Sanofi TheraCys Shortage Prompts Merck To “More Than Double” Supply Of TICE BCG
This article was originally published in The Pink Sheet Daily
Executive Summary
In its latest attempt to get out in front of drug shortage problems, FDA’s announcement that Sanofi Pasteur’s bladder cancer drug TheraCys is unavailable due to manufacturing problems also notifies patients that Merck is stepping into the breach.
Merck & Co. Inc. has more than doubled production of its bladder cancer drug TICE BCG (BCG Live) to make up for a shortfall caused by problems at Sanofi Pasteur’s manufacturing facility for TheraCys [BCG Live (Intravesical)].
TheraCys “is currently unavailable due to manufacturing issues and, according to Sanofi Pasteur Ltd., is forecast to remain unavailable until late 2013,” FDA said July 6, adding that the company had notified the agency of the issue on June 21. “FDA understands the critical need for BCG and is working diligently within our legal authority to help alleviate the shortage of this product.”
Sanofi Pasteur explained, “We have decided to temporarily suspend manufacturing in order to renovate the facility to improve environmental quality management within the production building. The company has informed appropriate regulatory authorities of our actions and the resulting supply interruption. We are working diligently to resume production and make the product available once again.”
In addition to TheraCys, a spokesman added, “our Pentacel and Daptacel combination pediatric vaccines are on allocation as well – we are limiting the number of doses a customer can order from us based on their historical usage.” These vaccines also are exported to the U.S.
The problems were discovered in an inspection FDA conducted from April 10 to 25 at Sanofi Pasteur’s Toronto, Canada facility, which found “numerous deviations relating to the isolation of mold within the aseptic processing areas … [and] failure of the re-validation of the firm’s sterility test method for TheraCys BCG,” according to FDA’s Inspectional Observations Form 483.
“As a result of the inspection, we have appointed new leadership and approved additional head count in our quality organization. We have retained the services of outside expert consultants [and begun] employee training programs,” the Sanofi Pasteur spokesman said, adding that these steps apply to the Toronto facility only.
Only BCG production has been halted there while the building undergoes renovation; production will resume when the line starts up again and the company obtains relevant regulatory approvals; other products are still being made in other parts of the facility.
Merck Is “Meeting The Full Market Demand”
The two attenuated live-culture BCG products from the Bacillus of Calmette and Guerin strain of Mycobacterium bovis are indicated for non-muscle invasive bladder cancer. The Merck and Sanofi products are the only BCG products licensed in the U.S.
Merck said in an emailed statement that it “currently is experiencing increased demand for TICE BCG (BCG Live) due to the unavailability of the one other BCG product marketed in the U.S. In response, Merck has increased production and more than doubled supply of TICE BCG to the U.S. market to meet customer and patient needs.”
While TICE BCG is available through wholesalers, “there may be times that customers who try to order from Merck may experience back-orders,” the company said, adding that, “We don't get into actual production numbers for proprietary reasons, but currently we are meeting the full market demand in the U.S.”
FDA said it has been working with and continues to work with Merck subsidiary Organon Teknika Corp. on ramping up TICE BCG production. The agency said it also is “reach[ing] out globally to manufacturers of BCG who are not licensed in the U.S. in an attempt to identify additional alternate suppliers to meet U.S. demand,” and urged physicians, distributors and others not to stockpile BCG.
“As several BCG strains are produced by different companies the situation is unique for the U.S.,” said Alexandre Zlotta, University of Toronto. “Theoretically all BCG strains should be equally effective. I am surprised as well that no fast-track process was implemented by the FDA to overcome the shortage.”
As shortages of critical drugs have become an increasingly high-profile headache for FDA, the agency has been emphasizing its regulatory flexibility when solving them. In February, Commissioner Margaret Hamburg held a high-profile press conference to announce that the agency was temporarily allowing Sun Pharma Global FZE and its authorized distributor Caraco Pharmaceutical Laboratories Ltd. to import their unapproved liposomal version of doxorubicin to address a shortage (Also see "FDA Drug Shortage Strategy: Enforcement Discretion, Patient Public Relations" - Pink Sheet, 21 Feb, 2012.).
Sanofi’s Problems Range From Polio Exposure To Nesting Birds
FDA’s 483 for Sanofi’s plant notes that the failure to revalidate the sterility test “called into question the current test method’s ability to detect yeast and mold, if present, in sterility test samples. Because of the characteristics of the product, BCG must be produced entirely in an aseptic processing environment which is intended to prevent contamination of the product with other potentially harmful microorganisms.”
“On 2-22-12 an employee was directly exposed to live Poliovirus in Building [redacted] and was taken to the site’s health center. No deviation was written for this incident nor was there any documentation indicating how the employee was decontaminated before being taken to the health center,” FDA says in an Inspectional Observations Form 483 that it posted to its website.
“There have been no less than 58 deviations relating to the isolation of mold within the aseptic operations areas” of one of the company’s buildings since August 2010, the agency says, adding among a long list of other items that the disinfection methods for the manufacturing areas were not proven adequate, disinfection methods specifically for poliovirus had not been validated under conditions of use, various SOPs were being violated, goggles worn by operators who performed aseptic filling weren’t sterilized, significant changes weren’t reported to FDA, environmental monitoring was insufficient in the filling suites and other high-grade areas, and birds were nesting in the intake grills for the air handling units.
The Canadian authorities inspected the facility during the first week of June, and Sanofi Pasteur responded to the inspection report they issued as well.