GRP’s approach to designing regulatory strategy employs our strong understanding of the global markets and regulatory systems to enable our clients to make confident, actionable decisions. We specialize in assisting pharmaceutical companies with their most difficult, complex endeavors in Asia, and can help our clients to develop intelligent solutions in all areas.
Our regulatory team in Canada has the expertise in developing effective and tailored regulatory strategies that helped many foreign companies to register their products quickly and efficiently.
To develop the correct regulatory strategy that meet companies’ goals, our local team:
- Identify and the latest regulatory requirements related to your pharmaceuticals, biologics, biosimilars and generics.
- Proactively identify challenges or issues that may delay the approval of your pharmaceutical in Canada.
- Identify potential risks and obstacles so that you can avoid any unexpected roadblocks during the registration process.
- Propose innovative solutions and approaches to circumvent these challenges ahead of time.
- Identify the most cost-effective way to get your pharmaceutical product registered in Canada.
Drugs are authorized for sale in Canada once they have successfully gone through the drug review process. This process is how a drug application is reviewed by scientists in the Health Products and Food Branch (HPFB) of Health Canada, and on occasion, outside experts, to assess the safety, efficacy and quality of a drug.
Throughout the process, the safety and well-being of Canadians is the paramount concern.
Research for new drugs begins with scientists developing various chemical or biological substances. Once a substance has been isolated and purified, it is administered to tissue cultures or to a variety of small animals to see whether or not there are significant changes. These changes may be biochemical, physiological or behavioural in nature.
If promising results are obtained from these initial studies, a variety of animal and laboratory tests are conducted to study other effects of the substance [for example (e.g.) how it affects the immune system or reproductive system] and to determine what dosage of the substance should be given to achieve a particular effect.
If these preclinical tests indicate that a substance produces the desired result and is not toxic, the sponsor [that is (i.e.) the person or company who takes responsibility for the application] may apply to HPFB for authorization to conduct a clinical trial in Canada.
Sponsors who wish to conduct Clinical Trials in Canada must submit a Clinical Trial Application (CTA). Information contained in a clinical trial application includes the results from preclinical tests, production methods, dosage form and information regarding the investigators who will be conducting the study.
If clinical trial studies prove that the drug has potential therapeutic value that outweighs the risks associated with its use (e.g. adverse effects, toxicity), the sponsor may choose to file a New Drug Submission with HPFB.
The steps in the review process:
- When a sponsor decides that it would like to market a drug in Canada, it files a “New Drug Submission”v(NDS) with HPFB. This contains information and data about the drug’s safety, effectiveness and quality. It includes the results of the preclinical and clinical studies, whether done in Canada or elsewhere, details regarding the production of the drug, packaging and labelling details, and information regarding therapeutic claims and side effects.
- HPFB performs a thorough review of the submitted information, sometimes using external consultants and advisory committees.
- HPFB evaluates the safety, efficacy and quality data to assess the potential benefits and risks of the drug.
- HPFB reviews the information that the sponsor proposes to provide to health care practitioners and consumers about the drug (e.g. the label, product brochure).
- If, at the completion of the review, the conclusion is that the benefits outweigh the risks and that the risks can be mitigated, the drug is issued a Notice of Compliance (NOC), as well as a Drug Identification Number (DIN) which permits the sponsor to market the drug in Canada and indicates the drug’s official approval in Canada.
- In addition, Health Canada laboratories may test certain biological products before and after authorization to sell in Canada has been issued. This is done through its Lot Release Process, in order to monitor safety, efficacy and quality.
HPFB has a Priority Review Process in place which allows for a faster review to make available promising drug products for life-threatening or severely debilitating conditions, such as cancer, AIDS, or Parkinson’s Disease, for which there are few effective therapies already on the market.
Health Canada has adopted the CTD format, and NDS submissions are required to be submitted as per CTD requirements.
Application Review Timelines by Health Canada
|New Active Substance: NDS||300 days|
|Clinical Supplements: SNDS||300 days|
|CMC supplements SNDS||180 days|
|Labelling supplements SNDS||60 days|
|Generic drugs: ANDS||180 days|
|CMC supplement SANDS||180 days|
|Biologics: NDS||300 days|
|Clinical Supplements SNDS||180 days|
|CTA and Amendments||30 days|
|CTA Bioequivalence||7 days|
Clinical Trial Application
The modules are organized and numbered consistently in an internationally adopted format – the Common Technical Document (CTD). Adhering to the CTD format facilitates evaluation by Health Canada and ensures consistency of documents in subsequent stages of the drug authorization process.
