OPINION OF ADVOCATE GENERAL

JACOBS

delivered on 8 July 2004 ( )

Case C-36/03

Approved Prescription Services Ltd

v

Licensing Authority (acting by the Medicines Control Agency)





1. This reference from the High Court of England and Wales (Queen’s Bench Division) concerns an application for national marketing authorisation for a medicinal product pursuant to Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use, (hereinafter, ‘the Directive’), ( ) as it stood prior to its recent amendment. ( )

2. Ordinarily, the Directive requires an applicant to supply a full set of data in order to show the safety and efficacy of its product. However, in derogation from that full procedure, the Directive also specifies various abridged procedures, whereby the applicant is relieved of the obligation to supply certain data, and may refer instead to data submitted in respect of another previously authorised product. Under one such procedure, as it operated at the material time, the applicant could make such reference where its product was essentially similar to the other product, and where the other product had been authorised for a stipulated period (fixed, for the purposes of the present case, at 10 years). Under another such procedure, the applicant could refer in part to the data submitted in respect of another product but could also submit additional ‘bridging’ data to deal with certain specified types of difference between the two otherwise similar products.

3. The present case concerns fluoxetine liquid, the generic name for an anti-depressant which is the active ingredient of products marketed under the name of Prozac. Marketing authorisation for Prozac capsules was first obtained in 1988, and authorisation for Prozac liquid (which was granted on the basis of bridging data supplementing the data already provided for the capsules) in 1992. In 1999, less than 10 years after the authorisation of Prozac liquid, a generic manufacturer applied for authorisation to market generic fluoxetine liquid, relying on the data supplied for the previous authorisation. The application was refused on the grounds that Prozac liquid had been authorised for less than 10 years, and that fluoxetine liquid was not essentially similar to Prozac capsules.

4. In the context of an application for judicial review of that refusal, the referring court wishes to know whether, under the relevant provisions, the applicant for a marketing authorisation for a new medicinal product (hereinafter, ‘the new product’ or ‘product C’) may rely upon data submitted in respect of an essentially similar product (hereinafter, ‘the variant’ or ‘product B’) which has been authorised within the Community for less than the stipulated period, but which is a version of a product (hereinafter, ‘the original product’ or ‘product A’) which has been authorised for at least that period, despite the fact that products A and B have a different pharmaceutical form or are otherwise lacking in essential similarity.

5. The Court has considered the interpretation of the Directive on several occasions, and the question referred falls to be determined in the light of its judgments in Generics ( ) and Novartis. ( ) Since the material time, the Directive has been revised in such a way as to give, for the future, a clear affirmative answer to the question raised in the present proceedings.

Legal framework

Community legislation

6. The Directive consolidates in one text a number of directives dealing with medicinal products and codifies amendments made to those directives. Chapter 1 of Title III of the Directive is made up of Articles 6 to 12, and deals with marketing authorisation for medicinal products. ( ) Since the material time, the Directive has been amended on several occasions. Of relevance to the issue raised by the present proceedings are the amendments effected by Directive 2004/27/EC, which are set out below. ( )

7. Article 6(1) provides that a medicinal product may be placed on the market in a Member State only if a marketing authorisation has been issued by the competent authorities of that Member State.

8. Articles 8 and 10 provide for several possible procedures for obtaining a national marketing authorisation. Article 8(3) identifies the particulars and documents which must be supplied in support of an application under what might be termed the full procedure. It provides that such information must be ‘submitted in accordance with Annex I’ of the Directive. Pursuant to Article 8(3)(i), ( ) the applicant must ordinarily provide the results of:

‘– physico-chemical, biological or microbiological tests

– pharmacological and toxicological tests;

– clinical trials.’

9. Article 10 lays down various procedures alternative to the full procedure, whereby, in certain specified circumstances, an applicant may be relieved of the obligation to provide some or all of the results of pharmacological and toxicological tests and of clinical trials normally required by Article 8(3)(i), and may rely instead on data submitted in respect of another ‘reference’ product which has already been authorised. The obligation to provide full particulars of the physico-chemical nature of the product is not affected.

