Create a free account to continue

The Incredible Egg-Opening Machine

Innovative use and integration of a laser egg opening system eliminates cross-contamination and increases processing efficiency.

Novartis Vaccines provides more than 20 vaccines to prevent viral and bacterial diseases, and is dedicated to delivering on its promise of prevention through the research, development and production of innovative, safe and effective vaccines. The company’s new MARS (Marburg Site) facility in Marburg, Germany was designed and built to be the company’s “Center of Excellence” for modern vaccine production.

The company’s efforts to design and build a flexible vaccine manufacturing facility incorporating a state-of-the-art laser egg-opening machine has resulted in the facility winning the Equipment Innovation award in the 2011 Facility of the Year award competition jointly sponsored by ISPE, INTERPHEX and Pharmaceutical Processing magazine.

MARS -- A Completed Integrated Site

The MARS Project integrated on to one site the manufacture of existing vaccine concentrates and the production of media, buffer and adjuvant products.

The project also integrated support functions, such as equipment cleaning and sterilizing, by centralizing the facilities at the Marburg site. Other accomplishment of the MARS Project included a new Quality Control building that consolidates the analytical and quality control functions for the Marburg sites. In the process of designing and building a state-of-the art vaccine facility, the company also seized upon the opportunity to enhance lean manufacturing techniques, to innovate processes and improve equipment design and operation, to ensure that the new buildings meet the latest sustainability trends and to create an excellent working environment for operations and QC staff with open views from all operating rooms to the country-side around the site.


The production facility is capable of manufacturing 20 million doses per year of rabies vaccine or 40 million doses per year of tick-born encephalitis vaccine or any combination of the two, utilizing two interchangeable production lines. The media, adjuvants and buffer production at the site supports all of the 20 vaccines within the Novartis portfolio.

The QC facility performs 35,000 to 40,000 analytical tests and more than 100,000 environmental and utility monitoring samples per year.

The warehouse serves an integral part of the production facility ensuring lean raw material and final product movement via a connecting spine. It has a capacity of 4,000 pallet spaces with chilled and ambient temperature storage.

Full Facility Flexibility

The design leverages the revised requirements for live vaccine processing issued by the FDA in October 2007 and made effective in July 2008. The design and operating concept allows concurrent manufacturing of two different live vaccines on two segregated manufacturing lines in the same production area. The changeover procedure allows the facility to switch manufacturing from one vaccine to the other and also enables the facility to manufacture two vaccines either concurrently or in campaign.

This inherent flexibility allows the facility to respond quickly to health and market needs and reduces the cost of running dedicated facilities.

Processing Steps

At the Marburg site a new process flow was implemented that enabled the facility to achieve a 10-fold increase in productivity. The basics of the process include:

  • Cell preparation: The upstream of the process is based on the infection of a suspension of chicken embryos fibroblasts with live virus. The cells and the viruses are incubated at controlled temperature for 5 days in single use cell factories and the virus suspension is harvested into a fixed stainless steel vessel.
  • Virus propagation: The harvest is then filtered in a second vessel in which the inactivation agent is added to the harvest and mixed. To complete the inactivation, a maturation step takes place in a third vessel.
  • Inactivation: A purification/concentration step by ultracentrifugation on sucrose gradients completes the process. The transfer between vessels and to the ultracentrifuges is with stainless steel lines.

From the harvest vessel to the ultracentrifuge, the bio-safety and the sterility of the product is ensured by a closed system. All transfers are driven by the automation system. Transfer lines and vessels are sterilized with clean steam (SIP), cleaning in place (CIP) by units dedicated to each of the two manufacturing lines.

The Heart of the Facility

It might seem odd and a bit old-fashioned in this modern age to consider that the manufacture of vaccines is still primarily based on eggs. But this is still the case in many facilities around the world. At the Marburg site the key to the dramatic production increase was the installation of a highly automated laser egg opening machine.

As mentioned above the production of TBE/rabies vaccine consists of three major production steps: preparation of the cell suspension; virus propagation and concentration of the inactivated virus.

In the first step of production, SPF (specific pathogen-free) eggs are used to produce cells for the next steps in the production flow. In the new MARS facility the process of opening of the eggs is performed using an industrial scale laser process under strict clean room conditions. The laser egg opener (LEO) automatically opens eggs in parallel while maintaining aseptic conditions. Within the new LEO handling system in the MARS facility, the pre-disinfected eggs are handled on trays with a capacity of 84 eggs with the potential to accommodate 3000 eggs/ hour. The trays are manipulated by the operator at the “front end” of the laser egg opener within a laminar flow tent. Transportation of the eggs through the egg opener is by means of a conveyor belt system controlled by optical sensors. These can detect tray position and occupation. This ensures that the laser is only distributed to the eggs present and not to the empty spaces. The layout of the trays and the conveyor system allows the opening of 4 eggs in parallel using 4 individual laser beams. The benefits of the LEO are: the elimination of cross contamination and increase process throughput contributing to the overall 10-fold productivity of the facility.

The opening of the eggs in the past was performed manually with the help of an “egg puncher” which operated pneumatically. The operator needed to manually open every single egg with this device. This older method is carried out under clean room classification and increases the risk of cross-contamination due to the contact and damage to the eggs.

Judges Impressed

In their selection of the Marburg site as a category winner, the judges mentioned several key factors that influenced their decision. Among them was the quick project execution of only 26 months, the impressive safety record of a 1.7 million manhours with no lost-time incidents; and finally the innovative use and integration of the laser egg opening system which eliminated cross-contamination and increased processing efficiency.