Product safety is a critical underpinning to the introduction and subsequent thriving of consumer products in the marketplace. For dietary supplements, ensuring product safety is not solely a premarket concern, but rather one that spans the entire product lifecycle. With ever-evolving science, technology and regulatory requirements, as well as shifts in retailer and consumer expectations, responsible manufacturers should have a strong grasp of the baseline regulatory requirements for safety. However, a comprehensive approach composed of “best practices” can help ensure overall product safety on an ongoing basis.
At the beginning of the product lifecycle, during the premarket safety assessment, much of the emphasis is on the individual ingredient(s). Whether old or new, each active ingredient in a formulation is carefully assessed for safety under the product’s intended conditions of use. Ideally, this is accomplished through a combination of reviewing the literature and gathering information from ingredient suppliers and the manufacturer’s ingredient-testing efforts.
When it comes to botanical ingredients, for example, the premarket safety assessment can become a complex process. The first, and most critical, step is to develop and apply identity-testing methods (including some combination of visual, analytical and DNA-based techniques). The next step is to characterize the active and/or market constituents, which are often the basis for botanical ingredients’ safety and benefit and reflected in the ingredient specifications.
With a shorter history of safe use and fewer safety studies in the literature, substantiating the safety of botanical ingredients can be a challenge. Animal toxicology studies are resource-intensive and difficult to conduct. Fortunately, a new technology is emerging as a safety screening approach for novel ingredients (including botanical ingredients) and mixtures. It uses in vitro and in silico models that simulate animal and/or human physiologic organ systems, but at a fraction of the cost (C.Food Chem Toxicol. 2017 Sep;107(Pt A):418-429). Although these models cannot be relied on exclusively to substantiate the safety of novel ingredients, they can be useful screening tools, especially for mixtures, to determine if safety issues exist that require further attention.
Properly characterized ingredients assessed for safety can be incorporated into a product formulation. Nevertheless, brands must still implement safety measures. Strict adherence to cGMPs (current good manufacturing practices) is critical while the product is manufactured, packaged and shipped (usually to a warehouse) for holding until it goes to a retail shelf or directly to the consumer.
Once the products ships, the “hand off” to post-market surveillance, commonly known in the industry as mandatory adverse event collection and reporting, occurs. While related, these two approaches are different.
Adverse event reporting (AER) refers to the specific requirements called for in the Dietary Supplement and Non-Prescription Drug Consumer Protection Act of 2006. Post-market surveillance is a level of surveillance and sophistication well above the basic requirements of mandatory AER, which involves a prescriptive process of receiving, documenting, tabulating and submitting adverse event data.
A post-market surveillance approach allows a manufacturer to establish comprehensive product safety profiles, which is particularly advantageous for companies with multiple products and/or global distribution. Analysis of this information can help a manufacturer determine if, and how, its product may have been causally involved in an adverse event and equip the firm to defend itself appropriately against allegations of harm, many of which are based on mere associations with a reported adverse event (J Med Toxicol. 2017 Sep;13(3):227-237).
Key areas addressed through a post-market surveillance system:
- Product usage and consumer experience trends.
- Potential interactions with other products (positive and negative).
- Clear understanding of “background noise.”
- Ability to detect rare, unexpected “sentinel” events.
- Determine incidence of adverse events and prediction of future events.
- Identification of adulterated products.
- Inform current product redesign and future product innovation.
How should a company integrate these “best practices” into a single, collaborative system to optimize resources? By utilizing a 360-degree approach driven by communication between functions, each providing key learnings in an ongoing information exchange.
For instance, during the premarket assessment phase, information about certain product or ingredient issues or attributes, such as ingredient stability issues, can inform the formulation process. Or information regarding high levels of ingredients, such as caffeine or fiber, can inform the PMS system and product safety profile to prepare for possible consumer complaints around “jitters” or gas and bloating. Premarket assessment might also identify the potential for interactions with other commonly used ingredients or products. These, in turn, can be potentially verified through the post-market surveillance system, once products enter the marketplace.
The safety profile of a product cannot be truly evaluated or known until it enters the market. At that point, a picture can be developed that reflects how the product is used, how safe complex ingredients and formulas are as consumers use them, and whether products are used alone or in combination with other products or even medications. Conversely, customer usage and experience trends identified through post-market surveillance can be used to inform modifications to product directions and formulations and even future product innovation.
Brands can learn which types of ingredients to avoid, and which combinations and conditions of use are best suited for consumers with an integrated 360-degree approach to safety. As products become more complex, consumers’ use becomes more varied, regulations become stricter, and threats of litigation and brand reputation consequences loom, it behooves manufacturers to evolve their approach to safety from one that is strictly adhering to the letter of the law, to one that examines and ensures safety throughout the product lifecycle.
Learn more about how supplement brands can best design a post market surveillance program in the webinar “A 360° Approach to Supplement Safety: Implications for Product Innovation and NDI Compliance.”
Andrew Shao is the interim senior vice president, scientific and regulatory affairs of the Council for Responsible Nutrition, a trade association for the dietary supplement and functional food industry.