FDA Public Meeting: Onshoring Manufacturing of Drugs and Biological Products, Recording Part 4

portion of the conversation here today.

Okay.

Again, I am Adam Fisher.

I am staff director in the office of quality assurance in Ceder, and I will be moderating the last part of our discussion here this afternoon.

We'll have our final two discussion questions, and then we will be joined by Grace Graham, who's the deputy commissioner for policy, legislation, and international affairs to give some closing remarks.

Now, before we get into the last part of our discussion here today, I just I do just want to say that um I went on one of our AI tools and asked for a little advice to keep a discussion lively as we head into the afternoon of a long meeting.

And it said to avoid being repetitive.

So with that in mind, let's go to question three from this morning, and we will talk about additional elements or implementation considerations that should be considered in the FDA pre-check proposal.

And again, the focus this afternoon is on API, so any insights we can get there on small molecule or large molecule will be very helpful.

Um and I think even some things that we discussed this morning may foreshadow some of the the themes that we may talk about this afternoon.

So, who would like to get us started here?

I see one light on already.

That's a good sign.

Please, you have the floor.

Um Andrea Briggs, API Innovation Center.

A couple of additional elements that I think would be very helpful.

API Innovation Center works closely with our academic partner, the University of Missouri.

I think if there was some sort of innovation track for academic and nonprofit-led facilities that could, you know, you could assist with as we move forward to bring APIs into the marketplace.

I think that would be very helpful.

Another thing I think would be helpful, and I am sure we've heard this this morning, is some sort of incentive for participating.

Maybe it's priority review of any filings that come out of it.

I think that would be extremely helpful, especially for our smaller nonprofits, to have some sort of flexibility, you know, with with joining this program.

Not only are we going to help to reshort critical medicines, but you know, there's a way that we don't have the big pockets as some of the big pharma that it could help us to help accelerate that growth and implementation of new APIs.

And and could I ask a clarifying question on the types of incentives that you were um having in mind there?

Um you know, if I don't know if you can hear us, but it's common knowledge that both China and India subsidize their chemical as well as their API division.

We're up against that, and there's got to be some way to level that playing field, whether all right, maybe um part of what API Innovation Center does is we have customers at the back end.

We have health care network within Missouri that has partnered with us to provide to medicines to them.

We also have a retail company as well as the government.

So if there's some way that we can, you know,

level that playing field for us, a small organization, that we can help get that medicine out.

Maybe it's more government contracts, longer-term contracts saying, hey, we're only going to buy from US source companies for like the VA or Medicaid, Medicare, and that would be some sort of way of leveling the field for our small players in the marketplace.

And and just another clarifying question.

You're primarily focused on small molecule chemical APIs as opposed to biologics.

Is that correct?

That is correct.

Okay.

Thank you.

Is that Peter?

Yeah, Peter Kueh-From Roche.

So, I guess uh it's not really specific for API, but in general, I think I just want to uh reiterate that the question topic we discussed about uh uh resources and also uh review or inspector training program.

So, with the new facilities and bringing facility new new facility new design, there are a lot of new technologies that companies are implementing like those are very novel uh facility design ideas and also uh novel technology,

for example, filling lines or uh DS facility design think I think Julia mentioned about single use or other tools.

So, I I don't know whether there's a as part of this program that to, you know, streamline the review and inspection process that we can build in some uh training program that for the agency reviewers inspector to be familiar with uh those advanced technology,

especially when when when they review uh new facilities and new equipment designs that will help them to uh in, you know, exit quick understanding to uh of the facility and also uh some issues that that potentially and address for example,

EM issues or things.

So, that may be something we can consider.

Thank you.

You know, Henry from a Cure Caring.

Um so, this morning we talked a little bit about uh around this question and trying to get clarity around how to leverage a type five drug master file submission, you know, that would be something that it would be important for drug substance as well.

And also a suggestions to communicate broader, you know, and in in in both, you know, like workshops, educational forums as we define this process, you know,

it would be important to uh to her point, you know, change the mindset.

