Unlike pharmaceutical drugs, which are made from chemicals, biotechnology drugs such as enzymes are derived from living organisms and their products. Biotechnology manufacturing requires the combination of several fields of science (e.g., microbiology, biochemistry, engineering) with large-scale industrial processes. The cost and difficulty involved in manufacturing these products are often higher than those of a conventional pharmaceutical drug.
What is an enzyme?
An enzyme is a protein that starts up or “triggers” a biochemical reaction. Some of the important functions of enzymes include:
 | Regulating the growth of the body from a single cell to a mature organism |
| Converting food to energy to satisfy the body's needs |
| Breaking down or building up certain substances within the cell |
Genetic engineering is the process that allows scientists to alter the genetic make-up of an organism so that it can produce human enzymes. This technology, also known as recombinant DNA technology, makes it possible for scientists to produce many enzymes that previously were only available in small quantities, if at all. These manufactured enzymes may then be given through regular injections to patients with enzyme deficiencies to replace the missing or malfunctioning enzyme. There are three main stages to producing recombinant human enzymes for use in enzyme replacement therapies (ERT).
Stage One: Cell Culture, Growth, and Harvest
Before genetic engineering, it was difficult to purify enough enzyme to treat even a single patient. Today, special "cell production lines" have been created for large-scale manufacturing. These cells are frozen in a cell bank or storage facility prior to use, and they provide the starter material for the genetic engineering process. The most commonly used cell production line in genetic engineering is the Chinese hamster ovary cell, commonly abbreviated as "CHO cell." To produce a certain enzyme, the gene for that enzyme is obtained from human DNA and inserted into the CHO cells, causing them to express or "manufacture" the enzyme.
Stage Two: Enzyme Purification
Because enzymes are proteins, they are digested if swallowed, making oral administration (such as by tablet or liquid, for example) difficult. As a result, enzyme replacement therapy must be injected directly into the bloodstream and must therefore meet very high purity standards. To purify the enzyme, unwanted substances are first removed. Afterwards, the product is ready for formulation (development to a final product) and transport to a sterile area, where it is put into its final packaging.
Stage Three: Filling and Finishing
In the last stage of the production process, the manufactured enzyme is filled into vials in "the fill room," which is kept sterile to prevent product contamination. At this point, the vials are ready to be sealed, labeled, and inspected. Samples of the finished product are sent to a lab for extensive Quality Control (QC) testing of factors such as appearance, potency, purity, and sterility. Then a Quality Assurance (QA) process reviews the documents associated with the manufacturing process to ensure that all procedures have been followed correctly. Only after QA approval can the enzyme be shipped from the manufacturing facility.
