Date: 20080729
Docket: T-837-07
Citation: 2008 FC 922
Ottawa, Ontario, July 29, 2008
PRESENT: The Honourable Madam Justice Simpson
BETWEEN:
PHARMASCIENCE
INC.
Applicant
and
THE MINISTER OF HEALTH and
THE ATTORNEY GENERAL OF CANADA
Respondents
REASONS FOR ORDER AND ORDER
[1]
Pharmascience Inc. (the
Applicant) seeks Judicial Review pursuant to section 18.1 of the Federal
Courts Act, R.S.C. 1985, c. F-7 of a
decision of the Minister of Health (the Minister) made on April 12, 2007 (the
Decision) in which he concluded that the Applicant was required to address the Canadian
Patents Nos. 2,382,387 and 2,382,549 (the 387 and 549 Patents) in respect of
its Supplementary Abbreviated New Drug Submission (the SANDS) for its generic 1.25
mg ramipril capsules under subsection 5(1) of the Patented Medicines (Notice
of Compliance) Regulations, S.O.R./93-133 (the NOC Regulations).
BACKGROUND
(This
section draws heavily on the Agreed Facts provided by the parties.)
[2]
Prior
to July 10, 2000, Sanofi-Aventis Canada Inc. (the Innovator) was granted
four Notices of Compliance (the Prior NOCs) for ramipril capsules, which it
marketed under the brand name ALTACE. It was first approved to treat
hypertension.
[3]
On
July 10,
2000,
the Applicant purchased ALTACE in 1.25 mg, 2.5 mg, 5 mg and 10 mg capsules for
use as Canadian reference products.
[4]
On
February 13, 2001, the Innovator was granted a further Notice of
Compliance (NOC) in association with submission number 066094 (the Fifth NOC).
[5]
Pharmascience’s
Abbreviated New Drug Submission #073405 (the ANDS) was received by the Minister
on September 4,
2001.
A copy of a letter dated September 13, 2001 from the Submission and
Information Policy Division, on behalf of the Minister acknowledging receipt of
the ANDS on September 4, 2001 is at Tab 3 of the Agreed Documents. As
acknowledged in that letter, as filed, Pharmascience’s ANDS #073405 was in
respect of ramipril 1.25 mg, 2.5 mg, 5 mg and 10 mg capsules.
[6]
The
Applicant’s ANDS was based the asserted bioequivalence of its 1.25 mg,
2.5 mg, 5 mg and 10 mg ramipril capsules with the Innovator’s 1.25 mg, 2.5
mg, 5 mg and 10 mg ALTACE ramipril capsules which had been purchased by
the Applicant as Canadian reference products. There is no issue that in
connection with this ANDS, the Applicant was obliged to address all the patents
listed on the Prior NOCs.
[7]
In
the ANDS, the Applicant submitted bioavailability data showing the
bioequivalence of its 10 mg tablet with the Innovator’s 10 mg ALTACE tablet.
Pursuant to the Proportional Formulations Policy, the Applicant requested a
waiver of the requirement to submit bioavailability studies showing
bioequivalence of its 1.25 mg, 2.5 mg and 5 mg tablets with the corresponding
ALTACE ramipril capsules strengths. Instead, the Applicant submitted data
demonstrating the proportionality of its 1.25 mg, 2.5 mg and 5 mg tables with
its 10 mg ramipril tablet.
[8]
The
ANDS included a copy of an invoice dated July 10, 2000, for the purchase
from the Innovator of samples of all four strengths of ALTACE capsules (the
Invoice).
[9]
The
ANDS also included a clinical report of Algorithme Pharma (March 23, 2001
as amended April 6, 2001) regarding bioequivalence between the Applicant’s
Ramipril 10 mg capsules and the ALTACE 10 mg ramipril capsules. The report
states that the samples of ALTACE were received by Algorithme Pharma on
December 15, 2000.
[10]
On
February 24, 2003, the Applicant withdrew its ANDS for the generic 1.25 mg
ramipril capsules at the request of Health Canada due to a
lack of stability data for those capsules. The review of the ANDS proceeded
only in respect of the generic 2.5 mg, 5 mg and 10 mg capsule strengths.
[11]
By
letter dated August 27, 2003, the Minister agreed that the 2.5 mg, 5 mg
and 10 mg ramipril capsules were bioequivalent to the respective ALTACE
capsules based on the bioequivalence studies in respect of the 10 mg capsules
and the demonstration of proportionality in respect of the 2.5 mg and 5 mg
capsules under the Proportional Formulation Policy. Accordingly, the Applicant
was entitled to a NOC for these capsules, subject only to compliance with the
NOC Regulations.
