Date: 20040923
Docket: T-644-02
Citation: 2004 FC 1302
BETWEEN:
GLAXOSMITHKLINE INC.
Applicant
- and-
ATTORNEY-GENERAL OF CANADA,
THE MINISTER OF HEALTH and APOTEX INC.
Respondents
[1] In this application filed under section 18 of the Federal Courts Act, Glaxosmithkline Inc. ("GSK") seeks to quash a notice of compliance ("NOC") issued on March 21, 2002, by the Minister of Health for Canada (the "Minister") to the respondent Apotex Inc. ("Apotex"). Apotex's NOC is in respect of its inhalation product Apo-Salvent CFC Free containing the medicine salbutamol sulphate.
[2] Briefly put, GSK says the Minister erred in issuing the NOC to Apotex because he failed to require Apotex to serve upon GSK a notice of allegation ("NOA") as required by section 5(1.1) of the Patented Medicines Notice of Compliance Regulations (the "Regulations"). GSK argues Apotex' product contains the same medicine as GSK's Ventolin, which is delivered by the same oral route of administration, in the same strength and in the same inhalation dosage form. It argues a purposive interpretation to section 5(1.1) mandates that Apotex must send a NOA to it to address its formulation patent on the patent list maintained by the Minister under the Regulations.
[3] The Minister and Apotex answer no NOA was required to be served on GSK pursuant to the Regulations.
[4] The Minister argues Apotex's submission for a NOC was a mere administrative submission, a cross-referenced submission arising out of Apotex's licensing agreement with 3M Canada ("3M") to market the medicine salbutamol sulphate administered through inhalation. 3M has a NOC for Airomir which means the Minister has approved it for safety and efficacy and it is covered by a patent which is on the patent list maintained under the Regulations.
[5] Apotex argues subsection 5(1.1) of the Regulations upon which GSK relies to compel a NOA has no application because that section is subject to section 5(1) of the Regulations which applies in the circumstances of this case. Apotex in its cross-referenced submission for a NOC compared its product with 3M's Airomir; it said its product was identical to Airomir.
THE REGULATIONS
[6] The Regulations were first enacted in 1993 in conjunction with amendments to the Patent Act terminating, in accordance with Canada's obligation under the Free Trade Agreement, compulsory licensing.
[7] As originally enacted in 1993, the material part of subsection 5(1.1) of the Regulations read:
| 5. (1) Where a person files or before the coming into force of these Regulations, as filed a submission for a notice of compliance in respect of a drug and wishes to compare that drug with, or make a reference to, a drug that has been marketed in Canada pursuant to a notice of compliance issued to a first person in respect of which a patent list has been submitted, the person shall, in the submission, with respect to each patent on the patent list, (a) state that the 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 pursuant to paragraph 4(2)(b) is false, (ii) the patent has expired, (iii) the patent is not valid, or (iv) no claim for the medicine itself and no claim for the use of the medicine would be infringed by the making, constructing, using or selling by that person of the drug for which the submission for the notice of compliance is filed. [emphasis mine] |
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5. (1) Lorsqu'une personne dépose ou, avant la date d'entrée en vigueur du présent règlement, a déposé une demande d'avis de conformité à l'égard d'une drogue et souhaite comparer cette drogue à une drogue qui a été et commercialisée au Canada aux termes d'un avis de conformité délivré à la première personne et à l'égard duquel une liste de brevets a été soumise ou qu'elle souhaite faire un renvoi à la drogue citée en second lieu, elle doit indiquer sur sa demande, à l'égard de chaque brevet énuméré dans la liste : 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 faite par la première personne aux termes de l'alinéa 4(2)b) est fausse, (ii) le brevet est expiré, (iii) le brevet n'est pas valide, (iv) aucune revendication pour le médicament en soi ni aucune revendication pour l'utilisation du médicament ne seraient contrefaites advenant l'utilisation, la fabrication, la construction ou la vente par elle de la drogue faisant l'objet de la demande d'avis de conformité.
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[8] Section 5 of the Regulations was amended in 1998 and 1999. It is the October 1999 amendment that is relevant to the issues in this case.
[9] Subsection 5(1) was amended by adding the words "for the purpose of demonstrating bioequivalence on the basis of pharmaceutical and, where applicable, bioavailability characteristics" qualifying the comparison or reference to the drug of a first person. In addition sections 5(1.1) and (1.2) were added to the section.
