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

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The FDA Center for Biologics Evaluation and Research (CBER) moved from the NIH to the FDA White Oak Campus in 2014. Since then, Buildings 29 and 29A have been vacant. NIH completed feasibility studies and determined in 2020 that it is not viable to reuse the buildings, and demolition is planned. As these are historic buildings on Federal property, Section 106 of the National Historic Preservation Act (NHPA) and its implementing regulations (36 CFR §800) must be followed. A Memorandum of Agreement (MOA) was entered into between the NIH and the State Historic Preservation Office, the Maryland Historical Trust (MHT), since demolition of buildings is an adverse effect to historic properties.

Historic American Buildings Survey (HABS) architectural documentation of Buildings 29 and 29A at the National Institutes of Health (NIH) is part of the efforts to mitigate the adverse effects of the planned demolition of the buildings. The HABS materials will be available on the Library of Congress website, in addition to portions of them being presented here. This online exhibition on Buildings 29 and 29A and the research conducted there is also a part of the mitigation process.

Biologics Regulation and Research: The People and Work of Buildings 29 & 29A

What are Biologics?

Biologics are biological products made to prevent or treat a disease. They include vaccines, blood and blood products, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins.

The Biologics Control Act (1902)

The Biologics Control Act or the Virus Toxin Act, was passed in 1902 after 13 children died in St. Louis from tetanus, which had contaminated the diphtheria antitoxin they had received in 1901. Dr. Joseph J. Kinyoun of Marine Hospital Service’s Hygienic Laboratory (the ancestor of the Division of Biologics Standards [DBS] and the NIH more broadly) recognized the danger posed by the availability of unstandardized and poorly tested diphtheria antitoxins. Kinyoun wanted to establish an independent testing laboratory, however it took an incident in 1901 in St. Louis to get Congress to act, when 13 children who had received the antitoxin died of tetanus. An investigation discovered that one of the horses used in the manufacture of the antitoxin had live tetanus organisms in its blood and was the source of the infection.  

Congress then introduced two bills, both enacted on July 1, 1902. One bill established the Public Health and Marine Hospital Service, the other authorized this new service to regulate the sale and transportation of any virus, therapeutic serum, toxin, or analogous product in interstate commerce or from a foreign country. All establishments engaged in the sale, barter, or exchange, or offering for sale, barter, or exchange of biological products in interstate commerce must be licensed, and each product must be licensed individually. Each licensee must be inspected annually by agents and officers of the Federal government. The second act is known as the Biologics Control Act or the Virus-Toxin Act. This act has been amended by Congress several times to incorporate additional product classes, including blood, blood components, and blood derivatives. Today the regulated biologics include vaccines, blood and blood products, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins.

The Federal Food and Drugs Act (1906)

In 1906, the Federal Food and Drugs Act made illegal adulterated and misbranded foods and drugs, although it did not specifically mention biological drugs. Unlike the 1902 Biologics Control Act, which passed easily in Congress, the 1906 Act sparked serious debate for decades. The 1906 had some shortcomings, which led to the passage of the Sherley Amendment in 1912 which prohibited labeling medicines with false therapeutic claims intended to defraud the purchaser.

The Federal Food, Drug, and Cosmetic Act (1938)

To strengthen consumer protection, the 1906 Act was replaced with the Federal Food, Drug, and Cosmetic Act of 1938. 107 people had died after consuming “Elixir Sulfanilamide” which was a misbranded commercial product that was made with toxic diethylene glycol instead of alcohol. Under the 1938 Act, a biological product was considered a drug. The 1938 Act did not modify or supersede the 1902 Biologics Control Act. After 1938, the appropriate provisions of the both the 1902 and 1938 acts were used to regulate biologics.

In 1951, the Durham-Humphrey Amendment to the Federal Food, Drug, and Cosmetic Act of 1938 was passed and required that the type of drugs that could not be used safely without medical supervision had to be sold “by prescription only.”

In 1962, the Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act of 1938 were passed after thalidomide, a sleeping pill used widely in Europe, was found to cause birth defects. Thalidomide had not been marketed in the US thanks to the FDA, but it had been used in a pharmaceutical company’s investigational trial and 624 of the 20,000 American participants were pregnant women. There were 17 documented cases of birth defects caused by thalidomide in the US. The 1962 amendments strengthened the regulations for drug safety and for testing drugs in clinical trials. They also required manufacturers to provide “substantial evidence” that their drugs were effective for their intended use and that the drugs had to be produced using “good manufacturing practices,” which required inspections of manufacturers every two years and yearly registration. The 1962 amendments also applied to blood banks. 

