Submitting a new drug to Health Canada can be a complex and time-consuming process. This post will provide essential information about the regulations, legal requirements, and specific steps involved in the submission process for new drugs in Canada.
Health Canada has been busy lately releasing several draft guidance documents related to drug compliance in Canada. In this blog we’re going to summarize all the following guidance documents for your convenience.
How to Prepare for a New Drug Submission?
Before submitting a new drug to Health Canada, it is important to make sure all clinical trials and other research related to the product have been completed. This includes testing for safety and efficacy, as well as documenting the manufacturing process for the drug. Additionally, it’s important to create documentation that explains how the drug works and its potential side effects. All this information must be submitted with the application for approval.
Who Can Apply for New Drug Submissions?
According to regulations set forth by Health Canada, only drug manufacturers and those with exclusive rights can submit a new drug for approval. Drug company owners and officers, research scientists, pharmacists, as well as individuals who have law degrees and specialized knowledge of pharmaceuticals are all eligible to submit an application for approval. Alternatively, companies that market drugs on behalf of drug makers are also authorized to apply for approval.
Health Canada’s Latest Draft Guidance for Drugs in Canada:
- Proposed Changes to Labelling of Pharmaceutical Drugs for Human Use
- Update Regulations for Biologic Drugs
- New Drug Submissions (NDSs) and Abbreviated New Drug Submissions (ANDSs)
- Management of Rolling Reviews for Drug Submissions
1.Proposed Changes to Labelling of Pharmaceutical Drugs for Human Use:
Health Canada launched a consultation on a proposal to amend the labelling of pharmaceutical drugs for human use guidance document on December 21, 2022. The proposed changes were to sections C.01.004(1)(a) and C.01.011 of the Food and Drug Regulations.
What are the Proposed Changes?
We have summarized the proposed regulatory amendments for your convenience:
2.1.1 Principal Display Panel
“The standard for the drug product, if any;” will no longer need to be displayed on the principal display panel.
126.96.36.199 Proper Name
It will no longer be a requirement to list the standard of manufacture near the proper name of the drug, instead Health Canada proposes leaving it up to the discretion of the sponsor whether or not they “would like to include the standard of manufacture”, but if they do, should still include it in close proximity to the proper name.
3.4.3 Standard of Manufacture
Health Canada is proposing removing “Pursuant to subsection C.01.004 (1) of the Regulations” from: Pursuant to subsection C.01.004 (1) of the Regulations, where a standard prescribed by the Regulations exists (see Section 188.8.131.52, “Prescribed Standard”) and it applies to the specific drug product, it shall be included on the principal display (main) panel of the inner and outer labels. Additionally, the proposal changes “it shall be included” to “it may be included” from the above statement.
184.108.40.206 Prescribed Standard
It will no longer be required to include on the label the CSD standard, however the drug substance must still conform in all aspects to that standard.
220.127.116.11 Manufacturer’s Standard
The proposal removes both references to sections C.01.011 & C.01.011 (4) of the Regulations:
In accordance with section C.01.011 of the Regulations, no person shall use a manufacturer’s standard for a drug that provides (a) lesser degree of purity than the highest degree of purity, or (b) a greater variation in potency than the least variation of potency, provided for that drug in any publication mentioned in Schedule B to the Act.
18.104.22.168 Placement of Standard on Labelling
The proposal removes “(see subsections 10(1) and (2) of the Act)”, and “this standard” from Where a standard of manufacture is to be shown on a label (see subsections 10(1) and (2) of the Act), this standard should be declared near the prescribed or proper name of the drug product. The quantitative amounts may be indicated before or after the prescribed or proper name (e.g., Conjugated Estrogen Tablets CSD 1.25 mg, Acetaminophen Tablets USP, 325 mg).
3.5.5 Declaration of Medicinal Ingredients
The proposal removes the footnote from “However, when a standard exists for the entire combination, then this standard must normally 10 be declared on the main panel of the label” and also changes “must” to “may”.
