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Addressing Development Challenges for Complex Biologic Drug Candidates

Addressing Development Challenges for Complex Biologic Drug Candidates

May 29, 2018PAP-Q2-18-CL-004

Biologic drugs are increasingly complex, creating numerous difficulties for biopharmaceutical companies from higher candidate failure rates to expression and manufacturing challenges. As a full-service contract development and manufacturing organization (CDMO), Lonza has the tools, techniques, capabilities and flexible capacity to help our customers overcome these hurdles and reduce the time for projects to move from development through commercial launch.

Selecting Candidates with Potential for Success

Biotherapeutics identified as potential drug candidates are increasingly complex. As drug makers focus on addressing unmet therapeutic needs, they are studying new and unexplored disease states and novel mechanisms of action. At the same time, payers and patients expect new drugs brought to market to be more effective and provide “clinical cost effectiveness.” This greater complexity and higher bar for approval make the development of manufacturable, safe and efficacious medicines more difficult, increasing the risk of candidate failure. 

It has become crucial for biopharma companies to reduce the risks associated with development projects by selecting biomolecules and their expression systems with the greatest likelihood of reaching the commercialization stage. Lonza has created Developability Assessment, a suite of services designed to help our customers gain a better understanding of which candidates have the greatest chances for clinical success and ease of manufacture. This service assesses structural stability, post-translational modifications and potential immunogenicity, among other factors. 

Most recently, we introduced a protein sequence variant analysis service. While some variants can be minor, others can impact efficacy and safety. Traditionally, studies to identify variants are performed during phase II/III trials, but finding the existence of a problematic variant at this stage presents real challenges. With our new service, protein sequence variant analysis can be performed at the preclinical stage, when the cell line is being selected, which enables early, proactive detection of variants. 

At Lonza, we are constantly looking to reduce the development timeline, giving our customers more control over their projects.

Many Hurdles in Biologic Drug Development

Drug companies are under growing pressure to reduce the time it takes to go from DNA to IND. Projects must be implemented as quickly as possible while minimizing risk and ensuring the development of safe and efficacious medicines. As projects progress through development to the clinic and on to commercialization, access to manufacturing capacity at the right scale when it is needed can also be a real challenge which increases supply chain complexity.

Expression and Manufacturing Solutions for Next-Gen Biologics

Next-generation biologics with the greatest potential include cancer immunotherapies such as checkpoint inhibitors and cancer vaccines. Next-generation biologics, for example, antibody-drug conjugates (ADCs), bispecific antibodies and novel scaffolds can offer improved efficacy and safety. All of these biomolecules are structurally complicated and typically operate via complex mechanisms of action. 

Facilitating Biologic Drug Development

Selection of an appropriate contract development and manufacturing organization (CDMO) can help alleviate the challenges of developing and manufacturing complex, next-generation biologic drugs. At Lonza, we are constantly looking to reduce the development timeline, giving our customers more control over their projects. We look for opportunities to introduce automation and find efficiencies by doing work in parallel or in nontraditional sequences. We have experience with many products with Breakthrough designation, including the commercial manufacture of ten products. 

We are also committed to having the right capacity available when it is needed. We are continually expanding capacity around the world to improve our flexibility. Recent examples include the acquisition of a facility near San Francisco, CA with 1000L and 2000L bioreactors and the expansion of our facility in Singapore with the addition of 2000L disposable bioreactors.

We have 35 years of experience developing biomolecules from early phase to commercialization. Our teams are able to anticipate potential problems and build in contingencies to avoid them. If problems arise, they are addressed rapidly to keep projects on track. Our regulatory team has broad experience; over the last five years we have supported 60+ IND filings and more than 10 marketing authorizations. We participate in regulatory agency meetings with customers and can help them implement the most effective regulatory strategies striving for right-first-time success.