Have you ever wondered what the actual steps are in the process of manufacturing custom dietary supplements and how long it will take? This article will provide you with a start-to-finish overview of the custom dietary supplement manufacturing process which, generally speaking, will take 4-6 weeks (90% other manufactures 14-18 weeks) from the date a payment is received.
Step 1: Formulation Discussions
Step 2: Raw Material Finalization
Step 3: Pricing Out the Custom Formulation
Step 4: Purchase Order Submission
Step 5: Ordering Raw Materials
Step 6: Raw Materials Arrive & Are Quarantined and Tested
Step 7: Mixing Pilot Batch
Step 8: Manufacturing Pilot Batch
Step 9: Approval Of Product
Step 10: Production Run and Testing
Step 11: Testing of Finished Products
Step 1: The Formula
It usually starts with the formula. As a brand owner, you have hopefully made sure that your dietary supplement formula is using the correct dosage of the right raw material ingredients to produce an evidence-based final product that will have efficacy, and will let you substantiate the functions or structure claims. While a well-formulated dietary supplement won’t guarantee initial sales, it will make it a lot more likely that you will get consistent repeat sales when your customers try it out the first time.
Step 2: Choosing Raw Materials
To create a well-formulated dietary supplement, you need to use evidence based ingredients to ensure product efficacy. Ingredients can be chosen worldwide on the basis of quality, and eyeing forms that have high bioavailability and proper potency.
For instance, lots of mineral supplements usually include well-absorbed mineral salts that are bonded to organic acids, including picolinates, citrates, and gluconates. Similarly, formulas featuring herbal extracts might include standardized extracts containing guaranteed amounts of the natural marker or active compounds within the herbs.
Timeline: Formulating the product and choosing the raw materials are part of the same process. The timeline for this will differ greatly from product to product. It could take anywhere from a few days to a few weeks or even months. In any case, the raw material selection and the original formulation are not counted as part of the production process.
Step 3: Pricing the Formulation
The initial step involved the brand owner submitting a request for pricing to the contract manufacturer (CM). The CM will in turn create their own version of the formula and then verify the raw material pricing for the key ingredients from different vendors. When this is done, the CM will give out a price quote to the brand owner.
Timeline: The process of developing a formulation and verifying the raw material pricing usually takes anywhere from 3 to 5 days.
Step 4: Ordering the Raw Materials
This is undoubtedly the step that takes the longest during the manufacturing phase. Wondering why? Here is an example.
Let’s imagine that the raw material in question is a probiotic. Since these are live microorganisms, they are usually made to order. They will be literally grown on a natural medium, and this can’t happen overnight. Growing probiotics is actually a 6-weeks (or more) affair. Now, if those probiotics come from Italy, the finished material will have to be shipped internationally, which will take another 1 to 2 weeks.
There are many other different kinds of raw materials that can be very different from probiotics. Some of them will actually have better stability and might even be stored by the CM. However, it’s likely that the raw materials you chose will not be stocked by the CM, or the CM might not have stocked it in sufficient quantities, meaning more will have to be ordered. This could take 2 to 4 weeks to arrive.
Timeline: Based on the raw material, it could take 2 to 4 weeks for it to get delivered once it has been ordered by the CM.
Step 6: Raw Materials Get Delivered, Quarantined, and Tested
When raw materials get delivered to the CM, the cGMP regulations will require that they are quarantined and tested before they get released into the inventory. The kind of testing required typically includes potency and identity, heavy metal compliance, and microbiological compliance.
Identity & Potency
When testing for potency and identity, there has to be some kind of established methodology for testing the ingredient raw materials. The methodology could be from the U.S. Pharmacopeia, or any other credible source. The methodology must not only be followed, but a standard will have to be purchased in case the CM currently doesn’t have the standard already.
For those who didn’t already know, a standard is a validated sample of the raw material ingredient the CM lab uses for comparison purposes. The raw material is tested against the standard through the appropriate lab equipment to find out if it matches. The right laboratory equipment might include UltraViolet-visible (UV-VIS0 Spectroscopy, Fourier Transform Infrared (FT-IR), High Performance Liquid Chromatography (HPLC), and Inductively Coupled Plasma – Mass Spectrometry (ICP-MS). This way, potency and identity can be established.
Microbiological testing: The next step is that the raw material is tested for microbial compliance to establish that it doesn’t contain dangerous levels of microorganisms like E. coli. For this purpose, specialized equipment will be required. And since all CMs won’t have the same in-house microbiological lab, this could mean having to send the raw material to a third-party lab for micro testing. Some CMs actually don’t even have a standard analytical lab, meaning that testing has to be done in a third-party lab. In such a case, you need to account for the additional time (could be around 2 weeks) if third party testing is involved.
Heavy-metal testing: Finally, the raw materials will also have to be tested for heavy metals like mercury, lead, cadmium, and arsenic. This is not only required, but also the right thing to do. The California Prop 65 requirements are associated with hefty fines in case a product fails to meet their rather strict heavy metal requirements.