[10] The relevant parts of section 5, as amended in 1999, reads:
| 5. (1) Where a person files or has filed a submission for a notice of compliance in respect of a drug and compares that drug with, or makes reference to, another drug for the purpose of demonstrating bioequivalence on the basis of pharmaceutical and, where applicable, bioavailability characteristics and that other drug has been marketed in Canada pursuant to a notice of compliance issued to a first person and in respect of which a patent list has been submitted, the person shall, in the submission, with respect to each patent on the register in respect of the other drug, (a) state that the 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 pursuant to paragraph 4(2)(b) is false, (ii) the patent has expired, (iii) the patent is not valid, or (iv) no claim for the medicine itself and no claim for the use of the medicine would be infringed by the making, constructing, using or selling by that person of the drug for which the submission for the notice of compliance is filed. (1.1) Subject to subsection (1.2), where subsection (1) does not apply and where a person files or has filed a submission for a notice of compliance in respect of a drug that contains a medicine found in another drug that has been marketed in Canada pursuant to a notice of compliance issued to a first person and in respect of which a patent list has been submitted, the person shall, in the submission, with respect to each patent included on the register in respect of the other drug containing the medicine, where the drug has the same route of administration and a comparable strength and dosage form, (a) . . . (b) . . . (1.2) Where a person referred to in subsection (1.1) has served, in accordance with paragraph (3)(b) or (c), a notice of allegation on a first person in respect of a patent included on the register, the person is not required to serve a notice of allegation in respect of the same submission, the same allegation and the same patent on another first person. [emphasis mine] |
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5. (1) Lorsqu'une personne dépose ou a déposé une demande d'avis de conformité pour une drogue et la compare, ou fait référence, à une autre drogue pour en démontrer la bioéquivalence d'après les caractéristiques pharmaceutiques et, le cas échéant, les caractéristiques en matière de biodisponibilité, cette autre drogue ayant été commercialisée au Canada aux termes d'un avis de conformité délivré à la première personne et à l'égard de laquelle une liste de brevets a été soumise, elle doit inclure dans la demande, à l'égard de chaque brevet inscrit au registre qui se rapporte à cette autre drogue : 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 faite par la première personne aux termes de l'alinéa 4(2)b) est fausse, (ii) le brevet est expiré, (iii) le brevet n'est pas valide, (iv) aucune revendication pour le médicament en soi ni aucune revendication pour l'utilisation du médicament ne seraient contrefaites advenant l'utilisation, la fabrication, la construction ou la vente pare elle de la drogue faisant l'objet de la demande d'avis de conformité. (1.1) Sous réserve du paragraphe (1.2), lorsque le paragraphe (1) ne s'applique pas, la personne qui dépose ou a déposé une demande d'avis de conformité pour une drogue contenant un médicament que l'on trouve dans une autre drogue qui a été commercialisée au Canada par suite de la délivrance d'un avis de conformité à la première personne et à l'égard de laquelle une liste de brevets a été soumise doit inclure dans la demande, à l'égard de chaque brevet inscrit au registre visant cette autre drogue contenant ce médicament, lorsque celle-ci présente la même voie d'administration et une forme posologique et une concentration comparables : a) . . . b) . . . (1.2) Si une personne visée au paragraphe (1.1) a signifié, conformément aux alinéas (3)b) ou c), un avis d'allégation à une première personne à l'égard d'un brevet inscrit au registre, elle n'est tenue de signifier un avis d'allégation à l'égard de la même demande, de la même allégation et du même brevet à aucune autre première personne.
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[11] The Regulatory Impact Analysis Statement accompanying the 1999 Regulations amendment explaining the changes reads in part:
| REGULATORY IMPACT ANALYSIS STATEMENT (This statement is not part of the Regulations)
Description
The Patented Medicines (Notice of Compliance) Regulations (Regulations) were enacted to ensure that second and subsequent entry manufacturers who apply for a notice of compliance (NOC) for their version of a patented drug will not obtain a NOC until the relevant patent expires, or until disputes respecting patent infringement or invalidity are resolved by the courts.
Currently, when a second or subsequent entry manufacturer seeks marketing approval from Health Canada and compares its drug with or makes reference to a patentee's drug already approved by Health Canada, the Regulations require that it address the relevant patents listed against that drug on the patent register maintained by the Minister of Health. In these circumstances, the manufacturer must either agree to await patent expiry for its NOC to issue, or file a Notice of Allegation (NOA), including a detailed statement of the legal and factual basis of the allegation, alleging that the patent is not valid or setting out why its product would not infringe the patents listed against the drug. The manufacturer must serve the NOA on the innovator who then decides whether to contest the allegation of non-infringement or invalidity. This provides the innovator with the opportunity to seek an order before the courts prohibiting the Minister of Health from issuing the NOC and allows the courts to determine the issue of that patent's application to the second or subsequent entry manufacturer's product.
It has recently become apparent that a second or subsequent entry manufacturer may seek to obtain a NOC without triggering the application of the Regulations, even though a patent list for the innovator's drug has been filed with the Minister of Health.
The present amendments are intended to clarify the law and reaffirm the application of the Regulations. This is accomplished by maintaining and clarifying the current subsection 5(1) while introducing a new subsection 5(1.1). The new subsection 5(1.1) is based on the proposed regulatory text published in the Canada Gazette, Part I, on July 31, 1999. As with the prepublished text, subsection 5(1.1) will address the cases where a second or subsequent entry manufacturer may seek to obtain a NOC without triggering the application of the Regulations under subsection 5(1).
Subsection 5(1), as is currently the case, will apply where the second or subsequent entry manufacturer makes a comparison with, or a reference to, another drug that has been marketed in Canada and for which a patent list has been submitted to the Minister of Health. The words "wishes to" have been deleted to reflect the factual analysis that is done under these Regulations. he words "compare with, or make reference to" has been modified by the phrase: "for the purposes of demonstrating bioequivalence on the basis of pharmaceutical and, where applicable, bioavailability characteristics" to clarify the intent that subsection 5(1) applies to a second or subsequent entry manufacturer who relies on a comparison with, or reference to a previously approved innovator drug in order to obtain a NOC for its version of the innovator drug, which had, itself, been proven safe and efficacious through extensive clinical testing.
Subsection 5(1.1) will apply where a second or subsequent entry manufacturer does not make such an explicit comparison or reference, but, in fact seeks a NOC for another version of a drug that has previously been marketed in Canada by a first person who has filed a patent list with the Minister of Health. Specifically, subsection 5(1.1) will be triggered when the second or subsequent entry manufacturer's drug contains the same medicine, employs the same route of administration and has a comparable strength and dosage form as the drug listed on the patent register. In this context, "comparable" is intended to operate as it does within the context of the drug approval process. In the phrase "drug that contains a medicine found in another drug", "medicine" is intended to refer to both the substance that is the subject of the NOC issued for the innovator's drug and the substance that is the subject of a second or subsequent entry manufacturer's drug submission for a NOC. [emphasis mine]
Subsection 5(1.2) addresses situations where, in respect of a specific submission and a specific allegation, subsection 5(1.1) would otherwise require the service of a NOA relating to a particular patent on more than one person |
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RÉSUMÉ DE L'ÉTUDE D'IMPACT DE LA RÉGLEMENTATION (Ce résumé ne fait pas partie du règlement.)
Description
Le Règlement sur les médicaments brevetés (avis de confirmité) (le règlement) a été pris pour que les deuxièmes fabricants, et les fabricants subséquents, qui demandent un avis de conformité pour leur version d'un médicament breveté, ne l'obtiennent pas avant l'expiration du brevet pertinent ou avant que les différends liés à une contrefaçon ou à une invalidité du brevet n'aient été résolus par les tribunaux.