5.4.5 Prescribing Information
The proposal removes “Standard of manufacture where required by the Regulations;” from the prescribing information (or professional information) for new drug products not conforming to the Product Monograph format or not subject to Division 8 of the Regulations.
2. Update to Health Canada Regulations for Biologic Drugs:
Health Canada issued a notice to stakeholders on December 16, 2022, regarding their proposal to amend the regulations for biologic drugs (Schedule D drugs) in Division 4, Part C of the Food and Drug Regulations.
This notice is for businesses that manufacture, package/label, test, store, import, distribute, and/or wholesale biologic drugs.
The goal of this proposal is to:
- support current biological drug practices.
- and better address scientific and technological advances.
This is true for drugs on Schedule D of the Food and Drug Act (FDA)
- Division 4 of Part C of the Food and Drugs Regulations applies to biologic drugs.
- The FDA’s Schedule D contains legislation for biologic drugs to which Division 4 applies.
What are the changes?
The amendments to Division 4 propose to:
- Replace existing Division 4 regulations (from C.04.001-C.04.683 to C.04.001-C.04.010)
- Add a new regulation to Division 2 (C.02.012.1)
- Amend a regulation in Division 8 (C.08.003.1)
Need help navigating the latest Health Canada draft guidance for OYTC drugs?
3. Proposed changes in New Drug Submissions (NDSs) and Abbreviated New Drug Submissions (ANDSs):
On December 22, 2022, Health Canada opened a consultation on a proposal to amend the Quality (Chemistry and Manufacturing) Guidance: New Drug Submissions (NDSs) and Abbreviated New Drug Submissions (ANDSs).
S.3.1 Structure and Other Characteristics Elucidation
Confirmation of structure should be provided based on the synthetic route and spectral analyses. Information such as the potential for isomerism, stereochemistry identification, and the ability to form polymorphs should also be included.
To: Confirmation of the molecular structure of the drug substance should be provided using spectroscopic and other relevant techniques. Data addressing potential isomerism, including absolute and relative stereochemistry, should be provided where applicable. The characterization should use appropriate techniques when elucidating the internal structure of the drug substance (such as amorphous or alternative crystalline forms) (such as single crystal and powder x-ray diffraction). Use samples that are representative of the proposed manufacturing process.
S.3.2 Impurities – Determining Potential and Actual Impurities
From: Potential impurities should be investigated for structural alert(s). When appropriate, any potentially mutagenic impurities should be assessed and controlled in accordance with ICH M7.
To: Potential impurities should be investigated for structural alertness (s). When appropriate, assess and control any potentially mutagenic impurities, including the potential formation or introduction of high-potency mutagenic carcinogens identified in the ICH M7 guideline as the cohort of concern (aflatoxin-like, N-nitroso, and alkyl-azoxy compounds).
S.4.1 Specification – Specifications
From: If a Schedule B compendial monograph applies to the drug substance, a sponsor may declare a Manufacturer’s Standard on the label (which indicates that the material may differ in some respect from the compendial standard). However, under section C.01.011 (4) of the Food and Drug Regulations, no one shall use a manufacturer’s standard for a drug that provides (a) a lesser degree of purity than the highest degree of purity and (b) a greater variation in potency than the least variation in potency provided for that drug in any publication mentioned in Schedule B to the Act.
To: If a Schedule B compendial monograph is applicable to the drug substance, a sponsor can choose to declare a Manufacturer’s Standard on the labelling (which indicates that the material may differ in some respect from the compendial standard).
Added: The drug substance specification should include routine testing for nitrosamine impurities when the risk for presence is high or the concentration of any nitrosamine is at significant levels (for example, greater than 30% of the acceptable intake limit).
P.2 Pharmaceutical Development – Dosage and Administration
Added: The measures taken during development to reduce the presence of high-potency mutagenic carcinogens (aflatoxin-like, N-nitroso, and alkyl-azoxy compounds) identified in the ICH M7 guideline as the cohort of concern in the drug product and its components
Sections 2.3 and 3.2.P.2 of the drug application include a risk assessment for the potential presence of nitrosamine impurities in the drug product.
