DCL Learning Series

Marianne Calilhanna

Hello and welcome to the DCL Learning Series. My name is Marianne Calilhanna. I'm the VP of Marketing here at Data Conversion Laboratory. Our presentation today is titled "SPL and SPM – Ask the Experts," in which we invited you to submit any question related to structured product labels and structured product monographs. We collected questions during the registration process and we also invite you to use the question box here in GoToWebinar if any additional questions come to mind. 

Today's agenda comprises a short bit of housekeeping from me, and then I'm going to introduce today's speakers. We'll get into your questions and we hope that you submit additional questions or any comments that come to mind. We'll close with a little more information about Data Conversion Laboratory and how we support structured markup, XML conversion, and more. This event is being recorded and it will be available in the on- demand webinar section of our website. Just go to dataconversionlaboratory.com, select "Resources" and "On-Demand Webinars" from the navigation, and you'll find a number of webinars related to this topic and many others. 

We also just pushed that URL via the chat dialogue box for easy reference. I'm delighted to introduce today's speakers. We have Howard Shatz and David Turner. Howard has been active in SPL since its development began in 2003. He's an active member of the SPL Working Group, and Howard serves on the Establishment Registration, Drug Listing, and OTC sub teams, as well as on the leadership team. Welcome, Howard. 

Howard Shatz

Hello. Glad to be here. 

Marianne Calilhanna

David is an industry veteran in the areas around content management and content structure. He is particularly adept at demonstrating the business benefits of digital transformation and helping organizations identify ROI KPIs to gauge investments in systems, structure, and semantics. Welcome, both of you. 

David Turner

Thanks so much. 

Marianne Calilhanna

David, how about you start us off with the first question? 

David Turner

Well, thanks very much. I do appreciate it, and thank you to everybody in the audience who's participating. We appreciate you just participating by being here. Special thank you to those who asked questions in advance. It was great to get some questions in advance. And then also I'm just going to thank you in advance now for asking the questions that I know will arise soon. 

So please don't hesitate to put those questions in the chat or in the questions box or whatever way so that we can answer them. It's intended to be a chance to ask an expert, specifically Howard, or there are some things I could talk about too. I will say this, we do have a really diverse audience today, very international, representing several countries, continents. Some of you are our clients and are people we know in the industry who already have a very solid understanding of concepts of things like SPL and XML. But there are others of you that I think might be newer to the industry or may need a little bit more of the basics. Some of the questions that have come in have indicated there's a little bit of that out there. And so any case, no matter who you are, you know, we're going to try to get those questions answered today. And I will say again, we are depending on you to ask some questions, so don't be shy and we want to make sure we get you what you need.

4:00

So anyway, let's get started. The first question, asked for kind of a simple definition. It was What is SPL? What is SPM and how do we tell the difference? Well, I'm going to start by just first of all defining SPL, and once we have that defined, I think you'll find that the SPM part will become clear. 

It'll be easier to see the differences. So at its very core, actually, go back a little bit there, Marianne. I don't want to confuse you. All right, NOW click forward. All right, there we go. So what is a structured product label? Well, first and foremost, it's a way to structure all of the details related to drug information, ultimately so that a computer can make sense of the text. And what I mean by that, helping a computer make sense of text, I mean obviously computers deal with lots of text all the time. I want to start with a non-pharma example. And go ahead, let's put that next thing up here. So here's a card catalog record. And if you're just an ordinary human being at the library and you ask somebody to read this card catalog, they'll say "Dickens, Charles" and you know that's the author's name, right? 

You just know that. In fact, I would say that probably most people would recognize that Charles is the first name and Dickens is the last name. You would also recognize A Christmas Carol in prose as the title. You'd see there's numbers all over this thing. If you look down here and you saw 1843 on here, I think you would probably surmise that it was published in 1843. The next line, there are 166 pages, and so on. So we humans, relatively simple. But to a computer, when it sees the letters D I C K E N S all put together, it doesn't know exactly what that is. 

Dickens, Charles, Christmas. Carol, 1843, 166. Those are all just words and sequences of characters, and sometimes that's okay, right? If you hit a search and you want to find where the word Dickens exists in a series of documents that will help you. But it doesn't really help you if you want to maybe do a search by the author name, or if you want to find a book by a specific title, or if you want to find a list of books that were published in 1843 or something like that. So to help the computer be able to help you with that, we've got to give it some clues. 

