Amendments to the Food and Drug Regulations to Replace the Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19 (ISAD IO)

As the COVID-19 pandemic continues and its unprecedented challenges rapidly evolve, Health Canada’s (HC) agile regulatory measures, called Interim Orders, continue to play a pivotal role in facilitating access to vaccines and drugs in relation to COVID-19. 

The Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19 (ISAD IO)¹,  was issued by the Minister of Health on September 16, 2020 and accompanied by a Guidance Document² (published on September 17, 2020), an Explanatory Note³, and a Notice⁴.

The ISAD IO introduced new authorization pathways to expedite access to drugs and vaccines for use in relation to COVID-19 (“COVID-19 drugs”) and provided three distinct pathways to accomplish this:

• Modified application and administrative requirements for drugs that are not authorized in Canada or other jurisdictions (with the potential for information to be submitted on a “rolling” basis as it becomes available).
•  Abbreviated application pathway for drugs that have been authorized by a foreign regulatory authority. Only drugs that have been listed on the List of foreign drugs in relation to the COVID-19 pandemic are eligible.⁵
• Application pathway to expand indications to include COVID-19 for currently authorized drugs. This is limited to those drugs that the Minister of Health has added to the List of new drugs for expanded indication in relation to the COVID-19 pandemic.⁶

The ISAD IO also provided modified requirements for drug establishment licence (DEL) applications for COVID-19 drugs, as well as a “pre-positioning” mechanism for their placement in Canadian facilities prior to the authorization to sell in Canada.   However, the ISAD IO is set to expire one year after coming into effect, potentially cancelling all authorizations and DELs issued under the Food and Drug Regulations that leveraged flexible ISAD IO mechanisms. This could lead to interrupted or delayed access to COVID-19 drugs for Canadians or disruptions in the supply chain.

To address this, HC opened a consultation (between November 30, 2020 and December 21, 2020) to seek feedback from stakeholders on a transitional approach to ensure COVID-19 drugs can continue to be authorized. A summary report of the responses received during the consultation was later published on January 23, 2021.⁷
 
On March 31, 2021, transitional provisions to the Food and Drug Regulations were published in the Canada Gazette, Part II and the accompanying Guidance on amendments to the Food and Drug Regulations for drugs for use in relation to COVID-19.^8,9 These amendments to the Food and Drug Regulations maintain some of the flexibilities provided through the ISAD IO. In particular, of the three pathways described above, the first pathway has been integrated into the Food and Drug Regulations; allowing Sponsors to leverage modified requirements, which include the ability to:

• File a “rolling” submission;
• Submit alternative safety and efficacy data packages where justified;
• Be exempted from providing mock-up labels, if draft labels are provided, which include package inserts and documents with supplementary information; and
• Be exempted from the requirement to conduct a brand name assessment.

Although the DEL provisions through the ISAD IO have been maintained in the amendments to the Food and Drug Regulations, HC now has the ability to impose or amend terms and conditions on DELs for a COVID-19 drug. Previously, this was limited to the tests to be performed in respect of a drug, and the equipment to be used, to ensure that the drug is not unsafe for use. The ISAD IO’s early importation (“pre-positioning”) mechanisms have also been carried forward to ensure timely distribution of COVID-19 drugs upon authorization. Sponsors are able to utilize this mechanism, if the Chief Public Health Officer has notified the Minister of Health that the COVID-19 drug is to be pre-positioned.
 
The amended Food and Drug Regulations also prescribes filing timelines for manufacturers seeking to maintain ISAD IO authorization:

•  For drugs authorized under the ISAD IO before the amendments came into force, 90 days following the coming into force of the amendments
•  For drugs authorized after the amendments came into force, 90 days following the issuance of an authorization under the ISAD IO

Although the 'Guidance on amendments to the Food and Drug Regulations for drugs for use in relation to COVID-19: Preparing a submission or supplement' is final, stakeholders are able to provide comments to Health Canada (hc.hpfb-covid19-dgpsa.sc@canada.ca) until April 30, 2021. 
 
At this time, the fate of the remaining Interim Orders, such as the 'Interim Order Respecting Drug Shortages (Safeguarding the Drug Supply)' and 'Interim Order respecting the prevention and alleviation of shortages of drugs in relation to COVID-19' remains unknown.^10,11 Nonetheless, Health Canada’s Interim Order measures, and now amendments to the Food and Drug Regulations to replace the ISAD IO, reflects the ongoing commitment and rapid adaptability to protect public health and safety during the pandemic.

References:

1.  Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19 - https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/interim-order-import-sale-advertising-drugs.html
2. Information and application requirements for drugs authorized under the Interim Order: Guidance document - https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/interim-order-import-sale-advertising-drugs/guidance.html
3. Explanatory note - https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/interim-order-import-sale-advertising-drugs/note.html
4.  Interim order and guidance document to import, sell and advertise COVID-19 related drugs and vaccines: Notice - https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/interim-order-import-sale-advertising-drugs/notice.html
5.  List of foreign drugs in relation to the COVID-19 pandemic - https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/authorization/foreign-drugs.html
6. List of new drugs for expanded indication in relation to the COVID-19 pandemic - https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/authorization/expanded-indication.html.  
7. What was heard: Consultation on interim order transition for COVID-19 drugs - https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/authorization/what-was-heard-consultation-interim-order-transition.html 
8. Regulations Amending the Food and Drug Regulations (Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19): SOR/2021-45 - https://canadagazette.gc.ca/rp-pr/p2/2021/2021-03-31/html/sor-dors45-eng.html
9.  Guidance on amendments to the Food and Drug Regulations for drugs for use in relation to COVID-19 - https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/food-drug-regulations-amendments-covid-19.html.  
10. Interim Order Respecting Drug Shortages (Safeguarding the Drug Supply) - https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/importation-exportation/interim-order-drug-shortages-protecting-supply.html
11. Interim Order respecting the prevention and alleviation of shortages of drugs in relation to COVID-19 - https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/interim-order-drug-shortages.html

Author:  Lydia To