10. At the material time, Article 10(1)(a) provided for the so-called ‘abridged’ procedure, which relieved the applicant of the obligation to supply any of the relevant types of data, if it could demonstrate:

‘…

(i) either that the medicinal product is essentially similar to a medicinal product authorised in the Member State concerned by the application and that the holder of the marketing authorisation for the original medicinal product has consented to the toxicological, pharmacological and/or clinical references contained in the file on the original medicinal product being used for the purpose of examining the application in question;

…

(iii) or that the medicinal product is essentially similar to a medicinal product which has been authorised within the Community, in accordance with Community provisions in force, for not less than 6 years and is marketed in the Member State for which the application is made … [A] Member State may … extend this period to 10 years by a single Decision covering all the medicinal products marketed on its territory where it considers this necessary in the interest of public health …’

11. At the material time, a further procedure, commonly referred to as the ‘hybrid abridged’ procedure, was laid down in the final paragraph of Article 10(1)(a), a provision commonly known as the proviso:

‘However, where the medicinal product is intended for a different therapeutic use from that of the other medicinal products marketed or is to be administered by different routes or in different doses, the results of appropriate toxicological and pharmacological tests and/or of appropriate clinical trials must be provided.’

12. Under the proviso, an applicant was therefore required to provide only the results of such pharmacological or toxicological tests and clinical trials as were appropriate in the light of the difference in therapeutic use, route of administration, or dose from the other medicinal products marketed. Otherwise, the applicant relied upon the data relating to the reference product which it was required to specify under Article 10(1)(a)(i) or (iii). The additional data which the applicant was required to supply under the proviso were commonly known as ‘bridging data’.

13. The objectives underlying the various procedures for obtaining a marketing authorisation are apparent from the preamble to the Directive. The second recital makes clear that the essential aim of any rules governing the production, distribution and use of medicinal products must be to safeguard public health. As appears from the 9th and 10th recitals, the procedures specified in Article 10(1)(a) are also aimed at ensuring that innovative firms are not placed at a disadvantage and at avoiding repetitive tests on humans or animals without over-riding cause.

The Notice to Applicants

14. As set out above, Article 8(3) of the Directive requires that the particulars and documents in support of an application for marketing authorisation must be ‘submitted in accordance with Annex I’.

15. The first paragraph in the introduction to that Annex requires the particulars and documents accompanying an application for marketing authorisation to be prepared in a manner which takes account of the guidance published by the Commission in a document which at the material time was entitled ‘The rules governing medicinal products in the European Community, Volume II: Notice to applicants for marketing authorisations for medicinal products for human use in the Member States of the European Community’. ( ) Volume II is generally known and is hereinafter referred to as the Notice to Applicants. ( )

16. As its foreword explains, the Notice to Applicants ‘has been prepared by the European Commission, in consultation with the competent authorities of the Member States and the European Agency for the Evaluation of Medicinal Products’. It therefore presents the ‘harmonised views’ of the Member States and the Agency on how the ‘legal requirements of the Directives and the Regulations … may be met’. At the same time, the foreword states that the Notice ‘has no legal force and does not necessarily represent the final views of the Commission’. In case of doubt, therefore, reference should be made to the appropriate Community legislation.

17. Volume 2A of the Notice to Applicants concerns procedures for marketing authorisation. Section 4.2 of chapter 1 thereof deals with applications under the abridged procedure. It states that:

‘The dossier of a new strength, new pharmaceutical form, new indication (called deliberately “line extensions” see section 5.2) of an existing medicinal product from the same marketing authorisation holder based on a complete dossier is also considered as a complete dossier. An essentially similar product (informed consent or generic) can refer to the dossier of the line extension of the original medicinal product. Therefore, a line extension for a generic medicinal product can be applied for by reference to the line extension of the original medicinal product.’

18. Section 4.2 also supplies the following definitions:

‘Essential similarity: the product applied for under the abridged procedure must be essentially similar to the original/reference medicinal product. In this context the following definitions are applicable.

An original medicinal product is a medicinal product that has been authorised within the Community for not less than 6 or 10 years. The marketing authorisation of this medicinal product is based on a complete dossier.

A reference medicinal product is a version of the original medicinal product which is marketed in the Member State for which the application is made and which is used to claim essential similarity. In this Member State the reference medicinal product can be authorised for less than 6 or 10 years. This reference medicinal product might be of another strength or pharmaceutical form or be approved for other indications or have other excipients than the original medicinal product.

A medicinal product used as comparison for bioequivalence study, where a bioequivalence study is applicable, is a version of the original medicinal product that is authorised within the Community. This medicinal product is normally the same as the reference medicinal product.’

