Scaling postbiotic production is challenging but necessary as demand grows. Postbiotics, derived from microorganisms, offer health benefits like boosting immunity, reducing inflammation, and supporting gut health. However, moving from small-scale to large-scale production requires meticulous planning to ensure quality, consistency, and safety while adhering to strict regulations. Here's a quick overview of the key points:
- Postbiotics Defined: Non-living byproducts of microorganisms, including enzymes, acids, and vitamins, that help with gut health and immunity.
- Production Steps: Start with fermentation using selected bacterial strains, monitor factors like pH and temperature, and carefully process to retain beneficial compounds.
- Challenges: Maintaining batch consistency, preventing contamination, ensuring stability, and scaling up processes without compromising quality.
- Regulations: U.S. FDA requires compliance with DSHEA, cGMP, and FSMA standards, alongside rigorous testing for safety, purity, and stability.
- Solutions: Advanced tools, automated systems, and detailed quality checks (e.g., 50+ checkpoints) help manufacturers meet demand without sacrificing product integrity.
Scaling safely requires precise controls, thorough testing, and adherence to regulations. Companies like Begin Rebirth demonstrate how innovation and strict protocols can ensure high-quality production at scale.
What Are Postbiotics and How They Help Us
Postbiotics: What They Are and What Types We Have
Postbiotics are small parts made when good germs break down food in your gut. They also form after these germs are killed. Unlike probiotics (live bugs) and prebiotics (food for those bugs), postbiotics are things made by bugs as they do their job in your gut.
There are many kinds of postbiotics, with each one giving help in its own way. Short-chain fats, like butyrate, propionate, and acetate, are made when tiny gut bugs break down some fibers, like inulin. These fats help keep your gut working well. Exopolysaccharides (EPS), made by lactic acid bugs, help make some foods last longer and have other health uses. Organic acids, like acetic and lactic acid, make your gut sourer and slow the growth of bad bugs. Some proteins on bug surfaces, like those from Enterococcus faecium, may help stop cell death and help your body's defenses.
Because there are many kinds of postbiotics, makers can pick which bug strains and how to make them for the best use. Each type works in its own way, so knowing what each does helps make better products for health.
How Postbiotics Help Your Body
Postbiotics help your body in many ways. For one, short-chain fats give food to gut cells, help make needed things, and keep the gut wall strong. These parts also help good bugs grow and make your gut better for you.
Studies show postbiotics can help your body fight germs and calm it down. Some work by helping certain cells in your body live longer and grow well. For instance, bits from Bifidobacterium breve help key cells grow and stay strong, raising levels of things that stop swelling, like IL-10, and lowering things that cause swelling, like TNF-α. This can help those with allergies or swelling issues.
Postbiotics may also protect against sickness from some viruses. In a study from 2025, proteins from Bifidobacterium adolescentis, grown in a lab, were tested against rotavirus. The study showed these postbiotics cut the virus’s power and kept gut cells safe. The test also found these postbiotics are safe at many doses for both kidney and gut cells.
All this shows postbiotics work in lots of ways, from making your gut wall strong, to helping keep your body's defenses good. By picking bugs that make the right postbiotics, makers can make their health products work better.
Picking Good Bug Strains and Making Quality Postbiotics
Getting good bug strains matters a lot when making postbiotic products. Different kinds of bugs, and even bugs of the same type, make different postbiotics. Each kind helps your body in its own way. Strains taken from people, called Human Origin Strains, are often best because they are made to help our bodies most.
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For example, Bifidobacterium adolescentis is known for making postbiotics with a lot of protein, which can help fight off viruses and keep cells safe. But, these helpful things may change a lot when you look at other kinds of Bifidobacterium. This means that makers need to look very close at each kind. They must study each one to know what postbiotics they make, how well they make them, and how those things work in the body, all before they make much more of it.
New ways to give postbiotics help make them last longer and make sure that the body can use them better. This helps keep the good effects in the product all through its life on the shelf. Picking the right kind and using these new ways together helps the product do what it is meant to do for your health.