Actuellement, dans le cas où un deuxième fabricant, ou un fabricant subséquent, cherche à faire approuver la commercialisation de son produit par Santé Canada et compare son produit à un médicament breveté du titulaire déjà approuvé par Santé Canada, ou y fait renvoi, le règlement exige que soient pris en compte les brevets pertinents protégeant ce médicament, qui sont répertoriés sur le registre des brevets tenu parle ministre de la Santé. Dans ces circonstances, le fabricant doit accepter d'attendre l'expiration du brevet pour que son avis de conformité soit émis, ou bien déposer un avis d'allégation contenant un énoncé détaillé du fondement juridique et factuel de l'allégation, alléguant que le brevet n'est pas valide ou décrivant pourquoi son produit ne porterait pasatteinte aux brevets répertoriés à l'égard de ce médicament. Le fabricant doit présenter l'avis d'allégation à l'égard de l'innovateur qui décide alors de contester ou non l'allégation de non-contrefaçon ou d'invalidité. Ainsi, l'innovateur a l'occasion de solliciter devant les tribunaux un décret interdisant au ministre de la Santé d'émettre l'avis de conformité, et permet aux tribunaux de trancher la question de l'application de ce brevet au produit du deuxième fabricant, ou du fabricant subséquent.
On a récemment constaté qu'un deuxième fabricant, ou un fabricant subséquent, pouvait chercher à obtenir un avis de conformité sans déclencher l'application du règlement, même si une liste de brevets a été déposée auprès du ministre de la Santé pour le médicament de l'innovateur.
Les présentes modifications visent à éclaircir la loi et à réitérer l'application du règlement. Ainsi, le paragraphe 5(1) actuel est maintenu et éclairci et un nouveau paragraphe 5(1.1) est introduit. Le nouveau paragraphe 5(1.1) est basé sur le texte réglementaire proposé, publié dans la Gazette du Canada Partie I le 31 juillet 1999. Comme dans le cas du texte de la publication préalable, le paragraphe 5(1.1) s'appliquera au cas où un deuxième fabricant, ou un fabricant subséquent peut chercher à obtenir un avis de conformité sans déclencher l'application du règlement en vertu du paragraphe 5(1.1).
Le paragraphe 5(1) s'appliquera, comme c'est le cas actuellement, lorsque le deuxième fabricant, ou le fabricant subséquent, compare son produit, ou fait renvoi, à un autre médicament qui a été commercialisé au Canada et pour lequel une liste de brevets a été présentée au ministre de la Santé. On a éliminé le verbe « souhaiter » pour rester fidèle à l'analyse factuelle effectuée en vertu du règlement. On a ajouté aux mots « comparer » et « faire renvoi » l'expression suivante : « pour en démontrer la bioéquivalence d'après les caractéristiques pharmaceutiques et, le cas échéant, les caractéristiques en matière de biodisponibilité » . Cet ajout éclaircit l'intention selon laquelle le paragraphe 5(1) s'applique à un deuxième fabricant, ou à un fabricant subséquent, qui se base sur une comparaison ou un renvoi à un médicament, antérieurement approuvé, d'un innovateur pour obtenir un avis de conformité pour sa version du médicament de l'innovateur, médicament qui s'est révélé sécuritaire et efficace après des essais cliniques approfondis.
Le paragraphe 5(1.1) s'appliquera dans le cas où un deuxième fabricant, ou un fabricant subséquent, ne fait pas ainsi une comparaison ou un renvoi explicites, mais cherche en fait à obtenir un avis de conformité pour une autre version d'un médicament qui a antérieurement été commercialisé au Canada par une première personne ayant déposé une liste de brevets auprès du ministre de la Santé. Plus particulièrement, le paragraphe 5(1.1) s'appliquera dans le cas où le médicament du deuxième fabricant, ou un fabricant subséquent, contient le même médicament, emploie la même voie d'administration et se présente en concentration et forme posologique comparables à celles du médicament figurant sur le registre des brevets. Dans ce contexte, le mot « comparable » doit être interprété comme dans le contexte du processus d'approbation des médicaments. Dans l'expression « une drogue contenant un médicament que l'on trouve dans une autre drogue » , le mot « médicament » s'applique à la fois à la substance qui fait l'objet de l'avis de conformité émis pourle médicament de l'innovateur et à la substance qui fait l'objet d'une demande d'avis de conformité de la part d'un deuxième fabricant, ou d'un fabricant subséquent.
Le paragraphe 5(1.2) vise les situations où, dans le cas d'une demande spécifique et d'une allégation spécifique, le paragraphe 5(1.1) exigerait autrement la présentation d'un avis d'allégation pour un brevet particulier, à l'égard de plus d'une personne. |
FACTS
[12] The material facts, which are not in dispute, may be summarized as follows.
[13] 3M obtained the following:
(i) on August 20, 1997, a NOC for its drug Airomir, a product which contains the medicinal ingredient salbutamol sulphate in 100 mcg oral inhalation preparation after filing a new drug submission ("NDS") on September 4, 1996;
(ii) on November 7, 2000, the grant of Canadian Patent 2,004,598 (the '598 Patent) in respect of the formulation of the medicine salbutamol sulphate as an aerosol for inhalation; and
(iii) on January 17, 2001, the listing of Airomir on the Patent Register maintained pursuant to the Regulations.
[14] GSK was born of a merger between Glaxo Welcome Inc. ("GWI") and Smithkline Beecham Inc. The following had occurred prior to the merger:
(i) on January 19, 2000, GWI obtained a NOC to market its drug Ventolin HFA, a product which contains the medicinal ingredient salbutamol sulphate in 100 mcg oral inhalation preparation after filing a NDS in July 2, 1998;
(ii) on June 13, 2000 Canadian Patent 2,125,667 (the '667 Patent) was issued to Glaxo Group Limited; it relates to aerosol formulations for administration of medicaments by inhalation;
(iii) on June 21, 2000 GWI obtained a listing on the Patent Register maintained pursuant to the Regulations; and
(iv) GSK has an exclusive license under the '667 Patent.
