CELGENE INC. v THE MINISTER OF HEALTH
Contents
1. b the new drug is bioequivalent with the Canadian reference product based on the pharmaceutical and where the Minister Page 28 n dans le cas d une drogue nouvelle destin e a tre administr e a des animaux producteurs de denr es alimentaires le d lai d attente applicable 3 Le fabricant de la drogue nouvelle doit a la demande du ministre lui fournir selon ce que celui ci estime n cessaire pour valuer l innocuit et l efficacit de la drogue dans le cadre de la pr sentation de drogue nouvelle les renseignements et le mat riel suivants a les nom et adresse des fabricants de chaque ingr dient de la drogue nouvelle et les nom et adresse des fabricants de la drogue nouvelle sous sa forme posologique propos e pour la vente b des chantillons des ingr dients de la drogue nouvelle c des chantillons de la drogue nouvelle sous sa forme posologique propos e pour la vente d tout renseignement ou mat riel suppl mentaire se rapportant l innocuit et l efficacit de la drogue nouvelle C 08 002 1 1 Le fabricant d une drogue nouvelle peut d poser l gard de celle ci une pr sentation abr g e de drogue nouvelle ou une pr sentation abr g e de drogue nouvelle pour usage exceptionnel si par comparaison un produit de r f rence canadien a la drogue nouvelle est un quivalent pharmaceutique du produit de r f rence canadien b elle est bio quivalente2. 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 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 5 Subsection 3 does not apply if the innovative drug is not being marketed in Canada Page 34 pr sentations avant l expiration d un d lai de six ans suivant la date laquelle le premier avis de conformit a t d livr l inno
3. conforme aux articles C 08 002 C 08 002 1 ou C 08 003 selon le cas et l article C 08 005 1 d livre un avis de conformit b si la pr sentation ou le suppl ment n est pas conforme aux articles C 08 002 C 08 002 1 ou C 08 003 selon le cas ou l article C 08 005 1 en informe le fabricant 4 L avis de conformit d livr l gard d une drogue nouvelle d apr s les renseignements et le mat riel contenus dans la pr sentation d pos e conform ment l article C 08 002 1 indique le nom du produit de r f rence canadien mentionn dans la pr sentation et constitue la d claration d quivalence de cette drogue C 08 004 1 1 Les d finitions qui suivent s appliquent au pr sent article drogue innovante S entend de toute drogue qui contient un ingr dient m dicinal non d j approuv dans une drogue par le ministre et qui ne constitue pas une variante d un ingr dient m dicinal d j approuv tel un changement de sel d ester d nantiom re de solvate ou de polymorphe innovative drug population p diatrique S entend de chacun des groupes suivants les b b s pr matur s n s avant la 37e semaine de gestation les b b s men s terme et g s de previously approved medicinal ingredient such as a salt ester enantiomer solvate or polymorph drogue innovante new drug submission includes an extraordinary use new drug submission pr se
4. Amendment to the provisions of the Food and Drug Regulations relating to approval of new drugs published January 11 1961 SOR 61 9 8 Thalidomide was one of two drugs the sale of which was absolutely prohibited pursuant to the amendments enacted by Bill C 3 on December 20 1962 which initiated the overhaul of the system for drug approval in Canada in response to the thalidomide tragedy It remained prohibited for sale in Canada until 1984 9 Despite its tragic history thalidomide was eventually found to be effective in the treatment of leprosy and other conditions including cancer In the early 1990s Celgene Corporation became interested in research into the drug thalidomide and its potential uses in tuberculosis and AIDS By 1994 Celgene Corporation was exclusively devoted to the commercialization of thalidomide to treat life threatening diseases including cancer and a painful condition associated with leprosy ENL 10 In July 1998 the U S Food and Drug Administration FDA approved the use of thalidomide marketed by Celgene Corporation as THALOMID for the acute treatment of the cutaneous manifestations of moderate to severe ENL The FDA mandated the strongest possible restricted distribution system to prevent birth defects Celgene Corporation created the system known in the U S as the S T E P S program In Canada the controlled distribution system for THALOMID is known as RevAid Celgene Corporation deve
5. bioavailability studies pharmacodynamic studies or clinical studies d evidence that all test batches of the new drug used in any studies conducted in connection with the submission were manufactured and controlled in a manner that is representative of market production and e for a drug intended for administration to food producing animals sufficient information to confirm that the withdrawal period is identical to that of the Canadian reference product 3 The manufacturer of a new drug shall at the request of the Minister provide the Minister where for the purposes of an abbreviated new drug submission or an abbreviated extraordinary use new drug submission the Minister considers it necessary to assess the safety and effectiveness of the new drug with the following information and material a the names and addresses of the manufacturers of each of the ingredients of the new drug and the names and addresses of the manufacturers of the new drug in the dosage form in which it is proposed that the new drug be sold b samples of the ingredients of the new drug Page 30 canadien ii d autre part si le ministre l estime n cessaire d apr s les caract ristiques pharmaceutiques et le cas ch ant d apr s les caract ristiques en mati re de biodisponibilit de celle ci est bio quivalente au produit de r f rence canadien selon les r sultats des tudes en mati re de biodisponibilit de
6. drogue y compris la posologie la voie d administration et la dur e d action et qui n a pas t vendue pour cet usage ou selon ce mode d emploi au Canada pendant assez longtemps et en quantit suffisante pour tablir au Canada l innocuit et l efficacit de cet usage ou de ce mode d emploi pour ladite drogue C 08 001 1 For the purposes of this Division Canadian reference product means a a drug in respect of which a notice of compliance is issued under section C 08 004 or C 08 004 01 and which is marketed in Canada by the innovator of the drug b a drug acceptable to the Minister that can be used for the purpose of demonstrating bioequivalence on the basis of pharmaceutical and where applicable bioavailability characteristics where a drug in respect of which a notice of compliance has been issued under section C 08 004 or C 08 004 01 cannot be used for that purpose because it is no longer marketed in Canada or c a drug acceptable to the Minister that can be used for the purpose of demonstrating bioequivalence on the basis of pharmaceutical and where applicable bioavailability characteristics in comparison to a drug referred to in paragraph a produit de r f rence canadien pharmaceutical equivalent means a new drug that in comparison with another drug Page 24 C 08 001 1 Les d finitions qui suivent s appliquent au pr sent titre quivalent pharmaceu
