Regulatory Drug Approval Process in Canada

Jimson Zachariah. C, Raju Kamaraj

Department of Pharmaceutical Regulatory Affairs, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur – 603203, Kanchipuram, Tamil Nadu, India.

*Corresponding Author E-mail: jimsonzachariah@gmail.com

ABSTRACT:

A regulatory procedure by which an applicant obtains the right to sell their products in their respective market of sale is called the drug approval process. Most of the products, including drugs to be marketed in Canada are authorized by the Health Products and Food Branch (HPFB) of Health Canada, more rightly, under the Therapeutic Product Directorate (TPD) for Drugs. The regulation of drugs varies from country to country. The drug approval procedure in Canada is examined closely by its regulatory body which is discussed. It consists of different stages of drug submission requisites for a safe and efficient regulatory strategy. This article specifically focuses on an elaborate study on Marketing Authorization of Drugs in Canada. HPFB of Health Canada is the National Regulatory Body which is accountable for assessing, and regulating the efficacy, safety and quality of drugs and other health products of Canada. The HPFB’s responsibility is to regulate the health-related risk-benefit ratio of health products and foods for Canadians.

KEYWORDS: Canada, New Drug Submission, Therapeutic Product Directorate, Health Canada, Health Products and Food Branch, Notice of Deficiency, Common Technical Document.

INTRODUCTION:

In the current times each country has different regulatory bodies and various other regulatory requirements which varies from country to country. The regulatory approach to each and every country is extremely difficult as each have different dossier formats. Therefore, to accomplish a suitable regulatory strategy, a deep and detailed knowledge on each country’s marketing authorization procedure and application requisites is highly required to attain high market potential on the drug to be marketed. Generally, there are 2 stages under New Drug Approval process as follows;

· Stage 1- Marketing Authorization Stage

· Stage 2-Clinical Trial Stage

The clinical trial phase is conducted from Phase 1 – Phase 4. These clinical studies are conducted to make sure safety and efficacy of the drug to be marketed. In addition to this Post-Marketing studies are also carried out.

Canada has a sophisticated approval process for the pharmaceutical drug sale into the Canadian market and a pre-market approval is required. All drug submissions are reviewed by Therapeutic Products Directorate of Health Canada. Once the product is successfully reviewed, a Drug Identification Number is assigned to that product indicating its approval.

New Drug Approval Process in Canada¹:

· Pharmaceutical drugs in Canada are regulated by Therapeutic Products Directorate of Health Canada. It also regulates medical device for human use.

· The pharmaceutical market of Canada is the 8-th largest one in the world with 2% of the world market by sales.

New Drug Submission (NDS) in Canada requires clinical trial data and information about production, labeling, usage and side-effects. When a New Drug Submission is submitted to the regulatory body of Canada, initially it undergoes an administrative screening procedure. This screening is done to ensure that all the required documents are enclosed in the optimal format. The target is to finish the screening process within a limit of 45 days from the receipt of NDS.

To complete a standard review the TPD has 300-day performance guideline and an 180-day timeline to complete priority review of NDS. The file is then passed on to the respective hierarchy of Bureaus for further review process.

STAGE 1: INITIAL DRUG RESEARCH:

To develop a DRUG, researchers begin with discovery & identification of certain synthetic substances, bio-chemical or other products. Once the new compound is found, tests for therapeutic activity, toxicity, efficacy and safety is performed. This initial stage may take several years of research and if optimal reports are obtained, researchers will advance to the next stage of developmental phase.

STAGE 2: PRE-CLINICAL STUDY PHASE:

In the next drug developmental stage drug is administered to chosen species of animals. The dosing range is obtained from this study along with PK/PD parameters & Safety levels of the drug.

STAGE 3: CLINICAL STUDY PHASE:

The drugs to be sold in Canada should have undergone clinical trial studies. The intention of conducting a clinical study is to obtain clinical data about the effectiveness of drug, its safety, the best dosing range in humans and so on.

a. Clinical Development:

1. During the termination of the clinical development plan; when such clinical studies have been previously conducted in Canada or other Countries applicant should apply for a New Drug Submission [NDS] with HPFB to obtain Marketing License of Drugs.

