Why powder testing is a powerful tool for healthcare

In this thought leadership piece, Todd Mollner, global product owner, Respiratory Powders, GSK, tells use about the importance of powder testing in pharmaceutical manufacturing. 

Can you tell us about your background and current role?

I’m an engineer with over a decade of experience working at the forefront of healthcare manufacturing. My role in GSK is to ensure that the Over-The-Counter (OTC) respiratory health products that we produce in powder dosage form meet the highest standards of quality and robustness and I provide leadership and guidance on all technical aspects of this portfolio. I have a long-standing interest in Process Analytical Technology and the application of analytical instrumentation to enhance manufacturing practice.

Why do you think powder testing is so important in the manufacture of healthcare products?

One of the challenges we face is establishing the supply chain needed to safeguard product consistency within a global marketplace that can change rapidly. Drug shortages in the US have been widely reported and are a major concern. The best defence is to have multiple- suppliers that make active ingredients, and key excipients, to the same high standards.

For us powder testing is central to defining those standards and determining which materials to use. Obviously, a new supplier will meet the market specification for a product but in terms of how that material will process that’s no guarantee of consistency. With the right powder testing strategy, it is possible to determine which properties define performance in any given process and the specifications of powders that will work well. We’ve done this work. We understand, for example, that compressibility is a key parameter when it comes to roller compaction – a routine process for the manufacture granulated products – and how to change roller compaction parameters to handle materials of varying compressibility. We’ve similarly scoped the influence of both compressibility and flowability for tableting formulations. With established specifications for powders that work well it’s far easier to identify alternative suppliers and build a robust supply chain – instead of failing in validation or having to run under compromised operating conditions.

The other reason that powder testing is critical is that it more generally supports efficient manufacturing. Inefficient manufacturing results in higher than necessary production costs that ultimately get passed on to the consumer. It’s crucial that product quality is excellent but if we can achieve that goal with less waste and at lower cost, then obviously that’s better.

What techniques and instrumentation have you found particularly helpful and why?

The powder tester I use most is our powder rheometer (FT4 Powder Rheometer, Freeman Technology) because we can run a whole gamut of tests with it, and we have, for just about every powder we use. It allows me to investigate flow properties, aeration behaviour and permeability, compressibility and to generate shear data which are particularly helpful for hopper troubleshooting. And it’s easy to use as the instrument pretty much defines what you need to do.

When we first purchased the instrument we decide to set up a library of powder property data for all our materials. Referring back to these properties in the event of a processing problem and checking the current supply – even for a packaging or dusting issue - provides a firm basis for troubleshooting and for discussions with the vendor as to the exact impact of a material or process change.

Why I particularly like this tester is that it puts a lot of power into the hands of the ‘average Joe’, the person solving the problems. For example, we had an issue with segregation through a vacuum transfer process that necessitated the use of a subsequent stabilisation period. This was less than ideal, and to check whether it was really necessary we took some external advice. There are some good powder handling consultants available and we received sound advice, based on the use of traditional testing techniques, after a couple of weeks. Now though I would carry out aeration testing and get to the same answer in around half a day. With this instrument I have the speed and independence to tackle problems as they arise.

Can you give some examples of problems that you’ve addressed?

I have a good example that illustrates how variable the ‘same’ material can be and what this can mean for processing. One of the actives we use in a roller compaction process typically has a compressibility of around 5%. Compressibility is the change in volume that occurs as the result of applying a defined consolidation pressure, so higher compressibility means that a greater compaction force is needed to squeeze the powder to a stable ribbon in the compactor. When we looked at the compressibility of alternative supplies we found one at 10% which was easily accommodated by increasing compaction force, within the established operating window.

Then we tested a new supply – remember these all meet the same spec – and it had a compressibility of 25% so the expectation was that this would be quite interesting to process and result in some extremely hard granules. However, with the existing process we couldn’t apply sufficient force to make the powder stick together, or, in fact make any granules at all. Here then, powder testing made it possible to differentiate between supplies we could work with and more importantly those we couldn’t.

A good example on the troubleshooting side is a problem we had with segregation in a hopper. At low hopper levels the product became inconsistent – either sub- or super-potent – suggesting that the hopper design was leading to segregation under certain circumstances. To solve this problem, I checked out the design by carrying out some shear cell testing with the FT4 Powder Rheometer and running the results through the integrated hopper design software. The answers suggested a significantly different design to the existing one with a 55% larger volume, and a different half angle and outlet size.

Videos from inside both hoppers clearly show the difference between them and why the new one solves the issue. In the old hopper there is evidence of funnel flow where the powder is flowing in the centre but not at the sides, providing a rationale for rolling segregation associated with interaction with the hopper walls. The new hopper, in contrast, maintains a ‘first in first out’ consistent mass flow regime with no edge effect, right until the point of complete emptying. And despite being larger it empties more rapidly, a much- improved solution.

Can you put any value on effective powder property measurement?

Yes, and it’s significant. So, taking that last hopper example, our previous solution resulted in wastage which we’ve been able to eliminate with the new hopper design. This has produced a 8% reduction in waste – a major saving.

Furthermore, it can be too easy to lose sight of just how much its costing to be sub-optimal with respect to raw materials because of incremental changes, made over time, to cope. For example, we had a legacy product that came with the advice ‘don’t change any of the materials’. Over time that became impractical and as a result tableting rates had steadily decreased by around 50%. When powder testing unlocks throughput gains like this it can easily deliver savings of up to 50 – 100 times the cost of the instrument.

What are the key lessons that you think your industry needs to learn about powder testing?

The supply chains associated with healthcare products – and pharmaceuticals are closely similar – are global and complex. Making them robust and secure is critical and relies on being able to identify what it is about a raw material that makes it optimal for any given application. I believe powder testing is a key part of that. We can’t impose more detailed specifications on all suppliers – the costs of doing so would be prohibitive, driving up costs for customers – but we can use the technology available to make sure that the materials chosen are the best available, suitable for the production of consistently, highly efficacious products.

The other point I’d make is that powder testing doesn’t have to be the preserve of experts. With a well-chosen instrument you can access the information you need quickly and easily and build the in-house competence needed to combine excellent product quality with competitive manufacturing costs. The right powder tester isn’t just something for the lab to get excited about, it’s a worthwhile company investment that can return many times its cost.