Community case-law

19. The Court of Justice has on several occasions considered the provisions which were at the time to which the present proceedings relate contained in Article 10(1)(a), most notably in the Generics and Novartis cases. ( ) Those cases have shed light upon the meaning of essential similarity; the operation of the hybrid abridged procedure laid down in the proviso; and the circumstances in which an applicant under Article 10(1)(a)(iii) may claim essential similarity with, and rely upon data submitted in respect of, a later version of the reference product, which later version was authorised less than 6 or 10 years previously.

The meaning of essential similarity

20. The Court held in Generics, ( ) and confirmed in Novartis, ( ) that one medicinal product is essentially similar to another ‘where it satisfies the criteria of having the same qualitative and quantitative composition in terms of active principles, of having the same pharmaceutical form and of being bioequivalent, unless it is apparent in the light of scientific knowledge that it differs significantly from the original product as regards safety or efficacy’.

21. As to the meaning of pharmaceutical form for the purpose of that test, the Court held in Novartis that, in determining the pharmaceutical form of a given product, ‘account must be taken of the form in which it is presented and the form in which it is administered, including the physical form’. ( )

The hybrid abridged procedure

22. As with the abridged procedure, the proviso clearly permits some reliance upon data previously submitted in respect of a reference product, but requires additional bridging data on account of a difference in therapeutic use, route of administration or dose between the reference product and the new product to which the application relates.

23. In Novartis, the Court held that the proviso may be used in conjunction with either Article 10(1)(a)(i) (where the reference product has been authorised in the country concerned by the application, and where the consent of the person responsible for marketing the reference product has been obtained) or Article 10(1)(a)(iii) (where the reference product has been authorised within the Community for not less than 6 or 10 years and is marketed in the Member State for which the application is made). ( )

24. The Court also held that under the hybrid abridged procedure, by contrast with the abridged procedure, the product for which authorisation is sought need not in all cases be essentially similar to the reference product.

25. The Court noted that if essential similarity were required, the proviso would be largely ineffective in the case of medicinal products to be administered by routes or in doses different from those of other medicinal products on the market, given that the former are generally not bioequivalent to the latter. ( )

26. The Court therefore held that an application for marketing authorisation may be made under the proviso with reference to an authorised medicinal product provided that the product in respect of which authorisation is sought is essentially similar to the authorised medicinal product, unless one or more of the differences set out in the proviso apply. ( )

The permissibility of reference to data submitted in respect of a variant of the original product

27. In Generics, the Court held that under Article 10(1)(a)(iii), a new medicinal product which is essentially similar to another product which has been authorised for not less than 6 or 10 years in the Community and is marketed in the Member State for which the application is made may be authorised for all therapeutic indications, dosage forms, doses and dosage schedules already authorised for the reference product, including those authorised for less than 6 or 10 years. ( )

28. The Generics judgment thus made clear that an applicant may in certain circumstances rely not only upon the data submitted to obtain the first authorisation of a reference product, not less than 6 or 10 years previously, but also data submitted subsequently, to obtain the further authorisation of some variant upon the reference product, even where the latter was filed within the last 6 or 10 years.

29. The Generics judgment gave rise to varying interpretations. According to one interpretation, it was necessary for an applicant to show not only that its product was essentially similar to the variant product, but also that the original product and its variant were themselves essentially similar to one another.

30. The problem with such an interpretation was that, given the definition of essential similarity adopted by the Court, several of the types of variation specified in Generics would unavoidably result in the original product and its variant lacking essential similarity to one another.

31. The preponderance of opinion among the national and Community regulators, as reflected in the Notice to Applicants, was that the Generics judgment must be interpreted as permitting reference, by the applicant for an authorisation of a new product under Article 10(1)(a)(iii), to data submitted in respect of a variant of the original product in the circumstances identified in that judgment even if the variant lacks essential similarity to the original product, provided that the new product is essentially similar to the variant.

32. In Novartis, the Court was able to elaborate upon its interpretation of Article 10(1)(a)(iii) in Generics.

33. First, the Court made clear that essential similarity is not always necessary as between the original product and its variant in order for reference to be made to data submitted in respect of the variant. Otherwise, the circumstances in which such reference could be made would effectively be limited to new therapeutic indications, given the likely impact of other types of change upon bioavailability, one of the criteria of essential similarity. ( )

34. Secondly, the Court revisited the types of variation between the original product and its variant which would permit reference to the variant’s data.

