SAFC Builds Bio-CMO Capacity

by Gil Roth

In May 2007, Sigma Aldrich Fine Chemicals (SAFC) acquired Molecular Medicine BioServices, Inc. (MMB), a Carlsbad, CA-based bio-CMO with a focus on vaccines and gene therapy products. Earlier this year, SAFC announced a $12 million expansion of that site, adding 8,000 sq. ft. of manufacturing space and providing 100 L batch production in stirred tank bioreactors and 1,000 L batch manufacturing in disposable bioreactors.

To find out more about these moves, the importance of disposable components in bio-manufacturing, and SAFC’s plans in dosage form manufacturing, I spoke to David Feldker, vice president, U.S. Sales & Manufacturing and David Backer, director, Virus Business Development & Pharma Marketing. Mr. Backer was previously president of MMB.

Contract Pharma: What was SAFC’s strategy in acquiring Molec-ular Medicine BioServices (MMB)?

David Feldker: The MMB acquisition was led on two fronts. SAFC had an important customer that we are working closely with and they were fairly far advanced into clinicals. Our SAFC Biosciences group happened to be doing a lot of work in media development and optimization for them and they loved working with us in that regard. They were also experiencing quite a bit of difficulty with their viral material supplier.

At that point, they were asking us to build capacity to help them. SAFC planned to get into the viral marketplace and had developed a variety of buy/build scenarios, so when Molecular Medicine BioServices became an option, we were able to move quickly to acquire them to take advantage of their existing capacity and expertise.

On the second front, SAFC has a lot of intellectual property and experience in the biotech area related to RNA. Viruses are considered one of the key methods of delivering RNA. A lot of major companies are spending billions in this area, so we needed a means of delivery to commercialize that kind of technology. Now, we have a commercial path for one of the avenues that the RNA technology provides.

CP: Why wouldn’t that customer of yours go directly to MMB itself?

DF: Smaller, developing customers — like this one — liked the value that Sigma-Aldrich could bring, its size and financial stability. Not only were they pleased with our capabilities, project management and technologies, they also saw SAFC as a very secure partner.

CP: So the acquisition can be seen as extending that brand into new capabilities?

DF: Absolutely. In fact, within the first days that we were talking to MMB, we were considering an expansion there to develop the type of capacity that we needed online. Not only for the project mentioned above, but for several others that we saw within MMB’s customer client base, both in gene therapy and vaccines. We saw a definite need to build commercial capacity. MMB had space within its existing facility; it just needed to be built out. Our expansion there was planned from the initial acquisition.

David Backer: As an acquiree, when we were considering with whom to partner, a key for us was deciding how we could best move our clients forward in their trials. SAFC’s acquisition provided an effective utilization of capital and allowed us to move faster than we could have if we had stayed on our own. So, what we wanted to do, and what SAFC wanted to do aligned very closely.

DF: All of this rolls into our vaccine strategy, which is now taking off. We see it as a great opportunity for growth and to serve our customers as we can offer them the full breadth of supply, from SAFC Biosciences’ services that include custom media and sera, to optimization capabilities for the medium. Being a part of Sigma-Aldrich provides us close alignment with our Research Biotech group’s novel IP. Add in our new viral capabilities and our strengths in commercial manufacturing for drug substance and drug product forms and a comprehensive supply chain falls into place for the customer.

CP: Given the number of major pharma players that are investing in vaccine R&D and manufacturing capabilities, what sort of client base are you pursuing: smaller companies with novel vaccines in development, or also those big pharma and biopharma players?

DB: Vaccines have definitely become an attractive marketplace, which wasn’t the case 10 years ago. It’s a combination of new technologies, new indications, and the push from governments and NGOs. There’s a clear movement to develop new vaccines.

SAFC got its start in contract manufacturing and has been involved in parts of API manufacturing and adjuvants for the pharma industry for a long time, so it’s a combination. Our involvement with pharma in a number of areas — including vaccines — has helped foster our Carlsbad site’s appeal.

CP: So it’s a mix of clients?

DB: I’d say so. The major players are probably interested in us for Phase I-II, and appreciate how we help them push their plans along. Eventually, the decision to use us as a commercial launch facility or take the job back in-house is a decision each client has to make for themselves.

