EU GMP Suspensions in Brief
This article was originally published in The Gold Sheet
Executive Summary
EU authorities in February suspended GMP certificates for manufacturers in China, Spain, France and Sweden.
EU suspends Dongying, China, firm's heparin
After finding irregularities in a Chinese firm's polymerase chain reaction testing of a supplier's crude heparin for ruminant DNA, a French inspectorate Feb. 25 suspended the company's European Union GMP certificate, effectively banning its heparin and enoxaparin sodium from France and the rest of the EU.
The company, Dongying Tiandong Pharmaceutical Co. Ltd., located in Dongying City in China's Shandong Province, manufactures porcine heparin sodium API. If there were DNA from ruminants in the crude heparin, it could also potentially carry transmissible spongiform encephalopathy, or mad cow disease.
During its Dec. 19 inspection, the French National Agency for Medicines and Health Products Safety also determined that the company's quality system for ensuring full traceability of crude heparin was "very weak." The agency also found a misunderstanding of basic GMP principles for handling out-of-specification results and deviations.
Additionally, there were concerns about the company's nuclear magnetic resonance testing. In carbon 13 NMR testing of enoxaparin sodium, a contract laboratory found an additional peak that the company did not investigate. For this reason, the European Directorate for the Quality of Medicines is suspending the company's certificate of suitability for enoxaparin sodium.
Poland: Chengdu Okay not OK
An Oct. 28 EU GMP inspection requested by Chengdu Okay Pharmaceutical Co. Ltd., did not go well. Poland's Main Pharmaceutical Inspectorate concluded Feb. 19 after identifying 21 deficiencies, five of them critical, that the facility in Qionglai, a city in China's Sichuan Province, failed to comply with EU GMP principles for active substances.
The Polish inspectorate found deficiencies in impurities calculations for diosmin active substance. There was no record of a reference standard, there were incorrect calculations, there were unconfirmed analytical conditions, there were no logins or passwords or access conditions for the high pressure liquid chromatography equipment, and a computer station used two different HPLC software systems. The pH measuring methods were inadequate, crude diosmin was dried in an area that had inappropriate conditions and some HVAC qualification data had been falsified.
Farma Mediterrania fails inspection
The Spanish Agency of Medicines and Medical Devices wasted no time in declaring Farma Mediterrania, S.L., of Sant Just Desvern, Spain, to be out of compliance with the EU GMPs.
The agency said Feb. 9 that a Jan. 13 inspection turned up some serious issues in the firm's manufacture of sterile drug products. Batches were released without any quality assurance checks using chromatographic equipment that hadn't been qualified and a computerized management system that hadn't been validated.
Also, the company had transferred some quality controls to a third party without also transferring the control methods – or obtaining authorization of the relevant health authorities. There were issues with failure investigations, visible particles, air treatment system qualification, batch records, unapproved facility modifications and failure to conduct medial fill testing.
Cargill's alginic acid failed inspection
The French National Agency for Medicines and Health Products Safety Feb. 9 published a finding it made Oct. 30, more than three months before, that Cargill France's facility in Lannilis, France, was non-compliant with EU GMPs.
The notice concerned production of an active drug substance, alginic acid.
Of the 14 observations made, one was deemed critical: The company failed to manage semi-finished batches and mixing operations in such a way as to guarantee that final batches met pharmacopoeial standards. There were four major deficiencies as well, including the manufacture of alginic acid API without agency authorization.
The agency noted that Cargill's sole pharmaceutical customer, Pierre Fabre Medicament of Gien, France, stopped making the Topaal oral suspension and oral solid products that contained alginic acid last year, and decided Oct. 5 to recall all batches remaining on the market.
The agency noted that on Sept. 25, it had called for Cargill to suspend manufacture of alginic acid and alginates at the site.
Deficiencies found at Svenska Bioforce
Even though it didn't find any critical deficiencies during an Aug. 11 inspection, Sweden's Medical Products Agency Feb. 7 suspended Svenska Bioforce AB's EU GMP certificate.
The agency explained in a notice of non-compliance that it found 42 deficiencies, of which 17 were major, during its inspection of the company's facility in Södra Sandby, Sweden.
The major deficiencies related to a range of issues including batch certification, change management, deviation handling and management responsibility. The company won't be able to resume its manufacture of non-sterile drug products for Sweden's domestic market until its quality system is re-inspected after it corrects all the issues.