In many parts of the world, probiotics are subject to different manufacturing and quality control standards than pharmaceuticals. Could these different standards have any implications for patient health?

Mary Ellen Sanders and colleagues recently wrote a commentary in the Journal of the American Pharmacists Association on probiotic use in at-risk populations. In the paper, they explained that health care providers recommend probiotics to individuals in cases where the evidence is convincing for a certain indication, and sometimes these patients belong to an at-risk group. The authors addressed the concept of quality standards for manufacturing probiotic products and highlighted special considerations for those who may be at risk.

Below, Sanders answers some questions for GMFH editors about the important messages that health care providers—especially pharmacists—should take from the recent paper.


In this context, what does it mean for an individual to be “at risk”? What are some examples of at risk populations?

Being ‘at-risk’ could mean many things. To use one word, I would say it refers to a ‘patient’ population. People who are at the very beginnings of life or at the very end of life, or those with substantively compromised immune systems could also be considered at-risk. What we try to do in the paper is distinguish the at-risk person from the generally healthy population. We are not saying that every person who is not healthy needs to consider probiotics a liability.


What prompted this paper on probiotic use in at-risk populations?

In 2014, a premature infant was given probiotics for the purposes of preventing a very serious disease, necrotizing enterocolitis. Evidence on probiotics indicates they are effective for this use. The infant died from mucormycosis, due to an opportunistic pathogen mold. The possibility that this mold originated as an unintentional contaminant from the probiotic finished product prompted the authors to consider writing this paper. We wanted pharmacists and healthcare providers to realize that even with evidence-based use, probiotic products are often manufactured for use in generally healthy populations. Use in patient populations is, in effect, an off-label use.


What’s the difference between probiotic safety and probiotic safety associated with microbiological quality? Why did you focus on the latter in this paper?

Probiotic safety addresses whether a particular probiotic is safe for its intended use. For example, is it safe to take a high dose fungal probiotic after a liver transplant?  Much data exists about the safety of probiotics for specific intended uses, and for the purposes of this paper we assumed that healthcare providers are indeed employing probiotics for intended uses that are safe. Then we focused on microbiological contamination issues that might arise during manufacturing.


In general, what should health care providers look for when they want to recommend a high quality probiotic product?

A high quality probiotic product is produced by a company that complies with all good manufacturing standards;  carries a label that discloses the genus, species and strain designation for each probiotic strain in the product; clearly states dose and shelf-life; has established safety profile for this dose; has clinical evidence to support efficacy for the intended use.  We also believe that the company should make research citations for such data readily available to providers.


Which health care providers do you think have the biggest role to play?

I think pharmacists and healthcare providers who recommend probiotics for patients have the biggest role to play. Pharmacists, especially ones responsible for what products to stock in a hospital formulary, need to be sure that the products meet quality standards. Requesting certificates of analysis or third party verification for all stocked products is a good start.

Healthcare providers can provide specific recommendations to patients. Telling a patient that it is OK to ‘take a probiotic’ misses the fact that not all probiotics are the same and some are manufactured with greater care than others.  Also since over half of patient care occurs in primary care settings and many patients are using these products to remain healthy, primary care physicians play a large role in their proper usage.


What are the key take-home points of this paper for health care providers?

The key take-home points are:

  • Probiotics are typically not sold as drugs (none in the US) and are not required to meet drug standards.
  • Probiotics sold as supplements may meet all requirements of a supplement, but more rigorous standards may be needed to be safe for at-risk populations.
  • Third party verification of probiotic quality provides confidence that minimum standards are met. Pharmacists can request certificates of verification from the manufacturers to be clear what standards are being met.
  • If a probiotic does not undergo third party verification program, certificates of analysis should specify the standards the product has met.

Particular vulnerabilities to pathogens or opportunistic pathogens should be known for patient populations. Since probiotic finished products are not sterile, any probiotic product given to a person with a particular vulnerability should be known to not carry pathogens of concern.

All this said, numerous independent reports, including one from RAND, support the finding that for the majority of consumers, oral consumption of probiotics is very safe.



Sanders ME, Merenstein DJ, Ouwehand AC, et al. Probiotic use in at-risk populations. Journal of the American Pharmacists Association. 2016; 56(6):680-686.