Analytical data, procedures, and proposed controls should be included in the appropriate sections of the drug application (e.g., 3.2.S.2, 3.2.S.4, 3.2.S.7, 3.2.P.3, 3.2.P.4, 3.2.P.5, 3.2.P.7, 3.2.P.8)
P.5.1 Control of Drug Product: Specification(s)
From: If a Schedule B compendial monograph is applicable to the drug product, a sponsor can choose to declare a Manufacturer’s Standard on the labelling which indicates that the material may differ in some respect from the compendial standard. However, according to section C.01.011 of the Food and Drug Regulations, no person shall use a manufacturer’s standard for a drug that provides (a) less purity than the highest degree of purity and (b) a greater variance in potency than the least variation in potency, provided for that drug in any publication mentioned in Schedule B to the Act.
To: If a Schedule B compendial monograph is applicable to the drug product, a sponsor can choose to declare a Manufacturer’s Standard on the labelling which indicates that the material may differ in some respect from the compendial standard. However, the specifications must be acceptable to the Minister.
Added: Routine testing for nitrosamine impurities should be included in the drug product specification when:
- the potential for nitrosamine introduction during drug product manufacturing, packaging, and storage is identified or
- a nitrosamine impurity is detected in the drug product during confirmatory testing and the root cause of its presence is unknown.
- Where such a risk is identified, a test and acceptance criteria for both release and shelf-life specifications should be included in the drug application.
4. Management of Rolling Reviews for Drug Submissions:
New amendments to the Food and Drug Regulations are being proposed by Health Canada. “New provisions that enable the rolling review of a new drug submission (NDS) or supplement to a new drug submission (SNDS) that meets specific eligibility conditions” are among the amendments.
If a sponsor meets certain eligibility criteria, the amendments will allow them to apply for rolling review status for future drug submissions.
This rolling review status will allow a sponsor to file a drug submission to Health Canada without providing all of the necessary information about the drug’s safety, efficacy, and quality. Once a drug submission has been filed, the sponsor will have a certain amount of time to provide the missing information. Eligibility for a rolling review will not change the safety, efficacy, and quality requirements outlined in Part C of the associated regulations.
Scope and Application:
This draft guidance document is intended for sponsors who want to apply for rolling review status for a future drug submission as well as sponsors who have already filed a submission that has been granted rolling review status.
The document also applies to rolling reviews of drug submissions that are related to vaccines under the “List of Influenza Vaccines for Which Supplements to New Drug Submissions Can be Filled”.
The Health Products and Food Branch is responsible for regulating drugs for human and veterinary use in accordance with the Food and Drugs Act (act) and its regulations.
This guidance document does not apply to the following submissions:
- drug submissions eligible for a rolling review for a public health emergency drug for COVID-19 or a condition described in the List of conditions that threaten public health in Canada.
- veterinary drug submissions undergoing joint or simultaneous reviews with foreign regulatory authorities.
The rolling review option does not apply to the following:
- abbreviated new drug submission (ANDS) pathway.
- supplement to an abbreviated new drug submission (SANDS) pathway.
- submission classes with a performance standard of 120 days or less.
Objectives of the Policy:
The goal of this change is to give Health Canada the option of receiving information for an eligible new drug submission or supplement to a new drug submission (SNDS) after the submission has already been filed. Furthermore, this change will aid in the resolution of issues earlier in the rolling review process and provide more opportunities for interactions between Health Canada and the sponsor. All of this will help to expedite access to the Canadian market if evidence of safety, efficacy, and quality is presented.
How Quality Smart Solutions can help
Are you looking to have your drug product registered with Health Canada? Quality Smart Solutions has a team of experts who are skilled with DIN applications. If you need help with your Drug Establishment License (DEL) Registration we can help with that as well. Please contact us today or call us at 1-800-396-5144 to learn about how we can help you.