You know, I think that we uh on both ends, you know, industry and FDA, um could benefit very much of education and understanding what is this program, how we're going to apply to it,

and then try to leverage a consistency as we move forward.

Uh and again, it could be conferences, workshop, uh public uh interchanges between the industry and those that we're doing today that will benefit uh both both ends of the equation here.

And ultimately, our patients.

Thank you.

Yep.

So Sergio from Novartis.

So, I just want I don't want to repeat what we said this morning.

Uh what I really want to re-emphasize a point, which is today we have limited opportunities uh for early feedback on site inspection and planning.

Uh I truly believe it's worth um continue doing early engagement, ongoing, informal conversations uh it's going to help us tremendous in both both of the phases uh that the pre-check program is looking to to to to do.

even in in line with the previous comment that was in previous discussion, uh we can work out what it what is meaningful to have a an an inspection and a visit from the FDA to our sites earlier.

Um it's totally workable.

So, so yes, just just the last point I wanted to mention that once again, early engagement is is is the key thing for us.

Thank you.

Um Simon Harchan, Amgen.

Um I think because of the way the conversation's been structured sort of focused on API, and and and finished product, um we're sort of focusing a lot of conversations on those parts of the manufacturing process.

But obviously, they all rely on on the starting materials and and other elements.

Um and although we don't control the manufacture of those, at times, you know, it would be great to have the ability to have a conversation about how we could accelerate a change in sourcing of one of those things to make sure that we're not,

you know, asking for more downstream process processing and data than is is needed so that we can make those changes quickly.

So, it feels a little out of scope of how the program has been proposed, but sort of thinking about is there a a component of that that could be handled within pre-check in in certain circumstances?

I think would be, you know, interesting to follow up at least.

Thank you.

So, will there be a manufacturing

manufacturing from Sanofi.

Uh will there a consideration be made to have a dedicated FDA division for having a such pre-check initiative because many sponsor will come and there there will be many sponsor will be applying for this one,

and how that would be handled?

It could create a lot of work.

So, that's one of the consideration.

Um I like to ask.

And then uh another thing

Could could you talk a little closer to the mic?

Yes.

And another um comment I want to make is the transparency of uh uh FDA 483 items for PAI because those are very difficult to uh get hand of it.

So, if that can be published with a blinded format, uh would be also helpful to industry so that they can see what are the finding and help get themselves uh ready uh for not having such observations.

So,

thank you.

Hi.

Uh Brian Dipollo from Moderna.

I think one of the things that um might also be helpful for us to take a look at is um in particular for existing facilities is um what can we do from an equipment standpoint?

Adding new bioreactors, adding a new fill finish line that's equivalent to what has currently been um used in the facility.

Um can there be areas to explore there that allows either, you know, quicker um approvals or um again, from a risk-based uh inspection point of view.

And so, I think uh you know, making sure we're considering all potential aspects, especially those again for um facilities that are already up and running um and making sure that those don' um overlooked as maybe quick wins um for implementing.

Yeah, Jim Breen from J&J.

I you know, just not to repeat, I think the the resource issue in terms of being consistent, clear, consistent be on, you know, the overall process.

I view this as a great opportunity for us to work together to develop a process here that would take into account both uh considerations.

Um I think the collaboration piece would be really good.

You've heard that word a couple times.

But you know, we we mentioned resources.

I think the only other one I wanted to mention, these projects usually take five to six years.

And so, there are, you know, that's not just all in the FDA's uh remit.

There's other government authorities really that help that also would be be a way to help reduce the overall timeline.

So, I think for us, we're looking at how we can reduce the overall timeline at looking at multiple different entities.

Yeah, I just have Peter Kueh-From Genentech.

Uh another question about this pre-check.

So, there are two phases, phase one, phase two.

I'm just wondering, you know, if based on the needs of uh each industry each company that is it possible that we industry only select one of the phase to start rather than have to go through both phases?

Like for example, if we have a existing facility that we are expanding, adding new product to it, and whether this could be I mean, this facility has already been been has already been built and they're just leveraging uh the pre-check phase two to uh you know,

get bring back the product to the US quickly.

Just something that's considered.

