Lonza “is working closely with the Food and Drug Administration (FDA) to address these issues,” which are expected to cause interruptions of the supply of the drug in June in the US and in August in Europe and the rest of the world, according to Ipsen. The company also said it does not expect supplies of the Insulin-Like Growth Factor Deficiency (IGFD) treatment to resume this year.
“Unfortunately several problems have occurred preventing the production of batches meeting the quality standards necessary for use in patients,” Didier Veron, a spokesman with Ipsen told Outsourcing-Pharma.com. “FDA inspections in 2011 and 2012 confirmed these findings. Corrective actions have been implemented and a concerted manufacturing campaign is underway to produce batches that meet the required quality standards.”
In 2011, the Massachusetts site was hit with a warning letter after the FDA took issue with the way it manufactures an API for Eisai’s oncology treatment Ontak.
Current lots of Increlex (mecasermin [rDNA origin] injection) in the marketplace were manufactured using an alternative drug substance manufacturing facility that has not been approved by the FDA, according to the agency. But Ipsen said it is working with the FDA to “minimize any supply disruption” and will seek approval for the third-party manufacturing facility.
In the meantime, the FDA exercised its regulatory discretion for Increlex lots #081603F and #121353F, and allowed them onto the market. These lots contain drug substance supplied by the other third-party manufacturing facility but Ipsen said they “have undergone a full Ipsen internal review to ensure that they meet quality and safety standards.”
The European Medicines Agency (EMA) also notified its member states of the shortage and manufacturing problems with Increlex, saying stocks will run out beginning in early August.
“The problems are linked to equipment failures at the site which are currently being addressed by” Lonza, the EMA said.
Ipsen, meanwhile, said it is not aware of any other approved IGF-1 pharmaceutical product in the EU or US and there are “only limited data on the clinical consequences of stopping Increlex treatment in patients with Severe Primary IGF-1 Deficiency,” the company said in a letter to health care providers.
“Despite supply shortage issues with Increlex, Ipsen confirms its 2013 guidance, both in terms of sales and recurring adjusted operating margin,” Marc de Garidel, Chairman and CEO of Ipsen said in a conference call on the company’s Q1 2013 results last week. In 2012, Increlex sales totaled €28.3m ($37m).
Ireland Site Closure
Earlier this year Lonza hinted at manufacturing costs at all of its sites, noting poor performance from its manufacturing sites. A spokeswoman also told us at the time that quality-related expenses at the Massachusetts plant negatively impacted the company’s bottom line.
In addition to the US dilemma, Lonza will close its manufacturing facility in Swords, Ireland in June. The 32 employees and 11 contracted staff will receive severance packages as part of the closure. The company will transfer all of the products manufactured at Swords to its plants in Rochester, NY, and Suzhou, China. The Swords site was part of the Arch Chemicals business acquired by Lonza in October 2011.