EDQM suspends, withdraws 19 API certificates in 2H10

The European Directorate for the Quality of Medicines and Healthcare (EDQM) suspended or withdrew 19 certificates for active pharmaceutical ingredients in the second half of 2010 because their manufacturers failed or refused inspections.

Marketing authorisation holders which cite the Certificates of Suitability (CEPs) must take the necessary measures to ensure that active substances from the concerned active substance manufacturer are not used, either permanently or for a defined period, notes the EDQM.

The APIs in question include: pyrazinamide, rifampicin and isoniazid for tuberculosis; a slew of general-use antibiotics (cefuroxime sodium, ceftriaxone sodium, doxycycline monohydrate, doxycycline hyclate, oxytetracycline, metronidazole, and phenoxymethyl penicillin potassium); caffeine; the insomnia treatment zopiclone; flunarizine for migraine and epilepsy; the antidiarrhoeal loperamide hydrochloride; the antihistamine cinnarizine; and allopurinol for gout.

All of the suppliers included in the list was from Asia, reflecting the huge number of API suppliers from that part of the world, with the exception of Northern Ireland's Norbrook Laboratories (whose suspended CEP for oxytetracycline hydrochloride has since been reinstated).

Nine of the suspended or withdrawn CEPs are assigned to six Chinese companies in the list, with two Indian firms accounting for another six CEPs. Two CEPs were from a Korean supplier and another was from a Thai company.

CEP Suspensions 2H 2010

Date	API	CEP number	Company	Country
10/12/10	Pyrazinamide	1998-070	Linaria Chem	Thailand
08/11/10	Oxytetracycline HCl	1999-162	Norbrook Labs	UK (since reinstated)
08/11/10	Phenoxymethyl penicillin K	2006-019	North China Pharma	China
26/10/10	Metronidazole	2002-119	Tianjin Zhongan Pharma	China
26/10/10	Caffeine	2005-116	Tianjin Zhongan Pharma	China
30/09/10	Pyrazinamide	2000-036	Calyx Pharma & Chem	India
30/09/10	Zopiclone	2001-203	Calyx Pharma & Chem	India
30/09/10	Isoniazid	2008-108	Calyx Pharma & Chem	India
08/07/10	Flunarizine dihydrochloride	2004-142	Fleming Laboratories	India
08/07/10	Loperamide HCl	2005-247	Fleming Laboratories	India
08/07/10	Cinnarizine	2007-257	Fleming Laboratories	India
22/10/10	Rifampicin	2004-295	Zhengzhou Minzhong Pharma	China
09/07/10	Oxytetracyline dihydrate	2004-177	Shandong Jinyang Pharma	China
09/07/10	Oxytetracyline HCl	2008-165	Shandong Jinyang Pharma	China

CEP Withdrawals 2H 2010

Date	API	CEP number	Company	Country
22/10/10	Doxycycline hyclate	1992-018	Shanghai International Pharmaceutical	China
22/10/10	Doxycycline monohydrate	1996-064	Shanghai International Pharmaceutical	China
04/10/10	Allopurinol	2004-189	Shanghai OSD	China
12/07/10	Ceftriaxone Na	2000-017	Kukje Pharmaceutical	Korea
12/07/10	Cefuroxime Na	2004-050	Kukje Pharmaceutical	Korea

A Certificate of Suitability (CEP) is awarded by the EDQM if a company provides a declaration that it is making ingredients in accordance with Good Manufacturing Practice (GMP) and does not depend on a pre-approval inspection.

Once a CEP is granted the supplier can sell its product for use in medicinal products sold in the EU, and EDQM carries out periodic inspections of API manufacturing sites to make sure they are in compliance. The main issue is inspection capacity, as the agency can generally only inspect around 25-30 sites a year and relies on inspections by recognised regulatory agencies to plug the gaps.


Related articles:

EDQM suspends five more API certificates

EDQM launches track-and-trace pilot for medicines

EDQM continues clampdown on API manufacturers

Denmark report on APIs finds supplier audits 'inadequate'

EDQM suspends certificates for Chinese ingredients