So, yeah, I think it's a it's a great question, and I would ask you, what are you leveraging if you're skipping phase one?

What are we leveraging in phase two?

Because if we have just we play this out, right?

We're talking about early engagement, we're talking about getting this information so that we can make these decisions in phase two.

So, for from our standpoint, understanding that within the program, you may not need all the elements, right?

Fair.

But if we don't do certain things up front, it makes it harder for us to be able to do the things downstream.

So, I when when you're proposing this, it would be helpful for us to to understand which if if if we took that under consideration, we said, okay, you can skip phase one, and we don't have all that information,

we don't have all that engagement, and we're getting you cold as we do in a normal submission, it's really a challenge for us to be able to leverage that information.

So, what what additional information or or approach would you suggest that would allow that to happen with with, you know, kind of the constraints that we've laid out?

Yeah, I mean, from my standpoint, what I'm I'm talking about hypothetical okay, if there's facility existing facility, and uh all the information or let's say for example, DMF the facility all they has a DMF with agency,

and uh all the company want is bring in a new product, and uh you need existing facility from overseas to to US side, and to try to leverage this uh stage two approach,

right?

On the uh into more interaction with uh the agency on the submission rather than on the facility because the facility has been already been built.

So, those kind of things scenarios.

As as we had mentioned, we're we're taking the comments under we're taking the comments under consideration, but would would just say, you know, at a high level that the the program really is geared for new facilities uh

uh to to get folks to to come here as well.

And we've heard the the post approval piece, which may actually obviate the need for for this program if the if the facility is built and you've got a strong quality system, you know, this program may not be the right program.

And I think there's a lot of other avenues that that be considered.

But if you have a strategy to to leverage those pieces, I would encourage you to submit that to the docket and how you would utilize the phase two for our consideration.

As we said, we're we're not saying yes or no to anything today.

We're just exploring hypotheticals, of course.

But also keeping in mind that there are other programs and that particularly if you're moving a product to an existing facility, the post approval change space seems like an other conversation that might be be worth having in the future.

Thank you.

Karen.

What I'm about to say might be a little bit in conflict to some of the things that was discussed this morning where we talked about frequent engagement being less formal.

And maybe that's an ideal state.

But understanding resource constraints all around, I think one thing that would be very helpful as this program is implemented is that there are clear parameters around the engagement.

So we all know what to expect if engagement is under the user fee act.

So timelines with briefing documents look like, things of that nature.

Moving forward with this program, I would hope that there would be analogous information so that we all understand how many times can we engage, at what phases, when briefing documents would need to be provided, if at all, or if it's the DMF,

when the last update needs to be, when we could expect a meeting to occur.

Because there's been a little less predictability around things like the CAT, for instance.

So I would hope that this would be more predictable.

Lisa.

Um Lisa Wright from Novo Nordisk.

Just to add on to Peter's question before.

That kind of gets to what I was asking this morning, you know, talking about that we've already done as a company a lot of investment in this country and we are rolling out new sites and new facilities within those sites and,

you know, asking how we engage with this and and, you know, to your point maybe it's not the right program for us, but we could come to you as an abbreviated phase one.

You know, here's all our plans for future sites, here's what they look like, here's how they're identical to each other.

And then, you know, skip ahead to phase two once you see like okay you haven't been able to be involved in the design construction aspect because that's already started, but we can give you some background to help fill you in.

You know, that is one potential way to like have a circumvented phase one to then jump ahead to phase two.

Just throwing it out there as an idea.

So, yeah.

No.

Oh, you know, Enrique I'm uh hearing uh I think that what we can add as an additional element for implementation will be measurements of success.

You know, how do we evaluate this program moving forward?

How do we say we have a successful program in place?

Um obviously that requires a comparison and clarity around what are the benefits that we're getting from this program?

What are we achieving with through this program?

Um time, resources.

Are we able to accelerate the time from application to having the drug available to patients?

That would be a a good indicator for our success, collective success, industry and FDA.

So I think that defining those uh those uh results and compare those results to the current timelines and will be selling points for all in terms of the of promoting this this program.

