Judgment — ECLI:EU:C:1999:614
Date: 1999-12-16
Language of the case: English
Court formation: Full Court
Based on: Treaty establishing the European Economic Community (1957)
Subject matter: Free movement of goods;Measures having equivalent effect;Approximation of laws;Quantitative restrictions
Concepts: Proprietary medicinal products
Procedure: Reference for a preliminary ruling
Origin: United Kingdom

summary of the dossier, (ii) chemical,pharmaceutical and biological tests of the medicinal products, (iii) toxicological andpharmacological tests, and (iv) clinical documentation. The application mustcontain all the information necessary to assess the product in question, includingany unfavourable information. Moreover, in order to monitor the positive andnegative effects after issue of the MA, the holder must notify the competentauthorities of all changes in data, new information not contained in the initialapplication and pharmacovigilance reports (see below, footnote 25 and relevantpart of text). 4. The competent authority may refuse to grant an MA only if, after examiningthe application, it determines that: (a) the information and documents supplied bythe applicant are irregular or incomplete, (b) the product is harmful under normalconditions of use, (c) its therapeutic efficacy is lacking or has not been sufficientlysubstantiated by the applicant, or (d) the qualitative and quantitative compositionof the product is not as declared (see Articles 5 and 21 of the Directive). An MA,which is valid for five years, may be renewed for like periods on application by theholder at least three months before expiry (Article 10, first paragraph). As Article9 of the Directive states, the grant of an MA does not affect the civil and criminalliability of the manufacturer and, where applicable, of the person responsible forplacing the product on the market. 5. Article 11 (in conjunction with Article 21) of the Directive goes on to saythat an MA may be suspended or revoked on the following grounds only: (a) theproduct proves to be harmful in normal conditions of use or (b) its therapeuticefficacy is lacking or (c) its qualitative and quantitative composition is not asdeclared by the applicant, (d) the information in the file is incorrect or has notbeen amended in accordance with Article 9a (concerning changes to methods ofpreparation and control to bring them into line with scientific and technicalprogress) or (e) checks have not been carried out on the ingredients, intermediateproducts and finished products in accordance with the methods described by theapplicant. As outlined in greater detail below (see point 10), the present case is concernedwith a measure ordering the revocation of an MA for a medicinal product. Thiscase, however, displays the peculiar feature that the revocation was ordered by thecompetent national authority in response to a request from the holder of the MA,purporting to be based on pressing reasons of protection of public health. Morespecifically, the issue in the main proceedings is whether and to what extentrevocation of the original MA may affect the freedom of economic operatorsoutside the official distribution channels of the holder of the MA to carry outparallel imports of a different variant of the product from other Member Stateswhere it is sold at lower prices than those charged in the importing country. 6. As this Court held in De Peijper, the freedom to undertake parallel importsof products properly placed on the market is recognised in Community law,notwithstanding the operation in the Member States of MA systems whose effectsare limited to national territory. According to the Court, the fact that parallelimporters quite often offer the goods at a price lower than that charged by the dulyappointed importer 'should ... encourage the public health authorities not to placeparallel imports at a disadvantage, since the effective protection of health and lifeof humans also demands that medicinal preparations should be sold at reasonableprices. (8) According to that judgment, it must be borne in mind that, in the sphere of free movement of medicinal products, the requirement of protecting publichealth has two aspects. First, it may justify application to the national MA systems,involving State measures equivalent to quantitative restrictions on imports, of thederogation provided for in Article 36 of the EC Treaty (which now, afteramendment, Article 30 EC) (9) from the prohibition of imposing such measures laiddown in Article 30 of the EC Treaty (now, after amendment, Article 28 EC). Secondly, where it is necessary to verify whether the requirements for thatderogation are fulfilled, including the requirement that any harm done by thenational measure restricting intra-Community trade is the minimum called for bythe general interest in protecting human health, it must be borne in mind that thatinterest can be effectively pursued by the Member States precisely by safeguardingthe freedom of economic operators to compete vigorously on prices thanks toparallel imports. 7. In De Peijper, the Rotterdam Kantonrechter (district public prosecutor) hadcommenced criminal proceedings for infringement of Netherlands health legislationagainst an unauthorised importer of certain medicinal products, who was operatingwithout having in his possession the file (concerning the medicinal product in theabstract) and the so-called 'records (relating to checks of individual batches ofimported goods) for the products in question. The accused, a director of acompany which had acquired the medicinal products from a British wholesaler,contended in his defence that he had not been able to obtain the documentsprescribed by the Netherlands legislation either from the manufacturer or from thelatter's exclusive concessionaire in the Netherlands. (10) In answer to the two questions on which the Kantonrechter, Rotterdam, sought a preliminary ruling, (11)the Court held, first of all, that Article 30 of the EC Treaty (now, after amendment,Article 28 EC) precludes national legislation or practice which results in thechannelling of imports in favour of only certain economic operators. The Courtthen interpreted Article 36 of the Treaty (now, after amendment, Article 30 EC)to the effect that it 'cannot be relied on to justify [national] rules or practiceswhich, even though they are beneficial, contain restrictions which are explainedprimarily by a concern to lighten the administration's burden or reduce publicexpenditure, unless, in the absence of the said rules or practices, this burden orexpenditure clearly would exceed the limits of what can reasonably be required. (12)In the circumstances described in the first question from the Netherlands Court(see footnote 10), the Court said, the principle of proportionality was infringed bylegislation or practice which made the grant of an MA for medicinal productssubject to the condition that the parallel importer must supply to the competentauthority in the Member State of importation documents identical to those alreadylodged by the manufacturer or its exclusive concessionaire; in such circumstances,the latter would be allowed to monopolise imports and marketing of the medicinalproduct in question by refusing to produce documents relating to the product ingeneral or to a particular batch. A national measure like the one at issue could,on the other hand, qualify for the derogation provided for in Article 36 of the ECTreaty (now, after amendment, Article 30 EC) where it was clear that any othermeasure would impose a clearly greater than normal burden on the national administration. (13) Finally, as is apparent from paragraph 3 of the operative partof the judgment in De Peijper, the principles mentioned there apply to each of theprocedures for authorisation which theoretically become necessary where it is clearfrom the documents deposited by the manufacturer or its exclusive representativein support of the application for the MA that: (i) that several variants of a uniformmedicinal product are produced and marketed under the same name in more thanone Member State and that (ii) the differences between the variants, regarding themanufacturing process or the qualitative and quantitative composition of theproduct in question, have an impact on its therapeutic effect. Only in suchcircumstances, according to the Court, would there be 'any justification for treatingthe variants as different medicinal preparations, for the purpose of authorisingthem to be placed on the market and as regards producing the relevantdocuments. (14) 8. Following the judgment in De Peijper, the Commission considered itappropriate to submit to the Council a proposal for a directive on parallel importsof proprietary medicinal preparations. (15) However, considering approval of thedocument by the Council to be 'improbable, in particular following objectionsfrom the Economic and Social Committee and the vote against it of 16 October1981 by the European Parliament, the Commission subsequently decided towithdraw that proposal. The principles inspiring the document were nevertheless published in the form of guidelines for Member States and the relevant economicoperators. (16) I think it is relevant to consider that Commission initiative at thisstage because, as is stated in the order for reference, great inspiration was drawnfrom that communication in 1984 by the Medicines Control Agency ('MCA) that