The importance of working with a GMP (Good Manufacturing Practices) manufacturer is immeasurable in the world of dietary supplements. The FDA’s regulations for quality control state that all products marketed in the United States must meet very high standards for:
- identity (what it actually is),
- purity (not tampered with or diluted),
- strength (how potent each dosage unit or tablet is),
- and consistency (a continuous level of quality).
One may ask “What does this have to do with me?” If you are thinking about starting your own pharmaceutical company or dietary supplement company, or even buying and selling private label supplements, then these regulations may affect you greatly.
Regulated Manufacturing Areas
There are three primary areas of regulation. The level of regulations will vary depending on what industry a company belongs to. The first is prescription drugs, which demand the most stringent requirements and must only be dispensed by a doctor’s prescription. The second area of regulation is that of over-the-counter (OTC) medications. For this, the requirement is that the product meet certain standards for identity, purity, strength, and quality. Other countries have their own regulations for OTC medications. However, manufacturers must guarantee these meet US standards when imported or exported into the USA. Lastly, there are dietary supplements.
Dietary Supplement GMPs
Dietary supplements do not include any substances beyond what normally occur in food.
Not only are GMPs necessary, but are crucial for dietary supplement manufacturing. This is because people can have allergic reactions to certain food colorings or additives. There are also “natural” substances that may be beneficial in smaller quantities but cause harmful side effects if taken in excess.
GMP stands for Good Manufacturing Practices. These are guidelines that state how processes should be carried out to ensure a high level of quality. These practices are the application of FDA regulations at the highest level of quality possible. This ensure the safety and efficacy of all products produced by a manufacturing facility.
GMPs consist of three separate areas: general manufacturing practices (GMP), design controls (DC), and equipment design and maintenance (ED&M). The GMP guidelines focus on the facility, which include all equipment and structures as well as quality control operations. A facility is regulated based on the type of substance it produces. For example, a facility making antibiotics must follow different GMPs than those used to make analgesics.
The DC (design control) guidelines cover design specifications such as ventilation, temperature, etc., while ED&M cover information such as calibration of instruments and personnel qualifications.
How GMPs Help Prevent Unnecessary Costs
Not only do these practices directly save lives by ensuring that medications are pure and properly dosed, but they also save money and time in the long run. A correctly produced product will not result in lawsuits or damage to brand image. This can potentially save companies thousands by preventing or limiting an inferior product from harming someone or a recall. Furthermore, production costs decrease if companies do not ever have to destroy those inferior products.
GMP guidelines are necessary for any industry where mass production occurs. They ensure that products are consistently well-made and can be trusted by their consumers. They are vital for nutritional supplement manufacturers as well as pharmaceutical companies. The FDA mandates GMP guidelines in order to ensure quality. Ultimately they end up helping any facility save time and money. And that is good for everybody.
GMP Implementation at an Active Facility
Dietary supplements are no exception. GMP guidelines have been developed over decades for the pharmaceutical industry and were later adapted for dietary supplement use.
These practices outline how a product should be manufactured, from raw materials and components, to finished goods. Specific requirements include:
- appropriate equipment and facility design
- employee training on standard operating procedures (SOPs)
- quality assurance (QA) of incoming material through supplier verification processes
- cleaning and maintenance of equipment and storage areas used in the manufacturing process
- and established written procedures for processing, testing and releasing of batches for distribution.
There are two main reasons why the dietary supplement industry needs to be concerned with and following GMP:
- quality control and product safety
- providing evidence that every product manufactured has been done so according to practices which ensure safety and efficacy.
The Importance of GMP Manufacturing for Dietary Supplements
Every company has a unique philosophy regarding the production methods they use to create dietary supplements, but there are many commonalities among them. For example, all manufacturers need equipment suited to their particular processes. They require ingredients whose composition is well understood through analysis. They must have adequate personnel training in standard operating procedures (SOPs). Established protocols must exist for equipment cleaning and sanitization during crucial steps of the manufacturing process. Storage facilities for raw material ingredients and finished products should be clean, orderly and well-maintained. Lastly, one must follow well-documented procedures for processing batches of dietary supplements.
When all these crucial factors are performed and implemented according to these recognized standards, they can be referenced in the marketing of a product, helping to establish an identity with consumers. Essentially, it is the difference between saying that a supplement is “made at home” versus “very carefully produced according to strict guidelines recognized internationally.”
Global Effects of GMPs
GMP facilitates an open relationship between manufacturers and regulatory agencies, which make certain practices (e.g. testing of every lot of finished goods manufactured) possible on an ongoing basis without having long interruptions due to noncompliance issues or unexpected surprises. Dietary supplement GMP manufacturing also ensures consistency among lots of finished products, creating marketplace confidence in the continuity of supply and quality, which is important for retailers and customers.
Several countries have recognized good manufacturing practices specifically designed for the dietary supplement industry, including the United States; Canada; Israel; Australia; New Zealand; Taiwan and most of the European Union. Manufacturing practices that meet these guidelines help prevent contamination factors like those outlined previously.
There is an increased focus on safety by regulatory agencies worldwide, particularly in light of high-profile contamination incidents involving tainted supplements leading to liver injuries or even deaths. All dietary supplement manufacturers must adhere to GMP principles if they want their products sold legally in many countries. Complying with good manufacturing practices is required by law for virtually all retailers selling dietary supplements.