Webinar 1: 5 steps into the Scale-Up of Microbial Fermentation Processes
Ways to Make Postbiotics
Making postbiotics for lots of people is a huge task. You must be careful with each step to make sure what you make is safe, works well, and turns out the same each time. The way you make postbiotics can change how strong they are, and how smooth the work goes in the factory. It is important to do things the right way but also to listen to the rules for safety.
Ways to Make Postbiotics
Making postbiotics starts with letting tiny germs grow. This is called fermentation, a way people have used for a long time, but now it is even better because of new tools. First, you pick the best germs, like Lactobacillus plantarum or several kinds of Bifidobacterium and other germs such as Lactococcus, Leuconostoc, Streptococcus, and Pediococcus. You let them grow in special tanks where you can control what goes on inside.
As they grow, these germs eat special foods called prebiotics, like fructooligosaccharides and inulin. They change prebiotics into good things for your gut called postbiotics, like short-chain fatty acids. These kinds of acids - propionate, acetate, and butyrate - help the gut and give fuel to the cells in your colon.
Now, makers use new ways like mixing in enzymes or trying out synthetic methods. These new ways help them decide better what kind and how much postbiotics they get. Some choose smart ways to change the germs so they make more of the postbiotic they want. In one case, workers at a big school - the Pontificia Universidad Javeriana - grew Bifidobacterium adolescentis in a small tank. They made the postbiotic safer and stronger so it could help the gut and help fight viruses [4].
To make lots of postbiotics in big places, you must keep tight control over each step so what you make at big scale is just as good as in small labs.
Watching Every Step
To get good postbiotics, you need to watch each step and keep things right. You must keep check on things like how warm it is, how sour or basic (pH) things are, how much air is in the tank, and what food the germs eat. These things change how much postbiotic comes out and how good it is.
One important thing is to keep the pH at the best level. This can help make acids like acetic and lactic acid, which help the work of postbiotics and stop bad germs from growing.
Begin Rebirth, a big maker, is careful in every step. They check pH, temperature, and many other things - 28 things in all - to get the best results. Their tanks do not use meat or milk, so they can keep the food mix just right for the germs. Begin Rebirth RE-1™ says:
"We optimize our biofermentation for pH, temperature, and 28 other critical growth factors." (Begin Rebirth RE-1™ [1])
"Our mediums contain no meat or dairy." (Begin Rebirth RE-1™ [1])
When you move from small lab tanks to big ones, you face new problems. You have to control heat, air, and how things blend. Giving the right amount of air is key, since bacteria need enough oxygen to grow well, and different types want different levels. Keeping the right temperature is also very important. It helps bacteria work the same way in each batch and keeps the product good.
After you know the best way to run your system, the next thing to do is to stop the bacteria safely but keep the good stuff inside them.
How to Stop and Get the Good Parts
When the process is done, you must stop the germs so the mix is safe but make sure the healthy bits are still there. Two main ways to do this are heating and using special helpers called enzymes.
Using heat is a sure way to kill the germs and lower the chance of bad stuff getting in. But you must pick the right heat and time so you do not ruin things the body needs, like proteins. Most times, the heat used is from 140 to 212 degrees F for about half an hour to one hour.
Enzymes can also help take out useful parts, which works well for mixes full of protein from Bifidobacterium adolescentis. This way lets you keep things like viral-fighting and cell-protecting pieces, which can break down if you use too much heat. The way you stop the germs or pull out good stuff depends on what you want - could be sugars, acids, or surface proteins. Each needs a special way.
To check if these ways work, people who make these mixes do tests. They can use cells called MA104, or C2BBe1 cells, to make sure the mix is both safe and still has its good parts. When selling these mixes, lots of checks for how steady and strong they are are done. All of these steps must be written down and shared to follow FDA rules and to stay within the law.
Problems When Making More Postbiotics
It is hard to go from small lab work to big plant work. Each step brings new problems. Things that work fine in the lab may need big changes to work well in a bigger space. Let’s look closer at the main problems you may see when making more.
