Date: 20130215
Docket: A-75-12
Citation: 2013 FCA 43
CORAM: NADON
J.A.
SHARLOW
J.A.
GAUTHIER
J.A.
BETWEEN:
THE MINISTER OF HEALTH
Appellant
and
CELGENE INC.
Respondent
and
CANADIAN GENERIC PHARMACEUTICAL
ASSOCIATION
Intervener
REASONS FOR JUDGMENT
GAUTHIER J.A.
[1]
This
is an appeal from the decision of de Montigny J. of the Federal Court (the
Judge), granting the application for judicial review of Celgene Inc. (Celgene)
and quashing the decision of the Minister of Health to refuse to register
Celgene’s drug THALOMID on the Register of Innovative Drugs.
[2]
The
main issue in this appeal is whether THALOMID contains a medicinal ingredient
not previously approved, and as such falls within the definition of an “Innovative
Drug” found in subsection C.08.004.1 (1) of the Food
and Drug Regulations, C.R.C. c. 870 (the Regulations) that
can benefit from the Data Protection Provisions (DPP) in the Regulations,
particularly market exclusivity usually for a period of 8 years. For the reasons that
follow, I would allow this appeal.
BACKGROUND
a. The history of thalidomide
[3]
The
medicinal ingredient in THALOMID is thalidomide. A drug containing this
ingredient was first launched commercially by a German pharmaceutical company
in October 1957. At the time, the drug was promoted for use for sleeplessness
and other minor ailments suffered by pregnant women.
[4]
In
Canada, W.M.S. Merrell Company received approval for the sale of a drug
including thalidomide under the brand name KEVADON on November 22, 1960. Frank
W. R. Homer Limited received a similar approval for a drug including thalidomide
under the brand name TALIMOL on October 11, 1961.
[5]
In
1961 and 1962, thalidomide was dramatically withdrawn from the world market
because of its teratogenicity or potential to produce fetal malformation. Thousands
of babies across the globe were born with deformed or missing limbs or other horrible
conditions. Many were born stillborn or died shortly after birth. (The Judge’s
reasons, at paragraph 5)
[6]
The
Department of Health ordered the permanent withdrawal of thalidomide from the
Canadian market on April 6, 1962. Among other things, the withdrawal letter
stated the following:
With the withdrawal
of this acceptance, thalidomide returns to the status of a new drug and must
not be sold except to qualified investigators for the purpose of obtaining
scientific and clinical information that could be used to support the safety of
its use under conditions to be recommended by the manufacturer. Such sale
does not include its sale through pharmacies.
(The Judge’s reasons, at paragraph 6)
[7]
As
noted in a Health Canada publication reviewing the history of drug regulations
in Canada, by 1951, manufacturers were required to file a New Drug Submissions
(NDS) prior to marketing their drug but the Regulations then in force under the
Food and Drugs Act, S.C. 1952-53 c. 38 (the Act) did
not prevent the thalidomide tragedy of the early 1960s. This tragedy prompted a
complete revision of the Regulations to strengthen the department’s regulatory
ability. The revision marked the first appearance of the requirement for
manufacturers to submit evidence of efficacy in seeking a Notice of Compliance
(NOC) (Health Canada, “Brief History of Drug Regulations in Canada”, Appeal Book Volume 2, at page 277).
[8]
Thalidomide
was one of two drugs (the other one being lysergic acid diethylamide (LSD)),
the sale of which was absolutely prohibited pursuant to the amendment enacted
by Bill C-3 on December 20, 1962, (1st Sess., 25th Parl., 1962) placing
thalidomide on Schedule “H” to the Act.
[9]
In 1968, this Schedule “H” was replaced by one which
contained a longer list of prohibited substances:
1: Thalidomide
2.
Lysergic acid diethylamide
3.
DET N,N-Diethyltryptamine and its salts
4.
DMT N,N-Dimethyltryptamine and its salts
5.
SMT (DOM) 4-Methy-2, 5-dimethoxyamphetamine
SOR/68-411
The Canada Gazette Part II, Volume 102, No. 18,
September 25, 1968
[10]
Then,
in 1969, the scheme for dealing with other restricted substances was reconfigured
and the drugs listed in 2 to 5 above (so-called street drugs) were included
under Schedule “J” of the Act (SOR/69-417, the Canada Gazette Part II,
Volume 103, No. 16, August 27, 1969). This left Thalidomide as the only drug
listed in Schedule “H”.
[11]
In
1970, Thalidomide was moved to Schedule “F” of the Act, which listed
drugs that were prohibited for sale in Canada. The old Schedule H now dealt
only with “restricted drugs” as defined in Part IV of the Act and three
new such drugs were added to the four already listed.
[12]
In
1984, Thalidomide was deleted from Schedule “F” and it is not mentioned
anywhere since then (SOR/84-566, The Canada Gazette Part II, Volume 118, No.
16, August 8, 1984)
[13]
Despite
its tragic history, thalidomide was eventually found to be effective in the
treatment of leprosy and other related conditions (ENL), as well as a form of
cancer. By 1994, Celgene Corporation was exclusively devoted to the
commercialization of THALOMID to treat life threatening diseases, including
cancer and ENL.
[14]
In
Canada, THALOMID was first available in 1995 through the Health Canada Special
Access Program (SAP) which was designed to provide exceptional access to drugs
not approved for sale in Canada and for which a manufacturer does not hold an
NOC. These sales are exempt from the formal comprehensive scientific and
medical review undertaken when products are reviewed for a full marketing
authorisation. Recently, this Court confirmed in Teva Canada
Limited v. Canada (Minister of Health), 2012
FCA 106 (Teva), that an authorization under the SAP is not an approval
within the meaning of the DPP in the Regulations.
[15]
Thalidomide
had never been approved in a drug in the U.S., and in July 1998, Celgene
obtained a first approval to use it as THALOMID for acute treatment of the
cutaneous manifestations of moderate to severe ENL. The approval by the U.S.
Food and Drug Administration (FDA) was subject to the strongest restricted
distribution system to prevent birth defects. This required Celgene to create
the controlled distribution system known in the U.S. as the “S.T.E.P.S. ®”
program. In Canada, the controlled distribution system of this drug is known as
“Rev. Aid ®”. In May 2006, the FDA approved THALOMID for the treatment of
patients with newly diagnosed multiple myeloma (a form of cancer).
[16]
Celgene
claims that Health Canada expected it to file a NDS for THALOMID in view of its
high profile, the high volume of requests under the SAP and because NOC approval
would better ensure safety. In order to obtain such an NOC, Celgene filed what
it described as highly sensitive preparatory and confidential information
comprised in 180 volumes of data, including pharmacology
and pharmacokinetic studies, toxicology studies (including toxicity,
carcinogenicity and reproductive/development toxicity studies), clinical
pharmacology studies and pivotal clinical trials. As noted by the Judge in his
reasons at paragraph 23, it is the strictly confidential nature of this
information that motivated Celgene to request that THALOMID be listed on the
Register of “Innovative Drugs”, (per C.08.004.1(9) of the Regulations).
[17]
After
hundreds of questions were answered and additional information was provided, an
NOC for THALOMID was finally issued on August 4, 2010. At that time, the
Minister advised Celgene that THALOMID would not be eligible for data
protection because its medicinal ingredient, thalidomide, had been previously
approved by the Minister in at least two drugs - KEVADON and TALIMOL.
[18]
Having
considered detailed submissions by Celgene, the Minister confirmed the decision
not to list Celgene’s product on the “Innovative Drugs” Register. It is this
final decision that was the subject of the application for judicial review
before the Judge.
B.