35. It held that an applicant may rely on such data whenever the original product and its variant differ in one of the respects identified in the proviso, namely in their therapeutic indication, route of administration or dose. ( ) The Court explained that:

‘In the light of the proviso, [the variant product] is a development of the original or reference product in the same way as a medicinal product intended for a different therapeutic use from that of the original or reference medicinal product.’ ( )

36. The Court made clear that the criteria explicitly specified in the proviso are not, however, exhaustive of the respects in which the variant product may exceed the parameters of essential similarity with the original product without thereby obtaining an additional period of data exclusivity.

37. Specifically, the Court held that where Products A and B are essentially similar but for their differing bioavailability, an applicant for marketing authorisation for Product C may none the less rely upon the data submitted in respect of Product B. ( ) The Court reasoned as follows:

‘If … the applicant for marketing authorisation for product C may refer to the … documentation in respect of product B, which is … essentially similar [to product A], apart from the route of administration or the dose, … since the differences in those two factors generally imply that products A and B are not bioequivalent … it must, a fortiori, be able to do so where products A and B are distinguishable only by their different bioavailability, even though the route of administration and dose remain unchanged.’ ( )

Subsequent amendments to the Directive

38. Although enacted after the material time, it is useful to consider several amendments to the Directive effected by Directive 2004/27/EC. ( ) Article 1(5) thereof adds the following subparagraph to Article 6(1) of the Directive:

‘When a medicinal product has been granted an initial marketing authorisation in accordance with the first subparagraph, any additional strengths, pharmaceutical forms, administrative routes, presentations, as well as any variations and extensions shall also be granted an authorisation in accordance with the first subparagraph and shall be included in the initial marketing authorisation. All these marketing authorisations shall be considered as belonging to the same global marketing authorisation, in particular for the purpose of the application of Article 10(1).’

39. Article 1(8) of Directive 2004/27/EC replaces the previous text of Article 10 with a new set of provisions. A revised version of the abridged procedure previously laid down in Article 10(1)(a)(iii) is now contained in Article 10(1). The concept of essential similarity has been replaced by a requirement upon applicants to show that their product is a generic of a reference medicinal product which has been authorised for not less than eight years.

40. A generic medicinal product is defined by Article 10(2)(b) to mean ‘a medicinal product which has the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product, and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies’.

41. Article 10(3) of the Directive provides for a variant on the hybrid abridged procedure. It states that:

‘In cases where the medicinal product does not fall within the definition of a generic medicinal product as provided in paragraph 2(b) or where the bioequivalence cannot be demonstrated through bioavailability studies or in case of changes in the active substance(s), therapeutic indications, strength, pharmaceutical form or route of administration, vis-à-vis the reference medicinal product, the results of the appropriate pre-clinical tests or clinical trials shall be provided.’

42. It follows from those amendments that the Directive explicitly now permits the authorisation of a new product which is the generic of (i.e. essentially similar to) a variant of an original product which has been authorised for the requisite period and which differs from the original product in terms of its pharmaceutical form. The data submitted in respect of the variant are to be regarded, pursuant to the second subparagraph of Article 6(1) of the Directive, as forming part of the initial marketing authorisation for the purposes of the application of Article 10(1) of the Directive.

National law

43. In the United Kingdom, the licensing authority established by the Medicines Act 1968 is designated as the competent authority for the purposes of the Directive. It operates administratively through an executive agency of the Department of Health, which at the material time was the Medicines Control Agency (‘the MCA’). The United Kingdom has exercised its option, pursuant to Article 10(1)(a)(iii), to extend the period specified in that provision from 6 to 10 years.

Facts

44. In the present case, Approved Prescription Services Limited (‘APS’), a generic pharmaceutical manufacturer based in the United Kingdom, challenges a decision of the MCA refusing to permit its application for a marketing authorisation to proceed under the abridged procedure which was at that time laid down in Article 10(1)(a)(iii) of the Directive.

45. In October 1999, APS applied to the MCA for a marketing authorisation for fluoxetine liquid 20mg/5ml, which is the generic name for an anti-depressive medication.

