00:00 Hello and welcome to NETV Prophet. I'm Monal Sanghvi and joining us is Ms. Sarah Macmillan,
00:05 the country head of USFDA. Thank you so much for taking out time to speak to us today.
00:10 USFDA has always been such a sensitive issue around the pharma industry and a lot of inspections
00:18 off late. So what do you think is the most concerning factor that you've been witnessing
00:23 across inspections in India? So let me tell you some good news first is we are starting to pick
00:27 up our inspection pace post COVID. And in fact, just this past year, we did over two and a half
00:32 times the number of surveillance inspections than we did the previous year. So we have seen
00:37 a increase in terms of compliance from Indian industry over the past year. And a lot of that
00:43 came right post COVID. We had a lot of compliance follow-up inspections. And so this past year saw
00:49 an increase in surveillance inspections and a lowering of the OEI rates of inspections here
00:55 in India. That being said, I think we do need to address some of the concerns, as you mentioned,
01:00 specifically surrounding data integrity. We've addressed data integrity issues in India and
01:06 globally for many years. And it's concerning to see them come up again and to come up in prevalence.
01:12 And so, you know, for us, when we see significant data integrity issues, it really speaks to quality
01:19 culture in facilities. And so we really want to see facilities take ownership for creating a
01:24 quality culture that empowers everybody at every level to make the right decisions about product
01:30 quality and also the accountability to follow that up. So when you talk about data integrity,
01:36 the Form 483 is always quite exhaustive and a little difficult to figure. So what exactly do
01:44 you think are the trigger points when we get a copy of the Form 483? What exactly are the points
01:52 that we should highlight as maybe a high risk versus a moderate risk? If you could just help
01:57 us understand how to do that. Sure. So any breaches in quality are undesirable, right? So whether it
02:04 be a moderate breach or a significant breach. And I think what you'll see when you look at our
02:08 483s is that they're really put in order by level of significance. So as you read through, the most
02:13 significant items should always be the ones that are listed at the top of the 483. And most of
02:18 those will be related to the quality system. So if there's any findings related to the quality system,
02:22 we take that very seriously because that could also give indications about systemic problems
02:26 within the quality system. So it's not just that one violation, it's that there might be a problem
02:31 within the system itself. So those are the concerns that we really address and take more significant
02:37 concerns about. And I mean, US drug shortages has also been quite a discussion for the last
02:45 couple of years. So are you taking any steps towards, is the ramp up also kind of related to
02:50 that? And do you believe that there are issues that are getting cleared out? And how are you
02:58 looking at addressing the whole drug shortage issue? So drug shortages are very complex. So
03:03 it's not just one set of issues that lead to drug shortage. We actually, and they're actually not new.
03:07 We have, we had a high amount of drug shortages dating all the way back to 2011, where we hit
03:14 our peak in terms of the number of drug shortages. And so Congress tasked us to work hard to mitigate
03:21 shortages. And so we instituted many things to help mitigate shortages. We actually did a study,
03:26 and in that study, we looked at drugs that had gone into shortage. And the majority of those went
03:30 into shortage because of production problems within facilities. So for us, we want to make
03:35 sure that we have a consistency of quality in facilities, which will lead to a consistency in
03:40 supply. Now there's other aspects of drug shortages, like a discontinuation in production,
03:45 or a sudden surge in demand. Those are other areas that we have other ways of addressing.
03:51 But really for us, ensuring that we have consistency of quality within facilities
03:55 is a pretty easy way to help ensure that there's fewer drug shortages.
03:59 There's always been a discussion that quality standards for the US FDA keep evolving. There's
04:06 a new issue every time. So how does this evolution take place? And the other question that stems off
04:12 from that is that maybe the cost of upkeep of facilities could also be very high because
04:18 of course, there's talks of bioconsolidation that's happening in the US. So there's pricing
04:25 pressure that companies are witnessing. So would it be possible that the cost of upkeep of the
04:30 facilities could also be extremely high, and that could have an impact on the quality or the
04:39 evolving standards at least? So I think I like the fact that you talk about evolving standards.
04:46 So technology evolves, right? So regulations must also evolve. So when you see us put out new
04:53 guidances, new information, a lot of that's really responding to innovations and advances that
04:58 industry itself is doing. So this is one of our ways to help understand and our engagement with
05:02 industry helps us understand where those innovations are, where potential risks may be,
05:06 and how to help mitigate that risk through guidances and increased information sharing.
05:11 Regarding the cost of maintenance, and I think you'll see in a lot of the 483s that a lot of the
05:16 items are related to the age of the facility, the upkeep of the facility, especially for sterile
05:22 products. And so I would urge industry to invest in the facilities themselves as one of the things
05:30 that they can do to help continue and achieve compliance. As you can imagine, when you have
05:35 automation and newer equipment and less opportunity for human intervention, that will lead to less
05:41 problems with non-compliances. And one thing that the companies could now do to ensure maximum
05:48 compliance, if you had to like pick one. So I would say invest in quality. So as an agency,
05:57 we really oversee product quality and process quality. And we really depend on industry to
06:04 prioritize quality. And so they need to invest in quality, quality systems, and we want to see it
06:09 go beyond a quality motto. Quality mottos are great, but it needs to be something that can be
06:14 implemented. It needs to give everybody in the facility ownership of making sure that quality
06:20 decisions are being made. So I would encourage industry to invest and prioritize quality.
06:26 And this is now trying to understand what sort of timeline does it take for the inspection. So
06:32 a lot of companies that we have conversations with, once the first form 483 is out,
06:37 they work on it, there's remediation that happens. Then they're always talking about,
06:43 okay, we're waiting for re-inspection. So what is the typical timeline within which you're going
06:48 for a re-inspection? So say if a facility is inspected today versus whenever they get the
06:53 final inspection report, what is the timeline that they look at? All right. So I'm going to
06:58 say my favorite answer is it depends. Nobody likes that answer, right? So there's a lot of
07:03 factors that go into the re-inspection consideration. Post an inspection where they
07:08 get a 483, one of our commitments under GDUFA is committing to let them know a final classification
07:14 within 90 days of their facility. So if their facility is classified as OAI, the timeframe for
07:19 that re-inspection will depend on many different things. And so when we talk about the prioritization
07:25 of inspections, it's a dynamic activity. There's mission critical inspections, there's inspections
07:32 for products in shortage. There's a lot of dynamic, when you put things into a queue,
07:39 they're all coming from different places. So it's really hard to predict when that timeframe for
07:43 re-inspection will roll back around. We know that industry is anxious for that re-inspection and we
07:48 make every effort to get to it in a timely fashion. But there's a lot of factors that
07:52 keep us from giving a specific timeframe. And does this mean that, is it only because
07:57 of these other factors or do you expect that there needs to be some ramp up on the staff that you have
08:03 conducting these inspections as well? I saw that question and I was like, yes.
08:06 So we actually have, we're going to be asking for more positions for drug inspectors here in India.
08:12 We know that the number of facilities is increasing. We see the government doing a lot
08:17 of investment into industry. If you look at the numbers over the past several years of facilities
08:22 that are registered with FDA and actually exporting products to the US, that number just continues to
08:27 go up and up. So the workload is just going to increase here. So we are in the process of
08:32 requesting additional positions. And I hope all the right people are listening that can help push
08:36 this along because that would be really helpful, I think, not only to FDA, but also to industry.
08:41 And yes, and I think the industry is also looking forward to shorter timelines on re-inspection,
08:45 including all investors that are just waiting for a couple of facilities to get clearances.
08:49 So thank you so much for this. It was a great chat. It was nice seeing you, sir.
08:54 Thank you so much.
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