is to say, the executive agency vested with the regulatory powers of theLicensing Authority set up by the Medicines Act 1968  when it in turn adoptedguidelines concerning the procedures to be observed when applying for MAs forparallel imports of medicinal preparations into the United Kingdom. (17) 9. MAL 2 (PI) defines 'parallel imports as meeting two requirements: theproduct is the subject of an MA in the United Kingdom and the applicant seeksto import from another Member State a version of that product which already hasan MA issued by another Member State. In such cases, the MCA follows asimplified procedure, which is generally more expeditious than that provided for bythe Directive, under which the applicant for an MA for parallel imports ofmedicinal products (known as the Product Licence (Parallel Import), hereinafter'PL (PI)) is required to provide less extensive information than is required for anapplication in accordance with the Directive. To qualify for that procedure, themedicinal product must satisfy several conditions, in particular it must have beenmade by or under licence to the manufacturer who made the product covered bythe United Kingdom MA or a member of the same group of companies. (18) 10. This Court delivered another important judgment concerning parallelimports of medicinal products in 1996, a little more than 20 years after De Peijper. The High Court of Justice (the court from which today's questions emanate) hadasked the Court of Justice to provide the requisite guidance for interpretation ofthe Directive, and of the obligations associated with MAs for medicinalpreparations, in order to determine disputes between Smith & NephewPharmaceuticals ('S&N) and the MCA and the competing company Primecrown,and secondly, between Primecrown and the MCA. (19) Those disputes arose fromthe grant in August 1993 of a PL(PI) to Primecrown for a medicinal productmanufactured in Belgium, where it was covered by an MA. The product of Belgianorigin had the same name and was manufactured under a licensing agreementconcluded with the same licensor for a product for which S&N had held a UnitedKingdom MA since January 1991. (20) Because the PL(PI) had been granted toPrimecrown on the false assumption that there existed between S&N and MarionMerrel Dow Belgium the corporate link required for application of the simplifiedprocedure (see above, footnote 17 and relevant part of the text), the licence wassubsequently annulled by the MCA after it discovered the error. The Court held,first, that the obligation of an applicant for an MA to produce the necessaryinformation and documents prescribed by the Directive in order to verify that amedicinal product is effective and harmless is justified only for medicinal productswhich are being put on the market for the first time. That obligation cannot,however, be relied on by the competent authority of a Member State in order toprotect public health in relation to a medicinal product already covered by an MAin another Member State and of which the import into the first country constitutesa parallel import of a product already covered by another MA. (21) According to theCourt, therefore, in a case such as this one  in which the medicinal productmanufactured in the importing State and the one brought in as a parallel import,even though manufactured under licence by independent companies, ultimatelyoriginated from the same licensor  the rule in De Peijper should apply (see point 7 above) otherwise such agreements could lead to partitioning of the nationalmarkets of the various Member States. (22) That case-law, said the Court inparagraph 26 of the judgment, is applicable not only where the proprietarymedicinal product covered by an original MA in the importing State and the onebrought in as a parallel import are identical in all respects, but also where the twomedicinal products 'have at least been manufactured according to the sameformulation, using the same active ingredients and ... have the same therapeuticeffects. Consequently, the Court concluded that the competent authority of aMember State  if it concludes that a medicinal product covered by an MA inanother Member State and a medicinal product for which it has already issued anMA, manufactured by independent companies under agreements with the samelicensor, although not identical in every respect, are at least manufactured inaccordance with the same formulation and using the same active ingredients andhaving the same therapeutic effects  must extend the benefit of that MA to theimported product. That obligation becomes inoperative only if there are reasonsrelating to effective protection of human life and health. Where, on the otherhand, the competent national authority reaches the conclusion that the medicinalproduct intended to be imported on a parallel basis does not satisfy the criteriamentioned here  and cannot, therefore, be regarded as already on the market inthe importing Member State  a new MA will become necessary, which may begranted only in accordance with the conditions laid down in Articles 3 and 4 of theDirective. (23) 11. That is the context, in terms of legislation and case-law, of the questionsreferred in this case. I shall now consider the facts giving rise to the mainproceedings, as described by the national court. In 1989 and 1993 the MCAgranted May & Baker ('M&B) a total of five marketing authorisations for theUnited Kingdom (24) for zopiclone, a hypnotic used for the short-term treatment ofinsomnia, marketed in most of the Member States under the brand name Imovaneand in the United Kingdom the name Zimovane. Under an agreement concludedin 1992, M&B appointed Rhône-Poulenc Rorer (the two companies beinghereinafter jointly referred to as 'RPR) as its agent for the production anddistribution of certain medicinal products, including Zimovane. In 1996 RPR improved, following research and development for more than three years, costingaround UKL 1 500 000, a new version of Zimovane which is particularly beneficialfor public health, described in the confidential annex to the order for reference('the confidential annex). The 'new Zimovane contains the same activeingredient and has the same therapeutic effect as the 'old Zimovane but isprepared by a different production process using different excipients (an excipientis a inert substance used as a diluent or vehicle for a pharmaceutical product). Inorder to place the new version of the product on the market in the UnitedKingdom, in July 1996 RPR, after providing the information and documentsprescribed by the Directive, obtained variations to two authorisations (numbers0012/0259 and 0012/0260) which had not yet been used. At the request of RPR,the MCA also revoked MA number 0012/0162 on the basis of which the old versionof Zimovane had been distributed in the United Kingdom, and of (unused)authorisations numbers 0012/0163 and 0012/0164. Thus, as from 1 August 1996,RPR ceased to market, directly or under licence, the old version of Zimovane inthe United Kingdom and distributes only the new version, in the form of 3.75 mgor 7.5 mg tablets. The old version of Zimovane nevertheless continues to bedistributed in the other Member States (with the exception of Portugal). However,it is RPR's intention to replace the old version by the new version of the medicinalproduct, as it had done in the United Kingdom, in step with the issue of marketingauthorisations by the competent authorities in the Member States. (25) RPRconsiders that it would be committing a criminal offence if it distributed the newversion of Zimovane on the basis of authorisations for the old version or if itmarketed the old version of Zimovane on the basis of the MA for the new product. 12. In accordance with paragraph 12 of MAL 2 (PI) (see footnote 17 above),seven authorisations for parallel imports of the old version of Zimovane into theUnited Kingdom, which had previously been granted to five operators, becameinvalid as from 31 July 1996 as a result of revocation of the 'mother authorisation,directed by the MCA at the request of RPR (see point 11 above). Upon beingnotified by the MCA (in accordance with paragraph 21 of MAL 2 (PI)), the holdersof the authorisations in question therefore applied for the variations needed to'anchor them to a valid reference MA, specifically MA number 0012/0259. TheMCA decision to grant or maintain in force, under the abridged procedure, theseven authorisations for the old version of Zimovane (in 7.5 mg tablets) is one ofthe two measures challenged by RPR in the main proceedings. The secondmeasure contested by RPR is the MCA's decision to grant to each of three otheroperators, again under the MAL 2 (PI) procedure, an authorisation for parallelimports of the old version of Zimovane (in 7.5 mg tablets) into the UnitedKingdom from Spain. 