How antibiotics are made/manufactured
By: Jessica DeMuro
Although most antibiotics occur in nature, they are typically not available in the
quantities necessary for large-scale production. As a result, antibiotics are produced
industrially by a process of fermentation, where the source microorganism is grown in
large containers containing a growth medium. Those containers are closely monitored
for oxygen concentration, temperature, and PH levels. This process involves isolating a
desired microorganism, fueling growth of the culture, and refining and isolating the final
antibiotic product. Sterile conditions must be maintained throughout the manufacturing
process, because contamination will ruin the fermentation.
Isolation process:
Before the fermentation process can begin, the desired antibiotic-producing organism
must be isolated in order to multiply its numbers. A starter culture from a sample of the
previously isolated organism is created in the lab. In order to grow the initial culture, a
sample of the organism is
transferred to a petri dish that
contains a growth medium
and nutrients. This culture is
then placed in shake flasks
along with food and other
nutrients necessary for
growth. When the cells begin
to multiply, they are then
transferred to a seed tank for
further growth.
Seed tanks:
Seed tanks are steel tanks designed to provide a supreme environment for
growing microorganisms. They are filled with many things deemed necessary
for the microorganism to survive such as warm water, and carbohydrate food
including lactose and glucose sugars. Additional growth factors including
vitamins, amino acids, and minor nutrients are also important contents of the
seed tank. The tanks are equipped with mixers to keep the growth medium
moving, and a pump to deliver sterilized air. After 24-28 hours in the tank, the
material is transferred to primary fermentation tanks where the growth process
may begin.
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Fermentation tanks:
The fermentation tank is much larger than the seed tank with a holding
capacity of approximately 30,000 gallons. The tank provides the same growth
media found in the seed tank along with an environment that induces cell
growth. This is where the microorganisms grow and multiply, excreting large
quantities of the antibiotic. The temperature of the tanks is constantly
monitored and kept between 78-81 degrees Fahrenheit. It is important to
ensure a continuous supply of sterilized air is being pumped in to the tank to
avoid contamination. Anti-foaming agents, and acids or bases are periodically
added to promote optimal growth.
Isolation:
The maximum amount of antibiotic is
produced after sitting in the fermentation
tanks for a 3-5 day period, and the isolation
process may now begin. The fermentation
broth is processed by various purification
methods depending on the specific
antibiotic.
Water-soluble antibiotic
compounds:
For antibiotics that are water
soluble, an ion exchange method
is used for purification. The
compound is first separated
from the waste organic materials
found in the broth, and then sent
through equipment. This equipment separates the other water-soluble
compounds from the desired one.
Oil soluble antibiotic compounds:
To isolate an oil-soluble antibiotic such as penicillin, a solvent extraction
method is used. This method uses organic solvents such as butyl acetate to
specifically dissolve the antibiotic. The dissolved antibiotic is then recovered
using various organic chemical means. The end result of this method is a
purified powdered form of antibiotic, which is then further refined in to
different product types.
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Purification:
Antibiotic products are available in several different forms. They can be sold in solutions
for syringes, in pill or gel capsule form, or they may be sold as powders, which are used
for topical ointments. Depending on the final form of the antibiotic, various steps must be
taken after the initial isolation of the antibiotic to further enhance the final product. For
gel capsules, the powdered antibiotic is physically filled into the bottom half of a capsule
and the top half is mechanically put in place. For topical ointments, the antibiotic is
physically mixed into the ointment. The final antibiotic product is now transported to the
final packaging stations where it is stacked and put in boxes. The boxes are transported to
various distributers, hospitals, and pharmacies. The entire manufacturing process of
fermentation, recovery, and processing may take anywhere from five to eight days.
Quality Assurance:
Quality assurance is the most important thing to consider when producing antibiotics.
Since the production of antibiotics involves a fermentation process, making sure there is
no contamination introduced at any point in the process is a vital step. For this reason,
frequent checks are made of the condition of the microorganism culture during the
fermentation process. The equipment used to process antibiotics must be thoroughly
steam sterilized before the process may begin. Various physical and chemical properties
of the finished product are also checked including pH, melting point, and moisture
content. Antibiotic production in the United States is highly regulated by the Food and
Drug Administration (FDA). The FDA requires that for certain antibiotics each batch
must be checked for effectiveness and purity before being sold for consumption.
The Future of Antibiotic Growth:
Antibiotics are not as effective at killing bacteria as when they were first introduced. It is
estimated that 77,000 people die of infections caused by resistant bacteria in the United
States every year. Due to their quick generation times and high numbers, bacteria have a
high capability to quickly adapt to changing environments. Scientists are suggesting that
this evolution of resistance to antibiotics is a result of the overuse and misuse of
antibiotics. As a result, scientists are recommending that the agricultural industry
discontinue the use of antibiotics on crops and livestock. Doctors must also refrain from
prescribing broad-spectrum antibiotics, which kill many different types of bacteria, and
must begin to focus on prescribing an antibiotic to specifically target the bacteria causing
the infection. Most “new” antibiotics manufactured today are modified from the older
ones, but often so similar to older versions that resistance is still evolving very quickly.
Although research on the optimal use of antibiotics is still under way today, it is still
unclear how exactly to decrease the rate of resistance to these “miracle” drugs.
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