7. nouvelle m les l ments de preuve tablissant que les lots d essai de la drogue nouvelle ayant servi aux tudes men es dans le cadre de la pr sentation ont t fabriqu s et contr l s d une mani re repr sentative de la production destin e au commerce n for a drug intended for administration to food producing animals the withdrawal period of the new drug 3 The manufacturer of a new drug shall at the request of the Minister provide the Minister where for the purposes of a new drug submission the Minister considers it necessary to assess the safety and effectiveness of the new drug with the following information and material a the names and addresses of the manufacturers of each of the ingredients of the new drug and the names and addresses of the manufacturers of the new drug in the dosage form in which it is proposed that the new drug be sold b samples of the ingredients of the new drug c samples of the new drug in the dosage form in which it is proposed that the new drug be sold and d any additional information or material respecting the safety and effectiveness of the new drug C 08 002 1 1 A manufacturer of a new drug may file an abbreviated new drug submission or an abbreviated extraordinary use new drug submission for the new drug where in comparison with a Canadian reference product a the new drug is the pharmaceutical equivalent of the Canadian reference product
8. of this data is claimed by Celgene to be highly sensitive proprietary and confidential information that was submitted to Health Canada in confidence and which is maintained strictly confidential by Celgene This is why Celgene has requested the OPML to list THALOMID on the Register of Innovative Drugs 3 Issue 24 The only issue in this application for judicial review is the proper interpretation to be given to the words innovative drug as defined in subsection C 08 004 1 1 of the Regulations In determining that issue the Court must decide whether the Minister s approval of thalidomide in 1960 and 1961 constituted an approval within the meaning of approved in the definition of innovative drug The Court is also called upon to decide whether the withdrawal of approval of thalidomide for safety reasons has the legal effect of nullifying the Minister s approval such that the initial approval is void ab initio thereby giving thalidomide the status of a new medicinal ingredient 4 Analysis 25 Both parties are in agreement that the issue is reviewable on a standard of correctness The Minister s interpretation of the definition of an innovative drug is a pure question of law on which the Minister has no specialized expertise The Minister s primary expertise is in the evaluation of scientific evidence not in the interpretation of legal provisions In any event this Page 10 Court has previously applie
9. pr sentation abr g e de drogue nouvelle pour usage exceptionnel abbreviated new drug submission pr sentation de drogue nouvelle S entend galement d une pr sentation de drogue nouvelle pour usage exceptionnel new drug submission 2 Le pr sent article s applique la mise en uvre de l article 1711 de l Accord de libre change nord am ricain au sens du terme Accord au paragraphe 2 1 de la Loi de mise en uvre de l Accord de libre change nord am ricain et du paragraphe 3 de l article 39 de l Accord sur les aspects des droits de propri t intellectuelle qui touchent au commerce figurant 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 ceuvre de l Accord sur I Organisation mondiale du commerce 3 Lorsque le fabricant demande la d livrance d un avis de conformit 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 d poser pour cette drogue nouvelle de pr sentation de drogue nouvelle de pr sentation abr g e de drogue nouvelle ou de suppl ment l une de ces 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
10. respect of a drug that contains a chemical or biological substance not previously approved for sale in Canada as a drug Mr Justice Evans found that it was more consistent with the overall purposes of the statutory scheme to read in the word human to qualify drug in other words he found the relevant inquiry when material is filed by the innovator of a drug intended for human use was to ask whether it contains a substance that had previously been approved for sale for human use 38 In coming to that conclusion Mr Justice Evans agreed that the fact that a drug contains a substance that had been approved for use in connection with animals had no bearing on whether it should be regarded as previously approved for sale so that it may safely be used in connection with humans It seems to me that the same can be said of a drug that has been approved in connection with some specific uses it cannot be inferred that this same drug can also be safely sold in connection with completely different uses especially when its originally approved use has subsequently been banned for safety reasons Page 18 39 Counsel for the Applicant also raised a more technical argument revolving around the exact meaning of the words previously approved Celgene argues essentially that a medicinal ingredient cannot be previously approved where approval was revoked In other words Celgene contends that in withdrawing the approval of t
11. 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 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 34 The Guidance Document on Data Protection under C 08 004 1 of the Regulations already referred to mentions that variations other than those referred to in the definition of innovative drugs will be assessed on a case by case basis It adds at p 3 An assessment will be made as to whether or not approval is being sought primarily on the basis of previously submitted clinical data i e without the support of new and significant data New and significant data is characterized as those clinical trials which provide the evidence to determine the efficacy properties and conditions of use of the drug eg pivotal trials 35 In the case at bar Celgene
12. Federal Court Cour f d rale Date 20120206 Docket T 148 11 Citation 2012 FC 154 Ottawa Ontario February 6 2012 PRESENT The Honourable Mr Justice de Montigny BETWEEN CELGENE INC Applicant and THE MINISTER OF HEALTH Respondent REASONS FOR JUDGMENT AND JUDGMENT 1 This is an application for judicial review of the decision of the Minister of Health through the Office of the Patented Medicines and Liaison OPML whereby the Minister refused to register the Applicant s drug THALOMID on the Register of Innovative Drugs That decision was taken on the basis that the medicinal ingredient in the drug thalidomide is not innovative contrary to subsection C 08 004 1 1 of the Food and Drug Regulations CRC c 870 the Regulations Relevant portions of the Regulations are reproduced in the Annex Page 2 2 The Applicant Celgene Inc argues for its part that its drug THALOMID should be considered as an innovative drug despite thalidomide having been previously approved by Health Canada in 1960 and 1961 The Applicant essentially submits that the prior approvals 1 were made pursuant to an earlier version of the Regulations which only required safety considerations and not efficacy considerations in contrast to the current requirements and 2 became null and void when Health Canada withdrew thalidomide s approval for safety reasons in 1962 3 In essence therefore the Court is called upon t
