Accelerating Drug Product Development for Rapid First-in-Man Studies in the Post COVID-19 Era

Oct 14, 2021

Guest Blog by Ahmed Besheer, Ph.D., Head Formulation Development, Lonza

The COVID-19 pandemic has had a severe impact on the global economy, and unfortunately cost millions of lives worldwide. Now, in the second half of 2021, with hundreds of millions vaccinated, economies are slowly recovering, and global leaders are carefully planning their countries’ future steps.

The pandemic – as tragic as it is – has shown how the pharma industry and regulatory bodies can react rapidly to address such a challenge in record timelines, with vaccines and antibody therapies receiving emergency authorization in less than 12 months from sequencing the viral genome. This has created expectations for biotech companies to apply similar approaches for faster drug development and accelerated chemistry, manufacturing, and control (CMC) timelines across the board. While development timelines for vaccines were condensed by very close cooperation between health authorities and sponsors, including finding methods to expedite toxicology and clinical studies, rolling submission, and emergency use application, there are also opportunities to fast-track programs following conventional submission pathways.

A Platform Approach for Monoclonal Antibodies

Options for accelerated drug development differ depending on the nature of the biologic. The industry has benefited greatly from years of experience with development and manufacturing of monoclonal antibodies, establishing a plethora of prior knowledge. Consequently, for these molecules, rapid in-silico screening, and occasionally forced degradation studies to establish molecular liabilities can enable selection of a winning candidate that matches platform formulation and manufacturing processes, as well as analytical methods. This platform approach saves time and costs (for example by using validated methods and proven processes) and allows the program to progress at full speed to clinic.

Rapid Tailored Development for Complex Proteins

More complex or designer proteins, such as fusion, or multi-valent proteins, may not fit a platform. This is because they usually have multiple domains that did not evolve naturally, have a low isoelectric point (pI), a low unfolding temperature, or high hydrophobicity, and would thus need a different approach. This involves rapid development of fit-for-purpose analytical methods which leverage an analytical toolbox, followed by high throughput identification of molecular liabilities and formulation design space, then finalizing the formulation after accelerated stability studies. In addition, a pilot drug product batch generates supportive stability data for establishing shelf-life and saves time with an Investigational New Drug (IND) filing.

It is important to note that with liquid formulations of complex proteins relatively short stability studies can create the risk of a short shelf-life. This can be mitigated by accepting a more limited liquid shelf-life and planning drug product resupplies, or by producing a more stable lyophilized or frozen-liquid format. For example, anti-COVID antibodies have reached the market as liquid formulations because they have benefitted from platform processes and prior knowledge, while mRNA vaccines have had to be developed as frozen liquid to alleviate stability risks.  

Communication is Key

Each of these drug development strategies has its advantages and disadvantages. An experienced drug product development team can tailor a program that matches these combined development requirements. This includes meeting milestones for pre-clinical toxicology and clinical studies and informing all stakeholders about potential risks and mitigation measures. For biotech companies working with contract development and manufacturing organizations (CDMOs), establishing a partnership, sharing knowledge and expectations of the target product profile, as well as discussing different development options and risk mitigation measures are key for rapidly delivering a safe and effective drug product to patients most in need.      

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Ahmed Besheer, Ph.D.
Head Formulation Development, Lonza

Ahmed Besheer has extensive experience in drug product development, with more than 10 years in the pharmaceutical industry. Before joining Lonza in 2018, Ahmed has been working at Novartis and Merck Serono in parenteral formulation development, as DP project lead and later as head of NBE formulation development. At Lonza, Ahmed leads a team that develops drug products of monoclonal antibodies, recombinant proteins, bioconjugates, and viral vectors. He has wide knowledge and expertise in the development of liquid and lyophilized early- and late-phase Drug Products for various administration routes.

Ahmed earned his pharmacy degree from Ain Shams University, Cairo (EG), holds a Ph.D. in pharmaceutical technology from the University of Halle (DE), and worked as an assistant professor at the University of Munich (DE).

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