46. APS sought to rely on the abridged procedure under Article 10(1)(a)(iii) on the basis that its product was essentially similar to Prozac liquid. Prozac liquid is the proprietary name for a product made by the pharmaceuticals company, Eli Lilly, which contains fluoxetine as its active ingredient.

47. In its application, APS specified the date of first marketing authorisation for its reference product as 25 November 1988. That was the date on which Prozac capsules were authorised in the United Kingdom, the first product containing fluoxetine as its active ingredient to obtain such authorisation.

48. Prozac liquid was first authorised within the Community on 14 October 1992, in Denmark. It obtained authorisation in the United Kingdom on 28 October 1992, following an application by Eli Lilly under the hybrid abridged procedure based on what was later to become Article 10(1)(a)(i) and the proviso. The reference product for that application was Prozac capsules. Eli Lilly had accepted that Prozac liquid was not essentially similar to Prozac capsules, by reason of its different pharmaceutical form, and had provided bridging data to demonstrate that the products were bioequivalent.

49. The MCA considered that APS could not rely upon Prozac liquid as a reference product for the purposes of Article 10(1)(a)(iii) because at the time of APS’ application, it had been authorised for less than 10 years. APS was therefore required to amend its application so as to cite the reference product as Prozac capsules, the first fluoxetine product, which had been authorised for more than 10 years. Because Prozac capsules are not essentially similar to fluoxetine liquid, APS would then need to proceed under the hybrid abridged procedure, and to submit bridging data in the form of a bioequivalence study comparing the two types of product.

National proceedings and questions referred

50. APS has applied to the High Court for judicial review of the MCA’s decision refusing to permit its application for a marketing authorisation for fluoxetine liquid to proceed as an abridged application under Article 10(1)(a)(iii) of the Directive. Citing the Court’s judgment in Generics and the Notice to Applicants, APS argued before the national court that it was entitled to rely upon the data submitted in respect of Prozac liquid.

51. The High Court decided to suspend the proceedings before it and to refer the following question to the Court of Justice:

‘Can an application for a marketing authorisation for a medicinal Product C validly be made under the first paragraph of Article 10(1)(a)(iii) of Directive 2001/83/EC, where the application seeks to demonstrate that Product C is essentially similar to another product, Product B, in circumstances where:

(1) product B is related to an original medicinal Product A, in that Product B has been authorised as a “line extension” of Product A, but has a different pharmaceutical form from Product A or is otherwise not “essentially similar” to Product A within the meaning of Article 10(1)(a)(iii); and

(2) product A has been authorised for marketing in the Community for more than the 6/10 year period stipulated in Article 10(1)(a)(iii); and

(3) product B has been authorised for marketing for less than the 6/10 year period stipulated in Article 10(1)(a)(iii).’

52. The reference made to the first paragraph of Article 10(1)(a)(iii) is presumably intended to make clear that the question relates only to the abridged procedure and not the hybrid abridged procedure laid down in the proviso. It is now clear following the Court’s judgment in Novartis that the proviso did not form part of Article 10(1)(a)(iii) but rather applied to Article 10(1)(a) in its entirety.

53. The Court has received written observations from APS, Eli Lilly, the Danish, French, Netherlands and United Kingdom Governments and from the Commission. APS, the Danish and United Kingdom Governments, and the Commission made oral submissions at the hearing.

Assessment

54. Following the hearing, three distinct positions are apparent from the observations before the Court.

55. First, APS, the Commission, Denmark, France and the Netherlands submit that reference may be made in support of an application for the marketing authorisation of product C, made under the abridged procedure laid down by Article 10(1)(a)(iii), to the data filed in respect of an essentially similar product B, where product B is a new pharmaceutical form of product A, and where product A has been licensed for the requisite period of 6 to 10 years. They therefore propose an affirmative response to the question referred.

56. Secondly, in their written observations, which were submitted before the Court delivered its judgment in Novartis, ( ) Eli Lilly and the United Kingdom Government argue, by contrast, that an applicant seeking authorisation to market product C under Article 10(1)(a)(iii) would need to show the essential similarity of that product to product A (the original product which had been licensed for at least the 6 or 10 year period), as well as product B (a variant or line extension of product A) in order to be able to rely on product B’s data. Under that approach, the question referred would be answered in the negative.