13. HALOMID for use in the treatment of multiple myeloma The NOC was issued on August 4 2010 13 However the Minister advised Celgene on that same date that THALOMID was not eligible for data protection because the medicinal ingredient thalidomide had been previously approved by the Minister in at least two drugs KEVADON in 1960 and TALIMOL in 1961 The Minister gave Celgene thirty days in which to file written submissions on the issue Page 6 14 By letter dated December 6 2010 Celgene filed written representations with the Minister Celgene took the position that thalidomide should not be considered as having been previously approved within the meaning of C 08 004 1 of the Regulations Celgene also argued that THALOMID should be added to the Register because the NDS contains new significant and independent data 15 In the final decision letter dated January 5 2011 the Minister wrote to Celgene and confirmed the decision that because thalidomide was previously approved as a drug THALOMID was not eligible to be added to the Register of Innovative Drugs 2 The Regulatory Framework 16 The Minister of Health is responsible for the review of drugs in Canada under the relevant provisions of the Food and Drugs Act RSC 1985 c F 27 and associated regulations The Food and Drugs Act was first introduced in Canada in 1920 and by the late 1920s the regulations were developed that established licensing requirements for drugs an
14. a 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 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 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 9 The Minister shall maintain a register of innovative drugs that includes information relating to the matters specified in subsections 3 and 4 Page 35 6 L alin a 3 a ne s applique pas au fabricant ult rieur dans le cas o l innovateur consent ce qu il d pose une pr sentation de drogue nouvelle une pr sentation abr g e de drogue nouvelle ou un suppl ment l une de ces pr sentations avant l expiration du d lai de six ans pr vu cet alin a 7 L alin a 3 a ne s applique pas au fabricant ult rieur s il d pose une demande d autorisation pour vendre cette
15. amounts of the identical medicinal ingredients in comparable dosage forms but that does not necessarily contain the same non medicinal ingredients quivalent pharmaceutique specifications means a detailed description of a new drug and of its ingredients and includes a a statement of all properties and qualities of the ingredients that are relevant to the manufacture and use of the new drug including the identity potency and purity of the ingredients b a detailed description of the methods used for testing and examining the ingredients and c a statement of the tolerances associated with the properties and qualities of the ingredients sp cifications C 08 002 1 No person shall sell or advertise a new drug unless a the manufacturer of the new drug has filed with the Minister a new drug submission an extraordinary use new drug submission an abbreviated new drug submission or an abbreviated extraordinary use new drug submission relating to the new drug that is satisfactory to the Minister b the Minister has issued under section C 08 004 or C 08 004 01 a notice of compliance to the manufacturer of the new drug in respect of the submission c the notice of compliance in respect of the submission has not been suspended pursuant Page 25 ingr dients notamment a la liste des propri t s et des qualit s des ingr dients qui ont trait la fabrication et a Vemploi de la drogue nouve
16. ated new drug submission a new drug for extraordinary use in respect of which a notice of compliance has been issued under section C 08 004 01 is not a Canadian reference product C 08 004 1 Subject to section C 08 004 1 the Minister shall after completing an examination of a new drug submission or abbreviated new drug submission or a supplement to either submission a if that submission or supplement complies with section C 08 002 C 08 002 1 or C 08 003 as the case may be and section C 08 005 1 issue a notice of compliance or b if that submission or supplement does not comply with section C 08 002 C 08 002 1 or C 08 003 as the case may be or section C 08 005 1 notify the manufacturer that the submission or supplement does not so comply 2 Where a new drug submission or abbreviated new drug submission or a supplement to either submission does not comply with section C 08 002 C 08 002 1 or C 08 003 as the case may be or section C 08 005 1 the manufacturer who filed the submission or supplement may amend the submission or supplement by filing additional information or material Page 31 c des chantillons de la drogue nouvelle sous sa forme posologique propos e pour la vente d tout renseignement ou mat riel suppl mentaire se rapportant a l innocuit et l efficacit de la drogue nouvelle 4 Pour l application du pr sent article dans le cas d une pr sentation abr g e de drog
17. au produit de r f rence canadien d apr s les caract ristiques pharmaceutiques et si le considers it necessary bioavailability characteristics c the route of administration of the new drug is the same as that of the Canadian reference product and d the conditions of use for the new drug fall within the conditions of use for the Canadian reference product 2 An abbreviated new drug submission or an abbreviated extraordinary use new drug submission shall contain sufficient information and material to enable the Minister to assess the safety and effectiveness of the new drug including the following a the information and material described in i paragraphs C 08 002 2 a to f and j to 1 in the case of an abbreviated new drug submission and ii paragraphs C 08 002 2 a to f and j to 1 and subparagraphs C 08 002 01 2 b ix and x in the case of an abbreviated extraordinary use new drug submission b information identifying the Canadian reference product used in any comparative studies conducted in connection with the submission c evidence from the comparative studies conducted in connection with the submission that the new drug is i the pharmaceutical equivalent of the Canadian reference product and Page 29 ministre l estime n cessaire d apr s les caract ristiques en mati re de biodisponibilit c la voie d administration de la drogue nouvelle est identiq
18. ble to the present system the distinguishing point being the addition of efficacy as a consideration 44 The Minister s prior approvals of thalidomide were made pursuant to the 1955 version of the Regulations Section C 01 301 sets out the content of the submissions to be filed by a person wishing to sell a new drug which included detailed reports of tests made to establish the safety of the drug for the purpose and under the conditions of use recommended There is no disagreement Page 20 between the parties that the regulatory regime in Canada was substantially overhauled as a result of the thalidomide tragedy in order to improve safety requirements and for the first time to require evidence of efficacy 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 Itis not entirely clear however how far this rule should apply when prior approval has been given pursuant to a scheme that has been substantively an
