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

Laboratory of Control Activities

The Laboratory of Control Activities (LCA) was formed in 1955 when the Division of Biologics Standards (DBS) was formed, as the continuation of a biologics regulatory function that had existed in what is now known as the National Institutes of Health (NIH) since 1902. Biologics include vaccines, blood and blood products, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins.

The LCA was responsible for the safety, purity, efficacy, and potency of all biologics before licensing. They were also responsible for the development and distribution of the United States standard and reference preparations used in establishing potency of biologics.

The LCA was formed—along with the DBS itself—in the wake of the Cutter polio vaccine incident. The formation of the LCA and DBS was also likely related to the change in regulations regarding polio vaccine production as well.

LCA was located in Building 29, Fourth Floor from 1960 to 1967, then moved to Building 29A, First Floor when it opened in 1967.

LCA included multiple sections within the lab, including Reference Standards, Control Test, Pyrogens, and in 1971 also included an Analytical Chemistry section.

Dr. Edward B. Seligmann (right) and William H. Berkeley demonstrate use of their recently patented freeze-drying tray. Photo by Tom Joy. The NIH Record 12.13.1966

Testing for endotoxins (a toxin present in a bacteria cell that is released when the cell disintegrates) in injectable biologics was revolutionized in Building 29A by a team led by Dr. Edward B. Seligmann and Dr. H. Donald Hochstein. Endotoxins are part of the outer membrane of the cell wall of Gram-negative bacteria and had been discovered to be the cause of fevers in some patients receiving injections.

They developed a new calibrated test, Limulus amebocyte lysate (LAL), for pyrogens (fever-causing endotoxins) using horseshoe crab blood instead of rabbits’ ears. LAL became the standard worldwide test for bacterial endotoxins.

Dr. Seligmann and Mr. William H. Berkeley also developed a patented direct-contact tray assembly for freeze-drying biologics. Since DBS annually prepared and distributed approximately 6,000 standard or reference preparations to establishments throughout the world for use in biologics standardization, it was essential that this material be meticulously and uniformly prepared. Their new tray had the advantage of allowing each vial to directly touch the freeze-dryer shelf, ensuring uniform freezing and heating for all of the vials when put into the chamber-type dryer.

Dr. Seligmann was appointed chief of the Laboratory of Control Activities by DBS Director, Dr. Roderick Murray, in 1968. He had served as the chief of the Section on Reference Standards since his arrival at the NIH in 1959.

When DBS was transferred administratively to the Food and Drug Administration (FDA), LCA became known as the Division of Product Quality Control.

Scan of the 1902 Biologics Control Act signed by Theodore Roosevelt

1902 Biologics Control Act image from 1968 publication. The Biologics Controls Act, or 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. 1968 publication "The Division of Biologics Standards" (Public Health Service Publication No. 1744) by Dr. Roderick Murray

Photograph of a guinea pig scanned from printed publication

Guinea pig image from 1968 Murray publication. In the 1960s, DBS was conducting approximately 35,000 control tests annually on samples of manufacturers’ products. Some 180,000 mice, 3,500 rabbits, 2,000 monkeys, and 8,600 guinea pigs were used annually for control tests.