9/10 September 2021
A judgement of the EU Court of Justice (Sixth Chamber) from 10 April 2014 on the suspension of the marketing and the withdrawal of certain medicinal products batches has been published. The judgement highlights the importance of the decisions taken by the EU Commission. Moreover it is pointed out that the EU Commission is entitled to initiate appropriate measures in case of critical GMP deviations found during a GMP inspection. These measures may include - for the location where the GMP deficiencies have been identified - the suspension of the manufacture for the EU market of medicinal products in question, and the recall of the marketed batches. According to the judgement, it is not required for the EU Commission to decidedly prove risks for public health. A critical deviation alone which endangers the GMP compliant manufacture is sufficient to initiate those measures.
The case which has led to the judgement addresses four medicinal products for human use from the company Acino containing the active ingredient Clopidogrel manufactured at a site in India (Visakhapatnam). A central marketing authorisation was available for those medicinal products according to Regulation No. 726/2004. From 23 to 26 February 2010, a GMP inspection of that factory was carried out in India by a German GMP Inspectorate. That inspection concerned compliance with principles of Directive 2001/83 - also known as the "GMP Guideline".
The GMP inspection resulted in a report establishing that production in Visakhapatnam didn't comply with the GMP requirements. The following GMP deviations were identified: "That report established as a critical breach the fact that 70 manufacturing standards have been re-written and that certain initial indications amended. That inspection also revealed eight other serious breaches, connected with the failure to implement a system ensuring basic quality and failure to observe fundamental obligations arising from the rules on good practice relating to the premises and equipment and the preventive maintenance and handling of solvents. Furthermore, the procedures for cleaning the premises and equipment were found to be inadequate for the purpose of ensuring there was no contamination or cross-contamination."
According to the inspection report, the recall of medicinal products was unnecessary in the absence of any evidence that the products at issue were harmful to patients. As part of the examination of the re-written manufacturing records, it couldn't be proven that the data relating to quality of the batches concerned had changed.
The judgement has now clarified that it is not the GMP inspector who has to decide over the measures to be taken. On the contrary, article 20 of Regulation EC No. 726/2004 lays down a procedure according to which the EMA issues an opinion and hears the medicinal products manufacturer. Based on the opinion of the EMA, the EU Commission decides over the measures to be taken. In the present case, the EU Commission has concluded the prohibition on the marketing of the products manufactured at that factory in India and the withdrawal from the market of the medicinal products at issue.
The judgement is of fundamental importance as it strengthens the procedure and the competence of the EU Commission. When critical GMP deviations are identified at a manufacturing location, there is no need for EU Commission to prove specific risk for public health. The potential risk for health hazard through GMP non-compliant production is sufficient.