19. d gave the Minister authority to cancel or suspend a licence 17 Under the current regime manufacturers who wish to advertise or sell a new drug in Canada must first obtain an NOC pursuant to Part C Division 8 of the Regulations by filing an NDS An NDS is typically filed by an innovative drug manufacturer pursuant to section C 08 002 of the Regulations and usually contains voluminous clinical trial data and detailed studies This data forms the basis on which the drug is approved for sale Page 7 18 An abbreviated new drug submission ANDS is available under section C 08 002 1 to generic drug manufacturers who wish to copy a marketed drug without having to provide clinical data demonstrating safety and efficacy The manufacturer must show instead that the generic drug is bioequivalent to a Canadian reference product based on pharmaceutical and where necessary bioavailability characteristics 19 Demonstrating bioequivalence by a comparison to a Canadian reference product permits a generic drug manufacturer to establish the safety and efficacy of its product without making a direct assessment on the basis of clinical studies In doing so the generic drug manufacturer is relying on the information established about the Canadian reference product as filed in the NDS by the brand name drug manufacturer which provides the primary knowledge about the safety and efficacy of the drug and its conditions of use 20 There i
20. d 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 Page 21 47 This case is obviously quite an exceptional one Not only are there most likely very few instances of approvals for NDS that have subsequently been withdrawn but thalidomide has a tragic and checkered history the likes of which are thankfully very rare It is therefore to be assumed that the present decision will have a limited impact in the foreseeable future 48 For all of the foregoing reasons this application for judicial review is granted with costs to the Applicant Page 22 JUDGMENT THIS COURT S JUDGMENT is that the appl
21. d tests or other data that they must provide to government entities in order to obtain approval for their new drugs Apotex Inc v Canada Minister of Health 2010 FCA 334 at para 110 413 NR 89 Apotex Inc Both treaties provide a scheme for protecting against the unfair commercial use of undisclosed data the origination of which involved considerable effort Epicept Corporation above at para 21 32 Counsel for the Respondent retorts that these provisions explicitly concern only those products that use new chemical entities and are therefore intended to protect only against unfair commercial use of data relating to new substances Furthermore it is argued that the language of subsection of C 08 004 1 1 implements that intention by using the term innovative drug as well as by limiting that term to include only medicinal ingredients in drugs that have not been previously approved According to that reasoning therefore the intent of the data protection provisions is to reserve the special market exclusivity period for genuinely new and innovative medicinal ingredients and not simply new uses of ingredients that have been previously approved for a different use Page 15 33 There are a number of flaws with respect to that construction of the DPR 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
22. d the correctness standard on at least two occasions relating to the interpretation of the definition of innovative drug in the DPR see Epicept Corporation v Canada Minister of Health 2010 FC 956 at paras 39 40 377 FTR 29 Epicept Corporation Teva Canada Limited v The Minister of Health et al 2011 FC 507 at para 35 95 CPR 4d 423 Teva Canada Limited See also Bristol Myers Squibb Co v Canada Attorney General 2005 SCC 26 at para 36 2005 1 SCR 533 Bristol Myers Squibb Co 26 Itis 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 Finding the correct interpretation requires a purposive analysis giving such fair large and liberal construction and interpretation as best ensures the attainment of the Act s objectives Trustco Mortgage Co v Canada 2005 SCC 54 at para 10 2005 2 SCR 601 Interpretation Act RSC 1985 c I 12 s 12 27 When interpreting regulations it is essential to read the words in the whole context of the authorizing statute which necessarily constrains the scope of the regulation Bristol Myers Squibb Co above at para 38 28 A contextual and purposive interpretation furthermore requires close examination of Canada s international obligations More specifically where domestic legislation implements an international treaty th
23. 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 Page 12 propri t intellectuelle qui touchent au commerce figurant l annexe 1C de l Accord sur POMC ALENA 1711 5 Lorsqu une Partie subordonne l approbation de la commercialisation de produits pharmaceutiques ou de produits chimiques pour l agriculture qui comportent des l ments chimiques nouveaux a la communication de donn es non divulgu es r sultant d essais ou d autres donn es non divulgu es n cessaires pour d terminer si l utilisation de ces produits est sans danger et efficace cette Partie prot gera ces donn es contre toute divulgation lorsque l tablissement de ces donn es demande un effort consid rable sauf si la divulgation est n cessaire pour prot ger le public ou moins que des mesures ne soient prises pour s assurer que les donn es sont prot g es contre toute exploitation d loyale dans le commerce 6 Chacune des Parties pr voira en ce qui concerne les donn es vis es au paragraphe 5 qui lui sont communiqu es apr s la date d entr e en vigueur du pr sent accord que seule la personne qui les a communiqu es peut sans autorisation de cette derni re autrui utiliser ces donn es l appui d une demande reasonable period of time after their subm
24. drogue nouvelle aux termes de l article C 07 003 8 L alin a 3 b ne s applique pas au fabricant ult rieur dans le cas o l innovateur consent ce que lui soit d livr un avis de conformit avant l expiration du d lai de huit ans pr vu cet alin a ou de huit ans et six mois pr vu au paragraphe 4 9 Le ministre tient un registre des drogues innovantes lequel contient les renseignements relatifs l application des paragraphes 3 et 4 FEDERAL COURT SOLICITORS OF RECORD DOCKET T 148 11 STYLE OF CAUSE CELGENE INC v THE MINISTER OF HEALTH PLACE OF HEARING Ottawa ON DATE OF HEARING November 21 2011 REASONS FOR JUDGMENT AND JUDGMENT de MONTIGNY J DATED February 6 2012 APPEARANCES William Vanveen FOR THE APPLICANT Wendy Wagner Eric Peterson FOR THE RESPONDENT SOLICITORS OF RECORD Gowling Lafleur Henderson LLP FOR THE APPLICANT Ottawa ON Myles J Kirvan FOR THE RESPONDENT Deputy Attorney General of Canada Ottawa ON
25. e as a drug including dosage route of administration or duration of action and that has not been sold for that use or condition of use in Canada for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that use or condition of use of that drug R glement sur les aliments et drogues C R C ch 870 Drogues nouvelles C 08 001 Pour l application de la Loi et du pr sent titre drogue nouvelle d signe a une drogue qui est constitu e d une substance ou renferme une substance sous forme d ingr dient actif ou inerte de v hicule d enrobage d excipient de solvant ou de tout autre constituant laquelle substance n a pas t vendue comme drogue au Canada pendant assez longtemps et en quantit suffisante pour tablir au Canada l innocuit et l efficacit de ladite substance employ e comme drogue b une drogue qui entre dans une association de deux drogues ou plus avec ou sans autre ingr dient qui n a pas t vendue dans cette association particuli re ou dans les proportions de ladite association pour ces drogues particuli res pendant assez longtemps et en quantit suffisante pour tablir au Canada l innocuit et l efficacit de cette association ou de ces proportions employ es comme drogue ou c une drogue pour laquelle le fabricant prescrit recommande propose ou d clare un usage comme drogue ou un mode d emploi comme
