Notice of Intent to Amend the Prescription Drug List: Vitamin D

August 19, 2020
Our file number: 20-110519-351

The purpose of this Notice of Intent to Amend is to notify that the Prescription Drug List (PDL) qualifier for Vitamin D will be amended to allow non-prescription status for products a) containing up to 62.5 µg or 2,500 International Units (IU)/dosage form for oral use; or b) with a maximum recommended daily oral intake of 2,500 IU. Only the Human part of the PDL will be revised.

The current listing is:

The new listing will be:

Consultation summary:

The proposal to amend the PDL in relation to the Vitamin D was communicated through a Notice of Consultation posted on Health Canada's website on May 22, 2019. The 75-day consultation period ended on July 22, 2019.

There were 9 comments in total that were received in response to this consultation: 2 comments opposed the change and 7 comments supported it.

Rationale:

Vitamin D (cholecalciferol and ergocalciferol) facilitates the absorption of calcium and phosphate, which play a significant role in bone mineralization. Vitamin D is synthesized in the skin under influence of the sun, but it can also be obtained from foods and supplements. It was added to Schedule F (now known as the PDL) in 1997, which restricted the amounts of vitamin D levels up to 1,000 IU/daily dose in non-prescription products.

Over the past few years, Health Canada has received requests from consumers, physicians and industry regarding potentially increasing the non-prescription vitamin D limit set out on the PDL. In addition, the Natural and Non-prescription Health Products Directorate (NNHPD) has received various product license applications (PLAs) ranging from 2,000 IU to 10,000 IU of vitamin D per daily dose.

With the mounting interest from stakeholders, and given that the scientific evidence regarding supplemental vitamin D has evolved since 1997, Health Canada's Food Directorate undertook a safety assessment to determine whether sufficient safety information existed to support raising the maximum non-prescription vitamin D level up to 2,500 IU (62.5 µg).

According to the Food Directorate's review^{Footnote 1}, 2,500 IU (62.5 µg) would provide a safe maximum level of vitamin D in non-prescription supplements for children 9 years and older, adolescents and adults. The Food Directorate's methodology for obtaining this level involved subtracting the current estimated intake at the high end (95th percentile) of vitamin D from food (~1,000 IU/day) and supplements (~500 IU/day) from the Institute of Medicine's (IOM 2011) Tolerable Upper Intake Level (UL) of 4,000 IU (100 µg)/day for children 9 years and older, adolescents and adults. It should be noted that the UL is not a recommended intake level. It reflects the highest average daily intake of a nutrient that is likely to pose no risk of adverse effects in the general population. The UL itself was set by adjusting for uncertainty from a "no observed adverse effect level" intake value of 10,000 IU (250 µg)/day. A maximum daily non-prescription vitamin D level of 2,500 IU (62.5 µg) would continue to allow an acceptable margin of safety in children 9 and older, adolescents and adults. This proposed PDL limit applies to both cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2).

It is important to note that the new maximum supplemental vitamin D daily dosage of 2,500 IU (62.5 µg) is not considered a safe dosage for all subpopulations. For children younger than 9 years of age, specific dosage recommendations will be addressed by NNHPD’s Class III review of product licence applications to establish the approved conditions of use.

The Recommended Dietary Allowance (RDA) is the daily amount of a nutrient required to meet the needs of about 97.5% of the population. Table 1.0 provides the RDA and Tolerable Upper Intake Level (UL) per day for Vitamin D for the different age groups:

There are other vulnerable subpopulations, documented adverse effects, drug interactions, cautions, warnings, and contraindications. These issues will be addressed by cautionary statements on the labels of high-dose vitamin D supplements when the need is identified during the mandatory premarket evaluation process.

It should be noted that, from a public health perspective, there is no nutritional or health requirement to increase the non-prescription limit of 1,000 IU (25 µg)/day. While the proposed maximum non-prescription limit of 2,500 IU/day is not based on a benefit-harms assessment, it is considered a safe dose for children above the age of 9, adolescents and adults.

Next Steps:

Health Canada will communicate with the Market Authorization Holders (MAH) that are impacted by the amendment.

Submissions for products providing levels of Vitamin D higher than 1,000 IU per dosage form or per day cannot be accepted by the Natural and Non-Prescription Health Products Directorate (NNHPD) before the PDL has been officially amended since, in the interim, these products are still drugs subject to the Food and Drug Regulations. Therefore, applications received by NNHPD after the notice of intent is posted would be rejected as these products would still be considered drugs. NNHPD would only accept submissions exceeding 1,000 IU and up to the 2,500 IU limit, after the PDL listing for Vitamin D has been amended.

Once the PDL listing for Vitamin D has been amended, sponsors seeking market authorizations for high dose Vitamin D under the Natural Health Products Regulations (> 1,000 IU/dosage form or per day up to 2,500 IU/dosage form or per day) can submit a Class III product licence application with safety and efficacy evidence to the Natural and Non-Prescription Health Products Directorate (NNHPD) for full assessment. Please refer to the Natural Health Products Management of Applications Policy (NHP MAP) for more information on the classes of Natural Health Product (NHP) applications and the application process. In addition, please refer to the Pathway for Licensing Natural Health Products Making Modern Health Claims guidance document for more information pertaining to evidence requirements linked to safety, efficacy and quality for NHP applications.

If needed, a pre-submission meeting can be scheduled with NNHPD prior to submitting an application. The purpose of a pre-submission meeting is to discuss the evidence required in support of a Class III application. Pre-submission meetings do not entail a full assessment by NNHPD of the evidence presented and, as such, the outcome of the meeting does not constitute a regulatory decision, nor will a regulatory decision be issued. A pre-submission meeting request must be submitted to the NNHPD Client Service Unit (nnhpd.consultation-dpsnso@hc-sc.gc.ca) no less than one month prior to the proposed meeting date. Please consult section 4.3 of the NHP MAP for more information.

Should you have any questions on this amendment to the PDL please contact:

Health Canada
Prescription Drug Status Committee
Address Locator 3102C3
Holland Cross, Tower B
1600 Scott Street
Ottawa, Ontario
K1A 0K9

Email: hc.drug.prescription.status-statut.dordonnance.des.drogues.sc@canada.ca