2. During the Clinical Development Program (CDP); when the applicant prefers to carry out the clinical trial study in Canada, then a Clinical Trial Application (CTA) must be submitted to HPFB. The results of these trials must be attached to the drug approval submissions.

b. Clinical Trial Application:

CTA is reviewed by HPFB and it addresses to the sponsor of the study within 30 calendar days from the date of application. The Canadian Clinical Trial Application report is plain and is listed as follows;

STAGE 4: DRUG APPROVAL PHASE:

NEW DRUG SUBMISSION PROCESS [NDS]:

· When the reports of all the pre-clinical and the clinical studies of the drug’s therapeutic benefit outweighs its risk and when all the necessary document is complete, only then the sponsor files an NDS with HFPB to gain marketing authorization of Drug in Canada.

· All such submissions ought to be presented to Health Canada in a e-CTD format as per ICH CTD Standards.

STAGE 5: AFTER-APPROVAL:

· Once a drug is approved to be marketed in Canada, the regulatory body requires the applicant to maintain the use of the drug product within the laid down standards of approval.

· In addition, Product Lifecycle Management(PLM) activities are necessary to affirm the evaluation of the drug product licensure.

· In short, the applicant should safeguard its unfailing conformity with the Food and Drug Regulations.

CTD Format Submission details for Drug Regulatory Activities in Canada²:

New Drug Submissions in Canada is submitted as per ICH CTD Format. It is a globally accepted format which is used by various regions. For medical devices Summary Technical Document(STED) by Global harmonization Task Force (GHTF) is recommended.

Table of contents in the CTD Submission guidance;

1	Introduction
1.1	Policy Objective
1.2	Policy Statement
1.3	Scope and Application
2	Guidance for Implementation
3	Structure of Drug Regulatory Activities in the CTD Format
3.1	Module 1: Administrative and Product Information
3.2	Module 2: CTD Summaries
3.3	Module 3: Quality
3.4	Module 4: Nonclinical Study Reports
3.5	Module 5: Clinical Study Reports
4	Presentation of Regulatory Activities
4.1	Identification of Regulatory Volumes
4.2	Identification of Information within Regulatory Activities
4.3	Language
4.4	Legibility and Font Size
5	Appendices
Appendix A	Canadian Module 1
Appendix B	Correlation of Original Versus Proposed Module 1
Appendix C	Post-Authorization Commitments
Appendix D	CTD Forma
Appendix A	Canadian Module 1

Reference

Table 1: Information in the CTD Format:

Module Number	Title and Main Section Headings	Cross-Reference to Modules	Binder/Label Color	Number of Label Copies
1	Administrative and Product Information	2,3,4 and 5	Red	1*
2	CTD Summaries	2 to 5	Yellow	1*
3	Quality		Blue	1*
4	Nonclinical Study Reports		Green	1
5	Clinical Study Reports		Black	1

*Note: For Combination Products that needs a joint review, an extra copy of modules 1,2 and 3 are required.

Steps to search the Drug Product Database of Health Canada ³:

Step 1:

Step 2:

Step 3:

Step4:

Search the Drug Product details with any one of the above listed criterias.

For Example:

Step 5: Search Result

Drug establishment License Application Form⁴:

Note: Refer the following link;

https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-health-products/compliance-enforcement/establishment-licenses/forms/drug-establsihment-licence-application-insytructioms-0033-eng.pdf

CONCLUSION:

Prior to authorization for sale in Canada Health Canada reviews them to levy their safety, efficacy and safety. Before obtaining marketing authorization the risk-benefit ratio along with the product’s quality must be assessed for a better market potential. New Drugs plays a significant role in modern medicine. Thus, a close scrutiny on the Drug licensing processes, by the governing regulatory body of Canada is a needful necessity for better consumer satisfaction and safety ratios. Such stringent guidance and laws for drug approval process will minimize the duplication of data for regulatory requirements of drug licensing and sale in Canada.

CONFLICT OF INTEREST:

The author does not declare any conflict of interest.

ACKNOWLEDGEMENT:

The author acknowledges the management of SRM College of Pharmacy, SRM Institute of Science and Technology for their valuable support.

REFERENCES:

1. www.ijpba.in/index.php/ijpba/article/download/19/19 accessed on 25-May,2019.

2. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/common-technical-document/preparation-drug-regulatory-activities-common-technical-document-format.html accessed on 30-May,2019.

3. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html accessed on 2-nd June,2019.

4. https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-health-products/compliance-enforcement/establishment-licences/forms/drug-establishment-licence-application-instructions-0033-eng.pdf accessed on 2-nd June,2019.

Received on 03.07.2019 Modified on 04.09.2019

Research J. Pharm. and Tech 2020; 13(4):2038-2042.

DOI: 10.5958/0974-360X.2020.00367.4