Step-by-Step Process of Manufacturing Dietary Supplements
Have you ever wondered what the actual steps are in the process of manufacturing dietary supplements and how long it will take? Well if so, you’ve opened the right blog. This article will provide you with a start-to-finish overview of the dietary supplement manufacturing process which, generally speaking, will take 12-16 weeks from the date a purchase order (P.O.) is received.
Let's understand the step-by-step process of manufacturing a good quality supplement from scratch-
- Step 1: The Formula
- Step 2: Selection of Raw Materials
- Step 3: Pricing Out the Formulation
- Step 4: Purchase Order Submission
- Step 5: Ordering Raw Materials
- Step 6: Raw Materials Arrive & Are Quarantined and Tested
- Step 7: Bench Work
- Step 8: Pilot Batch
- Step 9: Production Run and Testing
- Step 10: Testing of Finished Products
Step 1: The Formula
It all starts with the formula. Hopefully, as a brand owner, you’ve made sure that your dietary supplement formula uses the correct doses of the right raw material ingredients to provide an evidence-based product that will have efficacy, and that will allow you to substantiate structure/functions claims. Although a well-formulated dietary supplement will not guarantee initial sales, it does make it much more likely that you’ll have consistent repeat sales once consumers have used it for the first time.
Step 2: Selection of Raw Materials
A well-formulated dietary supplement requires the use of evidence-based ingredients to help assure product efficacy. Ingredients may be selected worldwide on the basis of quality, and eying forms that provide high potency and bio-availability. For example, many mineral supplements include well-absorbed mineral salts bonded to organic acids, including citrates, picolinates, and gluconates. Likewise, formulas with herbal extracts may include standardized extracts with guaranteed amounts of the natural active or marker compound within the herbs.
Timeline: The formulation of the product and the selection of raw materials are part of the same process. The timeline for this differs greatly from product to product. It may take as little as a week, or as much as a few years. In any case, we really don’t count the original formulation and raw material selection as part of the production process.
Step 3: Pricing Out the Formulation
The first step begins when a brand owner submits a request for pricing to the contract manufacturer (CM). In turn, the CM will create their own version of the formulation and verify raw material pricing for key ingredients with various vendors. Once all of this is done, the CM will provide a price quote to the brand owner.
Timeline: The CM’s process of developing their own version of formulation and verifying raw material pricing will typically take anywhere from 5-10 days.
Step 4: Purchase Order Submission
The real countdown begins once the brand owner submits the purchase order. Now that they know there is a commitment, the CM can go to town and really get the process going.
Timeline: This step is completely in the hands of the brand owner. Once they get the pricing, they can turn it around the same day and submit a P.O., or they can take a couple of weeks to generate and send one.
Step 5: Ordering Raw Materials
Without question, this is the step that takes the longest in the manufacturing process. Why? Here’s an example.
Let’s say that the raw material in question is a probiotic. As live microorganisms, probiotic ingredients are typically made to order. They literally must be grown on a natural medium, and that doesn’t happen overnight. In fact, growing probiotics may take 6 weeks or so. Now let’s say those probiotics come from Italy (which is often the case), so that means the finished material will be shipped internationally - which will take 1-2 weeks.
Of course, there are many raw materials other than probiotics - some of which have better stability and may even be stocked by the CM. Nevertheless, chances are that your chosen raw materials may not be stocked by the CM, or may not be stocked in sufficient quantity, so more will still have to be ordered. This will take 2-4 weeks to arrive.
Timeline: Depending upon the raw material, it may take 2-8 weeks for it to be delivered after it has been ordered by the CM.
Step 6: Raw Materials Arrive & Are Quarantined and Tested
Once the raw materials arrive at the CM, cGMP regulations require that they be quarantined and tested before they are released into inventory. The type of testing required includes identity and potency, microbiological compliance, and heavy metal compliance.
Identity and potency:
To test for identity and potency, there must be an established methodology for testing the raw material ingredient. That methodology may exist in the U.S. Pharmacopeia, or by provided by some other credible source. Not only must that methodology be followed, but a standard will need to be purchased if the CM doesn’t already have the standard. If you didn’t already know, a standard is a validated sample of the raw material ingredient that the CM’s laboratory will use for comparison purposes. The raw material will be tested against the standard using appropriate laboratory equipment to see if it matches. Appropriate lab equipment may include Fourier Transform Infrared (FT-IR) Spectroscopy, Ultra Violet-visible (UV-VIS) Spectroscopy, Inductively Coupled Plasma - Mass Spectrometry (ICP-MS), and High-Performance Liquid Chromatography (HPLC). In this way, identity and potency can be established.
Next, the raw material must be tested for microbiological compliance to verify that it does not contain dangerous levels of microorganisms such as E. coli. Special equipment in a separate microbiological laboratory will be required for this purpose. Since all CMs do not always have an in-house microbiological lab, this may mean that the raw material will have to be sent to a third-party lab for micro testing. In fact, some CMs do not even have a standard analytical lab, so all testing will have to be conducted by a third-party lab. Obviously, you have to factor in additional time (maybe 2 weeks) when raw materials are sent out to a third-party lab for testing.
Heavy metal testing
Finally, heavy metal testing for lead, mercury, cadmium and arsenic must also be conducted. Not only is this required and the right thing to do anyway, but California Prop 65 requirements are associated with some hefty fines if your product fails to meet their more stringent heavy metal requirements.
Timeline: The aforementioned testing may take anywhere from 1-2 weeks depending upon whether or not CM has in-house laboratory facilities, or if the raw materials have to be sent to a third-party lab. Once the raw materials have passed testing they can be released into inventory on the same day.
