Safer and More Effective Drugs, Food : Part 2

by Food and Drug Administration (FDA)

(Page 2 of 2)

The FDA's Role

Why is the FDA interested in encouraging the applications for approval of these new technologies? There are many reasons. The most important one, in my opinion, is bridging the data gaps that exist in preclinical and clinical studies used to assess the efficacy and safety of products regulated by the FDA.

Pharmaceutical companies develop drugs to alleviate or prevent human diseases. The process of drug discovery and approval includes identifying a chemical that targets a specific cellular molecule associated with a particular disease and assessing the safety and efficacy of the proposed drug.

The safety of these proposed compounds usually is evaluated initially in preclinical studies done in rats, mice, dogs, and sometimes monkeys. If these studies don't reveal unacceptable toxicity, safety and efficacy are evaluated in humans in clinical studies.

In many instances, the human studies are not large enough to identify a rare toxic or adverse event that a drug may induce in a small subset of susceptible individuals. To identify these events generally requires prescriptions of millions of doses of a drug. Scientists in the pharmaceutical industry and the FDA are interested in predicting these adverse events prior to the approval and marketing of a drug, thus the intense interest in determining the value of these new technologies in preclinical and clinical studies. The great value of these new tools is their application in the assessment of the safety of a product in non-human model systems and in the human. Such assessments result in the development of more relevant data used to identify the potential toxicity of a drug prior to prescribing it to many individuals.

Another reason the FDA is interested in these technologies is that they will be used not only in the discovery phase of potential products, but also in the safety evaluation phase of development and submission to the FDA. So, it is important for agency employees to become experts in understanding the value of these tools to avoid becoming a barrier to medical product development.

It benefits the FDA and the public to be actively involved in the development, standardization, and validation of these new technologies. One example of the FDA's role as a facilitator is the recent publication of a Pharmacogenomic Guideline for submission of data generated using these technologies to the FDA.

These technologies have great merit because they can be used to assess potential adverse events in patients and in animal model systems that are used to mimic the human. If a chemical or drug induces an adverse biological response, such as cancer, there are usually early indicators of this response or markers we call biomarkers that predict an adverse response. A biomarker that most people are familiar with is the metabolite called cholesterol. Scientists have shown that a certain quantity of cholesterol in the blood indicates an increased probability that the person with this level of cholesterol will have an increased risk of developing heart disease. To reduce the possibility of an adverse heart disease, drugs have been developed to reduce the amount of cholesterol and consequently reduce the risk of heart disease.

The scientific community, especially toxicologists, search for biomarkers of toxicity, cancer, reproductive problems, behavioral deficits, and other problems in an effort to prevent their occurrence.

Although I have concentrated on the use of these technologies in evaluating the safety of human drugs, they are applicable to understanding the safety of other FDA-regulated products such as medical devices, animal drugs, and biologics. Additionally, they are tailor-made for understanding the nutritional components in food and the safety of food additives, food contaminants, and dietary supplements.

The articles in this special issue of FDA Consumer expand upon some of the concepts described in this overview and explain the value of these new technologies and tools in helping the FDA to protect and promote the public health.

Genetics 101

Each person has a unique set of chemical blueprints that determine how his or her body looks and functions. These blueprints are contained in their own deoxyribonucleic acid, or DNA, which is made up of two twisting sequences or single strands that are able to be paired with another.

Each single-stranded DNA fragment is made up of four different coding molecules, or base pairs, called nucleotides: adenine (A), thymine (T), guanine (G), and cytosine (C) that are linked end to end. Each base on the opposite strand specifically pairs with, or is the complement of, the other: an A always pairs with a T, and a C always pairs with a G. A DNA molecule with the sequence A-T-T-G-C, for example, will stick to or complement another with the sequence T-A-A-C-G to form a double-stranded DNA. This sequence, or the order of these pairs, spells out the exact instructions for creating an organism, such as the human genome, with its own unique traits, or genetic code.

Specific segments of DNA that contain the instructions for making specific body proteins, such as those that determine the physical features of blue eyes or curly hair, are called genes. Other DNA segments provide the instructions for the body to produce important chemicals called enzymes that help to direct and control the chemical reactions that occur within the body. Depending on the codes of a specific gene, even a small error within the DNA structure sometimes can mean serious problems for the entire body. An error in just one gene can even result in a shortened life.

Genes are found in specific segments along the length of human DNA, neatly packaged within structures called chromosomes. Each chromosome consists of one piece of DNA about 4 centimeters long. Every human cell contains 46 chromosomes, arranged in 23 pairs, with one member of each pair inherited from each parent. These 46 chromosomes replicate again and again to pass on the same genetic information to each new cell as it develops.

According to the National Human Genome Research Institute (NHGRI), the DNA sequence of any two people is 99.9 percent identical. Slight variations in people's DNA sequences can have a major impact on whether or not they develop a disease and on their responses to such environmental factors as infectious microbes, toxins, and drugs. One of the most common types of sequence variations occurs in single nucleotide polymorphisms (SNPs), which are sites in the human genome where individuals differ in their DNA sequence.

Scientists now believe that all diseases have a genetic component, whether inherited or resulting from the body's response to environmental stresses like viruses or toxins. A genetic disorder is a disease caused by an unusual form, or "variation," of a gene. Other terms for problem genes include "mutation" and "alteration."

Genetic disorders can be passed on to family members who inherit abnormal genes. A small number of rare disorders are caused by a mistake in a single gene. But most disorders involving genetic factors — such as heart disease and many types of cancers — arise from multiple genetic changes and influences in the environment.

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.