Quality of medicines
Supplement for the delivery of substances within the scope of drug quality controls according to §76 AMG.
BASG is involved in the assessment of CEPs as the most active national competent authority. The application dossier for a medicinal product has to provide data on the quality, safety and efficacy of the medicinal product. In terms of quality, extensive data on both the active substance and the finished product have to be provided.
To avoid multiple assessments of identical active substance documentations by different authorities during different procedures, the documentation on an active substance can be submitted to the European Directorate for the Quality of Medicines & HealthCare (EDQM). After a positive centralized assessment by two assessors from different national competent authorities and one EDQM assessor, a Certificate of Suitability (CEP) is granted; the CEP certifies that the quality of the active substance in question is adequately documented. Future application dossiers only need to include a copy of the CEP rather than an extensive active substance documentation, eliminating the need for repeat assessments of the active substance.
Furthermore, the same procedure is in place to evaluate TSE (Transmissible Spongiform Encephalopathy) risk of active substances and excipients and hereby helps to guarantee TSE-free products.
Currently, the Austrian Medicines and Medical Devices Agency is sending 13 experienced assessors to the CEP working party of EDQM (eleven assessors regarding chemical evaluations and two assessors regarding TSE evaluation). Since years the Austrian Medicines and Medical Devices Agency is among the three most active national competent authorities within Europe, in 2013 for the very first time the top position was reached meaning that no other country sent more assessors to Strasbourg than Austria did. EDQM not only covers travel and accommodation expenses, furthermore, the loss of assessing capacities is reimbursed to the national competent authorities.
In addition, Austria (together with eight other countries) is represented in the Technical Advisory Board and, as a result, can actively participate in and shape professional and strategic decisions. Furthermore, an Austrian delegate is also member of the “Ad Hoc Committee” and thereby involved in discussions and decisions as regards CEP suspensions and withdrawals.
The Austrian Federal Office for Safety in Health Care (BASG) points out that marketing authorisation holders are obliged to ensure that the quality of their medicinal products is in accordance with Article 4 of the Austrian Medicines Act (Arzneimittelgesetz, AMG).
In cases where the quality of an active substance is documented by an EDQM certificate (CEP, COS), the continuous validity of the certificate has to be ensured. Certificates transiently suspended or declared invalid as a result of negative GMP inspections are listed on the EDQM website or can be queried from the ‘Certification’ database.
Analogously, the quality of an active substance referring to an Active Substance Master File (ASMF) cannot be ensured after GMP inspections with negative outcome. Corresponding Non-Compliance Reports (NCRs) are published under http://eudragmdp.ema.europa.eu/.
In both cases, the quality of the active substances concerned can, from the view point of BASG, no longer be ensured and, as a result, fails to meet the requirements of the Austrian Medicines Act.
If necessary a different/new active substance manufacturer including respective documentation has to be approved via variation procedure.
Finished Drug Product
If a GMP-inspection of a finished drug product manufacturer has a negative outcome, a corresponding Non-Compliance Report (NCR) will be published under http://eudragmdp.ema.europa.eu/. The quality of medicinal product(s) concerned can, from the view point of BASG, no longer be ensured and, as a result, fails to meet the requirements of the Austrian Medicines Act.
If necessary a different/new finished drug product manufacturer including respective documentation has to be approved via variation procedure.
Information for marketing authorisation holders: Request to evaluate the risk of the presence of nitrosamine impurities in human medicinal products containing chemically synthesised active pharmaceutical ingredients
After detection of nitrosamine impurities in sartans in 2018, within an Article 31 review of sartans at risk of containing nitrosamine impurities (i.e. sartans with a tetrazole ring) it was concluded that manufacturers must review and make necessary changes to their manufacturing processes to minimise nitrosamine impurities as much as possible. In addition, strict limits were set for nitrosamines in these products.
The findings of the review indicate that there is a potential for nitrosamines to be present in APIs for other medicines (i.e. non-sartans APIs), depending on the API and the finished product manufacturing processes.
Therefore, despite the low risk of nitrosamines being present, a scientific evaluation by the Committee for Medicinal Products for Human Use (CHMP) was initiated in September 2019 in accordance with Article 5(3) of Regulation (EC) No 726/2004.
All marketing authorisation holders are asked to review their manufacturing processes and take precautionary measures to mitigate the risk of nitrosamine formation or presence during the manufacture of all medicinal products containing chemically synthesized APIs.
Further information can be found
- on the homepage of the European Medicines Agency (EMA)
- and the Coordination Group (CMDh)
The risk evaluation should be performed in 3 sequential steps
- Step 1 – risk evaluation
- Step 2 – if applicable, confirmatory testing
- Step 3 – if applicable, changes to the marketing authorisation
Step 1 – risk evaluation
Results of the risk evaluation in regard to nitrosamine impurities have to be submitted until 1 October 2020 to BASG for all authorised human medicinal products containing chemically synthesised active pharmaceutical ingredients.
A procedure will be provided in eServices for all products concerned until 8 November 2019. Until 8 November 2019 it could happen that you will not see the procedure in eServices. The procedure is to be found by name Risikoevaluierung, the name of the medicinal product is to be found by subject in connection to each product concerned (see picture 1).
Please find for submission the 2 documents here, step 1 – no risk identified, step 1 – risk identified.
Please choose the document suitable for your marketing authorisation, fill this document completely and upload it to eService (see picture 2 and 3) by using the correct typ of document (step 1-no risk identified, step 1-risk identified).
To upload the document please open the procedure and choose voluntary response.
The Excel sheet mentioned in the practical guide (see CMDh website) is currently not necessary for Austria and has therefore not to be uploaded to eServices.
Please use for submission of the results of the risk evaluation for Austria only the procedure described above.
If you do not have access to the Austrian eServices or in case of questions please contact natbasg.gvat.
In regard to necessary actions for step 2 and 3 you will find here the respective information as soon as possible.