Legislative
framework for Data Protection
[19]
Under
subsection 30(3) of the Food and Drugs Act, R.S.C. 1985, c. F-27, the
Governor in Council is empowered to adopt provisions implementing Canada’s international
obligations under Article 1711(5) and (6) of North American Free Trade Agreement Implementation Act (NAFTA), and Article 39(3) of the Trade Related Aspects of Intellectual Property Rights Agreement (TRIPS). These
provisions read as follows:
|
|
|
|
NAFTA
1711. (5) If a Party requires, as a condition for approving the
marketing of pharmaceutical or agricultural chemical products that utilize
new chemical entities, the submission of undisclosed test or other data
necessary to determine whether the use of such products is safe and
effective, the Party shall protect against disclosure of the data of persons
making such submissions, where the origination of such data involves
considerable effort, except where the disclosure is necessary to protect the
public or unless steps are taken to ensure that the data is protected against
unfair commercial use.
(6) Each Party shall provide that for data subject to paragraph
5 that are submitted to the Party after the date of entry into force of this
Agreement, no person other than the person that submitted them may, without
the latter's permission, rely on such data in support of an application for
product approval during a reasonable period of time after their submission.
For this purpose, a reasonable period shall normally mean not less than five
years from the date on which the Party granted approval to the person that
produced the data for approval to market its product, taking account of the
nature of the data and the person's efforts and expenditures in producing
them. Subject to this provision, there shall be no limitation on any Party to
implement abbreviated approval procedures for such products on the basis of
bioequivalence and bioavailability studies.
|
ALÉNA
1711. (5) Lorsqu'une Partie subordonne l'approbation de la
commercialisation de produits pharmaceutiques ou de produits chimiques pour
l'agriculture qui comportent des éléments chimiques nouveaux, à la
communication de données non divulguées résultant d'essais ou d'autres
données non divulguées nécessaires pour déterminer si l'utilisation de ces
produits est sans danger et efficace, cette Partie protégera ces données
contre toute divulgation, lorsque l'établissement de ces données demande un
effort considérable, sauf si la divulgation est nécessaire pour protéger le
public, ou à moins que des mesures ne soient prises pour s'assurer que les
données sont protégées contre toute exploitation déloyale dans le commerce.
(6) Chacune des Parties prévoira, en ce qui concerne les données
visées au paragraphe 5 qui lui sont communiquées après la date d'entrée en
vigueur du présent accord, que seule la personne qui les a communiquées peut,
sans autorisation de cette dernière à autrui, utiliser ces données à l'appui
d'une demande d'approbation de produit au cours d'une période de temps
raisonnable suivant la date de leur communication. On entend généralement par
période de temps raisonnable, une période d'au moins cinq années à compter de
la date à laquelle la Partie en cause a donné son autorisation à la personne
ayant produit les données destinées à faire approuver la commercialisation de
son produit, compte tenu de la nature des données, ainsi que des efforts et
des frais consentis par cette personne pour les produire. Sous réserve de
cette disposition, rien n'empêchera une Partie d'adopter à l'égard de ces
produits des procédures d'homologation abrégées fondées sur des études de
bioéquivalence et de biodisponibilité.
|
|
Trade Related Aspects of Intellectual
Property Rights Agreement
Section 7: Protection of Undisclosed Information
Article 39
3. Members, when requiring, as a condition of approving the
marketing of pharmaceutical or of agricultural chemical products which
utilize new chemical entities, the submission of undisclosed test or other
data, the origination of which involves a considerable effort, shall protect
such data against unfair commercial use. In addition, Members shall protect
such data against disclosure, except where necessary to protect the public,
or unless steps are taken to ensure that the data are protected against
unfair commercial use.
|
Accord sur les droits de propriété qui
touchent au commerce
Section 7: Protection des renseignements non divulgués
Article 39
3. Lorsqu'ils subordonnent l'approbation de la
commercialisation de produits pharmaceutiques ou de produits chimiques pour
l'agriculture qui comportent des entités chimiques nouvelles à la
communication de données non divulguées résultant d'essais ou d'autres
données non divulguées, dont l'établissement demande un effort considérable,
les Membres protégeront ces données contre l'exploitation déloyale dans le
commerce. En outre, les Membres protégeront ces données contre la
divulgation, sauf si cela est nécessaire pour protéger le public, ou à moins
que des mesures ne soient prises pour s'assurer que les données sont
protégées contre l'exploitation déloyale dans le commerce.
|
[20]
The
first set of Data Protection Provisions (DPP) were adopted in 1995 (SOR/95-411,
now repealed). They applied as follows:
|
C.08.004.1. (1) Where
a manufacturer files a new drug submission, an abbreviated new drug
submission, a supplement to a new drug submission or a supplement to an
abbreviated new drug submission for the purpose of establishing the safety
and effectiveness of the new drug for which the submission or supplement is
filed, and the Minister examines any information or material filed with the
Minister, in a new drug submission, by the innovator of a drug that contains
a chemical or biological substance not previously approved for sale in Canada
as a drug, and the Minister, in support of the manufacturer’s submission or
supplement, relies on data contained in the information or material filed by
the innovator, the Minister shall not issue a notice of compliance in respect
of that submission or supplement earlier than five years after the date of
issuance to the innovator of the notice of compliance or approval to market
that drug, as the case may be, issued on the basis of the information or
material filed by the innovator for that drug.
|
C.08.004.1. (1) Lorsque
le fabricant dépose une présentation de drogue nouvelle, une présentation
abrégée de drogue nouvelle ou un supplément à l'une de ces présentations en
vue de faire déterminer l'innocuité et l'efficacité de la drogue nouvelle qui
en est l'objet, et que le ministre examine les renseignements et le matériel
présentés, dans une présentation de drogue nouvelle, par l'innovateur d'une
drogue contenant une substance chimique ou biologique dont la vente comme
drogue n'a pas été préalablement approuvée au Canada et s'appuie sur les données
y figurant pour étayer la présentation ou le supplément du fabricant, il ne
peut délivrer un avis de conformité à l'égard de cette présentation ou de ce
supplément avant l'expiration du délai de cinq ans suivant la date à laquelle
est délivré à l'innovateur l'avis de conformité ou l'approbation de
commercialiser cette drogue, selon le cas, d'après les renseignements ou le
matériel présentés par lui pour cette drogue.
|
[21]
The
current version of the DPP in the Regulations were adopted in 2006 and the
relevant provision (C.08.04.1(1)) reads in part as follows:
|
“innovative
drug”
“innovative drug” means a drug that contains a medicinal
ingredient not previously approved in a drug by the Minister and that is
not a variation of a previously approved medicinal ingredient such as a salt,
ester, enantiomer, solvate or polymorph. (drogue
innovante) [My emphasis]
|
« drogue innovante »
« drogue innovante » S’entend de toute drogue qui
contient un ingrédient médicinal non déjà approuvé dans une drogue par le
ministre et qui ne constitue pas une variante d’un ingrédient médicinal
déjà approuvé tel un changement de sel, d’ester, d’énantiomère, de solvate ou
de polymorphe. (innovative drug) [Mon souligné]
|
|
(2) This section
applies to the implementation of Article 1711 of the North American Free
Trade Agreement, as defined in the definition “Agreement” in
subsection 2(1) of the North
American Free Trade Agreement Implementation Act, and of
paragraph 3 of Article 39 of the Agreement on Trade-related Aspects of
Intellectual Property Rights set out in Annex 1C to the World Trade
Organization Agreement, as defined in the definition “Agreement”
in subsection 2(1) of the World
Trade Organization Agreement Implementation Act.
