Review of common medicines used to treat hypertension – valsartan – due to detection of impurity, N-nitrosodimethylamine (NDMA), a probable human carcinogen! (Part VI)

16 October 2018
active substance, API, Aurobindo Pharma, cancer, candesartan, carcinogen, CEP, corrective measures, drug product, EDQM, EMA, FDA, GMP, headspace GC/MS, human, hypertension, impurity, inspection, irbesartan, losartan, MAH, manufacturer, manufacturing, manufacturing site, marketing authorisation holders, medicinal product, medicines, method, monitor, N-nitrosodimethylamine, NDEA, NDMA, nitrosamine, non-compliance, N‑nitrosodiethylamine, olmesartan, OMCL, recall, review, sartans, specific ring structure, statement, suspension, test, tetrazole, UHPLC-APCI-MS/MS, valsartan, Zhejiang Huahai Pharmaceuticals,

EMA EU authorities are placing the Chinese company Zheijiang Huahai under increased supervision following European and US inspections which revealed weaknesses in quality management at the company’s Chuannan site in Linhai, China and will supervise the manufacture of other active substances produced by this company more closely. Low levels of NDEA have now also

Review of common medicines used to treat hypertension – valsartan – due to detection of impurity, N-nitrosodimethylamine (NDMA), a probable human carcinogen! (Part V)

3 October 2018
active substance, APCI-UHPLC-MS/MS, API, cancer, candesartan, carcinogen, CEP, drug product, EDQM, EMA, FDA, formation, GMP, headspace GC/MS, Hetero Labs Limited, HPLC-UV, human, hypertension, import alert, impurity, inspection, intermediate, irbesartan, losartan, MAH, manufacturer, manufacturing, manufacturing site, marketing authorisation holders, medicinal product, medicines, method, N-nitrosodimethylamine, NDEA, NDMA, nitrosamine, non-compliance, N‑nitrosodiethylamine, olmesartan, OMCL, patient, process, recall, review, risk, sartans, specific ring structure, statement, suspension, test, tetrazole, valsartan, Zhejiang Huahai Pharmaceuticals,

EMA The European Medicines Agency (EMA) is expanding its review of impurities in valsartan following the detection of very low levels of N-nitrosodiethylamine (NDEA) in another active substance, losartan, made by Hetero Labs in India. As a result of the detection of this impurity by German authorities, the review will now include medicines containing

Review of common medicines used to treat hypertension – valsartan – due to detection of impurity, N-nitrosodimethylamine (NDMA), a probable human carcinogen! (Part IV)

19 September 2018
active substance, API, cancer, carcinogen, CEP, EDQM, EMA, headspace GC/MS, human, hypertension, impurity, inspection, investigation, manufacturer, manufacturing, manufacturing site, medicinal product, medicines, method, N-nitrosodimethylamine, NDEA, NDMA, nitrosamine, N‑nitrosodiethylamine, OMCL, patient, process, recall, review, risk, sartans, test, valsartan, Zhejiang Huahai Pharmaceuticals, Zhejiang Tianyu Pharmaceutical Co. Ltd.,

EMA The European Medicines Agency (EMA) has updated its calculation of the risk from valsartan medicines containing N‑nitrosodimethylamine (NDMA), taking into account results from latest tests on the active substance from Zhejiang Huahai. In addition to NDMA, EMA is assessing the impact of a related substance, N‑nitrosodiethylamine (NDEA), which has been detected in valsartan

Review of common medicines used to treat hypertension – valsartan – due to detection of impurity, N-nitrosodimethylamine (NDMA), a probable human carcinogen! (Part III)

29 August 2018
active substance, API, cancer, carcinogen, CEP, detection, EDQM, FDA, final product, headspace GC/MS, Hetero Labs Limited, holder, human, hypertension, impurity, investigation, manufacturer, manufacturing, medicinal product, medicines, method, N-nitrosodimethylamine, NDMA, nitrosamine, OMCL, patient, process, quantification, recall, review, risk, suspension, Torrent Pharmaceuticals Limited, valsartan, Zhejiang Changming Pharmaceutical Co. Ltd., Zhejiang Huahai Pharmaceuticals, Zhejiang Tianyu Pharmaceutical Co. Ltd.,

