Regulatory Focus™ > News Articles > Swedish Regulators Halt Imports from AstraZeneca’s Indian API Plant

Swedish Regulators Halt Imports from AstraZeneca’s Indian API Plant

Posted 15 December 2015 | By Zachary Brennan 

Swedish Regulators Halt Imports from AstraZeneca’s Indian API Plant

European imports from AstraZeneca’s now-closed terbutaline sulphate active pharmaceutical ingredient (API) manufacturing facility in Bangalore, India were halted by Sweden’s Medical Products Agency after failed validation runs, according to a recent notice in EudraGMDP.

“The concerned API-batches or finished product containing the API should not be imported to the EEA [European Economic Area],” the agency said. “All API batches manufactured during the year 2014 are concerned. This includes all batch numbers starting with TAIO and TABO.”

These batches, which AstraZeneca claims are only for the Chinese market and will be manufactured into finished products (the beta-agonist Bricanyl) at its site in Wuxi, China, have also been sent to Sweden. The Swedish regulators said they expect the publication of this notice will “prevent the API and finished product from being imported to the EEA from China.

“It is recommended that the site is not approved in any new or ongoing applications before a re-inspection has confirmed GMP-compliance,” they said.

The site’s EU GMP certificate expired in February 2015.

The notice came a little more than a week after AstraZeneca announced that it would close the site due to “low demand” for product in export markets. However, it also says its “new state of the art tablet manufacturing plant will continue to operate” at the same site, as it’s been “ramping up” production volumes.

Abigail Bozarth, spokeswoman from AstraZeneca, told Focus the company received the non-compliance statement. "All batches of API terbutaline sulphate (TBS) manufactured at the site and released for formulation in 2014 met registered specifications," she said.

Inspection Results

Of the 24 deficiencies found during the inspection in January, none of the deficiencies was critical but four were major, including in the areas of documentation routines and data integrity (2), design and maintenance (1) and validation (1).

“After three CAPA responses from the company, the major deficiency regarding validation still remains,” the agency said.

Of the five validation runs from February to November 2014, the first four “failed and included several OOS [out of specification] results, adjustments, test batches and inappropriate root cause analysis. After the fifth validation run, the company stated that the process was successfully validated, despite a specification change (exclusion of a melting range) was necessary to approve the validation. After the validation, the rejection rate was very high (approximately 40%) and for this reason the company stopped the production in December 2014.”

Almost a year later, in October 2015, AstraZeneca “confirmed that a definite root cause has still not been identified and that no further manufacturing of the API is planned for this site.”

Eight API batches were released from the site in India without any restriction, but they were retested and released a second time in Sweden.

“The issuance of this NCS is not expected to have a negative impact on the supply [of terbutaline sulphate] to the EEA,” Sweden’s Medical Products Agency says, noting that even though it told the company in June to recall all terbutaline sulphate batches not supported by an acceptable validation, the batches “have not been recalled but the further use of them has been stopped.”

The Swedish regulator says it will request that Indian officials recall the written GMP confirmation for the site.



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