|
(2) Le présent
article s’applique à la mise en œuvre de l’article 1711 de l’Accord de
libre-échange nord-américain, au sens du terme « Accord » au
paragraphe 2(1) de la Loi de mise en œuvre de l’Accord de
libre-échange nord-américain, et du paragraphe 3 de
l’article 39 de l’Accord sur les aspects des droits de propriété
intellectuelle qui touchent au commerce figurant à l’annexe 1C de
l’Accord sur l’Organisation mondiale du commerce, au sens du terme «
Accord » au paragraphe 2(1) de la Loi de mise en œuvre de
l’Accord sur l’Organisation mondiale du commerce.
|
|
(3) If a
manufacturer seeks a notice of compliance for a new drug on the basis of a
direct or indirect comparison between the new drug and an innovative drug,
(a) the
manufacturer may not file a new drug submission, a supplement to a new drug
submission, an abbreviated new drug submission or a supplement to an
abbreviated new drug submission in respect of the new drug before the end of
a period of six years after the day on which the first notice of compliance
was issued to the innovator in respect of the innovative drug; and
(b) the
Minister shall not approve that submission or supplement and shall not issue
a notice of compliance in respect of the new drug before the end of a period
of eight years after the day on which the first notice of compliance was
issued to the innovator in respect of the innovative drug.
|
(3) Lorsque le
fabricant demande la délivrance d’un avis de conformité pour une drogue
nouvelle sur la base d’une comparaison directe ou indirecte entre celle-ci et
la drogue innovante :
a) le fabricant ne peut déposer pour
cette drogue nouvelle de présentation de drogue nouvelle, de présentation
abrégée de drogue nouvelle ou de supplément à l’une de ces présentations
avant l’expiration d’un délai de six ans suivant la date à laquelle le
premier avis de conformité a été délivré à l’innovateur pour la drogue
innovante;
b) le ministre ne peut approuver une telle présentation ou un
tel supplément et ne peut délivrer d’avis de conformité pour cette nouvelle
drogue avant l’expiration d’un délai de huit ans suivant la date à laquelle
le premier avis de conformité a été délivré à l’innovateur pour la drogue
innovante.
|
|
(4) The period
specified in paragraph (3)(b) is lengthened to eight years and six
months if
(a) the
innovator provides the Minister with the description and results of clinical
trials relating to the use of the innovative drug in relevant pediatric
populations in its first new drug submission for the innovative drug or in
any supplement to that submission that is filed within five years after the
issuance of the first notice of compliance for that innovative drug; and
(b) before
the end of a period of six years after the day on which the first notice of
compliance was issued to the innovator in respect of the innovative drug, the
Minister determines that the clinical trials were designed and conducted for
the purpose of increasing knowledge of the use of the innovative drug in those
pediatric populations and this knowledge would there-by provide a health
benefit to members of those populations.
|
(4) Le délai prévu
à l’alinéa (3)b) est porté à huit ans et six mois si, à la
fois :
a) l’innovateur fournit au ministre la
description et les résultats des essais cliniques concernant l’utilisation de
la drogue innovante dans les populations pédiatriques concernées dans sa
première présentation de drogue nouvelle à l’égard de la drogue innovante ou
dans tout supplément à une telle présentation déposé au cours des cinq années
suivant la délivrance du premier avis de conformité à l’égard de cette drogue
innovante;
b) le ministre conclut, avant
l’expiration du délai de six ans qui suit la date à laquelle le premier avis
de conformité a été délivré à l’innovateur pour la drogue innovante, que les
essais cliniques ont été conçus et menés en vue d’élargir les connaissances
sur l’utilisation de cette drogue dans les populations pédiatriques visées et
que ces connaissances se traduiraient par des avantages pour la santé des
membres de celles-ci.
|
|
(5) Subsection (3)
does not apply if the innovative drug is not being marketed in Canada.
|
(5) Le paragraphe
(3) ne s’applique pas si la drogue innovante n’est pas commercialisée au
Canada.
|
|
(6) Paragraph (3)(a)
does not apply to a subsequent manufacturer if the innovator consents to the
filing of a new drug submission, a supplement to a new drug submission, an
abbreviated new drug submission or a supplement to an abbreviated new drug
submission by the subsequent manufacturer before the end of the period of six
years specified in that paragraph.
|
(6) L’alinéa (3)a)
ne s’applique pas au fabricant ultérieur dans le cas où l’innovateur consent
à ce qu’il dépose une présentation de drogue nouvelle, une présentation abrégée
de drogue nouvelle ou un supplément à l’une de ces présentations avant
l’expiration du délai de six ans prévu à cet alinéa.
|
|
(7) Paragraph (3)(a)
does not apply to a subsequent manufacturer if the manufacturer files an
application for authorization to sell its new drug under section C.07.003.
|
(7) L’alinéa (3)a)
ne s’applique pas au fabricant ultérieur s’il dépose une demande
d’autorisation pour vendre cette drogue nouvelle aux termes de l’article
C.07.003.
|
|
(8) Paragraph (3)(b)
does not apply to a subsequent manufacturer if the innovator consents to the
issuance of a notice of compliance to the subsequent manufacturer before the
end of the period of eight years specified in that paragraph or of eight
years and six months specified in subsection (4).
|
(8) L’alinéa (3)b)
ne s’applique pas au fabricant ultérieur dans le cas où l’innovateur consent
à ce que lui soit délivré un avis de conformité avant l’expiration du délai
de huit ans prévu à cet alinéa ou de huit ans et six mois prévu au
paragraphe (4).
|
|
(9) The Minister shall
maintain a register of innovative drugs that includes information relating to
the matters specified in subsections (3) and (4).
|
(9) Le ministre
tient un registre des drogues innovantes, lequel contient les renseignements
relatifs à l’application des paragraphes (3) et (4).
|
C. The
Federal Court Judge’s Decision
[22]
The
Judge accepted the parties’ submissions that questions of law before the
Minister were to be reviewed on the standard of correctness.
[23]
He
then proceeded to apply the modern rule of statutory interpretation (paragraphs
26 and 27 of his reasons), noting particularly that as the DPP in the
Regulations are intended to implement international treaty obligations. He
explained that the said treaties are considered a primary aid to construction,
even where there is no ambiguity in the Regulations.
[24]
In
that respect, he noted that, as discussed in Apotex Inc., v. Canada
(Minister of Health), 2010 FCA 334 at paragraph 110, the relevant
provisions of NAFTA and TRIPS “seek to provide protection to innovators in
respect of ‘undisclosed tests or other data’ that they must provide to government
entities in order to obtain approval for their new drugs”. These treaties set
out a scheme for protection against the unfair commercial use of such
undisclosed data, the origination of which involved considerable effort. This
is not disputed.
[25]
However,
the Judge rejected the Minister’s position that this international scheme is
meant to protect only those products that use “new chemical entities” (In
French, “éléments chimiques nouveaux”), and that thalidomide is not a “new
chemical entity” as it was approved for marketing and sale in Canada in the 1960s.
[26]
At
paragraph 33 of his reasons, he said:
33. There
are a number of flaws with respect to that construction of the DPR [DPP]. First of all, thalidomide was not approved for any use
prior to the issuance of the NOC. Indeed, it was included in Schedule
"H" and then "F" of the Act and was therefore totally
banned in Canada. This is not a case, therefore, where the data was collected
for the different use of a drug already approved. The purpose of the DPR
[DPP] in requiring that the drug not be previously approved is to ensure a
company is not granted data protection for something in previous use and for
which no innovation was required. This is made clear by the exclusion from the
scope of data protection, in the definition of "innovative drugs", of
variations or minor changes to a drug previously approved such as salts,
esters, solvates, polymorphs or enantiomers. The Regulatory Impact Analysis
Statement explicitly states that these exclusions are aimed at preventing an
innovator from seeking additional data protection for a minor change to a drug.
