Product licence applications that contain pre-cleared information ingredients are subject to expedited review at the NHPD resulting in quicker processing, review and licensing times.
Pre-cleared information or PCI is a term developed by the Natural Health Products Directorate (NHPD) to refer to ingredients that have published monographs or abbreviated labelling standards (AbLS) published. As per the NHPD, “Pre-cleared information (PCI) is any form of information supporting the safety, efficacy or quality of a medicinal ingredient or natural health product (NHP) that NHPD has reviewed and determined to be acceptable. PCI can be used to speed up the evaluation of the NHP, and serves as a reliable source of product information for consumers.”1
NHPD publishes monographs for single, multiple (product) and AbLS ingredients for which they have received and evaluated sufficient safety, efficacy and quality information. A monograph/AbLS contains pre-cleared information including details such as the common and proper names of the ingredient, the doses at which it can be administered, acceptable claims, duration of use and risk information. Attesting to a monograph is equivalent to declaring that the ingredient meets all requirements in the monograph, as listed.
The NHPD has published many abbreviated labelling standards, single-ingredient and product (multiple ingredient) monographs. If a single medicinal-ingredient application attests to a monograph, it is called a compendial application. If there are multiple ingredients in the application and they all attest to monographs or AbLS, either individually or as a whole, it is called a pre-cleared information application. This pre-cleared information can be used to support the safety or efficacy of a Non-Traditional application. While compendial applications do not require submission of finished product specifications (FPSs), as the quality information on the monograph has been attested to, pre-cleared information applications must include a FPS. Furthermore, if an application contains multiple ingredients, referencing different monographs, then a combination rationale may be required.
When submitting a pre-cleared information application no IRNs are expected as the safety, efficacy and quality of the ingredients has been sufficiently established prior to an ingredient being listed as pre-cleared. By submitting such an application a significant reduction can be seen in both cost and time associated with completing and filing a product licence application. It is therefore to a company’s advantage to make products with pre-cleared ingredients and/or updating older submissions that are currently in queue and revising their presentation so that they can attest to being PCI. Moreover, NHPD has published a significant number of monographs, effectively building on their pre-cleared information ingredient database. This allows industry to formulate more products with all PCI ingredients, or have the majority of the ingredients as PCI, with only a few ingredients requiring a full length review, thereby making the entire submission process more efficient, effectively reducing the time it takes to take your product to market. Additionally, although changes in the quantities of medicinal ingredients in a product in queue are considered acceptable by NHPD if the adjustment falls within the PCI range listed in the monograph no further review of the file will be required. This is particularly significant as changes to medicinal ingredient amounts post licensing are generally considered fundamental changes and are not allowed by the NHPD.
Originally NHPD had committed to a submission review timeline of 60 days for completing assessment of compendial applications, with no timelines given for pre-cleared information applications. Although, it is our experience at dicentra that often times NHPD provides licenses for applications with PCIs within the 60-day time frame. However, under the new proposed framework by NHPD, compendial applications will receive their licence within 10 days of submission2. A specific time frame has not been indicated thus far for PCI applications, but the overall sense is that the review time will be substantially decreased.
It is important to thoroughly read the monograph in order to get a clear understanding of what one is attesting to prior to submitting the pre-cleared information application, as some monographs can be complicated. This is especially important for compendial applications because any deviation from the monograph results in a refusal of the file.
At dicentra we employ a team of scientific and regulatory experts that are available to help you determine whether the ingredients in your formulation could be considered pre-cleared and assist you in the completion of your product licence application.
References:
1. http://webprod.hc-sc.gc.ca/nhpid-bdipsn/monosReq.do?lang=eng&monotype=abls 2. http://www.hc-sc.gc.ca/dhp-mps/prodnatur/nhp-new-nouvelle-psn-eng.php