All right, let's go to the next slide and we'll put this in the context of pharma. If you want to be able to search for a drug on the DailyMed here, if you want to search by drug name, or by a manufacturer, or any number of different pieces of metadata, you have to help the computer to make sense of some text. It can't just take the words from a Word document and infer them. So we have to give hints. We have to structure the label information for each product to give the computer what it needs. And we do that through what are called XML tags. And here's what it looks like behind the scenes. It's kind of complex looking, but basically we're doing is we're using some start tags and some end tags, similar to what you see here with the little open brackets. And it tells things like, it tells the computer, this piece of text is the proprietary name. These characters represent the dosage form. This is the marketing start date. This is the marketing end date.

8:00

And ultimately what the SPL XML is doing is it's helping the computer make sense of all of this text so that when you try to search something, you can actually find all of these things. Incidentally, Howard wanted me to point out, he noticed there on this particular DailyMed screenshot that we took that it talks here about inactivated NDC code. 

Tuck that away for later. He's going to hit on that, but just for now we'll show it. So in ant case, go on the next slide here, Marianne, for me. And let me just kind of pick up on this idea of these XML tags. The fact that it's in this XML format, kind of behind the scenes, really there's a lot of benefits besides just helping the computer make sense of that text. First of all, the fact that it's in XML helps make sure that we can keep the standards that we set up-to-date because it's an international type of a standard. Secondly, XML stands for extensible markup language, which means we have flexibility to create the tags that we need for a specific use case like SPL. 

The idea behind XML is that there are different communities out there that might have different needs. Some of you may be familiar with, like, HTML for example. And that's more or less limited to very practical things like this is a paragraph, this is a table, this is a header one, this is a header two. And you include all those same things in other XML formats but XML gives you the benefit to say, for a specific use case, like if I'm a journal publisher, I wantto know, I need a tag for what's the volume of that year. And the example we used before, if I publish a book, I need a field that says this is the date this book was published. 

I also need a field that says this is the author's name. And in SPL we've been able to create very specific meaningful tags like we just talked about. Here's the marketing start date, here's the dosage form, on and on. So the fact that it's in XML gives us that ability to create. And over time if we need to, we might be able to add other pieces to it. We might be able to add additional fields as things change over time. Or if you have different health authorities, they might want to create certain specific things for them. Anyway, so that's kind of that. The next little bullet point here says it helps with search and discoverability. 

Another big key is when you put something in an XML format like this, it facilitates interoperability. It's something that SPL XML can be understood, processed by all sorts of different computers, as number five says, by different platforms. If something is in Word, you've got to have word to read it, right? If it's in PDF, you have to have a PDF reader. Most of you are probably much younger than me on this call, but Howard, you might remember. Back in the nineties before we had Microsoft Word, we all used to be users of this WordPerfect tool. And I think WordPerfect's still out there. But I can remember saving things and saving documents. 

All these things I saved as WordPerfect files. Fast-forward 10 years, I went to go and retrieve those. I couldn't read any of them because they were all in WordPerfect and I didn't own WordPerfect anymore. And we face that same kind of thing by keeping things in things like Word, but having it in XML, it gives computers hints where we could be able to extract that information without necessarily having to have a specific Microsoft Word software. I'm just going to hit on a couple other little benefits and then we'll get back to the SPL thing. I also want to say one other thing about XML, and this is something a lot of pharma companies are starting to see beyond just the use case of SPL and SPM, and that's the ability to create multiple outputs from the same source XML. 

12:09

With the right structured content management system and structured content management program, there are some really interesting things that you can do. With that, with your XML, you can take that and you might be able to create regulatory documents from multiple health authorities all from the same source file with small minor changes from each. You might be able to use that same XML file to create some HTML that needs to go to a website or to a mobile app. You might be able to use that to create your print label. Whereas traditionally we've had very separate workflows and very separate outputs and format types and document types. 

The fact that it's in XML gives you this ability to be able to go to those multiple outputs. All right, last thing on this slide is that XML promotes consistency, which actually leads me to our next slide, which is the other big thing that I want to say about the structured product label. Marianne, if you go to that next slide. So not only is the structured product label a way to help the computer make sense of the text, it also makes sure that we keep everybody on the same page, right? We want to make sure that no matter where in the world, if somebody is submitting something to the FDA, that we're using the same terms, that we've got the same vocabulary, that we've got the same measurement standards, so that what the FDA gets is consistent. 

If they get consistent information, then they can get that information out there to the world much faster. If you don't get it to them consistently, there's a whole process of trying to MAKE it consistent. So this, the structured product label, gives us that kind of standard. And Howard, I've been talking way too much here, but one of the things that, the examples I know you used to give is around the word "water." Can you talk a little bit about that? 

