AIDS vaccine manufacturing
Developing an AIDS vaccine is a complex task that involves many steps including laboratory experiments and clinical trials (see Primer). But identifying promising vaccine candidates is only part of the effort. Another major, often-overlooked area of AIDS vaccine development is the manufacturing process.
Many resources are needed to manufacture a vaccine. These include production facilities and specialized scientific equipment, highlytrained scientists and technicians, and supplies of the materials used to make the vaccine. These resources are needed long before a vaccine has proven effective and been licensed for widespread use because clinical trials cannot take place without sufficient, readily-available supplies of the candidate vaccine.
The AIDS vaccine field is paying increasing attention to manufacturing needs and has identified some key gaps in current resources. In 2003 many leaders in the AIDS vaccine field proposed an AIDS Vaccine Enterprise that would increase collaboration on key issues like manufacturing. In February 2004 the Enterprise working groups on manufacturing and product development began to draft a strategic plan to address needs in these areas.
The plan produced by the Enterprise will be an important effort to address shortages in manufacturing resources that could slow down the pace of clinical trials or even delay access to an effective AIDS vaccine once it has been developed.
Drugs are usually produced by combining a variety of chemical compounds. But vaccines are made using biological systems, meaning that living organisms are used to produce the vaccine. Vaccine developers take advantage of the fact that animal cells and bacteria produce many different substances as part of their normal functions, and adapt these capabilities to help make vaccines.
For example, DNA vaccines are copies of a small portion of HIV genetic material that cannot cause HIV infection. The most efficient way to make large quantities of these molecules is by getting microorganisms to produce them. Each microorganism functions like a miniature factory for the DNA vaccine.
From start to finish, it usually takes about nine months to produce a batch of vaccine. During this period, the vaccine is made, tested, packaged and labeled. Each step in this process is carefully monitored to ensure that the manufacturer meets international standards of “Quality Assurance” and “Quality Control.” These international standards are applied to both experimental vaccines and to licensed products. They ensure that all vaccines are safe and of high-quality and that the product is made the same way each time.
Challenges: Process development and manufacturing capacity
Before a vaccine can be manufactured, scientists must precisely identify all of the steps in the production process and work out how best to carry them out. This is known as “process development.” Most vaccines undergo several stages of process development. The first stage happens when a promising concept is identified in a laboratory and scientists develop a process to produce enough vaccine for trials in animals and, later, early trials in humans. The quantities of vaccine required for these safety trials are relatively small.
If a vaccine is shown to be safe in small-scale safety trials, it may then proceed to intermediate- and large scale trials. The largest of these trials may enroll thousands of volunteers. At this stage the manufacturing process must be further developed to produce much larger quantities of vaccine.
Process development requires biotechnology experts. At the moment much of this expertise is concentrated within large pharmaceutical companies, many of which are not developing AIDS vaccines. Some AIDS vaccine developers are concerned that this lack of human resources could lead to delays in bringing potential vaccine candidates through clinical trials.
A second key gap is in manufacturing capacity, including facilities equipped to make the types of AIDS vaccines that are currently being tested in clinical trials. There are already limited facilities for producing licensed vaccines such as those that help prevent measles, mumps and polio. Additional new facilities are needed for experimental AIDS vaccines. These manufacturing facilities must have the ability to manufacture vaccines that are made using several different biological systems, since we still do not know which processes will be used to make an effective vaccine.
The need to plan ahead
It will likely be many years before there is an effective preventive AIDS vaccine. However vaccine developers must already begin to plan for the day when such a vaccine is identified through clinical trials. Around the world, there will be urgent requests for this vaccine. The only way to meet these demands will be through large-scale production facilities that are equipped to make the new vaccine.
These factories cannot be built overnight. It usually takes between five and seven years and hundreds of millions of dollars to build and “validate” a new facility to ensure that it functions properly and meets all international regulatory requirements, including Quality Control and Quality Assurance standards.
It is not known if any of the vaccines that are currently being tested in clinical trials will help to prevent HIV infection or disease. However the field cannot wait for this information to begin investing in large-scale facilities. Such a delay could costs millions of lives. Instead, vaccine developers must take the risk of investing in manufacturing capacity before they know whether or not a vaccine is effective.
No single AIDS vaccine developer can address all of the field’s manufacturing capacity and process development needs. The strategic plan from the Vaccine Enterprise working groups could provide a starting point for increased collaboration and coordination throughout the field.
All articles written by Emily Bass