[12]
On
November 6, 2003, the Innovator was granted a further NOC in respect of
ALTACE following submission number 082094 the (Sixth NOC). It listed the 549
Patent after it was granted on March 17, 2005 and the 387 Patent after it
was granted on June 21, 2005. These Patents were listed in connection with
a new indication – treatment following a heart attack. The Applicant is not seeking
approval for its generic ramipril capsules for the treatment of heart attacks.
In other words, it does not seek to use the teaching of the 387 and 547
Patents.
[13]
On
December 30, 2005,
after the Sixth NOC and after the 387 and 549 Patents were listed, the
Applicant filed the SANDS for its generic 1.25 mg ramipril capsules.
[14]
In its
SANDS, the Applicant sought a waiver of the requirement to submit separate
bioavailability studies showing bioequivalence of its 1.25 mg generic ramipril
capsule to the 1.25 mg ALTACE capsule. Instead, it proposed to demonstrate the proportionality
of its 1.25 mg generic capsule to its 10.0 mg ramipril capsule which was the
subject of its original ANDS.
[15]
On
November 3, 2006, the Supreme Court of Canada released its decision in AstraZeneca
Canada Inc. v. Canada (Minister of Health), 2006 SCC 49, [2006] 2 S.C.R.
560.
[16]
In
AstraZeneca, Mr. Justice Ian Binnie, writing for a unanimous Supreme
Court, described the workings and relations between the Food and Drug Act,
R.S.C. 1985, c. F-27 and the Food and Drug Regulations, C.R.C., c. 870, the Patent
Act, R.S.C. 1985, c. P-4 and the NOC Regulations. He then turned to the
facts of the case and noted that AstraZeneca had developed Losec 20 to
treat stomach hyperacidity. It was Losec 20 formulated for this purpose that
Apotex sought permission to copy. However, patents were listed for a subsequent
new version of Losec 20. The 037 patent described a new oral dosage form and a
new manufacturing process and the 470 patent taught of a new form of
omeprazole. However, this new version of Losec 20, which was designed to treat H.
Pylori, was never marketed.
[17]
The
Supreme Court of Canada held in these circumstances that Apotex did not have to
address 037 and 470 patents because the drug described therein had never been
marketed and therefore could not have been the drug to which Apotex made
reference to establish bioequivalence.
[18]
The
Court referred to subsection 5(1) of the NOC Regulations. It provides that:
|
5. (1) If a
second person files a submission for a notice of compliance in respect of a
drug and the submission directly or indirectly compares the drug with, or
makes reference to, another drug marketed in Canada under a notice of
compliance issued to a first person and in respect of which a patent list has
been submitted, the second person shall, in the submission, with respect to
each patent on the register in respect of the other drug,
(a) state that the second person accepts that the
notice of compliance will not issue until the patent expires; or
(b) allege that
(i) the statement made by the first person under
paragraph 4(4)(d) is false,
(ii) the patent has expired,
(iii) the patent is not valid, or
(iv) no claim for the medicinal ingredient, no claim for
the formulation, no claim for the dosage form and no claim for the use of the
medicinal ingredient would be infringed by the second person making,
constructing, using or selling the drug for which the submission is filed.
|
5.
1) Dans le cas où la seconde personne dépose une
présentation pour un avis de conformité à l’égard d’une drogue, laquelle
présentation, directement ou indirectement, compare celle-ci à une autre
drogue commercialisée sur le marché canadien aux termes d’un avis de
conformité délivré à la première personne et à l’égard de laquelle une liste
de brevets a été présentée — ou y fait renvoi —, cette seconde personne doit,
à l’égard de chaque brevet ajouté au registre pour cette autre drogue,
inclure dans sa présentation :
a) soit une déclaration portant qu’elle accepte que l’avis de conformité
ne sera pas délivré avant l’expiration du brevet;
b) soit une allégation portant que, selon le cas :
(i) la déclaration
présentée par la première personne aux termes de l’alinéa 4(4)d) est
fausse,
(ii) le brevet est expiré,
(iii) le brevet n’est pas
valide,
(iv)
elle ne contreferait aucune revendication de l’ingrédient médicinal,
revendication de la formulation, revendication de la forme posologique ni
revendication de l’utilisation de l’ingrédient médicinal en fabriquant,
construisant, utilisant ou vendant la drogue pour laquelle la présentation
est déposée.
|
[19]
In
this regard, the Court said:
36 Viewed in this light, it seems to me
inescapable that the expression “another drug” in s. 5(1) refers to the actual
comparator drug — not a drug that never became available for comparison — and
that the words “with respect to each patent on the register in respect of the
other drug” carries the same meaning.
