Sweden says AstraZeneca used questionable asthma drug API from Indian plant

AstraZeneca ($AZN) said last week it was closing a plant in India that made the API for asthma drugs, noting there is not much demand any longer for the terbutaline sulfate it makes. But what the U.K. company did not say was that before its closing, the plant produced a year's worth of product that Swedish regulators say are suspect and want recalled.

The report says that AstraZeneca stopped production at the Bengaluru plant in Bangalore a year ago after batches of drugs failed repeated validation runs. It said that on Oct. 30 this year, the company confirmed that it could not determine the root cause of the problem and had decided to stop production of the API there. But the European Medicines Agency (EMA) says that before production was halted, the plant released API in Sweden and China even though the batches had failed some validation testing.

An AstraZeneca spokeswoman said in an emailed statement, "We can confirm we have received a non-compliance statement for the API unit of our manufacturing facility in Bangalore. The facility is no longer in use. All batches of API terbutaline sulphate (TBS) manufactured at the site and released for formulation in 2014 met registered specifications."

According to the report, the plant ran 5 validation runs between February and November 2014, the first four of which failed and included several out-of-specification results, adjustments, test batches and inappropriate root cause analysis. It said the fifth validation run was approved by the plant but only after a specification change for melting range. It said after the validation, "the rejection rate was very high (approximately 40%)," which is when production was halted.

Even with those issues, 8 API batches were released from the site without any restriction. Some were retested and then shipped to Sweden. It said 7 batches were sent to AstraZeneca's manufacturing site in Wuxi, China, to make bricanyl tablets that AstraZeneca says are intended for the Chinese market only.

Inspectors cited the plant with 24 deficiencies, with four having to do with validation, documentation routines and data integrity. AstraZeneca was asked to recall all of the terbutaline sulfate batches that were not supported by an acceptable validation, the report says. While that has not happened, it said "further use of them has been stopped. All API batches manufactured during the year 2014 are concerned." Sweden said it intends to follow up with all of the distribution and destruction records for any remaining API batches. It recommended that the EMA not allow any more products into the country from the site until a reinspection has confirmed GMP compliance.

In announcing last week that it was closing the API plant, AstraZeneca said that its tablet-manufacturing operation at that site will continue to manufacture products. The tablet facility opened in 2013 and has continued to ramp up to meet increasing supply requirements.

Testing and data integrity have been ongoing issues at plants throughout the country operated by both Indian and Western drugmakers. This action comes even as a top Indian business group has called on the domestic industry to improve standards to avoid issues with international regulators.

- access the EMA report here