Step 7: Bench Work
Once all of the raw materials have been released into inventory, the CM will next conduct bench work, A.K.A., an R&D batch. This is where the raw materials will all be mixed together, and a limited number of tablets and capsules will be produced in the lab to ascertain that the formulation will work in a finished dosage form. Depending upon the situation, the CM may provide samples of the tablets/capsules to the customer to evaluate. Once the customer approves the samples, the CM can then move onto the pilot batch.
Timeline: Benchwork may take from 1-7 days depending upon adjustments that may need to be made to the formula.
Step 8: Pilot Batch
Using what they learned during bench work, the CM will next run a pilot batch of the product on the actual production equipment. This is necessary to determine that the product will run correctly on the equipment during the actual production run. If there are any issues, the formulation may need to be adjusted, which may require approval by the brand owner. If everything goes well, the CM will then move onto the full production run.
Timeline: Like bench work, the pilot batch may take from 1-7 days depending upon adjustments that may need to be made to the formula.
Step 9: Production Run and Testing
The production run is when the finished product will actually be produced. There are several steps in the process, including some additional testing that needs to be done. This includes uniformity of mix, content uniformity, dissolution testing, and a repeat of the tests done on the raw materials (identity and potency, microbiological compliance, and heavy metal compliance).
Uniformity of mix:
All of the raw materials which comprise a given dietary supplement are mixed together in a large-scale commercial mixer. During this process, it is vital that the raw materials are completely and uniformly mixed to assure that there is an even distribution of each specified vitamin, mineral, herb, etc. (“nutrients”) throughout the entire batch. A uniform mix is important since we want all the capsules, tablets, powders or liquids which will be made from a batch of raw materials to consistently have the proper, predetermined amount of nutrients in them. A sample of the mixed blend is taken to the lab, and the levels of certain ingredients are tested to verify that the mix is indeed uniform.
Content uniformity (spot testing tablet weight):
After determining that the mix is uniform, the next step is to ensure that each tablet and capsule has the correct weight in order to verify its nutrient potency. This is known as “content uniformity.” While capsules are being filled or tablets are being punched during the manufacturing process, their weight is regularly spot tested. In addition, to capturing weight uniformity data, additional data regarding thickness and hardness is also recorded. For both capsules and tablets, content uniformity is charted to ensure results within the specified range. If for any reason, there is an unacceptable variation from the product specifications for content uniformity (weight, thickness, density), those capsules or tablets are rejected.
Dissolution testing is a process whereby the capsule or tablet falls is put into temperature-controlled water and then agitated (moved around in a small container) to similar the muscular action of digestion. If the tablets/capsules dissolve within 45 minutes in water, it is reasonable to believe that it will likewise dissolve in the human digestive tract, and its component nutrients will be ready for absorption.
If expiration dates appear on the label of a product, then stability testing must be conducted. Stability testing helps identify which nutrients are most vulnerable to damage and to what degree potency is affected. By accounting for such variables as specific ingredients, dosage form, packaging and storage conditions, it can determine how much of an increase in the potency for a given nutrient is needed to compensate for potency losses over time. There are two types of stability testing: 1) accelerated stability, and 2) ambient stability.
i. Accelerated stability:
During accelerated stability, a dietary supplement in its intended packaging is placed inside an environmental chamber that controls temperature and humidity. This chamber will create conditions that are designed to accelerate the normal aging of a product. For example, if a product spends one month in the accelerated machine, it may be the approximate equivalent of six months aging time. When the product is removed, we can then test it for potency loss and other effects.
ii. Ambient stability:
Ambient stability is determined by taking a sample of the packaged product we manufacture and holding it in a retain room under controlled, ambient temperature and humidity. The retain room is used to correlate and confirm shelf life results from accelerated testing. At regular intervals, during its shelf life, a product is pulled from the retain room and tested for potency which is then compared to the accelerated aging studies.
Step 10: Testing of Finished Products
Once the finished tablets from the production batch have been made, a repeat for the same types of tests done on the raw materials is performed, including identity and potency, microbiological compliance, and heavy metal compliance. The CM will then produce a certificate of analysis (COA) which will be sent to the brand owner. Once the brand owner approves the COA, the finished product can be shipped to the customer’s distribution facility, and the manufacturing process is complete.
Timeline: The production run, associated testing, and the testing of the finished product may take 1-3 weeks. This does not include the time associated with stability testing which many brand owners chose to conduct after the product has been shipped, relying on the CMs expertise with the ingredients in the supplement to establish expiration dating and then making any adjustments that may be necessary on the next production run.
Frequently Asked Questions
Q: What are the FDA regulations for dietary supplements?
A: 1. Supplement formulas must comply with the Dietary Supplement Health and Education Act of 1994, including the New Dietary Ingredient regulations (NDI). 2. New dietary ingredients recognized after 1994 are required to have a new ingredient notification submitted to the FDA. Click here for more information on FDA regulations.
Q: Who is responsible for determining that a supplement is safe?
A: The FDA regulates dietary supplements. The Dietary Supplement Health and Education Act (DSHEA) grants the FDA the authority to remove products from the market that are deemed “unsafe” and take action against misbranded or adulterated products.
Final Notes on the Dietary Supplement Manufacturing Process
To reiterate, the dietary supplement manufacturing process will generally take 12-16 weeks from the date a P.O. is received. Could it be faster? Yes, it could be - especially if the production run is simply a repeat run and not the first one. In that case - and assuming that the CM is given sufficient advance notice vis-à-vis reasonably accurate sales projections - the product may be able to be produced in as little as 8-12 weeks.
Do you still have questions about the process of manufacturing dietary supplements? Our team possesses over 120 years of industry experience and would be happy to assist you! Call 855-492-7388 to speak to one of our representatives or send us your request to receive a free price quote if you already have your requirements in order.