Date: 20071214
Docket: T-1693-06
Citation: 2007 FC 1323
Ottawa, Ontario, December 14, 2007
PRESENT: The Honourable Mr. Justice Kelen
BETWEEN:
PHARMASCIENCE
INC.
Applicant
and
ATTORNEY
GENERAL OF CANADA
Respondent
REASONS FOR ORDER AND ORDER
[1]
This is an
application for judicial review of a decision by the Therapeutic Products
Directorate of Health Canada (the TPD) dated August 21, 2006, whereby the TPD
concluded that the applicant’s application for a Notice of Compliance (NOC) for
a generic drug was considered withdrawn without prejudice to re-filing because
the applicant did not provide the required bioequivalence data in relation to
the Canadian reference product.
[2]
The
existence, contents, and status of the applicant’s submission for a NOC is
confidential. To preserve such confidentiality, the drug in question is
referred to as “pms-X/Y” rather than by its proposed brand name. The components
it contains are referred to as “component X” and “component Y” rather than by
their molecular names, and the condition for which approval is sought is
referred to as “condition A” rather than the condition itself. The applicant’s
submission for a NOC was made with reference to a Canadian reference product
which, for the same reasons of confidentiality, will be referred to as
“REFPRO,” manufactured by another company, “Pharmacompany.”
FACTS
[3]
On July
29, 2005, the applicant, Pharmascience Inc., filed an Abbreviated New Drug Submission
(ANDS) with the Minister of Health seeking a NOC for its product pms-X/Y, which
is used for treatment of condition A.
[4]
The
applicant’s product is a delayed release tablet containing two ingredients,
component X and component Y.
[5]
According
to the applicant, even though REFPRO is itself a generic, it has become the
Canadian reference product to which any new generic version is compared. This
is due to the fact that REFPRO is the only X/Y product available in Canada for the treatment of
condition A. In support of the claim that REFPRO is the appropriate Canadian
reference product, the applicant notes that Health Canada itself described the
applicant’s ANDS as the “first generic submitted for the combination” of components
X and Y.
[6]
On
December 16, 2002, prior to filing its ANDS, the applicant met with
representatives of the TPD to discuss the submission requirements of their
proposed drug. At the meeting, the applicant was informed that the TPD considered
that bioequivalence of both components X and Y should be demonstrated in the
applicant’s submission. The TPD also made clear that if the applicant decided
not to test for component Y, then it would have to justify why such a
measurement was not necessary. According to the respondent, such justification should
include clinical data demonstrating that component Y does not have a
significant therapeutic effect in the treatment of condition A. Despite this
notification, the applicant nevertheless decided that it would not conduct or
submit bioavailability studies for component Y. Accordingly, the applicant’s
ANDS only included comparative bioavailability studies with respect to component
X. It did not include comparative bioavailability studies for component Y.
[7]
On
September 30, 2005, after “screening” the applicant’s July 29, 2005
application, the TPD informed the applicant that its submission was incomplete
and, in particular, that a bioavailability study must be provided measuring the
formulation’s Y component. The TPD’s notification provided the applicant with 45
days to address each of the identified deficiencies.
[8]
On
November 9, 2005, the applicant provided its response to the deficiencies
identified by the TPD. In its response, the applicant raised four reasons why
it believed a comparative bioavailability study of component Y was not required.
Those reasons included: 1) that the Minister’s general approach to
bioequivalence reporting was not required for components of the class of
component Y; 2) that there was no scientific support suggesting that component
Y, at the dosage in the REFPRO formulation, had any therapeutic effect in the
treatment of condition A; 3) that REFPRO’s previously-issued Product Monograph did
not reference scientific support of such therapeutic effects; and 4) that the
amount of component Y in the product was known to be safe and was within the TPD’s
guidelines.
[9]
Despite its
arguments, on January 24, 2006, the applicant received a “screening rejection
letter” from the TPD, indicating that its ANDS was considered “withdrawn
without prejudice to refiling.” The TPD determined that the applicant’s ANDS
did not comply with Part C, Division 8 of the Food and Drug Regulations,
C.R.C., c. 870 (the Regulations), since the applicant had not filed comparative
bioavailability studies demonstrating bioequivalence of component Y with that
in the Canadian reference product, REFPRO.
[10]
On February
22, 2006, in accordance with the guidance document “Reconsideration of Final
Decisions Issued for Human Drug Submissions,” the applicant filed a letter
outlining its intent to request a reconsideration of the January 24, 2006
screening rejection letter. Subsequently, on April 18, 2006, the applicant
filed its formal “Request for Reconsideration” with the TPD.