Howard Shatz

Yes. So when you write a label for an FDA package insert, or for that matter, putting it into drug facts, you can say "distilled water," "purified water," all sorts of variations that end up having the word "water" in it. When you submit the file to the FDA, the FDA has basically two parts. There is a third part, but that's not important right now. The two big parts are what the FDA calls the content of labeling, which is a package insert. And the other part is the drug product information, which, in the case of DCL, we ask you to put it into a worksheet and then we convert that. 

In that drug product information, you have to put the names of the product. So the FDA requires that you use the preferred substance name for the ingredient. So in the case of water, you've got purified water, distilled water, H2O, I don't know what else you want to call it. Call what you want in the content of labeling, the FDA does not care. But when you put it into the drug product information, the only way you can put in that ingredient is to call it water with its unique ingredient identifier. So they standardize that. Now, water is a simple example. 

We've run into other types of things where the preferred substance name is totally different from what is written in the content of labeling, but yet in the ingredient name, you have to put in that preferred substance name even though it's wildly different from what you have in your content of labeling in your package insert or your drug facts. 

15:52

I contrast that, just quickly, I just contrast that with the SPM, with the HC product monograph XML, with the XML HC product monograph that Canada is now in the process of implementing, where there in the text, in the monograph itself, they want you to use, when it's a term that's subject to controlled vocabulary, they want you to use that term. So you should use "water" when you write up what's in the product, not "distilled water," not "purified water," and so on and so forth. 

David Turner

Thanks, sir. All right. So just to summarize again, the original question was what is SPL and SPM and how are they different? So we started kind of with the first part. What is SPL? That's a structured product label. It helps the computer to make sense of text and it gets everybody on the same page using the same terms, measurements, when they're submitting to the FDA. So now let's go on and let's talk about the SPM. So, Marianne, hit that next slide. So the SPM also uses XML, but it's a little bit different model. So remember I said XML is extensible. So Canada updated things with the tags and vocabularies that make sense for Health Canada. 

So as such, you could think of a structured product monograph, or SPM, as a way to help the computer make sense of text and a way to get everyone using the same vocabulary, measurements, et cetera, when submitting things, not to the FDA, but to Health Canada. By the way, don't expect it to stop here. Other XML labeling standards are in the works in other parts of the world. We've had a couple of questions about some of those and we are going to hit on some of those in a little bit. But Howard, let's let you hit the second half of this question, which is just kind of at a high level, what have you found to be the biggest differences between the SPL and the SPM? 

Howard Shatz

The biggest difference is in the writing. Obviously the format itself, what you have to write in a monograph, is different from a package insert. But it gets back to what I said before. The FDA is not enforcing the controlled vocabulary in the text that you write up in the package insert or the drug facts. But Health Canada is requiring that you use the proper terminology in the course of writing the monograph. One of our clients now - Health Canada also has the additional issue of you've got to do it in French and in English. 

So they have to have controlled vocabulary in French and controlled vocabulary in English. And when they're behind, at least in our client's mind, they're behind in translating the terms into French. They are catching up. They're doing a very good job of catching up on that. But there are still some holes in the French terms. So when you're writing up your monograph and when you have to use the controlled vocabulary, you're sort of stuck because you don't have the right term yet. You have to negotiate with Health Canada until they have the right term in place before you can have a final submission. 

But it works. Basically it works the same way. You submit the XML, just like when you go for an approval submission in the United States, you submit your package insert with SPL, and it's not mandatory yet, but Health Canada would like you to submit XML, along with your product monograph, and they will validate it for you. 

David Turner

Well, very good, and I think it's also safe to say we'll probably see some additional changes with Health Canada because it's a newer standard. So you've been doing SPL since what, the early 2000s? 

Howard Shatz

Yeah.

David Turner

And these SPMs are just here in the last couple years, so.

20:00

Anyway, but let's move on to the next question. Marianne, hit the next slide there. And the next question is, well, kind of broad. How do I comply with the regulatory requirements for SPL and SPM? I'll start by answering just a little bit broadly, which is both the FDA and Health Canada do publish comprehensive guidelines, and I think with enough time and energy spent, you can certainly go out there and make yourself an expert. We do, by the way, also have a handout available with some links that can get you started. But I'm kind of interested, Howard, in what you would've to say here. How would you answer this question? If you were at a conference with somebody and they said "How do I comply with these things?," What would be your thoughts? 

