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This article discusses FSMA-related regulations and stresses the impact the regulations will have on the dietary supplement industry.
Since the Food Safety Modernization Act (FSMA) was signed into law in January of 2011, regulatory professionals in the food and dietary supplement areas have been barraged.1 Seldom has one act had as many touch points in food regulation. For dietary supplement companies, FSMA's broad scope and hefty volume have made it a challenge to assess responsibilities. How much do new FSMA-driven regulations penetrate the dietary supplement arena? When exemptions are distilled, who has what responsibilities? What can we interpret from the updated lexicon? What changes do we need to make and what new underpinnings do we have to consider? With many of the final rules finally in place, now is a good time to look at the responsibilities of dietary supplement companies in today's regulatory environment since FSMA. This article is intended to give the reader bridges and supportive analysis for the transitions regulatory professionals will be explaining to industry for quite some time.
Studying the FSMA-driven regulations that affect the dietary supplement arena, regulatory professionals know to check the scope early in the game. Exemptions need parsing and careful reading of definitions can be invaluable. The scope for this article spans what can be covered reasonably in this short space. Table 1 lists most of the FSMA-driven regulations and statutes of interest to dietary supplement companies. Where there are clear exemptions in the subject regulations, those will be highlighted here to help narrow the scope. Dietary supplement manufacturers may want to follow-up by reading the FSMA Final Rule Fact Sheets and other FSMA resources provided for industry at the Food and Drug Administration's (FDA's) website.2, 3
§ 117.1 – 117.9
§ 117.10 – 117.110
§ 117.301 – 117.335
§ 117.5 (e)
Preventive Controls for Human Food
General Provisions (Subpart A)
CGMP (Subpart B)
Record Keeping (Subpart F)
Exemption from subparts C and G
Supplier Recall Requirements
Some of the simpler parts of FSMA-related changes are noted here.
FDA Registration - in the fourth quarter of even calendar years, FDA registrations are updated and those registrations now include a section where registrants identify the kinds of food products they produce at the registered site.
Administrative Detention - FDA can hold product under certain conditions and legally prevent it from being distributed.
Accredited Third-Party Certification - this part formalizes the regulations that apply to third party certifications and who checks those certification bodies. These are important because US companies will rely on third party certifications increasingly in the evolving environment.
FDA-Mandated Recall - if or when a company refuses to cooperate with FDA's request to recall product, FDA now has ability to require the Recall. The Act addresses FDA liability in case of an error.
Fees - FDA says they will start charging for their time when situations are prolonged due to situations marked by non-compliance, bringing the fee for a domestic eight-hour day close to $2,000.
Suggested Reading - dietary supplement companies will want to understand both of the following (regardless of exemptions.) At 21 CFR 117.136 and 117.137, there are provisions for a documented agreement between suppliers to sell goods that need further processing to control a hazard.5, 6 At 21 CFR 117.139, minimum recall procedure requirements for suppliers are spelled out.7
21 CFR 117 is Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Food.8 Part 117 appears as seven subparts, A through G; five of these subparts will be discussed in this article.9 Scope and exemptions for the core food regulations are found in part 117 – subpart A, where there is an exemption of special importance to dietary supplement companies. (For this article, part 117 subparts D and E will be set aside because they apply to very small companies and start-ups who file and receive or stand to lose "Qualified" status.) Dietary supplements are a subset of food as defined in the federal Food, Drug, and Cosmetic Act (the Act) at 21 USC 321 (ff.) Supplements are subject to the Good Manufacturing Practices for the Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements (GMPs at 21 CFR 111.) Due to the established framework for dietary supplements, FDA exempted supplements from two weighty subparts of 21 CFR 117. Found in the scope section of subpart A, the dietary supplement exemption reads:
