNA linearization approach to mRNA manufacturing, requiring a significant amount of starting pDNA and a master cell bank. To juxtapose the more novel methods to emerge from supply chain constraints, there has also been a resurgence of more traditional techniques to avoid the need for customized solutions that supply chains are struggling to support. An example of this is the use of CHO rather than HEK293 or SF9 platforms for the production of gene therapies. CHO platforms have been proven as a robust manufacturing method for monoclonal antibodies and many single use system vendors have the necessary equipment, packaging, and configurations for a CHO production system. While single use vendors also support HEK293 and SF9 platforms, sometimes these require custom solutions that strain the supply chain.
Briana Nunez, Lead Researcher, Sievers Instruments’ Microbiology Center of Excellence: Supply chain issues have touched many facets of production in biopharmaceutical companies which impact the greater market. From validating alternates sources and vendors to increasing financial commitments to secure parts and materials, biopharmaceutical companies have been forced to become more dynamic. Customers in the biopharmaceutical markets have been forced to accept longer lead times which could potentially reduce the overall growth of their company.
Another issue that has been brought into focus by the pandemic is hiring and staffing. Has this been a problem for the biopharmaceutical industry? What can the industry do to alleviate this moving forward?
Treichler: Hiring and retaining staff has undoubtedly been a challenge in the biopharma industry these past few years. Biologic development and manufacturing requires workers to have a unique skill set, and it can be hard to find people who are already equipped with all the necessary skills for the job. Some of the ways that biopharma companies have tried to address this are by partnering with universities to train students in the skills they need when they graduate. It has been important too to develop robust internal training programs for new hires who may not have the full complement of skills they will need, and will, as with any fresh recruit, require training in a company’s own individual culture, procedures and practices.
Vap: The biopharmaceutical industry struggled with hiring and staffing for some time before the pandemic as sectors within the industry such as cell and gene therapy were just beginning to grow out of their infancy. With that being said, historically there has only been a small fraction of individuals with the technical expertise necessary to excel in these fields, making it difficult to both hire and retain these individuals. There are now graduate programs specific to biopharmaceutical career paths along with experienced/seasoned individuals leading the effort to bring new cell and gene therapies to the market. Academic institutions operate similar to businesses in the sense that market demand needs to be present in order to pursue a business project, or in this case a degree field; therefore, in order to institute bachelor’s degrees specific to a biopharmaceutical career path, younger populations need to be made aware of the biopharmaceutical industry and its function. In doing so, this has the potential to broaden the candidate pool for hires into the cell and gene therapy industry.
Hayden Skalski, Life Sciences Product Application Specialist for the Sievers Instruments product line at Veolia Water Technologies & Solutions: The biopharmaceutical industry has battled this issue since the onset of the pandemic, and it has not been resolved currently. High turnover rates made it extremely difficult for companies in this industry to retain talent, especially in growing fields like cell and gene therapy due to the rapid expansion of this sector and a growing number of opportunities. If companies are worried about retaining employees to get their products out to market on time, they can look for ways to automate processes in quality control and manufacturing departments. For example, there are numerous automated assays for critical release tests that require less training, thus alleviating some of the strain on staffing. As turnover rates continue to be a concern, companies seek to implement simpler, automated instruments where training for departments can be conducted in less than a day.
Looking ahead, where do you see the biopharmaceutical segment of the industry heading in the next five years?
Treichler: I believe we will see more complexity in the types of biologics that are being developed. Multi-specific antibodies, antibody-drug conjugates, and antibody fusions are just some examples of complex proteins that I believe will continue to take a larger share of the biologics pipeline. As these modalities become more complex, it will become increasingly important to continue to develop expertise, technologies, and processes that will enable efficient development, scale up, analytical capabilities, and manufacturing to bring these therapies to patients quickly.
Vap: The accessibility and affordability of biosimilars to the patient populations needs to be addressed. To confront this problem, biopharmaceutical development and manufacturing practices need to be more efficient to control the consistency and scalability of drug product. For this reason, the development and adoption of continuous manufacturing and integrated software platforms will likely be an industry focus over the next five years. Instruments, controllers, and data warehouses need to speak the same language to aggregate, analyze, and distribute data. Building in machine learning, artificial intelligence, and predictive analytic capabilities will be key to design agile operations with the ability to automatically diagnose failures and optimize processes. With these things in mind, it will be critical for vendors/suppliers to collaborate to enable technological advancement for the biopharmaceutical industry with the intent of driving efficiency gains.
Nunez: The biopharmaceutical industry will continue to drive progress in automation, not only for efficiency, but also for data integrity. Subjective testing versus objective testing does not require struggling with decisions. A shortage of laboratory personnel has also increased the interest in automation. The ability to manage many laboratories at once, while balancing the reduced number of analysts has created a need to lean out many repetitive tasks such as pipetting and counting plates to decrease worker burnout.
Skalski: As the industry looks for ways to reduce human intervention in many processes, it’s safe to say that biopharmaceutical companies will be heading toward innovative automation and pharma 4.0 concepts. Automated processes allow users to maintain a state of control in their laboratories or manufacturing suites. Most often, with automation comes an increase in data connectivity. In order to lean out processes and reduce the potential for human error, companies must assess the capabilities of their processes to analyze data and predict/diagnose errors before they happen. Adopting new automated technologies and implementing processes that reduce the user footprint will be crucial in how the ever-evolving biopharma industry adapts in the future.
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