Testing boundaries

Polymerase chain reaction (PCR) is a complex, yet effective method to copy or “amplify” small segments of DNA or RNA. Recognised with a Nobel Prize in 1993, PCR testing is still the most relevant nucleic acid amplification technology (NAT) test used for the diagnosis of pathogenic viruses or bacteria.

The office of Thomas Gärtner, Head of Corporate NAT Operations, looks almost like an inventor’s laboratory. The walls are plastered with sketches of diagrams and DNA sequence figures, and his desk is covered with piles of technical manuals, reports and regulatory files which he frequently consults. But Thomas, who is also a passionate badminton player and nature lover, has anything but a chaotic mind. As a biologist who wrote his doctoral thesis on the expression of oncogenes in insect cells and the characterisation of proteins, he enjoys immersing himself in detail, without losing the wider perspective. He aims to achieve his goals with precision, efficiency, accuracy and elegance. And he also expects this from his team.

Ensuring viral safety

When Thomas joined Octapharma in 1994, Octapharma was faced with a challenge that had kept plasma fractionators and the pharmaceutical industry busy since the 1980s: how to find the best methods and procedures to reduce the risk of virus transmission through plasma proteins and ensure the highest level of viral safety.

For Octapharma, viral safety and viral clearance evaluation have always been high-profile areas for product safety. So, more than two decades ago, finding the best possible way to ensure viral safety was a clear goal for the company. It was in this context that Octapharma introduced PCR testing.

The techniques and methods used in the 1990s for PCR testing were very time-consuming. “Often two consecutive runs were used, known as nested PCR,” remembers Thomas. “Nested PCR is a modification of PCR that was designed to improve sensitivity and specificity, involving the use of two primer sets and two successive PCR reactions.”

The other challenge that many industry players were facing was that there were no common regulations for PCR validation. In addition, companies had to define their own in-house standards. “With no standardisation of PCR tests and methodologies, there was a risk you didn’t get acceptance from the authorities,” explains Thomas. “Fortunately for Octapharma, we were working with our own state-of-the-art standards and materials.”

Courage in our blood

Back in 1994, Octapharma was a pioneer in performing viral safety tests using PCR testing tools to check for the hepatitis A and C viruses (HAV and HCV) as well as for HIV. “In the beginning, I shared the laboratory space with my former PhD colleagues and other staff members from Georg-Speyer Haus (GSH),” he recalls. “Later on, in 1997, Octapharma launched its first PCR testing laboratory in the GSH building in Frankfurt am Main.”

In that same year, the company made significant strategic investments to develop in-house testing applications using the Nobel Prize-winning technology and the next step for Thomas was to assemble a strong team of technicians. With the technicians on board, the team was now able to develop and validate in-house PCR systems. “This was a huge success for all of us,” says Thomas. “Octapharma demonstrated that entrepreneurship, ownership and courage are in our blood.”

Meeting the challenge

In 1999, PCR testing of plasma pools for HCV became a regulatory requirement. In close collaboration with Thomas, the company’s PCR testing methods were validated and approved by all major regulatory authorities around the world. Indeed, PCR testing became a standard tool for testing for the presence of blood-borne viruses in human plasma and the PCR laboratory performed the first analyses for batch releases of Octapharma products.

By the late 1990s, new advanced PCR techniques were also introduced, such as the TaqMan method, “an elegant and reliable real-time technique,” explains Thomas. Overall, the TaqMan method was much faster and evaluation was more sensitive, precise and less laborious.

As Octapharma expanded, so did the work of the PCR testing team. In addition to the Vienna site, the company acquired production sites in Lingolsheim, France, Stockholm, Sweden and Springe, Germany, and plasma samples from all sites were sent to Frankfurt for PCR testing. Due to the increasing number of analyses, by 2005 it was time for the PCR team to relocate to larger facilities in the Frankfurt Biotechnology Innovation Center (FiZ). Since that time, the portfolio of work undertaken using the PCR method has continued to grow.

Today, Octapharma routinely performs PCR testing on all plasma pools for HIV, HAV, HBV and parvo B19 viruses, as well as for HCV. In addition to these tests at the plasma pool level, every individual donation is also tested.

Taking pride in their work

Occupying the spacious facilities of FiZ, Thomas and his team have managed to install a full range of equipment, from automated extraction robots to real-time thermal cyclers and other modern lab equipment. But it is here that the dedicated Octapharma PCR team works vigorously to provide the best viral safety for our medicines at the beginning of the drug production process.

Ulrike Brandt, who joined the team in 2014, is responsible for the PCR lab support team. “Our job is extremely versatile. We focus very much on viral safety and expect high-quality controls. Clear and targeted communication, persistence and a strong understanding of Good Manufacturing Practice rules are the keys to our success,” explains Ulrike.

Christiane Beckort, Research Specialist, Method Development & Validation, who joined the team more than 20 years ago, considers attention to detail and team spirit to be the secret behind the success of the PCR team.

For the past two decades, the PCR team has always delivered on time, whilst implementing sustainable PCR methods and achieving very good results in all proficiency studies. “Today, more than 20 years after the launch of the first Octapharma PCR laboratory, we can safely say that the team has taken up the challenge of viral safety and mastered it. Everyone involved can be more than proud of their work,” concludes Christiane.

References
https://www.nobelprize.org/prizes/chemistry/1993/mullis/lecture/