[15] After GSK was formed, it filed an administrative new drug submission on July 26, 2001, to reflect the change in the manufacturer's name for VENTOLIN HFA from GWI to GSK. This administrative submission cross-referenced the original GWI June 1998 NDS and GSK subsequently received a NOC for this change on August 27, 2001. I take it from the affidavit of Anne Elizabeth Bowes, who is employed by Health Canada in the Office of Patented Medicines and Liaison of the Therapeutic Products Directorate ("TPD") as Manager-Patents and Liaison, that with respect to GSK's administrative new drug submission, it did not serve a NOA on 3M in respect of 3M's '598 Patent despite the fact the two products contain the same medicinal ingredient.
[16] Sometime in early 2002, 3M and Apotex entered into a licencing agreement. Ms. Bowes advises at paragraph 21 of her affidavit that on March 12, 2002, the TPD was advised of the licencing agreement and the understanding of the TPD is that the licencing agreement essentially permits Apotex to sell 3M Canada's product under Apotex's own name.
[17] By way of a letter dated February 20, 2002, addressed to the Acting Director, Bureau of Pharmaceutical Assessment at TPD, Apotex Inc. applied "to market Apo-Salvent CFC Free Inhalation Aerosol, a product cross licenced to AiromirÔ, marketed in Canada by 3M" (application record, volume 1, page 11). In that letter, John Hems, Director, Regulatory Affairs at Apotex also wrote:
The following are included:
1. Completed Drug Submission Application Forms (HPB Form 3011), and Letter of Access from 3M. . . .
2. Product monographs for Apo-Salvent CFC Free and AiromirÔ.
3. Draft labels and patient information inserts for Apo-Salvent CFC Free.
4. . . .
[18] Accompanying Apotex's material was a letter dated November 27, 2001, addressed by 3M to the TPD as "... authorization for Apotex Inc. ... to make reference to our New Drug Submission for AiromirÔ Inhalation Aerosol ... for which Notices of Compliance were received on November 10, 2000, October 25, 2000 and August 20, 1997 respectively" [emphasis mine].
[19] The printed form which Mr. Hems enclosed is headed "Changes in Manufacturer's Name and/or Product Name Administrative Changes - Certification Form". Under "Nature of Change" the item "Change in Manufacturer's Name and Product Name" was checked off. Under the item "Reason for Change" the words "Licensing agreement (2 firms to market the same product). New DIN will be issued to the second firm" was checked off.
[20] Mr. Hems certified at the bottom of the form that:
...all aspects of the submission pertaining to: Apo-Salvent CFC Free submitted by: Apotex Incorporated are identical to Airomir... submission(s) except for a change in the manufacturer/sponsor's name and/or product name and that the product will be manufactured in the same location with identical specifications and procedures" (applicant's application record, volume 1, page 13). [emphasis mine]
[21] Anne Elizabeth Bowes, in her affidavit, confirms that in March 2002, Apotex filed an administrative new drug submission to obtain a NOC "to accurately reflect the manufacturer and product name resulting from the licensing agreement" and that the administrative new drug submission "required a proof of consent between Apotex and 3M Canada Company for Apotex to sell 3M's drug".
[22] In her affidavit, she had previously contrasted the content requirements in the Food and Drug Regulations for new drug submissions ("NDS") and those in respect of abbreviated new drug submissions ("ANDS"). She deposed that for an ANDS, unlike a NDS, the safety and efficacy of a new drug is not based on detailed reports and clinical trials but requires the use of a Canadian reference product for which the safety and efficacy has already been demonstrated through a previously accepted NDS.
[23] She states the TPD's drug submission requirements, in the event of licensing agreements and corporate restructuring transactions (such as mergers, buyouts and other commercial transactions) concluded between drug manufacturers, is set out in a policy document entitled "Changes in the Manufacturers' Name and/or Product Name" (the "policy").
[24] Anne Elizabeth Bowes deposes when a manufacturer of a currently marketed drug licences another manufacturer to sell the identical drug in Canada under a different name, the licencee is required to file an administrative new drug submission and such submission must be "cross-referenced" i.e. that it be a certification that all aspects of the drug product to be approved are identical to that of the previously approved product (the cross-referenced product) except for the manufacturer's name and/or product name.
[25] She adds a cross-referenced submission includes an explicit authorization from the manufacturer of the previously approved product in which its consent to the cross-reference is provided. She also confirms the only other essential element to a cross-referenced submission is the filing of a copy of the proposed product monograph ("PM") for the product to be approved.
[26] A detailed examination of Apotex' product monograph is not necessary to resolve this case except to mention the following in the PM:
(1) Under the heading "Adverse Reactions", the PM states at page 9 (applicant's record, volume 1, page 28):
A 12-week double-blind study compared HFA-134a salbutamol sulphate, Ventolin® salbutamol inhaler (US source), and HFA-134a placebo in 565 asthmatic patients.
The PM has a table listing the incidents of all adverse events for the three named products.
(2) There is no reference to Ventolin® under the chapter "Information for the Patient" and the heading "What you should know about APO-SALVENT CFC FREE Inhalation Aerosol : Please read this leaflet carefully before you start to take your medicine. For more information or advice, ask your doctor or your pharmacist" (application record, volume 1, page 36);
(3) Under the heading "Pharmacology", in terms of animal pharmacology, the reference to product is the general class of halocarbons including the CFCs as well as HFA-134a;
(4) Under the heading "APO-SALVENT CFC FREE INHALATION AEROSOL" and the sub-heading "Human Pharmacokinetics" there is a reference (applicant's record, volume page 45) to a number of clinical trials or studies. In five of these trials or studies, Ventolin® (US source), is one of the referenced products. HFA-134a was also a referenced product and sometimes Proventil® (US source) was also mentioned.
