Nutrasource Blog

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

The dietary supplement industry is growing rapidly in South Korea. On a case by case basis, Korean-manufactured products can now showcase a third-party certification label on their product packaging – the International Fish Oil Standards (IFOS™) certification label. This is a way for brands to distinguish themselves in a highly competitive market while building consumer trust.

Continue reading to learn how Certifications by Nutrasource can assist with achieving this certification.

Benefits of IFOS™ certification for Korean supplement brands:

• Elevate your brand’s reputation by demonstrating your commitment to providing high-quality products through an internationally recognized label.
• Confirm that the product meets the most stringent industry purity standards, which shows product quality.
• Gain recognition from the Korea Health Supplements Association (KHSA). highlighting that the necessary regulatory compliance for selling products in Korea has been obtained.
• Increase consumer confidence in the product and brand, ultimately leading to increased sales and customer loyalty.
  

Once the application has been approved, the IFOS™ logo can be added to product packaging and advertisements for Korean-manufactured Omega-3 supplements. This signifies that the product is reviewed and approved by the KHSA, providing consumers with added assurance of safety and quality.

Nutrasource Asia can assist Korean supplement brands in obtaining IFOS™ certification and reaping its benefits. Here's how:

Introduction to the IFOS™ program:

Nutrasource Asia provides expertise to Korean brands on obtaining IFOS™ certification. Despite the high awareness of IFOS™ in the Korean market, many supplement brands are not familiar with the program's origin or the certification process. The team can guide you through the entire process of obtaining IFOS™ certification.

Nutrasource Asia offers a professional solution for brands who require assistance in communicating with the Certifications by Nutrasource team in Canada but do not speak English. The team at Nutrasource Asia can seamlessly manage the entire process, from contracting to sending samples to Canada to receiving IFOS™ certification, ensuring a smooth and hassle-free experience for clients.

Assistance with market access strategy:

Nutrasource Asia offers a range of services to help clients navigate the complex regulatory landscape in Korea. Our team can provide guidance on Korean regulations, assist with the IFOS™ certification process, and explain the product launch process in Korea. Additionally, we offer support in coordinating production and testing plans to ensure a seamless market launch for your products.

Market monitoring for IFOS™ misuse or abuse:

Nutrasource Asia provides ongoing monitoring of the Korean marketplace for clients who have obtained IFOS™ certification, ensuring that the certification is not misused or abused. If any issues are identified, Nutrasource Asia works with clients to promptly correct them.

By following this step-by-step guide and working with Nutrasource Asia, eligible Korean brands can obtain an IFOS™ certification and take advantage of the program's benefits.

Ultimately, IFOS™ helps brands differentiate themselves in a competitive market and meet the demands of quality-conscious consumers.

Learn more the IFOS™ program.

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