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May 20, 2023

Mitigating fill, finish and CCI challenges for injectables

Primum non nocere. First, do no harm. The often-official motto of healthcare

Primum non nocere. First, do no harm.

The often-official motto of healthcare providers, organisations, and associations around the world sets the bar for the global pharma industry. Patient safety should always come first. However, this philosophy isn't just relegated to guiding the practices of medical professionals and drug developers. It extends all the way down to the healthcare sector's expectations for every component, instrument, and process orbiting the development and manufacture of medicine—especially parenteral drugs. Injectable therapies are some of the most highly sensitive drugs that require the most rigorous protective measures to ensure no particles, microbes or oxidisation jeopardises formulation integrity.

These high standards aren't reachable without serious commitments to Container Closure Integrity (CCI). CCI is the ability of a container closure system to maintain the sterility of final pharma, biological and vaccine products throughout their shelf life. It is also a regulatory requirement upon which to qualify closure designs. In the case of parenteral drugs, CCI aims to avoid adulteration of the drugs packaged in vials, syringes, and cartridges. Even though these types of packaging systems are sealed in a hermetic manner, there are still many risks to mitigate.

What factors threaten CCI?

CCI is subject to many threats from the ambient environment. Vials, cartridges, and syringes are often packaged one of two ways. The industry preference is with terminal sterilisation wherein the entire packaging system is sterilised. Alternatively, drug manufacturers can package drugs with components that have been sterilised individually, assembled, then filled aseptically by filtering the drug product through a 0.2-micron filter. However, drugs filled and packaged using either method are still subject to a few potential risks around leaks due to CCI failure:

What can drug manufacturers do to minimise these risks?

First, we must remember that every small component, like the stoppers, plungers, and caps, have critical roles to play in preserving drug integrity as part of the parenteral drug packaging system. Stoppers are placed at the top of syringes, vials, and cartridges to seal the barrels of these containers. Plungers glide through the barrel of syringes to deliver injectable drugs smoothly and effectively. Caps often top off vials and are comprised of both metal and rubber components. All must be designed with painstaking care to ensure compatibility with the drug product they interact with. Once that bar is cleared, there are many assessments, practices, and technologies available to help drug manufacturers enhance CCI:

Working toward CCI around the World!

No matter where drugs are manufactured, pharma companies are still subject to the CCI standards of the markets they serve. This can make the whole process complicated as pharmacopoeias vary with regions. For example, markets like Japan have had extremely strict regulations around sterility for closures compared to other markets that took significant R&D to develop elastomeric closures that met the standard. In the US, the Food and Drug Administration (FDA) prefers the deterministic CCI testing versus the probabilistic CCI testing of the past. The FDA asks drug manufacturers to use deterministic CCI testing instrumentation and technology because probabilistic methods are more subjective and contain more qualitative methodology while deterministic methods are quantitative and nondestructive while giving actionable insights. There is greater certainty in the deterministic testing methodology.

It is critical that drug manufacturers comprehend the differences between the markets they serve and work closely with their suppliers who understand the nuances of different regional regulations, and of course work toward the highest standards to do no harm.

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