What Would You Do in the Event of Contamination?- Transcript of an Interview with Lada Laenen

Gerald Clarke:          Hello, everyone, and welcome to this Pharma IQ podcast. I’m Gerald Clarke, Editor at Pharma IQ. Today I’m joined by Lada Laenen, Managing Principal Scientist, Head of Cell Culture and Microbiology at Genzyme, a Sanofi Company. Lana, it’s a pleasure to have you here.

 Lada Laenen:             Thank you very much.

 Clarke:           Lana, in 2008 and 2009, Genzyme sites were affected by the Vesivirus contamination. This resulted in two plants shutting down for de-contamination. How did this affect Genzyme?

 Lada Laenen:            The site in Belgium, the second plant infected with the virus, was at the time not yet in commercial production, so the impact to this plant we were just partly in the process of validation and was relatively minimal as we did not supply any patient material at the time. But of course cleaning the facility, restarting the facility, and then bringing it back to operational status is quite a large work to be done, it’s costly work, specifically as we have not been able to immediately identify the Vesivirus infection. It took us quite some time prior that we make a lot of work to getting this issue to the point and try to tackle the real problem.

 The facility in the US, they had been producing commercial material. Patients were affected; much of the material that needed to be delivered to patients at the time was not able to be delivered, so the impact to the patient community was quite large, and as a company extremely connected to our patients and they are connected to us, it made it extremely difficult to keep up and to try to resolve this problem at the time, and to now be able again to provide the material. So the impact was huge. It was not only financial, but also the image of Genzyme, the patient community, etc, so such a huge impact of such a contamination I think should never be underestimated.

 Clarke:           Could you tell us a little bit more about Genzyme development of an ‘organisms of concern’ list and how this helps the Company mitigate risk?

 Laenen:          We had decided at the time to have a very strong bio safety programme, and to really put bio safety as one of the major objectives to the side in order to ensure that we don’t have this type of contamination in the future, which we can just do a lot of actions in order to prevent having the contamination, but it’s not assurance that we are never going to get contamination. But we also want to have an overview of all different contaminants that eventually can enter production. So we have been developing a list of organisms that have been detected in the process flow, as we don’t product a sterile product. These products that are made here can have certain bio burden level, according to the specification and internal procedures, and if we discover a certain organism that we don’t know what this organism would be, and also when we detect it we look at the certain toxins, endotoxins, exotoxins impact to the product, impact to the patient, and we generate of this list in order to be able to classify this contamination or potential contamination in certain categories, which then help us to release the product or to make the process. So it’s quite a useful tool to the Company to really look, not only at organism detection, but also their potential impact and process, and based on this judgment make further firm decisions in processing the product further in process flow.

 Clarke:           What would you do if you received reports of suspected contamination tomorrow morning?

 Laenen:          There are many procedures in place today. We know exactly what we need to do. We have viral contamination or biological contamination response plan ready available on the site, so every department and every group knows exactly what they need to do and how to act in order to try to prevent further distribution of this contamination to the facility. So today it’s very strictly regulated by procedures and documents that are in place, and also we are very closely connected to the other sites, so they are also aware of this problem. So today if such a contamination happened, of course you are always worried and you always try to resolve the problem, but there are also very strict process flows that we need to follow in order to do it, not in a chaotic way, but in a very strict procedural way to address to contain certain processes to address de-contamination and to address the cleaning, to inform other sites etc. So it’s a quite well-organized process today.

 Clarke:           New technology such as massively parallel sequencing is increasingly being utilized for pathogen interaction: how difficult is to know when to use these, and what to test for?

 Laenen:          For example, the new technology, as massive parallel sequencing, I think it’s an extremely useful tool for development purposes, but also for trouble-shooting purposes. I think placing a real baseline to be able to know what the real contamination is or what a real contaminant is and what is some background noise or maybe some things coming out of the raw material, it’s still a topic to be tackled. So these techniques today that are available should be developed in time, and also so the baseline threshold should be placed in order to be able to distinguish between the real contaminant and then, as I said, the background noise. However, I think this technology certainly needs to be further explored and then in time when they are developed to support commercial production, because what we are really talking about today is commercial production, at the end of the day we really need to ensure that we also deliver a safe product to a patient, that we have the right tools to help us to deliver the product, so that there really should be a balance between the new technologies and new tools, and also how well they are developed to support commercial production. But as an investigation of those in that they are extremely useful, and then you should be testing for all, or you should understand all microbial or biological population that’s available in your samples and try to identify how significant these detection organisms are to your process.

 Clarke:           You mentioned the importance of establishing baseline measurements in pathogen detection; why is it so difficult to establish these baseline measurements

 Laenen:          Because today you use raw materials that are coming from everywhere, and some of us are using, let’s say, proprietary media; others are buying media from the vendors. These media are extremely complex media that contain many components, let’s say 50 to 100 different components that come from somewhere, and this is like a black box that we do not understand very well today, so all these different possible contaminants can be in a single component that is such a part of our media. And therefore knowing what the threshold is to understand that from where you should be really worried that it is something that you detect a real contaminant is extremely difficult. Also many of us are still using animal origin materials, some of us trying to move out of this, but this is still the reality for the company as well as Genzyme, so some of the signals can be due to this animal origin designed materials and not really related to real contaminants. So it’s, I think, still huge work in front of us to really establish these thresholds then too, because you also don’t want to miss something, and I think this is a discussion between trying to use the tools in order to detect potential contaminants, but also in another part not to oversee something, and therefore this is quite difficult, and it will take quite some time prior to being able to do so.

 Clarke:           Thank you very much, Lada, for sharing your insights and your time with us today. We look forward to hearing more from you at the pathogen safety event.

 Laenen:          Thank you very much.

 Clarke:           If you would like to find out more about this topic and the Pathogen Safety Summit this November 18-20 in Munich, Germany, visit us at www.pathogensafetysummit.com