[My emphasis]
[27]
He
also noted at paragraph 35 of his reasons that “Celgene's
innovation was to take something that was banned as dangerous and which had not
been found to be safe and efficacious and to show it to be a useful, lifesaving
drug”.
[28]
The Judge agreed with Celgene that, to make TRIPS and NAFTA obligations
meaningful, the protection of “new chemical entities” must arise when approval
is sought for a product containing an entity that does not have approval in a
drug in a particular jurisdiction. Thus, a member country could not avoid the
obligation to grant protection because the chemical entity in the product has
been approved elsewhere or is otherwise known.
[29]
Moreover, he went on to say that: “… it
would similarly be inconsistent with these treaties to refuse data protection
when a chemical entity is put to an entirely new use, on the basis of extensive
and genuinely new data ensuring its effectiveness and safety. In the same
way as variations of a drug not included in the definition of innovative drug,
new uses of previously approved ingredients must be considered on a
case-by-case basis to determine how innovative they are and whether the data
supporting them was ‘gathered at considerable cost which is not otherwise
publicly available in that assembled form’ ” (Judge’s
reasons at paragraph 36).
[30]
Although
he mentioned Celgene’s argument that an approval under the regulatory regime in
place prior to 1963 is not an approval under the DPP, the Judge did not decide
the issue, simply noting that this argument reinforces his conclusion that the
prior approval of KEVADON and TALIMOL in this case should not stand in the way
of data protection for THALOMID.
[31]
At
paragraph 46 of his reasons, he indicated that this conclusion is based on the
following combined facts:
i.
The
prior approval of thalidomide was short lived and should never have been given
at the time;
ii.
Thalidomide
was effectively banned until Celgene came up with its NDS for THALOMID; and,
iii.
The
2010 NOC approval was granted for Celgene’s product on the basis of completely
new studies and data.
[32]
Lastly,
although no evidence was presented in that respect, the Judge indicated that
this case was obviously quite an exceptional one, and that his decision should
therefore have a limited impact in the foreseeable future.
ANALYSIS
[33]
This
Court’s role is to determine whether the Judge hearing the application for
judicial review properly identified and applied the standard of review (Prairie
Acid Rain Coalition v. Canada, 2006 FCA 31 at paragraph 14; Telfer v. Canada (Revenue Agency), 2009 FCA 23 at paragraph 18).
[34]
The
Judge applied the correctness standard to the Minister’s interpretation of the
definition of “innovative drug” in the Regulations (a pure question of law). In
Takeda Canada Inc. v. The Minister of Health, 2013 FCA 13, this Court
held that this is the appropriate standard of review to be applied to such
questions.
[35]
Whether
the Judge correctly applied this standard essentially means that, to allow this
appeal, this Court must agree with the Minister’s interpretation of “innovative
drug” and more particularly of the words “not previously approved in a drug by
the Minister”. (in French, “ non déjà autorisé
dans une drogue par le ministre ”).
[36]
The
applicable principles of statutory interpretation are not in dispute. It is trite
law that the words of an Act must be read in their entire context and in their
grammatical and ordinary sense, harmoniously with the scheme of the Act, the
object of the Act and the intention of Parliament.
[37]
As
mentioned, THALOMID is a “new drug” within the meaning of the Regulations (at
section C.08.001).
Thus,
the Minister’s approval must be obtained before it can be sold in Canada. I note that as Celgene was seeking an approval for a new indication for
thalidomide, even if the 1960’s approvals had not been withdrawn, THALOMID would
still have fallen within the definition of “new drug”and would have been
required to file voluminous data obtained as a result of considerable effort
and expense.
[38]
However,
Celgene did not argue before the Minister and the Judge that it should qualify
as an “innovative drug” because of the new use or indication for which it submitted
its NDS for thalidomide. The parties indicated that the issue of whether a new
indication or new use of an approved medicinal ingredient qualifies under the
definition of “innovative drug” was not really argued before the Judge. In the
circumstances, I agree that the Judge should have refrained from commenting on
this question, which has never been the subject of adjudication. The comments
at paragraphs 36-38 of his reasons should therefore be given no precedential
value. This is especially so considering that: i) the definition of “innovative
drug” and the relevant provisions of the treaties aforementioned refer only to
the “medicinal ingredient” and the “chemical entity” in a drug, never to its
use; and ii) he did not consider clearly relevant passages of the Regulatory Impact Analysis Statements (RIAS) (such
as the passage of the RIAS dated October 5, 2006 cited and discussed at paragraphs
127 and 128 of Dawson J.A.’s reasons in Takeda, above, and the RIAS,
dated October 5, 2004, Canada Gazette, Part II, Volume 138, No. 50 Page 3713,
Note 1). Also, the periods of exclusivity granted for a “new indication or use”
in the United States and the European Union are less than the minimum period set
out in the relevant treaties. This would suggest that these parties understand
that the provisions of these treaties do not cover such cases. All this
militates against the view expressed by the Judge.
[39]
It
is not necessary to say more in this respect as this appeal does not require it.
[40]
Turning
back to the true question before us – Is thalidomide a “medicinal ingredient
not previously approved in a drug by the Minister”?
[41]
Here
the dispute is not as in Teva, above, where the issue was what type of
approval under the Regulations is covered by these words. Rather, what Celgene
is asking the Court to say is that the word “approved” refers to the status of
a medicinal ingredient in a drug at the time a NDS is submitted by the innovator.
In this respect, Celgene focussed on thalidomide’s status as a prohibited drug,
i.e. a banned drug at the relevant time. It did not argue that this drug was
never approved (i.e., that the approval was null ab initio). That said,
the interpretation proposed by Celgene would necessarily apply to any drug in
respect of which an approval (NOC) has been withdrawn because of a Minister’s
decision or even abandoned voluntarily before the filing of a second NDS for
this drug.
[42]
In
the Minister’s view, the word “approved” can only refer to the fact that an
approval (more particularly a NOC) has been issued by the Minister. In any
event, the Minister says that the word “approved” is qualified by the adverb “previously”
which clearly support its view that one must look at an action which took place
in the past rather than at the current status of the drug.
[43]
“Previously”
is defined in the Oxford English Dictionary (2d ed. (Oxford: Clarendon
Press, 1989), Volume XII) as an adverb meaning “at a previous or preceding
time, before, beforehand, antecently”. The word “déjà” in French has more
a complex definition. Its meaning depends on the context, but it has only one
common meaning with “previously”. In that context, it is defined in
the Le
Nouveau Petit Robert
(Paris : Dictionnaires Le Robert, 2002) as “auparavant,
avant (cf., Une première fois*)”.
[44]
These
words do not lend themselves easily to the construction proposed by Celgene,
which in fact would require to construe “previously” as meaning “currently”
or
to read in the words “and currently” before the word “approved” in the
definition.
[45]
Still,
Celgene submits that the Court should adopt its view and effectively read down
the definition because its interpretation is more in line with the primary
purpose and object of the scheme of the DPP and the relevant treaty provisions,
which is to promote innovation and protect innovators against unfair use of
their confidential data gathered at great cost. I do not accept that the
purpose and object of the relevant provisions of NAFTA and TRIPS is as wide as
Celgene suggests. In my view, the protection accorded to the confidential data
discussed above is limited to certain innovations only.
[46]
Recognizing
that the legislator clearly intended to avoid any duplication of the market
exclusivity period provided for in the DPP, Celgene argues that in this case,
there would be no such duplication. That may well true in this case, but I
cannot conclude that it would be true for all cases that could be affected by
the interpretation proposed by Celgene.
[47]
The
signatories of these treaties have agreed to grant the minimum protections set
out therein only in the context of approvals for the marketing of
pharmaceutical and agricultural products which utilize “new chemical entities”.