(5) In a large three-month open label observational post-marketing surveillance study carried out in the U.K., the safety of HFA-134a was compared with CFC-salbutamol inhalers in primary care setting. There was no mention of Ventolin®.
[27] As would be expected, the draft label on the inhaler and the carton label only pertain to Apotex's product.
[28] The record (application record, volume 1, page 66), contains the draft package insert for Apotex's Apo-Salvent CFC Free Aerosol. That insert makes no reference to Ventolin®.
[29] I should mention that in the product monograph the reference to HFA-134a appears in the following sentence: "APO-SALVENT CFC FREE Inhalation Aerosol contains a new propellant, HFA-134a, and does not contain chlorofluorocarbons (CFCs)" (application record, volume 1, page 171).
[30] In addition to the Rule 317 material, GSK filed the affidavit evidence of Janet Wagner who is Manager, Therapy Area, in the Regulatory Affairs Department for GSK and that of Janet Holden who is a consultant in regulatory and quality affairs for biologics, pharmaceuticals and medical devices. Neither was cross-examined.
[31] Apart from reciting the facts previously referred in these reasons, Janet Wagner stated at applicant's record, volume 1, page 79, that Ventolin® HFA does not contain CFC which is a commonly used propellant for various pressurized products. She states CFCs are believed to be harmful to the ozone layer and "therefore, GSK developed VENTOLIN HFA salbutamol sulphate which uses an alternative propellant called hydrofluoroalkane ("HFA")".
[32] The material part of Janet Holden's affidavit (applicant's record, volume 1, page 116) is in the following two paragraphs:
8. According to the Product Monograph of Apo-Salvent CFC Free, Apotex' drug [Apo-Salvent CFC Free] contains the same medicine as GSK's drug, namely salbutamol sulphate. Furthermore, Apotex' drug is delivered in the same dosage form (inhalation preparation), in the same strength (100 mcg), and by the same route of administration (oral) as GSK's salbutamol sulphate product. Attached as Exhibit D to my Affidavit is a copy of Apo-Salvent CFC Free's Product Monograph.
9. Additionally, the Clinical Studies section of Apo-Salvent CFC Free's Product Monograph makes comparison with GSK's product, namely VENTOLIN. Indeed, on page 27 of the Product Monograph, it is stated that Apo-Salvent CFC Free "produced outcomes that were clinically comparable to the Ventolin".
[33] The sentence at page 27 of Apotex's PM reads (applicant's record, volume 1, page 182):
Serial FEV, measurements demonstrated that two inhalations of HFA-134a salbutamol sulphate Inhalation Aerosol produced significantly greater improvement in pulmonary function than placebo and produced outcomes which were clinically comparable to the Ventolin®. [there is no mention of Apo-Salvent]
[34] Bernard Sherman, the Chair and Executive Officer of Apotex, filed an affidavit in this judicial review proceeding. He was not cross-examined.
[35] The purpose of Dr. Sherman's affidavit was to describe the regulatory approval process in Canada for pharmaceutical products and to relate that process with how Apotex received its NOC for Apo-Salvent.
[36] He described the methods whereby a pharmaceutical manufacturer in Canada receives a NOC which is necessary in order to advertise for sale and sell a new drug in Canada.
[37] The first method, Dr. Sherman tells us, is described in section C.08.002 of the Food and Drug Regulations which "requires a manufacturer to submit a New Drug Submission ("NDS") containing voluminous information, including detailed clinical studies, showing that the drug has been tested and has been shown to be safe and effective for its intended use. This method is typically employed by innovator or patentee manufacturers" (applicant's record, volume 2, page 193-94).
[38] According to Dr. Sherman, the second method is described as an ANDS in section C.08.002.1 of the Food and Drug Regulations, whereby "a manufacturer submits considerably less detailed information, including evidence from comparative studies, to show that testing of the drug product establishes that it is therapeutically equivalent to another drug, known as a Canadian reference product, whose safety and effectiveness has previously been established. This second method is typically employed by generic manufacturers" (applicant's record, volume 2, page 194).
[39] The next three paragraphs of Dr. Sherman's affidavit read (applicant's record, volume 2, page 194):
8. The second method, which requires a pharmaceutical manufacturer to submit an Abbreviated New Drug Submission ("ANDS"), therefore establishes safety and effectiveness by comparison or reference to another drug. The Patented Medicines (Notice of Compliance) Regulations ("NOC Regulations") require that, where such a comparison is made, and the patentee manufacturer whose drug product is the subject of the comparison has listed patents on the Patent Register, the generic manufacturer must serve a Notice of Allegation pursuant to the NOC Regulations.
9. A variant of the second method does not require the direct submission of comparative testing results. This type of drug submission is known informally as a "cross-referenced" drug submission.
10. In this type of submission, a manufacturer relies explicitly upon the information and materials submitted in an NDS filed by another manufacturer of that same drug for which a NOC has been previously issued. For such a submission, no independent data is submitted, as the first manufacturer authorizes the second manufacturer to rely upon the data which it has already submitted. Essentially, a cross-referenced submission consists of a letter from the submitting manufacturer indicating reliance on the material and information submitted by the first manufacturer, a letter from the first manufacturer authorizing such reliance, draft product labels, and a Product Monograph. [emphasis mine]
[40] Dr. Sherman then describes Apotex's approval for Apo-Salvent CFC Free. He states Apotex markets the drug Apo-Salvent CFC Free containing the medicine salbutamol sulphate in the form of a metered dose aerosol, 100 mcg per actuation strength for which Apotex obtained a NOC on March 21, 2002 as the result of a cross-referenced submission.
[41] Dr. Sherman, at paragraph 12, states the cross-referenced submission was made on the basis of a licensing agreement between Apotex and 3M whereby Apotex and 3M agreed that Apotex would market a product identical in all respects to 3M's salbutamol sulphate product save for the fact that Apotex's product would be sold under different labelling which gave the product a different name and identified Apotex as the manufacturer.
[42] From paragraphs 13 through 16, Dr. Sherman recites facts which have previously been identified in these reasons.