So just going back to the discussion on post approval because it is important, um

with a new product, the the capital investments in that product scale over time.

So your initial application has one facility and typically what you then do is add post approval.

So thinking about how

that risk-based investment in a new manufacturing facility, which is substantial capital, if you're not sure yet about the success of that drug and and how pre-check helps navigate that.

I think as it is a key part of this and it does get into the the post approval regulations and and how that works.

So I think to to really for many of these products, not all, some of them are smaller volume and have different circumstances, but it but it is important to have that as part of the consideration and not going to for site transfers and such.

It really is about how do you meet the demand for that product in country when your capital investments are happening too late because it does take some time to get there.

So so you end up with some phasing of that.

And I'm not sure if that was was what Peter was getting at, but I I think it's somehow important.

I just want to add on the Peter uh proposed.

I think that's a great idea.

It would be good to understand what is the criteria or um FDA consider that the completion of the phase one.

Uh what really needed, what kind of information FDA need to say hey you complete the phase one in uh in the pre-check program, no matter for new brand new facility or the um existing facility.

And then we can move to phase two.

Um so therefore from by doing so, I think the pre-check program can be more useful and and the the scope could be expanded, yeah.

Ruth.

Ruth Gourley of AstraZeneca.

Um yeah, I think I think we're dealing trying to think here about what kind of uh advantages we could have from the proposal in the first stage.

And I and I was thinking that if we can have a very collaborative work with FDA in that initial phase in order to address major CMC development challenges that require long time long timelines and and and planning beforehand for a long time such as

stability, which was mentioned here.

Um comparabilities that needs to be demonstrated, process validation, if that could be um discussed very early in order for companies to make better decisions about those constraints in the CMC timeline.

That would be a great incentive towards getting into this program as well.

Thank you.

Lucy, did you have another comment?

Uh yeah.

Okay.

What was yours?

All right.

Um another another question is um about how we can better leverage the ICH QMS uh with for the items that consider as a GMP to be further leveraged to reduce the review or the required information because um I think that uh for um our experience and we did uh see that FDA usually requested

uh more information than many global health authorities, including master batch record, packaging batch record, COA for raw material, um and uh you name it,

detailed facility information um on on on on those uh and also the very detailed description for the analytical method including transfer um especially for biologics.

I think all those information um if FDA FDA could uh you know have a a deep um dive and try to streamline further and that could also help industry in terms of reducing um the the burden for for good giving those information.

And actually those information um or checking on those uh can rely on the company in terms of their their quality system to manage.

Yeah.

Thank you.

So when a CMO is involved in um pre-FDA pre-check program and they are uh collaborating with FDA with type five uh DMF uh passing phase one and uh phase two and um at that time that is acceptable and a sponsor can just refer out get the LOA and have that application to be reviewed.

At the same time, I like to bring to the point that if we are going into the path of type five DMF uh when it comes to the biologics even sometime the synthetic API get disqualified to have the DMF uh when it comes to the life cycle management or the BLA application uh of the uh biologics whereas the same API could be in the NDA and has a

DMF.

So I think if we are going on to the route of uh type five DMF, I think we can also consider having DMFs included into the BLAs.

Thank you.

Any additional comments on additional elements or implementation considerations?

If not, we can move on to question four.

All right.

Question four.

Would your company be willing to provide information about manufacturing facilities relevant to FDA oversight in advance of or separate from an application submission?

And what concerns might you have about sharing this information?

And I do think this is a more interesting question for the API discussion than than maybe for the the morning discussion, some of which I think uh we just talked about here.

But kind of curious to hear from folks um what concerns you might have about sharing information, especially contract manufacturers, people people that make API and people that also on the other end might rely on DMF in order to get application approval.

So I think that we talked about this a little bit this morning and and I think the consensus is yes, we are we are interested in sharing information.

Um it's difficult to answer this question and say just yes, you know, obviously we want to make sure that um IP information, proprietary information is protected.

So that would be a question to the question, you know, what would be the mechanism to protect this information?

What type of information will be shared and how is the agency using that information?

That would be important to establish kind of a a how do you say a level set uh trust that everything is going to be okay.

