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  U.S. Department of Health and Human Services | National Institutes of Health

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 NIH since 1902. The LCA was responsible for the safety, purity, efficacy, and potency of all biologics before licensing.

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.

Testing for endotoxins 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.

two doctors in lab coats examining a tray of tubes, half-inserted into a large device which resembles an oven.

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
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.

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 Murray 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.

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.

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