Decision
under review
[11]
On August
21, 2006, the TPD advised that, on the basis of a recommendation from the TPD’s
Office of Science, the original decision was being upheld. In his decision, the
Director General of the TPD stated that:
The Directorate is maintaining the
initial decision since, on re-consideration, it is clear that [component Y has
a condition A-related effect]. Evidence of bioequivalence to the Canadian
reference product will be required for both [component Y and component X] of
the above-named product.
ISSUE
[12]
The sole
issue in this application is whether the TPD erred in rejecting the applicant’s
submission on the ground that the applicant failed to provide a comparative
bioavailability study for component Y.
RELEVANT
LEGISLATION
[13]
The
legislation relevant to this application is the Food and Drug Regulations,
C.R.C., c. 870. The relevant provisions are contained within Part C, Division
8, and have been attached to this judgment as Appendix “A.”
STANDARD
OF REVIEW
[14]
In Dr.
Q v. The College of Physicians and Surgeons of British Columbia, 2003 SCC
19, [2003] 1 S.C.R. 226, the Supreme Court of Canada reaffirmed the primacy of
the pragmatic and functional approach in relation to the review of
administrative decisions. Chief Justice McLachlin, writing for a unanimous
Court, stated at paragraph 25:
¶ 25 … it is no longer
sufficient to slot a particular issue into a pigeon hole of judicial review
and, on this basis, demand correctness from the decision-maker. Nor is a
reviewing court’s interpretation of a privative clause or mechanism of review
solely dispositive of a particular standard of review. … The pragmatic and
functional approach demands a more nuanced analysis based on consideration of a
number of factors. This approach applies whenever a court reviews the decision
of an administrative body. …
[Emphasis added.]
[15]
In Reddy-Cheminor
Inc. v. Canada (Attorney General), 2003 FCT 542, 233 F.T.R. 271, aff’d 2004
FCA 102, 319 N.R. 185, Madam Justice Layden-Stevenson considered the standard
of review to be applied by a reviewing court to the decisions of the Minister
of Health relating to drug approval. After applying the pragmatic and functional
approach, Madam Justice Layden-Stevenson found at paragraph 57:
¶
57 The balancing of these four factors suggests considerable deference and
thus a standard of review of patent unreasonableness. I refer to the comments
of MacKay J. in [Apotex Inc. v. Canada
(Attorney General) (1993), 59
F.T.R. 85] at p. 111-112:
“In this case the discretion granted to the executive
involves more than the determination of facts and the application of the law in
determining the rights of a party that do not directly affect the welfare of
others. More is here involved than is often the case where courts are called
upon in an application for judicial review to review the process followed by an
administrator or tribunal. Discretion here vested by the Act and Regulations requires
judgment in light of special expertise, in this case in related fields of
applied and basic sciences, which judgment affects not merely the rights of an
applicant party but is directed ultimately to the interests of, or prevention
of injury to, the health of others, purchasers and consumers. In my view,
discretion of this sort warrants judicial deference that recognizes the special
expertise and responsibilities of the Minister and his advisers within HPH (Health
Protection Branch) who must deal with numerous applications for approval of new
drugs … it is now accepted that a court will intervene only where the decision
maker has interpreted governing legislation in a manner that is so patently
unreasonable that it demands intervention by the court . . .”
[16]
This finding
was affirmed on appeal, with Mr. Justice Evans stating at paragraph 8 of the
appellate decision:
¶ 8 Second, I agree with
Layden-Stevenson, J., that the pragmatic and functional analysis indicates that
the decision under review is entitled to a high degree of deference. The drug
approval process is a complex and technical area of public administration with
a direct impact on the health of Canadians. Determining whether two products
contain “identical medicinal ingredients” requires scientific understanding and
regulatory experience, rather than knowledge of the law or legal principles.
[17]
In the case
at bar, the decision of whether a comparative bioavailability study is required
in an ANDS falls directly within the expertise of the scientists at the TPD.
Accordingly, the decision of the TPD will only be set aside if it is found to
be patently unreasonable.
[18]
In Law
Society of New Brunswick v. Ryan, 2003 SCC 20, [2003] 1 S.C.R. 247, the
Supreme Court of Canada stated at paragraph 52 that a patently unreasonable
defect is one that can be explained “simply and easily, leaving no
real possibility of doubting that the decision is defective.” This is a very
high standard. Accordingly, a decision will only be set aside as being patently unreasonable if it is
“clearly irrational” or “evidently not in accordance with reason.”
