Vol. 151, No. 25 — December 13, 2017

Registration

SOR/2017-259 December 1, 2017

FOOD AND DRUGS ACT

P.C. 2017-1501 December 1, 2017

Her Excellency the Governor General in Council, on the recommendation of the Minister of Health, pursuant to section 30 (see footnote a) of the Food and Drugs Act (see footnote b), makes the annexed Regulations Amending the Food and Drug Regulations (DIN Requirements for Drugs Listed in Schedule C to the Food and Drugs Act that are in Dosage Form).

Regulations Amending the Food and Drug Regulations (DIN Requirements for Drugs Listed in Schedule C to the Food and Drugs Act that are in Dosage Form)

Amendments

1 (1) The definition authorization holder in subsection C.01.001(1) of the Food and Drug Regulations (see footnote 1) is repealed.

(2) The definition discontinue in subsection C.01.001(1) of the Regulations is replaced by the following:

discontinue means, in respect of the sale of a drug by the manufacturer to whom a document was issued under subsection C.01.014.2(1) that sets out the drug identification number assigned for the drug, to permanently cease the sale of the drug; (cesser)

2 Subsection C.01.005(1) of the Regulations is replaced by the following:

C.01.005 (1) The principal display panel of both the inner label and outer label of a drug in dosage form shall show the drug identification number assigned for that drug, preceded by the expression “Drug Identification Number” or “Drogue : identification numérique”, or both, or the abbreviation “DIN”.

3 Subsection C.01.014(2) of the Regulations is replaced by the following:

(2) Subsection (1) does not apply in respect of a veterinary health product, a study drug as defined in section C.03.301 or a medicated feed as defined in subsection 2(1) of the Feeds Regulations, 1983.

4 (1) Subsection C.01.014.1(1) of the Regulations is replaced by the following:

C.01.014.1 (1) A manufacturer of a drug may make an application for a drug identification number for that drug.

(2) Paragraph C.01.014.1(2)(o) of the Regulations is replaced by the following:

5 (1) The portion of subsection C.01.014.2(1) of the Regulations before paragraph (a) is replaced by the following:

C.01.014.2 (1) Subject to subsection (2), if a manufacturer has provided all the information and material described in subsection C.01.014.1(2) or section C.08.002, C.08.002.01 or C.08.002.1, as the case may be, in respect of a drug, the Director shall issue to the manufacturer a document that

(2) Subparagraphs C.01.014.2(1)(a)(i) and (ii) of the English version of the Regulations are replaced by the following:

(3) The portion of subsection C.01.014.2(2) of the Regulations before paragraph (a) is replaced by the following:

(2) The Director may refuse to issue the document referred to in subsection (1) if he or she has reasonable grounds to believe that the product in respect of which an application referred to in section C.01.014.1 has been made

(4) Paragraph C.01.014.2(2)(b) of the Regulations is replaced by the following:

(5) The portion of subsection C.01.014.2(2) of the English version of the Regulations after paragraph (b) is repealed.

(6) Subsections C.01.014.2(3) and (4) of the Regulations are replaced by the following:

(3) If the Director refuses to issue the document under subsection (2), the manufacturer may submit additional information or material and request the Director to reconsider his or her decision.

(4) On the basis of the additional information or material submitted under subsection (3), the Director shall reconsider the grounds on which the refusal to issue the document was made.

6 Section C.01.014.3 of the Regulations is replaced by the following:

C.01.014.3 The manufacturer to whom a document was issued under subsection C.01.014.2(1) that sets out the drug identification number assigned for a drug shall, within 30 days after the day on which the drug is first sold following the issuance by the Director of the document, date and sign the document and return it to the Director with a statement set out on it that the information it contains is correct and with an indication of the date of that first sale.

7 Sections C.01.014.5 and C.01.014.6 of the Regulations are replaced by the following:

C.01.014.5 (1) The manufacturer to whom a document was issued under subsection C.01.014.2(1) that sets out the drug identification number assigned for a drug shall, annually before the first day of October and in a form established by the Director, provide the Director with a notification that is signed by them and that

(2) If any of the information that the manufacturer submitted under a provision referred to in paragraph (1)(b) is not correct as of the day on which the notification is sent, the manufacturer shall update that information in the notification.

