NIST Industrial Impact

Companies:
Amersham/MediPhysics, Illinois
Bristol-Myers Squibb, New Jersey
Du Pont Merck Pharmaceutical, Massachusetts
Mallinckrodt Medical, Missouri
Nordion International, Ontario, Canada
Packard Instruments, Illinois
Syncor International, California
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Inventing ways to see inside bodies without cutting into them is one of the medical community's shining successes. Radioactive isotopes that can be injected safely into patients' bloodstreams and tissues get a lot of credit for that success. These so-called radiopharmaceuticals work like transient spies sending diagnostic signals from inside the body to external detectors and computers, which construct images of internal body structures from those signals. Like good spies too, the isotopes quickly disappear once their job is done, either by transforming into non-radioactive products or by passing out of the body.

If they know precisely how much radioactivity each dose harbors, doctors can confidently inject patients with radioactive drugs such as thallium-201 for heart scans. Determining the exact amount of radioactivity is an especially demanding measurement task, however, since radioactive isotopes are produced at private or government facilities, made into radiopharmaceutical preparations by a number of different companies, and then put to diagnostic use at thousands of hospitals. All the while, the radioactivity contents to be measured are changing. Unlike the weight of a pill, which remains constant from maker to patient, the activity of radiopharmaceuticals continually decreases over time.

Regardless of the challenges, each radiopharmaceutical handler must have a way of assuring that their own radioactivity
measurements are accurate. Nuclear Regulatory Commission rules, for one, require such measurements. Good business and good medicine also critically depend on the quality of these measurements.

Assurance of that quality stems from the National Institute of Standards and Technology, remarks Tibor Schubert, manager of radiodiagnostics at Bristol-Myers Squibb. For the past 20 years, NIST and the Nuclear Energy Institute (formerly the United States Council for Energy Awareness), which represents the nuclear power and nuclear medicine industries, have collaborated to provide the industry with standards that everyone can use as benchmarks. "It helps make sure that everyone is on the same wavelength," says Schubert, who chairs a NIST/NEI steering group that sets the agenda for the collaboration. "It increases the confidence for everybody" who makes and uses radiopharmaceuticals, adds Michael S. Mosley, a quality control and government affairs specialist at Syncor International Corp., the country's fastest growing "nuclear pharmacy."

That confidence level has contributed to the ascent of radiopharmaceuticals both as a standard part of medical practice
and as big business, say Schubert, Mosley, and others in the industry. Each year, U.S. doctors perform over 7 million
diagnostic procedures using radiopharmaceuticals. About one out of every four patients entering hospitals undergoes some form of radioactive diagnostic or therapeutic procedure. Many cardiac patients undergo the thallium-201 stress test, which allows doctors to image the damaged heart for guidance in treating heart patients. The market for radiopharmaceutical preparations now approaches $1 billion.

When the NIST/NEI collaboration began in 1973, there were no standards for three out of four radiopharmaceuticals then available, nor were there uniformly adopted protocols by which instruments in different places were calibrated even when standards were available. These and other measurement problems slowed Food and Drug Administration approval of new drugs and led to disputes between vendors and buyers of radiopharmaceuticals since prices are determined not by weight but by the amount of radioactivity sold.

Out of the collaboration so far have come more than two dozen new Standard Reference Materials (SRMs), which are distributed as small sealed ampoules containing specific radiopharmaceuticals with NIST-certified amounts of radioactivity. Vendors and buyers use these to calibrate their own measurements. Among these SRMs, which are prepared and certified by three scientists at NIST who are supported by a fee paid by member companies, are standards for thallium-201; iodine-131, an agent for diagnosing and treating thyroid problems; and technetium-99m, which is used in procedures such as imaging brain tissue.

Besides the collaboration's intangible payoff in the form of product and industry confidence, the NIST-made SRMs have a more direct impact on companies' bottom lines. "If a company went out and developed these on its own, you are talking maybe $1 million," estimates Felix Killar, manager of Non-Utility Programs for NEI. "Participation in the program and having radiopharmaceuticals [whose activities are] traceable to NIST standards gives member companies a competitive advantage."

April 1994