13. According to the High Court of Justice, a preliminary ruling is needed onthe following questions in order to give judgment in the main proceedings: '1. In a case where medicinal product X is sought to be imported fromMember State A into Member State B, is it permissible for the person whoproposes to place the imported product upon the market in Member StateB to seek and obtain a marketing authorisation from the competentauthority in Member State B without complying with the requirements ofthe Council Directive 65/65/EEC (as amended) if: (i) medicinal product X is the subject of a marketing authorisationgranted in Member State A and was the subject of a marketingauthorisation which has ceased to have effect in Member State B; and (ii) medicinal product X has the same active ingredients and therapeuticeffect as medicinal product Y, but is not manufactured according tothe same formulation as medicinal product Y; and (iii) medicinal product Y is the subject of a marketing authorisationgranted in Member State B, but is not the subject of a marketingauthorisation granted in Member State A; and (iv) the marketing authorisations referred to in (i) and (iii) above weregranted to different members of the same group of companies and themanufacturers of medicinal products X and Y are also members ofthat group of companies; and (v) companies within the same group as the holder of the marketingauthorisation for product X continue to manufacture and marketproduct X in Member States other than Member State B? 2. To what extent is it relevant to the answer to Question 1 that: (i) the marketing authorisation for medicinal product X ceased to haveeffect in Member State B as a result of voluntary surrender on thepart of the person to whom it had been granted; and/or (ii) the formulation of medicinal product Y was developed and introducedin order to provide a benefit to public health which medicinal productX (manufactured according to a different formulation) does notprovide; and/or (iii) that benefit to public health would not be achieved if product X andproduct Y are both on the market in Member State B at the sametime; and/or (iv) the differences between the formulations of medicinal product X andmedicinal product Y are such that neither product may lawfully bemarketed under the marketing authorisation applicable to the other;and/or (v) the competent authority possesses the relevant data required underDirective 65/65 in relation to both product X and product Y; and/or (vi) the competent authority considers that the prohibition on imports ofproduct X from Member State A would have the effect of partitioningthe market; and/or (vii) the competent authority considers that there are no grounds withinArticle 36 of the EC Treaty [now, after amendment, Article 30 EC]which would justify a prohibition on imports and sales of product X? II  The submissions of the parties to the main proceedings and the observationsof the Member States and the Commission 14. RPR states that the Community provisions on parallel imports of medicinalproducts apply only if the product in question is covered by valid authorisations inboth the exporting and importing Member States. According to RPR, recourse tothe MAL 2 (PI) procedure for the purpose of authorising imports into the UnitedKingdom of the old version of Zimovane after 31 July 1996 was unlawful. First, the'mother MA for the old version of the product was revoked and, second, therequirement of 'manufacture according to the same formulation was likewise notsatisfied, that criterion having been established by the Court in Smith & Nephew,with the result that an imported medicinal product may not qualify for thesimplified procedure on the basis of an original MA issued for a similar product bythe competent authority in the importing Member State. RPR maintains that theold and new versions of Zimovane are not manufactured in accordance with thesame formulation. That term should in its view be construed as a synonym of'recipe and includes both the active ingredients and the excipient. Therefore, theMCA should have required the parallel importers to produce a complete dossier,in accordance with the procedure provided for and governed by the Directive. 15. RPR adds that its decision to distribute only the new version of Zimovanein the United Kingdom and surrender the marketing authorisations for the oldversion had neither the object nor the effect of artificially partitioning the domesticmarket. Precedence was given to introduction of the new version of Zimovane inthe United Kingdom because it was necessary to achieve first of all in that MemberState the public health benefit described in the confidential annex. That benefitcould not, however, be achieved if both the old and the new versions of the producthad been available on the British market. 16. According to the United Kingdom, in the circumstances of this case the MCAis required, pursuant to Article 30 of the EC Treaty (now, after amendment, Article28 EC), to allow parallel imports of the old version of Zimovane into the UnitedKingdom market to continue. There is no reason to regard the two versions asdifferent medicinal products, with the result that it would be necessary for theparallel importers of the old version of Zimovane to obtain an MA under theDirective, if indeed that were actually possible (regard being had to theunsurmountable difficulties presented by the chemical, pharmaceutical andbiological tests prescribed by the Directive). The old and the new medicinalproducts, manufactured by the same group of companies, are from thetherapeutical point of view, under normal conditions of use, equivalent versions ofa product having a common origin and the same active ingredient (zopiclone). Achange to the excipients in a medicinal product is in general neutral as regards itstherapeutic effect. Although conceding that the plaintiffs have not consciouslysought to isolate the United Kingdom market from the remainder of theCommunity, the United Kingdom authorities submit that voluntary withdrawal ofthe MA for the old version of Zimovane would result in such fragmentation, ifRPRs arguments were to be upheld. 17. The United Kingdom submits, finally, that the general interest in theprotection of public health, even if construed in the manner contended for by RPRand described in the confidential annex, does not call for a drastic measure suchas the total blocking of parallel imports of the old version of the product. Notwithstanding the formal revocation of the 'mother authorisation, the MCA stillhas at its disposal all the data, documents and details prescribed by Article 4 of theDirective to monitor the efficacy and harmlessness of the medicinal productintended to be the subject of parallel imports. The MCA states that it receivedthem from RPR in connection with the procedure for the issue of an MA for thenew version of the product in question, which contains the same active ingredientsand has the same therapeutic effects. 18. France and the Commission have submitted to the Court argumentssubstantially similar to those of RPR. The Commission maintains in particular thatthe claim that the MCA had relevant information at its disposal for both variantsof Zimovane (see point 17 above), although true when the MAs for the old versionwere surrendered, has ceased to be true with the passage of time. As from 1August 1996 RPR is no longer required to submit to the MCA, periodically orwhen applying for renewal of an MA, the information concerning the old versionof Zimovane required by the provisions on pharmacovigilance (see Article 29d of Directive 79/319/EEC and Article 10 of Directive 65/65/EEC). (26) Thoseobligations moreover do not apply to parallel importers either, regardless ofwhether those economic operators actually possess the relevant data. TheCommission therefore submits that the MCA is no longer in a position to assess thesafety of the version of the medicinal product imported into the United Kingdomon the basis of the most up-to-date scientific data. The United Kingdomauthorities contend that compliance with the pharmaceutical monitoringrequirements mentioned by the Commission could be ensured (i) by virtue ofRPR's obligation to provide up-to-date information regarding the new version ofZimovane or (ii) even if it were conceded that the two variants of the medicinalproduct constituted different products, by means of cooperation with the othernational authorities in accordance with the criterion laid down by the Court inparagraph 27 of the De Peijper judgment, through access to the documents and dataproduced by RPR or other companies in its group for the old version in theMember States in which it is still being marketed on the basis of a valid marketingauthorisation. III  Legal Analysis 19. This case, in my opinion, displays an important and unusual feature whichdistinguishes it both from the two earlier ones already referred to several times andfrom almost all the cases in which the Court is called on to interpret the Treatyprovisions on the free movement of goods. In this case a State administration isarguing that a particular measure invoked by an economic operator is, in thecircumstances of the case, contrary to Article 30 in that it unduly restricts parallelimports. That measure is the decision requiring an application to be submitted inaccordance with the Directive as a precondition for the issue of an authorisationto effect parallel imports of a medicinal product for which no 'mother MA existsany longer in the importing Member State. The other party contends, for its part, that the adoption of the measure in question is required in order to protect publichealth, on the basis of Article 36 of the EC Treaty (now, after amendment, Article30 EC). In addition, the analysis of today's preliminary questions cannot overlookthe specific nature of medicinal products, (27) by reason of which, as I have severaltimes observed, the freedom of movement guaranteed by the Treaty does not applyunconditionally to those goods. Indeed, as is clear from the case-law of the Court,'Member States are entitled, at the present stage of harmonisation and in theabsence of a procedure for Community authorisation or mutual recognition ofnational authorisations, to prohibit entirely the marketing of medicinal productswhich have not been authorised by the competent national authorities (28) (29) TheCourt's explanation for that finding was that it is the responsibility of the MemberStates, within the limits imposed by the Treaty, to decide what level of protectionof the health and life of humans they intend to ensure and to impose safeguardsof varying severity for that purpose. (30) The exclusive legislative power of theMember States extends, on the other hand  again subject to compliance with thefundamental principles of the Community legal order and having regard to theobjectives pursued by the Directive  to MAs for parallel imports of medicinalproducts. And the latter field has likewise not been the subject of harmonisation. 