The importance of working with a GMP 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 (who makes it), purity (what is actually in it), strength (how strong each dosage unit or tab is), and consistency (the level of potency). 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, then these regulations may affect you greatly.
The level of regulations will vary depending on what industry a company belongs to. There are three primary areas of regulation. The first is prescription drugs, which require the most stringent requirements and must be dispensed by a doctor’s prescription. The second area of regulation is over-the-counter (OTC) medications, which only require that the product meet certain standards for identity, purity, strength, and quality. Other countries have their own regulations for OTC medications; however, these are guaranteed by the manufacturer to meet US standards if they import or export them into this country. Lastly, there are dietary supplements.
Dietary supplements do not take any substances beyond what would normally occur in food in your diet.
Not only is GMP necessary, but it is crucial for dietary supplement manufacturers as many people have allergic reactions to certain food colorings or additives. There are also ‘natural’ substances that may be beneficial in smaller quantities but can cause harmful side effects if taken in excess.
GMP stands for Good Manufacturing Practices, which are guidelines that state how processes should be carried out to ensure quality. These practices work hand-in-hand with FDA regulations to ensure the safety and efficacy of all products produced by a facility. GMPs consists 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 includes all equipment and structures as well as quality control operations. A facility is regulated based on the type of drug it produces; for example, a facility making antibiotics must follow different GMPs than those used to make analgesics. The DC guidelines cover design specifications such as ventilation, temperature, etc., while ED&M covers information such as calibration of instruments and qualifications of personnel.
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 cause lawsuits or affect brand image. This can save companies thousands if an inferior product harms someone or results in a recall. Furthermore, production costs are decreased if companies do not have to destroy inferior products.
GMP guidelines are necessary for any industry where mass production is needed. It ensures that products are consistent and can be trusted by consumers, which is why it is important for nutritional supplement manufacturers as well as pharmaceutical companies. The FDA mandates GMP guidelines in order to ensure quality control, but ultimately they help the company save time and money – which is good for everybody.
GMP Manufacturing Implementation at an Active Facility
Good manufacturing practice (GMP) is a system for ensuring that products are consistently produced and controlled according to quality standards. Dietary supplements are no exception, as GMP guidelines have been developed over decades by the pharmaceutical industry, and later adapted for dietary supplement use.
These practices outline how a product should be manufactured, from starting materials to finished goods, with specific requirements including appropriate equipment and facility design; worker training on standard operating procedures; quality assurance of incoming materials through supplier verification activities; cleaning and maintenance of equipment as well as storage areas used in manufacturing; and established written procedures for processing, testing and releasing a batch for distribution.
There are two main reasons why the dietary supplement industry needs to be concerned with GMP: quality control and safety of products; providing evidence that every product manufactured has been done so consistently according to specific good practices that will ensure its 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, ingredients whose composition is well understood through analysis, appropriate personnel training in standard operating procedures (SOPs), protocols for cleaning equipment used in various steps of the process, storage facilities for ingredients and finished products, and well-documented procedures for processing batches of dietary supplements.
When all these things are done according to recognized standards, then they can be referenced in the marketing of a product, helping to establish its identity with consumers. Essentially it is the difference between saying that this supplement is very carefully produced according to guidelines recognized internationally versus “made at home.”
GMP facilitates an open relationship between manufacturers and regulatory agencies, which makes certain practices (for example testing every lot of finished goods manufactured) possible on an ongoing basis without having long interruptions due to noncompliance issues or unexpected surprises during inspections. Dietary supplement GMP manufacturing also ensures consistency among lots of finished products, creating marketplace confidence in the continuity of supply, which is important both for retailers and customers.
Manufacturers must also ensure the safety of dietary supplements, and 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, mixups between finished product lots, 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 hygiene could contaminate a supplement. If one worker fails to wash their hands before taking breaks five times during a shift it could easily result in thousands of bottles contaminated with dangerous ingredients.
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 are important to prevent contamination events 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 deaths. Although GMP does not specifically address issues related to product quality or safety, all dietary supplement manufacturers must adhere to GMP principles if they want their products sold legally in many countries. And complying with good manufacturing practices is required by law for virtually all retailers selling dietary supplements (see Is your Retailer Selling Tainted Supplements?).
GMP Manufacturing Related to Dietary Supplement Quality and Safety
Manufacturers must know the identity and purity of ingredients before processing begins. Whether they make supplements in bulk or 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). It also includes 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. Ingredients may be tested individually or through an integrated program that tests them as they come into the facility.
Completed product testing is important 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 that there will be problems decreases when documentation and testing are done at all steps in the manufacturing process. This is because knowing what makes up a supplement before processing begins leads to better decisions about how to process ingredients and what types of tests can be used to best verify identity, purity, and absence of contaminants during intermediate steps in the manufacturing process.
For 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 that can result in false negatives if they aren’t done properly.
The final step in GMP Manufacturing is generally the release of a finished batch, or lot, of dietary supplements based on laboratory testing that confirms it meets pre-determined specifications for identity and purity that have been set by the manufacturer.
Testing to confirm the absence of contaminants like heavy metals is also required by law in some countries. The U.S., Canada, and Australia all follow guidelines to test for at least 10 different metals and their compounds in finished dietary supplements. However, these guidelines 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 required by law.
Testing to confirm the absence of pathogenic bacteria such as Salmonella and E. coli requires additional considerations because there are no widely accepted reference standards for these microorganisms in dietary supplements, and FDA has never set an allowable limit for them that manufacturers can rely on as they do with heavy metals in pre-approved methods that meet good laboratory practices.
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 FDA’s limited resources for inspecting dietary supplement manufacturers and the fact that the public has little insight into how well (and how poorly) industry-funded inspections are conducted.
The biggest offender when it comes to knowing where unsafe processing conditions exist is probably proprietary information agreements required by contract manufacturers who make products under contract for other companies like retailers, distributors, and brand owners. These contracts typically include confidentiality clauses that prevent these third parties from sharing inspection findings with each other, so if a company has a problem with contamination or other product safety issue, the only people who can share that information and work together to prevent similar problems in the future are their contract manufacturer and regulators.
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 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 positioned differently.
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. The 3rd party certification programs/educators will also provide official reference standards in GMP Manufacturing for heavy metals in dietary supplements which manufacturers can use to conduct testing against when there are concerns about levels of these elements in raw materials or finished batches [NOTE: This doesn’t mean that heavy metals can be at any concentration because they have been found to cause organ damage from long-term exposure].
They will also provide a guide for packaging and labeling supplements, which includes information on required label statements, nutrition facts panels, warning statements, and Good Manufacturing Practices.
The supplement industry is taking steps forward by developing its own standards for good manufacturing practices, but more needs to be done to ensure manufacturers are following best practices thus protecting public health from defective products.
BL Bio Lab is an FDA-registered facility and as such, follows GMP manufacturing standards.