37 The whole obligation incurred by the generic manufacturer under
the NOC Regulations is based on its “early working” of patents embodied
in “another drug for the purpose of demonstrating bioequivalence”. The
only drug that fits the description is the version of Losec 20 approved
in the June 19, 1989 NOC.
H. The Broader Statutory Purpose
38 I repeat that Parliament’s stated purpose in authorizing the NOC
Regulations was to permit the “early working” of the patented invention
(s. 55.2(4)). As Apotex did not make use of the patented inventions
taught by the 037 and 470 patents, Apotex is not on this occasion within the
mischief aimed at by the NOC Regulations.
39 By imposing the 24-month delay called for by the NOC
Regulations, the decision of the Federal Court of Appeal undermines
achievement of the balance struck by Parliament between the objectives of the FDA
and regulations thereunder (making safe and effective drugs available to
the public) and the Patent Act and its regulations (preventing abuse of
the “early working” exception to patent infringement). Given the evident
(and entirely understandable) commercial strategy of the innovative drug companies
to evergreen their products by adding bells and whistles to a pioneering
product even after the original patent for that pioneering product has expired,
the decision of the Federal Court of Appeal would reward evergreening even if
the generic manufacturer (and thus the public) does not thereby derive any
benefit from the subsequently listed patents. In my view, s. 5(1) of
the NOC Regulations requires a patent-specific analysis, i.e. the
generic manufacturer is only required to address the cluster of patents listed
against submissions relevant to the NOC that gave rise to the comparator drug,
in this case the 1989 version of Losec 20.
40 If AstraZeneca had brought to market a Losec 20 product
pursuant to the later NOCs and if Apotex had made reference to that modified
product for the purpose of demonstrating bioequivalence, Apotex would have been
required to file a notice of allegation with respect to the 037 and 470
patents.
41 However, it is clear that AstraZeneca did not market any product
pursuant to the subsequent NOCs and that the preconditions to any obligations
of Apotex under s. 5(1) were therefore not triggered.
[20]
In
response to AstraZeneca, the Minister acknowledges that he developed an
informal policy (the First Policy) to the effect that generic companies were
not required to address patents listed against submissions filed after the
generic purchased an Innovator’s Canadian comparison drugs. This meant that, in
this case, the date of the Invoice would serve as the cut off date.
[21]
This
policy was described in the following manner by Mr. Justice Roger Hughes in Ferring
Inc. v. Canada (Minister of Health), 2007 FC 300,
55 C.P.R. (4th) 271 at paragraphs 63 and 64:
63
As soon as the AstraZeneca decision was released in
early November, 2006, the Minister, with some prompting from some generics, set
about to devise a process for dealing with the question of setting a procedure
for dealing with whether a generic is required to address any particular listed
patent. This process is set out in affidavits of Anne Elizabeth Bowes,
Associate Director of the Therapeutic Products Directorate (TPD) which is the
branch of the Minister's department dealing with the NOC Regulations.
This process involves only ANDS applications submitted by generics prior to the
change in the NOC Regulations of October 5, 2006. Ms. Bowes explains
that it involves two steps:
1. First,
the date on which the generic has purchased the comparator drug is used to
determine which notices of compliance have been issued in respect of that comparator
drug. The position of the Minister is that all patents listed in respect of the
relevant NOC as of that date must be addressed by the generic.
2. Second,
where further NOC's have been issued to the innovator after the date of the
purchase of the comparator drug, the Minister makes a determination as to
whether the generic has made use of changes made to the comparator drug since
the original date of purchase. If the generic has made use of such changes,
then all patents added to the patent list subsequent to the date of purchase as
are pertinent to the changes of which the generic has taken advantage must be
addressed.
64 The
evidence shows that the Minister has regard to submissions made by the generic
or its lawyers as to the date of purchase of the comparator drug and whether
the generic has taken advantage of any subsequent NOC's issued to the
innovator. As well, the Minister has regard to matters that are self evident on
the record of the ANDS application by the generic, such as the date upon which
data respecting the comparator drug was filed so as to establish a latest date
upon which such drug could have been purchased. The "default date"
for establishing the purchase of the comparator drug, in the absence of other
information, is taken to be the filing date of the ANDS.
[22]
Mr.