20. That said, I think it is appropriate first of all to consider whether or notvoluntary surrender of a currently valid MA by its holder can be regarded as beingin conformity with the system established by the Directive. Essentially, that is nota point at issue in the main proceedings but the High Court referred to it in itssecond question (in subparagraph (i)  see point 13 above), asking whether thatfact was relevant to the answer to be given to the first question. The doubt raisedis legitimate in view of the wording of the abovementioned Article 21 of theDirective, according to which '[a]n authorisation to market a proprietary medicinalproduct shall not be refused, suspended or revoked except on the grounds set outin this Directive (emphasis added; see points 4 and 5 above). The Commission,however, correctly observed that one of the fundamental principles of Communitypharmaceutical legislation, to which the concept of compulsory licensing is entirelyalien, is that the applicant is master throughout the procedure leading to the issueof an MA. The applicant is therefore entirely free to decide if and when to lodgean application, to withdraw an application before adoption of the final decision,and whether or not to apply for renewal of an authorisation that has expired (see Article 10 of the Directive). I do not therefore see how it can be contended thatthe holder is precluded from surrendering an MA which is still valid, that is to sayrelinquishing the benefit of a measure that is favourable to him and was grantedprimarily in his interests. I consider, therefore, that Article 21 is to be interpretedas relating only to cases of revocation in the strict sense, effected by the competentnational authority against the wishes of the holder. 21. In that light, the interpretation requested by the High Court to enable it togive judgment is concerned essentially with the question whether, in circumstanceslike those of this case, the absence of significant differences in therapeutic efficacybetween the old and new versions of the medicinal product is sufficient to relieveparallel importers of the obligation to provide the competent national authoritywith all the information prescribed by Article 4 of the Directive for monitoring theefficacy and harmlessness of the product in question, despite the fact that there isno valid 'mother MA for the old version in the importing Member State. TheUnited Kingdom authorities consider that to be the case: and they take that view as they made clear at the hearing  regardless of the fact that the old version ofZimovane was previously covered by an MA of United Kingdom origin which is nowinoperative. All that is important, they submit, is that the data, documents anddetails provided by RPR under the Directive in connection with the procedure forissue of the MA for the new version of Zimovane do not differ from those relatingto the old version, which is intended to be the subject of parallel imports. (31) Besides, under paragraph 4(d) of the MAL 2 (PI), it is sufficient that the productto be imported by way of parallel import does not display differences which have animpact on the therapeutic effect as compared with a product covered by an originalMA for the United Kingdom (see footnote 17 above). The United Kingdomsubmits that the position described here conforms with the rules for classifyingdifferent variants of a product as different medicinal products for the purposes ofthe marketing authorisation, which this Court laid down for the first time in DePeijper (see footnote 12 above and the relevant part of the text) and later referredto in paragraph 22 of Smith & Nephew. According to the United Kingdom, inaddition the threefold rule laid down by the Court in Smith & Nephew should beinterpreted as placing the emphasis on the active ingredient of the medicinalpreparation. If on the other hand the rule in question were to be applied literallyto every minor change in the formulation of a medicinal product, even those havingno impact on its therapeutic effects, it could lawfully achieve the result of stoppingparallel imports of the earlier version of the product. Moreover, according to theUnited Kingdom authorities, in Smith & Nephew the Court did not intend to lay down a rule that was universally applicable to all parallel imports but merelyapplied to the facts of that case the principles established in De Peijper. Therefore,the rule referred to is applicable only where the medicinal product brought in byway of parallel import and the product covered by an MA in the importingMember State are not manufactured by companies in the same group. 22. The objections raised are of some merit and substance. They bring to lightthe fundamental difference between a 'De Peijper type situation (product of thesame name produced by a single group of companies in several Member States, withnational variants containing different excipients) and a 'Smith & Nephew situation(product of the same name produced in several Member States under licence froma single producer, by manufacturers that are independent from each other, withnational variants containing different excipients) and the effects which areassociated with that diversity from the legal point of view. In the first case it islegitimate to ask  as Advocate General Mayras did in the past  'what interest amanufacturer of pharmaceutical products can have in manufacturing in differentforms a medicinal preparation intended to be marketed under the same name indifferent countries and which, looked at purely from the point of view ofrationalising production and costs, should be composed, prepared and checked inexactly the same way. There is no doubt that some of these different forms maybe obligatory under specific national health rules. But even allowing for theserules, the question often remains unanswered, unless the view is taken that thedifferences in question were introduced for purely commercial reasons with a viewto dividing up the market and taking advantage of a profitable situation. I believethat in De Peijper Advocate General Mayras was suggesting to the Court, for thereasons set out here, that it should presume that any differences of formulationbetween the products in question, having, objectively, no therapeutic importance,can be accounted for only by an intention on the part of the manufacturer toisolate individual markets. (32) As the Court went on to say, those differencescannot therefore be regarded as relevant in determining whether or not the variantintended to be the subject of parallel imports has already been marketed in theimporting Member State. Whilst pointing out that the solution of having therequirements of the free movement of goods take precedence over those of publichealth is a little dangerous, Advocate General Mayras took that view that incircumstances like those of De Peijper  having regard to the strong temptationfacing manufacturers to exploit differing legislation in order to make huge profitsand isolate markets  that solution involves a minor risk worth running. (33) Thatsolution is clearly based on the proposition  which I think reflects the technicaland scientific thinking of the time  that the fact that two medicinal products have the same therapeutic effect in itself implies that they are also the same as far asmonitoring users' safety is concerned. 