six months of exclusivity to encourage drug sponsors to do those studies it didn't require success it required three things before a secretary had to accept the studies that the studies were performed in accordance with basic science  that the studies were filed in accordance with the f d a is filing requirements and that the study's fairly respond to the written request now successful studies get the grand prize they get a new pediatric indicat approved but none of them is on the market yet and our exclusivity period if this court agrees with our arguments would run through september of twenty eight so there's no witness issue the difference between lol when you say successful you mean successful in the sense the study tends to show that the drug is safe and effective for children i d guess so you're so you're clearly right the study doesn't have to be successful in that sense but why doesn't the study have to be successful in the much weaker in the weaker sense of just meaningful data one way or the other it could be could be successful in the sense it proves that the drug shouldn't be used for children or it could be successful in the sense that you get a good valid study in the data is inconclusive and all of that it would be helpful to the f d a but none of it happened here and all of that is not what the f d a described as the fair response tendered so that fairly response jantar the f d a articulated in all three of its administrative decisions is that you either have to meet every single term of the written request or you have to produce what the f d a called a meaningful labeling across all age groups and uses and to your question judge katz's inclusiveness was not enough if you look at joint appendix seven o nine which is the third letter of the nile the last phase of review the culminating statement about what meaningful labeling means is i e not e g but i the study's lead to a conclusive finding eyes are positive or negative for each age group requests requested in the written request that is the f d a standard that they're holding us to and it cannot get comfortably packaged within their they respond to you have to you have a quarrel with the state but two prong standard that they've articulated on appeal a described clinically meaningful labeling to be if you look at joint appendix seven o three clinically meaningful i useful to practitioners public health information related to the use of the drug  pediatric populations as expressed in the drugs labeling so did the fact that the f d a is receding from its standard actually suggests that it's not really receding from a standard and in all events the standard that brought us on appeal is the standard the agency articulated not the government sorry with a i think you just restated your argument that they've changed standards which was what get into but i'm trying to find i'm trying to focus on right whether you asked me yes you asked me whether i had a quarrel with the current standard my first quarrel is procedural but my second world is that even though they have recast the standard this formulation doesn't appear anywhere below if they are talking now simply about cloning full clinically meaningful information the place that we would look to discover what that means is back into the record what has f d a said they need when they say clinically meaningful information and it's that quote that i just read to you which ends with as expressed in the drug's label and so the fact that they've taken out labeling from their current formulation doesn't mean it's not still in there it's just hidden all right so sorry to work where begins where right so there they say the key sentence to me is towards the middle of the paragraph where they say in addition where the specific terms of the study are not  information produced is clinically meaningful across all age groups i e where the f d a can apply its scientific expertise to determine that the objectives of the study have been mad yes the agency will consider the sponsor studies to a fairly responded yes that's sounds to me a lot like the standard they're defending in the red bird now go back up to the very top ok this is the definition that i goal of obtaining clinically meaningful useful to practitioners public health information related to the use of the drug in pediatric populations as expressed in the drug's labeling so all of this of course is setting aside the elusiveness of the standard compared to how it was articulated below and i want to make clear exactly what the board pediatrics assumed the board based its decision on below because it wasn't this if you look at joint appendix six forty three which is the first of the sri administrative problems what you'll find on joint appendix six forty three totality of safety information amgen submitted had provided an appropriate safety assessment in younger children and supported a label description it would have been found to a fairly responded that's the first decision second decision joint appendix six seventy five based upon the lack of meaningful labeling information the board determined that engendered not fairly respond to the written request third decision joint appendix seven zero nine that's the chart that i mentioned before where the agency describes a meaningful labeling by the study's lead to a conclusive finding either positive or negative for each age group requested in the written test those are the street agency articulated bases for finding that amgen falling short in one respect did not fairly respond to the written request because the bottom line here for the group  are questions as well that the statute that contemplates pediatric stays and labeling actually contemplates inconclusive results just like this it requires that even inconclusive results go on the labeling but that's not what  therefore it's inconclusive right at the statute that doesn't distinguish between the substantive and conclusiveness and procedural and conclusiveness it says if you reach the end of the study and your data are inconclusive even that goes on the label  make a reasonable point that there's a lot there's