ANALYSIS
Issue: Did the TPD
err in rejecting the applicant’s submission on the ground that the applicant
failed to provide a comparative bioavailability study for component Y?
Drug
approval regulatory framework
[19]
Drug
manufacturers wishing to sell a new drug in Canada must first obtain a NOC pursuant to Part
C, Division 8 of the Regulations. Manufacturers become eligible to receive a
NOC by filing a drug submission with the Minister of Health. There are several
types of drug submissions that may be filed pursuant to the Regulations.
[20]
Subsection
C.08.002(2) establishes the content requirements for a New Drug Submission
(NDS). In order to receive a NOC for a NDS, a manufacturer must establish the
safety and clinical effectiveness of the drug through the submission of
detailed reports and clinical testing results. Establishing the drug’s safety
means establishing that it is safe to use for the treatment of a specified
disease. Establishing the clinical effectiveness of the drug involves
establishing that the drug is effective in treating that disease or condition. Such
submissions are generally very extensive and are typically filed by brand name
or “innovative” drug manufacturers.
[21]
Where a
generic drug company seeks to copy a drug that has already been marketed in Canada, it need not file a NDS in
order to establish that its product is both safe and clinically effective. Rather,
the generic company can file an ANDS, which simply requires the manufacturer to
establish that its product is the same as a previously-approved Canadian
reference product. The content requirements for an ANDS submission are
contained within section C.08.002.1 of the Regulations.
[22]
Finally, where
a manufacturer has already received a NOC for a drug, any significant change
made to that drug requires a Supplemental New Drug Submission (SNDS), the content
requirements for which are set out in section C.08.003 of the Regulations.
Applicant filed an ANDS
[23]
In the case
at bar, the applicant filed an ANDS with the Minister of Health, seeking a NOC
for its drug, pms-X/Y. Accordingly, while the applicant was not required to
carry out clinical studies directly addressing the drug’s safety and clinical
effectiveness, it did need to include in its submission “sufficient information
and material to enable the Minister to assess the safety and effectiveness of
the new drug,” including a number of factors listed in subsection C.08.002.1(2)
of the Regulations.
[24]
The
respondent maintains that when reviewing an ANDS such as the one filed by the
applicant, the TPD will conclude that the proposed generic drug is safe and
clinically effective only where the evidence shows that the proposed generic
drug is essentially identical to a drug that has already been shown to be safe
and effective. Under subsection C.08.002.1(2) of the Regulations, this
comparison is accomplished through two principal components:
a. by the applicant showing that
its product is the “pharmaceutical equivalent” of the Canadian reference
product, REFPRO (C.08.002.1(2)(c)(i)); and
b. by the applicant showing,
where the Minister considers it necessary, that its product is “bioequivalent”
with the Canadian reference product (C.08.002.1(2)(c)(ii)).
[25]
The
respondent further maintains that since the applicant is seeking approval for a
generic version of a drug that was initially approved and sold as a
“combination drug” – meaning that it contains more than one medicinal
ingredient – then comparative bioavailability studies must be conducted measuring
each active ingredient in the drug. In essence, the respondent maintains
that where a drug has been sold as a “combination drug,” “the minister
considers it necessary” that each active ingredient of the drug be subject to a
bioavailability study.
The
parties’ submissions regarding the TPD decision
[26]
The
applicant raises a number of arguments why the TPD erred in its decision, all
of which relate to its position that a bioavailability study measuring
component Y is not necessary to support its ANDS. First, the applicant argues
that bioavailability data need not be proven for component Y since the TPD has
already confirmed that the drug is both safe and clinically effective. In
support of this position, the applicant points to the cross-examination of
Leslie Cockell, Manager of the Division of Biopharmaceutics Evaluation 2, in
the Bureau of Pharmaceutical Sciences, TPD, Health Canada, who stated in
relation to the safety of component Y in REFPRO:
Q. Is it just a safety issue or just an efficacy
issue, or both? Does the safety change depending on whether you claim [component
Y] as having [a condition A-related] effect?
A. I understand that levels of [component
Y] as far as safety has been established for a single dose, for a daily dose, so
in that respect I would say the safety may not change.
and in relation to the component’s clinical
effectiveness:
Q. So the Minister was satisfied as to
the safety and efficacy of the new product without the need for bioequivalence
data vis-à-vis the original product.