Manufacturers must also ensure the safety of dietary supplements. GMP principles help to make this possible by minimizing exposure to risk factors such as:
- contamination with microorganisms,
- adulteration or wrong ingredient substitution,
- cross-contamination between raw materials used in different steps of the process,
- incorrect labeling,
- mix ups between finished product lots,
- and employee health issues that could lead to contamination issues during manufacturing processes carried out by humans.
For example, there are many ways that poor hand-washing could contaminate a supplement. A worker failing to wash their hands before taking breaks even five times during a shift may easily cause thousands of products to be contaminated.
How GMPs Affect Quality Assurance and Quality Control Procedures
Manufacturers must know the identity and purity of ingredients before processing begins. Whether they make supplements in bulk or they repackage bulk supplements into tablets, capsules, or other finished products, this includes:
- screening for impurities like heavy metals (arsenic, cadmium, lead) and pesticides (chlorinated hydrocarbons)
- testing for microbial contamination (which can happen via contact with food sources like wheat flour during manufacturing steps performed by humans),
- identifying residues left behind from solvents used to extract botanical preparations,
- and verifying the absence of pathogenic bacteria is also included.
Ingredients may be tested individually or through an integrated program that tests each as they come into the facility.
Completed product testing is vital because dietary supplement manufacturers get one chance to get it right for each lot of finished goods. Whether it’s a simple multivitamin or a complex proprietary blend, the probability of problems decreases when documentation and testing are done at all steps of the process. Knowing initially the makeup of ingredients will lead to better decisions about how to process them and what types of tests can to use to best verify identity, purity, and the absence of contaminants during intermediate steps in the manufacturing process.
As an example, if you know your botanical starting material has been tested for microbial contamination by independent laboratories using culture-based methods (which have a very low probability of false negatives), then you may not need to test every lot of bulk ingredient with expensive DNA testing techniques which can result in false negatives if not done properly.
The final step in GMP Manufacturing is generally the release of a finished batch, or lot, of dietary supplements always based on laboratory testing that confirm it meets pre-determined identity and purity specifications that set up by the manufacturer.
In some countries, testing to confirm the absence of contaminants like heavy metals is also legally required. The U.S., Canada, and Australia all follow guidelines to test for at least 10 different metals and their compounds in finished dietary supplements. These guidelines however only specify limits for total contaminants rather than speciation (the identification of species) of each metal present. So testing beyond the quantity limits to confirm whether a heavy metal is lead or mercury or one of several other types may not be legally required.
Testing to confirm the absence of pathogenic bacteria such as Salmonella and E. coli requires additional consideration. There are no widely accepted reference standards for these microorganisms in dietary supplements. The FDA has not set an allowable limit that manufacturers can rely on.
When to Test and How
Deciding at what step in processing to test ingredients and finished batches of dietary supplements depends on the manufacturer’s approach to good manufacturing practices. What we know about testing and contamination risks associated with specific processing steps comes from published literature or surveys by regulatory agencies, while what we don’t know comes from the FDA’s limited resources for inspecting dietary supplement manufacturers. There is also the factor that the public has little insight into how well (or poorly) industry-funded inspections are conducted.
When it comes to locating unsafe processing conditions, the biggest offender is probably proprietary information agreements required by contract manufacturers. They may make products under contract for other companies like retailers, distributors, and brand owners. Oftentimes, these contracts typically include confidentiality clauses that prevent these third parties from sharing inspection findings with each other. So if a problem arises with contamination or some other product safety issue, the only individuals who can share that information and work together to prevent similar problems in the future are their contract manufacturer and regulators.
Dietary GMPs vs. Pharmaceutical
In general, the steps used in pharmaceutical GMP manufacturing are also followed by supplement manufacturers, but with some key differences because of the lack of an official list from the FDA as required under section 501(a) of the Federal Food Drug and Cosmetic Act (FD&C Act). This includes requirements for written procedures, employee training, equipment validation, and preventive maintenance, documenting all activities including complaint handling, and other areas not typically included in GMPs for pharmaceuticals. Dietary supplements are a different matter.
Some 3rd party certification programs will also provide a compendium with general chapters on compounding ingredients and finished drug products, along with specific details on ingredients used in dietary supplements such as vitamins and minerals. These certification programs and educators will also provide official reference standards in GMP Manufacturing for heavy metals in dietary supplements which manufacturers can use to conduct testing. This is useful when there are concerns about harmful levels of these elements in raw materials or finished batches. [NOTE: This does not mean that heavy metals can be at any concentration, because they have been found to cause organ damage over long-term exposure.]
These parties will also provide a guide for packaging and labeling supplements, which often include information on required label statements, nutrition facts panels, warning statements, and Good Manufacturing Practices in general.
Additional GMP Resources
Here are a list of links that provide additional data on GMPs and in-depth definitions and examples you should be familiar with for regulatory information.
The supplement industry is making great strides and is actively developing its own standards for good manufacturing practices. However, more needs to be done to ensure manufacturers are following them, thus protecting the public from defective products.
BL Bio Lab is an FDA-registered facility and as a private label supplement manufacturer, we ensure to follow GMP manufacturing standards.