"Subparts C and G do not apply to any facility with regard to the manufacturing, processing, packaging, or holding of a dietary supplement that is in compliance with the requirements of part 111 of this chapter (Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements) and section 761 of the Federal Food, Drug, and Cosmetic Act (Serious Adverse Event Reporting for Dietary Supplements)" - 21 CFR 117.5 (e) Exemptions
Note: compliance with Serious Adverse Event Reporting regulations is of equal importance as compliance with 21 CFR 111 GMPs to qualify for the exemption. Also note, the exemption does not apply to subparts A, B or F. At § 117.3(c), we read, "Food covered by specific current good manufacturing practice regulations also is subject to the requirements of those regulations." From these two points, it is apparent that although supplement companies are exempt from Subparts C and G, supplement companies have responsibility for compliance with subparts A, B, and F. The content of subpart A settles responsibility directly on the "owner, operator, or agent in charge" of any facility that makes, packs, or holds food (including supplements) for sale in the US. Subpart A also covers exemptions and definitions. Current Good Manufacturing Practices (CGMPs) are the focus of part 117 – subpart B and there will be further discussion of the CGMPs. Records and recordkeeping regulations at part 117 – subpart F require records to be available to FDA within 24 hours, settling an issue that was left open in 21 CFR 111 – subpart P. Also, records must "contain the actual values and observations obtained during monitoring; be created concurrently with the performance of the activity documented."
What are these parts C and G from which dietary supplements are exempt? Part C is Hazard Analysis and Risk-Based Preventive Controls (PC). Part C does not apply to foods covered by other sets of regulations, such as juice, seafood, low-acid canned foods, or acidified foods. In short, PCHF subpart C requires Food Safety Plans with a broad scope hazard analysis, risk-assessment and a production plan that includes control points (not just the critical control points of a HACCP program). Food Safety Plans require validation, verification and records. Subpart G requirements cover the supply chain and a mandate for documented responsibility for various preventive controls. Having established that dietary supplement manufacturers are exempt from part 117 – subparts C and G, are there other applicable exemptions in part 117? The answer is no. Subparts A, B and F are applicable to dietary supplement companies; there are no further exemptions and within the three subparts, there are definite responsibilities to be addressed.
Dietary supplement manufacturers sometimes make a few food products for humans or animals in addition to their supplement production. Companies making food products and dietary supplements in the same facility may be challenged to determine which regulatory responsibilities apply. What happens if regulatory requirements, between part 117 CGMPs and part 111 GMPs, appear in conflict? FDA anticipated the question and put clarification into part 117's preamble, saying:
"(Response 197) … As was the case when we issued the final rule to establish dietary supplement CGMPs and continues to be the case now, a manufacturer would be required to comply with the CGMP regulations in subpart B of part 117 in addition to the regulations in part 111, unless the regulations conflict. To the extent that the regulations conflict, the dietary supplement manufacturer would comply with the regulation in part 111.
(Comment 198) Some comments ask us to clarify how the exemption applies to foods, other than dietary supplements, that may be held in a facility that conducts activities in compliance with the dietary supplement CGMP regulation.
(Response 198) The exemption does not apply to foods, other than dietary supplements, that may be held in a facility that conducts activities in compliance with the dietary supplement CGMP regulation. The owner, operator or agent in charge of a facility that produces both dietary supplements and foods that are not dietary supplements must comply with the requirements of this rule for hazard analysis and risk-based preventive controls, unless another exemption applies as specified in § 117.5." – 80 FR 55908 at 55978 (2015)10
Distilling FDA's comments for those who make foods and supplements in the same facility, compliance will require some separation, perhaps physical or by scheduling, and there will be some distinct differences in documentation, all of which require procedures and training. If a company makes food products in a supplement facility, they will need to ensure that food production complies with part 117 (subparts A, B, C, F, and G) while still maintaining compliance with part 111 for their supplement production.
