26.02.2014
To the attention of stakeholder
NAMMD Press Release on the situation ensued from non-compliance of influenza seasonal vaccine batches manufactured by the Cantacuzino Institute for 2013-2014

According to Article 826 of Law 95/2006 on healthcare reform, as amended, Title XVII – The medicinal product, transposing Directive 2001/83/CE of the European Parliament and the Council on the Community code relating to medicinal products for human use, as amended, the National Agency for Medicines and Medical Devices (NAMMD) is in charge of official batch release for immunologic or blood/plasma-derived medicinal products manufactured in Romania, third countries or EU Member States for which official batch release has not been performed by a control authority and for which marketing is only performed in Romania.
Samples from all the eight batches of influenza vaccine manufactured by the Cantacuzino Institute have been tested in the NAMMD laboratories according to the corresponding monograph of the European Pharmacopoeia, in force. Following laboratory testing of samples submitted, out-of-specification results have been obtained for one of the tested parameters, i.e. Bacterial endotoxins for all samples tested. Mention should be made that, for all the other parameters tested, results have been within admitted limits. In consequence of the non-compliance found for all vaccine batches newly manufactured by the Cantacuzino Institute, re-testing of sample has been performed at the NAMMD site, followed by re-testing in the presence of the manufacturer.
Results found at re-testing at both the NAMMD site in the presence of Cantacuzino Institute representatives and at manufacturer’s site, with NAMMD representatives, have confirmed the non-compliance found regarding content of Bacterial Endotoxins over the accepted limits (max 100 IU/ vaccine dose). The method for testing of Bacterial Endotoxins content as indicated by the manufacturer and according to provisions of the European Pharmacopoeia monograph has been the gel-clot method (a qualitative method).
On 23.12.2013, the NAMMD sent a notification letter to the Ministry of Health, to the attention of Minister Eugen Nicolaescu, on the non-compliance found, determining as a consequence the impossibility to perform official batch release of the Cantacuzino Institute manufactured vaccine batch and the need to issue a Non-compliance notice.
On 24.12.2013, the Non-compliance notices were collected from the NAMMD headquarters by a representative of the Cantacuzino Institute.
Having in mind the potential impact of this non-compliant result on the public concerning the national seasonal influenza immunisation plan 2013-2014, in the context of Cantacuzino Institute reinstatement of manufacture and its strategic importance for Romania as well as the determination that NAMMD laboratory testing results be without doubt, the NAMMD management has decided to send a vaccine sample to be tested in the certified OMCL (Official Medicines Control Laboratories) laboratory of the French competent authority. The sample submitted for testing was part of a sample taken according to procedure in force for testing in the NAMMD laboratory. The method used by the French laboratory for testing of the Bacterial Endotoxins content is a quantitative method also included in the European Pharmacopoeia for this parameter, i.e. the kinetic-chromogenic method.
On 31.01.2014, the NAMMD received the first confirmation of the non-compliant result from the French laboratory concerning Bacterial Endotoxins content; on 05.02.2014, the result notified on 31.01.2014 was re-confirmed.
The result received from the French competent authority practically confirmed the accuracy of the result issued by the NAMMD in its Non-compliance notices, once again highlighting, in quantitative terms this time, the Bacterial Endotoxins content, ascertained to exceed the limits specified in the European Pharmacopoeia, i.e. maximum 100 IU/ vaccine dose.
To conclude, the NAMMD has not performed official batch release of the new influenza vaccine batches manufactured by the Cantacuzino Institute, which once again proves that the Romanian competent authority actually fulfils its primary mission as guarantor of the quality of medicinal products for human use authorised for marketing in Romania, protecting and promoting public health.