Uh but but uh I think the consensus at least what I'm perceiving is that yes, we will be glad to share information.

Like I said earlier, a lot of what we do is not a secret.

You know, we use common technologies, we use probably similar suppliers and vendors.

Uh so it's nothing that is there's not too much that is unique and proprietary and that we want to protect.

I think that that's the the bottom line.

Thank you.

All right, Christopher.

All right, Frank showing um Forge Biologics.

Yeah, I agree with that.

Um I think it's again the understanding the transaction of information between us and the agency.

I think there are already kind of guidelines on how to protect that information and ensure there's appropriate um uh you know oversight for maintaining information.

We'd be happy to engage with the agency in sharing uh you know in our business in the biologics we're talking kind of like some of the API might be considered also the the plasm ids we utilize or um in certain cell type products uh the viral vectors are going to them.

Um happy to share that information with the agency.

And then as we get into as a CDMO supporting our clients, those clients are going into those late in uh stage or commercial ready in site actions, we're being quite transparent with them.

That's a part of their um you know license application.

We are growing and evolving with them.

So there's also appropriate transaction with the client around that information as well that we'd be enabled to share that information.

Again, uh to uh to my colleague's point, um there's nothing that's dramatically unique about what we're doing.

It's just the know-how of how we've compiled it together.

There is some information we'd like to protect, but I think within the transactions we're having either with the agency or with our clients that that should be protected.

Yeah, I think uh Simon तीच्या again, I think we agree.

I mean it's uh no real concern about sharing that information provided it's managed with the normal confidentiality.

Just reflecting on some of the conversation we particularly had this afternoon, there's been a bit more discussion about, you know, early interaction with FDA, sharing some things early, maybe having inspectors come to the facility early.

I think in that context, we definitely welcome that idea.

I think it it it's a good idea for us to discuss further.

I think there just have to be some clarity about at what point or what information starts to be used for sort of regulatory decision making.

So we're all on the same page and and we're very clear about what is FDA looking at and for what purpose?

Is it just general background that you're looking at it right now or you're actually going to start making some decisions?

So that shouldn't come as a surprise to anybody when when you start to do that.

Hi.

Andrea Briggs, API Innovation Center.

Um is Many of you may not know, we are a small non-profit based in St. Louis and we do a lot of the upfront work of developing routes of synthesis for um their already approved APIs on the marketplace,

but we're taking back from the batch processing, which is common within the US and we're going into advanced manufacturing techniques such as flow chemistry as well as other um like electrochemistry.

So, we will not be manufacturing our API APIs or the finished drug products when we get to that next stage, but we will work closely with our CDMO.

So, your question about how that data knowledge will be shared, obviously we'll we'll work very closely with our partners to make sure that they're very open and honest and transparent with the FDA regarding the facility because that would be your type five DMF that we hope that they would pursue.

But then we would have our data that's in the filing for the DMF that we obviously would want to keep some of it proprietary because it is a new technique.

But I would hope that you know all of this could be presented to the FDA sooner than later in the process so that you're aware of what we're doing.

It's not a surprise, you know, it's some somewhat different for the United States.

It's used very heavily in petrochemical industry, but not so much in the pharma industry.

So, we're trying to to bring this new technology to the states to help expedite getting new APIs out there as and then into that finished drug product.

Uh Peter, I think you were next.

Yeah, I just want to add I think agreed that like we're discussing the morning, we are willing to share a facility relevant information to support application review inspections.

But uh my question is here is uh when looking in the looking the manufac- information related manufacturing facilities, very a broad question.

So, especially for for like existing facilities and there are a lot of information related to that facility.

So, I think that maybe you know what like for example if we're talking about the filling line for that particular product or manufacturing suite bioreactors for that particular product.

I think that will definitely be part of the assessment.

But I just need to need to understand the scope of the manufacturing information about the manufacturing facility.

How much information you know is required to in order to support the the phase one uh evaluation.

I think this is something maybe uh some clarification on that before you know we can fully understand that the scope and commit to it.

And we have FDA comment over here.

No.

Uh thank you.