26. e treaty is considered a primary aid to construction even where there is no ambiguity Pierre Andr C t The Interpretation of Legislation in Canada 3 ed Toronto Page 11 Thomson Canada Limited 2000 at p 368 citing National Corn Growers et al v Canada Import Tribunal 1990 2 SCR 1324 at p 1371 29 Counsel for the Applicant first argued that the Minister failed to apply a purposive interpretation of the DPR which it was submitted is to encourage and reward innovation by protecting the data an innovator must generate to obtain approval for a drug I fully agree with that argument 30 It is beyond dispute that the DPR was enacted pursuant to subsection 30 3 of the Food and Drugs Act which enables the Governor in Council to implement Canada s international obligations under Article 1711 5 and 6 of NAFTA and Article 39 3 of TRIPS These provisions read as follows Food and Drugs Act Regulations re the North American Free Trade Agreement and WTO Agreement 30 3 Without limiting or restricting the authority conferred by any other provisions of this Act or any Part thereof for carrying into effect the purposes and provisions of this Act or any Part thereof the Governor in Council may make such regulations as the Governor in Council deems necessary for the purpose of implementing in relation to drugs Article 1711 of the North American Free Trade Agreement or paragraph Loi sur l
27. es aliments et drogues R glements relatifs l Accord de libre change nord am ricain et l Accord sur POMC 3 Sans que soit limit le pouvoir conf r par toute autre disposition de la pr sente loi de prendre des r glements d application de la pr sente loi ou d une partie de celle ci le gouverneur en conseil peut prendre concernant les drogues les r glements qu il estime n cessaires pour la mise en oeuvre de l article 1711 de P Accord de libre change nord am ricain ou du paragraphe 3 de l article 39 de l Accord sur les aspects des droits de 3 of Article 39 of the Agreement on Trade related Aspects of Intellectual Property Rights set out in Annex 1C to the WTO Agreement 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
28. es frais consentis par cette personne pour les produire Sous r serve de cette disposition rien n emp chera une Partie d adopter l gard de ces produits des proc dures d homologation abr g es fond es sur des tudes de bio quivalence et de biodisponibilit Accord sur les droits de propri t qui touchent au commerce Section 7 Protection des renseignements non divulgu s Article 39 3 Lorsqu ils subordonnent l approbation de la commercialisation de produits pharmaceutiques ou de produits chimiques pour l agriculture qui comportent des entit s chimiques nouvelles la communication de donn es non divulgu es r sultant d essais ou d autres donn es non divulgu es dont l tablissement demande un effort consid rable Page 13 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 Page 14 les Membres prot geront ces donn es contre l exploitation d loyale dans le commerce En outre les Membres prot geront ces donn es contre la divulgation sauf si cela est n cessaire pour prot ger le public ou moins que des mesures ne soient prises pour s assurer que les donn es sont prot g es contre l exploitation d loyale dans le commerce 31 Article 1711 of the NAFTA and Article 39 3 of TRIPS seek to provide protection to innovators in respect of undisclose
29. he drug submissions for thalidomide in 1962 this medicinal ingredient reverted to the status of a new drug wiping the slate clean such that thalidomide now qualifies as an innovative drug 40 Counsel for the Respondent opposes that interpretation arguing that withdrawing an approval or taking it back is not the same as nullifying it ab initio Indeed counsel submits that the Minister did not have the power to render the approval void ab initio and that courts may only nullify executive acts in those limited cases where the executive lacked jurisdiction 41 Ido 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 The fact of the matter is that thalidomide was determined to be unsafe and returned to the status of a new drug From April 6 1962 a generic manufacturer could not submit an ANDS for approval of a generic version of thalidomide by referencing KEVADON AND TALIMOL because both drugs had reverted to a new drug status 42 Itis 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 Page 19 has been withdraw
30. ication for judicial review is granted with costs to the Applicant The decision of the Minister not to add THALOMID to the Register of Innovative Drugs is therefore quashed and set aside It is further declared that THALOMID is an innovative drug and eligible for listing on the Register maintained pursuant to the Data Protection Regulations as of the date of issuance of the Notice of Compliance for THALOMID namely August 4 2010 Yves de Montigny Judge Page 23 Annex Food and Drug Regulations C R C c 870 New Drugs C 08 001 For the purposes of the Act and this Division new drug means a a drug that contains or consists of a substance whether as an active or inactive ingredient carrier coating excipient menstruum or other component that has not been sold as a drug in Canada for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that substance for use as a drug b a drug that is a combination of two or more drugs with or without other ingredients and that has not been sold in that combination or in the proportion in which those drugs are combined in that drug for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that combination and proportion for use as a drug or c a drug with respect to which the manufacturer prescribes recommends proposes or claims a use as a drug or a condition of us
31. id the obligation to accord protection to the data filed to obtain approval in their jurisdiction because the chemical entity in the product has been approved elsewhere or is otherwise known 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 see Canadian Generic Pharmaceutical Association v Canada Minister of Page 17 Health 2009 FC 725 at paras 120 123 348 FTR 29 rev d on other grounds in Apotex Inc above at para 77 37 This finding bears some resemblance and is consistent with the decision of Mr Justice Evans as he then was in Bayer Inc v Canada Attorney General 1999 1 FC 553 conf d 1999 87 CPR 3d 293 In that case the Court had to decide inter alia whether the fact that a drug contained a chemical or biological substance found in a drug previously approved for sale in connection with an animal disease excluded it from the scope of s C 08 004 1 As in the present case that section only applied in
32. ission 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 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 d approbation de produit au cours d une p riode de temps raisonnable suivant la date de leur communication On entend g n ralement par p riode de temps raisonnable une p riode d au moins cing ann es a compter de la date a laquelle la Partie en cause a donn son autorisation la personne ayant produit les donn es destin es a faire approuver la commercialisation de son produit compte tenu de la nature des donn es ainsi que des efforts et d
