Why was penicillin difficult to produce after Alexander Fleming discovered it?

After Alexander Fleming discovered penicillin in 1928, it remained difficult to produce for clinical use primarily because the necessary techniques for its isolation and purification had not yet been developed. Fleming was unable to produce the substance in sufficient quantities or in a pure enough form to treat patients effectively.1

The challenge was largely logistical and technical. Early production relied on growing the mold Penicillium notatum in small containers, which yielded very little of the drug. It was not until the late 1930s that Howard Florey and Ernst Boris Chain at the University of Oxford successfully isolated and purified the substance.231

Scaling up production required further innovation, as the original mold strain did not grow well in large industrial fermentation vats. Eventually, researchers in the United States identified a more productive strain, Penicillium chrysogenum, which allowed for mass production to meet the urgent needs of World War II.21