Celgene submits that this limitation does not apply in Canada because the Regulations make no reference to “new chemical entities” (Respondent’s
memorandum, at paragraph 61). I do not agree.
[48]
In
my view, the words “medicinal ingredient” as used in the Regulations are the
equivalent of “chemical entity”, as are the words “active ingredient” and
“active moiety” in the American Regulations, “active substance” in the European
Regulations, and “active component” in Australia. It is quite usual for the
words of a treaty to be harmonized with the language used in one’s own
regulatory scheme.
[49]
This
view is supported by the following note in the RIAS dated October 5, 2004, explaining
the use of the word “medicinal ingredient”:
Although the
NAFTA and TRIPS agreements use the term “new chemical entity”, “new medicinal
ingredient” is used here to correspond to the terminology already used in the Food
and Drugs Regulations.
[50]
The
word “new” (or “nouveau” in French) is defined in the Canadian Oxford
Dictionary
(Don Mills: Oxford University Press, 2001) as:
a) of
recent origin or arrival;
b) made,
invented, discovered, acquired or experienced recently or now for the first
time.
[51]
The
parties agree that, read in the context of a provision dealing with approval of
pharmaceutical product for marketing in the territory of a signatory state, “new”
does not mean “unknown”, “made”, “invented” or “discovered recently”. In my
view, it can reasonably be understood to mean submitted for approval for the
first time to the appropriate authority in the territory of a signatory state.
[52]
No
evidence or foreign case law has been submitted to show that such an
interpretation would be at odds with the general understanding of the
signatories. Nor was any such evidence or case law produced to establish that
other parties to these treaties consider banned drugs or drugs for which a
previous approval for marketing has been withdrawn as “new” within the meaning
of the provision under review.
[53]
When
Celgene sought an approval for THALOMID in 1998 in the U.S., thalidomide qualified as a new active substance as it had never been approved in
1960s in that country.
[54]
My
understanding of the relevant treaties is in line with the construction
proposed by the Minister. It also reads harmoniously with subsections 3 (a)
and (b) of the DPP, which provide that the period of exclusivity starts
on “the day on which the first NOC was issued to the innovator”.
[55]
The
fact that Celgene had to submit a considerable amount of confidential data
gathered at great cost does not, in and of itself, justify stretching the
language of the definition of “innovative drug”. It is only one of two
necessary pre-requisites for the application of the treaties’ provisions.
[56]
Parliament
had the power to extend the protection granted under the DPP to other “new drugs”
as defined in the Regulations, which also require the filing of similarly
substantial confidential data. From the definition adopted, in my view, it is
clear that the legislator chose not to do so.
[57]
That
is not to say that I assume that the legislator had banned drugs in mind when
he made his choice and adopted the definition of “innovative drug” in the
Regulations.
[58]
At
the hearing, the parties confirmed that there was no evidence as to how many
drugs have been banned throughout the years and how many NOCs have been withdrawn
or abandoned.
[59]
It
is obvious that the Judge was troubled by what he perceived as a great
injustice. He said at paragraph 42:
It
is equally clear that safety and effectiveness are the main considerations with
respect to a drug approved for public use. This is indeed the position that was
taken by the Minister in Teva Canada Limited, above
at para 21. Would it then be fair to say that a drug, the approval of which has
been withdrawn for safety reasons, should nevertheless be considered as having
been previously approved? In my view, such a finding would be entirely
perverse.
[60]
Still,
it appears that he was not prepared to simply exclude from the definition, all
drugs in respect of which an NOC had been withdrawn. As noted, in paragraph 28
above, he justified his conclusion on the basis of combined facts, setting
stricter parameters to the application of the exclusion.
[61]
Although
I recognize the exceptional history of thalidomide, I do not see any cogent legal
basis to create an exception even using the strict parameters set out by the
Judge.
[62]
The
change in the regulatory regime that occurred in 1963 may have been major, but
the issue with thalidomide was not in respect of its efficacy, which was the
most important change to the requirements introduced in 1963 [SOR/63-386]. How
many other changes in the regulatory requirements throughout the years since
then could be argued to be significant enough to warrant another exception to
the rule?
[63]
Should
Courts have to inquire as to why a NOC was suspended or withdrawn? Should a
drug be treated differently depending on whether its NOC was withdrawn because
it was based on inaccurate or even fraudulent data, as opposed to an alleged
error by the regulatory authority of the time?
[64]
What
if a drug is banned after the innovator enjoyed six months of exclusivity on
the market before the revocation of its NOC? Should it be treated in the same
way as a banned drug that enjoyed one, two or three years of market
exclusivity?
[65]
If
I were to read the words “and currently” into the DPP, it could well open the
door to all kinds of unintended scenarios.
[66]
Celgene
insisted before us that “facts do matter”. I agree, but as the adage goes “hard
facts often make bad law”.
[67]
I
would allow this appeal with costs. I would set aside the judgment of the
Federal Court and, rendering the judgment which ought to have been rendered, I
would dismiss the application for judicial review with costs.
"Johanne
Gauthier"
« I
agree
K. Sharlow”
NADON J.A. (Dissenting)
[68]
I
have carefully reviewed the reasons of my colleague Gauthier J.A. and, with
respect, I cannot agree with her disposition of the appeal. I would dismiss the
appeal and affirm the judgment of de Montigny J. in its result.
[69]
This
appeal is about the interpretation of the phrase “previously approved” in the
definition of an “innovative drug”, as defined in subsection C.08.004.1(1) of
the Food and Drug Regulations, C.R.C. c. 870 (“the Regulations”),
and whether that phrase should encompass a medicinal ingredient that briefly
satisfied Canadian regulatory requirements before its approval was revoked.
Gauthier J.A. concludes that the fact that the medicinal ingredient thalidomide
once received the regulatory green light in Canada means that it was previously
approved for the purposes of the Regulations, despite the outright ban
that quickly replaced that approval and effectively persisted for 33 years. In
her view, courts should not inquire into why a notice of compliance (NOC) was
suspended or revoked, but should strictly construe the phrase “previously
approved”. Further, my colleague sees the contrary interpretation as leading to
any number of unintended scenarios. I do not agree.
[70]
The
1962 legislative response to the thalidomide tragedy introduced a new schedule
to the Food and Drugs Act, R.S.C. 1985, c. F-27 (“the Act”)
to expressly prohibit the sale of thalidomide. This legislation, and its
successors, have made thalidomide both generally unavailable in Canada and unavailable to serve as a Canadian reference product for drug manufacturers.
Accordingly, thalidomide was unable to appropriately occupy the space carved
out for an “innovative drug” within the overall scheme of the Regulations.
The key fact that the Minister of Health communicated an expectation that
Celgene should submit a New Drug Submission (NDS) to obtain regulatory
approval, as opposed to an Abbreviated New Drug Submission (ANDS), belies an
underlying belief that thalidomide was, although not strictly innovative, best
suited to occupy the space set out for an “innovative drug” within the Regulations.
In Gauthier J.A.’s opinion, interpreting the term “previously” to mean
“currently” inappropriately stretches the meaning of the term and could lead to
inadvertent consequences. Yet, as I will demonstrate below, concluding that
thalidomide was indeed previously approved is at odds with the manner in which
the Regulations prescribes roles for innovative and generic drugs.
[71]
Considering
the 1960 and 1961 approvals of KEVADON and TALIMOL, respectively, as sufficient
to bar thalidomide from achieving innovative drug status in Canada disregards the intention of the Regulations. The Patented Medicine (Notice of
Compliance) regime demarcates separate roles for innovative and generic drugs,
and their manufacturers. Drugs are either innovative—drugs containing medicinal
ingredients or indications appearing in the Canadian market for the first time,
or generic—versions of innovative drugs made by non-research based companies,
which achieve approval through an abbreviated compliance mechanism by
demonstrating bioequivalence to the innovative drug. Since thalidomide was not
on the Canadian market prior to its reintroduction by Celgene, and therefore
not available to serve as a reference product for a generic manufacturer, it
follows that the more appropriate space for thalidomide to occupy is that of an
innovative drug. It is not, as the Minister suggests, most appropriate to
conclude that it should occupy neither.
