The concept of a natural health product (NHP) master file as it specifically relates to the licensing of natural health products in Canada by the Natural Health Products Directorate (NHPD) of Health Canada has often been surrounded by common misconceptions. But the potential benefits of a natural health product master file are too important to ignore.
What is an NHP Master File?
A natural health product master file is a submission package that is sent to the NHPD containing the relevant safety, efficacy, and quality data for a particular active ingredient. The master file should be constructed to provide support for an active ingredient, not a finished product. In the latter case a product license application (PLA) should be constructed.
While a master file may be constructed to contain all of the aforementioned information (safety, efficacy and quality data), there is no requirement as to its content and the master file could contain any of this information. For example, a master file could be constructed to contain only information relating to the quality (i.e. chemistry and manufacturing) of an ingredient.
What will the NHPD do with the file?
Once a master file is received by the NHPD, it is assigned a master file submission number and kept on file. Unlike a product license application, the master file is not immediately reviewed and the initial review will occur the first time the master file is referenced by a PLA to support the registration of a finished dose product.
Why should I register a Master File with the NHPD?
If you are an active ingredient supplier, many of your customers will likely be seeking to register their products with the NHPD and will be requesting from you the required active ingredient information. By having the required information on file with the NHPD you have merely to grant permission for your customer to reference the file and provide them with the master file submission number and a letter of access on a company letter head. This is a far more efficient approach than having to provide a separate information package to each of your customers for each of their products. This also represents a potential savings on the part of your customers as their product license application will hold less information, require less work and therefore cost less money for them to assemble.
Apart from reduced time and paper work, another advantage of a master file is that any proprietary information (e.g. formulations, manufacturing methods) contained in the master file is held in the strictest confidence by the NHPD. As such, the NHPD reviews the information without your customer or any other third party seeing the information. Additionally, master files are easily updated over time as new data becomes available or as any manufacturing processes change. This allows for new studies supporting the safety and efficacy of a product to be added to a file.
Many companies maintain active scientific research programs supporting their ingredients. This includes studies focused on new and expanded clinical indications than what the product is currently licensed for. As the results of these studies are compiled into reports supporting these new indications, they are simply added to the ingredient master file thus supporting new health claims. Companies then notify their customers that clinical information supporting new health claims is available and provide them with the master file number and a letter of access so that these claims can be added to their licensed product through an amendment.
Another example of the versatility of using a master file relates specifically to probiotic strains. The NHPD now requests that all manufacturers of probiotic strains maintain an ongoing monitoring plan involving a number of laboratory tests (e.g. antibiotic resistance, strain identity). The use of master files for each specific strain permits easy updating of this information.
How secure is the information contained in the Master File?
As previously mentioned, third parties can only reference your master file if they receive written permission from the master file holder. The permission must appear on a company letterhead and must be signed by the company senior official or by the contact person for the master file. This letter must accompany third party submissions that cite your master file. Even in the event of an access to information request, only those sections of the master file deemed non-proprietary will be released to a third party as part of this request. Non-proprietary includes any information that has already been made available in the public domain. For example, through published papers and information in advertisements.
Some companies who supply ingredients are not eligible for patent protection due to a variety of reasons. As part of the NHPD requirements for licensing a product in Canada, clinical studies supporting the safety and efficacy of the product or its ingredients are absolutely required. When clinical data is not available it is recommend that they conduct clinical trials rather than face the removal of these products or ingredients from the Canadian marketplace due to the evidentiary requirements. As these ingredients are not patentable, companies then file the resulting clinical safety and efficacy data with the NHPD as part of a master file. This ensures the confidentiality of the data and guarantees this information cannot be used by competitors as support for their ingredients. It also safeguards the investment in a clinical trial and ensures the proprietary nature of the data. It is strongly recommended that companies work with an experienced firm to help them get through the rigorous path laid down by the NHPD.
If there is a deficiency in the information, to whom will the NHPD send the Information Request Notice?
Upon review, any deficiencies relating to the information that is contained within the master file will be communicated to the master file holder, not the product license applicant. Any product license application deficiencies will be communicated to the applicant. This ensures the confidentiality of any information contained in the master file.
Peter Wojewnik is Director of Business Development at dicentra Inc., a Toronto, Canada-based international scientific and regulatory consulting firm with specialized expertise in the areas of natural health products, dietary supplements, food and nutrition, and cosmetics. dicentra has assisted clients resolve complex scientific issues, develop safe and effective market-leading products, and facilitate timely regulatory global approvals. dicentra is also a member of the US-based Consultants Association (www.Cani-Consultants-org.) Peter may be contacted at 416.361.3400. We can be reached at 1-866-647-3279 or at dicentra.com
The information presented in the article is accurate and current as this publication went to press. However, the Master File submission process is still under development by the NHPD and certain aspects may change in the future. If you have a product Master File ready for to submission to the NHPD, dicentra can provide review assistance. Jon-Paul Powers, Ph.D. dicentra scientific advisor formerly held the regulatory role at the Natural Health Products Directorate of Health Canada where he served as an assessment officer and acting unit head in the clinical trial division. During his time at the NHPD, Dr. Powers assessed a wealth of clinical trial applications involving a broad range of disease states and interventions including both natural health and drug products. He also assisted in the design of clinical trial protocols for industrial and academic sponsors, participated in working groups and workshops focusing on clinical trials, and has detailed experience working with the Food and Drugs Act and its associated regulations. dicentra may be contacted at 416.361.3400.