Probiotic Quality Control Challenges

It is probiotics time to shine, but the spotlight on the big stage often reveals imperfectionsin this case a few quality-control challenges or issues suppliers and manufacturers need tend to in order to capitalize on the newfound popularity.

As a living organism, a probiotic is not effective if it does not remain viable upon reaching the target body site. Unfortunately, this viability is challenged throughout the entire supply-to-shelf chain. Light, heat, oxygen and moisture can all severely dampen the number of beneficial bacteria that survive shipping, processing, manufacturing, storage and final delivery.

A Probiotic Census

A basic approach is to start with way more probiotic bacteria than is ultimately needed, assuming some of these will perish before the product ends up in consumers hands. While this seems like a method prone to a large margin of error, there are things a company can do to best determine how many beneficial bacteria will survive. Mike Bush, vice president of development for Ganeden Labs, explained stability testing can help a manufacturer learn and verify viable probiotic quantities over a specified period of time. Bush noted many companies perform these tests under ideal conditions, which is fine if they detail these aspects to customers. The consumer wants to know how much is in the product when they buy and consume it, he said.

There has been some confusion in the marketplace over the labeling of bacteria quantity, with some manufacturers listing the amount of viable bacteria at time of manufacture, while others list the expected delivered amount. The viable amount of probiotics should be at the time of expiration, said Connie Falkenstein, RD, director of marketing and education for UAS Labs, noting colony-forming units per gram (CFU/g) is an industry standard probiotic manufacturers should use.

The use of CFU/g can both differentiate one product from the next and provide consumers with some sort of dosing platform, but it also provides an indication of the quality-control procedures undertaken by the manufacturer. The difference between being able to list an expected quantity of bacteria through a given date and simply labeling the amount of probiotic at time of manufacture is likely to be the amount of testing performed.

Tim Gamble, senior vice president of sales and marketing at Nutraceutix, reported another questionable labeling issue seen in the industry occasionally is the use of soil-based organisms (SBOs) or spore-forming organisms to inflate viable CFU counts. These organisms are not always considered true probiotics in academia, nor do they possess the wealth of scientific research of traditional, natural probiotics, he reasoned. Their spores do not die off as readily on the shelf and are, therefore, used to spike probiotic products, often solely to maintain organism counts when an investment has not been made in utilizing specialized probiotic manufacturing processes or delivery technologies. He noted products utilizing a blend of natural probiotics and these soil or spore organisms may test as viable, perhaps even meet label claim, but it is the spore-formers that maintain counts while most, if not all, of the natural probiotics informed consumers are seeking, have died off.

Per current federal labeling regulations, whatever is in the product must be represented on the labeling; so the issue here is companies not listing SBOs and spores, yet using them to boost general viable CFU counts in a formula for, say, lactic acid probiotics. This is similar to spiking issues that have surfaced in other parts of the nutraceutical industry, namely herbal products, although the extent to which this is a problem in the probiotics market is not clear.

Most companies comply with the label requirements, assured S.K. Dash, Ph.D., founder of UAS Labs, who confirmed labeling requirements have been dictated by FDA, FTC and other agencies.

What is clear is the top-quality companies test their probiotics at many stages, both internally and via independent labs. For instance, blessed with its own microbiology lab, NOW Foods tests incoming probiotic material to verify the suppliers certificate of analysis (CofA), in addition to testing at each stage of manufacturing to see how many bacteria are lost due to various processing steps. Combined with its own real-time stability testing, NOW Foods learns how much bacteria must be put in the product initially and what will be left over by a specified date. The company also makes use of suppliers stability data on specific strains.

The counting of and accounting for viable probiotics is more than mere numbers. As research has moved beyond simple species-focused specificity, so too have science-based suppliers and manufacturers. As health condition research on probiotics increasingly focuses on specific strains, the support for health benefits can not responsibly be borrowed by other probiotics, even ones in the same species.

Probiotics are strain-specific, dose-specific and condition-specific, so it is very important to state not only the genus and species but also the strain, Dash advised, adding UAS designates the L. acidophilus DDS-1 strain of on its probioticsNebraska Cultures founder Khem Shanani, Ph.D., named this strain for the Department of Dairy Science (DDS).

Manufacturers absolutely must list the strain, Bush concurred, noting similarly his company conducts research specifically on its Bacillius coagulans GBI30 strain.

There are no federal label requirements on this strain issue, so the industry has leaned on guidelines published by the World Health Organization (WHO) back in 2002. In addition to stating research suggests beneficial effects are strain-specific, WHO concluded: Speciation of the bacteria must be established using the most current, valid methodologya combination of phenotype and genetic tests. Additionally, the WHO guidelines on probiotics for food use include a flowchart of recommended research and analysis to determine function, efficacy and safety. It also provides details on each of these recommended steps, including full labeling guidelines that suggest listing genus; species; strain; minimum viable quantities of each strain at the end of shelf-life; effective dose linked to the benefit claim based on research; proper storage conditions; and a contact for consumer information.

While FDA and FTC have general supplement and food labeling regulations that oversee the probiotics market, the lack of federal guidelines addressing these probiotic-specific labeling concerns has left the industry in a state of self-policing.