C.01.014.6 (1) The Director shall cancel the assignment of a drug identification number if

(2) The Director may cancel the assignment of a drug identification number if the manufacturer to whom a document was issued under subsection C.01.014.2(1) that sets out the drug identification number

8 Sections C.01.014.7 and C.01.014.8 of the Regulations are replaced by the following:

C.01.014.7 The manufacturer to whom a document was issued under subsection C.01.014.2(1) that sets out the drug identification number assigned for a drug shall, within 30 days after the day on which they discontinue the sale of the drug, submit the following information to the Minister:

C.01.014.71 If a period of 12 months has elapsed since the day on which the manufacturer to whom a document was issued under subsection C.01.014.2(1) that sets out the drug identification number assigned for a drug as defined in section C.01.014.8 last sold the drug, the manufacturer shall so notify the Minister in writing within 30 days after the day on which that period ends.

C.01.014.72 If the manufacturer to whom a document was issued under subsection C.01.014.2(1) that sets out the drug identification number assigned for a drug resumes the sale of the drug after a period of 12 months has elapsed since the day on which they last sold the drug, the manufacturer shall so notify the Minister in writing within 30 days after the day on which they resume the sale of the drug.

C.01.014.8 The following definitions apply in this section and in sections C.01.014.9 and C.01.014.10.

drug means any of the following drugs for human use for which a drug identification number has been assigned:

shortage means, in respect of a drug, a situation in which the manufacturer to whom a document was issued under subsection C.01.014.2(1) that sets out the drug identification number assigned for the drug is unable to meet the demand for the drug. (pénurie)

9 (1) The portion of subsection C.01.014.9(1) of the Regulations before paragraph (c) is replaced by the following:

C.01.014.9 (1) If a shortage of a drug exists or is likely to occur, the manufacturer to whom a document was issued under subsection C.01.014.2(1) that sets out the drug identification number assigned for the drug shall post the following information in English and French on a website that is operated by a party for that purpose with whom Her Majesty in right of Canada has entered into a contract to make that information available to the public:

(2) Paragraph C.01.014.9(1)(k) of the Regulations is replaced by the following:

(3) The portion of subsection C.01.014.9(2) of the Regulations before paragraph (a) is replaced by the following:

(2) The manufacturer shall post the information

(4) Subsections C.01.014.9(3) and (4) of the Regulations are replaced by the following:

(3) If any of the information that was posted by the manufacturer changes, they shall update that information on the website within two days after the day on which they make or become aware of the change.

(4) Within two days after the day on which the manufacturer is able to meet the demand for the drug, they shall post information on the website to that effect.

10 (1) The portion of subsection C.01.014.10(1) of the Regulations before paragraph (c) is replaced by the following:

C.01.014.10 (1) If the manufacturer to whom a document was issued under subsection C.01.014.2(1) that sets out the drug identification number assigned for a drug decides to discontinue the sale of the drug, they shall post the following information in English and French on the website referred to in subsection C.01.014.9(1):

(2) Paragraph C.01.014.10(1)(j) of the Regulations is replaced by the following:

(3) The portion of subsection C.01.014.10(2) of the Regulations before paragraph (a) is replaced by the following:

(2) The manufacturer shall post the information

(4) Subsection C.01.014.10(3) of the Regulations is replaced by the following:

(3) If any of the information that was posted by the manufacturer changes, they shall update that information on the website within two days after the day on which they make or become aware of the change.

11 Sections C.01.014.11 to C.01.014.13 of the Regulations are replaced by the following:

C.01.014.11 The Minister shall ensure that a hyperlink to the website referred to in subsection C.01.014.9(1) is on the Government of Canada website.

12 Paragraph C.01A.003(a) of the Regulations is replaced by the following:

13 Paragraphs C.01A.004(1)(c) and (d) of the Regulations are replaced by the following:

14 (1) Item 4 of Table I to section C.01A.008 of the Regulations is replaced by the following:

Item

Activities

4

Distribute as a distributor referred to in paragraph C.01A.003(a) an active ingredient that is not an active pharmaceutical ingredient or an active ingredient that is used in the fabrication of a drug that is of non-biological origin and that is listed in Schedule C to the Act

(2) Item 5 of Table I to section C.01A.008 of the English version of the Regulations is replaced by the following:

Item

Activities

5

Distribute as a distributor referred to in paragraph C.01A.003(b)

(3) Item 7 of Table I to section C.01A.008 of the Regulations is replaced by the following:

Item

Activities

7

Wholesale a drug that is not an active pharmaceutical ingredient or an active ingredient that is used in the fabrication of a drug that is of non-biological origin and that is listed in Schedule C to the Act

15 Paragraph C.02.020(1)(a) of the Regulations is replaced by the following:

16 (1) Paragraph C.03.202(1)(a) of the Regulations is amended by striking out “and” at the end of subparagraph (ii) and by adding the following after subparagraph (iii):

(2) Subparagraph C.03.202(1)(b)(v) of the Regulations is repealed.