A. Correct.
[…]
Q. … We have established that the
minister does not always need that bioequivalence data in the case of this
product – in the case of [X/Y], the Minister does not require bioequivalence
data to be satisfied as to the safety and efficacy. Is that fair to say?
A. That’s fair to say.
[27]
Further, in
relation to the safety of component Y, the applicant submits that Ms. Cockell’s
testimony is consistent with:
a. statements in REFPRO’s
previously-issued Product Monograph that “[component Y] is generally recognized
as having no adverse effects”;
b. the Minister’s approach to not
require bioavailability studies for components in the class of component Y in
Drug Identification Number (DIN) submissions; and
c. the fact that the daily amount
of component Y in the applicant’s drug is well within the maximum daily limit
in the Minister’s guidelines.
[28]
Accordingly,
the applicant argues that the TPD’s decision to reject its ANDS on the basis
that it did not contain comparative bioavailability data relating to component
Y was arbitrary, contrary to the Regulations, and unreasonable on its face.
[29]
The
respondent, however, argues that the TPD’s decision in this regard was not
arbitrary or inconsistent with the Regulations or the TPD’s internal policy. First,
the respondent submits that the applicant’s reliance on the Minister’s
guideline document, Preparation of Drug Identification Number Submissions,
is inappropriate since that document has no application to a product such as pms-X/Y.
According to the respondent, this guideline applies solely to the class of
low-risk products regulated under the less stringent drug review framework set
out in Part C, Division 1 of the Regulations. New drugs, with complex
risk/benefit profiles such as pms-X/Y, are not “DIN submissions,” and are
completely outside the scope of the guideline document.
[30]
The
difference, in the respondent’s submission, is that use of component Y is “so
well-understood” and of “sufficiently low risk” that it does not require
bioavailability data in order to provide the necessary level of confidence in
the safety and clinical effectiveness of the product. However, where a compound
such as component Y is used in combination with another compound to treat a
serious condition – such as the treatment of condition A – then the compound
must be assessed in the same way as any other active ingredient pursuant to the
framework contained in Part C, Division 8 of the Regulations.
[31]
As well, the
respondent disagrees with the applicant that the safety of component Y need not
be established since REFPRO’s previously-issued Product Monograph does not
contain any clinical references conclusively demonstrating any therapeutic role
for component Y alone in the treatment of condition A. The respondent submits
that such an argument must fail since it does not recognize that REFPRO was
approved as a combination product, thereby meaning that the drug’s safety and
clinical effectiveness was determined based on studies using the active
ingredients in combination, rather than in isolation.
[32]
Further,
in recognizing that the Regulations only require evidence of bioequivalence where
the Minister “considers it necessary,” the respondent points to the fact that
the applicant was notified of the TPD’s position regarding the need for
bioavailability data well before the applicant filed its ANDS in July 2005.
[33]
The
applicant notes that Ms. Cockell’s testimony concerning the safety and clinical
effectiveness of component Y was made in reference to Pharmacompany’s SNDS for
a new formulation of REFPRO, and not in reference to the applicant’s ANDS.
However, the applicant maintains that there is no relevant substantive or
regulatory distinction between the two submissions. Regarding the regulatory
frameworks, both the requirements applicable to a SNDS – found in subsection
C.08.003(3) of the Regulations – and those applicable to an ANDS – found in
subsection C.08.002.1(2) – state that the submission must contain “sufficient
information and material to enable the Minister to assess the safety and
effectiveness of the new drug.”
[34]
However,
the two frameworks differ in that the requirements for an ANDS go on to
explicitly list a number of factors that must be included to aid the Minister’s
assessment. These factors include paragraph (c), which refers to:
|
(c) evidence from the comparative studies
conducted in connection with the submission that the new drug is
(i) the pharmaceutical equivalent of the Canadian
reference product, and
(ii) where the Minister considers it necessary on the
basis of the pharmaceutical and, where applicable, bioavailability
characteristics of the new drug, bioequivalent with the Canadian reference
product as demonstrated using bioavailability studies, pharmacodynamic
studies or clinical studies;
|
c) les
éléments de preuve, provenant des études comparatives menées dans le cadre de
la présentation, établissant que la drogue nouvelle:
(i) d’une part, est
un équivalent pharmaceutique du produit de référence canadien,
(ii) d’autre part,
si le ministre l’estime nécessaire d’après les caractéristiques
pharmaceutiques et, le cas échéant, d’après les caractéristiques en matière
de biodisponibilité de celle-ci, est bioéquivalente au produit de référence
canadien selon les résultats des études en matière de biodisponibilité, des
études pharmacodynamiques ou des études cliniques;
|
[35]
No such express
requirements exist in regards to a SNDS, thereby suggesting that the Minister
may be satisfied of a drug’s safety and effectiveness without requiring
comparative bioavailability data measuring the components of a new drug’s
formulation. While the applicant recognizes that the framework governing a SNDS
does not contain a list of particular factors that must be included in the
submission, it nevertheless maintains that there is no material difference
since both sections expressly require “sufficient information” to be included,
and the ANDS framework only requires proof of bioequivalence where the Minister
considers it necessary.
