Probiotics As Drugs?

If FDA gets its way, probiotics and other health ingredients could be reclassified as drugs in the future.

By Douglas Kalman, PhD, MS, RD, CCRC, FACN

The regulations for dietary supplements, and their cousins, functional foods, will most likely tighten in the future for a variety of reasons: new GMPs, a new administration, negative supplement studies, etc. One area that has come into question recently is probiotics. The Center for Biological Evaluation and Research within FDA (CBER) has spoken openly about probiotics being “biological” in nature. As such, industry should start paying attention to where this road might lead in the future.

Who’s Behind CBER?

According to CBER’s website, its mission is to protect and enhance public health through the regulation of biological and related products including blood, vaccines, allergenics, tissues and cellular and gene therapies. Biologics, in contrast to drugs that are chemically synthesized, are derived from living sources (such as humans, animals and microorganisms); they are not easily identified or characterized; and many are manufactured using biotechnology. CBER believes that these products represent cutting-edge biomedical research that, in time, may offer the most effective means to treat a variety of medical illnesses and conditions that presently have few or no other treatment options.

CBER’s review of new biological products, and new indications for already approved products, requires evaluating scientific and clinical data submitted by manufacturers to determine whether the product meets CBER’s standards for approval. After a thorough assessment of the data, CBER makes a decision based on the risk-benefit for the intended population and the product’s intended use.

Finally, and perhaps most important, CBER’s authority resides in the Public Health Service Act and in specific sections of the Food Drug and Cosmetic Act. Specifically, section 912 creates the new section 301 (II) of the Federal Food, Drug and Cosmetic Act (FFDCA), banning—with certain exceptions—interstate commerce of foods to which approved drugs or licensed biologic products have been added. (For more details on section 912, see the side bar in Industry News, pgs. 18-19.)

Further, it prohibits the addition of a drug or biologic product for which “substantial clinical investigations” have been instituted and made public. These sections raise important issues for dietary supplements and functional foods, particularly probiotics.

Although medical products are required to be safe, safety does not mean zero risk—all medical products are associated with some level of risk. CBER says a safe biological product is one that has reasonable risks, given the patient’s condition, the magnitude of the benefit expected and the alternatives available. It believes the choice to use a biological product involves balancing the benefits to be gained with the potential risks.

Delving Deeper

On the CBER homepage there is no section for foods, dietary supplements, beverages or other natural products. So, how did probiotics get into this mix and what does CBER plan to do with this category?
Believe it or not, as early as 2002, CBER started to think of probiotics as biologicals. The move to regulate probiotics as drugs actually stems from something found in DSHEA: If intended for “diagnosis, cure, mitigation, treatment, or prevention of disease in man, then it is a drug and requires an IND [Investigational New Drug application].”

Several years ago, CBER began viewing this disclaimer on dietary supplements as a way to reclassify a product as a biological, and thus an undeclared drug, and have it pulled from the market—or require many different types of studies and legal consultations to keep it on the market. So why is the DSHEA disclaimer being viewed by the agency in this manner? It all comes down to claims (intended and implied).

CBER and FDA representatives have explained that marketing claims in any form by any company can trigger a response for classification or reclassification. Even companies sharing data with the agency are at risk—even mail sent to the agency for another purpose (again, not marketing material per se), which contains written statements regarding the effects of a product in humans might be considered a form of marketing.

Mostly recently, there was a case in which a food company shared data with the agency regarding in vitro studies showing the “immune enhancing” benefits of a product, along with potential cancer protection benefits. FDA took the sharing of data to be a form of marketing. As a result, it told the food manufacturer that the product was considered a biological. Remember, the agency may use a definition of “biological” as anything that demonstrates an effect in vivo (i.e., in a person, affects how agents in the blood react or are produced).

The weakness in this argument, of course, comes from the fact that all foods, or almost all foods, affect biological systems. For example, would one call fish oil a biological drug because it can decrease certain inflammatory cytokines?

CBER does state that if a probiotic is being evaluated in a clinical trial—the type that universities, hospitals and private research groups carry out—and the study is evaluating the probiotic for its effect on a condition such as diarrhea (meaning the occurrence and incidence of), then CBER can automatically classify the probiotic as a drug for which the study sponsor must file an IND application in order to carry out the study. The agency notes, however, that if the product is being evaluated for “quality of life” and NOT disease modification, then the aforementioned may not apply.

Summary

The fact that FDA and CBER are renewing interest in the classifications of certain nutrients through the Public Health Service Act should put the industry on high alert. These recent moves might be signs of greater regulations to come. And the only defense in this case will be a solid intellectual property (IP) portfolio.