After seven people died in 2013 from serious allergic reactions to Omontys, an injectable anemia drug marketed by Takeda Pharmaceutical (TYO:4502) and Affymax, the companies recalled the product and regulators launched an investigation to find out the cause of such an unexpected rate of anaphylaxis.
Omontys was made and cleared in a single-use vial and a multi-use vial, which sported different formulations. The companies used the single-use vial’s formulation in clinical trials but only marketed the multi-use vial.
Using an imaging system from Fluid Imaging Technologies, the FDA was able to evaluate the chemical composition of Omontys and discovered that the multi-use vial’s formulation had a significantly higher concentration of subvisible particles compared to the single-use vial.
Although the FDA didn’t establish a causal relationship between the particulates and the rate of anaphylaxis, Fluid Imaging Technologies CEO Kent Peterson told Drug Delivery Business News that the case study further highlights the importance of visualizing and characterizing a drug product’s composition early in the development process.
“Very early on, [drug companies are] looking at the interactions of molecules and the behavior of molecules, the stability of emulsions and formulations. So we inject ourselves at the very start of formulation development, all the way through QC or even post-QC,” he said.
The company’s system, called the FlowCam, takes thousands of pictures every second as a drug product flows through the instrument. The system then produces a report using image recognition software to classify the size, shape and identity of particles present in the sample.
“The image recognition software pulls out all the particle cells, air bubbles, fibers – anything – and then one by one analyzes each one, assigning it up to 40 different descriptive statistics,” Peterson explained.
Users can also train the software using a representative sample to form a reference library of different particles.
“There’s a number of technologies for counting or measuring particles,” he said. “Not only can we count, but we can use the pattern-matching algorithms to identify what kind of particles they are.”
That’s an essential component of the company’s technology, according to Peterson. It’s good to know if you have particles in your formulation, but it’s even better to know what kinds of unwanted materials are floating around.
“The FlowCam, using imaging identification, will provide data indicating that, ‘You may have too much silicon lining the tube of your syringe,’ or ‘Through mishandling of the product, you’ve created protein agglomerates out of the protein molecules.’ So it gives you guidance as to how to then back upstream to figure out what to do better or differently,” Peterson said.
The company’s latest product, the FlowCam Nano, hit the market last year. Using oil-immersion flow microscopy, the system produces high-resolution images of nanoparticles in liquid samples.
Fluid Imaging Technologies sells its instruments directly to formulation developers and regulators, but it is also engaged in collaborative efforts to determine new uses for its imaging tech. Peterson cited a relationship that it established with Mayo Clinic, studying the company’s fluid imaging instrument as a means to assess a cancer therapy’s efficacy in real-time.
“Over the past 18 years now, we’ve done everything from moondust to particles in fuel lines for SpaceX rockets to analyzing explosive powders to food ingredients, juice ingredients, pesticide analysis of pollen – it just goes on and on and on,” he touted. “We can’t replace all microscopes, but we could probably expedite 80% of the applications by one-thousandfold.”