The Public Health Service Act (1944)

In 1944, laws related to the Public Health Service (PHS) were revised and consolidated into one act, which helped to define medical research in the post-World War II era. The 1902 Biologics Control Act was incorporated into the 1944 Act. One change was that the Laboratory of Biologics Control was authorized to license biological products as well as the establishments where they were produced. The 1944 Act also provided them authority to manufacture biologics if the need arose. 

Division of Biologics Standards

In 1955, the Division of Biologics Standards (DBS) was formed, as an independent entity at the NIH, but as the continuation of a biologics regulatory function that had existed in what is now known as the NIH since 1902. The predecessor of the DBS was known as the Division of Biologics Control, formed in 1937, whose name was changed to the Laboratory of Biologics Control in 1944, and its staff were spread out amongst multiple buildings on the NIH campus. The DBS was responsible for establishing and maintaining standards of quality and safety of all biological products. The safety, purity, and potency of all biologics must be established before the product was licensed by DBS. 

The DBS was formed in the wake of the “Cutter Incident.” In 1955, the year following a field trial that showed the Salk inactivated (killed) polio vaccine to be safe and effective, the DBS licensed several firms to produce the vaccine. One firm, Cutter Laboratories, accidentally released vaccine that retained live polio virus, resulting in 260 paralytic cases of the disease, a disaster that caused panic among parents and scientists alike. The vaccine from Cutter Laboratories was pulled from the market on April 27, 1955, but the damage had already been done. The “Cutter Incident” became a defining moment in the history of vaccine manufacture and government oversight of vaccines. It occurred because the rigorous safety precautions used in the field trials were not required, at the time, for the production of commercially-produced licensed vaccines. The government realized it needed to strengthen its role in biologics regulation. The “Cutter Incident” led directly to the transfer of the regulation of biologics from the Laboratory of Biologic Controls to the DBS, a new independent entity with NIH.

In 1960, Building 29 opened, providing a consolidated space where the staff of DBS could work together. The 1950s through the 1970s were exciting and busy times for biologics regulation, as vaccine research flourished, new scientific advances in tissue culture were made, and important changes were made for regulating blood and blood products. This necessitated the construction of Building 29A in 1967, to provide an annex of laboratory space for the DBS staff. Buildings 29 and 29A are nationally significant to the history of medicine and public health because within the laboratories of Buildings 29 and 29A, the National Institutes of Health (NIH) and then the Food and Drug Administration (FDA) staff helped to conquer some of the deadliest infectious diseases. In their regulatory role they had the national responsibility to license vaccines, antitoxins, blood products, and other biologics to ensure their safety and effectiveness. To support this role, they did scientific research which resulted in the development of important standards and even new vaccines. Some of the most well-known scientists and administrators of the twentieth century worked in these buildings, first for the NIH and then for the FDA and 22 of them are profiled here in the biographies section. This online exhibition will share information about the research, regulations, and work conducted in these two laboratory buildings between 1960 and 2014. A variety of diseases, vaccines, and other biologics are discussed here, with links to articles and other websites for further research. While the buildings are no longer in use, their legendary staff and their important work lives on.

Transfer to FDA and Biological Products Review

The legislative history leading to the codification of the 1902 Biologics Control Act into the 1944 Public Health Service Act included a proposal that biological products have ‘efficaciousness’ in addition to the safety, potency, and purity requirements already in the statute.   However However, the proposed additional requirement of efficaciousness was not carried into the 1944 Act.   In  In March 1972 the Government Accounting (later called Accountability) Office (GAO) reported that DBS had not required effectiveness of biological products despite the fact that they were also ‘drugs’ under the statutory definition, and drugs had to be effective as well as safe under the 1962 Drug Amendments to the Food, Drug, and Cosmetic Act.   In  In the same month NIH announced its intention to review all of its biological products and issued a call for substantial evidence of effectiveness, the standard that was applied to drugs.   During  During a May 1972 Congressional hearing HEW Department of Health, Education, and Welfare (DHEW) Secretary Elliott Richardson announced that DBS should be transferred to FDA, and the following month he did just that.

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