Ontario Guidelines for Biosimilar Products
Submission requirements and review process
Introduction
The Ontario Public Drug Programs (OPDP) provides funding for a number of publicly funded drug programs. The largest program is the Ontario Drug Benefit (ODB) program and eligible benefits are listed on the ODB Formulary/Comparative Drug Index (the “Formulary”). Additional coverage may be provided through case by case review under the Exceptional Access Program (EAP).
For drug products to be considered for funding under the OPDP, a drug manufacturer must provide a complete submission in accordance with the applicable conditions set out in Ontario Regulation 201/96 made under the Ontario Drug Benefit Act (the “ODBA Regulation”) and these Guidelines.
Objective
The objective of this document is to provide guidance on submission requirements and the ministry’s review process for biosimilar products. A biosimilar product is a biologic drug product that has been approved for sale in Canada by Health Canada based on information comparing the biosimilar product to an original biologic product.
The Guidelines are to be used in the preparation of a drug product submission provided to the Ministry of Health (ministry). Some sections of the Guidelines are general in nature and must be read in conjunction with applicable legislation. The manufacturers, or those filing submissions on their behalf, are responsible for ensuring that all drug product submissions filed with the ministry contain sufficient information to satisfy the applicable requirements of the legislation and the Guidelines.
1. Checklist for preparing submissions
The manufacturer may use the below checklist to help ensure that all submission requirements have been included.
| Requirement: | Included |
|---|---|
| Signed cover letter | |
| Table of contents | |
| Health Canada Documentation: | |
| Notice of Compliance; and | |
| Product Monograph | |
| Letter of Consent | |
| Proposed Drug Benefit Price | |
| Ability to Supply Letter | |
| Certification of Providing No Rebate Letter | |
| Financial Impact Analysis: | |
| Budget Impact Analysis (report and model); and | |
| OPDP Financial Impact Analysis Summary Sheet | |
2. Submission requirements for biosimilar products
Cover letter and table of contents
A cover letter and table of contents must accompany the submission. The cover letter must clearly state:
- The name of the drug product, the DIN of the product, its active pharmaceutical ingredient(s), strength(s), and dosage form(s) (including the various package sizes).
- The type of listing requested (e.g. General Benefit, Limited Use, Exceptional Access Program, New Drug Funding Program etc.).
- Whether the manufacturer has any business agreements with any third party (e.g. consultant, cross-licensed, co-marketing, etc.) with respect to the drug product, and, if so, the name of the third party / third parties. See additional information in section 7.1 of these Guidelines.
Evidence of approval from Health Canada, including:
- A copy of the Notice of Compliance (NOC), if applicable; and
- A copy of the most recent Product Monograph approved by Health Canada.
Letter of Consent
A letter from the holder of the Health Canada approval authorizing the Executive Officer to gain access to all information with respect to the Drug Product in the possession of Health Canada, the Patented Medicines Pricing Review Board, the government of any province or territory in Canada or the Canadian Agency for Drugs and Technologies in Health and authorizing the Executive Officer to disclose any information with respect to the Drug Product in the possession of the ministry to Health Canada, the Patented Medicine Prices Review Board, the government of a province or territory in Canada or the Canadian Agency for Drugs and Technologies in Health.
See Template Letter of Consent in section 6 below.
Proposed drug benefit price
Submit a proposed drug benefit price (DBP) for the Drug Product. The proposed DBP (to four decimal places) should include, where applicable:
- The price per smallest unit (e.g. tablet, capsule, gram, millilitre, etc.); and
- The price per smallest dispensable unit for each package size (e.g. bottle, kit, ampoule, pre-filled syringe, vial combination package, etc.).
If the price of the smallest unit is accepted by the ministry and listed on the Formulary, it will apply to all package sizes of the product.
Evidence confirming ability to supply
Confirmation that that the manufacturer is able to supply the Drug Product at the proposed drug benefit price in a quantity sufficient to meet the anticipated demand for the Drug Product.
See Template Letter of Ability to Supply in section 6 below.
Certification confirming that no rebates were provided
The manufacturer must certify in writing that no rebates were provided to persons listed under subsection 11.5(1) of the Ontario Drug Benefit Act (ODBA) with respect to the Drug Product from the time that Health Canada approved the Drug Product for sale in Canada.
See Template Letter Certification of Providing No Rebate in section 6 below.
Financial impact analysis
The manufacturer must provide an estimate of the net costs to the OPDP in three-year period including:
- Budget Impact Analysis (report and model; must include an estimate of the net costs to the OPDP in a three-year period).
- OPDP Financial Impact Analysis Summary Sheet (see section 6 below).
In assessing financial impact, the ministry is interested in yearly expenditures (drug costs only) for the product(s) under consideration.
Drug costs must exclude upcharge (mark-up) and dispensing fee. The expenditures must be projected for three consecutive twelve-month periods irrespective of the anticipated date of funding.