Justice Hughes held that the Minister’s First Policy was consistent with the
reasons of the Supreme Court in AstraZeneca (Ferring para. 65)
and his decision was upheld by the Federal Court of Appeal (2007 FCA 276).
[23]
However,
in obiter, in Ferring, Mr. Justice Hughes went on to suggest a
revision to the Minister’s First Policy. Starting at para. 65,
Justice Hughes stated:
If I were to modify this policy, I would
do so in two respects…A better date [than the date of purchase of the
comparator drug] would be the filing date of the ANDS by the generic as that is
a date of record and is logically, the last date upon which the comparator drug
could have been obtained by the generic.
[24]
Following
Justice Hughes’s suggestion in Ferring, the Minister changed his
policy so that all patents had to be addressed as of the date an ANDS or a SANDS
for the generic version of a drug was filed (the Second Policy)
[25]
Based on AstraZeneca
and the First Policy, the Applicant asked the Minister to confirm that it was
not required to address the 387 and 549 Patents in connection with its SANDS
for the 1.25 mg generic ramipril capsules. The Minister did not reply to this
request although apparently Novopharm and Apotex received approvals for their
generic versions of ramipril on the basis of the First Policy.
[26]
On April 12,
2007, the Minister Issued the Decision requiring the Applicant to address the 387
and 549 Patents under section 5 of the NOC Regulations in connection with the
1.25 mg generic ramipril capsules which were the subject of the SANDS of
December 30, 2005.
[27]
By letter
dated April 30, 2007, the Applicant requested reconsideration of the part
of the Decision relating to the 1.25 mg capsules and by letter dated
June 8, 2007, the Minister denied the Applicant’s request.
[28]
By letter
dated May 17, 2007, the Minister granted the waiver of bioavailability data
for the SANDS and accepted that the Applicant’s 1.25 mg strength of ramipril is
bioequivalent to 1.25 mg ALTACE capsules under the Proportional Formulations
Policy. Accordingly, the Applicant is entitled to a NOC for the 1.25 mg
capsules, subject to compliance with the NOC Regulations.
[29]
The
following table is based on one provided in the Agreed Statement of Facts. It
lists the NOCs that were issued to the Innovator for ALTACE and the submissions
that gave rise to those NOCs and the patents listed on the Patent Register in
respect of those submissions:
|
NOC Date
|
Submission
No.
|
Submission
Date of Filing
|
Reason for
Submission
|
Patent No.
|
Patent Date
of Filing
|
Date Added
|
|
|
|
|
|
|
|
|
The Prior NOCs
|
Oct 3, 1993
|
08257
|
Jul 7, 1992
|
New drug submission
|
206
|
Oct 20,
1981
|
Apr 11,
2001
|
|
|
|
|
|
948
|
Nov 26,
1991
|
Jun 25,
2004
|
|
Sep 30,
1994
|
24206
|
Mar 10,
1994
|
Provides for a revised
manufacturing process
|
206
089
948
|
Oct 20,
1981
Aug 10,
1990
Nov 26,
1991
|
Apr 11,
2001
Nov 10,
2003
Jun 25,
2004
|
|
Jun 5, 1996
|
043465
|
May 13,
1996
|
(Company merger)
|
206
089
948
|
Oct 20,
1981
Aug 10,
1990
Nov 26,
1991
|
Apr 11,
2001
Nov 10,
2003
Jun 25,
2004
|
|
Dec 31,
1996
|
033131
|
Dec 24,
1994
|
Additional indication:
treatment following acute myorcardia infarction
|
206
089
948
|
Oct 20,
1981
Aug 10,
1990
Nov 26,
1991
|
Apr 11,
2001
Nov 10,
2003
Jun 25,
2004
|
|
|
|
|
|
|
|
|
July 10, 2000 - The
Invoice
The Fifth NOC
|
Feb 13,
2001
|
066094
|
Apr 3, 2000
|
New indication:
management of patients at increased risk of cardiovascular events
|
206
089
948
|
Oct 20,
1981
Aug 10,
1990
Nov 26,
1991
|
Apr 11,
2001
Nov 10,
2003
Jun 25,
2004
|
Sept. 4, 2001 – The ANDS
The Sixth NOC
|
Nov 6, 2003
|
082094
|
Jan 15,
2003
|
Update the Action and
Clinical Pharmacology Section of the Product Monograph with regards to
management of patients with increased risk of cardiovascular events
|
206
948
549
387
|
Oct 20,
1981
Nov 26,
1991
Aug 30,
2000
Aug 25,
2000
|
Nov 19,
2003
Jun 30,
2004
Mar 17,
2005
Jun 28,
2005
|
|
Dec. 30, 2005 – The
SANDS
|
|
May 29,
2006
|
105810
|
May 8, 2006
|
Manufacturer name
change
|
206
089
948
549
387
|
Oct 20,
1981
Aug 10,
1990
Nov 26,
1991
Aug 30,
2000
Aug 25,
2000
|
Jun 2, 2006
Jun 2, 2006
Jun 2, 2006
Jun 2, 2006
Jun 2, 2006
[my
emphasis]
|
[30]
As
shown in the above table, as of July 10, 2000, the date of purchase of the
ALTACE samples used for the purposes of the Applicant’s comparative testing,
the NOCs issued to the Innovator in respect of ramipril were the Prior NOCs. As
of September 4, 2001, the date of filing of the Applicant’s ANDS, the
Fifth NOC had also been issued to the Innovator in respect of Submission
#066094 but no new patents had been listed in association with the Fifth NOC.