What regulations apply if a supplement company is making or packaging pet products? Due to FSMA, a set of Preventive Control regulations for Animal Food is found starting at 21 CFR 507.11 These regulations parallel the human food regulations, but have some unique aspects. 21 CFR 507.1 (d) allows that a facility producing animal food may elect to comply with part 117 regulations instead of the PCs for animal food. Companies making pet products with glucosamine, chondroitin and botanical ingredients will want to consider their options carefully because, technically, some of the ingredients may not be permitted in human food. PC for animal food, part 507, allows for slightly different ingredients and might be a better choice for some companies in this position. FDA's Technical Assistance Network ( TAN) may be a resource for clarity and they can be contacted for this (or any other FSMA-related questions).
TAN has been swamped and their response may take several weeks, but their responses can be valuable references. In any case, careful separation and documentation is recommended if pet products are being made or packaged in a supplement facility because pet products are a food of some kind, but not dietary supplements.
21 CFR part 110 GMPs are the parent regulations for subpart B of part 117.12 Through the 1980s and 1990s, part 110 covered fundamental safety and sanitation principles for personnel, the plant, processes and procedures. Often known as the "Umbrella Clauses," part 110 GMPs formed a basic underpinning for all food processing plants (including supplements.) For example, part 110 dictated that some food processors monitor water activity (Aw) or pH as a means of controlling pathogens, but as time passed, it was clear that part 110 GMPs were not geared toward preventing problems. Even as they were writing part 111, FDA was planning updates for Food GMPs. FDA was intent on a more proactive stance. FSMA was the perfect vehicle for rolling out preventive controls. Now in effect for all but the smallest food manufacturers, part 117 – subpart B covers Current GMP for Food and it alone replaces all of 21 CFR 110. Part 110 will be archived in September of 2018 and by then, all companies producing, packaging, labeling, and/or holding dietary supplements must comply with both part 111 and subpart B of part 117. Use of GMPs at part 111 and part 117, together, leads to a robust system for food safety. Not only does the combination fill gaps for non-traditional forms of supplements, such as bars, gummies, and beverages, but it also directly addresses the major reason for recalls in the last five years, allergen content.
Dietary supplement manufacturers and packagers will benefit from parsing part 117 B, CGMPs, for responsibilities relative to controlling allergens. Everyone (ingredient manufacturers and handlers at all intermediary processing, packaging and storage points, including supplement manufacturers and packagers) must be proactive and implement controls according to the new CGMPs. The only products outside the requirements for allergen controls are those secured in their finished goods packaging in warehouses dedicated to labeled and sealed finished goods. A simple search for "allergen" will show that the subject comes up in part 117, subpart B more than 35 times. Note: FDA has adopted "allergen cross-contact" as the new term for the hazard, replacing the term "cross-contamination." The following citations show the definition and typical use:
"Allergen cross-contact means the unintentional incorporation of a food allergen into a food." – 21 CFR 117.3 Definitions
"Raw materials and other ingredients that are food allergens, and rework that contains food allergens, must be identified and held in a manner that prevents allergen cross-contact." – 21 CFR 117.80 (b)(8) Processes and Controls
Presence of undeclared allergens continues to be a serious matter; "undeclared allergen reports have steadily increased since Reportable Food Registry inception, representing 30% of reports in Year 1 and rising to 47% of reports in Year 5" according to FDA's 5th Reportable Food Registry Annual Report.13 Dietary supplement reports are not filed through the Reportable Food Registry, but statistics explain why FDA decided to focus attention on allergens. Threshold studies are in the works, and sometime in the future, we may see some of the allergens handled like sulfites or gluten, where there are slight allowances for content below set limits when tested by prescribed methods. Meanwhile, nearly all supplement manufacturers have significant allergen controls, but it is essential that the full range of requirements identified in part 117 subpart B are folded into supplement company practices and procedures. In the study of FSMA-related responsibilities for dietary supplement companies, perhaps the most significant is the lengthy list of requirements to prevent allergen cross-contact found in the CGMPs, subpart B, starting at § 117.10.