Howard Shatz

Okay, so in terms of writing the monograph or the package insert, we leave that to the pharmaceutical companies. But the regulatory requirements for submissions, come to DCL and we'll walk you through it. But basically there are the links that David referenced that we'll be providing to you but you should be familiar with them. And one of the things that I found now, well, let's back up a minute. SPM right now, the XML for Health Canada, is really focused on just the monographs. That's all that they're doing. The FDA has additional uses for SPL, which is establishment registration, NDC label code requests, NDC label code registrations, the blank notation certification, which we'll talk be talking about later, the lot distribution reports. 

REMS is now becoming mandatory, for those who may be familiar with it. I won't go into detail on that one yet today, but there are all sorts of uses that they found for SPL and you need to conform to those. So they do offer training. They have an SPL, one of the links that we'll provide to you is the FDA's SPL resources page, which has a lot of links for you to look at, or again, you can come to DCL and we can walk you through all that. 

David Turner

I think another helpful hint here is one of the things I've discovered is that sometimes the people who are working on labeling in an organization for the US for SPL a lot of times don't talk to the people who are dealing with labeling for Canada or other parts of the world. So just another recommendation I would have as you're moving down this, use each other in your organization. Make sure the other labeling people. If you work in the US on label, make sure you know who's doing it in Canada. And if you're in Canada, make sure you know who's doing it in the US. But the next question that came in is actually kind of a similar question here. Marianne, go ahead and hit that one. And it just says, how does somebody submit SPL and SPM? 

If I took this question, I would probably give the stereotypical consultant response, which is: it depends. And because it does, it does depend, and there is a lot of underlying complexity to this simple question. But Howard, in your years of experience in doing this, what would you say to the person who asks this question beyond simply it depends. 

Howard Shatz

Okay. So the SPM one is a simple one because what you can do there is put it into an ECTD, which is the only way at this point that Health Canada will accept it and they will then review it. In the United States, when you submit SPL, we'll talk about that in a minute about how you can submit that, but it goes through an automated validation process and you get the results pretty quickly.

24:10

But with Health Canada, you submit it to Health Canada and the business rules that they've associated with their SPM are validated at the Health Canada end. And then they send you a report, which is a very nice report. I think it's very nice. It tells you, it's like a checklist. It's broken up into sections and into subsections and they tell you in each subsection, did you pass or did you not pass. Or do we have to give you a warning because there's some flexibility. You don't have to necessarily fix the issue that they cited. So anyway, that's very nice. But that's a very simple thing. You just send it, put in into an ECTD. If you don't know how to do that, you have to work with Health Canada and find out how they want their ECTD set up. But the SPL, you have options in the United States. 

Now, when you are submitting, I mentioned before about our approval submission. You're applying as a new drug or an abbreviated new drug and you need to submit that. That goes through the review division. And there too, you've got the ECTD as organized by the FDA and you put the right files in the right modules and you go and submit that. But if you have a drug listing, and for OTC customers that's the only way, the only you thing you have to know, is you submit things through to the office of, what they call the Office of the Commissioner. 

And there you go through their gateway. They have an electronic gateway for all sorts of submissions. So you can have an account there and you can submit your drug listing that way or your establishment registration, your OTC label code, et cetera, et cetera. The other way you can do it, and it may cost us some business, while we provide the gateway submission as a service, you can do it yourself through your publisher. If you have prescription drugs, you have a publisher and they can submit it for you as a drug listing or you can do it yourself. 

And for you OTC customers, that's a possibility that you can use CDER Direct. You can set up an account with FDA CDER Direct. That's a freebie, and they have an interface with the gateway. So when you've prepared your SPL and you say submit it, it submits it to the gateway. The gateway, if it has validation errors, it sends it back to the CDER Direct and CDER Direct has an interface to try to make the error messages a little bit more meaningful. And you can do the same thing with the files that we that we deliver to you. If you're a DCL customer and we prepare the SPL for you, you can use CDER Direct. You just upload. The SPL will be delivered to you and then you say "submit it" and you can do it that way. And we have customers who do it just that way.

David Turner

Yeah. So you do have a lot of different options. And I mean, it kind of depends on what is your technical expertise, how comfortable are you with this? Do you have a greater peace of mind by submitting it yourself or do you have a greater piece of mind with letting somebody else do it for you?

28:03

So, again, we can help with some of these things, with some of the submission pieces that are along the way. We also have some partners. Some people, some great organizations out there that we work with to outsource some of these things. And we could talk through all these options with you and we'll make sure you have our contact information at the end. We're always glad to help in whatever way. 

