On March 30, 2019, the government published proposed amendments to the Food and Drug Regulations (FDR) intended to clarify whether a generic version of a drug can be approved using the abbreviated new drug submission (ANDS) pathway. These amendments affect how the FDR apply to a generic drug product if it contains a different medicinal ingredient than the Canadian reference product (CRP), but the same therapeutically active component. They also include changes to (i) labelling requirements and (ii) data protection eligibility for variations of previously-approved medicinal ingredients.
The proposed amendments follow a consultation on the topic conducted by Health Canada in 2017, and will supersede Health Canada’s 2017 Interim Policy on Health Canada’s Interpretation of Medicinal Ingredient and Assessment of Identical Medicinal Ingredient.
Interested persons have 70 days from the date of publication to make representations concerning the proposed regulations.
Drugs approvable via the ANDS pathway
Currently, a generic drug product must contain the identical medicinal ingredient to the CRP in order to be considered pharmaceutically equivalent and assessed via the ANDS pathway. The proposed amendments would change the test to require that the generic and the CRP share an identical “therapeutically active component”.
The “therapeutically active component” is defined for all new drugs as the medicinal ingredient, excluding those appended portions, if any, that cause the medicinal ingredient to be a salt, hydrate or solvate. The proposed amendments also clarify that the “medicinal ingredient” of a new drug refers to the ingredient as it exists in dosage form (rather than the input ingredient used in the manufacture of the dosage form), as determined by the Minister.
The proposed amendments would thus allow for generic drug products with the following differences in the medicinal ingredient to be assessed via the ANDS pathway, provided they have the same therapeutically active component as the CRP:
- different hydrated or solvated forms,
- different polymorphic forms, and
- different salt forms.
If Health Canada has reasonable grounds to believe there is a difference between generic and CRP, the proposed amendments permit it to request information from the generic manufacturer to demonstrate that the difference in safety and effectiveness, if any, is inconsequential.
According to the Regulatory Impact Analysis Statement (RIAS) accompanying the proposed amendments, complexes, clathrates, esters, and isomers or mixtures with different proportions of isomers would not be eligible to be assessed via the ANDS pathway.
Biologic drugs are specifically excluded from the ANDS pathway by the amendments. The RIAS notes that there is no change to how generic radiopharmaceuticals are approved.
The proposed amendments introduce changes to labelling requirements for all drugs, based on the newly-defined therapeutically active component and the revised definition of medicinal ingredient discussed above. If the therapeutically active component and the medicinal ingredient of a drug are not the same, both the name of the medicinal ingredient and the name and amount of therapeutically active components of the drug must appear on the label.
The proposed amendments alter the data protection provisions in the FDR in order to provide additional detail regarding the “variations” of a medicinal ingredient that are excluded from eligibility. These changes are intended to make the description of a “variation” consistent with the terminology used to describe medicinal ingredients in relation to a “therapeutically active component”.
The existing definition of “innovative drug” excludes a “variation of a previously approved medicinal ingredient such as a salt, ester, enantiomer, solvate or polymorph”. The proposed amendments provide that variations will be excluded and define variation to mean:
(a) an enantiomer or a mixture of enantiomers;
(b) a polymorph;
(c) a medicinal ingredient that, when compared to a previously approved medicinal ingredient, is identical, excluding those appended portions, if any, that cause either medicinal ingredient to be a salt, ester, hydrate, or solvate; or
(d) any combination of the variations found in paragraphs (a) to (c).
Coming-into-force & transition
The regulations will come into force 90 days after they are registered. The proposed amendments would not apply to drugs where the submission was filed before the coming-into-force date.