Europe suspends Chinese APIs

European quality regulator acts against 4 more APIs made in two Chinese facilities.

Four active pharmaceutical ingredients (APIs) manufactured in China have been suspended by the European Directorate on the Quality of Medicines (EDQM).

Two benzylpenicillin APIs (CEP Nos. 2004-001 & CEP 2004-017) made by Chinese company Hebei Huari Pharmaceuticals, and dihydrostreptomycin sulphate (CEP No.2000-069) and neomycin sulphate (CEP No 2001-317) made by Sichuan Long March Pharmaceutical Company, are the products whose the certificates of suitability (CEPs) got suspended by EDQM in April.

In March 2008, another similar action by EDQM led to a recall of 14 clindamycin phosphate products by the Spanish Ministry of Health.

However, there have been no such reports of product recall so far by any of the EU member countries, following the latest EDQM action against these Chinese APIs. Health authorities of individual countries in Europe are expected to carry out their own risk assessment based on the suspension in the coming weeks.

No other active pharmaceutical ingredients (API) made at Hebei Huari or Sichuan Long March facilities in China has been affected by the action.

But a German company Blue Inspection GmbH, which offers audits and inspections for starting materials and APIs for pharmaceutical clients, has advised other EU based companies to reassess products they receive from the plants.

The EDQM (Council of Europe) is a key European organisation involved in harmonisation & co-ordination of standardisation, regulation & quality control of medicines, blood transfusion, organ transplantation, pharmaceuticals and pharmaceutical care.

This type of action is usually taken by the EDQM if carries out a regulatory inspection and finds that the API manufacturer is not acting in compliance with the cGMP requirements as laid down in ICH Q7 regulations.

The EDQM can also suspend a CEP certificate if a company refuses to allow an inspection, or the information in the CEP dossier itself is not kept up to date and current.

The EDQM can suspend a CEP in case of: 1) inspection of a company carried out in the framework of the EDQM Certification scheme showing critical and/or major deficiencies leading to the conclusion that the company does not operate in compliance with GMP, and/or showing that manufacture does not comply with the dossier submitted for the CEP application; 2) inspection of a company carried out by an inspectorate of a European

Economical Area (EEA) member state leading to the conclusion that the company does not operate in compliance with GMP and 3) refusal by a company to be inspected in the framework of the EDQM.

Normally, a suspension is limited in time for a period of two years. Failure to meet the conditions to lift a suspension leads, if no justified extension of the suspension has been requested by the CEP holder and accepted by EDQM, to the final cancellation of the CEP.

When EDQM decides to cancel or suspend a CEP, the holder is given the possibility to appeal the decision. He will be asked to provide detailed justification to the Ad’Hoc Committee during a meeting held on the premises of the EDQM in case of appeal.

Once a CEP has been suspended or cancelled, the holder has to inform its customers of the situation to allow them to take responsibility with regard to the concerned substance and any related marketing authorisation or marketing authorisation application.

The status of the CEP (suspended or withdrawn) is published in the Certification database available on the EDQM website.

Though a CEP is suspended for 2 years, in exceptional cases the suspension may be extended, provided the holder of the CEP submits a justified request for extension, for review by the Internal Decision Board, before the end of the 2-year period.

After a suspension, a CEP may be restored as soon as the conditions for lifting the suspension are met by the CEP holder. In this case, a revised CEP is granted, which supersedes the suspended one.