somebody ness here to the extent that they are mixing and matching the actual say very part of the statute with the labeling part of the statute right but when you when you go to the labeling part of the statute it seems awfully broad what goes on the label right if the study is shows safety and efficacy that goes on the label if the study shows the opposite that goes on the way but one of the study is inconclusive that goes on the way so even if they did sort of this odd cross reference what's the harm to you where the wailing provision seems to say that any scientifically meaningful all information including a valid study that it's inconclusive goes on the label well to be to be clear the information from our study one on the label if you look in the joint appendix starting i think it five eighty seven it's the host studies label and the information about our study how many subjects were studied for how long what happened that the results  inconclusive all of that is on the label but the believe in your specific study they didn't like the one which had only four respondents instead of fifteen each of the studies each of the three studies that were requested and required to go into the label were mentioned on the label yes but with respect to the the statute talking about inclusiveness the reason i think that's important is because you can't set aside inclusiveness for purposes of labeling and require study was done and they weren't certain of the results of the criticism is that there just weren't enough young children in the study to know the information they need to know to decide whether to go forward that that was indeed the criticism that was exactly the criticism that the f d a leveled at merck in the merck case their work was supposed to study about approximately thirty five was the written request thirty five women studied five the a denied it exclusivity merck took them to court the f d a said close enough isn't good enough for fairly respond and judge roberts and said fairly respond plainly does not contemplate that every time of a written request must be satisfied fairly respond means if the studies as a whole answered the request that's a fair response so the fact that the studies were completed boat to both of your questions doesn't mean that they didn't fairly respond to the written request when you take these studies as a whole there were hundreds and hundreds of pages of studies that were submitted to f d a we did fall short in one request in one respect we satisfy the f d a in every single other respect and merck made exactly this point in saying that that is a fair response now f d a claims deference and i want to make an important point on this this does not warrant any from difference this is an unpublished on public informal adjudication it doesn't have any of the conditions that this court has looked at before when it comes to awarding chevron deference it's very similar to regulatory letters of the kind of issue here it was a letter but milan specifically says it relied on the regulations and two published decisions so that was my point of saying that even the letter rulings that they point are backed by something else they are either backed by a long standing interpretation a regulation or in some of the cases novartis and tether publicly docketed publicly commented upon findings so this is i think an unusual case when it comes to f d a because normally when you get an f you challenge there is something behind it there's a regulation or there's a citizen petition or there's a public process here there is none of that if you like the unpublished nature cuts in your favor i'll give you that but i mean need is sort of open ended on what counts or doesn't count cutting in the agency's favor participant only that wouldn't even have been public work not for this litigation there was an iterative process as the f d a calls it in its brief back and forth between this party and the f d a it was exactly the same iterative process and focused child that didn't warrant any extra treatment or any extra deference due to the agency there the question in need is did the agency intend by this pronouncement for it to carry the force of law and when you have a pronouncement that is backed by something like a regulation i like that public process then the answer's almost always yes but when you have a pronouncement that is not published nonpublic informal non presidential that doesn't satisfy chevron what do you how do you answer their response to that that a lot of these kinds of rulings are not published because they tend to contain proprietary information to benefit the drug drug compan i think there's two responses one of them is that proprietary information could be redacted but the second use if they're not published and informal and non presidential then they just don't get chevron deference it's not it's not a reason to give them deference that doesn't count for anything in the che and if we are at step chevron step zero then i think the answer is very clear and if i make an issue of the couple points the first is there is nothing in that statute that talks about profiling protocols scientific protocols and fairly respond that warrants importing an entire labeling inquiry into the question of what fairly was was there is an entirely different statute section twenty one u s c three fifty five v that in detail gives what has to go into a secretary or the f d a is finding of labeling there is no support for the idea that that comes into the fairly response gendered last point i would make is even if this interpretation survives the whole chevron gauntlet you are left then with a significant fair notice question and i would point you to general electric and i would point you to the gates and fox case that cited there and because in both of those cases  court ultimately found was yes this interpretation is tolerable it's reasonable but there was not it was not available to the regulated party with ascertainable certainty f d a doesn't even contest that this was  available it says that we should have been aware of the framework the only thing we