Quality, regulatory, safety: Meeting a collective compliance need

The list of regulatory activities required of pharma companies to get and keep a therapy on the market is extensive and continues to evolve as the Canadian regulatory landscape changes. Health Canada issues and enforces regulations to provide for the safety and quality of products both prior to and following their market entry. The regulations, policies, and guidelines define the monitoring requirements for marketing authorization holders (MAHs) to observe throughout the product life cycle.¹

MAH’s may face challenges in navigating how and when to address the various monitoring requirements, the subtleties of regulatory changes, and how different aspects of the product life cycle monitoring interact with each other.

Understanding nuances across the regulated environment

As the landscape of health authority regulations evolves, MAHs need to apply guidance documents to address regulatory requirements. In our experience, navigating the intricate details involved in meeting a regulation, including timelines, can require specialized expertise to help ensure compliance.

This is where partnering with an outsourcing provider that combines practical expertise in regulatory, quality, and pharmacovigilance expertise with real–world commercialization experience can offer significant advantages and efficiencies.

One emerging area of focus in many markets, including Canada, is the management and use of data generated from patient support programs². These programs generate real-world data that can support regulatory filings, such as priority review requests. Having access to this data, along with regulatory partners who understand how to maximize its value, can strengthen Health Canada filings and helps key stakeholders such as prescribers and Health Technology Assessors understand the value of a new therapy. 

Meeting Health Canada’s unique requirements 

There are a number of regulated activities that have unique requirements in Canada. Engaging experts who can navigate these activities can greatly support product approval and maintenance. 

There is a requirement in Canada for “local agent” representation, whether it is for (a) submission certification of a regulatory dossier to enable filing, (b) serving as a medical information contact, or (c) acting as an importer of record³.  It is common to see global pharma companies with internal regulatory teams in the European Union or United States without any equivalent Canadian team or function. Having a trusted local outsourcing partner and representation with expertise and service offerings across many areas to represent the company in Canada can be an effective way to addresses these barriers.

Health Canada requires a drug establishment license to enable the sale of a drug or medical device. For example, a drug establishment license (DEL)⁴  must be held by all Canadian physical sites that, among other activities, fabricate, package, label, or test a drug product or active pharmaceutical ingredients. When these activities are conducted at a foreign facility, a Canadian importer must ensure each site is listed on their DEL. This is achieved by submitting evidence of GMP (Good Manufacturing Practices) compliance specific to each foreign site to Health Canada⁵. This evidence includes an inspection report or certificate of compliance (CofC) from a Pharmaceutical Inspection Co-operation Scheme (PIC/S) member country that is no more than three years old and specific to the dosage form and activity conducted⁶.  Challenges can arise, however, if inspection reports are older than three years or pertain to a different dosage form or activity. For instance, an inspection report focused on solid oral dosage forms would not be applicable for supporting the addition of a sterile injectable.

For countries with a mutual recognition agreement (MRA) with Canada, MAHs can leverage a CofC instead of submitting a PIC/S member inspection report⁷. The same requirements regarding the age of the inspection report, the activity, and dosage form remain applicable. In these cases, Health Canada will request the CofC directly from the regulatory agency that completed the GMP inspection⁸.

Another Canada-specific requirement is the need for bilingual medical information–available in both English and Quebec French–and a local in-country contact. This differs from Europe’s requirement for a qualified person for pharmacovigilance (QPPV) or a local person for pharmacovigilance (LPPV), which means companies with established European operations may need to adapt their processes to meet Canadian expectations. In Canada, any adverse event must be reported to a Canadian-based medical information reporting center, with relevant information submitted to Health Canada within a specified timeframe². 

Health Canada also has specific requirements for pharmacovigilance activities, including foreign risk notifications. These requirements place the responsibility on the MAH to stay informed about global regulatory and safety activities and to notify Health Canada of any manufacturing issues, regulatory changes, or labelling updates that impact their product worldwide.

