Quality of medicines
Further inquiry note
Assessment of Certificates of Suitability (CEP)
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.
Further Information
Information regarding suspended and withdrawn CEPs is published on the EDQM website.
Database for information on CEPs granted by the EDQM: Search Certification Database.
Validity of the Active Substance Manufacturer and Finished Drug Product Manufacturer
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).
Active Substance
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.
In case of questions regarding NCRs please contact am-qualitaetsmangel@basg.gv.at, in case of questions regarding concerned products please contact lcm@basg.gv.at.
Risk assessment of nitrosamines in medicinal products
Information for marketing authorisation holders: Request to evaluate the risk of the presence of nitrosamine impurities in human medicinal products.
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, finalised July 2020.
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
Practical Guidance Austria in relation to the Art. 5(3) Referral on Nitrosamines
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
Human Medicinal Products
Chemically Synthetisised Active Substances
Step 1 – risk evaluation
Results of the risk evaluation in regard to nitrosamine impurities have to be submitted until 31 March 2021 to BASG for all authorised human medicinal products containing chemically synthesised active pharmaceutical ingredients.
A procedure is provided in eServices for all products concerned. If this has not happend in your case please contact nat@basg.gv.at.
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).
You will be provided with 2 documents by CMDh with the respective document names (step 1 - no risk identified, step 1 - risk identified).
Please choose the document suitable for your marketing authorisation, fill in this document completely and upload it to eService (see picture 2 and 3) by using the correct type 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 nat@basg.gv.at.
Step 2 – Testing
CAVE: only relevant if a risk has been identified in Step 1
A procedure is provided in eServices for all products concerned anf –if a risk has been identified- the procedures stays open. A procedure is provided in eServices for all products concerned.If this has not happend in your case please contact natdasg.at. 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).
You will be provided with 2 documents by CMDh with the respective document names (step 1 - no risk identified, step 1 - risk identified).
Please choose the document suitable for your marketing authorisation, fill in this document completely and upload it to eService (see picture 2 and 3) by using the correct type of document (step 2 - no nitrosamine detected, step 2 - nitrosamine detected).
To upload the document please open the procedure and choose voluntary response.
Please use for submission of the results of the risk evaluation for Austria only the procedure described above.
Biologicals Step 1 – risk evaluation
If your biological medicinal product requires a risk evaluation regarding possible nitrosamine contamination, the result of the risk evaluation must be submitted to the BASG by 01.07.2021 at the latest.
A procedure is provided in eServices for all products concerned. If this has not happend in your case please contact nat@basg.gv.at.
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).
CMDh will provide you with 2 documents with the respective document designations (step 1 - no risk identified, step 1 - risk identified).
Please choose the document suitable for your marketing authorisation, fill in this document completely and upload it to eService (see picture 2 and 3) by using the correct type 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 spreadsheet mentioned in the corresponding practical guidance (see CMDh website) is - as also indicated there - not mandatory required in Austria at the moment and therefore not necessarily to be uploaded.
Please use only the procedure described above for your reports in Austria.
If you do not have access to the portal or if you have any questions, please contact nat@basg.gv.at.
Step 2 – Testing
CAVE: only relevant if a risk has been identified in Step 1
A procedure is provided in eServices for all products concerned anf –if a risk has been identified- the procedures stays open. A procedure is provided in eServices for all products concerned.If this has not happend in your case please contact natdasg.at. 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).
You will be provided with 2 documents by CMDh with the respective document names (step 1 - no risk identified, step 1 - risk identified).
Please choose the document suitable for your marketing authorisation, fill in this document completely and upload it to eService (see picture 2 and 3) by using the correct type of document (step 1 – no risk identified, step 1 – risk identified).
To upload the document please open the procedure and choose voluntary response.
Please use for submission of the results of the risk evaluation for Austria only the procedure described above.
Nitrosamins in sartan medicines
Update March 2021- Recommendations for sartans are aligned with those for other medicines
EMA’s human medicines committee (CHMP) has aligned recommendations for limiting nitrosamine impurities in sartan medicines with recent recommendations from the Article 5 (3) procedure, which concluded on June 2020.
Concerning this matter the European Comission has adopted a legally binding decision on 19.02.2021 which is addressed to the member states.
Commission Implementing Decision
https://ec.europa.eu/health/documents/community-register/html/ho26820.htm
Further information and details on how to proceed can be found on the following pages:
For details on the procedure please click on the following link to the homepage of the European Medicines Agency (EMA) https://www.ema.europa.eu/en/medicines/human/referrals/angiotensin-ii-receptor-antagonists-sartans-containing-tetrazole-group
Press release of the CMDh
Current guidelines for the procedure can be found in the Questions & Answers of the Coordination Group, CMDh