But I see Marianne has moved us on to the next slide. So I think that's my cue to keep this thing moving. Which, here's a question about FHIR. We love to talk about FHIR. FHIR is another one of those things where you hear when you hear talks about SPL and SPM and IDMP and all of this stuff. In fact, we actually got a question in from the audience as well about FHIR, asking specifically, what are your thoughts on the FHIR standard as discussed in Europe for EPI? So Howard, can you give us a brief overview of FHIR and what it means and how it fits and all of those things? 

Howard Shatz

To keep it brief, I'll describe it as another way of structuring data. However, unlike SPL, or SPM for that matter, where the focus is on the textual part and the product information, again, the product monograph or the package insert or the drug facts along with the drug product information, what is the exact name, what is the valid name for the active ingredient, and what is the strength of the active ingredient in scientific terms, and so on and so forth, FHIR is designed to exchange all sorts of health information, including health records. 

So it's evolving. To be honest, I haven't looked at it, I'm not looking at it that closely because I've been burnt too many times because there've been a few standards that have evolved over the years in an attempt to solve this problem of being able to exchange information across industries, well, across countries, the regulatory authorities of countries and also hospitals and all sorts of things. But the FDA's position on it is interesting because they already have SPL but SPL does not, it's a square peg in a round hole trying to fit SPL to FHIR. 

There is a tool out there. There's a GitHub you can get where you can actually transform an SPL file into FHIR. But again, there have been a few, some of you may have been veterans of the PIM modules that Europe was looking at 15 years ago, and that never got any place and IBMP even that may not be the end all and be all for Europe. So we shall see where FHIR goes. But we have great links. If you need links for FHIR information, I can get those to you if you want. 

David Turner

And if your interest is EPI, I know there have been some different experiments with EPI, a couple organizations using custom XML models to create. There is an industry consortium called PharmaLedger that is doing some things around EPI and working with some different XML models and things like that. I will put something here in the chat. I don't know if I can get this sent out to everybody. Entire audience, there we go.

32:03

It's just a link to another webinar that's out there that talks a little bit about EPI and to the PharmaLedger organization. You might check that out there. They're great folks and they are trying to do something. 

Anyway, I will say this about FHIR. If you want to have more of a deep-dive discussion, I mean we could do an entire afternoon of webinar about just this particular topic, but if you have more specific questions about this topic, we are happy to set up a call at any time, walk through, talk through, give you more thoughts, answer more questions, that kind of good thing.

So, all right, Marianne, let's hit the next question. All right, question five. How do I make sure a drug is listed properly? We actually talked about this one a little bit ahead of time, and Howard, I know you have some helpful tips already. Marianne, let's go ahead and go to that next slide and let's let Howard walk through these tips. 

Howard Shatz

Okay, so, tips. This is a very brief number of bullet items here, but the important thing is marketing category. So if you have an active pharmaceutical ingredient, an API, the document type that you need to use for submitting to the FDA is bulk ingredient. If you are, on the other hand, manufacturing an actual drug that's taking an API and mixing it with inactive ingredients and maybe other active ingredients and producing the drug let's say in a tablet form, and you're manufacturing the tablets, not to confuse things, but people refer to it as manufacturing the tablets in bulk. 

That's not a bulk ingredient, that's a bulk drug. So if you're shipping it that way in bulk in a drug, let's say, or in bags not ready for retail distribution, that's called a drug for further processing. So when you list that drug, and domestic and foreign manufacturers are required to list those drugs that they manufacture, and if they're doing it for further processing, then you list it as for further processing. Then the next category, well, it's not a bullet item, but there's a simple case. If you're making a drug and you're packaging it and labeling it, and when you ship it's ready for retail distribution, that's a drug that's manufactured under contract. 

So that's the marketing category you use. Those will not appear any place, not on the DailyMed or NDC directory, but the FDA will know that you're manufacturing those drugs under contract. Then you have, well, the last bullet item. I'm sorry, I got ahead of myself. The appropriate time for the final drug listing if manufactured under contract, there you're going to use a submission type of human prescription drug label or human OTC drug label. So pick one of those document types. Bulk ingredient, if you're making APIs. Drug for further processing if you're making drugs, but you're shipping them in bulk for somebody else to package. And then if it's a final drug listing, whether it's manufactured under contract or it's an approved drug or an OTC drug, you choose the appropriate category of either human prescription drug label or human OTC drug label.

36:02

There are exceptions to these rules: biological drugs and blood products, but they're few and far between, so I'm not going to bore you with that. When you submit these SPL files, you have to have a DUNS number for the labeler and for the establishments. So you have to make sure you're using the right DUNS number and the right company name for the drug. In other words, whatever Dun & Bradstreet has on their record for that DUNS number.