A strong quality management system is fundamental to dietary supplement part 111 GMPs. When part 111 was finalized, many companies were concerned that regulations precluded ingredient suppliers, leaving the burden on dietary supplement companies to police ingredient safety and quality. For dietary supplements, the definition of quality summarizes the charter for dietary supplement manufacturing and requires more than is required of food in general.
"Quality means that the dietary supplement consistently meets the established specifications for identity, purity, strength, and composition, and limits on contaminants, and has been manufactured, packaged, labeled, and held under conditions to prevent adulteration …" – 21 CFR 111.3 Definitions (Dietary Supplements)
"Quality control operation means a planned and systematic procedure for taking all actions necessary to prevent food from being adulterated." – 21 CFR 117.3 Definitions (Food)
Part 111 requirement to set specifications for identity, purity, strength, and composition is unique to dietary supplements. The definition for "quality control operation" is the same in part 110 food GMPs and part 117 – subpart B CGMPs for Food. The difference now, with part 117 – subpart C requirement for Hazard Analysis and Risk-based Preventive Controls, is that ingredient suppliers must develop Food Safety Plans and be considerably more diligent with their production controls than in the past. With part 117 – subpart G requirements for a Supply Chain Program, ingredient suppliers will shore up issues of concern to dietary supplement companies. Some ingredient suppliers, by going beyond the part 110 GMP requirements, have been ahead of the game and deserve credit for their commitments. Now that part 117 subparts C and G are in play, the rules for ingredient producers are set across the board with the bar at a much higher level. Receiving safer ingredients means that dietary supplement companies can focus on processing to ensure identity, purity, strength, and composition, and, more frequently, rely on the prerequisite controls of part 117 – subpart B to make, package, and store goods without contaminating them in the process. Ingredient suppliers have mandated responsibilities and dietary supplement companies should be able to set up more robust supplier qualification programs, effectively tightening that loop.
The requirement for qualified personnel to perform assigned functions is not new to supplement companies. In part 111, personnel must be qualified through education, training or experience to perform their assigned functions. With FSMA, FDA has identified that subject matter experts are needed to perform certain functions, defining "Qualified Individuals"(QIs). Qualified Individuals are required in part 117 and other new FSMA-related regulations. These new designations are distinctly oriented to the sections in which they appear. The Qualified Individual (QI) overseeing Food Safety Plans, per 117 – subpart C, needs expertise in process controls, food safety plans, and how to review the plans. Most will take a course to get the necessary training and orientation, but some food scientists, Process Authorities, and food engineers are already qualified. For mitigating intentional adulteration, per part 121, the Qualified Individual is a trained security specialist, who must know how to recognize vulnerabilities, assess risks, and protect food from known or unknown parties with malicious intent. For the Foreign Supplier Verification Program, a Qualified Individual must perform required activities and the Qualified Individual must know the Foreign Supplier's language well enough to communicate and review detailed supplier records.
Mitigation Strategies to Protect Against Intentional Adulteration
Foreign Supplier Verification Program
for Importers of Food
for Humans and Animals
CGMP, Hazard Analysis, and Risk-Based Preventive Controls for Human Food
CGMP, Hazard Analysis, and Risk-Based Preventive Controls for Animal Food
FSMA made provisions for supplying all these subject matter experts by funding a program to develop curriculum and training at the Food Safety Preventive Controls Alliance (FSPCA) at the Institute for Food Safety and Health in the Illinois Institute of Technology. To learn more about available food safety-related subjects and training for the various Qualified Individual roles, check on-line at FSPCA. Regulations do not require Qualified Individuals to be employees, so companies can seek outside expertise to help ensure compliance. (FSVP Importers must be employees.) Dietary supplement companies may want to insert identification of Qualified Individuals into supplier qualification programs. Knowing that a supplier has properly qualified personnel in the required places could be a useful and non-confidential factor for determining the supplier's compliance with part 117.