33. lle y compris leur identit leur activit et leur puret b la description d taill e des m thodes d analyse et d examen des ingr dients c la liste des tol rances relatives aux propri t s et aux qualit s des ingr dients specifications C 08 002 1 Il est interdit de vendre ou d annoncer une drogue nouvelle moins que les conditions suivantes ne soient r unies a le fabricant de la drogue nouvelle a relativement a celle ci d pos aupr s du ministre une pr sentation de drogue nouvelle une pr sentation de drogue nouvelle pour usage exceptionnel une pr sentation abr g e de drogue nouvelle ou une pr sentation abr g e de drogue nouvelle pour usage exceptionnel que celui ci juge acceptable b le ministre a d livr au fabricant de la drogue nouvelle en application des articles C 08 004 ou C 08 004 01 un avis de conformit relativement a la pr sentation c l avis de conformit relatif la pr sentation n a pas t suspendu aux termes to section C 08 006 and d the manufacturer of the new drug has submitted to the Minister specimens of the final version of any labels including package inserts product brochures and file cards intended for use in connection with that new drug and a statement setting out the proposed date on which those labels will first be used 2 A new drug submission shall contain sufficient information and material to enable the Minister to as
34. loped a medical regulatory infrastructure for approval of thalidomide that was based on clinical trials in diverse diseases In May 2006 the FDA approved THALOMID for the treatment of patients with newly diagnosed multiple myeloma a form of cancer Page 5 11 In Canada THALOMID was first made available through Health Canada s Special Access Programme SAP in 1995 This program is designed to provide exceptional access to drugs not approved for sale in Canada and essentially permits the sale of a new drug that could not otherwise be sold in Canada because it does not hold a Notice of Compliance NOC These sales are exempt from the formal comprehensive scientific and medical review that is conducted when products are reviewed for full marketing authorization Health Canada apparently approved the sale of THALOMID through this program in response to requests for leprosy treatment and for treatment of other immune related conditions associated with AIDS and certain forms of cancer The Applicant claims that Health Canada expected it to file a new drug submission NDS for the drug in view of its high profile the high volume of requests under the SAP and the fact that approval in the form of an NOC would better ensure safety 12 On May 19 2009 Celgene did file an NDS with the Minister of Health seeking market approval for 50 mg 100 mg 150 mg and 200 mg strength thalidomide capsules in Canada under the trade name T
35. n 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 It is to encourage the research and development of these new medicines that the DPR was enacted so as to provide an eight year period of market exclusivity to innovative manufacturers This generated extensive data to ensure that a product is both safe and effective for its intended use 43 One last point need be made Celgene also argues that the term approved in the definition of innovative drug should be construed as limited to approvals made pursuant to the current regulatory regime for drug approvals or earlier regimes that required both safety and efficacy considerations in the approval process Celgene argues that the 1963 version of the Regulations marks the bright line between prior schemes of drug approval that are compara
36. nt other persons from making unfair commercial use of the data and from relying on the data in their own applications for approval for a reasonable period of time 22 The administration of the data protection provisions by the OPML is outlined in Health Canada s guidance document entitled Data Protection under C 08 004 1 of the Food and Drug Regulations For the purpose of determining whether the submission filed by a generic drug manufacturer is based directly or indirectly on a comparison to an innovative drug the OPML must first consider whether the medicinal ingredient was previously approved in a drug by the Minister This follows from the definition of an innovative drug in subsection C 08 004 1 1 as 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 As previously mentioned at the outset the interpretation of this definition and more particularly of the words previously approved is the nub of the present application for judicial review Page 9 23 The NDS that was filed for THALOMID comprised 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 All
37. ntation de drogue nouvelle pediatric populations means the following groups premature babies born before the 37th week of gestation full term babies from 0 to 27 days of age and all children from 28 days to 2 years of age 2 years plus 1 day to 11 years of age and 11 years plus 1 day to 18 years of age population p diatrique 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 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 Page 33 0 27 jours tous les enfants g s de 28 jours deux ans ceux g s de deux ans et un jour 11 ans et ceux g s de 11 ans et un jour a 18 ans pediatric populations pr sentation abr g e de drogue nouvelle S entend galement d une
38. o determine the correct interpretation of the words previously approved in the definition of innovative drug found in the Data Protection Regulations DPR contained in the Regulations 1 Factual Background 4 The drug thalidomide was launched commercially by a German pharmaceutical company in October 1957 It was promoted as completely safe and was used for sleeplessness minor ailments and was also given to thousands of pregnant women for morning sickness In Canada W M S Merrell Company received approval for thalidomide under the brand name KEVADON on November 22 1960 and Frank W Homer Limited received approval for the same drug under the brand name TALIMOL on October 11 1961 5 By 1959 the medical community had begun to detect a possible connection between long term thalidomide use and polyneuritis numbness and tingling in the hands and feet By 1961 physicians had begun to link thalidomide with serious birth defects and deaths In 1961 and 1962 thalidomide was dramatically withdrawn from the market worldwide because of its teratogenicity Page 3 or capability of producing foetal malformation Thousands of babies were born worldwide with phocomelia and other horrific conditions Many were stillborn or died soon after birth In Canada the Food and Drug Directorate of the Department of Health ordered first the temporary withdrawal of KEVADON and TALIMOL in March 1962 and then its permanent withdrawal from
39. ration of the new drug ii the proposed dosage of the new drug iii the claims to be made for the new drug and iv the contra indications and side effects of the new drug 1 a description of the dosage form in which it is proposed that the new drug be sold m evidence that all test batches of the new drug used in any studies conducted in connection with the submission were manufactured and controlled in a manner that is representative of market production and Page 27 effectu es en vue d tablir l innocuit de la drogue nouvelle aux fins et selon le mode d emploi recommand s h des preuves substantielles de l efficacit clinique de la drogue nouvelle aux fins et selon le mode d emploi recommand s 1 la d claration des noms et titres professionnels de tous les chercheurs qui la drogue nouvelle a t vendue j une esquisse de chacune des tiquettes qui doivent tre employ es relativement la drogue nouvelle k la d claration de toutes les recommandations qui doivent tre faites dans la r clame pour la drogue nouvelle au sujet 1 de la voie d administration recommand e pour la drogue nouvelle ii de la posologie propos e pour la drogue nouvelle ili des propri t s attribu es la drogue nouvelle iv des contre indications et les effets secondaires de la drogue nouvelle 1 la description de la forme posologique propos e pour la vente de la drogue