In our experience, Health Canada inspections have become increasingly stringent in recent years, posing challenges for pharma companies working to meet compliance standards.    When inspection findings occur, it can leave companies searching for the best way to address the gaps identified. Developing and implementing a robust corrective action or remediation plan is critical to resolving these issues effectively, and having the right expertise and support can make all the difference.

When MAHs receive a non-compliant rating, our experience has found that they may be required to engage a local consultant as interim management and supervisor of quality assurance activities to help navigate the remediation process. Developing a thorough and effective remediation plan to address critical inspection findings is essential to maintaining compliance and mitigating potential risks, such as product recalls, revocation of marketing authorization or cancellation of the DEL altogether. With the right local expertise and guidance, pharma companies can often successfully overcome these challenges and safeguard their operations. 

In these situations, pharma companies that use external consultants must inform Health Canada who they have engaged, and if they change their quality consultant, they must inform Health Canada that they have done so. This is an important consideration, as Health Canada’s inspectorates often build trusted relationships with local consultants over time.

Reaching across the activity aisle

Outsourcing can often be fragmented–separating regulatory, safety, and quality functions, can create operational inefficiencies. Bringing these outsourced services under one umbrella facilitates direct and seamless interaction between teams, eliminating the need to coordinate across different processes and organizations. Another advantage of a single outsourcing partner with expertise across the product life cycle is the ability to quickly address issues between regulatory, quality, and safety functions.

Problems can and do arise. When faced with challenges, cross-functional outsourced expertise enables companies to gain immediate assistance and access to additional resources. For example, if a company’s head of quality becomes ill or suddenly resigns, an outsourced partner with QA professionals can temporarily step into the role to help maintain operations and provide compliance support until a more permanent solution is in place.

With the ongoing need for pharma companies to reduce operational expenses, the value of outsourcing partners that provide comprehensive support across the product life cycle is clear. By leveraging the expertise of outsourcing partners, organizations can significantly reduce the fixed overhead costs associated with maintaining full-time internal teams. This strategy not only provides flexibility to scale resources in response to fluctuating demands but also grants access to specialized expertise and improved operational efficiency.

¹ Keeping health products in Canada safe, Health Canada. https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/keeping-health-products-canada-safe.html

² Questions and Answers: Plain Language Labelling Regulations for Prescription Drugs – document, Health Canada. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/questions-answers-plain-language-labelling-2019/document.html#s4

 ²  Wills A, Mitha A, Cheung WY. Data collection within patient support programs in Canada and implications for real-world evidence generation: the authors' perspective. J Pharm Pharm Sci. 2023 Oct 13. https://www.frontierspartnerships.org/journals/journal-of-pharmacy-pharmaceutical-sciences/articles/10.3389/jpps.2023.11877/full

³ Section C.08.005.1 of the Food and Drug Regulations, Health Canada. https://laws-lois.justice.gc.ca/eng/regulations/C.R.C.,_c._870/section-C.08.005.1.html

⁴ Drug establishment licences, Health Canada. https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/establishment-licences/drug-establishment-licences.html

 ⁵ Drug good manufacturing practices (GMP) and drug establishment licence (DEL) enforcement policy (POL-0004), Health Canada. https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/establishment-licences/directives-guidance-documents-policies/drug-good-manufacturing-practices-establishment-licensing-enforcement-directive-0004.html

⁶ Good manufacturing practices inspection policy for drug establishments (POL-0011), Health Canada. https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/good-manufacturing-practices/policies-standards/inspection-policy-canadian-drug-establishments.html

⁷ Health Canada Mutual Recognition Agreement (MRA) Programme, Health Canada presentation. https://www.afdo.org/wp-content/uploads/2020/08/1330-1530_IGR-Committee_Kimby-Barton.pdf

⁸ Mutual Recognition Agreement Evaluation Guide of Good Manufacturing Practices Compliance Programs, Health Canada. https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/international/mutual-recognition-agreements/evaluation-guide-good-manufacturing-practices-compliance-programs.html