Same Quality Each Time and Getting Good Results
One big problem is keeping each batch the same. In the lab, you watch every small batch. You can change what you do and fix things fast. But when you make a lot, even small changes make big problems in how much you get and how good it is.
For instance, bacteria do not act the same in big tanks as in small ones. Things like heat spread, how well things mix, and air levels all change in big tanks, and this can change what you end up with. Also, when you buy materials in big lots, changes in what is inside - like the food for the bacteria - show up more and can hurt how much you get if you do not watch closely.
What works in small tanks may not work the same in big tanks. Things like heat and how sour the mix is - easy to check in small tanks - can change in bigger ones. If it takes too long for things to look and feel the same everywhere in the tank, the bacteria may not grow right, and you may not get the same results.
Making Sure It Lasts and Stays Good
To make sure postbiotics stay good and work well is more tricky when you make more. Small batches may stay good, but bigger batches can show new problems because things like how you make and keep them are not the same.
Getting other stuff in the mix is a big risk. In the lab, it is easy to clean tools and spot problems. But in a big plant, there are many places where bad things can get in. Even a small slip can ruin all you made. To try and stop this, makers must follow strict rules, use steps that keep things clean, check things often, and write down all they do to lower risks.
Testing if postbiotics stay good is more work when you make a lot. You have to check them in many ways and for longer times. Changes in heat, what you put them in, and how you move them can all make them less strong. As you make more, you need better ways to check for problems and fix them fast, so you also need better tools to find issues in a short time.
Picking Gear and Making More at Once
The gear you use matters a lot when you try to make more. How you build big tanks has a big part in making sure you still get good batches like before. Moving from small lab tanks to big plant tanks brings many new problems.
For example, mixing in big tanks can make zones where bacteria do not get enough food or air, and this can make less postbiotic. Some people at a group called Pontificia Universidad Javeriana saw these problems while using Bifidobacterium adolescentis in a small tank. They set up things just right to make postbiotics that fight viruses, but when they moved up to bigger tanks, mixing, air, and heat all became harder to control and brought new problems they had to solve [4].
Moving heat is also a problem. Small tanks change heat fast, but big ones take much more time to get hot or cold. This can hurt how bugs grow. Cleaning is harder too when things get big. You need smart machines to clean big gear right, so no mix-up or germs get in.
Machines that run by themselves help a lot when you make things in huge amounts. Smart tools can watch key things all the time, like pH, heat, and air. This means people do not have to check as much. It keeps things steady and helps make sure each big batch stays just as good as the last one.
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Safety Steps and Rules You Must Follow
When you make more postbiotics, you must take care and follow all the main safety steps and rules. In the U.S., the rules are not the same as in small labs. There are many rules, and you must know them all as you move from small work to big work in a plant.
U.S. Rules and What You Must Do
If you make or sell postbiotics in the U.S., the FDA is in charge. When postbiotics go in pills or are added to food, you must follow laws like DSHEA. This law says you must keep your product safe and prove what it does. If you put postbiotics in food, you need to prove they are safe to eat by getting GRAS OK from the FDA or from a group of experts. You must also follow cGMP and FSMA rules. These rules talk about your work place, tools, and how your team learns the job and checks on outside vendors.
Postbiotics are not the same as probiotics. Probiotics have live germs. Postbiotics do not. They are made from dead germs or bits of germs. This makes checking them hard, as you must make sure of what they are made of, if they stay safe to use, and that no live germs are left. To meet all the rules, you must use strong steps to check quality.
How To Test and Check Quality
To keep postbiotics safe, you need to run tests and check your work. Some key steps are:
- Endotoxin Test: Use the LAL test to make sure there are not too many toxins - keep it below 175 EU for each use.
- Allergen Check: Use ELISA or other tests to make sure your product does not have things that can cause harm if people are allergic.
- Germ Test: Check your postbiotics so they do not have bad germs like Salmonella, E. coli, Listeria, or bad mold and yeast.