23. In its judgment in Smith & Nephew, however, the Court took the view, if Iam not mistaken, that it is wholly legitimate for individual national licensees notlinked by membership of the same group of companies to decide to manufacturemedicinal products under licence according to different specifications, in particularas regards the excipients employed, without it being possible to attribute that fact,even merely by way of presumption, to a concerted intent to isolate the nationalmarkets. It should be remembered that S&N had been required to carry outadditional clinical studies and to change the formulation (more precisely, theexcipients used) of the Ditropan manufactured in the United Kingdom ascompared with that produced in the United States by the licensor company, MarionMerrel Dow (and in Belgium by one of its subsidiaries), in view of the need toprove to the MCA that the product was not potentially carcinogenic. (34) 24. The Smith & Nephew judgment also recognised, at least by implication, thateven where the differences of formulation as between the variants of a product arenot reflected by differences in their respective therapeutic effects, those differencesstill fall within the range of factors of which the competent authority (subject toreview by the national courts) must take into account when monitoring, the quality,safety and efficacy of the variants in question for the purpose of classifying themas similar or different medicinal products with a view to authorising theirmarketing. (35) As stated by the plaintiffs in the main proceedings, France and theCommission, the principle that the competent authority is required to take accountnot only of the therapeutic efficacy but also of the composition in terms of activeingredients and excipients of the various versions of a given medicinal product canbe inferred from numerous pieces of legislation. I have already stated that thecompetent national authorities are required to examine applications forauthorisation on the basis of the protocols described in the abovementioned annexto Directive 75/318 (footnote 6 above and the relevant part of the text). Pursuantto those protocols, the qualitative particulars of all the constituents of the proprietarymedicinal product  which an applicant for an MA must supply in accordance withpoint 3 of the second paragraph of Article 4 of the Directive  consist in thedesignation or description not only of the active ingredients and of the constituentsof the pharmaceutical form to be administered to the patient but also of theconstituents of the excipients, whatever their nature or the quantity used (includingcolouring matter, preservatives, stabilizers, thickeners, emulsifiers, flavouring and aromatic substances). The constituents of the excipient of which details are neededfor proper administration of the medicinal product also form part  again in thecontext of qualitative and quantitative composition  of the summary of productcharacteristics which must be supplied by an applicant for an MA (see point 9 ofthe second paragraph of Article 4 of the Directive). (36) The person concerned isalso required to explain the function envisaged for the excipients in the finishedproduct, at the same time providing scientific data relating to medical development. Also, in the context of the description of the method of preparation  which mustaccompany the application under point 4 of the second paragraph of Article 4  theactual manufacturing formulation must give a quantitative breakdown of all thesubstances used, including the excipients (although for the latter approximate termsmay be used 'in so far as the pharmaceutical form makes this necessary). Moreover, the identification and dosage of the excipient constituents are part of theinformation relating to controls carried out on the finished product which theapplicant is required to provide under point 7 of the second paragraph of Article4 of the Directive. (37) The introductory part of the annex to Directive 75/318 also provides that, inassembling the dossier, applicants must take into account the Community guidelinesrelating to the quality, safety and efficacy of medicinal products published by theCommission in its guide to the rules on medicinal products in the European Union. From both the Commissions observations and from the latest edition of that guide, (38)it is apparent that changes to the formulation of a medicinal product affectingexcipients can affect the shelf-life and bio-availability of the product; (39) moreover, the excipients can raise safety problems, and thus even where there is definite bio-equivalence between two medicinal products, they cannot necessarily be consideredas equivalent as regards therapeutic effect (see footnote 38 above and the relevantpart of the text). On the basis of the principles to which I have referred, the Courtrecognised in its recent judgment in the Generics case that one of the instances inwhich a generic product  although satisfying the requirement of having the samequalitative and quantitative composition in terms of active principles, the samepharmaceutical form and displaying bio-equivalence  cannot be regarded as 'essentially similar to an original medicinal product for the purposes of admittingthe second applicant for an MA to the abridged procedure provided for by Article4.8(a)(iii) of the Directive is precisely a case in which it is apparent in the light ofscientific knowledge that the product in question differs significantly from theoriginal product as regards safety or efficacy in relation to the excipients which itcontains. (40) 25. I wonder, at this stage, what considerations might possibly preclude theapplication to this case of the Smith & Nephew doctrine which, as I have just noted(point 24), has the merit of reflecting the results achieved following the most recenttechnical and scientific developments. The national court indicated in its firstquestion (in subparagraph (iv)) that the holders of the MAs and the producers ofthe old and new versions of Zimovane are members of the same group ofcompanies. It is therefore appropriate in this case to apply the presumptionreferred to in De Peijper (see point 22 above). I consider, however, that that ruleneeds to be clarified in an important respect. The United Kingdom proposes thatit be applied automatically. More precisely, it interprets it as an irrebuttablepresumption (juris et de jure), whereby two variants of a medicinal product havingthe same therapeutic effect must be treated as one and the same product. And thatshould always be the case: regardless of any differences in the excipients used orin the 'recipe and whatever the reasons for such differences. I cannot agree withthe United Kingdom's view. 26. As Advocate General Mayras noted in De Peijper, in this area it is necessaryto seek a delicate balance between the opposing requirements of free movementof goods and protection of public health, between the aim of eliminating any Statemeasure which reserves imports of a medicinal product to operators belonging tothe official distribution network of the holder of the MA and the aim of ensuringstrict monitoring of the efficacy and harmlessness of the products available on thenational market, even though in some cases there may be duplication of therelevant administrative checks. Freedom of parallel imports must be dulysafeguarded  and affects the applicability of the derogation under Article 36 of theEC Treaty (now, after amendment, Article 30 EC) to the restrictive measure,consisting of the need for an MA for the import of medicinal products which arealready covered by an MA in another Member State  where it is apparent or canbe inferred that the manufacturer of the different variants of a medicinal productintends partitioning the Community market and, in particular, isolating the nationalmarkets in which it might be able to charge the highest prices. That freedomshould not however be seen as a dogma. In my view, therefore, the competentstate authority will be required to treat as different products, for the purposes ofMAs for the national market, the variants of a medicinal product with differentformulations where recourse to that policy of diversification by the solemanufacturer appears to be based on genuine and objectively verifiable reasonsrelating to the protection of public health. It should also be noticed mutatismutandis that even according to Smith & Nephew the obligation of the competentnational authority of a Member State to extend the original MA granted in thatState so as to cover a variant of a medicinal product that is (i) imported as aparallel import from another Member State in which its marketing is dulyauthorised and (ii) is identical to the one authorised in the importing Member Stateaccording to the three parameters laid down by the Court, does not apply wherethere are countervailing considerations relating to effective protection of the healthand life of humans. (41) 27. I conclude therefore that the presumption established in De Peijper(differences of formulation without any impact on therapeutic effect = same levelof quality and safety for users of the various national variants = intention of themanufacturer to divide up the market) is to be seen as a rebuttable presumption(juris tantum), which can be set aside in the face of evidence to the contrary. If themanufacturer is able to demonstrate to the full satisfaction of the competentnational authority that the difference of formulation is a response to genuine andobjective concerns of public health  and only in such circumstances  it will haveto be concluded that the variants of the medicinal product in question are differentproducts and that, in consequence, that authority does not possess for both certaininformation prescribed by the directive. I would add that the factors which thecompetent authority (and possibly the courts) of the importing Member State musttake into account when assessing the gravity and reality of the grounds of protection of public health relied on by the manufacturer to justify the differencesof formulation of the diverse variants include the possibility that the versionwithdrawn from the national market in question may nevertheless still beingmanufactured and marketed by the same firm or by a company in the same groupin other Member States. Convincing reasons must therefore be given for thatsituation, including an explanation why those public health concerns do not arisein relation to the countries in question, or other factors such as, for example, thecharacteristics of the market for the medicinal product in question or the existenceof particular contractual relationships in the Member States concerned, otherwisethe balance might be tipped towards the conclusion that the variants aresubstantially the same. As far as this case is concerned, it is not possible toidentify, from the documents before the Court, the reasons for which an MA forthe new version of Zimovane was not applied for in France, Greece, Italy andSpain (see point 11 and footnote 24 above). However, as the national court hasobserved, in this case it was the United Kingdom authorities themselves whichstated that the purpose of developing and introducing the new formulation ofZimovane was not to isolate the United Kingdom market from the remainder ofthe Community (see point 16 above). 