Biotech Devices: Replacing Test Animals, Improving Diagnoses

by Food and Drug Administration (FDA)

This is the first of two articles on biotechnology and medical devices.

The young woman hadn't been feeling well. She tired easily, and her breasts were sore. When her menstrual period was a week overdue, she bought a home pregnancy test kit. The next morning, she placed a few drops of her urine onto an applicator stick, then spent five very nervous minutes pacing. Finally, a blue spot appeared on the applicator. She broke into a broad grin — she was pregnant!

A generation ago, when the young woman's mother suspected she was pregnant, confirming her suspicions wasn't as easy. After two missed menstrual periods, the doctor sent a sample of her urine to a lab, where it was injected into a female rabbit. The rabbit was killed, and its ovaries examined. If they were swollen, it meant the urine contained human chorionic gonadotropin (HCG) — the very same hormone indicating pregnancy that today is detected in minutes, and weeks earlier, with a home pregnancy test kit.

A pregnancy test kit is one of the most familiar medical devices made possible by biotechnology — the use of biochemicals, cells, or other components of living organisms to make or modify products. Not only has biotechnology replaced the use of animals in some medical tests, but it now routinely diagnoses a variety of illnesses faster and more accurately than standard laboratory procedures.

In a home pregnancy test kit, a protein called a monoclonal antibody (MAb) binds to HCG, causing a color change. HCG is present in a woman's urine only during pregnancy. MAb test kits are the most common type of biotech device regulated by FDA. The agency has cleared for marketing more than 635 biotech devices, a growing subdivision of the broader area of medical devices.

"A medical device is any health-care product that does not achieve its primary purpose by chemical action in or on the body or by being metabolized [altered to a different chemical]," says Kiki Hellman, Ph.D., senior scientist and manager of the biotechnology program at the Center for Devices and Radiological Health. MAb-based devices are used in vitro (in laboratory glassware) to detect infections, hormone levels, drug levels (therapeutic and "recreational"), and cancer cells.

A second major type of biotech device uses a DNA probe, which diagnoses infectious or genetic diseases by detecting specific sequences of DNA (deoxyribonucleic acid), the biochemical components of genes. Other biotech devices include new drug delivery systems, replacement cells and tissues that combine natural and synthetic components, and biosensors (devices that detect a biochemical reaction and convert it into an electronic signal). Biotech devices are used in hospital and private labs, physicians' offices, and in consumers' homes.

Biotech-based diagnostic devices are often more direct than their conventional counterparts. Monoclonal antibodies and DNA probes rapidly recognize proteins or genes distinct to a particular disease-causing microbe or virus. These techniques are also able to spot an errant biochemical that makes up a very small part of a specimen (such as blood or urine).

"Biotechnology has provided significant improvement in the specificity and reproducibility of diagnostic tests," says Hellman.

Biotechnology offers different approaches to a single problem. Consider detecting the human immunodeficiency virus (HIV). The most widely used test detects antibodies that a person's immune system manufactures in response to encountering HIV. If that test (using a technique called enzyme-linked immunosorbent assay, or ELISA) is positive, the result is confirmed with a Western blot test, which detects a protein unique to HIV.

Still other HIV tests using biotechnology are experimental. These include growing the virus; finding other HIV-specific proteins; and using various gene amplification techniques to make enough copies of HIV's genetic material in a body fluid sample to detect it. And a biosensor HIV test is being developed that couples binding of a person's antibodies against HIV to a change in capacitance (the ability to store charge) of an electrical system.

The aim of these experimental HIV tests is to be more precise and to do this by directly detecting part of HIV. (In contrast, antibody-based tests detect the body's response to HIV, which can appear six weeks to a year after infection.)

Four areas where biotech devices are having an exciting impact are biomaterials, biosensors, monoclonal antibodies, and DNA probes.

New Materials

Developing replacement body parts has long been a goal of medicine, but one surrounded by steep obstacles. Donor organs and tissues are exceedingly scarce, and even when they are available and transplanted, the recipient must take immunosuppressant drugs such as cyclosporin for life. Yet a synthetic implant can be toxic or walled off by scar tissue.

"Many of the synthetic materials now used pose all sorts of problems, such as toxicity and bioincompatability, so there is a push to use more natural derivatives or biotech-derived materials," says Hellman.

For example, elastin is a naturally occurring connective tissue protein that is useful in surgery. When applied as a foam, powder or sheet, the biocompatible protein prevents scar tissue adhesions from forming at the sites of surgery.

Where does elastin come from? Synthesizing it chemically is time-consuming and costly, yet obtaining elastin, or any biomolecule, from cadavers introduces the risk of infection. Enter recombinant DNA technology. Bacteria given human genes encoding elastin produce pure, plentiful amounts of the valuable protein.

New products resulting from recombinant DNA technology are proteins or peptides (pieces of proteins), because these are the types of molecules that genes instruct a cell to manufacture. These drugs and biologics include insulin (to control diabetes), human growth hormone (to treat some forms of dwarfism), the immune system biochemicals interferon and interleukin (used to treat some cancers), and erythropoietin (to treat severe anemia in kidney transplant recipients).

Protein products require special delivery systems to enable them to circumvent biochemicals that dismantle them along the digestive tract, such as stomach acid and protein-digesting enzymes in the small intestine. Several biotechnology companies are developing biomaterials to surround these drugs so that they can reach their sites of action.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.