- Module 1 – contains administrative and clinical information about the proposed trial
- Module 2 – contains Quality (Chemistry and Manufacturing) information about the drug product(s) to be used in the proposed trial
- Module 3 – contains additional supporting Quality information
For Health Canada’s official guidance document on CTA’s please check the website at:http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.php
New Drug Submissions
|Module||Content||Binder/ Label colour|
|1||Administrative and Product Information
1.1 Table of Contents (Modules 1 to 5)
1.2 Administrative Information
1.3 Product Information
1.4 Health Canada Summaries
1.5 Environmental Assessment Statement
1.6 Regional Clinical Information
1.7 Clinical Trial Application and Clinical Trial Application- Amendment Specific Requirements
|2||Common Technical Document (CTD) Summaries
2.1 CTD Table of Contents (Modules 2 to 5)
2.2 CTD Introduction
2.3 Quality Overall Summary
2.4 Nonclinical Overview
2.5 Clinical Overview
2.6 Nonclinical Written and Tabulated Summaries
2.7 Clinical Summary
3.1 Table of Contents of Module 3
3.2 Body of Data
3.3 Literature References
|4||Nonclinical Study Reports
4.1 Table of Contents of Module 4
4.2 Study Reports
4.3 Literature References
|5||Clinical Study Reports
5.1 Table of Contents of Module 5
5.2 Tabular Listing of All Clinical Studies
5.3 Clinical Study Reports
5.4 Literature References
- Single copy of each document is usually required.
- For combination products that require a joint review an additional copy of Modules 1, 2, and 3 is required.
- For more information, visit the ICH website at:http://www.ich.org/home.html
- Guidance Document: Preparation of Drug Regulatory Activities in the Common Technical Document (CTD) Format:http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/ctd/ctd_prep_nds-eng.php
To comply with Canadian GMP regulations, companies first must register their domestic and global establishments.
In Canada, a drug establishment performing any of six licensable activities (fabricating, packaging/labeling, testing, importing, distributing and wholesaling) must apply for a Health Canada drug establishment license pursuant to Division 1A of the Food and Drug Regulations
QUALITY MANAGEMENT SYSTEM FOR PHARMACEUTICALS IN CANADA
Health Canada’s Health Products and Food Branch Inspectorate (HPFBI) primarily is responsible for health product compliance monitoring activities, such as industry inspection and product investigation. HPFBI develops and implements enforcement strategies in these areas. Establishment licensing and related laboratory functions support these compliance and enforcement activities. Applicable and useful Health Canada GMP regulations and guidance documents are listed below
Health Canada GMP Guidance Documents
|Good Manufacturing Practices Guidelines–2009 Edition, Version 2 (GUI-0001)||Provides interpretive guidance for Part C, Division 2, of the Food and Drug Regulations. These guidelines are designed to facilitate compliance by the regulated industry and to enhance consistency in the application of the regulatory requirements.|
|Annex 2 to the current edition of GMP Guidelines Schedule D Drugs (Biological Drugs) (GUI-0027)||Provides further guidance for Part C, Division 2, of the Food and Drug Regulations as they relate to biologic products.|
|Good Manufacturing Practices (GMP) Inspection Summary Reports||Define how inspection works, what inspectors look for and inspection ratings|
|Alternate Sample Retention Site Guidelines (GUI-0014)||These guidelines facilitate compliance to Section C.02.025 of the Food and Drug Regulations and enhance consistency in the application of the regulatory requirements by describing the requirements regarding Alternate Sample Retention (ASR) sites for finished drug products.|
|Guidelines for Temperature Control of Drug Products during Storage and Transportation (GUI-069)||Shipping container requirements7|
|Good Manufacturing Practices for Medical Gases (GUI-0031)||The guidance is regarding the fabrication, packaging, labelling, testing, distribution, and importation of medical gases.|
In Canada, biologics generally are defined as products under Schedule D of the Food & Drug Act. Health Canada’s Biologics and Genetic Therapies Directorate (BGTD) is the Canadian federal authority responsible for overseeing biological drugs for human use. BGTD, in concert with other partners, namely HPFBI, the Marketed Health Products Directorate (MHPD) and the Public Health Agency of Canada (PHAC), monitor product safety and effectiveness throughout the product lifecycle.
