Fraud and Major GMP Violations at API Manufacturers in India and China

 

Two Non-Compliance reports to API manufacturers from the Far East  published in the EudraGMDP database reveal once more that basic requirements laid down in the ICH Q7 Guideline are not implemented. Read more details about those Non-Compliance Reports.

http://www.gmp-compliance.org/enews_05225_Fraud-and-Major-GMP-Violations-at-API-Manufacturers-in-India-and-China_15165,15339,S-WKS_n.html

 

The Non-Compliance reports in the Eudra-GMDP database of the European Medicines Agency (EMA) are – to a certain extent – the European counterpart of FDA’s Warning Letters. These reports are first drawn up then put in the database after a GMP inspection performed by a representative of the European national competent authorities at an API or medicinal product manufacturer showed serious GMP deficiencies. Similar to Warning Letters, the consequences of Non-Compliance reports are for the companies concerned critical, e.g. withdrawal of the GMP certificate or product recalls.

Two Non-Compliance reports issued at the end of last year concerned API production sites in China and India.

Regarding the Chinese manufacturer “Minsheng Group Shaoxing Pharmaceutical Co. Ltd“, GMP inspectors from the French competent authority found 2 critical and 4 “major” deficiencies. Those deficiencies are summarised below:

  • Falsification of source of starting materials: the starting materials supposed to have been manufactured in-house actually came from an external non GMP-compliant supplier and have been repackaged and relabelled accordingly (critical deficiency).
  • The API manufactured according to the Chinese Pharmacopoeia was wrongly and intentionally released as USP quality; there was no traceability of the testing activities (critical deficiency).
  • The cleaning and maintenance operations of the manufacturing line were insufficient (major).
  • Deficient equipment design (pipelines); non-compliant transfer of the intermediate solution using nitrogen; non-compliant change management with regard to equipment (major).
  • Hoses were lying on a dirty floor of an area not mentioned in the general layout of the site. Those hoses were unidentified and their cleaning status was unclear (major).
  • Audit trail function in the chromatographic system was deactivated; there was no procedure in place for audit trail (major).

By the way, the inspection of the Chinese manufacturer performed by the French authority was part of the prequalification programme of the WHO which means that it had been initiated by the manufacturer himself within the framework of his application for the inclusion of his products in the list of prequalified pharmaceutical APIs of the WHO.

Secondly, the inspection of the Indian company “AstraZeneca Pharma India Ltd.” was carried our by inspectors of the Swedish competent authority. The GMP deviations observed are summarised below:

  • The manufacturing process of the API was not sufficiently validated (major).
  • The documentation routine was not GMP-compliant (major).
  • Data integrity wasn’t assured (major).
  • Design and maintenance of the equipment was insufficient (major).

The GMP deficiencies discovered in both production sites concern essential GMP requirements for the manufacture of APIs as laid down in the ICH Q7 Guideline and in the EG GMP Guide Part II since already 16 years. Unfortunately, GMP inspectors from European authorities, the EDQM and the FDA are – again and again – confronted to such GMP deficiencies, mainly in Indian and Chinese manufacturing sites.

 

///////// gmp Violations, API Manufacturers, India,  China

Advertisements

Author: DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......http://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

One thought on “Fraud and Major GMP Violations at API Manufacturers in India and China”

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

w

Connecting to %s