Studying the new lexicon a little further, there are definitions for the terms "verification" and "validation" in part 117. In part 111, FDA chose not to set definitions for these terms, as we know from their comment in the preamble, where FDA says, "we decline to define "validation" and "verification" because the final rules does not establish any requirements that use these terms." (72 FR 34752 at 34805.) The part 117 requirements for verification and validation are in the regulations within subparts C and G. Knowing that dietary supplement manufacturers are exempt from subpart C and G, we can set the record straight on a burdensome point. Some companies may want to read the regulations differently, but using plain logic, dietary supplement manufacturers are exempt from the regulations in which validation is required, therefore validation, as defined in part 117, is not required of dietary supplement manufacturers. Regulatory professionals may want to discuss this distinction with senior management and counsel to set policy.
The Foreign Supplier Verification Program (FSVP) is included in this discussion because it opens avenues of liability that dietary supplement companies will want to understand.18 The FSVP requires a person in the US to take responsibility for each imported shipment. This rule is not about logistics – it is about verifying that the foreign manufacturer is in compliance with set requirements for preventive controls for safe food. As of September 2017, Australia, Canada and New Zealand have been recognized by FDA as countries with acceptably equivalent preventive control systems, meaning that products from these countries pass into the US under modified FSVP requirements. Incoming shipments from other countries will be handled according to the full FSVP, without abbreviations.
FSVP is intensely complicated and requires handlers that almost definitely need specialized orientation and training. Qualified Individuals and Qualified Auditors will be involved and it is unlikely that these roles will be filled by just one person. The FSVP Importer must be in the US. A significant burden of personal responsibility, rivaling that of the business owner, chief executive, or general manager, will fall on the individual who accepts the role of FSVP Importer. For each and every imported product, each importer must have a Foreign Supplier Verification Program (FSVP plan) in writing. Again, this rule is about verifying that the foreign supplier has complied with FSVP requirements for product safety, and not about importing. When the FSVP Importer puts their name on import documents, they are verifying that the incoming goods were made using the FSVP, methodically limiting risk of serious adverse health consequences or death to humans or animals (SAHCODHA.)
Well-organized, conscientious, domestic suppliers and US-based distributors have already developed capabilities to take the lead role with the FSVP burden. Dietary supplement companies will have to go on record for ingredients purchased from suppliers who carried the FSVP burden, confirming both intended use and their own compliance standard, e.g., part 111, part 117, part 507, etc. For any dietary supplement company importing supplements in bulk for US packaging, FSVP will be a major responsibility, requiring a skilled team of individuals to meet requirements, handle extensive monitoring, and manage conformational testing. The main concern for a dietary supplement ingredient buyer is that the FSVP responsibilities must be settled in writing by various parties in advance of entry to the US. If that responsibility is not assigned, the goods may be refused by US Customs officials. Theoretically, responsibilities can be assigned to the party issuing a purchase order (regardless of who owns or receives what when) and there could be circumstances where a domestic dietary supplement company might prefer to be the FSVP importer. Dietary supplement companies may want an FSVP-trained specialist on staff as a resource for handling the company's best interests while still allowing for strategic buying. If dietary supplement companies want secure supply chains, a competitive supply environment, and minimal delays, they will have to understand the FSVP, decide how to work with their suppliers, and use FSVP responsibilities to best advantage.
Methodical protection of the food supply is the central theme of FSMA and part 121 regulations round out the FSMA system.19 The purpose of 21 CFR Part 121, Mitigation Strategies to Protect Food Against Intentional Adulteration (IA Rule), is to protect the domestic food supply from tampering that might lead to wide spread disaster. Three definitions from 21 CFR 121.3 combine to form valuable insight about this rule:
Food defense - for purposes of this part, the effort to protect food from intentional acts of adulteration where there is an intent to cause wide scale public health harm.
Contaminant - for purposes of this part, any biological, chemical, physical, or radiological agent that may be added to food to intentionally cause illness, injury, or death.
