The field of biologics is vast and growing, with tremendous potential to improve patients’ lives and public health. Novel biologics and biosimilars – or biologics highly similar to an existing biologic already approved – also hold great promise to help increase availability of quality biologic medicines for conditions ranging from diabetes to cancer. When compared to conventional medicine modalities, the complexity of developing and manufacturing large-molecule biologic drugs requires that we think differently about how to measure their quality attributes to help bring more quality-assured therapies to market faster.
Supporting biopharmaceutical innovation
While the principles that govern characterizing and defining quality attributes for small molecule drugs can be applied to large molecule medicines, the industry is witnessing a paradigm shift with relatively more complex biologics, including personalized medicines like cell and gene therapies, advanced monoclonal antibody (mAb) treatments, and messenger ribonucleic acid (mRNA) vaccines. When thinking about quality and how it is measured for biologics, traditional quality measures and compendial standards – such as those that focus on identity, strength and purity – are being reassessed in some cases to establish consistent and appropriate expectations for quality.
For biologics to reach their full potential, guidelines, best practices and standards are essential to help set expectations for quality, reduce potential risks, speed approval and support public trust. In turn, this will allow manufacturers and regulators to focus less of their time and resources on developing in-house methods and protocols to help reduce time-to-market.
Building a framework for biologics quality
To help expand the supply of quality biologic medicines, USP provides materials and quality standards manufacturers can use to develop, validate and monitor analytical methods. Since we know many biological modalities and associated manufacturing platforms face similar analytical challenges and use similar methodologies, USP’s approach to biologics standards development seeks to broaden their impact by defining a framework for quality that can be used across multiple biologics.
Many biologics leverage a common molecular scaffold (e,g. an antibody, mRNA, or cell) to which changes are made to target different diseases. Because the underlying scaffold is common across multiple medicines, the biotech industry often uses platform approaches for manufacturing and quality testing. To help biologics manufacturers ensure quality throughout the product lifecycle, we have adapted our work to focus on solutions to support platforms and technologies that apply to families and classes of products. For example, USP mAb Reference Standards can be used in method development and analysis of quality attributes for a range of mAb therapeutics.
The platform-based approach proved successful during the COVID-19 public health emergency when manufacturers had to accelerate the clinical development of complex biologics to meet emerging needs.
Shortening development timelines
In 2018, it took approximately 18 months to bring a new mAb drug from discovery stage to the first human clinical trials. By 2022, that time was nearly cut in half, at nine to 12 months, and even shorter development timelines are expected in the next few years. This advancement was achieved, in part, by platforming processes and analytical methods, and performing more systematic risk analysis and risk mitigation along the drug development and manufacturing process.
Another example is mRNA vaccines. In the past, scaling up the production of a new vaccine could take up to three years. During the COVID-19 pandemic, however, manufacturers were able to generate clinical batches of their mRNA vaccines within weeks of the publication of the SARS-CoV-2 genome. This is because the same process used to develop one mRNA vaccine can be used to produce vaccines against new variants or even new diseases with only a minimal number of changes to the processes and formulation. The modality is the same regardless of the disease target. This reduces the resources needed for creating in-house standards for quality control and helps accelerate the development of new therapeutics.
Knowledge sharing is critical for faster development timelines. During the pandemic, USP understood it needed to move quickly and leverage both traditional and non-traditional pathways to ensure stakeholders working on the production of COVID vaccines had the information they needed to uphold the quality of these new vaccines.
Compiling USP documentary standards relevant to vaccines into the USP Vaccine Quality Assessment Toolkit provided a foundational resource that was used around the world to help implement quality testing and train regulators and stakeholders on new analytical methods to ensure the quality of these new vaccine modalities.
USP’s publication of draft guidelines for mRNA and viral vectored vaccines was an innovative approach to getting early stakeholder feedback and alignment on quality attributes for new modalities. The response to these guidelines surpassed expectations and showed how important early engagement can be for new modalities. The stakeholder engagement also opened new avenues for collaboration and alignment that will help USP advance our work – from the development of physical reference standards and documentary standards to new opportunities to support regulators and public health with education, training, and other tools.
Through its engagement with its stakeholders, USP has enhanced its understanding of the challenges biologic drug developers and manufacturers face, and developed solutions that meet their needs. These needs can differ depending on factors such as which type of biologic drugs manufacturers produce, the clinical development stage of the biologic, and whether the drug is pre- or post-approval.
Engagement with industry, government, and academia across the globe is essential to ensure our standards are appropriately flexible, agile, and iterative so that they may continue to facilitate innovation and accelerate the development of high-quality, safe, and effective biologic drugs that improve the health and well-being of patients.
To learn more about USP’s approach to biologics standards development, click here.