DF: Several large pharma companies have approached us to look at jointly building larger vaccine production capacity. These projects are client-financed and government-supported programs, as well.

CP: But the Carlsbad facility is only making clinical materials at present?

DB: That is correct, our current work is clinical to this point, but commercial manufacturing is a major factor of our expansion. As you know, there are no gene therapy products on the marketplace — outside of China — but we’re working with our partners to move them forward. Gene therapy represents a sort of boom-and-bust business, but we have to move forward to help our customers; we have a very full schedule of gene therapy projects to work on. It’s a very similar process for manufacturing vaccines, but the dosages for them are usually much smaller.

CP: Gene therapy development runs the risk of government shutdowns; we’ve seen it before. In that respect, is vaccine manufacturing seen almost as a hedge against a future ban of gene therapy trials?

DB: MMB started out as a joint venture owned by Roche and the university [University of California-San Diego], before several of us led a management buyout. We saw not only gene therapy, but vaccines as growing businesses. From a contract manufacturing perspective, vaccines certainly helped us smooth out some of lumps and cope with the volatility of gene therapy. In that respect, I suppose it is a hedge of sorts, but both of these areas are growing.

CP: MMB used disposable components for years, and the expansion is going to continue that trend. How important are disposables in biomanufacturing?

DB: We’ve been using disposable components and bioreactors for quite some time. It started back when we were at the university due to space constraints as much as anything else. As a virus manufacturer, we like it because it’s an extra layer of containment. The product stays in the reactor, and then you’re able to decontaminate it and dispose of it, which really mitigates cross-contamination risks and reduces cleaning validation. The pharma players are using disposables more and more in their mixing. A lot of cell trains are starting with Wave bags and other bioreactors.

When you look at it, a 25L Wave reactor bag in our facility can generate as many as one million doses of a vaccine. When you have potent products for vaccines and you combine them with disposable manufacturing, you really have a very interesting utilization of technology.

Now, clearly there’s still a demand for stir tanks and stainless steel reactors, so we have those, too. At SAFC Carlsbad, we’ve been involved in disposables and single-use throughout the process, but also with the bioreactors, for years. We’ve made clinical products very successfully. It works well with different cell lines and different viruses; we’ve done comparables against traditional stir-tank reactors and we’ve seen similar productivity.

So we’re quite satisfied with it. The issue now is scale: will disposables be able to get up into the 500L or 1000L scale? Some new technologies are moving in that area, driven primarily by antibodies.

DF: The expansion space will be able to handle larger disposable systems.

DB: We have designs and equipment for 100L stir tank, but everything is going to be on a skid so that we’ll be able to adjust. We intend to use those rooms with flexibility in mind. Larger scale disposable operations will be available.

CP: What do you consider the biggest advance in disposables in recent years?

DB: I’d say the Wave bioreactor has done the most at getting confirmation of use through productivity. There’s an acceptance of the product, and acceptance doesn’t tend to occur unless a number of different advantages are seen.

We have a process for adenovirus manufacturing, for example. It uses disposable reactors. Our clients come in with a tech transfer process. Sometimes they’re transient transfections using Cell Factory, another disposable setup. Sometimes they come in and they want to stick with stainless steel, and we’re very comfortable with that. As a CMO we need to have a breadth of capabilities, both upstream and downstream, to move projects along, especially when projects are being tech-transferred in.

Disposables are keeping pace. We’re probably a little ahead of the marketplace in their utilization, but it’s not like we’ve made a decision to go 100% in that direction, because the market isn’t there yet.

CP: Does the site perform fill/finish only for its own manufacturing projects, or is it handling fill/finish for outside projects, too?

DF: We do both, especially in the virus area.

DB: From a filling standpoint, one of our primary design characteristics is that we use disposable needles, tubing, and everything else we can, for rapid turnaround.

When you have a containment facility, and the whole idea is keeping one batch separate from all the other batches, then we’ll do whatever we can with single-use or dedicated equipment.

CP: Correct me if I’m wrong, but SAFC hasn’t had any play in final dosage manufacturing before this. Why enter that area now?

DF: This is our first foray into drug product fill and finish. We’ve already started discussions to continue investing in analytical capabilities to support drug product manufacturing and to expand our fill finish capabilities for both APIs and biologics.

Gil Roth has been the editor of Contract Pharma since its inception in 1999.