(3) Section C.03.202 of the Regulations is amended by adding the following after subsection (1):

(2) Subparagraph (1)(a)(iv) does not apply to a radiopharmaceutical that is

17 (1) Paragraph C.03.203(1)(e) of the Regulations is replaced by the following:

(2) Section C.03.203 of the Regulations is amended by adding the following after subsection (2):

(3) Section C.01.005 does not apply to a radionuclide generator.

18 The heading before section C.03.205 of the French version of the Regulations is replaced by the following:

Drogues, autres que les radionucléides, vendues pour être employées dans la préparation de produits pharmaceutiques radioactifs ou représentées comme pouvant servir à cette fin

19 Section C.03.205 of the Regulations is replaced by the following:

C.03.205 The following definitions apply in this section and in sections C.03.206 to C.03.209.

component means

kit means a package that is intended to be used in the preparation of radiopharmaceuticals and that

20 Section C.03.207 of the Regulations is renumbered as subsection C.03.207(1) and is amended by adding the following:

(2) The component of a kit that is intended to contain the prepared radiopharmaceutical shall be labelled to display the drug identification number assigned for the kit, preceded by the expression “Drug Identification Number” or “Drogue : identification numérique”, or both, or the abbreviation “DIN”.

21 Paragraph C.03.208(e) of the Regulations is replaced by the following:

22 Paragraph C.08.002(2)(o) of the Regulations is replaced by the following:

23 Subparagraph C.08.003(3.1)(b)(i) of the Regulations is replaced by the following:

Transitional Provisions

24 In sections 25 and 26, drug means a drug that is listed in Schedule C to the Food and Drugs Act, that is in dosage form and that was available for sale in Canada before the day on which these Regulations come into force.

25 (1) Despite these Regulations, if the labels of a drug display information in accordance with one of the following provisions of the Food and Drug Regulations, as they read immediately before the day on which these Regulations come into force, that provision continues to apply in respect of the drug:

(2) Subsection (1) ceases to apply in respect of a drug

26 (1) Despite these Regulations, subsection C.01.014(2) of the Food and Drug Regulations, as it read immediately before the day on which these Regulations come into force, continues to apply in respect of a drug.

(2) Subsection (1) ceases to apply in respect of a drug

Coming into Force

27 These Regulations come into force on the day that, in the sixth month after the month in which they are published in the Canada Gazette, Part II, has the same calendar number as the day on which they are published or, if that sixth month has no day with that number, the last day of that sixth month.

REGULATORY IMPACT ANALYSIS STATEMENT

(This statement is not part of the regulations.)

Issues

These regulations amend the Food and Drug Regulations (FDR) to address the following issues:

1. Lack of Drug Identification Number (DIN) Requirements for Schedule C Drugs

When Health Canada grants market authorization to a drug, a DIN is issued and printed on the label of the drug. This DIN is used for a variety of regulatory purposes, including tracking of market status. Radiopharmaceuticals and drugs that are sold or represented for use in the preparation of radiopharmaceuticals (other than radionuclides) are listed in Schedule C to the Food and Drugs Act. Schedule C drugs are presently exempt from the DIN issuance requirement, thus Health Canada does not have a mechanism to efficiently track their market authorization status and cannot easily ascertain which of them are currently available on the Canadian market. This exemption has led to difficulties finding accurate and timely information about Schedule C drugs, such as identifying which products are on the market during drug shortage situations.