[36]
Further,
the applicant argues that even though section C.08.003 may “theoretically”
allow a manufacturer to establish the effectiveness of its SNDS through a means
other than including information addressing bioequivalence, there is no
evidence of what such other methods might be, nor is there any evidence that Pharmacompany
adopted such other methods in order to independently establish the safety and effectiveness
of component Y in REFPRO.
[37]
The
applicant goes on to compare the requirements placed on it by the TPD with Pharmacompany’s
SNDS for a new delayed-release formulation of REFPRO, stating that that
submission did not contain a comparative bioavailability study in the “fasted
and fed” states demonstrating the bioequivalence of component Y in the new
formulation with reference to the old formulation. Accordingly, the applicant
submits that this fact is clear evidence that a comparative bioavailability
study for component Y is not actually considered necessary by the TPD in order
to assess the safety and clinical effectiveness of an X/Y product. In relying
on this argument, the applicant submits that the TPD’s decision to reject the
applicant’s ANDS directly contradicts the evidence and was, therefore,
unreasonable.
[38]
The
respondent notes the differences between the two regulatory frameworks and the
fact that the requirements for a SNDS are silent with respect to the type
information needed to “enable the Minister to assess the safety and
effectiveness of the new drug.” Accordingly, the respondent argues that the TPD
has “broad discretion” as to what information and material will be sufficient
to support the proposed change under a SNDS, and that this framework is
completely different from that required with respect to an ANDS.
[39]
The
respondent does, however, take note of the unique circumstances surrounding Pharmacompany’s
SNDS. The respondent submits that while bioavailability studies are commonly
part of a SNDS concerning a change in formulation, such a study was not
possible in the circumstances surrounding Pharmacompany’s submission.
Accordingly, the TPD was required to find an alternate means of assessing the
new formulation’s safety and clinical effectiveness. The respondent maintains,
however, that despite these unique circumstances, the alternate means taken by
the TPD were justified by the SNDS requirements, which are substantially
different from the content requirements for an ANDS.
Court’s
analysis
[40]
In the
case at bar, the TPD considered it necessary for the applicant to file
bioavailability studies for both component X and component Y of its proposed new
drug in order to show that the drug was bioequivalent with the Canadian
reference product, REFPRO.
[41]
Understanding
this consideration, the question then becomes whether the TPD’s outright
rejection of the applicant’s ANDS was inconsistent with the requirements
provided for in the Regulations in a way that was patently unreasonable. In my
view, the TPD’s requirement that the applicant file bioavailability studies for
both component X and component Y was not patently unreasonable. Such a decision
was entirely within the purview of the TPD. The decision stated that “it is
clear that [component Y has a condition A-related effect].” The applicant
has not provided any scientific evidence that this component does not work to
offset the effects of condition A in this product.
[42]
The
respondent directed the Court to the evidence that component Y has a condition
A-related effect. The evidence was:
1.
the NOC
for REFPRO that the medicinal ingredients are component X and component Y and
that their therapeutic classification is as a treatment for condition A. This
means that both ingredients have this therapeutic effect;
2.
the new
REFPRO Product Monograph states at page 9 that the drug provides the
action of two unrelated compounds which provide treatment for condition A. This
shows that both ingredients have a role to play, and the drug would not be
approved in combination if component Y did not have any therapeutic role; and
3.
two
scientific studies were before the TPD. The titles of these studies show that component
Y is used for the treatment of condition A. Therefore, when used in combination
with component X, it acts as much more than in its usual role.
The Court is satisfied that the decision, based on this evidence,
was reasonably open to the decision-maker, and was not “patently unreasonable,”
i.e., clearly irrational.
[43]
The
applicant filed its ANDS in reference to REFPRO. This drug contains identical
amounts of the two active ingredients as the applicant’s product. The applicant
submitted that since the Minister of Health recently approved a SNDS for the
new REFPRO without requiring the manufacturer to file a study comparing the
bioavailability of component Y in the new formulation to that in the old
formulation, or any other evidence of the effectiveness of component Y in the
new formulation, then the applicant should not have had to do so either.
