Name:
RMN-2020-004
Description:
Mike Brewer - Interview V10
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Duration:
T00H05M50S
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Upload Date:
2020-02-26T12:50:42.8630000Z
Transcript:
Language: EN.
Segment:0 .
[MUSIC PLAYING]
MIKE BREWER: My name is Mike Brewer. I am the director and global principal consultant on the regulatory side for Thermo Fisher Scientific (MA, USA). Specifically, our bio-production business unit.
Segment:1 How severe a problem is the presence of mycoplasma?.
MIKE BREWER: Rapid mycoplasma testing is critically important for cellular therapies, because many of these, they are required to be tested for the presence of mycoplasma. But they do not have the shelf life that enables testing with a 28-day culture-based test, so you have to be able to test them in a time period that's appropriate for the expiry or the shelf-life of the product, to enable infusion into the patient. And it needs to be an accurate test. And it needs to be sensitive, because, you know, this is – in the cellular therapy, the cells are the drug. If they were contaminated and that was not detected, that could be problematic for the patients. So you want to have the highest level of confidence in the test you're using. And I think our test enables that.
Segment:2 How does the MycoSeq system work?.
MIKE BREWER: So the Thermo Fisher MycoSEQ system is based on qPCR for the detection. We also have a sample preparation component of that, as well, because it's important to be able to extract the maximum amount of nucleic acid out of a test sample prior to testing it with a very sensitive qPCR-based assay. We actually share the sample preparation chemistry with our quantitative host cell DNA assay, which our customers validate greater than 90% recovery of the nucleic acid in the samples using that chemistry. So, combining that with our highly sensitive dye intercalation based qPCR detection technology, it enables us meeting or exceeding the most rigorous regulatory expectations in a validation.
Segment:3 What were the challenges in developing the MycoSeq system?.
MIKE BREWER: So the challenge we had in developing the method – we were aware of what the regulatory expectations were from the US FDA (MD, USA) meeting that took place in 2009, as well as the European Pharmacopoeia published some guidance on nucleic acid-based tests for mycoplasma and what the sensitivity and specificity expectations were. So we had a target to go after.
MIKE BREWER: What we found is – we initially were using a probe-based taqman-based qPCR assay. And what we found is that in order to cover all the species of mycoplasma that regulators expected the assay to be able to provide detection of, with the adequate specificity – that is, no detection of off-target organisms – we found that with the taqman technology, the assay was becoming increasingly complex.
MIKE BREWER: So we explored another approach using a dye intercalation based chemistry, where a dye becomes fluorescent when bound to double stranded DNA that's created in a qPCR cycle. And we combined that with a highly multiplexed approach with primer design. There's 32 primers in the assay. So it enables essentially comprehensive detection of the mycoplasma species that needed to be targeted and detected. And it provides the detectability in a very highly sensitive manner, slightly more sensitive than taqman at the lower end, or near the limit of detection of the assay. But I think most importantly, we are able to overcome that challenge of variability across the species that we were encountering with the taqman approach.
Segment:4 How has the biotech industry changed over the last 30 years?.
MIKE BREWER: Yeah. So I have been in the industry for a significantly long time. And certainly, there's been remarkable tremendous change from what we were doing in bio-therapeutics in the early 80s. The type of molecules we're making – it was mainly, we're cloning human genes and expressing human proteins. Now, we've gone to a multitude of therapeutic modalities: monoclonal antibodies, the use of those has expanded tremendously. But also, as we're here, facilitate, cellular gene therapies have taken off tremendously.
Segment:5 How has advanced therapy manufacturing changed?.
MIKE BREWER: We've seen changes in how companies manufacturer their products, both the manufacturing technologies and the flexible and re-configurable single-use-based bioreactors and purification systems. Going away from US$50 million stainless steel facilities that we're required to build, to manufacture your drugs before you even knew if you're going to be able to get it approved. So that's been a huge change. And also, the role of, I guess, contract manufacturing organizations. You don't have to – you can use a contract manufacturer to generate clinical and even commercial product. So you don't have to make that big investment in a manufacturing facility before you know if your drug is going to be successful.
Segment:6 What will be the next hurdle in contaminant and purity testing?.
MIKE BREWER: The next big hurdle for contaminant and impurity testing is likely to be the use and ultimately regulatory acceptance of next generation sequencing-based technologies to detect virus and hopefully supplementing or even replacing the 28-day or 14-day based cell culture-based advantageous agent test.
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