2. Discrepancies in the Notification of 12 Months of no Sale Requirements for Certain DIN Products

Health Canada’s publicly accessible Drug Product Database (DPD) is a repository of information for all drugs authorized for sale in Canada which use the DIN as the primary identifier. As part of the Regulations Amending the Food and Drug Regulations (Shortages of Drugs and Discontinuation of Sale of Drugs) (see footnote 2) [the Shortages and Discontinuation Regulations], a new provision was introduced that requires manufacturers to notify Health Canada within 30 days when a drug has not been sold for a period of 12 months. Once Health Canada has been notified, the status of the drug in the DPD is changed from “marketed” to “dormant” to better reflect the market status. With this information, practitioners can make informed decisions on treatment options for their patients. This requirement, however, only covers certain classes of drugs and does not apply to all DIN products, such as non-prescription drugs, and veterinary drugs. As a result, discrepancies exist between the current market statuses of all classes of DIN products in the DPD. This is problematic when practitioners, patients and Health Canada are relying on the DPD for accurate information.

Background

DINs for Schedule C drugs

Radiopharmaceuticals are drugs that exhibit radioactive properties and are used for diagnostic and therapeutic purposes. Radiopharmaceuticals are listed in Schedule C to the Food and Drugs Act, along with kits for the preparation of radiopharmaceuticals.

Prior to 1998, Schedule C licences were issued to manufacturers annually for Schedule C drugs. Each Schedule C licence listed all the products that were being marketed by a manufacturer at that time, and these were renewed on an annual basis. These licences were replaced by Establishment Licences in 1998. Since then, Schedule C drugs have been required to be labelled with the Establishment Licence number.

For other classes of drugs, a DIN is issued for each drug product that is authorized for sale in Canada and serves as a unique identifier that has, historically, been primarily used for reimbursement purposes by insurance companies. As most radiopharmaceuticals are administered parenterally (i.e. intravenously or via intramuscular injection) and are commonly prepared and administered by health care professionals in a clinical or hospital setting, DINs were deemed not to be required for reimbursement purposes. As such, Schedule C drugs were exempt from the DIN requirement.

Over time, the purpose of the DIN has evolved. Today, Health Canada uses a DIN for a variety of regulatory activities such as the tracking of market status of a drug and displaying associated information within the DPD. The Canada Border Services Agency (CBSA) uses a DIN to aid in compliance and enforcement activities with respect to the importation of drugs. A manufacturer’s authority to sell a product on the Canadian market is represented through the issuance of a DIN. Health Canada can similarly revoke the authority to sell a product which has been shown in the post-market context to be unsafe or for other reasons, such as non-compliance with the regulations, through the cancellation of a DIN.

Currently, once a DIN has been assigned, the manufacturer of the drug must provide Health Canada with a notification within 30 days of selling a drug in Canada. By means of an Annual Drug Notification Form, they also confirm that all the information previously supplied with respect to that drug is correct. This information is used by Health Canada for a variety of regulatory activities, such as the tracking of market status of the drug in the DPD.

As Schedule C drugs are currently exempt from the DIN requirement, they are not required to provide market notification or an Annual Drug Notification Form. In the absence of such information on Schedule C drugs in the DPD, it has been difficult to determine which radiopharmaceutical products are available on the Canadian market. This was particularly evident during the isotope shortages that followed the shutdowns of the Chalk River National Research Universal (NRU) nuclear reactor facility in 2007–2008 and 2009–2010. (see footnote 3) It was difficult for Health Canada to identify radioisotope alternatives during this shortage period due to the lack of an up-to-date list of Schedule C drugs on the market.

Notifications to Health Canada

Presently, when a drug product receives approval from Health Canada and is issued a DIN, it is listed on the DPD as “approved.” Once a manufacturer notifies Health Canada that sale of this product has commenced, the status is changed to “marketed.” When the product is discontinued and the DIN cancelled, the status is changed to “cancelled.” If at any time sale of the product stops, but the DIN is still active, the status of the drug remains “marketed” even though it is not available on the Canadian market.

On March 14, 2017, a provision in the FDR came into force as part of the Shortages and Discontinuation Regulations that requires manufacturers (authorization holders) of certain drugs to notify Health Canada within 30 days when a period of 12 months of no sale has elapsed. Since this provision came into force, a new “dormant” status has been introduced in the DPD. When a manufacturer notifies Health Canada that a product has not been sold for a period of 12 months, the status of the drug in the DPD will be changed from “marketed” to “dormant” to better reflect the market status and allow the public to easily distinguish drug products that are readily available on the Canadian market.

Objectives

The objectives of these regulations are to

  1. Remove the DIN exemption and clearly outline the labelling requirements for Schedule C drugs in order to align the DIN application process and labelling requirements for Schedule C drugs with all other drug products that have DINs.
  2. Require Schedule C drug manufacturers to notify Health Canada within 30 days of a product being marketed or discontinued.
  3. Broaden the scope of the 12 months no sale notification to require manufacturers of all DIN products not covered under the shortage and discontinuation regulations, to notify Health Canada after a 12-month period of no sale as part of the annual notification process.

