Small steps: making pharmaceutical process development and manufacturing more sustainable

It’s becoming more and more important for the pharmaceutical industry to become more sustainable. And that’s a good thing. Every day, the pharmaceutical and supporting industries are involved in some pretty dirty work around the globe. We use a lot of reagents and solvents (most of which come from the petrochemical industry) and catalysts based on rare precious metals. These consumables are used and then thrown away, ending up in the incinerator, releasing carbon dioxide into the atmosphere, which is contributing to the climate emergency.

This is a big problem for making complex active pharmaceutical ingredients (APIs). These usually need 6-10 chemical steps to make enough for just one kilogram, and they create a lot of waste. Because of the difficulties involved in drug discovery, most of these APIs never even make it to clinical trials.

What new analytical techniques can you use to achieve greener drug development and manufacturing processes?

Let’s take the current standard for elemental analysis: inductively coupled plasma (ICP) spectroscopy. This is which is the go-to method in the pharmaceutical industry for determining the purity of pharmaceuticals. There are lots of reasons why ICP is so popular. But it also has some drawbacks:

• The use of aggressive acids in preparing samples creates chemical waste

• The high energy consumption required to generate and maintain the high-temperature plasma contributes to carbon emissions

A more sustainable method is available in X-Ray Fluorescence for pharmaceuticals. XRF is a great alternative to ICP. It’s sensitive enough to meet the requirements of ICH-Q3D, and it generates robust results. Plus, the whole method from sample to result is faster and doesn’t require any aggressive chemicals. It’s also less energy intensive, so it’ll help you reduce your carbon footprint as part of a cohesive carbon reduction program.

The problem with ICP

When making pharmaceutical APIs, it’s crucial to get rid of any impurities that come from the metal catalysts before moving on to the next step. So, development scientists need to come up with ways to purify the APIs without losing any of their effectiveness.

ICP is often used to check whether these purification steps have been a success. To get this kind of precise analysis, pharmaceutical samples must be digested in acids like highly corrosive nitric acid and hydrochloric acid before they can be measured. 

Alkali, like ammonium hydroxide and tetramethylammonium hydroxide, is also often used as a diluent. Since not all elements are soluble at alkaline pH, ethylenediaminetetraacetic acid (EDTA) is often used as a chelating agent—a substance that has raised concerns for its persistent organic pollutant effect.

The sustainable benefits of XRF

XRF instruments like Revontium and Epsilon meet the sensitivity standards set by the ICH, and they do so in a way that’s more sustainable and efficient. For instance, measuring vanadium using ICP means dissolving the sample in acids. XRF doesn’t need this sample prep step, which saves money and gets rid of toxic chemicals that harm the environment (and pose health and safety risks to operators).

Another plus for the environment is that XRF instruments use less power than ICP ones. The main environmental issue with ICP analysis is the energy needed to generate and maintain the high-temperature plasma. High energy consumption contributes to carbon emissions. For instance, Revontium uses just 200 watts per hour, whereas a typical ICP instrument will use 2kW per hour. Reducing energy consumption is one of the best ways to reduce environmental impact, making XRF a more sustainable choice in many cases.

All this makes XRF a safer and more sustainable solution than ICP, while also being faster, more efficient, and easier to use for solid-form analysis. It’s definitely a technique that can answer the calls for more sustainability in pharmaceutical practices!

Interested in XRF for elemental analysis? Please contact Malvern Panalytical for more information or to arrange a demonstration.