Biologics Regulation and ResearchThe People and Work of Buildings 29 & 29A

Hepatitis A, hepatitis B, and hepatitis C are liver infections caused by three different viruses. Although each can cause similar symptoms, they are spread in different ways and can affect the liver differently. Hepatitis A is usually a short-term infection and does not become chronic. Hepatitis B and hepatitis C can also begin as short-term, acute infections, but in some people, the virus remains in the body, resulting in chronic disease and long-term liver problems. There are vaccines to prevent hepatitis A and hepatitis B; however, there is no vaccine for hepatitis C.

Hepatitis B is a liver disease that can cause mild illness lasting a few weeks, or it can lead to serious, lifelong illness. Hepatitis B is spread when blood, semen, or other body fluid of an infected person enters the body of a person who is not infected.

The first reported case of hepatitis after a blood transfusion was in 1938 by R. Junet and W. Junet in the Revue Médicale Suisse (a medical journal published in French).  This became a big issue during WWII when they pooled plasma: World War II when plasma was pooled; one infected donor would affect infect everyone.

Hepatitis was a major focus of the Bureau of Biologics’ blood regulatory program early on, from checking the proficiency of blood banks to conduct hepatitis tests, to collaborative research on the virus using animal models with NIH's National Institute of Allergy and Infectious Diseases (NIAID) and the Centers for Disease Control and Prevention (CDC), to further study of donor selection criteria.

Following two meetings of its external advisory Panel on Safety and Effectiveness, which considered published and unpublished data on coordinated clinical trials conducted across the nation, the advisors broadly concurred with the Bureau that Hepatitis hepatitis B immune globulin was safe and effective for Hepatitis hepatitis B prophylaxis. Thus, in 1977 the Bureau issued the first license for this product in post-exposure prophylaxis in the event of accidental encounters such as needle sticks, laboratory accidents, and similar situations.

In 1978, and following efforts over several years, FDA finalized regulations to help lessen the likelihood of hepatitis contamination of blood through labeling. Research suggested a significant difference in likelihood of such contamination from paid blood donors rather than volunteers. Henceforth, blood intended for transfusion had to be labeled as either paid or volunteer sourced.

FDA licensed two tests in 1990 to detect Hepatitis Cnon-A, non-B hepatitis. Previously, researchers from CDC and industry constructed a non-A, non-B viral protein from a single stranded ribonucleic acid isolated from an animal model infected with non-A, non-B hepatitis. Recombinant DNA manipulation of this protein produced enough quantity to enable development of a commercial assay to detect antibodies to this viral protein. Clinical trials assessed the ability of this assay to detect antibodies formed against this viral protein, now designated c100-3, in donor blood. The trials showed that eliminating units that tested positive for antibodies to the c100-3 protein could eliminate non-A, non-B hepatitis, and that there was one major non-A, non-B virus, subsequently designated Hepatitis hepatitis C. The first anti-HCV antibody test was licensed in May, and the second two months later.

In July 1986, OBRR licensed the first recombinant viral vaccine, for Hepatitis hepatitis B. The same manufacturer, Merck, Sharp & Dohme, had received a license for a Hepatitis hepatitis B vaccine some years earlier.

In July 1992, the Center for Biologics Evaluation and Research (CBER), which is what biologics regulation is still called at the FDA today, issued the first license for a treatment of chronic Hepatitis hepatitis B for recombinant interferon alfa-2b. FDA had previously approved this for other indications, including hairy cell leukemia. CDC estimated at that time 750,000 to 1 million Americans had the Hepatitis hepatitis B virus, and one-quarter would develop chronic, active hepatitis.

Development of the present killed hepatitis A vaccine depended on a series of breakthrough discoveries made during the last half of the 20th century. These were marmoset propagation (1967), definition of virus attributes (1974-1975), development of diagnostic tests and seroepidemiology (1974-1975), and the preparation and proof of efficacy of a prototype killed hepatitis A vaccine (1976). Successful cultivation of hepatitis A virus in cell culture in 1979 quickly led to development of both live and killed hepatitis A vaccines for tests in humans (1980-1990). The year 1991 marks the initiation of protective efficacy trials of two different killed virus vaccines in human beings. The safety and protective efficacy of the first hepatitis A vaccine (manufactured by Merck) was reported on in an article by Maurice Hilleman in 1993.

Also, the NIH's National Institute of Allergy and Infectious Diseases (NIAID) Drs. Robert H. Purcell, Suzanne U. Emerson, and Jeffrey I. Cohen, and the FDA’s Drs. Stephen Feinstone and Richard Daemer of the Center for Biologics Evaluation and Research (CBER), developed and patented a hepatitis A virus (HAV) and related technology used to develop the vaccine. The patents cover a strain of human HAV, HM175, an attenuated form of HM175 and the methods developed to isolate and grow the viruses in cultures of kidney cells derived from African green monkeys. In 1985, based on the scientific and commercial potentials of the NIAID inventions, SmithKline Beecham took a nonexclusive license on the patents and, in 1986, established a cooperative research and development agreement to develop HAVRIX, the world’s first commercially available HAV vaccine. HAVRIX uses an inactivated HM175 strain of HAV. In 1994, SmithKline received the European Prix Gallen award for HAVRIX in honor of its overall contribution to medicine in terms of safety, efficacy, and innovation. Currently, HAVRIX is registered in more than 40 countries.