Description

These regulations remove the exemptions to DIN requirements with respect to Schedule C drugs, thus aligning the DIN application process and labelling requirements for Schedule C drugs with all other drug products that presently hold a DIN. They also harmonize the 12 months no sale notification requirement for all DIN products and create a means for Health Canada to maintain a current and accurate list of marketed products.

DIN requirements

These regulations amend Part C of the FDR to remove the exemption from the requirement to be issued a DIN in order to be sold in Canada for all Schedule C Drugs. In turn, manufacturers of Schedule C drugs that are currently on the market, being sold pursuant to a Notice of Compliance will be required to submit an application for a DIN. When authorized, the manufacturer will be issued a Drug Notification Form, through which the DIN is assigned. The exemption will continue to apply for positron-emitting radiopharmaceuticals used in a study, medicated feed, and veterinary health products.

For all other Schedule C new drugs that have not yet received a Notice of Compliance, manufacturers of those drugs will be required to file a New Drug Submission or Abbreviated New Drug Submission as per Part C of the FDR and, if authorized, will be assigned a DIN.

A second amendment to Part C requires that manufacturers of Schedule C drugs, like all other drugs assigned a DIN, notify Health Canada within 30 days of commencing sale once a Drug Notification Form has been issued. Additional provisions in Part C of the FDR that require the manufacturer to either re-submit the application or notify Health Canada should any information as part of the DIN application change, will now also be applicable to Schedule C drugs.

Labelling requirements

The regulations amend the labelling requirements for Schedule C drugs in Part C of the FDR to make them consistent with the requirements of all DIN assigned drugs. Establishment Licence numbers will no longer be required on product labels and will be replaced by the DIN.

Distributors and distribution activities

The regulations amend the rule that sets out which distributors must hold an establishment licence in Division 1A of Part C in order to reflect the issuance of DINs for Schedule C drugs. Likewise, the regulations amend the list of activities for Establishment Licence holders to encompass the distribution of active ingredients that are used in the making of Schedule C non-biologic drugs.

Alignment of DIN provisions

Several provisions in Part C of the FDR are written in such a way that drug products with a DIN, radiopharmaceuticals, and kits for the preparation of radiopharmaceuticals are listed separately. Since the regulations include Schedule C drugs in the category of drugs that have been assigned a DIN, these sections have also been amended to reflect one single category of drugs.

Notification of 12 months with no sale

When the Shortages and Discontinuation Regulations came into force in spring of 2017, the provisions regarding the requirement to notify Health Canada of 12 months with no sale only applied to those products that met the definition of “drug” under those regulations (e.g. prescription drugs). In order to bring uniformity to the FDR, the regulations require notification for all products that have received a DIN (i.e. all DIN assigned drug products are required to notify Health Canada).

Language consistency between English and French regulations

Several provisions were identified by the Department of Justice where the English and French text is inconsistent. The following provisions have been amended in order to harmonize the wording between the English and French versions with no change to the original intent:

Consequential amendments — Assignment and cancellation of Drug Identification Numbers

In order to accurately reflect how the FDR have been administered and eliminate unnecessary language, references to “the importer” and to “a person authorized by a manufacturer” have been removed from the provisions regarding the assignment and cancellation of DINs. References to “the manufacturer” have been aligned with those found in the provisions regarding drug shortages and discontinuations. These amendments improve the wording of the FDR without changing the original intent or the current operational process.

The provision regarding the annual notification process has been amended to specify the information to be submitted as part of the notification. This amendment brings more transparency to the regulations with respect to the manufacturer’s obligation without changing the original intent or current practice.

Consequential amendments — Drug shortage and discontinuation provisions

With the addition of DIN requirements for Schedule C drugs, the Shortages and Discontinuation Regulations have been updated to reflect this change. The new definition for “authorization holder” that was instituted to ensure that manufacturers of Schedule C drugs were captured under the new provisions has been removed; this change is reflected throughout the provisions.

