Drug quality and supply chain requirements in light of Russia's invasion of Ukraine

Drug Establishment Licensing Bulletin 131, March 28, 2022

Health Canada is closely monitoring Russia's invasion of Ukraine for any potential impacts on the drug supply for Canada.

This DEL bulletin has been issued to:

• provide guidance on good manufacturing practices (GMP) during transportation and storage disruptions
• remind you of your regulatory requirements related to drug quality and shortages

On this page

• Transportation and storage considerations
• Requirements to report drug shortages and discontinuations
• Requirement to report GMP compliance issues
• Requirement to file amendments for clinical trials
• Expedited reviews of drug establishment licence (DEL) amendment applications

Transportation and storage considerations

Actions taken related to Russia's invasion of Ukraine have resulted in decreased shipping methods and routes. This may lead to Canadian suppliers using new shipping methods or routes.

Canadian importers, distributors and wholesalers must ensure that shipping conditions will not impact the safety, efficacy or quality of the drugs that we rely on.

To this end, please ensure such changes are evaluated in accordance with quality risk management (QRM) principles. You should also:

• evaluate the new shipping route/method to determine potential risks and extreme environmental conditions, including weather events
• review known information about the product, such as all stability data and freeze/thaw and high temperature cycling studies, where available
  • wholesalers should seek guidance and recommendations from their suppliers if they don't have this information
• apply mitigation strategies such as adding temperature monitoring points throughout the load to better assess transportation conditions
• review and update your risk evaluations from time to time

For more information on shipping and storage requirements, consult the following guidance document:

• Guidelines for temperature control of drug products during storage and transportation (GUI-0069)

Requirements to report drug shortages and discontinuations

The ongoing crisis in Ukraine may affect the drug supply. Therefore, we would like to remind all market authorization holders (MAHs) and DEL holders that they must notify or report drug shortages and discontinuations to Health Canada. MAHs are to report drug shortages and discontinuations on drugshortagescanada.ca.

Early reporting helps stakeholders who are affected to implement mitigation actions that will help them prevent or manage the adverse health effects of drug shortages and discontinuations.

The Food and Drug Regulations (FDR) outline the timelines for reporting discontinuations and shortages:

• at least 6 months before the day an anticipated shortage or discontinuation is expected to start (if more than 6 months away) or within 5 days of becoming aware of an anticipated shortage or discontinuation (if less than 6 months away)
• within 5 days of becoming aware of an actual drug shortage or an unanticipated discontinuation

Stakeholders are to post information on the website within 2 days of becoming aware of the shortage or discontinuation.

For more information on how to comply with the FDR, consult the following guidance document:

• Guide to reporting drug shortages and discontinuations

An MAH should also notify the Drug Shortages Unit of any shortages or discontinuations if:

• you hold a significant market share of the affected drug in Canada (are a sole supplier) or
• the drug is currently being used to treat COVID-19

To notify the unit, send an email to drug.shortages-penurie.de.medicament@hc-sc.gc.ca.

Requirement to report GMP compliance issues

DEL holders must report any event that may affect the quality, safety or efficacy of a drug they or their suppliers fabricate, package/label, test or store. This is set out in section C.01A.013 of the FDR. To report:

• send notifications using the subject "C.01A.013 notification" to el.applications-le@hc-sc.gc.ca
• include a description of the event and of the impact it may have on drug quality, safety and/or efficacy
• include any actions that have been taken or are planned to address the product risks, if known at the time of notification

Please review the information in the section "Expedited reviews of DEL amendment applications" if:

• the drug is medically necessary or
• the drug is used to treat COVID-19 and you wish to add a new supplier to your DEL

Requirement to file amendments for clinical trials

Sponsors of Health Canada-approved clinical trials must file a clinical trial application amendment (CTA-A) or notification (CTA-N) if the changes may affect the quality or safety of the clinical trial drug supply. A CTA-A or CTA-N may be needed if you are importing clinical trial drug supplies from impacted areas and thus must change the chemistry and manufacturing information.

For examples of situations that warrant filing a quality CTA-A or CTA-N, please consult the following guidance document:

• Guidance document for clinical trial sponsors: Clinical trial applications

Sponsors must ensure that:

• clinical trials are conducted in accordance with good clinical practices and
• systems and procedures are in place to ensure the quality of every aspect of the clinical trial

Expedited reviews of drug establishment licence (DEL) amendment applications

Health Canada will consider expediting foreign building applications if:

• your foreign building has been affected by Russia's invasion of Ukraine and
• the supply chain for medically necessary drugs and/or drugs deemed important to mitigate the risks of COVID-19 is affected

To help us prioritize requests, you must:

• complete the template for determining the medical necessity of a drug product (FRM-0378)
  • request a copy of this form by sending an email to:
    hc.del.questions-leppp.sc@canada.ca
• clearly indicate the following information in your cover letter:
  • drug brand name
  • drug identification number (DIN)
  • drug active ingredients
  • DEL application number (if an application has previously been submitted for this foreign building)
• submit requests to the Drug Establishment Licensing Unit at el.applications-le@hc-sc.gc.ca and include "COVID-19" or "Medically Necessary" in the subject line of any email correspondence related to these critical products

Once we receive your request, we will assess it and let you know if we are expediting the review.

A medically necessary drug is one that has been approved in Canada to prevent, treat or diagnose a serious or life-threatening disease or medical condition for which there is no available alternative. Patient inconvenience alone is not a good enough reason to classify a drug as medically necessary. If there are other market-authorized drugs available, please provide detailed market data demonstrating that these products are not available.

Note: The quality control department in Canada for each DEL holder is responsible for making sure that drug products comply with the Food and Drugs Act, the FDR and applicable market authorizations.

If you have questions or wish to inform us of any challenges you have experienced, please email us at drug.gmp.questions-bpf.medicaments@hc-sc.gc.ca.