were aware of of course was merck which said what i read to you earlier and the public statement on the f d a is website that said pediatric exclusivity is not tied to labeling which is exactly what they determined here for the question between having studies that are inconclusive this charge will cause point out as and having studies that just don't furnish enough data to make any conclusions that labeling decision about not being having sufficient data is not something that the issue here it's a subtle fact how do you distinguish this from merck i recognize it was just a district court case for i will what f d a has done is taken the lessons of merck which with this had a specific ruling that a couldn't require that the only criteria used the meet all of the terms of the written request that's opinion goes on to say that the f d a should look at the entire study as a whole and see if that is a number of finishers but what f d a now does after after merck is to take a look further at the study as a whole to understand what has been learned from the study and and look to see if that produces quite was the it was rejected first for not meeting the specific terms of the written request later the f d a looked further additional information relating to merck found that the written request had been had basically been met the entire atmosphere correct there is the other three studies had met the written request and so there weren't any questions about the whether those studies would have qualified for pediatric exclusivity study three was with only four of fifteen  just not enough data to provide any sort of conclusions about safety and efficacy and that's that's when the label and the idea here is under the statute is the f d a is looking for information that goes to the use of the drug and may produce health benefits and that's the language of the statute of when the f d a issues a written request so it uses that language to look for actual information that provides a health benefit that provides physicians with here such that the written request can be changed to accommodate something like that should it shook so so that's the way that it should be resolved just by amending the written request rather saying well what happened fairly respond to  that it would be proper to say you know we would mend the request but to the extent the study is that it's possible that it's going to still result in meaningful data there wouldn't necessarily be a reason to to  alter the written request that is your question that back to merck for a second so the primary holding that you can apply of comply with all terms standard doesn't really hurt you here but there's this further piece from or quitters court statement that disappointment with the data is not a sufficient grounds for denying pediatric of the idea of you know not looking just specifically for positive data did disappointed because a valid study shows that this drug is won't work for kids that's how i mean that's a ye so there was plenty of time to discuss what the standards and the objectives were and but merck was decided and then two thousand and one seventeen years ago and so far as one can tell there's no public statement of the two part test or whatever else the commission's position might be in light of mark that seems a little troubling there is well there's no specific guidance that's been given out it goes back to what i was starting to talk about through the the process which makes this piece unique from from from much of these other in the street walker says which is the parties are working together on th there should be clear expectations there can be expectations shared between the two that these are the objectives of the study and keep in mind that this is this is science theory and it's a clinical trials run for a reason and so the reason is to find some sort of answer to a question whether positive or negative and so the idea that f d a was expecting the objectives of a study giving that such that you know the safety and efficacy of a drug can be described in evaluated that  there would be a requirement that there be clinically meaningful information coming out about as being an indication that the study met its objectives as it is is pretty basic and almost goes without saying there were there was at least in two thousand and thirteen brother i should say the f d a did not believe that the current program was sufficient to inform the public on the safe use a cynical sets and would not be adequate to support a written request so the least to the extent that there's the civic interactions we can point to that as well as just the the the the general reading of the statute which again goes to a very specific purpose getting information that physicians can use there's any number of indications that it's what the standard would be how do you respond to the point about the arguably shifting nature of prong two on the question whether it requires clinically meaningful information in the abstract or something that's meaningful on the label just is that we not a difference that matters or well the the three letters at issue are all very clear and i should go even goes back after after the decision and merck you can find writers going back to two thousand have thought that the paragraph in the middle of seven o three tide that down pretty well and conforms to what you say in the read brief but i have to say missed the steps and made a pretty good point and noted that it's whether this clinical meaningful information or rather let me start again if there's labeling meaningful labeling that is an indication of whether the the studies ha discussing that they consider whether labeling had been met again consider is it's are can be is being used can be used as an addition to the three letters themselves all at the start start with very clear language and talk about if a study doesn't result in interpret the language or i'm sorry interpret of all of the studies not interpret all i e if it doesn't have enough data it's most likely going to be denied so that's set out very clearly at the beginning of all three of these