[72]
Moreover,
the phrase “previously approved” cannot be intended to apply as suggested by
Gauthier J.A. or the Minister of Health, i.e., because the drug was once
allowed to be sold in Canada, it remains previously approved even after its
sale was disallowed. This view of the phrase leads to an incoherent result.
After being removed from the market by legislative decree in 1962, thalidomide
was not “previously approved” by either a common sense understanding of the
term, or by the definition offered in previous case law. The approval was
revoked. For all intents and purposes, the manner in which thalidomide has been
treated has amounted to a nullification of any previous approval. Accordingly,
it should be considered to meet the definition of an “innovative drug” and be
entitled to data protection.
[73]
In
these reasons, I begin by briefly discussing how the legislative treatment of
thalidomide has prevented its use in Canada since 1962. I then survey relevant
case law from this Court and the Federal Court, discussing other judicial
interpretations of the phrase “previously approved” and how this interpretation
fits into the innovative drug regime. I depart from the contextual approach of
de Montigny J. (the judge) to more explicitly consider whether the revocation
of thalidomide’s ministerial approval amounts to a nullification and conclude
that it does. Finally, I address the argument of whether the changes to
Canada’s drug approval regulations, which were precipitated by the thalidomide
tragedy itself, impact whether a drug approved under the 1955 Regulations should
still be considered approved under the modern scheme. I conclude that this does
not matter: the withdrawal of the approval is sufficient to determine that
thalidomide should not be considered previously approved. This analysis leads
me to the conclusion that the appeal should be dismissed.
a. Legislative History of
Thalidomide
[74]
Gauthier
J.A. surveys the legislative history at paragraphs 3 – 18 of her reasons. This
history demonstrates that various legislative mechanisms were in place to
prohibit use of thalidomide in Canada from 1962 until 1984. As indicated by the
letter from the Minister of Health my colleague quotes at paragraph 6 of her
reasons, the 1962 withdrawal caused thalidomide to revert to the status of a
new drug. The tragic circumstances that accompanied the use of thalidomide also
provided the impetus for extraordinary measures to be taken in the House of
Commons: the Act was amended with a new schedule that expressly
prohibited the use of thalidomide in Canada. Illustrating the deeply felt
effects of thalidomide in Canada, the Respondent quotes from the member from
Simcoe East, Mr. P.B. Rynard from House of Commons debate on October 26, 1962
as saying the following:
Thalidomide
is no longer the name of a drug; it is the name of a tragedy that forces one to
think of the accidental deaths of hundreds of children across Canada every year.
[75]
Parliament’s
many legislative responses over the years also demonstrate the unique situation
presented by thalidomide. It was the only medicinal ingredient to ever be
expressly prohibited alongside various illegal street drugs; it, at times,
received its very own sections and schedules within the Act; and it
persisted within the Act even after dramatic overhauls further modified
the administration of restricted substances—relegating those street drugs that
were previously considered alongside it to other pieces of legislation.
[76]
Even
more importantly, the prohibition was consistent and complete. There were no
gaps in this legislative scheme and no opportunities for manufacturers to
return thalidomide to the Canadian marketplace. Before us, the Appellant
suggested that after thalidomide was removed from Schedule F in 1984, it was no
longer expressly prohibited in Canada. Neither party made submissions on why
thalidomide was taken out of the Act or where Health Canada came to see its place within the larger regulatory scheme. Regardless, the Special
Access Programme (SAP), further described below, was already in place by 1984.
Therefore, thalidomide would have been theoretically available through SAP
since its express prohibitions were removed. This means there has always been
some method of regulating thalidomide within the existing scheme. THALOMID was
first made available through the SAP in 1995. By that time, it had been absent
from the Canadian market for 33 years.
[77]
Because
thalidomide reverted to the status of a “new drug” with the 1962 withdrawal, it
would nonetheless have been unavailable for doctors to generally prescribe or
to serve as a Canadian reference product for a generic manufacturer. In order
to be generally prescribed by physicians or available other than through the
SAP, thalidomide would have required the submission of an NDS and to receive
the corresponding approvals. Moreover, physicians would not have been
particularly interested in prescribing thalidomide until its therapeutic value
was once again demonstrated. It was only with the research efforts of Celgene
in the early 1990s that thalidomide became a viable treatment option for ailments
including severe erythema nodosum leprosum (ENL) and multiple myeloma. As my
colleague mentions, THALOMID was approved in the United States for the
treatment of ENL in 1998. As thalidomide had never before been approved for use
in the United States, no similar situation arose.
[78]
I
now turn my attention to the access through the SAP and what use of this
programme means for the interpretation of the phrase “previously approved.”
B.
The
Meaning of Previously Approved
[79]
Since
the amendments to the Regulations, only a few cases have dealt with the
concept of an innovative drug and the appropriate interpretation of its
definition. Fewer still specifically address the meaning of the phrase
“previously approved.” However, in Teva Canada Ltd. v. The Minister of
Health and Sanofi-Aventis Canada Inc., 2012 FCA 106 (Teva), this
Court did consider the meaning of the term “previously approved” in the
definition of an “innovative drug”, albeit in different circumstances. Teva had
contested the Minister’s decision to list the drug Eloxatin on the register of
innovative drugs and the corresponding grant of data protection that
accompanied it. The key question was whether thousands of ministerial
authorizations to use Eloxatin for emergency treatment under the SAP
constituted previous approval within the scope of the Regulations. If
these authorizations were considered tantamount to previous approval, Eloxatin
would not be entitled to receive data protection under the Regulations.
[80]
This
Court affirmed the decision of the Federal Court and concluded that Eloxatin
was indeed entitled to data protection: the uses permitted under the SAP did
not amount to previous approval of the drug under the Regulations. For a
unanimous court, Stratas J.A. explained the architecture and wording of the Regulations
and how this interpretation was consistent with Canada’s treaty
obligations. The appeal was dismissed.
[81]
Teva
illustrates
two important points. First, it delineates how the SAP fits into the scheme of
the Regulations. Stratas J.A. describes the programme as follows:
[25]
The Special Access Programme is different. It allows for the use of certain
drugs despite the absence of data and studies demonstrating the safety and
efficacy of the drug.
[26]The
Programme is set out in sections C.08.010 and C.08.011 of the Regulations under
the heading “Sale of New Drug for Emergency Treatment.”
[27]
This Court has described the Special Access Programme in the following way:
[4] … [T]he
Director (Assistant Deputy Minister, Health Products and Food Branch, Health
Canada) may authorize the sale of a new drug to a physician under the Special
Access Programme (“SAP”) for the emergency treatment of a patient.
….
[10] When
requesting Health Canada for an authorization under the SAP, a physician must:
(i) describe the patient’s medical condition; (ii) explain why the medicine is
the best choice for treating the condition; and (iii) provide data on the use,
safety and efficacy of the medicine requested. If granted, an SAP authorization
authorizes, but does not require, a manufacturer to sell a specified quantity
of the medicine to the requesting physician for the emergency treatment of a
specified condition of a named patient under the care of the physician. The
physician must report to Health Canada on the use of the medicine, including
any adverse effects.