3. Drug submission review process
Filing of drug submissions
A manufacturer that wishes to have a drug product considered for funding under OPDP must file a submission with the ministry.
Written/verbal communication
All written and verbal communication between the ministry and a manufacturer takes place through a single primary contact from the manufacturer. The ministry requires written notification in order to change a manufacturer’s primary contact, or any other information related to contact information (e.g. address, telephone number, e-mail address etc.). It is the manufacturer’s responsibility to keep this information current and accurate.
Submission receipt and review
Biosimilar drug product submissions are screened for compliance with applicable requirements in the legislation and these Guidelines by ministry staff in sequence, according to the date and time of receipt.
The targeted time frame for screening is approximately three weeks from the date the submission is received by the ministry.
Only complete submissions (i.e. those that meet all applicable requirements) are eligible for review and consideration for funding under OPDP. Manufacturers must ensure a submission has been deemed complete before finalizing any product listing agreement for the drug product. The complete submission date refers to the date the Notice of Drug Submission Status (NDSS) letter is sent.
New biosimilar products and their new indications approved by Health Canada will not require a routine review by the CED or the OSCCD, the ministry’s expert drug advisory committees for non-cancer and cancer drugs respectively.
This will improve efficiencies and better align with national processes for the funding consideration of biosimilar products, including the pan-Canadian Pharmaceutical Alliance and the Canadian Agency for Drugs and Technologies in Health (CADTH).
On a case-by-case basis, the OPDP may seek advice from the provincial drug expert reviewers as needed.
Ministry communication
Once a submission is screened by the ministry, an NDSS is issued to the manufacturer. Each submission is assigned a unique master file number, and each individual drug product within the same submission is assigned a unique drug product file number. The NDSS will indicate the status of the submission (i.e. complete or incomplete) as well as the assigned file numbers. The NDSS for an incomplete submission will state the reasons why the submission was deemed incomplete.
The ministry reserves the right to request additional information needed to address any uncertainties associated with a submission or to resolve questions that may arise during the review. The ministry may request additional information from manufacturers at any time during the screening and/or review process.
Manufacturer’s response
A manufacturer should make reference to the drug product (product name/generic name/strength/dosage form/package format and size), the DIN, the master file number and the drug product file number(s) in all subsequent correspondence to the ministry. If a manufacturer receives an NDSS, which indicates that the submission was deemed incomplete, the manufacturer will be provided with 60 calendar days in which to provide the information required to complete the submission.
Manufacturers are encouraged to respond to requests for additional information in a timely manner to avoid delays in the submission review process.
4. Format and organization of submissions
The Health Programs and Delivery Division accepts e-mail submissions. The submissions must be well organized and indexed/tabbed with description. Manufacturers must not provide submission information in one continuous document. If the submission is too large to be sent by a single e-mail, the ministry will accept the whole submission via multiple e-mails. If the manufacturer is sending multiple e-mails for one submission, clearly identify that the e-mails belong to the same submission and how many total e-mails pertain to that particular submission.
The ministry expects manufacturers to follow the Guidelines when preparing submissions. The onus is on a manufacturer to provide the ministry with a submission that is complete, accurate and complies with applicable legislative and policy requirements. The ministry will not assume responsibility for advising manufacturers of the completeness of their submissions prior to the ministry screening and review. Also, the ministry reserves the right to request additional information at any time during the review process.
5. Filing of drug submissions
All submissions and any additional related information must be sent to:
Senior Manager
Drug Benefits Management Unit
Drug Programs Policy and Strategy Branch
Health Programs and Delivery Division
Ministry of Health
Please email the submissions to DrugSubmissions.MOH@ontario.ca
6. Templates and checklists
Templates:
- Template Letter of Consent
- Template Letter of Ability to Supply
- Template Letter Certification of Providing No Rebate
Checklist:
The ministry’s template letters and checklists are available on the ministry’s website. All template letters must be prepared using the appropriate manufacturer’s letterhead, dated and signed by a senior company official.
7. Additional information
Third party involvement
Where a third party is involved with a submission, a letter must be submitted from each of the NOC/DIN holder and the third party confirming the business arrangement between the submitting party and the NOC/DIN holder. The letter from the NOC/DIN holder must authorize the submitting party to file and discuss the submission with the ministry, on behalf of the NOC/DIN holder.
Withdrawal process
The submitting manufacturer may voluntarily withdraw a submission any time throughout the review process. A written request must be provided by the manufacturer to the ministry with an explanation to withdraw a submission.
List of Abbreviations CADTH Canadian Agency for Drugs and Technology in Health CED Committee to Evaluate Drugs DBP Drug Benefit Price DIN Drug Identification Number EAP Exceptional Access Program NDSS Notice of Drug Submission Status NOC Notice of Compliance ODB Ontario Drug Benefit ODBA Ontario Drug Benefit Act OPDP Ontario Public Drug Programs OSCCD Ontario Steering Committee for Cancer Drugs