Timeline: The testing mentioned earlier may take anywhere between 1 and 2 weeks based on whether the CM has an inhouse lab facility or if the raw materials need to be sent to a third-party lab. After testing, the raw materials can be released to the inventory the same day.
Step 7: Bench Work
When all of the raw materials have been released into the inventory, the CM will then conduct the bench work, or the R&D part. This is where the raw materials are mixed together and a limited number of capsules or tablets are produced in a lab to confirm that the formulation will work as intended in a finished form. Based on the situation at hand, the CM could provide samples of the capsules or tablets to a customer for evaluation. If the customer approves the samples, the CM can proceed to creating the pilot batch.
Timeline: Benchwork takes anywhere from 1 to 7 days after making the necessary adjustments to the formula.
Step 8: Pilot Batch
Following what was learnt during the bench work, the next step is running a pilot batch of the product to the actual production equipment. This is done to determine whether the product will run correctly on the equipment during the actual production run. In case there are any issues, the formulation can be adjusted at this stage, though it may require approval from the owner of the brand. If all goes well, the CM will move onto the full production run.
Timeline: Just as with bench work, the pilot run may run for 1 to 7 days based on the kind of adjustments that need to be made to the formula.
Step 9: Production Run and Testing
This is when the finished product is actually produced. There are a number of steps followed in the process, including a few additional testing that might need to get done. This includes content uniformity, uniformity of the mix, dissolution testing, and a repeat of tests done on the raw materials, such as potency, identity, heavy metal compliance, and microbiological compliance.
Uniformity of the mix: The raw materials in a certain dietary supplement will be uniformly mixed to ensure that each of the specified mineral, vitamin, herb etc. is distributed evenly throughout the entire batch. Making sure that the mix is uniform is crucial because you want all of the capsules, tablets, liquids, or powders made from a batch of raw materials to be consistent in terms of having the predetermined amount of nutrients in them. A sample of the mixed blend can be tested in a lab to verify that the levels of each ingredient in the mix is actually uniform.
Content uniformity (tablet weight spot testing): Once you establish that the mix is indeed uniform, you also want to make sure that every capsule and tablet has an accurate weight to verify its nutrient potency. This is also referred to as “content uniformity”. Although the tablets are being punched or capsules are being filled during manufacturing, their weight will be regularly spot tested. Aside from capturing the weight and uniformity data, data regarding hardness and thickness will also be recorded. For both tablets and capsules, content uniformity is usually charted to ensure that the results fall within a specific range. If there is an unacceptable level of variation from the product specifications for uniformity (density, weight, and thickness), the tablets and/or capsules will be rejected.
Dissolution testing: This is a process where the tablet or capsule is put in a temperature-controlled water and then is agitated or moved around in a small container, similar to the action of digestion. If the capsules or tablets dissolve within 45 minutes in water, it’s considered reasonable to assume that it should dissolve in the human gut in a similar way, and the contained nutrients are therefore ready for absorption.
Stability testing: If the expiration date is to appear on a product label, then stability testing must be done. Stability testing will help to determine which nutrients are most vulnerable to damage and to what extent they are vulnerable. It can help establish how much of an increase in potency of a certain nutrient will be needed to compensate for the losses in potency over time, accounting for variables such as dosage form, specific ingredients, storage, and packaging conditions, etc. There are two forms of stability testing: accelerated stability and ambient stability.
- Accelerated stability
With accelerated stability, the dietary supplement is placed inside an environmental chamber in its intended packaging. The chamber ideally controls the humidity and temperature conditions. It then creates conditions designed to accelerate the normal aging of the product. For instance, when a product spends a month in the accelerated machine, it could be the approximate equivalent of six months of aging time. When the time elapses, the product can be tested for potency loss and other effects.
- Ambient stability
Ambient stability is usually determined by taking a small amount of the packaged product and holding it in a special retaining room under controlled ambient humidity and temperature conditions. The retain room is typically used for confirming and correlating shelf-life results from accelerated testing. During its shelf life, the product will be pulled from the retail room at regular intervals and tested for potency. This will then be compared to the accelerated aging research.
Step 10: Testing the Finished Products
When the finished tablets from the production batch are made, a repeat of the same kinds of tests done on the raw materials is done, including potency and identity, heavy metal compliance, and microbial compliance. The CM then produces a certificate of analysis (COA), which is then sent to the owner of the brand. If the brand owner approves the COA, the finished product will then be shipped to the customer’s distribution facility, and the product’s manufacturing process is now complete.
Timeline: The production run, along with the associated testing and finished product testing will take 1 to 3 weeks. This doesn’t include the time associated with stability testing that many brand owners usually do once the product is shipped. Don’t forget that the brand owners will also utilize the CM’s expertise with the different ingredients in order to establish the right expiration dating, and make any necessary adjustments on the next production run, whose time is not also included in this phase’s timeline.