Mitigation strategies - those risk-based, reasonably appropriate measures that a person knowledgeable about food defense would employ to significantly minimize or prevent significant vulnerabilities identified at actionable process steps, and that are consistent with the current scientific understanding of food defense at the time of the analysis. – 21 CFR 121.3 Definitions
The Intentional Adulteration part 121 rule applies to all facilities in the US or any other country that are required to register with FDA, with some exemptions for careful study at 21 CFR 121.5. Very small businesses and start-ups may apply for exemption and sites that hold only packaged goods are generally exempt. One or more Qualified Individual(s) must develop and implement a site-specific Food Defense Plan that includes an analysis of vulnerabilities, appropriate mitigation strategies, monitoring, procedures, and records. The IA Rule requires training and involvement from supervisors and personnel at each significant processing step through to the Qualified Individual assigned with overall responsibility for the food defense plan. Like other FSMA-related regulations, the owner, operator, or agent in charge of the facility has personal responsibilities and must sign off on the completed food defense plan and subsequent modifications. Qualified Individuals for this Intentional Adulteration part 121 require specialized education, training and/or experience, so companies will have suitably Qualified Individuals on staff or contract independent Qualified Individuals to fill the required roles. Resources for education, training, and a plan builder will be available at FDA's website and the FSPCA has started to work on a recognized training course for IA-Rule Qualified Individuals. FDA notes that the IA-Rule is the first of its kind and so the compliance deadlines start rolling in towards the end of May in 2019.
As regulatory professionals know, a good part of our work is to absorb regulations and help others interpret, prioritize, and adjust to them as needed for compliance. When FSMA phased in, FDA's outreach to industry helped many people see the scope of the changes. Unfortunately, in daily practice, there are still people considering FSMA as a whole, rather than the driver for new and updated regulations. FSMA-driven regulations affect dietary supplement companies directly and indirectly. Dietary supplement companies will happily accept the exemptions from part 117 subparts C and G, but need to absorb what those subparts dictate to suppliers, both domestic and foreign. The newer regulations show similarities to each other in construction and focal commonalities, like calling out roles for qualified individuals, requiring hazard or vulnerability analysis, and considering risks. The new lexicon includes pivotal terms that help with understanding requirements for suppliers. Regulations now interlace pragmatically and dietary supplements should have safer ingredients. Regulatory professionals can serve dietary supplement companies by helping with direct requirements and by explaining where vested interests are affected by FSMA-related regulations that apply to suppliers. Ultimately, dietary supplement companies are responsible for integrating today's regulations with existing procedures and suppliers are finally engaged in a system that should yield fundamentally safer ingredients. When dietary supplement companies and their ingredient suppliers live up to their responsibilities as set out in the new regulations efforts, the FSMA's proactive practices will yield enhanced product safety across the board.
Gisele Atkinson is vice president, Quality and Technical Affairs at the Council for Responsible Nutrition (CRN). As part of the Scientific and Regulatory Affairs team, she assists with understanding and complying with federal CGMP regulations and other regulatory requirements. She has more than 15 years of experience in quality control and management, having served in management positions for a number of dietary supplement companies. Atkinson has a BS in microbiology with a minor in biotechnology from the University of Guelph in Ontario, Canada. She can be contacted at firstname.lastname@example.org.
Nicki Jacobs is a graduate of the University of California at Riverside with 35 years of industry experience. She founded Jacobs Compliance Services in 2009 to help dietary supplement brand owners, supplement manufacturers, and dietary ingredient processors understand and comply with regulations. She has served on the Council for Responsible Nutrition's Regulatory Affairs Committee for more than 10 years, is certified to audit for quality and HACCP, and speaks in webinars, conferences, and workshops. She can be contacted at email@example.com.
Cite as: Atkinson, G. and Jacobs, N.H. "FSMA and its Impact on Dietary Supplement Companies." Regulatory Focus. October 2017. Regulatory Affairs Professionals Society.
Tags: Dietary Supplements, FSMA, Food