EDQM The EDQM is continuing the investigations and actions which started in July 2018 to address the issue related to the detection of a nitrosamine (N-nitrosodimethylamine (NDMA)) in a source of active substance valsartan. Following the suspension of the CEP on valsartan held by Zhejiang Huahai Pharmaceutical Co. Ltd, the EDQM has also

Revision of the EU GMP Guide – Annex 17 (Part II)

23 August 2018
Annex 17, batch, CAPA, change, CoA, control, control strategy, decision, deviation, EC, finished product, GMP, MA, parametric release, PAT, pharmaceutical development, PQS, predictor, program, QbD, QRM, release, RTRT, strategy,

Recently, the European Commission published a revised version of Annex 17: Real Time Release Testing and Parametric Release of the EU GMP Guide. The new annex will come into operation on 26 December 2018. We have already informed on our website about a consultation document on Annex 17: Real Time Release Testing, published by European

Review of common medicines used to treat hypertension – valsartan – due to detection of impurity, N-nitrosodimethylamine (NDMA), a probable human carcinogen! (Part II)

20 August 2018
active substance, API, carcinogen, CEP, distribution, EDQM, EMA, human, hypertension, impurity, manufacturer, manufacturing, medicinal product, medicines, N-nitrosodimethylamine, NDMA, recall, review, stopping, suspension, valsartan, Zhejiang Tianyu,

The company Zhejiang Tianyu is no longer authorised to manufacture the valsartan active substance for EU medicines following the suspension of its CEP – a certificate verifying that the quality of its valsartan meets European requirements. The suspension of the certificate by the European Directorate for the Quality of Medicines and Healthcare (EDQM) comes after

Review of common medicines used to treat hypertension – valsartan – due to detection of impurity, N-nitrosodimethylamine (NDMA), a probable human carcinogen! (Part I)

16 August 2018
active substance, animal test, API, cancer, carcinogen, CEP, change, EDQM, EMA, FDA, final product, formation, health effect, Hetero Labs Limited, human, hypertension, impurity, manufacturer, manufacturing, medicinal product, medicines, N-nitrosodimethylamine, NDMA, OMCL, patient, process, recall, review, risk, safety profile, side product, suspension, valsartan, Zhejiang Huahai Pharmaceuticals, Zhejiang Tianyu,

The European Medicines Agency (EMA) is reviewing medicines containing the active substance valsartan. Valsartan medicines are used to treat patients with high blood pressure in order to reduce complications such as heart attack and stroke. It is also used in patients who have had heart failure or a recent heart attack. It should be noted

GMP for Advanced Therapy Medicinal Products (ATMPs) (Part II) and hospital exemption (HE)

14 February 2018
advanced therapy medicinal product, aseptic manufacturing, ATMP, biosafety, clinical trials authorisation, CTA, data integrity, decentralized manufacturing, GMO, GMP, HE, hospital exemption, IMP, investigational medicinal product, MAH, manufacturer, manufacturing, manufacturing platform, marketing authorisation, marketing authorisation holder, operating theatre, process validation, risk assessment, sponsor, unmet medical needs,

On 22 November 2017, the European Commission (EC) has adopted and published Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products, one of the initiatives of the Action Plan for ATMPs launched in October 2017 to foster the development of ATMPs. Advanced Therapy Medicinal Products (ATMPs) manufacturers should comply with these Guidelines

Revised guideline on manufacture of the finished dosage form (Part II)

7 December 2017
bulk, control strategy, CPP, critical process parameter, CTD, design space, finished product, hold time, intermediate, manufacture, process description, RTRT, storage, transport, validation,

On 14 August 2017, the European Medicines Agency (EMA) published revised version of Guideline on manufacture of the finished dosage form. This revised document will become effective on 14 February 2018. We have already informed on our website about a draft of the revised guideline published by the European Medicines Agency (EMA) for public consultation

Pharmaceutical industry Brexit preparedness and its legal consequences for MAH

13 November 2017
API, batch release, Brexit, CMDh, CMDv, CP, DCP, EC, EMA, finished product, GMP, impact, import, legal consequences, MA, MAH, manufacture, marketing authorisation, marketing authorisation holder, medicinal products, MRP, notice, QPPV, RMS, site, transfer, UK's withdrawal, variation,

On 2 May 2017, the European Commission and EMA published a Notice to marketing authorisation holders of centrally authorised medicinal products for human and veterinary use, stating: “The United Kingdom submitted on 29 March 2017 the notification of its intention to withdraw from the Union pursuant to Article 50 of the Treaty on European Union.