57. Thirdly, at the hearing, the United Kingdom Government modified its position in the light of Novartis. It accepted that reference could be made in support of product C’s application to product B’s data, despite a difference of pharmaceutical form between products A and B. However, it submitted that the application in respect of product C would need to be made under the hybrid abridged procedure laid down in the proviso. It therefore persisted in proposing a negative response to the question referred in the present proceedings, which is framed in terms of the abridged procedure provided for, at the material time, in Article 10(1)(a)(iii).

58. It appears to me that the first position, which is adopted by APS, the Commission, Denmark, France and the Netherlands, is the correct one.

59. It is now clear from the Court’s judgment in Novartis that reference may in certain circumstances be made to data submitted in respect of a variant of an original product, where the original product has been authorised for the stipulated period even though the variant has not been so authorised. ( ) The position taken by Eli Lilly and the United Kingdom in their written submissions can therefore no longer be sustained.

60. Two issues then remain to be considered. The first is whether such reference could be made where the difference between products A and B relates to their pharmaceutical form. The second is whether the application may proceed under Article 10(1)(a)(iii) as APS, the Commission, Denmark, France and the Netherlands contend, or whether it should instead be made under the proviso.

61. All of the parties except Eli Lilly (which has made no further submissions since the Court’s judgment in Novartis) have now affirmed, as regards the former issue, that reference may be made in support of product C’s application to product B’s data in circumstances where products A and B differ in their pharmaceutical form.

62. For several reasons, that conclusion appears to me correct.

63. First, it is not clear whether there is any difference between pharmaceutical form and dosage form, which is specifically identified in the Generics judgment as one of the types of variation which is insufficient to merit an additional period of data exclusivity. ( ) Eli Lilly and the Commission both suggest that dosage form is the arcane terminology for pharmaceutical form. The Notice to Applicants makes the same claim. ( ) It is therefore arguable that the question at issue has already been settled by the Court in Generics. The Court’s reference in that case to the need for essential similarity to be shown must be read, in the light of Novartis, as requiring only essential similarity as between products B and C rather than products A and B.

64. Secondly, and in any event, following Novartis, ( ) it is clear that the categories of difference expressly identified in the proviso are not the only ones which may separate products A and B without excluding the possibility of an applicant in respect of product C relying upon product B’s data.

65. The Court in Novartis specifically confirmed that reference to product B’s data is permissible when products A and B are not bioequivalent, even if the difference in bioavailability is not as a consequence of one of the changes identified in the proviso. ( )

66. The Court reasoned that if an applicant is entitled to refer to data in respect of a variant product which differs from the original or reference product in its route of administration or dose, since the differences in those factors generally imply that products A and B are not bioequivalent, it must, a fortiori, be able to do so where the original and the variant product are distinguishable only by their different bioavailability, even though the route of administration remains the same. ( )

67. It seems to me that, as APS submitted at the hearing, the same argument can be applied by analogy to a change in pharmaceutical form. A change in the route of administration amounts to a development of the original or reference product so that the data submitted in respect of such a variation may be relied upon by a new applicant referencing the original product. Such a change will normally also entail a change of pharmaceutical form. Thus, in accordance with the Court’s reasoning in Novartis, an applicant must, a fortiori, be able to refer to data in respect of product B where products A and B are distinguishable only by their different pharmaceutical forms, even though the route of administration remains the same.

68. Thirdly, several of the parties submit that whether a product resulting from the development of the reference medicinal product differs in terms of pharmaceutical form does not necessarily bear any relationship to the cost or difficulty involved in that development. The Court in Novartis found that factor to be relevant when concluding that essential similarity was not always necessary between products A and B in order for reliance to be placed on product B’s data. ( )

69. Finally, the Notice to Applicants identifies pharmaceutical form as one of the types of variation which may exist between an original product and what it terms a ‘reference product’ or ‘line extension’ of the original product. It states that such a product may be used by an applicant to claim essential similarity even though it has been authorised for less than 6 or 10 years, provided that the original product has been authorised for at least that period.

70. It is undoubtedly the case that the Notice to Applicants lacks legal force in the sense that it is not in itself legally binding. Nor could it be used to support a position which was clearly at odds with the Directive. In my view, however, it must be accorded some weight when interpreting the Directive.

