Suppose you are looking for multivitamin supplements. You pick up two containers of multivitamins and wonder which one you should get. At first glance, they have similar labels, but then you notice that one has a comment indicating that the supplement was manufactured in a registered GMP-compliant facility, and the other does not.
Then you ask yourself the following questions: How much of what ingredients are included in proprietary blends? Where do the ingredients come from? How do you know that these ingredients are safe? Where and how are these supplements manufactured? What does “GMP compliant” mean? You are in the right place if you have ever asked yourself these questions.
Interest in nutrition and dietary supplements has been skyrocketing. Not all supplements are created equal. Unfortunately, multiple supplements are not adequately controlled, leading to adverse events and deaths. Consumers and health care providers need basic dietary supplement literacy to make informed choices. In this piece, I will introduce the GMP (Good Manufacturing Practice) concept, one of the fundamental pillars in the supplements/pharmaceutical industries. GMP provides a practical framework for evaluating dietary supplements.
We can compare dietary supplement manufacturing to cooking. The recipe—or the formulation of supplements—includes information about the amount and identity of each ingredient, the sequence in which ingredients are combined, the cooking apparatus, and physical parameters such as mixing and cooking time.
What are dietary supplements?
The Food and Drug Administration (FDA) defines a dietary supplement as “a product intended for ingestion that […] contains a ‘dietary ingredient’ intended to supplement the diet” (FDA, 2024). “Dietary ingredient” includes vitamins and minerals, herbs and other botanicals, amino acids, “dietary substances” including enzymes and live microbes (probiotics), concentrates, metabolites, constituents, extracts, or a combination of the categories above.
What is GMP?
GMP tells a consumer how the supplement is made and whether the manufacturing process meets certain standards. Good Manufacturing Practice (GMP) requires certain activities to ensure dietary supplements’ identity, purity, quality, strength, and composition. These activities assure consumers that they are purchasing the type and amount of ingredients declared. The scope of GMP includes the entire supplement manufacturing process from the procurement of raw materials to the final product release and distribution. GMP does not address efficacy and potency in a pharmacological sense.
The term “GMP-compliant/certified” indicates that: 1) the supplement manufacturer follows the recipe; and 2) label claim information is verified, e.g., the product truly contains 5,000 IU of Vitamin D3. GMP certification is typically issued by regulatory or third-party certification bodies upon the facility inspection by GMP auditors. Certified facilities can state that the product was manufactured in a GMP-compliant facility. Looking for this statement on the product packaging or the company’s website is one of the easiest and quickest ways to check the manufacturing facility’s quality control system.
Before we dive into the manufacturing process, it is important to know that the brand owners on the package do not necessarily manufacture supplements at their facilities. They often outsource production to contract manufacturers. What does this mean? Suppose you find pieces of metal in your protein powder. You call the brand owner’s customer service number on the back of the package. The brand owner then transfers the complaint and investigation instructions to the contract manufacturer. The contract manufacturer initiates an investigation, including personnel interviews and a review of documentation/records, and relays the results to the brand owner.
Since the brand owner does not manufacture the product, the scope of responsibilities for brand owners and contract manufacturers needs to be clearly defined. GMP auditors typically scrutinize the following: 1) Who creates the recipe?; 2) Who is responsible for raw materials procurement? Are ingredient suppliers selected by the brand owners?; 3) Who is responsible for ingredient and final product testing?
Now, let’s dive into supplement manufacturing, aka the cooking process.
Step 1: Ingredient picking and testing
Similar to how we look for grocery markets that sell quality ingredients, manufacturing facilities select raw material suppliers and purchase ingredients from approved suppliers. As we need to pick the freshest ingredients to make the best tomato sauce, facilities must be picky with ingredient selection. They need a robust vetting program or supplier management process to ensure the safety and quality of ingredients. This is often done by auditing suppliers on-site, requiring them to fill out GMP surveys, reviewing their qualifications, and scrutinizing the Certificates of Analysis (CoA) for their raw materials. GMP auditors evaluate the thoroughness of the facility’s supplier control procedure by reviewing documents and records for initial qualification, re-qualification, and supplier approval/disapproval processes. This procedure is critical because what you put in is what you get out. If the supplier control is not adequately implemented, the quality of ingredients, and hence supplements, suffer (e.g., contaminated with impurities and/or counterfeit materials).
Once the facility selects the suppliers and receives the raw materials, they perform identity testing for each ingredient. The purpose of identity testing is to verify that the received ingredient is indeed the ingredient the supplier claims it to be. For a proprietary blend/premix, the supplier of the blend needs to disclose its composition using proper testing methods. For example, if you use a vitamin premix, the supplier must present the test results showing how many grams of each vitamin are included in the blend.
The identity testing procedure needs to be: 1) validated (if using in-house testing methods) or follow standardized methods per accredited institutions such as the USP (U.S. Pharmacopeia); and 2) fit-for-purpose, which means that the facility must demonstrate that its ingredient testing methods are appropriate for each ingredient. The one-size-fits-all approach to ingredient testing is not going to work, especially if you are handling herbal ingredients and similar materials. For example, popular forms of algae such as chlorella and spirulina would show a similar pattern on FT-IR spectroscopy, a commonly used identity testing method. To distinguish the two, the facility needs another verification method such as HPLC (High-Performance Liquid Chromatography)/HPTLC (High-Performance Thin Layer Chromatography).
Step 2: Manufacturing
After the identity testing, each ingredient is weighed and processed per the recipe. The manufacturing process needs to demonstrate the safe handling of raw materials. This includes equipment cleaning and sanitization, pre-operational inspection and maintenance of equipment, and procedures to handle any deviations. Cleaning and sanitization ensure that cross-contamination is minimized. As we wash cooking appliances thoroughly, especially after handling poultry, the facility must document every cleaning and sanitization procedure before and after each production run. They must establish manufacturing procedures to prevent cross-contamination from allergens, microbes, dust/particles, and foreign materials.
GMP also requires that the facility establish procedures for handling and recording deviations from the established recipes. When you realize your cake batter is too sweet and watery, are you throwing it away, or making adjustments? When you adjust, do you record the precise actions you took and update your current recipe? If you are working at a restaurant, who is authorized to approve or disapprove modifications to the recipe? Is it the head chef or the sous chef? How does intra- and inter-departmental communication work? GMP auditors evaluate the strength of quality control via personnel interviews and manufacturing record reviews. GMP indicates that process controls are in place to ensure that the final product is made per the recipe without introducing contamination.
Step 3: Final product release
This is where the kitchen manager checks the plating, food’s appearance, and taste before serving. In supplement manufacturing, the process includes a manufacturing record review by the Quality Control department and final product testing. Final product testing ranges from appearance (size, dimension, shape, and color), to microbiological testing, to label claim testing such as assays. Label claim testing is critical because the result serves as the final stamp of approval. It demonstrates that the multivitamin capsule you are taking indeed contains all of the vitamins listed on the package in the specified amounts. Once all the testing results are reviewed and approved by Quality Control, final products are released to the warehouse that handles distribution to end users (consumers like us) or brand owners.
The above steps are a whirlwind tour of GMP. Understanding what GMP means is critical for consumers and health care providers, especially for those in primary care as more and more individuals become curious about nutrition and inquire about the quality of supplements. In the ever-changing nutrition and health science field, we need a universal, time-tested standard to empower us as health consumers.
Alisa Sano is a public health auditor.