[11] SAP
authorizations…are normally granted for serious or life-threatening conditions
when conventional treatments have proved ineffective or are not suitable for
the particular patient. Typically, medicines authorized under the SAP are
treatments of last resort and are not subject to the same level of scrutiny for
safety and efficacy as medicines for which an NOC has been issued. Nonetheless,
Health Canada reviews the SAP request and any other available data on the new
medicine in order to “manage the risk” of its use.
See Hospira
Healthcare Corp. v. Canada (Attorney General), 2010 FCA 345 (CanLII),
2010 FCA 345; see also Canada (Attorney General) v. Celgene
Corporation, 2009 FCA 378 (CanLII),
2009 FCA 378, aff’d 2011 SCC 1 (CanLII),
2011 SCC 1, [2011] S.C.R. 3.
[28]
Drugs available under the Special Access Programme are not founded upon data
and studies that, in the Minister’s view, have established safety and
effectiveness. Rather, they are made available in emergency situations as a
treatment of last resort where conventional treatments have failed or are
unavailable. As this Court has already held, sales under the Special Access
Programme alone are not evidence of a determination by the Minister of the
safety and efficacy of a drug: Hospira, supra at paragraph 6. Indeed, it
is theoretically possible that drugs available under the Special Access
Programme are not entirely safe or effective, but, owing to the grievous
circumstances of the patient, they may have some upside and are worth the risk.
Authorizations under the Special Access Programme are best seen as
compassionate permissions, not as approvals for the drug.
[82]
This
understanding of the SAP demonstrates that the drugs being accessed through the
programme cannot be considered to be approved for use in Canada. These drugs do not have an NOC and they have not received the scrutiny regarding safety and
efficacy that is associated with acquiring one. It follows that since
thalidomide was being accessed through the SAP, it was not approved for use in Canada. The necessary implication is it cannot be “previously approved.” A common sense
interpretation of the phrase cannot lead to the conclusion that a one-time
approval, quickly revoked and replaced with a prohibition that has remained
consistently in force since 1962 is sufficient to be called “previous
approval.”
[83]
Additionally,
this supports the conclusion that thalidomide, after being found to be unsafe,
can no longer be considered as having been “previously approved” for an
approval process based on safety. Since its therapeutic use became known in the
1990s, thalidomide has only been available through the SAP. As indicated in Teva,
it is “theoretically possible” that drugs under the SAP are “not entirely safe or
effective.” In this situation, thalidomide had definitively found to be unsafe
in 1962 and had not gone through additional regulatory approvals necessary to
reverse that finding.
[84]
Second,
Teva is helpful in defining what “previously approved” means in the
context of the Regulations as a codification of Canada’s treaty obligations under the North American Free Trade Agreement and the Trade
Related Aspects of Intellectual Property Rights Agreement. This is
instructive, particularly since the Appellant makes arguments about how section
C.08.004.1 should be read based on Canada’s treaty obligations. The Appellant
focuses on how data protection is limited to new chemical entities in the
treaties and how the Governor in Council subsequently integrated this concept
into Canadian law through its definition of “innovative drug.” The Respondent
replies that the spirit of the data protection provisions in NAFTA and TRIPS is
to provide protection for data that is gathered through considerable effort and
to guard against its unfair commercial use. Thus, the data set produced on
thalidomide is captured by this purpose. At paragraph 42 of her reasons,
Gauthier J.A. does not accept that the object and purpose of these provisions
is as broad as the Respondent suggests.
[85]
In
my opinion, however, Gauthier J.A.’s treatment of international instruments is
ultimately unhelpful. Quite simply, this case turns on whether thalidomide can
be considered to be previously approved. It is that phrase that should be the
focus of our attention. Stratas J.A. addresses very similar submissions in the Teva
decision:
[36] As mentioned in paragraph 16,
above, Teva emphasizes that the
treaty provisions require consideration of whether the drug contains a new
chemical entity, whether the drug submission contains undisclosed data
necessary to determine safety and efficacy, and whether the data involved
considerable effort. That may be true, but that does not shed direct light on
the meaning of “previously approved” in subsection C.08.004.1(1) of the Regulations.
[37] Of more relevance to the meaning of
“previously approved” is the repeated mention in these treaty provisions of the
concept of marketing approval or, as Teva puts it, market authorization.
Article 1171, paragraphs 5 and 6 of the North American Free Trade
Agreement obligate Canada to protect data
necessary for “approving of marketing” of pharmaceutical products for at least
five years from when Canada granted “approval to the person that produced the
data for approval to market its product.” Article 39, paragraph 3 of the Trade
Related Aspects of Intellectual Property Rights Agreement similarly refers to data required “as a
condition of approving the marketing of pharmaceutical” products. In Canada, market approval under the Regulations means the issuance of a notice of compliance and a drug
information number.
[38] Given that the definition of
“innovative drug” in subsection C.08.004.1(1) of the Regulations was intended to implement these
treaty provisions, “previously approved” in subsection C.08.004.1(1) must
mean a previous marketing approval, i.e., the previous
issuance of a notice of compliance and a drug information number. If someone
has previously received a notice of compliance and a drug identification number
for a particular drug, providing that person with data protection would go
beyond the scope of the treaty provisions. Accordingly, the definition of
“innovative drug” in subsection C.08.004.1(1) does not include drugs that have
been “previously approved.”
[86]
Based
on this reasoning, the fact that thalidomide’s NOC was revoked supports the
conclusion that it should not be held to have been previously approved. Without
its NOC, thalidomide is unable to satisfy the requirements for market approval
in Canada. It is impossible to accept that thalidomide has nonetheless been
previously approved without having market approval.
[87]
At
paragraph 89 of its submissions, the Respondent argues that the Teva case
stands for the proposition that approval by the Minister is a two-step process
that includes determinations of both safety and effectiveness. In this view, a
finding by the Minister that a drug is both safe and effective is a condition
precedent to the granting of market approval. The Respondent therefore argues
that it is inconsistent to deny data protection to THALOMID because KEVADON and
TALIMOL were specifically found to be unsafe. This determination leaves the
condition precedent unsatisfied.
[88]
While
this argument may overstate how the Minister’s authorization operates within
the regime, it does illustrate an important difference between the current
regulatory regime and the regime that was in place when approvals were granted
to KEVADON and TALIMOL. In 1960, some of the requirements that a drug now must
meet in order to be permissible in Canada were absent from the regulatory
scheme. As discussed below, approvals under previous versions of regulations
generally remain in force unless expressly contrary direction is provided.
Nonetheless, I am unable to accept that the very drug that provided the impetus
to change the Regulations could now be denied data protection by a
decades-old approval that was swiftly rescinded. It cannot be that when
thalidomide was removed from the Canadian market, with much fanfare, it could
still have been considered as having been “previously approved.”
[89]
Therefore,
the question to ask is not whether the change in scheme negates the previous
approval, but instead whether the 1962 withdrawal constituted an altogether
nullification of regulatory approval, such that thalidomide could never be
considered “previously approved.” At paragraph 41 of his reasons, the judge
declines to comment on whether the prior approvals were nullified. He writes:
[41] I do not think it necessary to determine, for the purposes of
this application for judicial review, whether the withdrawal from the market of
KEVADON and TALIMOL amounted to the nullification of Health Canada’s prior approvals of thalidomide.
[90]
This
determination may not have been required for the contextual, purposive approach
taken by the judge, however, determining whether it was nullified is paramount
for the determination of whether thalidomide remains “previously approved” in
the context of the definition of an innovative drug. In my view, the
combination of the above legislative history and the manner in which the SAP
functions is sufficient evidence to conclude that the steps taken by the
Minister and Parliament in 1962 nullified the approval that was once extended
to KEVADON and TALIMOL. This conclusion therefore allows data protection to be
extended to thalidomide: the “previously approved” condition in the definition
of innovative drug has not been met.
