The set of guidelines titled “Demonstrating the Quality of Listed Probiotic Medicines”, published by regulator the Therapeutic Goods Administration (TGA) last week, is meant to help probiotics manufacturers and sponsors meet technical, scientific and regulatory requirements.
This will ensure that the quality of their probiotic medicine is acceptable under the Therapeutic Goods Act 1989 (the Act).
For example, the guidelines seek to help manufacturers ensure that the amount of probiotics that they claim to be present in the product would stay “live” and “viable” till the end of the products' shelf-life.
While not mandatory, the guidelines can help manufacturers understand the criteria that the regulator looks for during a compliance review.
According to industry body Complementary Medicines Australia (CMA), the guidelines have provided greater clarity. The CMA, alongside the International Probiotics Association (IPA), was involved in the probiotics technical guidelines with the TGA.
One of the clarifications, the CMA said, was that the Quantification by Input (QBI) method can be used for products containing multiple probiotic strains.
The TGA said in the document that “depending on the circumstance, QBI with an evidence-based justification and/or an assay at genus level may be sufficient to demonstrate that the quantity of a strain has been adequately controlled."
The QBI method is especially useful when it comes to testing the quantity of probiotic strains that are genetically identical.
Strains from the Bifidobacterium lactis species are the classic examples in this case, Craig Silbery, founder and CEO of Specialty Probiotics Australia, also the founder and former CEO of Life-Space told NutraIngredients-Asia.
Silbery pointed out that there tests have shown that commercially available Bifidobacterium lactis probiotic strains could be 99.7 per cent identical.
While polymerase chain reaction (PCR) can test and quantify probiotics at the strain level, this is a highly expensive method which can cost tens of thousands.
In contrast, the QBI method will be more affordable for smaller size firms as well.
“Let’s say you’ve got a 15 strains probiotic blend. You can get that tested for each individual strains, but you would need to send that to the USA for a PCR test.
“It’s an exhaustive test and might cost you $40k or $50k. That’s very different to the new guidelines which says that that if there is justification for the QBI method, i.e. if some strains are difficult to test for, then you can use QBI and that may be a $2k test,” he said.
The lower testing costs also mean that smaller brands are more willing to send their products for quantification tests.
Another benefit is that this can encourage new players to enter the sector as well.
“At the end of the day, if you’re pushing these $50k test costs onto a small brand, there won’t be any new brands in Australia because they couldn’t afford to take on that cost.”
With the guidelines providing greater clarity, he believes that this could eliminate “grey areas” and the room for companies to conduct different types of practices.
This can also reduce the chance for companies in releasing products that could be potentially inferior.
“Without that clarity and when there’s grey areas, there may be some companies that are doing things differently for their own reasons.
“With the new guidelines, it is very clear on what the industry needs to do, and that is a good thing for the complementary medicines industry in Australia.”
Still, he believes that the onus is on the brands, the product manufacturers and sponsors in ensuring that they use the QBI method wisely.
“Using the QBI method doesn’t mean that you can put whatever you want into it. It means you have to work with credible suppliers who have stability data in the particular application that you are putting your formulation into.”
Commenting on the new guidelines, the CMA said that the guidelines also showed that TGA’s recognition of the current limitations on the availability of sophisticated methods of analysis in Australia, and its acceptance of methods such as plate count for strain identification and enumeration.
What would the future look like?
In the future, Silbery believes that sophisticated methods would be available for use at a lower cost.
Flow cytometry is one of these methods and is “highly” precise and accurate as compared to testing conducted by humans - where the error rate could hit 30 per cent.
“The future I see is where there are new technologies will be available from the industry, and those new technologies would have been validated, and the TGA would accept the validation.
“Because at the moment, testing is still done by a human as an example, and the actual Lactobacillus testing for the human has a very high error rate. It can be plus or minus 30 per cent, and 30 per cent error rate is quite high in any sort of analytical field.
“And so I do believe that in the future, there will be computers and systems and AI that will be doing the tests to reduce the error rate very very significantly,” he said.
Aside from identifying live organisms, flow cytometry can also identify damaged and dead organisms present in a product.
Such data also provides indications on where a product is at in its life cycle.
He added that his company would be incorporating such technologies in its production processes for their customers' benefit.
“It’s not a requirement by the TGA, but I believe these sorts of technologies will be adopted in the future that will improve the reliability by reducing the error rate that humans looking in a microscope will make when they conduct these tests.”
A paper published in BMC Microbiology in 2023 reported that using flow cytometry has resulted in the detection of higher numbers of viable bacteria, and with a greater level of repeatability than plate counting.
However, when certain probiotic mixtures contained preparations with high numbers of non-viable cells in their total population, flow cytometry had the potential for overestimation of the viable population.
The research compared the use of flow cytometry and plate counting to number mixed populations of probiotic bacteria, including L. acidophilus, L. paracasei, L. plantarum, L. salivarius, B. lactis and B. bifidum.