- Keep It Stable Test: Test postbiotics by putting them in hot and wet spots (about 104°F and 75% air wetness for 6 months) and in a normal spot (about 77°F and 60% air wetness for up to 3 years). This is done to see how long they last and if they go bad, as said in ICH rules.
- Chemical Check: Use ways like HPLC or GC-MS to look at the key parts like short fatty acids. You must also make sure there are no bad metals or unsafe farm sprays, as FDA asks.
By doing all these, you help to make sure your postbiotics are safe for all.
In a 2025 study, postbiotics derived from Bifidobacterium adolescentis were tested for cytotoxicity and found safe across various concentrations, supporting their use in food and supplements. [4]
Extra safety checks, like tests with gut cells called Caco-2, help show that postbiotics do not harm people’s cells.
After checks for quality are done, keeping good notes can help trace each batch and make it easy to fix safety issues fast.
Keeping Records and Tracking Batches
Good notes matter for rule-following and for getting recalled products back quick. Makers should keep full notes for each batch made. These notes need to have:
- What raw stuff was used
- Steps for growing (heat, acid, air)
- Ways to stop germs
- How things were taken out and cleaned
- Test results for quality and safety
Checking the makers of stuff is also key. Sellers must meet strict rules and give papers that show their tests. Each batch must have notes on the type of germ used, its key numbers, and any changes made to it.
Using computer tools like chains of data or batch tracking systems makes it easy to track each batch. These help find batches fast if something goes wrong and a safety problem comes up.
In March 2025, a U.S. postbiotic supplement manufacturer implemented automated batch record management and digital traceability systems. This initiative, led by Quality Assurance Director Emily Carter, reduced recall response times by 30% and ensured compliance with FSMA and cGMP audits. The company also reported zero regulatory violations and an increase in customer trust. [3]
Clean ways to wash things, which are checked often, are a must when making more than one type of postbiotic in one place. You need to keep notes and keep them for two years past the last day the product is good, or longer if the law says so. Every year, you should act out a recall to see if it works right. If things do not go as planned, write down what went wrong, find out why, and fix it, so all is safe and good.
Begin Rebirth RE‑1™ is a good case of these strict rules. It has more than 50 steps to check for quality and care, so you know where each piece came from and that the product is pure.
"We do extensive lot-to-lot testing at each step and on the final product. With 50+ QA/QC checkpoints, we monitor purity and strength under both US and EU protocols, including GMP + HACCP."
- Begin Rebirth RE‑1™ website
This careful way of tracking and writing things down helps meet rules. It also lets makers fix safety issues fast and well.
Case Study: Begin Rebirth RE-1™ Production Methods
Begin Rebirth RE-1™ delivers postbiotics on a large scale, with each sachet packing an impressive 500 billion CFU while maintaining both effectiveness and stability. To achieve this, the company follows strict quality protocols and utilizes cutting-edge technologies to address the challenges of scaling up postbiotic production. Let’s dive into the advanced delivery system and meticulous controls that make this high-potency manufacturing possible.
Advanced Delivery System Implementation
At the heart of Begin Rebirth RE-1™'s performance is its proprietary Lyosublime™ delivery system. By removing the need for traditional capsules, this system allows postbiotics to be absorbed more efficiently throughout the gastrointestinal tract. It also ensures the stability of the postbiotics during production, storage, and shipping, guaranteeing that every batch meets the highest quality standards.
One standout feature of this system is that it eliminates the need for refrigeration. Without the complexities of cold storage, logistics become more straightforward, significantly cutting distribution costs. This innovation not only simplifies the supply chain but also ensures that the product remains potent and effective, right up until it reaches the consumer.
High-Potency Manufacturing Considerations
Producing a serving with 500 billion CFU is no small feat. Begin Rebirth RE-1™ relies on Human Origin Strains (HOSt™), which are derived from healthy human gut microbiota. These strains are known to produce a variety of beneficial compounds. For instance, some bacteria generate acids that aid digestive health, while others support immune function [5][6].