[44]
First, the
requirements for a SNDS are substantially different from the requirements for
an ANDS, as the lack of express requirements in relation to a SNDS gives the
TPD more discretion in determining what is necessary to enable the Minister to
assess a drug’s safety and clinical effectiveness. This significant difference
was addressed by the Federal Court of Appeal in Reddy-Cheminor, above,
where Mr. Justice Evans stated at paragraph 11:
¶ 11 In my opinion, this argument is
misconceived because the statutory criteria for obtaining a NOC on the basis of
a SNDS are materially different from those governing the issue of a NOC on the
basis of an ANDS. A SNDS may be filed by a person when a NOC has been issued in
respect of a drug and some change has been made to the product, its manufacture
or marketing.
[45]
Second,
the jurisprudence establishes that while consistency in drug regulation is an
admirable objective, it cannot overrule the objective consideration of
individual submissions on a case-by-case basis. Moreover, the existence of a
conflict in administrative decisions, if a conflict does in fact exist, does
not constitute a basis for the Court setting aside a decision for drug approval:
see Reddy-Cheminor, above, per Layden-Stevenson J. at paragraphs 35-36
(affirmed on appeal).
[46]
Instead of
requiring Pharmacompany to conduct and file a bioavailability study on
component Y, Health Canada accepted the two years of
post-market data, which showed how the new product performed in the market. As
the applicant submitted, this post-market data does not show that the new
product is as effective, only that it is safe. However, Health Canada was prepared to grant the
concession since Pharmacompany was introducing an extended release of its
product, which had actually been sold in Canada for quite some time.
[47]
With
respect to the differences between the TPD’s consideration of Pharmacompany’s SNDS
and the applicant’s ANDS in the case at bar, such different treatment is
reflective of the significant differences in the regulatory framework governing
the different types of submissions. Further, the issue of the TPD’s treatment
of the Pharmacompany SNDS is not before the Court in this matter. All the Court
is concerned with here is whether the TPD was patently unreasonable in
requiring the applicant to file bioavailability studies supporting its ANDS for
pms-X/Y. As outlined above, such a requirement was within the expertise of the
TPD, and will not be set aside by this Court as being patently unreasonable.
CONCLUSION
[48]
The Court
concludes that:
1.
the
decision under review was reasonably open to the decision-maker on the basis of
the evidence;
2.
the
applicant’s reliance upon the regulatory approval for the Canadian reference
product is misguided. The Canadian reference product was approved under the
regulations for a SNDS, which are different than the regulations applicable to
the applicant’s product;
3.
even
if Health Canada made a mistake in approving the Canadian reference product,
that mistake does not affect the obligation of Health Canada to undertake an
objective consideration of the applicant’s submission on a stand alone basis.
Otherwise, Health Canada would be repeating its
previous mistake. Moreover, the existence of a conflict in administrative
decisions with respect to drug approvals does not constitute a basis for the
Court to intervene; and
4.
the
fact that component Y, when used alone, is well known to be safe and effective,
does not mean that it is safe and effective when used in combination with
another medicinal ingredient. In such cases, Health Canada requires a
bioavailability study for all the ingredients, including component Y.
ORDER
THIS COURT ORDERS that:
This application for judicial
review is dismissed with costs.
“Michael
A. Kelen”
APPENDIX “A”
Food and Drug Regulations, C.R.C., c. 870
|
C.08.002.1 (1) A manufacturer of a new drug may file
an abbreviated new drug submission for the new drug where, in comparison with
a Canadian reference product,
(a) the new drug is the
pharmaceutical equivalent of the Canadian reference product;
(b) the new drug is
bioequivalent with the Canadian reference product, based on the
pharmaceutical and, where the Minister considers it necessary, bioavailability
characteristics;
(c) the route of
administration of the new drug is the same as that of the Canadian reference
product; and
(d) the conditions of
use for the new drug fall within the conditions of use for the Canadian
reference product.
