Safety Doesn’t Stop After Approval

Safety Doesn’t Stop After Approval

How microbial testing keeps vaccines safe

Vaccine development typically takes years, even decades. How then could companies deliver COVID-19 vaccines in a matter of months? Can we trust the process? These two questions have been dominating the airwaves ever since the first three candidates in the pipeline were authorized by regulators, a mere 11 months after SARS-CoV-2 emerged in China. We hope Eureka’s five-part series, The Vaccine Journey, on how vaccines are developed—from discovery through manufacturing—helps answer some of these questions and reassures readers that vaccines are generally very safe. Christine Farrance, Senior Director of Scientific Affairs, shares how microbial testing during manufacturing keeps safety standards high after vaccine approval.

“The requirement for safety in modern prophylactic vaccines is extremely stringent because the vaccines are administered to healthy individuals.”

So, your vaccine has been developed, safety tested, clinically tested, and approved for use in people. Now you are in the clear, right? Well, not quite.

Vaccine and drug safety never stops. Manufacturers must have a contamination control strategy and no matter how long a product has been in use, the processes to make that product are constantly monitored, and quality controlled and will be for as long as manufacturers produce that medical product. This includes everything from individual factory safety standards to government-level regulations, and everything in between. For Microbial Solutions, that means helping to detect and identify foreign microbes or particulates that could sneak in to the manufacturing process and make people sick.

Microbial testing

When manufacturing an injectable pharmaceutical, like vaccines, every contact point must be sterile. Contact points like machinery and people are tested frequently, and other materials like the water, containers, and especially air are also subject to scrutiny.

Endotoxin testing is one method used to check for bacterial cell wall contaminants whose presence in a vaccine or other injectable product can lead to serious illness or death. These tests are extremely sensitive and will fail a sample at very small traces of contamination. All injectable pharmaceuticals and implantable medical devices need to be tested to guarantee there is no endotoxin in the product.

Rapid microbial detection is another way manufacturers can test their product for contamination. The total amount of viable organisms – bacteria and fungi – must be determined for a product. These live organisms can come from the raw materials, from the people, or the process used to make the vaccine. For vaccines and injectable products that must be sterile – the sterility test confirms that the products are free from viable bacteria and fungi.

Safety is reassured by knowing that the product is free of bits of bacterial cell wall material (endotoxin) and free of living microorganisms both of which can make you very sick.

Ensuring the vaccine manufacturing process is sterile and safe means that there is zero tolerance for any contamination. However, these tests only detect the presence or absence of contamination – they do not identify the type. It isn’t enough to know whether there is contamination – manufacturers need to know what kind, and where it might have come from.

Microbial identification

This step is trickier, but invaluable to keeping manufacturing safe. Microbial identification involves gathering samples of whatever is threatening a product – be it a bacteria, fungus, or other contaminant, and figuring out exactly what species and strain it is.

Monitoring the manufacturing environment and putting names to the isolated organisms helps to understand the microflora and dictates everything from how you clean to where the organisms are coming from and what controls need to be added to protect the product.

For example, a manufacturer might place a sample of their product in a sterility bottle. If the nutrient media in the bottle gets cloudy – or a rapid detection method indicates microbial growth is positive – they know that something is wrong with their process, or that somehow, a microbe has snuck in.

By sending the sample to companies like Accugenix, they can find out exactly what the microbe is. If it is, for example, Micrococcus luteus or Cutibacterium acnes, that is a sign that the contaminating factor was an employee. These common skin organisms could be a sign that workers are not gloved and gowned properly, or that the gloves and gowns are defective in some way. Knowing the species means narrowing down the possible points of entry for the contaminant.

The regulations regarding drug and vaccine manufacturing are very clear. Every surface, every raw material, and every employee are tested and retested, and any contamination results in a step by step investigation of where the problem came from. Patient safety is not only the moral and economic imperative for manufacturers – it is also the law.

Dr. Christine Farrance has more than 25 years’ experience conducting both applied and basic research using molecular, microbial, and biochemical techniques. Her work has included developing plant-based production systems for recombinant vaccines, monoclonal antibodies, and protein therapeutics, and research in the food safety industry.