From Production To Patient: Manufacturing

Pneumonia, measles, and malaria kill nearly two million people on the continent of Africa every year. Comparatively, the U.S. had 55 thousand deaths from pneumonia, with measles and malaria being a non-issue. One of the few means of prevention lie in vaccines and other preventative measures. Determining relationships and optimizing stability from production to administration is a vital part of success against the war on disease. But how does it work? How can one be sure a vaccine is well researched, properly attenuated, and stabilized?

This series details the process of crafting these life-saving products and how they are able to reach locations globally. Vaccine manufacturers are subject to strict safety protocols and processes; if a product is poorly produced or guidelines are improperly followed, it could be a wasted investment –especially when people’s lives hang in the balance.

Vaccines are produced in several different forms –often as weakened or inert versions of the virus to be treated. Vaccines are designed to force an immunological response to the disease, and activate Memory B cells to create specific antibodies in case a person is exposed to the virus or bacteria again.

Before a vaccine can be made, researchers must spend time isolating and studying the virus or bacteria in question and learning how it causes disease. Researchers then begin studying how to prevent the disease, keeping it in an isolated, sanitary environment. There are three phases of studies: Phase I, Phase II, and Phase III that need to be completed before the vaccine can be used by the general population. Phase I trials determine if the product produces an immunological response, where Phase II and III studies use increasingly larger populations for the sake of determining the safety and overall efficacy of the vaccine.

Once strains have been isolated from blood samples, viruses are carefully replicated in a cell factory with a growth medium. The virus must be free of impurities, including other similar viruses and even variations of the same type of virus. Most vaccines must be kept under ideal conditions, often between 35°F and 45°F. Otherwise the virus could become too strong or too weak to be used as a vaccine. Stored in small containers, viruses are grown by the millions and will eventually lead to several hundred liters of vaccine. Virus cells need to accumulate and multiply efficiently, so most mediums include proteins from purified cow blood or a similar source.

When examining the production strategies of a pharmaceutical brand, solution pH plays a significant role in the stability of a vaccine. pH is a measure of acidity or basicity, measured on a scale from 0 to 14.  Viruses must be kept at a stable pH within the cell factory, such as water, which has a neutral pH of 7 often makes for an ideal medium in both reproduction and storage. Throughout this stage are sensors that monitor both temperature and pH. Without them, a power outage or prolonged outside exposure could lead to production slowdown or even contamination of the batch. During an increase in swine flu outbreaks in 2009, production slowed to a crawl in-part because of issues in the growing stages.

After initial replication, the virus is then separated from the medium and placed into a second medium for additional, more concentrated growth. “Beads” (near-microscopic particles) are placed in the new medium to allow for a surface on which the disease can densely grow, and enzymes are added as catalysts to speed up production.

When the culture has grown large enough, it is separated from the beads in one of several ways. The solution is forced through a filter with openings large enough to allow the viruses to pass through, but small enough to prevent the beads from doing so as well. Another option is for the mixture to be centrifuged several times to separate the virus from the beads in a container where they can then be drawn off.

Earlier, we noted that viruses are vetted or “attenuated” so that only the right viruses are used to produce a vaccine. Some viruses grow too strong when cultured, whereas others become too weak and are unusable. Only those that are somewhere between can be utilized for vaccinations. Monitoring devices like the ones made by SmartSense are vital to the entire research & production process of ensuring clean, safe, and effective vaccines. Once the vaccine has been produced, tested, and approved by the CDC and the FDA, it’s time for them to be packaged and shipped to where they need to go.

Look for next week’s installment of Production to Patient to see just how the CDC gets vaccines to their locations without harm!