[43] The balance of Dr. Sherman's affidavit speaks to the issue of no comparison to GSK's product and the applicability of subsection 5(1.1) of the Regulations.
[44] At paragraph 17, he states GSK commenced this proceeding "apparently based upon a speculation that a comparison had been made to GSK's salbutamol sulphate product, Ventolin, by either Apotex or 3M and that, accordingly, Apotex ought to have served a Notice of Allegation upon GSK prior to receiving its NOC for Apo-Salvent CFC Free". He states neither Apotex nor 3M made any such comparison.
[45] Paragraphs 18 and 19 of Dr. Sherman's affidavit read:
18. It is clear that 3M could not have made any comparison to GSK's Ventolin product in its submission for a NOC for Airomir. 3M's NOC for Airomir issued as a result of an NDS based upon full clinical data. Moreover, 3M received its NOC for Airomir nearly two and half years before GSK received its first NOC for Ventolin. As indicated above, 3M's NOC for Airomir issued on August 20, 1997, while GSK's first NOC for Ventolin issued January 19, 2000. A copy of GSK's NOC for Ventolin dated January 19, 2000 is attached hereto as Exhibit "G".
19. Since Apotex "compared" its product to 3M's Airomir (and in fact the two products are identical, as aforesaid), Apotex too did not make any comparison of its Apo-Salvent CFC Free to GSK's Ventolin product. While Apotex' product Product Monograph discusses the fact that Apotex' product is clinically comparable to GSK's product, this does not constitute a "comparison" for the purposes of subsection 5(1) of the NOC Regulations, which is directed to a comparison for the purposes of securing a NOC. Rather, the comment is directed to the performance of the two products in the marketplace. Apotex' approval for its product was not and could not have been based upon this type of comment, but rather, was based upon the cross-reference to 3M's product.
[46] In terms of the applicability of subsection 5(1.1) of the NOC Regulations, Dr. Sherman states:
20. Because Apotex' NOC issued on the basis of a cross-reference to 3M's product, Apotex clearly referenced and relied upon 3M's product and the data submitted by 3M in respect of that product. Accordingly, subsection 5(1) of the NOC Regulations applied to Apotex in respect of Apotex' comparison and referring to 3M's Airomir. The requirements of that subsection were satisfied by virtue of the consent and licence provided by 3M permitting Apotex to market its Apo-Salvent CFC Free product. [Emphasis mine]
21. Subsection 5(1.1) of the NOC Regulations explicitly states that the subsection applies only where subsection 5(1) does not apply. In the circumstances, subsection 5(1) clearly does apply on the basis of Apotex' reference to 3M's product. Hence, subsection 5(1.1) does not apply so as to require Apotex to serve a Notice of Allegation upon GSK. [emphasis mine]
ANALYSIS
[47] The issue in this case is whether the Minister properly interpreted the Regulations when he determined section 5 had no application to the circumstances of this case and, in particular, he could issue a NOC to Apotex without Apotex having to serve a NOA on GSK.
[48] The standard of review is whether the Minister was correct in interpreting the Regulations (see, Merck & Co. et al. v. Canada (Attorney General) et al.) (1999), 176 F.T.R. 21, and Bristol-Myers Squibb Co. v. Canada (Attorney General) [Biolyse Pharma], [2002] F.C.T. 1205).
[49] In matters of statutory interpretation, the Supreme Court of Canada established the approach to be taken in its decision (Re) Rizzo & Rizzo Shoes Ltd., [1998] 1 S.C.R. 27, at paragraphs 21, 22 and 23, where Justice Iacobucci wrote the following:
¶ 21 Although much has been written about the interpretation of legislation (see, e.g., Ruth Sullivan, Statutory Interpretation (1997); Ruth Sullivan, Driedger on the Construction of Statutes (3rd ed. 1994) (hereinafter "Construction of Statutes"); Pierre-André Côté, The Interpretation of Legislation in Canada (2nd ed. 1991)), Elmer Driedger in Construction of Statutes (2nd ed. 1983) best encapsulates the approach upon which I prefer to rely. He recognizes that statutory interpretation cannot be founded on the wording of the legislation alone. At p. 87 he states:
Today there is only one principle or approach, namely, the words of an Act are to 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.
Recent cases which have cited the above passage with approval include: R. v. Hydro-Québec, [1997] 1 S.C.R. 213; Royal Bank of Canada v. Sparrow Electric Corp., [1997] 1 S.C.R. 411; Verdun v. Toronto-Dominion Bank, [1996] 3 S.C.R. 550; Friesen v. Canada, [1995] 3 S.C.R. 103.
¶ 22 I also rely upon s. 10 of the Interpretation Act, R.S.O. 1980, c. 219, which provides that every Act "shall be deemed to be remedial" and directs that every Act shall "receive such fair, large and liberal construction and interpretation as will best ensure the attainment of the object of the Act according to its true intent, meaning and spirit".
¶ 23 Although the Court of Appeal looked to the plain meaning of the specific provisions in question in the present case, with respect, I believe that the court did not pay sufficient attention to the scheme of the ESA, its object or the intention of the legislature; nor was the context of the words in issue appropriately recognized. I now turn to a discussion of these issues.
[50] It has been consistently held by this Court and by the Federal Court of Appeal that the purpose of the Regulations is to protect the research and development initiatives of innovator pharmaceutical companies (see, Nu-Pharm Inc. v. Canada (Attorney General) (1997), 73 C.P.R. (3d) 510 (T.D.) upheld by the Federal Court of Appeal (1998), 80 C.P.R. (3d) 74.
[51] Moreover, I am prepared to take a purposive approach to the interpretation of the Regulations and, in particular, to subsection 5(1.1) (see, Bristol-Myers Squibb Co., supra, upheld by the Federal Court of Appeal cited Biolyse Pharma Corp. v. Bristol Myers Squibb Co., [2003] F.C.A. 180.