28. If it should be proved that the variations in the formulation of the differentvariants are intended to protect public health, there must be declared lawful underArticle 36 of the EC Treaty (now, after amendment, Article 30 EC) any refusal bythe competent national authority to allow under the simplified ad hoc procedurethe parallel import of a medicinal product of the same name as that for whichthere is a valid MA in the importing Member State, even if the former has thesame therapeutic effect and contains the same active principle as the latter. In anysuch case, in fact, it must be concluded, first, that the overriding requirement of theprotection of public health and life of humans cannot be satisfied as effectively bymeans of measures which restrict Community trade to a lesser extent than theimposition on the parallel importer of the burden of applying for an MA inaccordance with the provisions of the Directive. Second, in the circumstancesdescribed, there are no grounds for saying that the requirement of an MA forproducts imported from other Member States in which their release onto themarket is authorised is being used so as to deviate from its true purpose with aview to discriminating in an arbitrary manner against medicinal products originatingin other Member States or indirectly protecting domestic production. The solutionwhich I suggest here, moreover, makes it possible to avoid a situation where theproducers of a given medicinal product are able, by deliberately introducing somemarginal change to the formulation of the product, to block parallel imports of avariant of that product which has been proved safe, as is feared by the UnitedKingdom authorities. 29. That said, it must be repeated that it is incumbent on the United Kingdom,after considering the degree of harmonisation of Community law in the areaconcerned, to establish, within the limits imposed by the Treaty, the level at whichit intends to ensure protection of the life and health of humans within its territory (see footnote 28 above and relevant part of text). The MCA has decided that thereare no doubts as to the harmlessness of the medicinal product at issue undernormal conditions of use and that the reasons set out in the confidential annex,which in 1996 prompted RPR to market the new version of Zimovane and at thesame time to withdraw the earlier version from circulation, cannot be linked withthe general interest in ensuring the protection of human health, as that concept isunderstood in United Kingdom law. However, the applicability of Article 36 of theEC Treaty (now, after amendment, Article 30 EC) to this case was ruled out by theMCA because of the alleged absence of concrete proof of the factual circumstancesgiving rise to the concerns regarding the protection of public health mentioned byRPR rather than because it considered in the abstract that the reasons relied onby the plaintiffs were inadequate. Without prejudice to the fact that the final wordremains with the national court when evaluating the views of the defendantadministration, I would observe, in passing, that that administration does notappear in principle to dispute that checks on the safety of medicinal productsplaced on the market must extend to adverse side effects under actual conditionsof use. That is, not by chance, a fundamental principle forming part of theCommunity rules on this matter. It is relevant to note the obligations mentionedby France and the Commission in their observations, which derive from the ruleson the exchange of information and cooperation between national authorities in thearea of pharmacovigilance. (42) In particular, Article 29a of Directive 75/319, underwhich the Member States are required to establish national systems for thecollection and scientific evaluation of useful information concerning adversereactions on the part of humans, provides that such systems must 'also collateinformation on frequently observed misuse and serious abuse of medicinal products. I agree, finally, with the submissions of the French authorities to the effect that thecompetent authority or the national courts of the importing Member State, inanalysing the level at which the protection of human life and health is ensured innational law, are required to establish whether the precautionary principle and theprinciple that preventive action should be taken  principles analogous to thosewhich, under the Treaty, apply to the action of the Community authorities  areapplicable. (43) IV  Conclusions 30. In view of all the foregoing considerations, I propose that the Court give thefollowing answers to the questions referred to it by the High Court of Justice: 'Articles 30 and 36 of the EC Treaty (now, after amendment, Articles 28and 30 EC, respectively) must be interpreted as meaning that any personproposing to import from Member State A into Member State B amedicinal product X, which uses the same active ingredient and has thesame therapeutic effects but is manufactured according to a differentformulation from that of a medicinal product Y, which is covered by amarketing authorisation in Member State B, is required to apply for andobtain a marketing authorisation from the competent authorities of MemberState B in accordance with and for the purposes of Council Directive65/65/EEC of 26 January 1965 on the approximation of provisions laid downby law, regulation or administrative action relating to proprietary medicinalproducts, as amended, where: (i) medicinal product X is the subject of an MA granted in MemberState A but not an MA granted in Member State B, (ii) medicinal product Y is the subject of an MA granted in MemberState B but not of an MA granted in Member State A, (iii) the marketing authorisations mentioned under (i) and (ii) above weregranted to different members of the same group of companies and themanufacturers of the medicinal products X and Y are also membersof that group of companies, (iv) the formulation of medicinal product Y was developed and introducedin order to secure a public health benefit which medicinal product X(produced according to a different formulation) does not provide, (v) it is not possible to secure that public health benefit where medicinalproduct X and medicinal product Y are available at the same time onthe market of Member State B, and (vi) companies in the same group as the holder of the MA for medicinalproduct X continue to manufacture and market that product inMember States other than Member State B, provided that the holderof the MA is able to prove, on the basis of objective justifications, thatthe marketing of medicinal product X in those Member States doesnot present public health risks similar to those to which it would giverise in Member State B. In the absence of Community harmonisation of national requirements forthe placing of parallel imports of medicinal products on the market, it isincumbent on the authority responsible for issuing marketing authorisations, and if appropriate the national courts, to determine whether the reasons forwhich the formulation of medicinal product Y was developed andintroduced can be linked with the general interest in protecting human lifeand health, as that concept is understood in national law. 1: Original language: Italian. 2:  OJ English Special Edition 1965-66, p. 20. The amendments to the directive which arerelevant here are those made by the following instruments: Second Council Directive75/319/EEC of 20 May 1975 on the approximation of provisions laid down by law,regulation or administrative action relating to proprietary medicinal products (OJ 1975 L147, p. 13; see Articles 35 and 36); Council Directive 83/570/EEC of 26 October 1983amending Directives 65/65/EEC, 75/318/EEC and 75/319/EEC on the approximation of theprovisions laid down by law, regulation or administrative action relating to proprietarymedicinal products (OJ 1983 L 332, p. 1; see Article 1(1) to (6)); Council Directive87/21/EEC of 22 December 1986 amending Directive 65/65/EEC on the approximation ofprovisions laid down by law, regulation or administrative action relating to proprietarymedicinal products (OJ 1987 L 15, p. 36; see Article 1(1)); Council Directive 89/341/EECof 3 May 1989 amending Directives 65/65/EEC, 75/318/EEC and 75/319/EEC (OJ 1989 L142, p. 11; see Article 1(1) to (4)); and Council Directive 93/39/EEC of 14 June 1993amending Directive 65/65/EEC, 75/318/EEC and 75/319/EEC (OJ 1993 L 214, p. 22; seeArticle 1). Directive 93/39 established, with effect from 1 January 1995, a decentralisedprocedure for mutual recognition of national marketing authorisations, together withbinding arbitration by the Community in the event of disagreement between MemberStates (see Article 4, second paragraph, subparagraph 11, Article 7(2) and 7(a) of Directive65/65/EEC and Articles 8 to 15c of Directive 75/319/EEC). The independent nationalprocedures remain, but as from 1 January 1998 (the end of the transitional period for thenew procedure) they are strictly limited to the initial phase (issue of the marketingauthorisation by the 'reference Member State and to medicinal preparations notmarketed in more than one Member State. 