Um this is uh Souleymane from uh Office of Pharmaceutical Quality.

I do have a question to the our industry colleague.

I mean, I think I we hear a lot of our comments about the type five DMF and um like we we're still in the design phase to to understand like how to construct this uh type five uh DMF approach to be useful to uh all of us.

And one question I do have because I we have been working with uh EMA in many like pilot program under the IC MRA and we did hear that uh they are using uh the same master files um in in uh Europe.

So, I think uh if you guys can share some of the experience in that area, it may be help it may be helpful to us to understand because I think uh Corinne I mean I think uh you may actually uh submit some facility information uh in that area.

So, I think if you have anything can share to help us in design um more detail implementation of uh this pre-check will be greatly appreciated.

Thank you.

All right.

I think you made everyone's light to go off.

So, oh we got we got one back on again.

Yeah, Corinne please go ahead.

Everybody else is down.

Okay.

Um to address your question about the same master file following the the PIC/S format, um that is typically done, but from my experience, the SMF has a certain level of detail.

The DMF has a bit more.

Briefing documents to really get into the details have a lot more.

The 3.2.A.1s sit somewhere in between.

So, mechanistically um we've actually structured our DMF to also align with the SMF so that we're not updating two different documents.

But again, going back to how unencumbered do you want a site master file to be because it needs to be cared for every inspection that's following the PIC/S format.

And from a life cycle management perspective, that can be really difficult as we're going through multiple phases of assessment for this program.

And uh uh Mandar Sarkar from Sanofi.

Uh site master file is not always been maintained by every site not not that been shared most of the time the content of the information is shared.

Uh in Europe it's completely different.

The the the GMP authority is completely different than the health authority.

So, that's helps.

Uh there are a different there is a schedule in fact inspection happens and GMP certificate is been issued and that's ease a lot of the pressure uh when when going going global.

Uh that's something could be considered uh when we are getting into this uh when we are considering the EMA.

Uh another thing like I think I would like to bring here is uh the digital twin.

Uh could that uh help uh to produce the batch uh batches like not going the full three batches, but could use one and use the digital twin as a supportive information.

Thank you.

I have two points to make.

Yes, the willingness to provide information is there, but I think we need a bit more clarity about the type of information that again is not typically provided in a submission, which is and this was brought up earlier,

the pilot program QMM, which is still being developed and that language is specifically in what's been released about this program is inclusion of QMM information.

That's potentially a little bit risky when that program is still being developed.

So, exactly what type of information around the QMM, also QMS information, that's that's difficult to package up, right?

So, that's usually looked at in inspection.

So, if there're specific elements of what should be provided in QMS, and by the way, QMM for a new facility is even more challenging because it's not a mature facility yet.

So, yes, we may be adopting elements of QMS from other facilities that are in the network and the framework is there, but certainly metric data is not going to be available, you know, indicators of of maturity may not be be present.

So, that that's a a a caution.

The other thing that I think it was brought up earlier is the risks of having FDA engagement early.

So, construction phase when you're in hard hats and things of that nature and what if there are problems.

Um there's also opportunities to talk about how those problems are being addressed, but to have the full transparency see there's a vulnerability on the side of industry or CDMO inviting the FDA in early on.

So, one thing to consider is the proprietary nature of the interactions under this program.

So, there are things like FDA inspections where 483s are foia-ble.

And we if there's an assessment that's going to be part of this, we also have to think about whether or not that can enter into the public domain.

Thank you.

Let me let me ask a question um generally because I think a few comments have now uh sort of emphasized that you're willing to share information, but you would need details of the program,

you know, in order to determine whether that amount of information was appropriate or not.

But let me let me kind of turn that question around and ask you what type of information do you think would be helpful to share in this program and where would you draw the line where that it crosses over to to being too much or too problematic?

All right, Kevin.

Go ahead.

Appreciate appreciate you stepping up.

I I don't know where the line is.

Um to start that to my answer.

But I think there's been a theme here over the last 10, 20 years.

I mean, we worked on a pharma initiative with FDA about five years ago to talk about what information belongs in a regulatory application, the NDA or BLA, and what is GMP information that should not be in the NDA or BLA.

