Agency to monitor Chiron processes as flu vaccine manufacturing resumes

04/01/2005

BY CAROLYN MATHAS

EMERYVILLE, CA-The United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) has restored Chiron Corp.’s (www.chiron.com) license to manufacture Fluvirin vaccine at its Liverpool, U.K., facility, but the agency will continue to monitor the company’s manufacturing process remediation steps.

Production of the flu vaccine was halted last fall after certain lots were found to be contaminated with the serratia marcescens bacteria-known to cause urinary tract and wound infections, as well as pneumonia, and to be resistant to antibiotics. The company was later cited by both the MHRA and the FDA for failure to adhere to several cGMPs at the Liverpool plant.

In December, Chiron received a warning letter from the FDA based on its own inspection observations, and asking for additional detail regarding investigations into cGMP deviations. The same month, Chiron also received notice from the MHRA proposing a continuation of the suspension for an additional three months-designed, according to the MHRA, to “give Chiron more time to carry out its remediation plan.”

The MHRA, which has jurisdiction over FDA-licensed companies on U.K. soil, had based its suspension on the belief that despite Chiron’s internal investigation and testing, the process to ensure contamination-free vaccine to the U.K. was not safely in place. A separate on-site investigation by the FDA later determined “significant deficiencies in quality control and concerns regarding test results.”

Under the condition of the restoration, announced in early March, Chiron must maintain a high level of commitment to its remediation plan and continue ongoing improvements, reporting to the MHRA weekly to ensure its plan is on target.

Chiron spokesperson Alison Marquiss says, “We haven’t given much in the way of details as to exactly what Chiron has improved, but it encompasses our manufacturing processes, quality, and governance-our people.” But CEO and Chairman Howard Pien acknowledges, “We wanted to look at the training and indoctrination programs that reflect the changes that we’re making because being able to sustain those changes that we make, and doing it reliably, is one of the hallmarks of the standards of quality from a regulatory standpoint.”

Pien adds, “Our goal is not to get our license back alone. Our goal is that once we achieve the restoration of the license, that we’re going to be able to sustain it because we want to be in a position to be consistent and reliable in providing the vaccines to the public.”

Chiron is in the process of building a new facility in Liverpool, which Pien says will implement state-of-the-art procedures, machineries, and work flow. The new facility is expected to be ready for manufacturing in 2007 or 2008.

Meanwhile, Pien says, Chiron will be going “full force ahead” on vaccine production for the 2005-2006 flu season. He says the company has adopted a “comprehensive and systemic approach to manufacturing quality, as well as taken steps to strengthen our management capabilities and team.”

In order to manufacture its Fluvirin vaccine for the U.S. market in time for the 2005-2006 influenza season, Chiron says it must begin the process-which requires the use of hundreds of millions of specialty raised chicken eggs-this spring. The company already has a cell culture flu vaccine program underway. Cell culture has an advantage over the use of chicken eggs because it is based on a much shorter process cycle. According to Pien, “Reliance on eggs necessarily increases the total duration of manufacturing because you have to put the seed intothe eggs and allow the seeds to grow and then harvest the product out of the egg. It takes a considerable length of the total four to five month duration that is estimated to be the production cycle.” III