The development of a generic drug is very different from that of an innovative drug with a novel chemical composition. It must be sufficiently comparable to the latter to determine whether a generic drug is therapeutically equivalent to an innovator product. To be market-effective, drug companies must develop generic drugs that achieve the same level of therapeutic safety, efficacy, and functionality as branded drugs1.
The Canadian Health Authority (Health Canada) seeks to increase the availability of generic drugs to make them more affordable, safe, and accessible. Currently, generic drugs receive approvals 15 to 20 times more often than new drugs. Health Canada’s Health Products and Food Branch (HPFB) regulates, evaluates, and monitors the safety, efficacy, and quality therapeutic and diagnostic products available to the public. Several guidelines explain to what extent data must be provided before Health Canada approves a drug. As a result, for a generic drug to be approved and introduced on the market, a submission must be made to the HPFB. Upon a positive review by the HPFB, the generic drug is granted a Notice of Compliance (NOC) and a Drug Identification Number (DIN). A crucial component of regulatory approval of the generic drug is the Abbreviated New Drug Submission (ANDS) process2.
Abbreviated New Drugs Submission: The Pathway to Generic Drug Approval
A sponsor must submit an ANDS if a generic version of a previously approved drug is deemed ‘pharmacologically equivalent’ or ‘bioequivalent’ to the Canadian Reference Product (CRP). The following criteria must be met in accordance with the FDA Regulations (FDR) to file an ANDS:
- The generic drug is bioequivalent or pharmaceutically equivalent to the Canadian Reference Product (CRP)
- The generic drug has the same medicinal ingredients, in the same amount, with the same dosage form as the CRP
- The generic drug is administered by the same route as that of CRP2
There may be differences in non-medicinal ingredients (excipients) between generic drugs and CRPs. However, the company must demonstrate that these differences do not affect the generic drug’s safety, efficacy, or quality.
Although these are the main points to remember, there are also many other aspects to consider for the successful approval of an ANDS.
Generic Drug Submission in Canada: Common Pitfalls to Avoid
A generic drug submission, or ANDS, goes through the same review process as a brand-name drug submission. The following points should be considered when filling out the ANDS to avoid common mistakes.
- Suitable studies should be conducted to design and test a generic drug.
- A generic drug must meet all national and international patent and data protection requirements. ANDS cannot be submitted before a patent expires or a manufacturer challenges it2.
- The generic drug must comply with current laws and regulations and follow the recommendations laid out in Health Canada’s guidance documents3.
- Certified Product Information Document – Chemical Entities (CPID-CE) must accompany the original submission of an ANDS, which will help the Review Division reserve, plan, and allocate the necessary resources3.
- A bioequivalence study between the generic drug and CRP must be conducted per Health Canada’s recommendations.
- Foreign sourced reference products could be used instead of CRP if the following conditions are met4.
- The foreign-sourced reference product is approved by a comparable regulatory authority (US, EU, Japan, Australia, Switzerland).
- The same innovator company markets foreign-sourced reference products.
- Comparative in vitro studies between CRP and foreign-sourced reference products are submitted.
- Other conditions laid down in the Health Canada guidance document are met4.
- If the generic drug is intended to be imported into Canada, then the importer in Canada should be identified well in advance. The establishment license of the importer in Canada must list the foreign manufacturing sites of drug substance and drug product.
- Non-medicinal ingredients, shape, size, and color of a generic drug, can differ from CRP as long as it is bioequivalent to the CRP.
All generic drugs must adhere to regulatory guidelines for good manufacturing practices in their manufacturing processes and facilities. Each drug batch must also undergo both pre-and post-production tests to meet its intended use5.
Generic drugs have a large market potential in Canada, and it is expected to grow exponentially in the coming years. Multinational pharmaceutical companies and small companies can expand their generic drug portfolios in the Canadian generic drug market. Marketing authorizations denied by the HPFB can be supplemented, resubmitted with new information, or have the decision reviewed. Several best practices are recommended for ANDS that will aid the approval of generic drugs:
- To ensure that the technical information meets the requirements of Health Canada, a gap analysis should be performed.
- Attestation checklists are an important part of the ANDS screening process to help sponsors ensure that their submissions are complete and include all of the necessary information.
- The quality part of the ANDS must comply with Health Canada’s recommendations. Compliance with guidance documents on recent topics e.g., nitrosamine impurities, and elemental impurities should be ensured3.
- Before submitting an ANDS application, all manufacturing facilities should be ready for inspection.
- The original ANDS must include a detailed justification, including supporting data, of why they use an alternative bioequivalence method to those recommended in the relevant product-specific guidance.
- For maximum success, ANDS submission strategies and guidance on risk mitigation plans should be tailored as per Health Canada requirements6.
About The Author
Guriqbal Sigh is responsible for the execution and sourcing of regulatory product licenses on a regional and/or national scale. He works with clients and business partners in order to facilitate regulatory submissions by managing projects with supporting documents and samples. In addition, he maintains compliance with applicable regulatory obligations while ensuring milestones are met.
ClinChoice is a leading global Contract Research Organization (CRO), with over 3400 clinical research professionals across North America, Asia, and Europe. For more than 27 years, ClinChoice has been providing high-quality contract research services to pharmaceutical, biotechnology, medical device, and consumer products clients, encompassing a broad range of services and therapeutic areas. ClinChoice offers cutting-edge, full-service solutions for Clinical Trials, Regulatory Affairs, Medical Device Safety, Toxicology, and Medical Affairs.
- 1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3555014/
- 2) https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/fact-sheets/access-to-generic-drugs.html
- 3) https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/chemical-entity-products-quality/guidance-document-quality-chemistry-manufacturing-guidance-new-drug-submissions-ndss-abbreviated-new-drug-submissions.html
- 4) Microsoft Word – canadian-reference-product-guidance.docx (canada.ca)
- 5) https://www.canada.ca/en/health-canada/services/healthy-living/your-health/medical-information/safety-effectiveness-generic-drugs.html
- 6) https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/forms/notice-updated-screening-criteria-generic-drug-submissions.html