The end is nigh! Or so we hope for the Covid-19 pandemic. The cavalry horns of Pfizer-BioNTech, Moderna, Oxford/AstraZeneca, Sputnik and more, are sounding, and the world awaits the changing of the tide. Yes, the vaccines are here to the rescue and I, for one, embrace their arrival.

Figure 1. The vaccines are coming. Photo by Daniel Schludi on Unsplash

The scientific endeavours to develop, test and approve these vaccines for global use has been nothing short of astounding. Next up is the supply chain, which will need to deliver safe and effective doses to billions of people. Any delay in this process could be precious time lost. For example, if a batch of vaccine fails a quality test, then the batch will be considered unsafe for use and be scrapped. But, to prevent further failures and a drop in the supply, the root cause of that failure will need to be found and controlled, or eliminated altogether.

Pharmacopeial Safety Standards on Particulate Matter

The Covid-19 vaccines, like most other biotherapeutics, are delivered by injection to ensure that the active ingredient is intact when it’s distributed by the blood to the site of action. However, this does expose the patient to the safety risks caused by particulate material. Hence, regulatory authorities have pharmacopeial guidelines on testing and control of particulates. One such guideline for vaccine developers is the USP general chapter <1787> that describes three different categories of particulate matter:

  • Inherent: particles derived from the product, such as protein or excipient
  • Intrinsic: particles derived from the process, such as silicone oil, rubber or glass
  • Extrinsic: particles derived from unknown sources.

Join our discussion with KBI Biopharma here on the different technologies used in this application.

Technology to Support the Supply Chain

Figure 2. The Morphologi 4-ID uses Morphologically Directed Raman Spectroscopy to test for Foreign Particulate Matter in injectables

One of the techniques for particle identification described in USP <1787> is Raman Microspectroscopy, which involves using a light microscope to target individual particles for Raman spectroscopy. The identification can be rapid for single particles and can take place in the native suspension or when filtered. However, finding these particles can be laborious and quantifying them is beyond the time-scale typically available for such tests. The solution is to automate the test using a technique known as Morphologically-Directed Raman Spectroscopy (MDRS), performed using the Morphologi 4-ID. Find out here how recent updates to this technology has improved the Raman spectral quality to better identify particulates, at reduced analysis times.

Figure 3. Using MDRS to guide root cause analysis and assess risk. The particles are identified as protein by comparison of their Raman spectra to a library of reference spectra using correlation scores. These would be classified as Inherent particles.

Where vaccines and other injectables are concerned, “particle identity will guide the root cause analysis, risk assessment, corrective actions, and control strategy” (USP <1787>). We truly hope that the technology deployed in this guideline and others will help to deliver the Covid-19 vaccines, and scores of other biotherapeutic products, in a timely manner.