Consequential amendments — Fees in Respect of Drugs and Medical Devices Regulations

Amendments have also been made to the Fees in Respect of Drugs and Medical Devices Regulations (Fee Regulations) in order to exempt manufacturers of Schedule C drugs from the fees associated with the review of a DIN application. Schedule C drug manufacturers will also be exempt from the annual right to sell fee. Current fees levied to Schedule C drug manufacturers, such as the New Drug Submission fee and the Establishment Licence fee, will continue to apply with no change to the fee level. This is a temporary measure as Health Canada is working to consult on, and revise its fees, including an expansion of the scope of the fees related to possession of a DIN to encompass Schedule C drugs.

Transitional provisions

Schedule C drugs that received authorizations, and are labelled in accordance with the current Part C of the FDR, can continue to be sold on the Canadian market for a specified period of time (as outlined below) after these regulations come into force.

Coming into force

The regulations come into force six months after the day on which they are published in the Canada Gazette, Part II.

“One-for-One” Rule

For the purpose of the “One-for-One” Rule, these regulations are considered to be an “IN” of $13,885 (calculated in 2012 dollars). The number is based on data provided by industry in response to a survey sent by Health Canada and calculated over a 10-year period and using a 7% discount rate in accordance with the Red Tape Reduction Regulations and reported in 2012 dollars.

Industry indicated that the cost to complete the Annual Drug Notification Form is expected to be $56 based on 30 minutes per form and an hourly rate of $112. Assuming that there are 250 Schedule C drugs on the market, this would represent an annualized burden of $14,000, or a present value cost of $98,330 over 10 years.

The regulations require manufacturers of the remaining DIN products not included in previous amendments within the FDR to notify Health Canada if their product has not been sold for a period of 12 months. There is an estimated backlog of 1 150 dormant DIN products, and 200 dormant products are anticipated to be reported annually. In order to save industry from an unnecessary administrative burden, Health Canada has decided to include a check box on the Annual Drug Notification Form for industry to report a 12-month period of no sales. Industry had previously estimated that the administrative cost of the notification of no sales would have been $75,600 (in 2017 dollars) the first year, and $11,200 every year thereafter if it had been required to provide a separate report to Health Canada concerning a period of no sales.

Industry will also have to notify Health Canada of the resumption of sales for a previously dormant DIN within 30 days. Industry’s response to Health Canada’s survey tool estimated the task would take 15 minutes as the data being provided is essentially the same as when the product was first put on the market. Minor updates to the data on the form would be required. It is assumed that roughly 200 products a year would meet this requirement, creating an annualized administrative burden of $5,474 or $38,447 over 10 years reported in 2012 dollars.

Current initiative is an:

“IN” (One-for-One Rule)

Annualized administrative costs (constant $2012)

$13,885

Annualized administrative costs per business ($2012)

$9

Current initiative is an:

“IN”

Small business lens

The small business lens does not apply to these regulations, as the total costs of the amendments are less than $1 million.

Consultation

In July 2007, a Notice of Intent outlining Health Canada’s intent to develop regulations to remove the DIN exemption for Schedule C drugs was published in Canada Gazette, Part I. During the 30-day consultation period, two comments were received from industry stakeholders and both were supportive of the proposal. Stakeholders did not express any concerns regarding the potential for an increased burden associated with a DIN application and confirmed that there would not be any undue financial burden with respect to changing labels given that non-DIN labelled product could continue to be sold during the transition period.

On September 20, 2011, Health Canada sent a letter to radiopharmaceutical stakeholders to inform and solicit input regarding the proposed changes for the DIN requirements for Schedule C drugs; feedback was positive.

Throughout the development of the amendments, Health Canada communicated with industry via regular stakeholder meetings and workshops. These meetings include a biannual meeting with the Nuclear Medicine Alliance, a group representing nuclear medicine companies; and a biannual meeting with the Canadian Association of Nuclear Medicine and the Canadian Association of Radiopharmaceutical Scientists, representing non-industry radiopharmaceutical stakeholders. Health Canada will continue to provide information and updates to stakeholders through its Radiopharmaceutical Regulatory Workshops.

A survey regarding the notification of no sale after 12 months for products that do not fall under the Shortages and Discontinuation Regulations was sent out to stakeholders on July 19, 2016. Respondents indicated that, while supportive of the proposal to expand the scope to capture all products assigned a DIN, the burden of notifying Health Canada would be greatly reduced if it was possible to do so as part of the annual notification process. Health Canada agreed, and the proposal was amended so that products captured under the definition of drug by the Shortages and Discontinuation Regulations will continue to be required to report within 30 days after a period of 12 months of no sale has elapsed, while all other products assigned a DIN would be required to report as part of the annual notification process.