40. rogue nouvelle notamment a une description de la drogue nouvelle et une mention de son nom propre ou d faut de son nom usuel b une mention de la marque nominative de la drogue nouvelle ou du nom ou code d identification projet pour celle ci c la liste quantitative des ingr dients de la drogue nouvelle et les sp cifications relatives chaque ingr dient d la description des installations et de l quipement utiliser pour la fabrication la pr paration et l emballage de la drogue nouvelle e des pr cisions sur la m thode de fabrication et les m canismes de contr le appliquer pour la fabrication la pr paration et emballage de la drogue nouvelle f le d tail des preuves qui doivent tre effectu es pour contr ler l activit la puret la stabilit et l innocuit de la drogue nouvelle g les rapports d taill s des preuves establish the safety of the new drug for the purpose and under the conditions of use recommended h substantial evidence of the clinical effectiveness of the new drug for the purpose and under the conditions of use recommended i a statement of the names and qualifications of all the investigators to whom the new drug has been sold j a draft of every label to be used in conjunction with the new drug k a statement of all the representations to be made for the promotion of the new drug respecting i the recommended route of administ
41. s tudes pharmacodynamiques ou des tudes cliniques d les l ments de preuve tablissant que les lots d essai de la drogue nouvelle ayant servi aux tudes men es dans le cadre de la pr sentation ont t fabriqu s et contr l s d une mani re repr sentative de la production destin e au commerce e dans le cas d une drogue destin e tre administr e des animaux producteurs de denr es alimentaires les renseignements permettant de confirmer que le d lai d attente est identique celui du produit de r f rence canadien 3 Le fabricant de la drogue nouvelle doit la demande du ministre lui fournir selon ce que celui ci estime n cessaire pour valuer l innocuit et l efficacit de la drogue dans le cadre de la pr sentation abr g e de drogue nouvelle ou de la pr sentation abr g e de drogue nouvelle pour usage exceptionnel les renseignements et le mat riel suivants a les nom et adresse des fabricants de chaque ingr dient de la drogue nouvelle et les nom et adresse des fabricants de la drogue nouvelle sous sa forme posologique propos e pour la vente b des chantillons des ingr dients de la drogue nouvelle c samples of the new drug in the dosage form in which it is proposed that the new drug be sold and d any additional information or material respecting the safety and effectiveness of the new drug 4 For the purposes of this section in the case of an abbrevi
42. s another aspect though of the legislated framework within which drugs are regulated Prior to the enactment in 1995 of the DPR found in the Regulations the only obstacle to a generic drug manufacturer s ability to obtain approval of the right to market a generic drug was the existence of an unexpired patent With the enactment of the DPR the current version of which came into force on October 5 2006 a generic drug manufacturer may not file a submission on the basis of a comparison to an innovative drug within the first six years of the eight year period after the drug has received an NOC In addition the Minister may not issue an NOC to the generic drug manufacturer before the end of the eight year period It is these prohibitions that result in what is known as data protection Page 8 21 These provisions found in section C 08 004 1 of the Regulations came into force on October 5 2006 and were adopted pursuant to section 30 3 of the Food and Drugs Act as amended As specified in subsection C 08 004 1 2 these provisions are meant to implement Article 1711 of the North American Free Trade Agreement NAFTA and paragraph 3 of Article 39 of the Trade Related Aspects of Intellectual Property Rights Agreement TRIPS Under these commitments where a person submits undisclosed data for approval of a pharmaceutical product and the product utilizes a new chemical entity signatories are required to take steps to preve
43. 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 To do so Celgene did not and could not rely on old data but had to produce the very data that Page 16 had not ever been produced previously and which was required to obtain an NOC In an uncontradicted affidavit the Senior Director of Pharmacovigilence amp Regulatory Affairs at Celgene Inc testified that 108 volumes of data were filed with the NDS in seeking approval for THALOMID 36 Moreover the purpose of the DPR is clearly to encourage and reward innovation by protecting the data an innovator must generate to obtain approval for a drug Interpreting the DPR as proposed by Celgene is therefore completely in keeping with its purpose While the relevant treaty provisions obligate member countries to confer the protection for pharmaceutical or agricultural products which utilize new chemical entities this notion is nowhere to be found in the DPR Moreover the focus in the treaties is clearly on the protection of undisclosed data the origination of which involved a considerable effort I agree with the Applicant that to make TRIPS and NAFTA obligations meaningful the protection must arise when approval is sought for a product containing a chemical entity that does not have approval in a drug in a particular jurisdiction Just as a member country could not avo
44. sess the safety and effectiveness of the new drug including the following a a description of the new drug and a statement of its proper name or its common name if there is no proper name b a statement of the brand name of the new drug or the identifying name or code proposed for the new drug c a list of the ingredients of the new drug stated quantitatively and the specifications for each of those ingredients d a description of the plant and equipment to be used in the manufacture preparation and packaging of the new drug e details of the method of manufacture and the controls to be used in the manufacture preparation and packaging of the new drug f details of the tests to be applied to control the potency purity stability and safety of the new drug g detailed reports of the tests made to Page 26 de l article C 08 006 d le fabricant de la drogue nouvelle a pr sent au ministre sous leur forme d finitive des chantillons des tiquettes y compris toute notice jointe l emballage tout d pliant et toute fiche sur le produit destin es tre utilis es pour la drogue nouvelle ainsi qu une d claration indiquant la date laquelle il est pr vu de commencer utiliser ces tiquettes 2 La pr sentation de drogue nouvelle doit contenir suffisamment de renseignements et de mat riel pour permettre au ministre d valuer l innocuit et l efficacit de la d