Good Manufacturing Practices Guidelines–2009 Edition, Version 2 (GUI-0001), generally is applicable to biologics. Also, as part of Health Canada’s efforts in harmonizing standards with the EU and the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S), several annexes (Table 4) have been added to the current edition of the guidance.
|Annex 2 to the current edition of the Good Manufacturing Practices Guidelines—Schedule D Drugs, Biological Drugs (GUI-0027)|
|Annex 13 to the current edition of the Good Manufacturing Practices Guidelines—Drugs Used in Clinical Trials (GUI-0036)|
|Annex 14 to the current edition of the Good Manufacturing Practices Guideline—Schedule D Drugs, Human Blood and Blood Components (GUI-0032)|
Pharmaceutical Quality Systems for Drugs Products
Pharmaceutical companies are responsible for complying with FDA and Health Canada regulations to maintain a high level of safety, efficacy and quality of their products. Compliance can be achieved by implementing a pharmaceutical quality system. Adherence to the internal PQS can ensure the identity, strength, quality and purity of drug products by requiring stringent control of every step in the lifecycle. It is important to know CGMPs only are minimum (baseline) standards. A well-designed PQS should exceed these standards
Our medical device quality assurance (QA) and regulatory affairs (RA) outsourcing services include:
- Full or “as needed” consulting for ISO and/or GMP quality assurance and regulatory affairs.
- Audits of your quality management system or a supplier’s quality system.
- Review of corrective actions and recommendations for resolution.
- Supporting quality metrics and analysis as part of the management review meetings.
- Internal auditor training, risk management, quality system, or other training needs.
- Complaint handling, contract review and surveillance audits.
- Document control and maintenance of the quality system.
Local Agent Representation for Medical Products in Canada
Canada is one of the few countries with a well-developed regulatory system for drugs and pharmaceuticals where a local representative is not required to market a product within its borders. Foreign manufacturers can register and market their drugs and devices in Canada without a local representative, except in the case of devices containing wireless technology.
Manufacturer’s or sponsors who wish to conduct investigational tests for pharmaceuticals in Canada must submit a Clinical Trial Authorization Application.
Requirements for Approval of Clinical Trial Initiation
The process for gaining approval to conduct a clinical trial in Canada is efficient and straightforward, resulting in one of the world’s fastest trial start-up timelines. If applications are processed without encountering any difficulties, approval can be granted in 30 days.
An Drug sponsors seeking approval to conduct Phase I-III trials must submit a Clinical Trial Application (CTA) to Health Canada. (Some sponsors depend upon their clinical trial partners to complete the CTA.) The agency is required to respond within 30 days, either with an approval (in the form of a No Objection Letter (NOL)), a request for more information, or a denial. Sponsors are required to have the CTA signed by a scientific medical advisor who must be a physician or Ph.D and residing in Canada. The information required on the CTA is very similar to that needed for an Investigational New Drug (IND) application in the U.S., and information prepared for one form can easily be “cut and pasted” into the other. Note that at this writing, CTAs are still submitted in hard copy form, however, Health Canada is piloting an e-submission process with the goal of moving to electronic-only submission. Sponsors must also get approval on their final protocols from the Ethics Committees at investigator sites or through a central IRB, although this effort can run in parallel with the CTA approval described above to save time. The documentation required from each site before it can be activated includes
- A Clinical Trial Site Information Form. This can be sent to Health Canada as part of the CTA, although usually sponsors have not completed their investigator recruitment at the time that they file their CTAs
- A Research Ethics Board Attestation (REBA) or equivalent
- A Qualified Investigator Form
Requirements for conducting clinical trials
All investigational testing carried out in Canada must conform to the principles of the Declaration of Helsinki and the Medical Research Council’s “Code of Ethical Conduct for Research Involving Humans – May 1997.
Clinical trials involving pharmaceuticals should be compliant with ICH: E6 good clinical practices.