Much has been made of Dr. Ajaz Hussain’s departure from FDA’s process analytical technology (PAT) team; Hussain has moved on to become VP and global head of biopharmaceutical development for Sandoz, and now faces the daunting challenge of commercializing biosimilars. If there were any doubts about the sustainability of the PAT initiative, FDA’s growing PAT team and the PAT champions within industry have taken the ball that Hussain tossed into the air and run with it.
As was made abundantly clear at last month’s IFPAC 2006 conference and exhibit in Arlington, Va., PAT is not only in good hands, it is in the hands of many. Within FDA, the PAT team has just begun training a new crop of contributors, including members of the Center for Biologics.
And PAT’s no longer being driven by FDA, say Chris Watts, Ph.D., and Ali Afnan, Ph.D., key members of FDA’s PAT Policy Development team who now help to carry the baton within the Agency. FDA’s role is to set the tone for continued innovation within the PAT framework and to further open dialogue and trust-building with industry, the two said in an interview with Pharmaceutical Manufacturing’s editors at IFPAC.
The major hurdle for PAT is now getting the international community on board, in harmonization efforts with EU and the rest of the world (ROW). As Ruhi Ahmed, Ph.D., regulatory lead at BioMarin, Inc. (Novato, Calif.), described her predicament of selling PAT initiatives to her management: PAT makes complete sense and may ease regulatory approval in the U.S., but what about the 26 other countries in which the firm markets its products?
Pharmaceutical Manufacturing’s editors sat down with Watts and Afnan to discuss PAT’s present and future. The group was joined by near-infrared spectroscopy and PAT expert Emil Ciurczak, a consultant and member of this magazine’s editorial review board. Excerpts from that interview follow.
P.M.: What’s new with the PAT team these days?
Watts: The changes are really only in the form of additions, with the exception of Ajaz’s departure obviously. At the end of January, we started the next round of training for the team, which includes the centers for Biologics, Drugs, Veterinary Medicine and Office of Regulatory Affairs. This group is much larger, with nearly three times the number we sent through the last time. Then we had 13, and now we have 36. And we try to cover all of the eight regions in ORA — though not every district because that would be impossible.
Afnan: Within OPS, [Director] Helen [Winkle] now chairs the steering committee, replacing Ajaz. Chris and I now report to Helen.
P.M.: What are your top goals and priorities for this year?
Watts: We’re really focusing on getting the next round of training going and implemented. We’re also trying to expand PAT concepts internally. There’s now a section on PAT in the PI [Pharmaceutical Inspectorate] training program, for example. It’s important for us to go beyond the small group that we have and to communicate these concepts throughout the Agency.
Afnan: We’re also looking closely at how we approach PAT as a regulator and how we encourage industry to function as manufacturers. Implementing PAT throughout all the offices of FDA would be a major achievement toward our objectives.
Watts: The thing that I’m most proud of is how the team that we have functions together. They really do work well and value each others’ opinions. And if we can increase that interaction between the review, inspection and compliance officers, then we’ve made significant steps forward.
Ciurczak: A testimony to the work that you guys have done is the fact that none of the team seems to be leaving for what would obviously be higher-paying jobs in the industry.
Afnan: Maybe the pay is better in industry, but Chris said it right. I don’t know how much more we can convey how unique and rewarding working on this team is. We see the need to challenge the norms that we’re used to, and to find different ways of working for change.
Ciurczak: Is there any effort to encourage more companies to say which product they’re applying PAT to — to “name names”? This would allow others can go to their companies and say, ‘Look, Pfizer’s doing this with this drug, AstraZeneca’s doing this. Here’s a product we have that should look at as well.”
Watts: I think we’ve encouraged all the companies that we’ve interacted with. Sanofi-Aventis is one case where a company has been very open, though they haven’t mentioned the product. But the name that you put on it is really irrelevant. The details of the process and the learning that they’ve achieved are most important.
Afnan: Give it five years and that may happen. Manufacturers may promote PAT in the same way that we stick a USP label or a mark of quality on a product. That will take a little time. The industry has wrapped itself in secrecy for so long. But it will come as PAT becomes part of the warp and woof of FDA and the industry. Manufacturers will say, “My product is better because [its manufacturing and development were] done this way.”