45. the Canadian market one month later 6 The withdrawal letters sent to the manufacturers by the Department of Health stated in part The acceptance of the new drug submission received by you on October 11 1961 November 22 1960 is withdrawn in view of the recent evidence that raises a strong suspicion that thalidomide has a very undesirable action on the human foetus 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 Ex D to the Leshuk Affidavit A R Vol 1 Tab 28 pp 259 265 Ex E to the Ciesielski Affidavit A R Vol 3 Tab 67 pp 973 976 7 At the time new drug was defined to mean New drug means a drug that because of its a composition b method of manufacture c dosage or d route of administration is not generally recognized by persons qualified to evaluate the safety of the drug as safe for the use for which it is proposed or recommended and includes a drug for which a new drug submission has been filed in accordance with section C 01 302 or C 01 304 but the safety of which has not been established by use for a material time or to a material extent Page 4
46. tique S entend d une drogue nouvelle qui par comparaison une autre drogue contient les m mes quantit s d ingr dients m dicinaux identiques sous des formes posologiques comparables mais pas n cessairement les m mes ingr dients non m dicinaux pharmaceutical equivalent produit de r f rence canadien Selon le cas a une drogue l gard de laquelle un avis de conformit a t d livr en application des articles C 08 004 ou C 08 004 01 et qui est commercialis e au Canada par son innovateur b une drogue jug e acceptable par le ministre et qui peut tre utilis e pour la d termination de la bio quivalence d apr s les caract ristiques pharmaceutiques et le cas ch ant les caract ristiques en mati re de biodisponibilit lorsqu une drogue pour laquelle un avis de conformit a t d livr en application des articles C 08 004 ou C 08 004 01 ne peut tre utilis e cette fin parce qu elle n est plus commercialis e au Canada c une drogue jug e acceptable par le ministre qui peut tre utilis e pour la d termination de la bio quivalence d apr s les caract ristiques pharmaceutiques et le cas ch ant les caract ristiques en mati re de biodisponibilit par comparaison une drogue vis e l alin a a Canadian reference product sp cifications S entend de la description d taill e d une drogue nouvelle et de ses contains identical
47. ubmission or supplement complies with section C 08 002 C 08 002 1 or C 08 003 as the case may be and section C 08 005 1 issue a notice of compliance or b if that submission or supplement does not comply with the requirements of section C 08 002 C 08 002 1 or C 08 003 as the case may be or section C 08 005 1 notify the manufacturer that the submission or supplement does not so comply 4 A notice of compliance issued in respect of a new drug on the basis of information and material contained in a submission filed pursuant to section C 08 002 1 shall state the name of the Canadian reference product referred to in the submission and shall constitute a declaration of equivalence for that new drug C 08 004 1 1 The following definitions apply in this section abbreviated new drug submission includes an abbreviated extraordinary use new drug submission pr sentation abr g e de drogue nouvelle 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 Page 32 3 Sous r serve de l article C 08 004 1 apr s avoir termin l examen des renseignements et du mat riel suppl mentaires d pos s relativement une pr sentation de drogue nouvelle une pr sentation abr g e de drogue nouvelle ou un suppl ment l une de ces pr sentations le ministre a si la pr sentation ou le suppl ment est
48. ue celle du produit de r f rence canadien d les conditions th rapeutiques relatives la drogue nouvelle figurent parmi celles qui s appliquent au produit de r f rence canadien 2 La pr sentation abr g e de drogue nouvelle ou la pr sentation abr g e de drogue nouvelle pour usage exceptionnel doit contenir suffisamment de renseignements et de mat riel pour permettre au ministre d valuer l innocuit et l efficacit de la drogue nouvelle notamment a les renseignements et le mat riel vis s i aux alin as C 08 002 2 a f et j D dans le cas d une pr sentation abr g e de drogue nouvelle ii aux alin as C 08 002 2 a f et j a1 et aux sous alin as C 08 002 01 2 b ix et x dans le cas d une pr sentation abr g e de drogue nouvelle pour usage exceptionnel b les renseignements permettant d identifier le produit de r f rence canadien utilis pour les tudes comparatives men es dans le cadre de la pr sentation c les l ments de preuve provenant des tudes comparatives men es dans le cadre de la pr sentation tablissant que la drogue nouvelle i d une part est un quivalent pharmaceutique du produit de r f rence ii where the Minister considers it necessary on the basis of the pharmaceutical and where applicable bioavailability characteristics of the new drug bioequivalent with the Canadian reference product as demonstrated using
49. ue nouvelle la drogue nouvelle pour usage exceptionnel l gard de laquelle un avis de conformit a t d livr en application de l article C 08 004 01 n est pas un produit de r f rence canadien C 08 004 1 Sous r serve de l article C 08 004 1 apr s avoir termin l examen d une pr sentation de drogue nouvelle d une pr sentation abr g e de drogue nouvelle ou d un suppl ment l une de ces pr sentations le ministre a si la pr sentation ou le suppl ment est conforme aux articles C 08 002 C 08 002 1 ou C 08 003 selon le cas et l article C 08 005 1 d livre un avis de conformit b si la pr sentation ou le suppl ment n est pas conforme aux articles C 08 002 C 08 002 1 ou C 08 003 selon le cas ou a l article C 08 005 1 en informe le fabricant 2 Lorsqu une pr sentation de drogue nouvelle une pr sentation abr g e de drogue nouvelle ou un suppl ment l une de ces pr sentations n est pas conforme aux articles C 08 002 C 08 002 1 ou C 08 003 selon le cas ou l article C 08 005 1 le fabricant qui l a d pos peut le modifier en d posant des renseignements ou du mat riel suppl mentaires 3 Subject to section C 08 004 1 the Minister shall after completing an examination of any additional information or material filed in respect of a new drug submission or an abbreviated new drug submission or a supplement to either submission a if that s
50. vateur pour la drogue innovante b le ministre ne peut approuver une telle pr sentation ou un tel suppl ment et ne peut d livrer d avis de conformit pour cette nouvelle drogue avant l expiration d un d lai de huit ans suivant la date laquelle le premier avis de conformit a t d livr Vinnovateur pour la drogue innovante 4 Le d lai pr vu l alin a 3 b est port huit ans et six mois si la fois a l innovateur fournit au ministre la description et les r sultats des essais cliniques concernant l utilisation de la drogue innovante dans les populations p diatriques concern es dans sa premi re pr sentation de drogue nouvelle l gard de la drogue innovante ou dans tout suppl ment une telle pr sentation d pos au cours des cinq ann es suivant la d livrance du premier avis de conformit l gard de cette drogue innovante b le ministre conclut avant l expiration du d lai de six ans qui suit la date laquelle le premier avis de conformit a t d livr Vinnovateur pour la drogue innovante que les essais cliniques ont t con us et men s en vue d largir les connaissances sur l utilisation de cette drogue dans les populations p diatriques vis es et que ces connaissances se traduiraient par des avantages pour la sant des membres de celles ci 5 Le paragraphe 3 ne s applique pas si la drogue innovante n est pas commercialis e au Canad
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