3:  The abovementioned Directives 89/341/EEC and 93/39/EEC (see footnote 1 above),however, were adopted on the basis of Article 100a of the EC Treaty (now, afteramendment, Article 95 EC). 4:  See the preamble to Directive 65/65/EEC (cited above, footnote 1, and relevant part oftext), in particular the first recital. 5:  Or a Community MA granted in accordance with Council Regulation (EEC) No 2309/93of 22 July 1993 laying down Community procedures for the authorisation and supervisionof medicinal products for human and veterinary use and establishing a European Agencyfor the Evaluation of Medicinal Products (OJ 1993 L 214, p. 1). 6:  As the Court has emphasised (see Case C-440/93 Scotia Pharmaceuticals [1995] ECRI-2851, paragraphs 21 to 25), the discretion available to the competent authority for issueof authorisations in a Member State is rather limited in the context of the Directive. There is thus no possibility of issuing an MA when all the information specified in Article4 has not been provided or the prescribed tests have not been carried out (fisico-chemico,biological or microbiological, pharmacological and toxicological, and clinical tests). 7:  See Council Directive 75/318/EEC of 20 May 1975 on the approximation of the laws ofMember States relating to analytical, pharmaco-toxicological and clinical standards andprotocols in respect of the testing of proprietary medicinal products (OJ 1997 L 147, p. 1). In order to facilitate the issue of marketing authorisations for the same medicinal productin several Member States, Directives 75/318/EEC and 75/319/EEC (cited in footnote 1above) harmonised the methods for controlling medicinal products put on to the market,in particular by requiring the national authorities to examine applications for authorisationon the basis of the protocols described in the annex referred to in the text. That annexwas replaced by Commission Directive 91/507/EEC of 19 July 1991 amending the annexto Directive 75/318/EEC (OJ 1991 L 270, p. 32) in order to bring it into line with technicalprogress. 8:  See Case 104/75 De Peijper [1976] ECR 613, paragraph 25. 9:  According to the said Article 30 EC, 'the provisions of Articles 28 and 29 shall notpreclude prohibitions or restrictions on imports ... justified on grounds of ... the protectionof health and the life of humans ... Such prohibitions or restrictions shall not, however,constitute a means of arbitrary discrimination or a disguised restriction on trade betweenMember States. The Court has consistently held that Article 36 of the EC Treaty (now,after amendment, Article 30 EC) remains applicable to the production and marketing ofpharmaceutical products until the national provisions have been entirely harmonised (see,amongst many, Case 215/87 Schumacher [1989] ECR 617, paragraph 15, Case C-369/88Delattre [1991] ECR I-1487, paragraph 48, Case C-347/89 Eurim-Pharm [1991] ECR I-1747,paragraph 26, Case C-62/90 Commission v Germany [1992] ECR I-2575, paragraph 10, CaseC-317/92 Commission v Germany [1994] ECR I-2039, paragraph 14, and Case C-320/93Ortscheit [1994] ECR I-5243, paragraph 14. 10:  It should be noted that the medicinal product imported by the appointed distributor forthe Netherlands and the one marketed by the parallel importer had common origins: theywere produced  in Switzerland and the United Kingdom  by manufacturers belonging tothe same group of companies. 11:  In De Peijper, the Netherlands judge asked the Court (I) whether Article 30 of the ECTreaty (now, after amendment, Article 28 EC) was to be interpreted as meaning that anational measure which makes the grant of the MA for a medicinal product subject to thecondition that the parallel importer must provide the competent authority with documentsidentical to those already lodged by the manufacturer or his exclusive concessionaire iscompatible with that article, where: (i) the medicinal product in question, prepared inaccordance with uniform methods and having a homogeneous qualitative and quantitativecomposition, is marketed in one or more Member States on the basis of properauthorisations, (ii) in each of those Member States the competent authority informed thirdparties of the grant of the MA by means of appropriate official publication, (iii) anoperator established in one of those Member States who intends making parallel importsof the medicinal product in question can obtain the data concerning the preparation andqualitative and quantitative composition of it only if the producer or official distributorsin the importing State are prepared to provide him with them, and (iv) the healthauthorities of that State already hold the relevant documents, produced at an earlier stagein support of the application for the MA; and (II) whether the answer given to the firstquestion was also valid where there were differences between the product authorised in theMember State of importation and the product of the same name imported in parallel fromanother Member State (differences concerning the manufacturing processes or thequalitative and quantitative composition), which were irrelevant such that 'it is likely thatthe manufacturer ... [had the] ... exclusive intention of using the differences ... in order toprevent or impede the possibility of the parallel importation (see De Peijper, cited infootnote 8, paragraphs 10, 11 and 33). 12:  See De Peijper (cited in footnote 8 above), paragraph 18. 13:  See paragraphs 20 to 32. The Court, first, made it clear that the derogation under thatarticle cannot be invoked regarding the parallel importer's obligation to produce adocument such as the file provided for by the Netherlands legislation: 'If the public healthauthorities of the importing Member State already have in their possession, as a result ofimportation on a previous occasion, all the pharmaceutical particulars relating to themedicinal preparation in question and considered to be absolutely necessary for thepurpose of checking that the medicinal preparation is effective and not harmful, it isclearly unnecessary, in order to protect the health and life of humans, for the saidauthorities to require a second trader who has imported a medicinal preparation which isin every respect the same to produce the abovementioned particulars to them again(paragraph 21, emphasis added). As regards, on the other hand, the obligation to producedocuments like the records for each batch of products imported in parallel, the Courtobserved that it is undeniable that the national competent authorities must be able toverify, with absolute certainty and at any time, whether or not a particular batch conformswith the information given in the file. However, according to the Court, even where theadministrative rules in force in the importing Member State include the requirement thata parallel importer must prove that an imported batch conforms to the description of themedicinal product, there would '... be no justification under Article 36 [now, afteramendment, Article 30 EC] for compelling him [to produce] documents to which he doesnot have access when the administration, or as the case may be, the court, finds thatevidence can be produced by other means, such as the exchange between nationaladministrations of 'the documents necessary for checking certain largely standardised andwidely distributed products (see paragraphs 29 and 27). 14:  See paragraph 36 of the grounds and paragraph 3 of the operative part. 15:  See proposal for an amendment of Directive 65/65/EEC and 75/319/EEC of 2 June 1980(OJ 1980 C 143, p. 8). 16:  See Commission communication on parallel imports of proprietary medicinal products forwhich marketing authorisations have already been granted (OJ 1982 C 115, p. 5). 17:  See Notes on Application for Product Licences (Parallel Importing) (Medicines for HumanUse), as amended (hereinafter 'MAL 2 (PI)). 18:  Under Paragraph 4 of MAL 2 (PI), the medicinal product sought to be imported by wayof parallel import must be: (a) a product which is to be imported from a Member State of the EuropeanCommunities; (b) a proprietary medicinal product (as defined in Article 1 of the Directive) for humanuse; (c) covered by a valid MA granted in accordance with Article 3 of the Directive by theregulatory authority of a Member State; (d) have no differences, having therapeutic effect, from a product covered by a UnitedKingdom MA; (e) made by or under licence to: (i) the manufacturer who made the product coveredby the UK MA or (ii) a member of the same group of companies. If even one of those conditions is not met, the application for the PL(PI) cannot begranted and the applicant is invited to apply for an MA under the normal procedure (MAL2). Pursuant to paragraph 12 of MAL 2 (PI), a PL(PI) remains in force only so long as both the United Kingdom MA (sometimes referred to as the reference or 'motherauthorisation) and the Community reference MA are in force. If either ceases to be validfor any reason (for example, it may lapse or be revoked) the PL(PI) also ceases to be valid. Paragraph 21 of MAL 2 (PI) provides, finally, that the normal arrangements apply withregard to variations to a PL(PI) made at the request of the licence holder. The competentauthority verifies that the terms of the authorisation still conform with the relevantprovisions of the applicable MA and notifies the PL(PI) holder of any action necessary asa result of a variation to the United Kingdom reference MA. The holder of a PL(PI) isrequired to notify the competent authority of any variation to the Community MA thatcomes to his attention and is required to obtain a variation to the PL(PI) before he canmarket the varied product in the United Kingdom. 