Prepublication in the Canada Gazette, Part I

The proposed Regulations amending the Food and Drug Regulations and the Regulations Amending the Food and Drug Regulations (Shortages of Drugs and Discontinuation of Sale of Drugs) and Regulations Amending the Fees in Respect of Drugs and Medical Devices Regulations were prepublished in the Canada Gazette, Part I, on March 4, 2017. The proposed regulations were open for comment for a 75-day period. Over the course of the consultation period, the Department received five comments on the proposed regulations from drug industry representatives and associations.

Comments received from radiopharmaceutical manufacturers were supportive of the proposal to assign DINs to Schedule C drugs, adding that this initiative will enhance drug access for patients. Clarifications were requested on the DIN application process that Schedule C drugs will be required to follow. These clarifications on the application process will be provided to stakeholders prior to the coming into force of these regulations. Current guidance documents will also be updated in order to reflect the new status of Schedule C drugs.

Comments were also received from a drug manufacturer and three industry associations representing disinfectants and self-care products, regarding the amendment to the provision requiring notification to Health Canada following a period of 12 months with no sale. The drug manufacturer was in full agreement with the expansion of scope of the 12 month no sale provision, but requested clarification on the process of submitting a Drug Notification Form when a product comes out of dormancy. The current guidance document on DIN cancellation contains information on the submission of Drug Notification Forms for dormant drugs and will be updated to reflect the requirements for all products that have been assigned a DIN.

The industry associations expressed three main concerns with the amendment to the 12 months no sale provision:

The Department agrees with the industry associations that disinfectants and self-care products should remain outside of the scope of the drug shortage requirements. As such, the shortage and discontinuation reporting requirements will remain unchanged. Only those classes of products outlined in C.01.014.8 are, and will continue to be, required to report shortages and discontinuations to the third-party website. The shortage and discontinuation reporting requirements will continue to focus on drugs for which a drug shortage or discontinuation would have the highest impact on patient health and safety.

The 12 month no sale provision, while originally introduced as part of the Regulations Amending the Food and Drug Regulations (Shortages of Drugs and Discontinuation of Sale of Drugs), was always intended by the Department to be applicable to all DIN products and not solely those defined in C.01.014.8. The amendments to this provision will bring consistency and transparency to the DPD. The changes will streamline operations, bring efficiencies to processes and facilitate post market activities when safety issues, such as product recalls and labelling safety updates, arise. DIN owners will be able to maintain their product’s DIN in the event that they decide to resume market sales.

As disinfectants and self-care products will be required to notify 12 months no sale as part of the annual notification process, no additional burden will be required for the original notification. In fact, given that notification via the annual notification process will automatically initiate the fee remittance process, this notification will eliminate the need for separate remission requests.

A product is not considered to be dormant until a period of 12 months has ended where the product has not been sold onto the Canadian market. For classes of drugs not defined under C.01.014.8, if this period ends in the months between annual notifications, it is possible for the product to have not been sold for up to two years before Health Canada is notified, making the status update a year out of date. In response to comments heard through the July 2016 survey, and in order to reduce the administrative burden to industry, the Department has deemed this risk to be acceptable.

Following the consultation period, no amendments were made to the prepublished regulations due to stakeholder concerns.

Rationale

DINs for Schedule C drugs

All drugs in dosage form, other than Schedule C drugs, regulated under the FDR have a DIN assigned upon authorization by Health Canada which must appear on the product label. A number of regulatory inconsistencies have arisen by not requiring that a DIN be assigned to Schedule C drugs. Specifically, Schedule C drugs are not required to notify Health Canada once sale on the Canadian market has begun, nor are notices required to be given when sales of radiopharmaceuticals are discontinued. Furthermore, since no mechanism exists to cancel a Notice of Compliance (the type of market authorization that Schedule C drugs receive), Health Canada does not have the authority to cancel market authorizations for these drugs.

With these amendments, Schedule C drugs will be subjected to the same requirements as all DIN products, such as market notification and discontinuance of sales notification. This will bring the regulatory oversight of these products into alignment with other products that have been assigned a DIN.

