Avian Flu Prompts Preparation for a Flu Pandemic
From 2003 to 2006 multiple cases of the avian flu (H5N1 bird flu) were reported throughout the world. Although only a few outbreaks occurred in the US, scientists and government officials were concerned that a flu pandemic could occur because humans have little or no immune protection against the virus. To prepare for a possible future pandemic, the US government created a National Strategy for Pandemic Influenza in November 2005.
The strategy states, "In combination with traditional public health measures, vaccines and antiviral drugs form the foundation of our infection control strategy. Vaccination is the most important element of this strategy."1 To support this strategy, the US government will, "establish domestic production capacity and stockpiles of countermeasures to ensure … sufficient vaccine to vaccinate the entire U.S. population within six months of the emergence of a virus with pandemic potential."2
As part of this strategy, in January 2009 the US Department of Health and Human Services awarded Novartis a $486 million contract for a flu vaccine facility.3 Plans were already underway to complete a vaccine production facility in Holly Springs, NC by 2012. This facility would provide the US government a supply of flu vaccine and capacity to manufacture 150 million doses of pandemic vaccine within six months after a flu pandemic is declared.4
Collaboration with OEM’s
In April, 2009 the H1N1 flu, commonly referred to as the swine flu, was first detected. The virus spread globally with unprecedented speed and in early June the World Health Organization (WHO) declared the outbreak to be a pandemic. Shortly after the outbreak, the US government began working closely with drug manufacturers to make a H1N1 vaccine available in 2009 and to increase production capacity in the US.
Construction at the Holly Springs, NC facility began in 2007, which includes a number of bioreactors, fermentation skids, and other processes including MF59 adjuvant required to produce the flu cell culture based vaccine. Novartis contracted several OEMs (Original Equipment Manufacturers) to build the skids. To construct the skids, OEMs would need hundreds of valves in multiple configurations. ITT provided technical support and valve manufacturing for the OEMs working on the Novartis facility.
Success through Teamwork
In order to provide assurance that Novartis could meet all H1N1 pandemic demand requirements, the MF59 adjuvant area of the Holly Springs facility was greatly accelerated. During the Spring and Summer of 2009, ITT worked closely with individuals at Novartis, its distributors Fail Safe and MG Newell, and multiple OEMs. In May, one OEM contacted Andrew Mahoney, Channel Relationship Manager at ITT Pure-Flo to see how quickly ITT could provide valves for the adjuvant skid. An adjuvant is what Novartis adds to the vaccine to help stimulate the human body's immune response. That same day Mahoney responded to the OEM with a commitment date. On May 20, ITT received the first purchase order for valves and began working on the large job.
To ensure that all the valves had the correct orientation and end connections necessary for the skid, ITT worked closely with the OEM and Fail Safe in Milwaukee, WI. Normally, it takes several weeks to get final drawings through the design, review, and approval process. Since there was no time to spare, ITT provided additional services to expedite the design review process. Mahoney met for several hours with OEM Engineers and Bruce Tucker from Fail Safe to review the P&ID (piping and instrumentation diagram) for the skid.
Bruce Tucker said it was, "An amazing amount of detail compressed into a short amount of time." During the meeting the team looked at each valve to determine the orientation, end connections, and actuation required to work with the piping design. In the end, only one of the valve specifications had to be modified later, which is a testimony to the team. What usually takes several weeks took only one day!
The final list of valves for the adjuvant skid included 46 standard two way valves, 18 sterile access fabrications, 2 three valve fabrications, 6 multi-port divert valves, and 9 custom block body valves. The standard valves and fabrications shipped in only three weeks while the multi-port diverts and custom block valves shipped in four weeks.
One of the custom block valves shipped in only three weeks even though it had only been manufactured a few times before. The unique design was an inverted IDSA (integral dual sterile access valve). The IDSA integrates access on either side of the valve, with minimal deadlegs and hold up volumes. The integrated block design provides the versatility to orient the sterile access valves up or down, which can not be easily accommodated in a sterile access fabrication.
Inverted Integral Dual Sterile Access (IDSA)
In addition to the valves for the adjuvant skid, ITT manufactured valves for several other areas of the Novartis facility including the bulk building, fill finish, and central utilities building. To complete the projects, ITT Product Specialist Miles Chamblee worked closely with ITT distributor MG Newell in Greensboro, NC and several other OEMs assigned to the projects. Some of the skids built for these areas included filtration skids, point of use coolers, COP stations, media transfer skids, and ultra filtration skids.
Dave Johnson, BioPharm Market Manager for MG Newell and Chamblee communicated directly with Novartis to prioritize the critical path valves. Novartis identified the valves that were directly related to the vaccine production process. This allowed ITT to expedite the critical path valves.
Communication, Hard Work, and Flexibility
To manufacture all the valves required in a short time period, hard work, flexibility, and communication were essential. The ITT production team in Lancaster, PA worked seven days a week. Several valves were modified in the middle of production, which required mid stream rework and flexibility. The production team worked hard to manufacture valves for Novartis while still meeting deadlines for other customer's orders.
Communication was necessary to plan for the large amount of valves on order. To keep communication flowing, the production, sales, and customer service departments joined together for update meetings every other day. These meetings allowed the production team to reschedule work as required. Then the sales and customer service team could contact customers to communicate changes in the production schedule. Since a large number of valves were required in a short time period for Novartis, some other orders were delayed. Customers understood and accepted the situation when ITT communicated to them the need to manufacture valves for the H1N1 vaccine production.
Lancaster Site Manager Mark Steele reported that despite the long hours, "Employees in Lancaster were excited to have a positive impact on a global health issue. We are proud to manufacture valves that will help produce the H1N1 vaccine and benefit thousands of Americans."
In 2009 ITT supplied 192 valves, including 69 standard two way valves, 41 two or three valve fabrications, 41 multi port divert valves, and 41 custom block body valves for the vaccine facility. In total Novartis has received 1121 valves from ITT for this project.
The Future of Vaccine Production
Although the majority of valves have been delivered, ITT's work is not complete. ITT will supply after market support in the form of maintenance training and local inventory through MG Newell. The valves will be analyzed to determine the type and quantity of critical spare parts required to support production at the facility.
In addition to the valves supplied to Novartis, ITT is a key manufacturer for drug makers around the world. To support health concerns globally, Chuck Graves, Director of Sales & Marketing for the valve group said, "ITT is expanding valve production to the Asia market to support drug and vaccine production overseas."
1. Homeland Security Council, "National Strategy for Pandemic Influenza," (November 2005): 5
3. Development of Novartis' cell-based influenza vaccine, construction of the cell-based influenza manufacturing facility at Holly Springs, NC and purchase of H1N1 antigen and adjuvant are being funded in whole or in part with Federal funds from the Office of Public Health Emergency Preparedness, Office of Research and Development Coordination, under Contract Numbers HHSO100200600012C, HHSO100200900101C and HHSO100200800072I, respectively. (http://www.novartis.com/newsroom/media-releases/en/2009/1339223.shtml)
4. Dr. Andrin Oswald, CEO of Novartis Vaccines and Diagnostics, "US Department of Health and Human Services awards Novartis USD 486 million contract to build manufacturing facility for pandemic flu vaccine" Jan. 15, 2009 Media Release (http://www.novartis.com/newsroom/media-releases/en/2009/1282432.shtml)