And then for drug product information, there are all sorts of FDA validation resources if you go to the SPL resources page. I'll also put in a plug for the free pragmatic data validator. You can submit your SPL and validate against that. That will catch 90 to 95% of all validation issues the FDA would find. So we recommend that you do that. Any drug label that we ship has passed validation with the pragmatic data validator. It may fail validation at the FDA because the FDA validator uses FDA databases to validate the data. Nobody other than the FDA can use those databases to validate it. Okay? And then to make sure that it's been listed, if you go to the next slide, we have the National Drug Code Directory. 

So any drug that was listed as an approved drug or under a monograph, that's a finished product. So you can look it up that way. If it's a drug for further processing or an API, you can look it up as an unfinished product. So these are all the - and they have various ways of searching. You can go by NDC number, you can go by the proprietary name, non-proprietary name, and so on and so forth. So, you can do that search, and when you do the search, it will come up and show you what results it has and it tell you what it's certified through. 

And this is the point at which I'll bring up, well, on the next slide, I'll, in a couple minutes I'll get to the inactivated codes that David had referenced before. But that's how you verify. If it's a drug manufacturer under contract, the only way you can make sure it's been listed is to contact EDRLS. And we will give you the link to their email because the drug manufacturer and the contract listings are not made public by the FDA at this time. It's subject to FDA's decisions. Okay, we're ready to move on. 

David Turner

Yeah. Well, before we go to the next question, I'm going to insert an editorial comment here. I know specifically that there are a handful of you sitting there, and you know who I'm talking about, who have a question and you're thinking to yourself, I don't want to ask it because I might sound stupid. Go ahead and ask the question. Put it in there. We do have a good list of questions that have come in already, but we want to make sure we get yours answered too. So even if you think it's a dumb question or whatever, just go ahead and put it in there. You can do it. All right. Now back to the pre-, the questions that we got in advance. The next one: how do I go about certifying a drug? Howard, do you want to talk a little bit about certification and what that means? 

39:54

Howard Shatz

Okay, yeah. This is a little bit confusing to people, but certification in the FDA regulations means that you have reviewed the drug listing come June and December of each year. You make sure that all of the information in the drug listing, that the last listing that you did, you make sure everything is correct. That includes the text that's in there, as well as the product information, as well as the manufacturing information. And if it's not up to date, they want you to update the label. 

When you submit that label with the revised information, you have certified the drug for that year and the next year. Well, it is actually for the next year, the way it works. But if you have not had any changes, don't do anything during the course of the year. Come June, you review, you don't have any changes. Come December, you don't have any changes. Then in that last quarter of the year, between October 1st and December 31st, if there are no changes to that drug label for that year, then you either submit the label if you want to or you go about submitting a blanket no-change certification. And we have a slide for that.

David Turner

We have a slide for that, I think.

Howard Shatz

And it's about to pop up.

David Turner

There it is. 

Howard Shatz

Okay. It's convenient, easy to create but not without validation complexity. So what you do in a blanket no-change certification, we're not going through all the details, but the essence of it is you put in the product codes that you want certified. You can put in as many as you want. There's no limit and there's no limit to how many people submit blanket no-change certifications with that product code. But with that product code, you put the manufacturer of that product, you put the establishment name, the manufacturer of the product, not the distributor. You don't put in CVS as the establishment name with CVS's DUNS number and CVS's product code. 

That will fail validation because CVS does not manufacture any drugs. You put in the manufacturer of that drug for CVS and you put it in with their DUNS number. Now, also, the challenge here is that the last listing that you did needs to pass current validation. This happens automatically when it sees the product code in the BNCC. The FDA, you know, goes through all of its electronic submissions, finds the electronic submission for that product code and validates it automatically. As far I know there's no human intervention in this process, and things can happen when it goes to validate that last listing that didn't pass validation a year ago, even six months ago, but they'll be found to, validation errors will be found and the entire BNCC will be ruled invalid and you then have to go and do it again.

Also, it will check, among the other things it's doing, is the BNCC is restricted to only drugs that have active marketing dates. In other words, they do not have any end marketing dates. They are considered to be currently in production. If you had delisted the drug product, even though it's not going to be delisted until 2023, but it has an end marketing date in its last listing, they will find the BNCC is invalid. Another thing that happens, this other bullet item, the third bullet item, is that it specifies a company that is not currently registered as an establishment.