[52] Counsel for GSK points to Nu-Pharm Inc. v. Canada (Attorney General), supra, as an instance which the Federal Court and the Federal Court of Appeal applied a purposive interpretation to former section 5 of the Regulations to thwart Nu-Pharm's efforts to do an end run of the Regulations.
[53] He states subsection 5(1.1) was introduced to ensure that in every situation where a second person is seeking marketing approval of a product where there is a patent list, a NOA has to be sent to a first person who had submitted patent lists to the Minister even in the circumstances where the second entry manufacturer did not rely upon the innovator's (the first person) product to demonstrate bioequivalence of its product and, in particular, where the generic's submission is a cross-reference submission to another party's submission.
[54] Briefly put, I uphold both the Minister's argument and that of Apotex.
[55] I cannot accept GSK's interpretation. To accept it, on the facts of this case, would have the Court ignore the opening words in subsection 5(1.1) "where subsection 5(1) does not apply" which qualifies the section's operation. I cannot re-write the section. Plainly put, subsection 5(1.1) does not operate if subsection 5(1) does. Furthermore, Apotex is not piggy-backing on GSK's NOC submission.
[56] Furthermore, on the facts of this case, Apotex is not doing an end run on the Regulations. Its NOC is based on the NOC which 3M, a patent holder whose product is on the patent list received from the Minister. The Minister's policy applies.
(i) The Minister's position
[57] As stated, the Minister's position is that the NOC Apotex received was the result of a cross-referenced "Administrative New Drug Submission" filed in accordance with the Minister's policy for changes in manufacturer's name and/or product name.
[58] Counsel for GSK did not challenge the Minister's policy as being contrary to the provisions of the Food and Drug Regulations. If he had, he would not have succeeded.
[59] I am of the opinion the Minister's policy is solidly anchored in paragraph C.08.003 of the Food and Drug Regulations which provides in subsection (1) that notwithstanding section C.08.002, "no person shall sell a new drug in respect of which a notice of compliance has been issued to the manufacturer of that new drug and has not been suspended ... if any of the matters specified in subsection (2) are significantly different from the information or material contained in the new drug submission or abbreviated new drug submission, unless (a) the manufacturer of the new drug has filed with the Minister (i) a supplement that a new drug submission or (ii) a supplement to that abbreviated new drug submission, (b) the Minister has issued a notice of compliance to the manufacturer of the new drug in respect of the supplement" [emphasis mine].
[60] The matters prescribed in subsection (2) of section C.08.003 are as follows:
| (2) The matters specified for the purposes of subsection (1), in relation to the new drug, are the following: (a) the description of the new drug; (b) the brand name of the new drug or the identifying name or code proposed for the new drug;(c) the specifications of the ingredients of the new drug; (d) the plant and equipment used in manufacturing, preparation and packaging the new drug; (e) the method of manufacture and the controls used in manufacturing, preparation and packaging the new drug; (f) the tests applied to control the potency, purity, stability and safety of the new drug; (g) the labels used in connection with the new drug; (h) the representations made with regard to the new drug respecting (i) the recommended route of administration of the new drug, (ii) the dosage of the new drug, (iii) the claims made for the new drug, (iv) the contra-indications and side effects of the new drug, and (v) the withdrawal period of the new drug; and (i) the dosage form in which it is proposed that the new drug be sold. |
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(2) Pour l'application du paragraphe (1), les éléments ayant trait à la drogue nouvelle sont les suivants : a) sa description; b) sa marque nominative ou le nom ou code sous lequel il est proposé de l'identifier; c) les spécifications de ses ingrédients; d) les installations et l'équipement à utiliser pour sa fabrication, sa préparation et son emballage; e) la méthode de fabrication et les mécanismes de contrôle à appliquer pour sa fabrication, sa préparation et son emballage; f) les analyses effectuées pour contrôler son activité, sa pureté, sa stabilité et son innocuité; g) les étiquettes à utiliser pour la drogue nouvelle; h) les observations faites relativement : (i) à la voie d'administration recommandée pour la drogue nouvelle, (ii) à sa posologie, (iii) aux propriétés qui lui sont attribuées, (iv) à ses contre-indications et à ses effets secondaires, (v) au délai d'attente applicable à celle-ci; i) sa forme posologique proposée pour la vente.
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[61] Moreover, subsection (3) to that same section provides a supplement to a NDS or a ANDS, with respect to the matters that are significantly different from those contained in the submission, shall contain sufficient information and material to enable the Minister to assess the safety and effectiveness of the new drug in relation to those matters.
[62] As I see it, the Minister's policy outlines those matters which the Minister considers are not significantly different from the information or material contained in a previous NDS or ANDS and as a result such changes do not require a supplement and do not require another assessment of the safety and effectiveness of the drug in relation to those changes.
[63] As has been observed by many judges of this Court and the Federal Court of Appeal, the Regulations are linked to the Food and Drug Regulations through the definition in the Regulations of the term "notice of compliance" in section 2 of the Regulations. That term is defined to mean "a notice issued under section C.08.004 of the Food and Drug Regulations".
[64] Because of that linkage, I find that an administrative new drug submission filed pursuant to the policy is not a submission for a notice of compliance within the meaning of those words as found in subsections 5(1) or (1.1) of the Regulations.
[65] I base my view on the interpretation given by Justice McGillis in Apotex Inc. v. Canada (Minister of Health) (1999), 87 C.P.R. (3d) 271 to the words "submission for a notice of compliance" as found in section 4 of the Regulations.
[66] Justice McGillis observed a review of Division 8 of the Food and Drug Act indicates its purpose is to enable the Minister to assess the safety and effectiveness of a new drug in order to ensure the protection of Canadians and, in order to achieve that objective, those Regulations prescribe various means by which a manufacturer must provide the requisite information to the Minister to enable him to discharge his legislatively mandated duty. She noted that, in particular, the Food and Drug Regulations contemplate the flow of information from the manufacturer to the Minister by various mechanisms including a new drug submission, an abbreviated new drug submission, a supplement to a new drug submission and a supplement to an abbreviated new drug submission.
