US ban for levonorgestrel supplier Qinhuangdao Zizhu raises WHO concerns

Discovery of data problems at Qinhuangdao Zizhu’s Hebei API plant indicates the firm did not follow a remediation plan agreed after a prequalification inspection in 2015 according to the WHO.

The US Food and Drug Administration (FDA) banned Qinhuangdao Zizhu Pharmaceutical from supplying drug actives made at its plant in Hebei, China this month after finding “data integrity” problems during an inspection in December.

The US import alert raised concern at the World Health Organisation (WHO) because the Qinhuangdao site is the only source of the hormone levonorgestrel in two contraceptive products used in its programmes.

Because of the lack of an alternative source the WHO said procurement agencies can continue to buy contraceptives containing levonorgestrel supplied by Qinhuangdao, but urged drug manufacturers to implement additional testing procedures on receipt.

The WHO approved Qinhuangdao to supply levonorgestrel as well as mifepristone and ethinylestradiol in 2015 despite identifying data integrity issues during an inspection of the facility in October of that year.

At the time the WHO said Qinhuangdao had provided it with corrective and preventive actions (CAPAs) that addressed all the deficiencies and approved the firm as a supplier without re-inspecting the facility.

Inspection history

The US FDA’s discovery of “broadly” similar problems is a worry according to a WHO spokesman.

He told us “The fact that the FDA found similar issues is very much a concern since this appears to indicate improvements were not made as they should have been as indicated in the company response.”

He declined to share details of Qinhuangdao CAPAs but did say the responses provided by the company were considered to be adequate.

When reviewing CAPAs WHO can, and does, insist upon follow-up inspections to confirm the CAPAs were adequately implemented, but this was not considered necessary in this instance” the spokesman continued, adding that once prequalified sites undergo routine inspections.

He also said that: “Of course, if events were occurred in the reverse order, then the availability of the US FDA information would presumably mean we would have insisted upon a follow up inspection, but this was not the case.”

Alternatives

The WHO confirmed it has two API prequalification applications under assessment for levonorgestrel and one for ethinylestradiol. 

No manufacturer has applied to supply mifepristone for WHO programmes.

Qinhuangdao Zizhu did not respond to a request for comment.