And I think kind of what you're hearing this morning was there's a lot there's more and more GMP type information making its way into the BLA.

And so, could this be a mechanism to carve that out so that our BLA is closer to what ICH intended it to be um as opposed to what it turns into by the end of the submission process.

So, could this type five DMF be a place for us to include that information, those information requests we get about environmental monitoring I believe was the example this morning.

To me, I think for us if we could stick all that in this type five DMF and I don't know where the exact line is, but that would be helpful for industry and then our module three would be more of a pure module three kind of as ICH intended it to be originally.

Go ahead.

So, it's a really good question and it's a really hard question to answer.

Um and I think it's

it's because we have to shift this mindset thing, right?

So, um like thinking through all the documents that we have and what you could use and what you need.

I think that needs a more transformative look than just saying take some bits and pieces of what what exists and and smush them together.

Um so, in in in it it is going to be different whether you're biologic synthetic, what you what your circumstance is.

And it may be as pre-check starts that some of the early discussion is like what could you provide, what would make sense, what's too much, what's too little.

You could say, hey, we don't want to see like a thousand pages of your QMS, but we do want to see your microbial control.

You know, so so I think there's going to need to be some of this.

There's also like as you go through if you talk about starting early, right?

Like we have a lot of protocols that we use whether it's IQ, OQ, PQ, like engage you along those lines and it's you probably would typically never see like an IQ or an OQ protocol ahead of time,

but it might be useful and maybe you see it once and you're like that helps and then you're like never again.

But I think there may be some things we can collaborate on in that space that that that we can kind of co-create together.

I I I do worry we're going to kind of like cram and jam stuff that we currently have and it's not quite fit for purpose and then we're just going to be adding bureaucracy and time and and review on your end that isn't needed.

And you know, my own commentary there, too much information isn't helpful for us either, right?

It just it slows things down on both ends.

Uh Peter, I think you were next.

Yeah, so I agree this is a very difficult question to answer.

So, that's I think one the reason why we're here try to understand and the whole scope of the pre-check.

So, I guess my my personal take on this one is really depend on how the agency is going to use that.

I mean, obviously we discussed about what information should be in a submission if it's related to demonstrate sterility assurance.

I mean, those information related equipment that should be in the application.

But I think if you want use those information facility information to support uh decision to waive uh inspection or support alternative tools, yeah, that's certain product related information should be in the application.

Or if it's early stage just to facilitate design and the the flow facility flowchart all the things, that should be that can be included.

I think bottom line is

you know, it's not like any industry not willing to submit industry willing to support or work with any is try to understand uh how the agency is going to use those information at what stage,

how much relevant and like you said, too much information is not really good.

So, it's really try to understand this uh how the agency the reviewing is going to use those information at various stages and then you know we can respond to what should be uh appropriate information to submit.

You know, right now it's talking about you know information related to manufacturing facility.

That's a very like I said, it's a very broad in the inf- information there.

So, try to understand what how you're going to use it at what stage.

I think that's what will be more important for us to understand.

Thank you.

Um you know Corinne from Corinne.

Um so, the way I look at this is this information sharing should be uh an iterative process along the way.

So, we should be defining as we go what type of information will be relevant and important to share in order to support the process.

Obviously, there's already information and guidance as part of the uh pre-operational review uh that we are willing to share, you know, like facility design uh drawings,

we can uh materials and people flow, environmental classification of the areas, high-level description of the process.

I think that I don't think that anybody will have a problem sharing those high level documents.

Um I think again where it needs to be very well defined and and there's some legal implication is when you're sharing material information that is probably proprietary to the to the company.

And at the very beginning also another consideration is that you may be uh well we will be contracting an additional suppliers and and design and construction companies that also have some legal protection of their uh information.

So we need to make sure that we are sensitive to that and complying with those requirements as well.

Okay.

I think that the information to be submitted needs to all funnel up to the overall strategy of what you're trying to attain through the interactions, which I see as agreement and alignment on the design and the controls concomitant with the product and product types that are going to be in the facility.

