How a Cepheid Molecular Test is Made with Dr. Fred Tenover

Hi, I'm Dr. Fred Tenover. I'm the [former] Vice President for Scientific Affairs at Cepheid, a molecular diagnostics company here in Silicon Valley in California. Prior to coming to Cepheid, I worked for the centers for disease control and prevention in Atlanta for about 20 years where I focused on antimicrobial resistance and healthcare associated infections.

When I think about designing a diagnostic test, four things come to mind. Number one, the need. Number two, the impact. Number three, customer input. And finally, developing the right team.

So if you look around us, there are hundreds of viruses, thousands of bacteria that can cause infections and multiple genes involved in oncology. And the question is do they all need a test? No, they really don't. So we're going to look at the unmet clinical need. We're going to look at where we really need a new test to make a difference, the impact, and we're going to take the test that has the biggest impact on helping doctors, helping microbiologists, helping infection control people to do their jobs better.

So we've narrowed it down from the big need to the best impact, and now we're going to go back to the customer and say, “hey we've got this idea what do you think about this?” And so we're looking for that buy-in from them from the people in the laboratory from the doctors.

And remember, it's not just a doctor in a hospital because doctors in the emergency department will have a slightly different idea from a surgeon. They will have a different idea from an infectious disease specialist. They'll have a different idea from the people who whose job it is to control infectious spread in the hospital.

We're going to ask all these people what they think, and then we'll throw in some nurses, some pharmacists, and maybe even some quality assurance people, and we'll take all these opinions together. We'll put them together and say this is the test we want to build and then we'll go assemble the team within cepheid to make that test a reality.

So how long does this whole process take from the time we get our idea until the time it's actually on the shelf and ready to sell to people? People might be surprised if I tell you it usually takes about two to three years. Why is that? Well, here's the thing that you need to remember and that is it's more than just the research and development part of the equation.

We need to build that test. We need to make sure it works in the hospital or in the outpatient clinic which means we need a clinical trial. That alone can take four to six months. Then we need to make sure that we can take this product and build it. So, there's a whole manufacturing process that goes into this.

When we hand that off from the research and development people to the manufacturing people, we say here go build this and they say okay we can now build it. And then we have to launch it. We need to make the product readily available to people in the laboratory and after that whole period of time, now we have an accurate test that does its job – that works in a laboratory that people can then use to give a great diagnosis to a physician who can then act on those results.

Okay, so we've talked about this process where we've developed a test. We've done the clinical trials. We've showed its accuracy. We've taken our data to the Food and Drug Administration. They've looked at it, and they've said this is great, you can market this test. That approval process again can take a number of months, so all in all, two to three years.

Well, we didn't have two or three years to make a new assay for SARS-CoV-2 because there was such a need to have a diagnostic test available rapidly. The Food and Drug Administration allows you to take this new pathway. The Emergency Use Authorization which says you have to still do all the basics. You have to prove it's sensitive. You have to prove it’s specific. You have to prove that it works in the hands of the laboratory, but the usual clinical trial gets dramatically shortened.

You know, there's a lot of different ways that we can approach making a diagnosis for an infectious disease. We can look at the nucleic acid that is the genetic signature of the particular organism. In this case SARS-CoV-2, it's an RNA virus. We can look at the protein that's around the outside of that virus. Or we can basically go into the human and say hey did you make a response to this? Did you get an infection already?

In the case of Cepheid, we have focused on the first way – detecting that genetic signature in the RNA and the virus. Why do we do that? Because it's the most sensitive. It's the most specific. For those reasons, we look at the nucleic acid amplification test or PCR as the best approach for this particular infectious disease.

So what makes a test accurate? What makes a good test? Well, there's really two major things we look at. That's the sensitivity of the test and that means do we detect every patient that has the disease and specificity? That is we want our tests to be negative in people that do not have this this particular disease and sometimes that's a challenge because remember there's more than one Coronavirus out there.

As a matter of fact, there are hundreds of Coronaviruses. It's one of the most common causes of the of the common cold as a matter of fact. And then there's some that are more pathogenic. The original severe acute respiratory syndrome virus and the Middle East respiratory syndrome.

Those are both Coronaviruses but this one's unique. So that genetic fingerprint that's in that virus allows us to hone in on what makes it unique. So once we make our test, then we do test it against a whole host of different coronaviruses and say is it positive only for SARS-CoV-2. So now at the end of the day, we recognize just the SARS-CoV-2 virus and nothing else. Highly sensitive, highly specific. That's accuracy.

So now we have the situation where the research and development team has done their job. They've developed this assay. Now we have to hand it off to manufacturing and say build this for us. So what does that actually mean? Well, this is a pretty complicated process because we have a cartridge, a very intricate piece of plastic. We have reagents and buffers and beads that need to go into that. We need to put this all together have a label on it and in order to do that we need a pretty competent team of people to put everything together.

One of the things we learned very early on about infectious diseases is they are not static organisms. They are constantly adapting, constantly changing, in order to be able to infect other people. So we're aware of this and we are trying to keep one step ahead of the infectious diseases by making sure that once it's out there, it stays robust. It stays accurate and it does its job.