[91]
Regardless,
the judge goes on to use similar rationale in the context of his purposive
approach. He is alive to the key issue involving Canadian reference products:
the Regulations carve out a specific home for new drugs as acting as the
comparator for subsequent generics. The NDS/ANDS scheme reflects these dual
roles. The fact that thalidomide was unavailable to serve as a reference
product is important as the Respondent did not have any other manner of getting
its drug approved in Canada. It had no comparator to demonstrate bioequivalence
with: it had to start from scratch and create a data set to prove to the
Minister that thalidomide was safe and effective. Acknowledging this fact, the
judge writes:
[42]
It is equally clear that safety and effectiveness are the main considerations
with respect to a drug approved for public use. This is indeed the position
that was taken by the Minister in Teva Canada Limited, above at para 21.
Would it then be fair to say that a drug, the approval of which has been
withdrawn for safety reasons, should nevertheless be considered as having been
previously approved? In my view, such a finding would be entirely perverse. It
is apparent that the approvals should never have been granted in view of the
absence of data relating to the severe deleterious effects of the drug. This is
precisely why KEVADON and TALIMOL could not be considered as “Canadian
reference products” for the purpose of an ANDS. Even if these products were not
voided but only withdrawn from sale, it remains that Canadians could not
benefit from the discovery and development of thalidomide unless and until new
medicines could be approved on the basis of new information and data
demonstrating their safety and efficacy.
[92]
The
paragraph he cites from Teva states the following:
[21] As for drug identification numbers, no manufacturer may sell
a drug in dosage form unless one has been assigned: Regulations at
subsection C.01.014(1). A drug identification number is an eight-digit
numerical code that identifies drug product characteristics including
manufacturer, brand name, medicinal ingredient, strength of the medicinal
ingredient, pharmaceutical form, and route of administration. Through the drug
identification number, a drug can readily be tracked or recalled in the event
of an adverse drug reaction in the population.
[93]
The
Appellant disputes the argument respecting Canadian reference products. At
paragraph 47 of her submissions, she argues that whether something can serve as
a reference product is not important for the definition of an innovative drug,
because not all new drugs are innovative drugs. The Appellant goes on to argue,
at paragraph 49, that the determination that thalidomide cannot serve as a
Canadian reference product is separate from the definition of innovative drug.
The Appellant invokes the drug DEXILANT from the case Takeda Canada Inc. v.
The Minister of Health et al., 2011 FC 1444 (Takeda) and
suggests that there is no reason that it could not serve as a reference
product, despite not receiving data protection.
[94]
In
my respectful opinion, this approach is unhelpful in the instant case. While
reference products and innovative drugs are separate definitions within the Regulations,
they are necessarily related. Because there was no available drug to serve as a
reference, the Respondent had to submit an NDS to obtain approval for
thalidomide. Indeed, the Appellant specifically requested it and the Respondent
undertook to produce 180 volumes of data in order to satisfy the request. The
absence of a reference product supports the view that there is no prior
approval, justifies the way in which the Respondent proceeded in this case, and
bolsters the rationale for extending data protection.
C.
Changes
to the Regulatory Framework
[95]
The
manner in which Canada’s regulatory framework has been modified over the past
half-century was largely precipitated by the thalidomide tragedy itself. The
additional criterion of efficacy was introduced in 1963 in a direct response
[SOR/63-386]. Still, the changes in the regulatory process that stemmed from
that watershed moment, and further modifications in the intervening years, do
not negate the approvals that were given under previous legislative schemes, i.e.,
drugs that were previously approved for use in Canada are not invalidated
merely on the changes in regulatory structure or the inclusion of new
conditions precedent. The Respondent has consistently suggested that because
the 1963 amendment to the Regulations adds the consideration of efficacy
before the granting of a regulatory approval, it marks a bright line between
previous schemes and the current one and lessens the value of the approval that
thalidomide received under the 1955 version of the Regulations.
[96]
The
Appellant submits that the judge correctly dismissed the Respondent’s argument
to this effect. The Respondent argues, at paragraph 93 of its memorandum, that
the judge never actually made this determination:
At paragraph 46, he did not make a determination on the point but
did acknowledge it as an argument reinforcing the conclusion that the prior
approvals should not stand in the way of data protection in this case. This
again shows that Justice de Montigny considered a number of factors in applying
a purposive interpretation.
[97]
The
“Related Provisions” addendum to the Food and Drug Regulations provides
the associated SOR/2006-241 in an effort to clarify any questions around the
transition or coming into force of the Regulations:
2. Section C.08.004.1 of the Food and Drug
Regulations, as it read
immediately before the coming into force of these Regulations, applies to a
drug in respect of which a notice of compliance was issued before June 17,
2006.
[98]
In
my view, while the judge agreed that the general rule is that prior approvals
persist irrespective of subsequent legislative changes, he remained alive to
the possibility that thalidomide is worthy of being granted an exception to the
general rule. This is clear when he writes:
[45] The Minister is no doubt correct that, generally speaking,
the ministerial approval to which a legislative or regulatory provision refers,
need not have been made under the current version of that provision. Since
there is nothing in the definition of “innovative drug” to suggest that an
approval made under an earlier version of the Regulations cannot come
within the meaning of “approved”, all that matters should therefore be that the
Minister approved the drug, based on the requirements of the regulatory
framework in effect at the time of the determination.
[46] It is not entirely clear, however, how far this rule should
apply when prior approval has been given pursuant to a scheme that has been
substantively and significantly modified over the years. Be that as it may, I
am of the view that it is, at the very least, an argument reinforcing the
conclusion that prior approvals of KEVADON and TALIMOL should not stand in the
way of data protection for a later approved product. Submissions filed
post-1963 necessarily include new and more extensive data, including data
relating to efficacy, as compared to data filed in a pre-1963 submission. This,
combined with the fact that 1) prior approval for thalidomide was short-lived
and should never have been given at the time, 2) this new drug was effectively
banned until Celgene came up with its NDS for THALOMID, and 3) approval was
granted for Celgene’s product on the basis of completely new studies and data,
militate in favour of a declaration that THALOMID is an “innovative drug” and
eligible for listing on the Register maintained pursuant to the DPR.
[99]
The
judge’s purposive interpretation is helpful, and concurrent in result, but is
not determinative for the disposition of this appeal. The result arrived at by
the judge can be affirmed simply with reference to the meaning of “previously
approved” in the definition of innovative drug, the manner in which thalidomide
has been treated under the SAP, and the jurisprudence of this Court in Teva.
The withdrawal of the previous approval, in my view, is sufficient to allow
THALOMID to receive data protection in accordance with the Regulations.
[100] Finally, it should be
noted that, on appeal, the Appellant repeatedly raised the argument that
allowing the Respondent data protection for THALOMID would set a dangerous
precedent, opening the floodgates to any number of other drug companies that
would try to attain data protection for drugs with an inconsistent Canadian
approval history. This would in turn disadvantage the generic drug industry and
the consumer by allowing innovative drug companies to unfairly extend data
protection over drugs that had been approved under the former regime. It could,
the Appellant argued, have the effect of unduly extending patent rights by
employing data protection as an alternative means of granting a monopoly to an
innovator.
[101] With respect, the fact
situation of thalidomide is highly unusual and unlikely to reoccur. It was the
only therapeutic drug listed in Schedule H (later Schedule F) of the Act and
has a tragic history associated with no other drug. The only other drugs that
received similar legislative treatment were street drugs (e.g., LSD,
DET, DMT) that would never have received regulatory approval. Any precedent set
by this decision is necessarily narrow in scope and does not generate these
slippery slope concerns.
Disposition
[102] For all of these
reasons, I would dismiss the appeal with costs.
“M. Nadon”
Email this Content