HOSt™ strains are carefully selected to deliver targeted benefits, and their impact is monitored throughout the production process. The manufacturing process itself is guided by over 50 quality checkpoints, which track crucial factors like agitation speed, inoculum concentration, and nutrient composition. These controls have been shown to enhance bacterial growth by 84.64% compared to simpler techniques [7].
To ensure consistency and effectiveness, the final product is packaged in protective sachets. These sachets shield the postbiotics from air and moisture, so every dose delivers the intended benefits to consumers without compromise.
Conclusion: Safe Postbiotic Production at Scale
Producing postbiotics on a large scale requires a careful balance of innovation and strict adherence to regulatory standards. Success hinges on implementing strong process controls, maintaining high-quality benchmarks, and utilizing advanced delivery systems to ensure both stability and effectiveness of the final product.
One crucial aspect is ensuring consistency in production. Manufacturers achieve this by using statistical process optimization and running more than 50 QA/QC checkpoints to verify batch uniformity [1]. Comprehensive documentation and traceability systems further reinforce compliance with established manufacturing protocols [2].
Technological advancements play a big role here. Tools like CRISPR-Cas9 and metabolic engineering help optimize microbial strains for better yields and stability. When paired with automated bioreactors and precise process parameter controls, these innovations not only enhance production efficiency but also significantly lower contamination risks [2].
Safety is another critical focus. Rigorous testing protocols, including cytotoxicity assays, microbial safety checks, and accelerated stability studies, are employed to ensure product quality and safety at every stage [4].
Research underscores the impact of optimized fermentation techniques, which can increase biomass production by 84.64%. Consistent bioreactor performance has also been demonstrated, achieving 2.109 g/L biomass with a doubling time of approximately 10 hours [7].
As demand continues to grow, companies that invest in real-time analytics, detailed documentation, and adaptable processes are better positioned for sustainable success.
Ultimately, scaling postbiotic production requires treating safety and quality as absolute priorities. By blending advanced technology with rigorous regulatory compliance and precise process management, manufacturers can deliver potent, reliable products that meet consumer expectations while maintaining the highest safety standards.
FAQs
What challenges do manufacturers face when scaling postbiotic production from lab-scale to large-scale operations?
Scaling up postbiotic production from a lab environment to a full-scale facility comes with its fair share of challenges. Manufacturers need to ensure consistent product quality, strictly follow regulatory standards, and establish rigorous safety protocols to protect both the product and the consumers who rely on it.
Some of the biggest hurdles include fine-tuning production methods to handle larger volumes, sourcing top-quality raw materials, and confirming that the final product maintains its effectiveness and stability on a larger scale. On top of this, facilities must be equipped with advanced systems to monitor critical factors like temperature, humidity, and potential contamination risks throughout the production process.
With thoughtful planning and a strong focus on compliance, manufacturers can overcome these obstacles, scaling their operations while maintaining the safety and reliability of their postbiotic products.
How can manufacturers safely scale up postbiotic production while maintaining quality?
Manufacturers can maintain the safety and quality of postbiotics during large-scale production by adhering to strict regulatory guidelines and implementing thorough quality control measures. This involves sourcing premium raw materials, employing validated production methods, and conducting regular safety tests to ensure compliance with industry standards.
Additionally, investing in advanced delivery technologies, such as Lyosublime™, is essential to preserve the potency and bioavailability of postbiotics during production and distribution. By focusing on safety and regulatory standards, manufacturers can deliver top-tier postbiotics that promote gut health and overall wellness.
What are the U.S. regulations for postbiotic production, and how do they influence manufacturing?
In the United States, producing postbiotics comes with strict regulatory guidelines aimed at ensuring safety, quality, and adherence to FDA standards. Manufacturers are required to follow Current Good Manufacturing Practices (cGMP), which govern all aspects of production, from sourcing ingredients to processing and labeling.
These rules significantly influence how products are made. They demand thorough testing, detailed documentation, and robust quality control measures to guarantee that the end product is safe for consumers. Complying with these standards not only protects public health but also strengthens trust with both customers and regulatory authorities.