19:  See Case C-201/94 Smith & Nephew and Primecrown [1996] ECR I-5819. 20:  More specifically, the United States company Marion Merrel Dow had licensed the rightto produce and market the medicinal product Ditropan to S&N for the United Kingdomand to Marion Merrel Dow Belgium for Belgium. 21:  See Case C-201/94 (cited above, footnote 18), paragraphs 19 to 21. 22:  See Case C-201/94 (cited above, footnote 18), paragraph 25. 23:  See paragraph 1 of the operative part of the judgment in the same case. 'It wouldtherefore be contrary to [the Directive] the Court observed, '... for a competent nationalauthority, in the context of an application for a marketing authorisation falling within thescope of that Directive, to use information supplied by an independent company, withoutits agreement, in support of an application for a marketing authorisation concerninganother proprietary medicinal product (see, ibid., paragraph 31). 24:  They are authorisations numbers 0012/0162 (Zimovane 7.5 mg tablets), 0012/0163(Zimovane in 3.75 mg capsules), 0012/0164 (Zimovane in 7.5 mg capsules), 0012/0259(Zolerim in 7.5 mg tablets) and 0012/0260 (Zimovane in 3.75 mg tablets). Only marketingauthorisation number 0012/0162 was in fact used. 25:  RPR'S representative stated at the hearing that an MA for the new version of Zimovanehas already been granted in Sweden, and the old version would no longer be distributedin that country. An MA for the new version of Zimovane has been applied for in eightfurther Member States (Ireland, Denmark, France, Germany, Belgium, Luxembourg,Finland and the Netherlands) and in Norway. 26:  Under Article 29d of Directive 75/319/EEC, the person responsible for placing themedicinal product on the market is required (i) to report all suspected serious adversereactions which are brought to his attention by a health care professional to the competentauthorities without delay and (ii) to maintain detailed records of all other suspectedadverse reactions, accompanied by a scientific evaluation, presenting the same to thecompetent authorities immediately on request or at least every six months for the first twoyears following authorisation, and once a year for the following three years. Before givinga decision on a request for renewal of an MA the competent authority must in additionexamine a file containing up-to-date pharmacovigilance data (see Article 10, firstparagraph, of Directive 65/65). I think it is also appropriate to note here the provisionsof Article 4b, second paragraph, and Article 7, second paragraph, of Directive 65/65, which,for the dual purpose of ensuring better protection of pubic health and avoiding pointlessduplication in the examination of applications for MAs require the Member Statessystematically to draw up evaluation reports for every medicinal product authorised bythem, to exchange them on request when in respect of a medicinal product alreadyauthorised in one Member State there is an application pending for an MA in anotherMember State and to update them whenever new information is received that is relevant toevaluation of the quality, safety or efficacy of the medicinal product in question. 27:  It has been rightly pointed out that a medicinal product is a paradoxical product in thesense that although its essential function is clearly therapeutic it may also give rise topathological conditions if it is defective or misused (see E. Cadeau and J.-Y. Richeux, 'LeJuge Communautaire et le Médicament. Libre Circulation des Marchandises et Protectionde la Santé Publique in Les Petites Affiches No 7/1996, p. 4). 28:  But see footnotes 1 and 5 above. 29:  See Case C-320/93 Ortscheit, cited above, footnote 8, paragraph 18. 30:  Ibid., paragraph 16, and paragraph 15 of the 1976 case cited in footnote 7 above. 31:  The United Kingdom authorities seem, therefore, implicitly to admit in principle that inthe event of revocation (or non-renewal) of an original MA or voluntary surrender notfollowed by an application for an MA for a different variant of the medicinal product inquestion, it is not in any event permissible to authorise on the basis of MAL 2 (PI) parallelimports of the product from other Member States in which it is covered by validauthorisations, with the result that it is necessary for the MCA to undertake theprocedure for complete evaluation provided for by the Directive. 32:  See the Opinion of Advocate General Mayras in De Peijper [1976] ECR 641, particularlyat 650 and 651. 33:  Ibid. 34:  Smith & Nephew, cited in footnote 18 above, paragraph 9. 35:  It should be borne in mind that the 'criteria of quality, safety and efficacy are those onwhich, in the interests of public health and for the benefit of users of the medicinalproducts, the decision of the competent national authority on an application for an MAmust be exclusively based (see the third recital in the preamble to Directive 93/39, cited infootnote 1 above). 36:  The summary of the product characteristics must contain the information listed in Article4a of the Directive. Under Article 4b, when the marketing authorisation is issued theperson responsible for placing that product on the market is to be informed, by thecompetent authorities of the Member State concerned, of the summary of the productcharacteristics as approved by them. The competent authorities are to take all necessarymeasures to ensure that the information given in the summary is in conformity with thataccepted when the marketing authorisation is issued or subsequently. 37:  See the Annex to Directive 75/318 (cited in footnote 6), paragraph 3, part 2, points A.1.1.,A.4.1, B.1 and E.1.3. 38:  See European Commission, The Rules governing medicinal products in the European Union,Volume IIIC, Guidelines on the quality, safety and efficacy of medicinal products for humanuse. Efficacy, Luxembourg 1998, pp. 233-235. 39:  Bio-availability means the proportion of active substance or therapeutic moiety (forexample salts, esters, etc.) delivered from a pharmaceutical form which reaches the centralcirculatory system of a patient to whom the medicinal product is administered. Differencesin the excipients and/or in the production process for two medicinal products may lead todiffering rates of dissolution or absorption. Two medicinal products, which are'pharmaceutical equivalents (that is to say they contain the same quantity of the sameactive substance in the same dosage forms) or 'pharmaceutical alternatives (having thesame therapeutic moiety but in a different chemical form or dosage form) are said to bebio-equivalent if their respective bio-availabilities are so similar as to give rise to essentially identical effects in terms of efficacy and safety. In practice, the proof of bio-equivalencebetween pharmaceutical equivalents or alternatives is also the most adequate proof oftherapeutic equivalence as between the medicinal products in question, provided that theycontain excipients generally recognised as safe and bear the same instructions for use(ibid.). 40:  See Case C-368/96 The Queen v The Licensing Authority established by the Medicines Act1968, ex parte Generics [1998] ECR 0000, paragraphs 32, 33 and 36. The abovementionedpoint 8(a) of the second paragraph of Article 4 provides for three alternatives in which theapplicant for an MA is not required to furnish the results of pharmacological andtoxicological tests or of clinical trials. The abridged procedure referred to in the text,however, 'in no way relaxes the requirements of safety and efficacy which must be met bymedicinal products (see Case C-440/93, cited in footnote 5 above, paragraph 17). Ageneric medicinal product is a copy of an innovative medicinal product whose formulationcan be reproduced by other manufacturers and which can be sold under the same name ata price that is usually lower than that of the original product. 41:  See Smith & Nephew, cited above (footnote 18), paragraph 1(a) of the operative part. 42:  See Article 29a to 29i of Directive 75/319, introduced by Article 3(3) of Directive 93/39(cited in footnote 1 above). 43:  It follows from the principles mentioned in the text that, where there are uncertaintiesregarding the existence or scope of risks to consumers' health, the institutions may adoptprotective measures without having to wait until the reality and seriousness of those riskshave become fully apparent (see Case C-157/96 R v MAFF, ex parte National Farmers'Union and Others [1998] ECR I-2211, paragraph 63, and Case C-180/96 United Kingdomv Commission [1998] ECR I-2265, paragraphs 99 and 100).