44:01

So now this is an interesting one because this the FDA does during the course of the year. So you can submit a drug listing in December of 2021, or let's talk about this year. December 2022, you can submit a drug listing, and it has an establishment that was registered through 2022, it will pass validation. But in mid-January to late, early February, I'm not quite sure of the timings, but the FDA checks all of the drug listings that they have and looks at the establishments in those drug listings, and if any of those did not renew in 2022, they will kick out the drug listings. So they have two checks on this. This is something that occurs during the year. They are looking for drugs that have establishments that were not listed. And also in a BNCC, if it encounters a BNCC that has an establishment that is not currently registered, they will flag that as invalid. And again, the entire BNCC is invalid.

And then the last point is what I had referenced earlier. If you put in an establishment name that is really a distributor and the distributor's DUNS number, it's going to be invalid. So there are all sorts of checks that they do with a BNCC. But what we recommend is that if you do get these validation errors on specific product codes, take out those product codes and resubmit the little things with the BNCC without those product codes and you should be good to go for those. And the ones that had validation errors, you've got to address separately, submit labels. Once you submit those labels, you don't have to worry about a BNCC again for that year because submitting the valid label will get you around that. 

David Turner

Excellent, very useful information. A lot of detail there. Again, if you have questions about this, something we can dive into in more detail afterwards anytime. We're here to help. We want to see things move forward, so just let us know. All right, let's hit the last question that, at least the last of the ones that came in advance, and it wasn't really so much of a question as much as it was more of a request: Can you please share the Health Canada SPM regulation references? We actually do have those in a handout. Marianne, is there a way to bring the handout up? I wasn't sure if there is or not. I don't know if I'm throwing too much at you here.

Marianne Calilhanna

If everyone just clicks on the box that says handouts, you should be able to access that PDF. We'll also send it in a follow-up email as well. 

David Turner

Great. Howard, is there anything on that sheet you want to point, any particular- 

Howard Shatz

Yeah. I just wanted to highlight that, you know, you have some great resources. Well, the DCL SPL page. DailyMed, I'm sure you guys know about. Make sure you check the Global Substance Registration System search page when you have to find the ingredient names and the unique ingredient identifiers. SPL Resources is a great place to find all sorts of information. If you want to look at things on the FDA online label repository, that's like a DailyMed. It's the same thing as DailyMed, but it's run by the FDA. And by the way, that site will almost assuredly be updated with a revised listing before DailyMed because of the nature of the beast. 

48:00

DailyMed updates only on business days. FDA online label repository is 24/7. The DECR site makes sure you have the right information for your establishments. And there's another one that has a caveat, the drug nomenclature, monographs. These are monographs the FDA has produced over the years that define FDA terms. I give examples. The caveat is that some terms may not be allowed in SPL. And basically we highlight some of the other specific sites, you get to them through the SPL resources page. Also for the CFR Title 21 online but we recommend that if you want to look up regulations. 

Pragmatic, I've mentioned. You can also use, we say to validate and view SPL, if you get an error report from the FDA if you do the submission on your own and you want to know what it means, what the error report means, if you go to the Pragmatic Data Validator light and you go to their "view report," that will open up the file, make it more readable, allow you to click and find things. And everybody I'm sure knows about the FDA SPL group email. That's how you get to Lonnie Smith. And then EDRLS, of course, if you have regulatory questions. 

For the SPM recources, I've given you the ones that are available that I use. These are my bookmarks. So use those to look further. There's an online query that's to look up, the drug product database online query is just to look up drugs, kind of like the NDC directory is here in the United States. And then they have some other places to go. 

David Turner

All right. Okay, let's get to the questions now that have come in during the webinar. The first one we got had to do with the FHIR standard. We already talked a little bit about that. I do want to pass along, somebody made a comment about when we had the conversation about EPI and PharmaLedger and all of that, and I'm going to send their comment out to the audience here. It talks about some YouTube videos that might be useful out there and the EMA gateway. So definitely something you might want to check out there. And I think I'm seeing all the questions. I don't think I'm going to have to ask you, Marianne, but if anymore come in, you might let me know. So I see there's one here that asks kind of a philosophical question, and that is Will JSON replace XML? 

So we have the big XML conversation at the beginning and JSON is something that has really come on as a structured content format. We're seeing some large systems that are built on JSON. I think JSON and XML do work together and it's not necessarily an either-or. And I think it depends on who you ask about whether it'll replace XML or not. If you ask my son the engineer, he's always done everything he could not to work with XML. So he'd probably be very on board with the JSON replacing it. But there are just a lot of benefits in the community to XML and some of the XML standards that are out there. Anyway, interesting to see how that goes. 

Next question, Howard, I'll give to you. And it asks are Health Canada and the FDA using the same controlled vocabularies for SPL and SPM? 