So if it's a multi-product facility that's one thing, if it's single product facility that's another, if it's a chemical synthesis type of a product very different from biologics.

And so the elements of the type of information need to be aligned with where you're trying to get concurrence.

So what is the level of control that's needed for that facility to ensure cross-contamination control, segregation controls, contamination controls based on the different product types.

Because I see that as potentially an area where there's real disconnect in the design phase.

Is your HVAC appropriately designed or is it over designed for this particular specific product type, whether it's parenteral, whether it's going to be oral.

So fundamentally I think the type of of information to be submitted has to align to getting that strategy agreed upon.

And and you think you would have the information on the different types of products that would be made over the life cycle of the facility let's say at facility design or enough to be helpful?

Typically yes.

Yes.

So that's part of you know as a CDMO that's part of the strategy.

What types of products do we want in what facilities and then design accordingly.

Can things change in the future?

Yes, but you know chemical synthesis products here, the biologics here, cell and gene here.

Sometimes there's a combination, but usually that strategy is defined well ahead.

Thank you.

Let's see.

Yeah, maybe just a um one last point to um to add is that in terms of information to give um we don't have a concern but it's more about what are the uh guidance in terms of the maintenance,

what it demanded to the company in the life cycle management, right?

And you we gave the information and for the first time and does that mean if in the future we have and make any changes what it demand for the company and that maintenance or the effort could be huge if there is and clear not clear guidance from the FDA.

Yeah.

Any other comments on willingness to provide information or any concerns you may have about sharing?

I think I think with that then we've we've had our discussions for today.

So uh

give yourselves a hand.

I think it's a great day.

Thank you.

So as I mentioned we are fortunate to have Grace Graham who is the Deputy Commissioner for Policy, Legislation and Internal Affairs close us out here today.

And so I'm very happy to hand the floor over to Grace.

I could stand for an hour and a half or whatever how long you've been up here.

And I heard that enthusiastic applause so I will keep my remarks short.

Um but I do want to thank you both to all my colleagues at FDA, Cedar, CBER, OII, our OEA folks for both coming up with the pre-check program, facilitating putting all the hard work to coming in this meeting today.

Um I am Grace Graham, Deputy Commissioner, Policy, Legislation and International Affairs at the agency.

I've been here about seven months and was on Capital Hill almost 15 years before that.

So very familiar and had lots of pressure in that previous role about how do we build more in the United States and I will say it is one of the first meetings I had starting here was what's FDA's role in domestic manufacturing,

how can we facilitate and make it faster?

Um so I also want to thank all of you from the private sector.

It's been a big day of pharma announcements from the administration and it is not lost um how valuable your time is with your companies doing your day jobs, but the input and the back-and-forth today I've been able to tune in between meetings when I can has been extremely valuable uh and I really appreciate it and I know the commissioner does as well.

Without you all uh the patients in this country wouldn't have access to the drugs they need wherever they are made.

Um and I also want to say I know it came up today that FDA is a wants to be a partner um but is only one piece of the pie, chain, uh however you want to look at it whatever analogy you want to use.

And so part of what I do at the agency is also when we announce this meeting I think I probably have colleagues from EPA, Commerce, State, others that have tuned in.

Um and we are working across the government to try to get barriers out of the way and be partners where we can.

State and local as well as is under my purview.

So to the extent that we can ever be helpful in facilitating more of that we want to continue to do so.

Think some of the sort of key themes that that I heard uh today and many of which um I think we anticipated some we didn't um is that decoupling, streamlining,

and more upfront communication is helpful um and would be useful as well as streamlining requirements for where we're either copy-pasting or product transfers, how can we streamline some of those?

As as I'm not really surprised about but we'll have to think about how to manage interest in broadening the scope uh of who could qualify for a program like this in total.

But all these need to be balanced and I appreciate the acknowledgement that we need to balance all of those goals with uh the ongoing work meeting user fee deadlines and getting what we need to do done.

So again want to thank everybody uh for spending all day with us today whether you're online or in person and the great conversation.

Please do submit more civic feedback to the docket and look forward to to following up with all of our colleagues internally and continuing to work on this externally.

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