Case C‑29/17

Novartis Farma SpA

v

Agenzia Italiana del Farmaco (AIFA) and Others

(Request for a preliminary ruling from the Consiglio di Stato)

(Reference for a preliminary ruling — Medicinal products for human use — Directive 2001/83/EC — Article 3(1) — Article 6 — Directive 89/105/EEC — Regulation (EC) No 726/2004 — Articles 3, 25 and 26 — Repackaging of a medicinal product for use as a treatment not covered by its marketing authorisation (off-label use) — Reimbursement by the national healthcare insurance system)

Summary — Judgment of the Court (First Chamber), 21 November 2018

1. Member States — Retained powers — Adjustment of social security systems — Limits — Compliance with EU law — Protection of public health — Discretion of the Member States

   (Art. 168(7) TFEU; European Parliament Council Regulation No 726/2004, Art. 1, second para.; European Parliament Council Directive 2001/83, Art. 4(3); Council Directive 89/105)

2. Approximation of laws — Medicinal products for human use — Directive 2001/83 — Scope — Repackaging of a medicinal product for use as a treatment not covered by its marketing authorisation — Included

   (European Parliament Council Directive 2001/83, as amended by Directive 2012/26, Art. 3(1))

3. Approximation of laws — Medicinal products for human use — Directive 2001/83 — Authorization to market — Scope — Repackaging of a medicinal product for use as a treatment not covered by its marketing authorisation — Adoption of national measures specifying repackaging conditions — Lawfulness

   (European Parliament Council Directive 2001/83, as amended by Directive 2012/26, Art. 6)

4. EU agencies — European Medicines Agency (EMA) — Powers — Exclusive responsibility for evaluating applications for marketing authorisation — National legislation providing for supervision by a national authority of medicine for off-label use reimbursed by the national health service — Lawfulness

   (European Parliament Council Regulation No 726/2004, as amended by Regulation No 1027/2012, Arts 3, 25 and 26)

1.  See the text of the decision.

   (see paras 48 -51)

2.  Article 3(1) of 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, as amended by Directive 2012/26/EU of the European Parliament and of the Council of 25 October 2012, must be interpreted as meaning that Avastin, after being repackaged according to the conditions laid down by the national measures at issue in the main proceedings, falls within the scope of Directive 2001/83, as amended by Directive 2012/26.

   The Court must therefore hold that the exclusion from the scope of Directive 2001/83 set out in Article 3 thereof covers only medicinal products ‘prepared’ in a pharmacy, that is to say those produced in a pharmacy, namely magistral formulas and officinal formulas. Avastin does not fall within either of those categories. It is not produced in dispensing or hospital pharmacies, but industrially in Roche’s laboratories, which holds its MA. It is also clear from the file before the Court that the processes for repackaging Avastin undertaken in accordance with the national measures at issue in the main proceedings do not significantly change the composition, form or other fundamental characteristics of that medicinal product. Those repackaging processes cannot be regarded as the ‘preparation’ of a new medicinal product derived from Avastin by means of a magistral formula or an officinal formula. They do not therefore fall within the scope of Article 3 of Directive 2001/83.

   (see paras 57, 58, 65, operative part 1)

3.  Article 6 of Directive 2001/83, as amended by Directive 2012/26, must be interpreted as not precluding national measures such as those at issue in the main proceedings which lay down the conditions under which Avastin may be repackaged in order to be used for the treatment of ophthalmological indications not covered by its market authorisation.

   In a case similar to that at issue in the main proceedings, the Court held that the repackaging of Avastin for off-label use in the treatment of eye diseases did not require a new MA, provided that that process does not result in any modification of the medicinal product and that it is carried out solely on the basis of individual prescriptions making provision for that process (judgment of 11 April 2013, Novartis Pharma, C‑535/11, EU:C:2013:226, paragraph 42). Subject to factual findings to be made by the referring court, the repackaging of Avastin under the conditions laid down in the national measures at issue in the main proceedings, does not therefore require an MA to be obtained in so far as that process is prescribed by a doctor by means of an individual prescription and undertaken by pharmacists for that medicinal product to be administered in hospitals.

   (see paras 72, 75, 79, operative part 2)

4.  Articles 3, 25 and 26 of Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, as amended by Regulation (EU) No 1027/2012 of the European Parliament and of the Council of 25 October 2012, must be interpreted as not precluding a national measure such as that taken pursuant to Article 1(4)bis of decreto-legge 21 ottobre 1996, n. 536, recante ‘Misure per il contenimento della spesa farmaceutica e la rideterminazione del tetto di spesa per l’anno 1996’, convertito dalla legge del 23 dicembre 1996, n. 648 (Decree-Law No 536 of 21 October 1996 on ‘Measures for containing pharmaceutical expenditure and for adjusting the maximum level of expenditure for 1996’, converted into statute by Law No 648 of 23 December 1996), as amended by decreto-legge del 20 marzo 2014, n. 36, convertito dalla legge del 16 maggio 2014, n. 79 (Decree-Law No 36 of 20 March 2014, converted into statute by Law No 79 of 16 May 2014) which authorises the Agenzia Italiana del Farmaco (AIFA) (Italian Medicines Agency (AIFA)) to monitor medicinal products such as Avastin the off-label use of which is reimbursed by the Servizio Sanitario Nazionale (National Health Service, Italy) and, where relevant, to introduce measures necessary to safeguard patient safety.

   (see para. 86, operative part 3)