Nutrasource Blog

When it comes to food and supplement labeling, there are significant differences between the US and Canada – even spelling the word “labelling (labeling)” is different. Both markets have their own set of regulations which detail the mandatory content required on a product label. The regulations also give guidance on voluntary content such as claims. It’s important to know which governing bodies have oversight, which regulations apply and how to properly classify your product to make sure you use the right set of regulations from the beginning.

Thinking about getting your toxicological results published? Go no further until you read this article.

Thinking about placing a toxicological test on your novel ingredient? Go no further until you read this article.

On August 2, 2024, just a few days before their Annual Meeting, AAFCO announced that the long-standing Memorandum of Understand (MOU) between AAFCO and the FDA¹ would not be renewed at the end of its term. Effective October 1, 2024, ingredients destined for use in animal feed (including pet food) in the US have two regulatory pathways – Generally Recognized as Safe (GRAS) and Food Additive Petition (FAP). The AAFCO Ingredient Definition will no longer be an option for new ingredients; however, a new “Animal Food Ingredient Consultation” (AFIC) pathway has been proposed by FDA and is currently open for public comment.²

You may have a blockbuster food or dietary supplement ingredient, but if the manufacturing process introduces contaminants, it may not be safe to consume. Contaminants may be introduced into a botanical ingredient during growth, such as heavy metals or herbicides from soil or pesticides or antifungal agents applied to plants. Toxins can be produced by plants or be introduced into plants during storage by fungal contamination. Ingredients that are produced by chemical synthesis may be contaminated with solvents or unintended metabolites, and ingredients that are manufactured by microbial fermentation can be contaminated with the microbes or toxins produced by them. Other sources of contaminants include water, processing aids, filters/columns, fermentation media ingredients and packaging materials. Use of Good Manufacturing Practice (GMP), potable water and food grade materials (by U.S. standards) can help reduce levels of contaminants in an ingredient. However, even if these procedures are in place, contaminants may be present in your ingredient.

Drug development is a complex, multi-phase process, involving rigorous testing to ensure safety and efficacy. Prior to drug or biologic testing in human subjects, approval must be obtained from regulatory authorities like the United States (US) Food and Drug Administration (FDA) if the drug or biologic is to be marketed in the US and Health Canada if Canada is the market of interest. In the US, approval is obtained through an Investigational New Drug (IND) application, while in Canada, the application required is a Clinical Trial Application (CTA).

The current paradigm used to determine the safety of an ingredient involves several in vitro, animal, and human studies. However, recent advances in in vitro methodologies have spurred the development of new approach methods, or NAMs. A NAM is defined by the US Environmental Protection Agency (EPA) as, “a technology, methodology, approach, or combination that can provide information on chemical hazard and risk assessment to avoid the use of animal testing”. NAMs are also commonly defined to include in silico, in chemico, and in vitro assays, as well as information about the exposure of chemicals in the context of hazard assessment. In silico methods are computational in nature, in chemico refers to purely chemical methods, such as testing a chemical by seeing if it reacts with another chemical or isolated protein in the absence of cells or tissues, and in vitro refers to experiments conducted in cell or tissue cultures. The ultimate goal of NAMs is to replace, reduce, or refine the use of animal testing in chemical safety assessment.

Natural Health Products (NHPs) are naturally occurring substances that maintain, promote, or restore good health.¹ To receive Health Canada approval, an NHP must carry at least one health claim and that health claim must have a health context. For example, “Source of antioxidants for the maintenance of good health.” In addition to the recommended use or purpose statement(s), there are several parameters that form part of an NHP’s Product Licence or Terms of Market Authorization (TMA), including product classification, product representation, composition / ingredients, directions for use, duration of use, risk information, allergen source disclosure, storage conditions, etc.² Marketing claims can be made around any of these aspects, and while they do not typically appear in the Product Licence Application (PLA) since they lack the required health context, they need to be consistent with the product’s TMA. Product performance, content, comparisons, representations of opinion and authorization, and side effect claims may also be considered marketing language.³ Some examples of acceptable advertising claims are provided in the Table below.

UNDERSTANDING MASTER FILES 

Master Files (MFs) are reference documents that contain proprietary and/or publicly-available data on aspects of drug or Natural Health Product (NHP) safety, efficacy, and/or quality that are submitted to regulatory authorities in support of various application types, including Clinical Trial Applications (CTAs), Investigational New Drugs (INDs), Abbreviated New Drug Applications or Submissions (ANDAs / ANDS), New Drug Applications or Submissions (NDAs / NDS), and Product Licence Applications (PLAs).

MASTER FILES SUBMISSION

MFs are submitted by individuals or companies that develop, manufacture, or supply drugs or NHPs, and are known as the MF Holders. In some jurisdictions the entire MF is strictly confidential between the MF Holder and the regulatory Agency, whereas in others restricted access is granted to Applicants authorized by the MF Holder. Once authorized, the Applicant is allowed to reference the MF in their own submission(s).

The purpose of a MF is to provide sufficient details to the regulatory Agency to satisfy safety, efficacy, and/or quality requirements. The information used in a MF can include specifics about the facilities, processes, and components used in manufacturing, processing, packaging, and storage, without disclosing proprietary information to the Applicant. The MF Holder is responsible for maintaining the MF and ensuring that it is kept up-to-date throughout its lifecycle.

TYPES OF MASTER FILES BY JURISDICTION 

In Canada, an NHP-MF serves the same purpose and follows a similar submission process as that of a Drug Master File (DMF). The United States (US) also has DMFs, whereas they are referred to as Active Substance Master Files (ASMFs) in Europe – both regions do not have a MF pathway for dietary or food supplements.

The type of MF needed depends on the regulated category and information intended to be communicated to the regulatory authority. For example, Health Canada and the US Food and Drug Administration (FDA) recognize five (5) different types of DMFs, yet the European Medicines Agency (EMA) only uses one (i.e., ASMF). Health Canada’s Natural and Non-prescription Health Products Directorate (NNHPD) also has a standalone MF specific to NHPs. The table below provides a summary of the different MF types across each of the three jurisdictions.

FIND OUT MORE:

Nutrasource’s NHP & Pharmaceutical Regulatory Sciences team is well-versed in MF dossier preparation and submission to various regulatory authorities.

Our experts can help navigate between MF types and the requirements for each section. Contact us today. 

REFERENCES:

1. Drug MF https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/master-files-procedures-administrative-requirements.html

2. NHP MF https://www.canada.ca/en/health-canada/services/drugs-health-products/natural-non-prescription/legislation-guidelines/guidance-documents/master-file-procedures.html

3. Drug MF https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/master-files-procedures-administrative-requirements.html#a21

4. Drug MF https://www.fda.gov/drugs/guidances-drugs/drug-master-files-guidelines

5. Drug MF https://www.fda.gov/drugs/forms-submission-requirements/drug-master-files-dmfs

6. US Dietary Supplement https://www.fda.gov/news-events/press-announcements/fda-updates-draft-guidance-premarket-safety-notifications-dietary-supplement-industry

7. Drug MF https://www.fda.gov/media/85079/download

8. Active Substance Master File https://www.ema.europa.eu/en/documents/report/final-guideline-active-substance-master-file-procedure-revision-4_en.pdf