In PP Nature-Balance Lizenz GmbH v Commission, the Claimants questioned the legality of the Commission's Decision ordering Member States to modify marketing authorisations (MAs) of medicines containing Tolperisone, a muscle relaxant licensed to treat spasticity resulting from neurological disorders, so as to remove one of its other licensed therapeutic indications, namely the treatment of painful muscle tension.

Article 116 of the Medicinal Code (Directive 2001/83 on the Community code relating to medicinal products for human use) requires relevant authorities to suspend, revoke, withdraw or modify MAs if the risk-benefit balance of a particular medicine is found to be negative.

The Commission had based its Decision on a recommendation issued by the EMA (the European Medicine Agency) which carried out a full risk-benefit analysis of Tolperisone in all approved indications at the request of the German health authorities. Indeed, the German authorities believed that the efficacy of the drug was not scientifically proven and questioned its safety as its use has been associated with a significant number of hypersensitivity reactions in Germany.

The EMA concluded that there was no conclusive scientific evidence of the efficacy of Tolperisone for the treatment of muscle tension. Having also found the risk of hypersensitivity to be greater than previously considered, the EMA came to the conclusion that the risk-benefit balance for Tolperisone was negative and recommended that MAs for medicines containing the drug be modified accordingly.

The Claimants, German manufacturers of Mydocalm, a drug containing Tolperisone, requested a partial annulment of the Commission's Decision, claiming inter alia that the Commission cannot request the withdrawal of an authorised indication unless the lack of efficacy of a drug has been scientifically proven.  Indeed, neither the Commission nor the EMA had established that Tolperisone was not efficacious.

However, the General Court of the European Union rejected the Claimant’s application on the grounds that the precautionary principle justified the Commission’s Decision that the indication for the treatment of painful muscle tension be removed from Tolperisone MAs.

The precautionary principle has been the basis for the suspension, revocation, withdrawal or modification of MAs. The principle was first applied in the context of the EU environmental field before being expanded to the assessment of risks to human health in Pfizer Animal Health SA v Council. In this case it was claimed that an antibiotic feedstuff-additive used as a growth promoter in animals presented a potential risk to public health on the basis that, whilst unproven, there were scientific concerns that resistance to the antibiotic in question may transfer from the relevant bacterial populations affecting animals to those affecting humans. The growth promoter was consequently banned by health authorities and it was held that in cases of scientific uncertainty, public authorities are able to take such measures where there is a risk to human health.

The principle has since progressed to drugs for human use in cases such as Acino v Commission where it was held that “where there is uncertainty as to the existence or extent of risks to human health, protective measures may be taken without having to wait until the reality and seriousness of those risks become fully apparent” (Acino v Commission, C-269/13 P, EU:C: 2014:255, point 57). In that case, breaches of rules on good practice which led to a lack of confidence in a particular drug were held to justify the application of the precautionary principle despite lack of scientific evidence that the substance presented a risk to public health.

In the present case, the Claimants appealed the General Court’s judgment claiming that the precautionary principle only applied to the assessment of a drug’s safety and therefore had been improperly applied to the assessment of a drug’s efficacy.

The CJEU confirmed the judgment of the General Court and reiterated its previous case law on the precautionary principle, namely that risks need only be potential and not specific (Acino), but the CJEU went a step further by extending its application to the assessment of a drug’s efficacy. 

Such a judgment contributes towards increasing the discretion afforded to national health   authorities to sanction MA holders by suspending or withdrawing MAs in cases of scientific uncertainty.