(2) An abbreviated new drug submission
shall contain sufficient information and material to enable the Minister to
assess the safety and effectiveness of the new drug, including the following:
(a) the information and
material described in paragraphs C.08.002(2)(a) to (f) and (j)
to (l);
(b) information
identifying the Canadian reference product used in any comparative studies
conducted in connection with the submission;
(c) evidence from the
comparative studies conducted in connection with the submission that the new
drug is
(i) the pharmaceutical
equivalent of the Canadian reference product, and
(ii) where the Minister
considers it necessary on the basis of the pharmaceutical and, where
applicable, bioavailability characteristics of the new drug, bioequivalent
with the Canadian reference product as demonstrated using bioavailability
studies, pharmacodynamic studies or clinical studies;
(d) evidence that all
test batches of the new drug used in any studies conducted in connection with
the submission were manufactured and controlled in a manner that is
representative of market production; and
(e) for a drug intended for
administration to food-producing animals, sufficient information to confirm
that the withdrawal period is identical to that of the Canadian reference
product.
(3) The manufacturer of a new drug shall,
at the request of the Minister, provide the Minister, where for the purposes
of an abbreviated new drug submission the Minister considers it necessary to
assess the safety and effectiveness of the new drug, with the following
information and material:
(a) the names and
addresses of the manufacturers of each of the ingredients of the new drug and
the names and addresses of the manufacturers of the new drug in the dosage
form in which it is proposed that the new drug be sold;
(b) samples of the
ingredients of the new drug;
(c) samples of the new
drug in the dosage form in which it is proposed that the new drug be sold;
and
(d) any additional
information or material respecting the safety and effectiveness of the new
drug.
C.08.003 (1) Notwithstanding section C.08.002, no
person shall sell a new drug in respect of which a notice of compliance has
been issued to the manufacturer of that new drug and has not been suspended
pursuant to section C.08.006, if any of the matters specified in subsection
(2) are significantly different from the information or material contained in
the new drug submission or abbreviated new drug submission, unless
(a) the manufacturer of
the new drug has filed with the Minister
(i) a supplement to that new
drug submission, or
(ii) a supplement to that
abbreviated new drug submission;
(b) the Minister has
issued a notice of compliance to the manufacturer of the new drug in respect
of the supplement;
(c) the notice of
compliance in respect of the supplement has not been suspended pursuant to
section C.08.006; and
(d) the manufacturer of
the new drug has submitted to the Minister specimens of the final version of
any label, including any package insert, product brochure and file card,
intended for use in connection with the new drug, where a change with respect
to any of the matters specified in subsection (2) is made that would require
a change to the label.
(2) The matters specified for the purposes
of subsection (1), in relation to the new drug, are the following:
(a) the description of
the new drug;
(b) the brand name of
the new drug or the identifying name or code proposed for the new drug;
(c) the specifications
of the ingredients of the new drug;
(d) the plant and
equipment used in manufacturing, preparation and packaging the new drug;
(e) the method of
manufacture and the controls used in manufacturing, preparation and packaging
the new drug;
(f) the tests applied to
control the potency, purity, stability and safety of the new drug;
(g) the labels used in
connection with the new drug;
(h) the representations
made with regard to the new drug respecting
(i) the recommended route of
administration of the new drug,
(ii) the dosage of the new
drug,
(iii) the claims made for the
new drug,
(iv) the contra-indications and
side effects of the new drug, and
(v) the withdrawal period of
the new drug; and
(i) the dosage form in
which it is proposed that the new drug be sold.
(3) A supplement to a new drug submission
or to an abbreviated new drug submission, with respect to the matters that
are significantly different from those contained in the submission, shall
contain sufficient information and material to enable the Minister to assess
the safety and effectiveness of the new drug in relation to those matters.
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C.08.002.1 (1)
Le
fabricant d’une drogue nouvelle peut déposer à l’égard de celle-ci une
présentation abrégée de drogue nouvelle si, par comparaison à un produit de
référence canadien :
a) la drogue nouvelle est un équivalent pharmaceutique du produit
de référence canadien;
b) elle est bioéquivalente au produit de référence canadien d’après
les caractéristiques pharmaceutiques et, si le ministre l’estime nécessaire,
d’après les caractéristiques en matière de biodisponibilité;
c) la voie d’administration de la drogue nouvelle est identique à
celle du produit de référence canadien;
d) les conditions thérapeutiques relatives à la drogue nouvelle
figurent parmi celles qui s’appliquent au produit de référence canadien.
