Historically, during drug trials, the biopharmaceutical industry has used technologies that have been ill-suited for biologics characterization, an essential foundation for devising a proper therapeutic strategy. These legacy tools — which measure distribution of a particular drug or treatment — have required a lot of time and samples and can only be deployed in the latest stages of drug distribution, which is already too late if a pharmaceutical is ineffective or potentially harmful. But new platforms that utilize modalities such as membrane microscopy are shortening the time and sample volume requirements necessary for adequate testing.
Light obscuration — passing a stream of particles between a light source and detector — is a common protocol that was adapted from the aviation sector (which used it for fuel analysis) by the biopharmaceutical industry for differentiating particles in drugs. But due to its high volume requirement, observing particles in the early stages of development was not possible with light obscuration. In addition, biologics are nearly invisible in liquid when imaged because the biologics and the media that they are in have the same refractive index. And light obscuration does not enable individual particle identification, leaving drug developers either scratching their heads about where the particles came from, or inaccurately characterizing the drugs’ therapies.
Companies in the biopharmaceutical industry have sought to develop technologies that couple foundational principles of treatment with advanced imaging to help biologics developers commercialize stable and safe drugs for patients. For Halo Labs, these goals led to the creation of technology that utilizes fluorescence membrane microscopy and background imaging in a single platform. Further developments in the industry will be designed to fill the needs of emerging markets such as cell and gene therapeutics.
We hope the new wave of therapy developers learn from the mistakes of the past and partner with scientists and developers to ensure that safe drugs are put on the shelf.
The biopharmaceutical landscape itself is changing as the FDA takes a closer look at what constitutes a safe drug and what testing is necessary to assess whether a drug is safe for release to the general public. Initially, U.S. Pharmacopeia (USP) <788> Particulate Matter in Injections provided testing standards that used light obscuration or microscopy to assess for subvisible particles in drugs. These particles are dangerous to patients and are the most prominent cause for drug product recalls, but light obscuration often misses these particles completely.
A prime and unfortunate example of the dangers of missing the presence of particles is the dissolved company Affymax, which developed Omontys, a drug intended to treat anemia in people with chronic kidney disease. The initial testing of the drug’s safety and effectiveness was performed with light obscuration, which failed to accurately assess for subvisible particles. The drug was later taken off the market.
Over time, the FDA recognized the shortcomings of its standards and revised USP <1788> to allow for newer methods, such as automated membrane microscopy, to provide better detection, and to provide guidance for the protocols established under USP <788>, specifically targeting particles in the 2- to 10-µm range.
In membrane microscopy, particles are filtered through a membrane. The method was developed specifically for biologics and the life sciences space. Each membrane is unique and designed for biologics, formulations, and harsh chemicals. High-powered optics, intricate lighting methods, and image capture techniques — for example, side illumination and background membrane imaging — are used, along with complex algorithms to detect, count, identify, and characterize particles from 1 µm to 5 mm. One of the biggest advancements of membrane microscopy is complete automation — from the filtration process to image capture and analysis. This provides objective analysis of drugs, removing user-biased assessments and errors in particle count and identification.
As the adoption of modern biologics characterization increases in the marketplace and as the FDA adjusts its protocols for particle analysis to help ensure drug safety, biopharma companies and regulators are heading in the right direction to ensure not only patient safety, but company security and prosperity. Cell and gene therapy clinical trials are sprouting everywhere, but, as a market, these therapies are in the infancy stage as compared to the biologics market. And we hope the new wave of therapy developers learn from the mistakes of the past and partner with scientists and developers who can help provide them with the right tools to ensure that safe drugs are put on the shelf.
Meet the author
Steven Le is director of marketing for Halo Labs. He has spent his entire career in the life sciences, pursuing endeavors to ultimately improve the environment and human health. He has a Bachelor of Science in biochemistry and molecular and cellular biology, a Master of Science in systems engineering, and a Master of Business Administration; email: [email protected].
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We hope the new wave of therapy developers learn from the mistakes of the past and partner with scientists and developers to ensure that safe drugs are put on the shelf.