Despite the addition of Schedule C drugs to the DPD in 2015, the information within the database is still incomplete. Affected stakeholders may be unable to find adequate information relating to available alternatives when faced with a possible drug shortage. As the DPD is a publicly available database, these amendments will make market status information for Schedule C drugs available to physicians and other health care stakeholders. This is an important mitigation measure during shortages, discontinuations, and when a drug is not sold for a period of 12 months or more. Additionally, a DIN for Schedule C drugs will allow for easier identification, monitoring, and recall of these products. For example, the CBSA will be able to access the DPD for complete and reliable information to aid in compliance and enforcement of drug importation. Health care institutions (hospitals and clinics) will be able to easily identify affected drugs during product recall situations.

Lastly, these amendments will bring Schedule C drugs into the scope of products more readily eligible for reimbursement through public and private insurance. Some stakeholders identified the lack of a DIN as being the primary reason why some insurers would refuse a claim.

The change in labelling requirements associated with these amendments is expected to result in costs of $1,000 per product, considering a sufficient coming into force period to reduce costs associated with packaging change. Assuming that there are 250 radiopharmaceuticals currently authorized to be marketed in Canada, this requirement is expected to result in a one-time cost of $250,000. The amendments will also require manufacturers to fill out and submit a DIN application form and market notification, as well as an Annual Drug Notification Form to confirm that the information previously supplied with regard to the product is correct. This will cost industry $28,000 the first year, and $14,000 in annual notifications to Health Canada every year thereafter in 2017 dollars. The cost to Health Canada of issuing and processing DINs is estimated to be $35,360 in 2017 dollars. Amendments to add non-application provisions to the Fee Regulations ensure that there will not be any new or higher user fees paid by manufacturers of Schedule C products. These fees, expected to add up to $282,000 annually, will instead be absorbed by Health Canada until consultations are completed and user fees can be updated.

Notifications to Health Canada

As of March 14, 2017, new regulatory rules require manufacturers to notify Health Canada within 30 days when a period of 12 months of no sale has elapsed. This provision currently only applies to certain classes of drugs, but not all DIN products. This has created discrepancies in the DPD where some products with active DINs not being sold in Canada have a status of “marketed” while others have a status of “dormant.”

The amendment to this provision aligns all DIN products in the DPD by broadening the scope of the notification to require manufactures of all DIN products to notify Health Canada after a 12-month period of no sale within 30 days for drugs captured under the definition of drug by the Shortages and Discontinuation Regulations and as part of the annual notification process for all other products that have been assigned a DIN. It allows Health Canada to clearly and easily distinguish between products that have been granted an authorization to be sold in Canada but are not actively being sold, and those that are presently available for sale on the Canadian market. Having this distinction on Health Canada’s website will help patients, health care practitioners, and other health care stakeholders to have a clear and current picture of which drugs are available on the Canadian market. The changes will also streamline operations, bring efficiencies to processes and facilitate post market activities when safety issues, such as product recalls and labelling safety updates, arise. Furthermore, it allows DIN holders to maintain their DIN in the event that they decide to resume marketing their product.

There are approximately 1 150 DIN products which are not actively being sold, and it is expected that there will be 200 dormant products annually. Notifying Health Canada of these products is expected to cost industry $75,600 the first year, and $11,200 every year thereafter, if done separately from the annual notification process. However, since industry will be able to notify Health Canada of dormant products through the annual notification process, these costs are assumed to be zero.

Industry will also have to notify Health Canada when the sale of dormant products resumes in Canada. Assuming that 200 products are removed from dormancy each year, the annual cost to industry is estimated to be $6,000 in 2017 dollars.

Health Canada will be required to process the backlog of notifications at a cost of $34,466 the first year. Every year, Health Canada will also be required to process the notifications for the 200 products that are reported dormant and the 200 products that are moved from dormancy, at a cost of $13,788 per year.

The benefits of these amendments, as stated above, outweigh the costs to industry of applying for DINs, changing labels and notifying Health Canada following a period of no sale, as well as the costs to Health Canada for processing and issuing said DINs, and processing notifications for dormant DIN products.

Contact

Bruno Rodrigue
Director
Office of Legislative and Regulatory Modernization
Policy, Planning and International Affairs Directorate
Health Products and Food Branch
Health Canada
Address Locator: 3105A
Holland Cross, Tower B, 5th Floor
1600 Scott Street
Ottawa, Ontario
K1A 0K9
Email: LRM_MLR_consultations@hc-sc.gc.ca