(2) La présentation abrégée de
drogue nouvelle doit contenir suffisamment de renseignements et de matériel
pour permettre au ministre d’évaluer l’innocuité et l’efficacité de la drogue
nouvelle, notamment :
a) les renseignements et le matériel visés aux alinéas C.08.002(2)a)
à f) et j) à l);
b) les renseignements permettant d’identifier le produit de
référence canadien utilisé pour les études comparatives menées dans le cadre
de la présentation;
c) les éléments de preuve, provenant des études comparatives menées
dans le cadre de la présentation, établissant que la drogue nouvelle :
(i) d’une
part, est un équivalent pharmaceutique du produit de référence canadien,
(ii) d’autre
part, si le ministre l’estime nécessaire d’après les caractéristiques
pharmaceutiques et, le cas échéant, d’après les caractéristiques en matière
de biodisponibilité de celle-ci, est bioéquivalente au produit de référence
canadien selon les résultats des études en matière de biodisponibilité, des
études pharmacodynamiques ou des études cliniques;
d) les éléments de preuve établissant que les lots d’essai de la
drogue nouvelle ayant servi aux études menées dans le cadre de la
présentation ont été fabriqués et contrôlés d’une manière représentative de
la production destinée au commerce;
e) dans le cas d’une drogue destinée à être administrée à des
animaux producteurs de denrées alimentaires, les renseignements permettant de
confirmer que le délai d’attente est identique à celui du produit de
référence canadien.
(3) Le fabricant de la drogue
nouvelle doit, à la demande du ministre, lui fournir, selon ce que celui-ci
estime nécessaire pour évaluer l’innocuité et l’efficacité de la drogue dans
le cadre de la présentation abrégée de drogue nouvelle, les renseignements et
le matériel suivants:
a) les nom et adresse des fabricants de chaque ingrédient de la
drogue nouvelle et les nom et adresse des fabricants de la drogue nouvelle
sous sa forme posologique proposée pour la vente;
b) des échantillons des ingrédients de la drogue nouvelle;
c) des échantillons de la drogue nouvelle sous sa forme posologique
proposée pour la vente;
d) tout renseignement ou matériel supplémentaire se rapportant à
l'innocuité et à l’efficacité de la drogue nouvelle.
C.08.003 (1) Malgré l'article C.08.002,
il est interdit de vendre une drogue nouvelle à l'égard de laquelle un avis
de conformité a été délivré à son fabricant et n'a pas été suspendu aux
termes de l'article C.08.006, lorsqu'un des éléments visés au paragraphe (2)
diffère sensiblement des renseignements ou du matériel contenus dans la
présentation de drogue nouvelle ou la présentation abrégée de drogue
nouvelle, à moins que les conditions suivantes ne soient réunies :
a) le fabricant de la drogue nouvelle a déposé auprès du ministre :
(i) soit un
supplément à la présentation de drogue nouvelle,
(ii) soit un
supplément à la présentation abrégée de drogue nouvelle;
b) le ministre a délivré au fabricant un avis de conformité
relativement au supplément;
c) l'avis de conformité relatif au supplément n'a pas été suspendu
aux termes de l'article C.08.006;
d) le fabricant de la drogue nouvelle a présenté au ministre, sous
leur forme définitive, des échantillons de toute étiquette—y compris une
notice jointe à l'emballage, un dépliant et une fiche sur le produit—destinée
à être utilisée pour la drogue nouvelle, dans le cas où la modification d'un
des éléments visés au paragraphe (2) nécessite un changement dans
l'étiquette.
(2) Pour l'application du
paragraphe (1), les éléments ayant trait à la drogue nouvelle sont les
suivants :
a) sa description;
b) sa marque nominative ou le nom ou code sous lequel il est
proposé de l'identifier;
c) les spécifications de ses ingrédients;
d) les installations et l'équipement à utiliser pour sa
fabrication, sa préparation et son emballage;
e) la méthode de fabrication et les mécanismes de contrôle à
appliquer pour sa fabrication, sa préparation et son emballage;
f) les analyses effectuées pour contrôler son activité, sa pureté,
sa stabilité et son innocuité;
g) les étiquettes à utiliser pour la drogue nouvelle;
h) les observations faites relativement :
(i) à la voie
d'administration recommandée pour la drogue nouvelle,
(ii) à sa
posologie,
(iii) aux
propriétés qui lui sont attribuées,
(iv) à ses
contre-indications et à ses effets secondaires,
(v) au délai
d'attente applicable à celle-ci;
i) sa forme posologique proposée pour la vente.
(3) Le supplément à la
présentation de drogue nouvelle ou à la présentation abrégée de drogue nouvelle
doit contenir, à l'égard des éléments qui diffèrent sensiblement de ce qui
figure dans la présentation, les renseignements et le matériel nécessaires
pour permettre au ministre d'évaluer l'innocuité et l'efficacité de la drogue
nouvelle relativement à ces éléments.
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