51:51

Howard Shatz

No. The short answer to that is No. But I think you can use the substance page for looking up things, but your safest bet is to go to the controlled vocabulary list and look up whatever terms you're trying to look up. I mean even for, what was it, for scoring, if you have a tablet, one of the things you have to put in is what's the scoring type? How many scores? You think 0, 1, 2, 3 or 4. I think it was up to four. But Health Canada uses "no score" for one of the values if there's no scoring and there's a French equivalent, which I won't even try to pronounce, but I don't off the top of my head remember it. 

Basically, go to the control book. I think you can find overlaps with the colors and some of the other terms, but they also have, I think their attributes are different. Their IDs for what you put in to the XML is different, I believe even for the columns and things like that. They seem to have commonality, textually but not in terms of attributes. 

David Turner

Gotcha. All right. Got a question here about structured content management. I mentioned that when I was talking about XML, must have. Basically when we talk about a structured content management system, what that is that's a way to create the XML in a structured content format like XML or JSON, something like that, without having to do a Word step. So right now, in much of the industry, people create a Word document and then they hand it over to a developer or they give it to a company like us who then goes and creates the XML. And then when a change is made, you make a change in the Word document, you reconvert the XML and it's always kind of an XML-last type of a process. 

Well, there are those in the industry, and I think it's a fantastic move in the industry, who are really starting to follow the lead of what other industries have done, which is more of an XML-first or an XML-early type of a workflow. And so what you do is you have a system that helps you to manage, not Word documents, but all those component parts in the Word documents. So you're actually working with XML, but you're not having to code and do all those brackets and things that we showed you. There are tools that allow you to work in something that looks like a Word document but it actually breaks those things into components. And then it enables you in the end to be able to put those components together into different parts so that when you make a change to your core data sheet, instead of having to go to all the different presentations and PAC sizes and health authority documents and make a change all the way down the line, you can make the change just to the core data sheet and then use some of the automations in the system to automatically create all those other pieces. 

Which leads us to the next question, which is Can we use the same XML format to generate SPL and SPM? There's not like an easy out-of-the-box way to do that. They are different but there certainly are ways, and we're part of some different things that are happening right now where organizations are using an XML model and then they're creating the different XML formats that they need from that based on the specific requirements of that. So yes, that is definitely possible. Contact me about that. I'd be happy to talk some more. 

56:03

Howard Shatz

Yeah. I mean, just add to that, I mean I think what you're alluding to is that what you write for FDA and what you write for Health Canada is different text. So you can't just take one and map it to the other. That's a no-no. But that's what David is alluding to, is that if you get into an XML structure of some sort, you can then do transformations to make that happen for FDA and for Health Canada. 

David Turner

Yeah. And as we're starting to wrap up here, this is the part where I talk a little bit about DCL. I do want to thank you guys for attending today and certainly if you've got SPL needs, we've been doing it a long time and Howard's an expert. His team is fantastic, so we'd be glad to help you with that. If you have other content challenges we may be able to help too. Some common things we've seen in life sciences are things like converting and transforming content for one of these structured content management initiatives. Or maybe it's transforming content for an EPI initiative. We've seen some of that.

Sometimes it's just scanning old documents, getting those in. We can help with that. We've helped get things extracted from existing content to make research more efficient or to help make translations more cost effective. A lot of time is spent on copy-and-paste in pharma from things like tables that could possibly be done a lot more effectively. So another interesting thing that I would say you might want to look at, especially if you're looking at kind of multiple geographies, is doing a bit of a reuse analysis. Taking a look at, you know, here's one of my submissions to the US, here's one of my submissions to the UK, here's one of my submissions to Australia: what's the same and what's different? We have a fantastic technology that can look across and identify both exact matches of paragraphs, things that you're using exactly the same, and things that are kind of close matches where maybe you could manage those things in like a structured content way. That's a tool we have that's called Harmonizer and glad to help you with that as well.

So anyway, just please let us know if we can help in any way. And as this last slide says, you can certainly reach out to us. I've got a QR code there that you can scan that has all of my contact info. You can follow us on Twitter. You can reach out at info@dclab.com and all of that. Well anyway, now that it's one minute left, I'm going to turn it over to Marianne so that she can do the closing and get us out of here. 

Marianne Calilhanna

Thanks, David. So I just want to thank everyone again for attending the webinar. The DCL Learning Series comprises things such as webinars. We also have a monthly newsletter, a blog, and you can access many other webinars related to content structure, XML standards and more from the On-Demand section of our website at dataconconversionlaboratory.com. We do hope to see you at future webinars, but for today, this concludes our program. Thanks.