[67] She noted section C.08.003 addressed the situation where a notice of compliance is issued to a manufacturer but where certain specified matters in relation to a new drug differ "significantly" from the information originally provided in the new drug submission or in the abbreviated new drug submission. In that case, the manufacturer must file a supplement to either of those submissions.
[68] She observed subsection C.08.004(1) gave the Minister the power to issue a Notice of Compliance where a NDS, an ANDS or a supplement to either one of those met the requirements of the corresponding section of the Food and Drug Regulations.
[69] Looking at the Regulations, Justice McGillis was of the view, as I am, that the definition of "notice of compliance" in section 2 of those Regulations "incorporates by reference section C.08.004 of the Food and Drug Regulations... which accords the Minister the power to issue a notice of compliance in response to a new drug submission, an abbreviated new drug submission or a supplement to either submission.
[70] She concluded as follows at paragraph 36 of her reasons:
[36] In considering the expression "a submission for a notice of compliance" in sections 4 and 5 of the Patented Medicines (Notice of Compliance) Regulations, the mechanisms which trigger the issuance of a notice of compliance are, by virtue of the definition of "notice of compliance" in section 2, those specified in section C.08.004 of the Food and Drug Regulations, namely a new drug submission, an abbreviated new drug submission and a supplement to a new drug submission or to an abbreviated new drug submission. In the circumstances, the expression "submission for a notice of compliance", as used in sections 4 and 5 of the Patented Medicines (Notice of Compliance) Regulations means a new drug submission, an abbreviated new drug submission and a supplement to a new drug submission or to an abbreviated new drug submission.
[71] The Federal Court of Appeal dismissed Apotex's appeal from Justice McGillis' decision. (See, [2001] F.C.J. 143).
[72] I conclude on this point by ruling the Minister was correct in issuing a NOC to Apotex, in the circumstances of this case, without requiring Apotex to serve a NOA on GSK. Apotex' submission was in accordance with the Minister's policy for minor changes in materials previously filed in support of a NOC which had issued to 3M. That submission fell outside the Regulations.
(ii) Apotex' interpretation
[73] Alternatively, should I be wrong and the Regulations apply to an administrative new drug submission of the type in play here, I accept Apotex' submission the provisions of section 5(1.1) do not apply because section 5(1) applies since Apotex compared its drug with or made reference to 3M's Airomir for the purpose of demonstrating bioequivalency on the basis of pharmaceutical characteristics.
[74] Such reference or comparison flowed from the nature of a cross-referenced new drug submission. Justice Richard, then of the Trial Division, came to this conclusion in Nu-Pharm, supra, a case where Nu-Pharm, rather than referencing the first person innovator, referenced the product of a generic who had, in the ANDS for its NOC chosen for comparative purposes the product of the innovator.
[75] Justice Richard found there was a comparison from Nu-Pharm's cross-referenced submission through the generic's ANDS to the drug appearing on the patent list submitted by the innovator. He concluded at page 517:
Accordingly, Nu-Pharm's submissions compare its drugs with, or make reference to a drug that has been marketed in Canada pursuant to a Notice of Compliance issued to a first person in respect of which a patent list has been submitted.
[76] As noted, an appeal from Justice Richard's decision was dismissed by the Federal Court of Appeal. Justice MacDonald stated Nu-Pharm's new drug submissions were cross-referenced and relied explicitly on the information and material submitted previously by another generic drug manufacturer which, in turn, had filed an abbreviated drug submission incorporating the testing of the original patentee of the drug. He held Nu-Pharm could not piggy-back its claim on the generic drug company who relied on the tests of the patentee and then state it need not comply with the Act because the generic company did not issue a patent list. He concluded "the fact remains that although it is one step removed, Nu-Pharm is relying on the tests and other work done by the patentees, whom the Generic Company relied on". He ruled, in essence, Nu-Pharm was comparing its drug with that of the original patentee because the generic company had compared its drug to that patentee.
[77] Counsel for GSK relied heavily upon Justice Blanchard's decision in the Bristol-Myers case, supra, [Biolyse]. The case which Justice Blanchard had before him was completely different than the one before me. In Biolyse, supra, Justice Blanchard ruled section 5(1) did not apply because Biolyse did not compare its drug with that of BMS for the purpose of demonstrating bioequivalence. Section 5(1) having no application, he then went on to consider whether subsection 5(1.1) applied and found it did. The situation before me is the converse. I find section 5(1) applies because Apotex compared its drug to that of 3M and therefore section 5(1.1) cannot apply.
[78] For all of these reasons, this judicial review application is dismissed with costs.
"François Lemieux"
J U D G E
OTTAWA, ONTARIO
SEPTEMBER 23, 2004
FEDERAL COURT
NAMES OF COUNSEL AND SOLICITORS OF RECORD
DOCKET: T-644-02
STYLE OF CAUSE:
GLAXOSMITHKLINE INC.
- and-
ATTORNEY-GENERAL OF CANADA,
THE MINISTER OF HEALTH and APOTEX INC.
PLACE OF HEARING: Ottawa, Ontario
DATE OF HEARING: May 31, 2004
REASONS FOR ORDER : Lemieux J.
DATED: September 23, 2004
APPEARANCES:
James E. Mills for APPLICANT
Kristi Rowe
Frederick Woyiwada for RESPONDENT The Minister of Health
Andrew Brodkin for RESPONDENT Apotex Inc.
SOLICITORS OF RECORD:
Gowling Lafleur Henderson LLP for APPLICANT
2600 - 160 Elgin Street
Ottawa, Ontario K1P 1C3
(613) 786-8669/786-8838 fax: (613) 563-9869
Department of Justice for RESPONDENT The Minister of Health
234 Wellington Street
Bank of Canada Building - East Tower
Ottawa, Ontario K1A OH9
(613) 941-2353 Fax: (613) 954-1920
Goodmans LLP for RESPONDENT Apotex Inc.
2400 - 250 Yonge Street
Toronto, Ontario M5B 2M6
(416) 979-2211 Fax: (416) 979-1234