71. In a technically complex field, it seems reasonable to give careful consideration to a document which represents the harmonised views of the Commission and the competent authorities of the Member States as to how the Community legislation might workably be put into effect. The Directive itself requires that applications be presented in a way which takes account of the Notice. ( )

72. Moreover, the Court has emphasised the importance of ensuring a uniform administration of the marketing authorisation regime across the Member States. ( ) The Notice to Applicants has an obvious and important role to play in that regard.

73. It is therefore unsurprising that the Court has on several occasions in the past had regard to the Notice to Applicants when interpreting the Directive. ( )

74. The only remaining issue to be addressed is whether it is necessary (as the United Kingdom considers) for an applicant wishing to refer to product B’s data to proceed under the proviso or whether (as APS, the Commission, Denmark, France and the Netherlands contend) the application may be made under the abridged procedure specified in Article 10(1)(a)(iii).

75. It would appear that the issue is purely procedural in nature. I do not take the United Kingdom Government to be suggesting that any more data would be required of applicants seeking to rely upon the essential similarity of their product to product B if they were made to proceed under the proviso. The issue is rather one of form.

76. The United Kingdom bases its assertion that the proviso is the appropriate procedure upon its reading of the Court’s judgment in Novartis.

77. It is true that in Novartis, the application to which the main proceedings related had been made under the hybrid abridged procedure. ( ) It is also true that in the relevant passages of the judgment, the Court does incorporate the proviso in its reasoning. ( )

78. However, the Court’s reasoning in Novartis in relation to the first two questions cannot in my view be read as confined to the proviso.

79. It is to be noted that the first two questions referred to the Court in Novartis did not mention the proviso, but were framed instead in terms of the provision which later became Article 10(1)(a)(iii).

80. Moreover, in its discussion of those questions, the Court referred to the proviso only as a basis for identifying categories of difference between products A and B which would allow product B legitimately to be considered as a development of product A.

81. Its analysis involved instead an interpretation of the meaning of medicinal product, as that term appeared in Article 10(1)(a)(iii). The Court concluded that variants of a medicinal product differing in the various respects identified are not sufficiently distinct from that product for them to be considered as entirely new products, so as to qualify for their own additional period of data exclusivity. ( )

82. There is thus nothing in the Court’s analysis in Novartis which suggests that it applies only to applications made pursuant to the proviso.

83. Indeed, there are good reasons against requiring an application in respect of product C to proceed under the proviso. The proviso operates in circumstances where bridging data are required because of a difference between the new product and the earlier product or products to whose data reference is made. Where product C claims essential similarity to product B which is a variant of product A, no additional data are required. There is therefore no need to proceed under the proviso.

84. The Court’s interpretation of Article 10(1)(a)(iii) is to my mind entirely in accordance with the text of that provision. An applicant is still required to show both essential similarity to one or another form of the reference product and that the product in question has been authorised within the Community for not less than 6 or 10 years.

85. Article 10(1)(a)(iii) nowhere states that the data to which reference is made in support of an application must have been submitted to an authority at least 6 or 10 years previously. Rather, it is the product which must have been authorised for at least that period.

86. I note that the approach which I have adopted here arrives at a result which is now explicitly required under the Directive as recently amended. ( ) Clearly, earlier versions of the Directive fall to be interpreted independently of such subsequent developments. None the less, I am reassured by the fact that the interpretation of the previously operative provisions which I have proposed has recently been explicitly revalidated by the Community legislature.

87. For all of the reasons set out above, I am therefore of the view that an applicant seeking the authorisation of product C should be permitted to make reference under Article 10(1)(a)(iii) to data submitted in support of an essentially similar product B which is a development of another product A, which has been licensed for the requisite period but which differs from product A in its pharmaceutical form.

Conclusion

88. It is therefore my opinion that the question referred for a preliminary ruling by the High Court of England and Wales (Queen’s Bench Division) should be answered as follows:

An application for the marketing authorisation for a medicinal product C may be made under Article 10(1)(a)(iii) of Directive 2001/83/EC, without the need to submit any additional data under the final paragraph of Article 10(1)(a), where the application seeks to demonstrate that its new product (product C) is essentially similar to another product (product B) in circumstances where:

– product B is a new pharmaceutical form of another product (product A) although not essentially similar to product A within the meaning of Article 10(1)(a)(iii); and

– product A, but not product B, has been authorised for marketing in the Community for at least the 6 or 10 year period stipulated in Article 10(1)(a)(iii).