Particle Analysis for the QbD Era

ASPEX Corp. draws from its experience in other industries to provide an automated characterization solution for pharma.

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The current climate of risk management and Quality by Design has pharmaceutical R&D and manufacturing professionals searching for fast, automated analysis of microparticles for raw materials, drug powders, or parenterals. ASPEX Corp. (Delmont, Penn.), in conjunction with a major pharma company, has developed an automated means of in-process particle characterization that aims to speed and simplify materials analysis for drug manufacturers.

Part scanning electron microscope, part energy dispersive spectrometer, the ASPEX Rx has a variety of applications beyond basic quality control, and also has dedicated software and compliance features.

Pharmaceutical Manufacturing spoke with applications specialist Dr. Marie Vicens and field sales director Tom Powers about current trends and their high-throughput electron beam analysis technology. Vicens also garnered attention with her presentation at the recent Rocky Mountain Conference on Analytical Chemistry, which takes a broader look at the technology behind the Rx. To view the presentation, click here.

PhM: I'd like to ask you about the current climate and what you're seeing in the industry. Are you seeing additional caution regarding particle analysis on the part of your clients?

Marie: Well, everybody is always concerned about foreign particle material.  People that have worked with us in the past have contacted us because they're looking for product quality. And many times, not only are they looking at their bulk materials, but sometimes they have to send products out for different purposes like milling, and they want to make sure that it comes back with the same quality it had the first time.

PhM: Could you paint a picture of what the landscape is for particle analysis technologies out there and how your ASPEX Rx technology fits into that?

Tom: Conventionally, there is just particle size information, which is a one-dimensional analysis. And then size and shape is an indication of multiple dimensions, so we then classify morphological differences, like when they might mill a powder: Is it more needle-like in formation than spherical?  There are laser-diffraction techniques that are conventionally employed.  Our reproducibility is superior to that sort of technology. And then we give the advantage of providing the elemental composition of each individual particle in a very rapid manner.

The USP standard, <788>, is purely particle-size-driven and that's what every one of our customers is using. But even though the landscape is size and shape, we’re also imaging each individual particle, so you get the perceived third dimension of the particle, as well as the elemental composition.

PhM: Tell us exactly what the analysis is, how it's done, and how you're able to get all those dimensions.

Tom: We have a sieving type of a process where we dynamically scan a beam across the surface. We employ a contrast mechanism where we can look at inorganic particulate on carbonaceous background, or organic particulate on a metallic background. And that's the kind of contrast mechanism that we employ. 

The competition is a very old and time-proven technique of image processing, but it's very slow.

PhM: The Rx technology is a combination of scanning electron microscope (SEM) and energy dispersive spectrometer (EDS). . . .

Marie: . . . to get the images and chemical composition.

PhM: How does this compare to what else is out there?

Tom: We're unique in the fact that we're a single-source vendor. This technology is old—we’ll say forty years old for the SEM side. As soon as we developed the SEM, the elemental analysis followed rapidly. But there typically might be two vendors out there that would do what we do as a single vendor, and then, even a third vendor that would provide a software solution; and even a fourth vendor that would provide validation services. 

We provide all these things, including IQ, OQ, and PQ, as part of a single-source solution. Clients come to us wondering what are the black flakes in the powder and we'll get them an A to Z solution.

PhM: Could give me a general picture of what your clients are asking you to do?

Marie: One of the common applications that we’ve had is companies trying to follow the guidelines of USP <788>. Before they can actually submit any data to the FDA, they need to make sure that their materials and any foreign particles are quantified and meet the criteria.

Another thing we do is look at product quality and at any other particulate contaminants that may have been mixed with the drug powder, like stainless particulates or Teflon particles. So there are two different types of client: first, the manufacturer of the product, and second, those who buy a product from a third-party vendor and want to make sure that it's clean enough, in terms of its particulate content.

PhM: How much are the FDA initiatives for PAT and Quality by Design affecting your business and driving what you do?

Marie: Right now, Quality by Design is driving our efforts. Whenever we speak, we’re highlighting the advantage of using this technology within the Quality by Design process. If a company manufactures a product and has any kind of contamination or particulate materials, they know they’ve tested it beforehand. They know what they have in their products, and then can move forward.

PhM: And have your clients been receptive to that line of thinking?

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