Watts: But there are some terrific examples already from the generics industry, OTC, vet med [veterinary medicine], and so on. I think the biggest misconception is that PAT is specific to Big Pharma.
Ciurczak: The way I look at it, Ajaz was the Orville and Wilbur Wright, and [the current PAT team] are Boeing and Lockheed. He tried a few things but now you have got to make it work. It’s not as glamorous, but you guys have got a much harder job to do.
Afnan: Culture changes are slow by nature, but I think we’re going faster than I could have imagined.
Watts: When you talk about innovation, it has to be led by the industry. We don’t make the product, we just set the attitude.
P.M.: At the commissioner level, is there more support for what you do? Will there be more funding to come?
Watts: It’s a tricky issue. When you are a government agency, everything from the war in Iraq to the war on terror has an impact on the budget and what we can do.
Afnan: Having said that, let’s be honest: The PAT team has never been starved of funding. We have never been held back because we haven’t had the money.
Watts: There’s been a lot of support, top down. Maybe CDER has been more open and out front, but it’s an Agencywide initiative. A great example is veterinary medicine. And it’s really an extension of the GMP initiative, the Critical Path initiative, but applying them a little more broadly.
Ciurczak: A lot of people felt that that might change when Ajaz left the Agency, but it’s not going to happen. The cat’s already out of the bag.
Afnan: It’s actually being driven by industry, and that’s the way it should be. Our role is not to tell them how to run their processes, or what to do and what not to do. If you look at what’s happening in ASTM E-55, it’s industry that’s taking the lead.
Ciurczak: And each company only gets one vote!
Afnan: That’s right. Pfizer, the largest pharmaceutical company, gets one vote.
Ciurczak: And a little 10-person pharmaceutical company gets one vote.
P.M.: What do you see happening with PAT for biologics? What do you want to accomplish in this regard?
Watts: Neither one of us is in the Center for Biologics, but they’ve been on board since the beginning. And now it’s very good to get them involved in the training program. I’m not just saying they have to learn what we have to offer, because the training was very collaborative.
If we could get some biologics examples of PAT into the Agency so that people would talk about them, that would be great also. But there are a lot of biotech companies involved already — Genentech and Amgen have both been very outspoken.
P.M.: Will further guidance be introduced related to PAT?
Watts: Anything we’re doing certainly fits well within existing regulations. There’s no need for companies to feel that we’ll do something contrary to the current regs.
Afnan: We have stated explicitly that we would not write another guidance specifically related to PAT. And all such efforts will come through ASTM. Our reasoning for that is that that’s a open, consensus process that engages the people whom it will impact most.
P.M.: Are you seeing any evidence of a change in the mindset of people in the industry?
Afnan: Come to the next ASTM meeting. There is an environment growing in the pharma industry that is different than what we’re used to. Once we go further down the process of talking to each other on mutual ground, without fear of reprisal, with the understanding that the reason for the existence of FDA is to ensure the quality of products, and the reason for the existence of the pharma companies is to put quality product out there, the systems that we are used to won’t make sense. And that’s very clear in ASTM.
P.M.: Everyone seems to have their own definition of PAT. How concerned are you that it’s being defined too liberally or inconsistently?
Watts: Considering how young the initiative is, just the fact that people are using the term is good. Any conversation dealing with PAT says that there are people out there thinking about it, even if they’re not on the same page as we are in terms of definition.
Afnan: I feel slightly different. How frequently it’s used? No concern. The only concern I have is that people would think by putting the label “PAT” on something that they’ll end up with product quality. They won’t. It’s what you do with PAT. Whether you call it PAT, PAC, process control or something else, it doesn’t matter as long as people take one further step every day towards understanding how their manufacturing process functions.
P.M.: We often hear, and this may be exaggerated, about difficult inspectors. As you train the new Inspectorate, what is being done about inspectors — perhaps some older inspectors — who are “set in their ways” and who may not embrace the spirit of PAT and 21st Century GMPs?
Afnan: We haven’t encountered any such inspectors. Right now, I have an inspection file on my desk from an inspector who is less than five years away from retirement, and he has used process understanding and the spirit of the PAT framework to guide his inspections. It’s not an issue.