letters that concept now some of the language as we get in there gets a little bit money in it and right big bottom line is they are separate inquiries you already see a case is it isn't the case itself is the following legal proposition true which is if there is a scientifically valid study on the usefulness safety advocacy of this drug for children that either points one way or the other or is inconclusive good good study just the data don't resolve with that as a matter of law go on the label yes well first off to clarify there is the section three five a j which means anything anything goes on the way yeah that's what i was that's what i was reading and i would have thought that least that would lead to an argument on your side that doesn't really matter whether you said clinically meaningful or clinically meaningful on the label because everything that's clinically meaningful goes on a label like that but i don't think your brief well some point quite that crisply no no no it does answer to the extent that it gets mentioned we're carrying this idea that just because something is mentioned on the label it ought to be of a magically means that should've got pediatric exclusivity which we would say is not the case because there is basically no bar to getting on the label under three fifty five a j it becomes a question of whether that's actual meaningful labeling and again we're referring back to the statute the statute specifically asking for information what would be done well it becomes a question i think of a specific analysis and then the data that comes in to the extent you're talking about studies that garner enough data that can be analyzed and you can look is there a connection between that the evidence in the in the data i mean there is also well there is this idea that the dosage on these children was very slowly going up and so you need to look at that you do so to the extent you need to make sure you understood how the drug was reacting fifteen data points isn't very much and so if you have one less finish or it could could dramatically change what the results were particularly if we are talking about children who were titrated at that sort of a different rate i mean if there is some potential plex ability to amend the request if there is some reason evaluate this can you describe the sort of safety profile and then it becomes a scientific discussion about you know how tight the statistics are and and what sort of trends we can actually discuss and how robust th actually get enough enroll patients in and the the you know the study sponsors at this point as i was saying earlier often also still looking for an indication in meaningful labeling and so they're going to be interested in trying the terms of the written request in to the extent that there are starting to be difficulties with that bring it to the f d a is attention to amend the complete man and the written request if needed and to explain you know potential problems with the with the that are just listed in the in the documents here in the on this record at some point when discovered that there was going to be a problem completing study him brought that to the f correctness not not on appeal and i think the background of that is just some point you know this study needed to wrap up and there had been sufficient reason to to reduce that the number of correctly that sometimes for whatever reason there are perfectly good studies that doll and up on the label you sat right right ok if that's if that's true then why isn't it a problem for you to the extent your articulation of the standard sometimes in a muddy way whatever sometimes suggests that you need studies that will end up on the label but we're looking at the studies as as not necessary but a sufficient indication and so it's not a requirement if you did to get the labeling but it's that's looked at and it's you know the district and i think also the bottom line to keep fish sufficient but not necessary rush you're right and so there's no indication that the inquiry stops at that point and i think also just to keep in mind the extent we're talking about labeling fifteen it was granted because this is what the f d a says it joint appendix six sixty seven the agency followed the finding of the court to recognize exclusivity based upon the determination that merck had substantially met the written request terms even though not meeting the exact terms that's why merck exclusivity on chevron the government counsel talked a lot about the process in this case but the process that triggers chevron is a public process not a lengthy no matter how lengthy iterative process between one regular regulated party in the agency what gets you chevron deference is a prison ousmane that is intended to carry the force of law and there was no such pronouncement in this case not even this decision would be public were it not for this litigation third on clinically meaningful i want to be very clear the board based its decision joint appendix six seventy five based upon the lack of meaningful labeling information the board determined that amgen did not fairly respond i agree there's a lot of money miss in those rulings that is not m the last thing i would say with respect to september twenty third teen mr bureau mentioned that there was an exchange at that point there was what mr bureau neglected to mention is that that is the meeting where and jan put this question the f d a do you agree that we should stop these studies and the f d a said no we disagree we have learned a lot from the clinical data that you have collected during these studies so the idea that the data that we did not prove that we produced those hundreds of pages were clinically meaningless so meaningless that they somehow go on a label and they have no meaning whatsoever it's a little bit difficult to take even inconclusive results are clinically meaningful physicians look at that label then make a decision based on that label they can look at the public studies that resulted from our studies and they can make clinical determinations so if we are in a clinically meaningful world not tied to