However, this is no Wild West. The International Probiotics Association (IPA) was created to bridge academia and industry in a common pursuit towards breakthrough research, technology and product development. IPAs second World Congress, held in mid-April 2010, planned to tackle these quality-control issues, tied to the ongoing effort to come up with good labeling practices and methods (a seal, perhaps?)  to show how the industry and responsible manufacturers are following the highest quality control standards for probiotics.

IPA has released its own guidelines on probiotic labeling, echoing WHOs advice on guaranteed CFU minimums at time of expiration, ideal storage conditions and contact information. But IPA elaborated on the need for probiotic identity, proposing strain listing as the preferred standard, but accepting a minimum of genus and species based on widely accepted nomenclature. If a trademarked name is used to identify the bacteria, the actual genus and species should also be included on the label, IPA stressed. This information gives consumers the knowledge and chance to research the strains. Additionally, IPA suggested labels include directions for suggested usageanimal probiotic supplements should include target animal speciesand the lot number or production code should be on every package.

Another industry-driven group, the International Scientific Association for Probiotics and Prebiotics (ISAPP), is also focused on high-quality research and product development and has worked to establish labeling and marketing standards. In 2005, the group met with the US Pharmacopeia (USP) to discuss developing such standards. The summary generated from these talks noted at the time, there were at least 14 peer-reviewed publications showing many commercially available probiotics did not meet label claim. While ISAPP called some of the test methods used in these evaluations questionable, it recognized there was an issue with meeting label claims, responsible formulation and labeling of probiotic products. In addition to the viability, nomenclature and scientific substantiation of efficacy concerns mirrored in WHO and IPA guidelines, ISAPP also noted the term probiotic was sometimes used on labels for products that had no established record of health benefit in humans.

This tied back to the long-standing WHO definition of probioticslive microorganisms which when administered in adequate amounts confer a health benefit on the hostwhich ISAPP said had long been prone to misinterpretation and misuse. ISAPP enhanced this definition to exclude the use of bacterial byproducts, dead bacteria in the scientific arena, as well as the use of the term probiotics in products that have no substantiated health benefits in humans.

Getting Everyone on Board

No matter how controlled a supplier or manufacturers processes and protocols are, the sensitive cargo of probiotic inventory passes through the hands of retailers and, possibly, distributors before then. How these products are stored and handled can be a buzzer-beater in either a good or bad way.

Falkenstein stressed the importance of understanding the source of the probiotics and how the products are handled. For distributors, this means being intimately knowledgeable about the manufacturer, she said. For stores, they must understand the warehousing and shipping policies of the distributors; and for consumers, they must understand the sources of the probiotics and should ask these questions when not buying from a store but on the Internet. She noted supply chain members should know also how to handle probiotics.

In recent ConsumerLab.com testing on probiotic finished products, a number of products were found to contain less than the labeled quantities of probiotics (substantially less, in some cases), and there were confusing inconsistencies in the use of at time of manufacture versus at time of expiration. In subsequent updates to the testing results, ConsumerLab.com reported several manufacturers of products that failed the label claim testing emphatically asserted their labeling was correct and the products used in testing likely had been mishandled and/or were stored in less-than-ideal conditions. In one instance, the manufacturer noted one retailer who supplied test product ships it via non-refrigerated service, which likely led to the substandard results. Many questions about ConsumerLab.coms methods and motives abound, but the testing seemed to showcase the issues of handling and storage of probiotics. Consequently, the contamination analysis performed by the site showed all products were free from those QC failures, as all passed. What was less clear was their analysis of proper delivery of probiotic payload to the intestines.

Special Delivery

The issue of delivery is an area where committed companies have spent tons of resources developing new methods and technologies. Gamble quipped, With probiotic products, its all about delivery: delivery of the proper strains by the producer; delivery of live, viable organisms at the time of retail purchas;, and delivery of live organisms to the body. If all of those things happen, then labeling becomes easier and more accurate for the quality conscious brand.

A companion to the companys shelf-life-extending technology, its patented delivery technology ensures a significantly higher percentage of organisms survive passage through the stomach to reach and colonize the intestinal tract. Other companies such as NOW Foods and UAS Labs utilize freeze-drying technology to render the probiotics temporarily inert until they are reactivated in the moisture of the digestive system. Another technology used to enhance delivery is microencapsulation, as used by Institut Rosell.

Then there is B. coagulans, which relies on its natural advantage of spore-forming protection. Inside the bacterial cell is a germ or seed that is safe from heat and pressure during manufacturing. Once germinated in the gut, this gram-positive bacterium produces lactic acid probiotic bacteria. Debate might persist on whether this spore is rightfully classified as a probiotic, since it produces probiotic in the gut, but Bush said Ganeden has clinical trials on its product showing digestive and immune benefits linked to the probiotic produced.

QC issues in the probiotic market, which appear to center on labeling and viability, might not pose the dangers that issues like the contamination and adulteration that bedevil some other product markets, but with the star status of probiotics in the mainstream and increased regulatory attention (at least in the area of health claims), it is important for consumers to know they are getting efficacious probiotic products for digestive health, immune function or other health benefits. This segments progress on self-regulation methods, coupled with the greater responsibility (including testing) newly effective GMPs (good manufacturing practices) demand, should go a long way in deciding whether probiotics capture a large audience long term or if they risk losing consumer confidence.