However, by the time the SANDS was filed, the Sixth NOC had been issued and the
549 and 387 Patents had been listed.
DISCUSSION
[31]
The
Applicant says that AstraZeneca applies on the facts of this case.
However, there are factual differences. In this case, unlike AstraZeneca,
the drug to which the 387 and 549 patents apply is being marketed. However, the
evidence is that, as in AstraZeneca, the comparator drug, which was
approved for the treatment of hypertension, is not the subject of the 387 and 549
patents and the Applicant does not seek approval for the drug in connection
with treatment of patients with increased risk of heart attack. This means that
the Applicant, to paraphrase the words of AstraZeneca at paragraph 38,
has not, in fact, made use of the patented inventions taught by the 387 and 549
patents.
[32]
The
fact that the Applicant in this case could have made use of the later patents
(while in AstraZeneca, such use was an impossibility) doesn’t alter what
I view to be the gravamen of AstraZeneca. AstraZeneca stands for
the proposition that a generic company need only address patents listed against
NOC’s filed at the time it purchases the comparator drug it selects for the
purposes of its ANDS. The Minister therefore erred in law when he required the
Applicant to address the 387 and 549 patents.
Standard of Review
[33]
In
AstraZeneca at para. 25, the Supreme Court said that the applicable
standard of review is correctness. However, in light of its decision in Dunsmuir
v. New Brunswick¸ 2008 SCC 9, the Court might now conclude that the
standard is reasonableness. Even if that were the case, the application of the
Minister’s Second Policy in the Decision in this case, does not represent a
reasonable interpretation of AstraZeneca because the Decision ignores
the requirement to make a patent specific analysis, ignores the reality of the
Invoice and requires the Applicant to address patents which have nothing to do
with the purpose for which it is making a generic version of ramipril.
The Minister’s
Submissions
[34]
The
Minister wants to avoid the requirement to conduct the patent specific analysis
mandated by the Supreme Court in AstraZeneca. He suggested that, if
there were issues about which patents should be addressed, a prohibition
proceeding should be undertaken and any such issues could then be resolved by
the Court on a motion for summary judgment under subsection 6(5) of the NOC
Regulations.
[35]
I
have rejected this approach for three reasons:
(a)
First,
in paragraph 22 of the AstraZeneca, the Supreme Court of Canada says
that it is the Minister’s role to identify the precise patents which are
relevant to a generic manufacturer’s early working of a copycat product.
(b)
Second,
since prohibition proceedings under the NOC Regulations have been described as
“draconian” by the Supreme Court of Canada, because of the automatic stay they
mandate, they should not be used as a tool to relieve the Minister of his
responsibilities (see Merck Frosst Canada Inc. v. Canada (Minister of
National Health and Welfare, [1998] 2 S.C.R. 193 at paragraph 33).
(c)
Third,
patent specific analysis is not difficult. In most cases invoices will show
which drug was purchased by the generic company as the reference or comparator
drug. In other cases, related study reports or FDA filings may show which drugs
were used as comparators and it can be assumed that they were purchased prior
to the study. However, if there is a dispute or lack of credible evidence, the
submission date of the ANDS or SANDS can be used as a fallback position. If
there is a problem with the Minister’s decision, it can be judicially reviewed.
ORDER
UPON reviewing
the material filed and hearing the submission of counsel for both parties in Toronto, Ontario on
February 12, 2008;
NOW THIS
COURT ORDERS that, for the reasons given
above, that this application for judicial review is hereby allowed and the Minister
is directed to reconsider the Applicant’s request applying the First Policy so
that the Applicant need not address the 387 and 549 Patents.
“Sandra
J. Simpson”
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