PMRA SUBMISSION PROCESS

         MS. LANGE: Hello. My name is Lisa Lange. One of my functions is as the joint review coordinator for both chemical pesticides as well as biopesticides at PMRA. So I'm involved in both ends of the registration on joint reviews. I also have been involved with a lot of the coordination of the biopesticides that come into Canada. This is just to give you an idea of what my role is.

         I hope everybody isn't completely processed out. There's been a lot of discussion today about process so I won't try to make this too long. My key goal right now is to give you some idea about the front end process at PMRA. I will go over the whole thing, but my main point will be talking about the presubmission consultation and the screening and the deficiencies that we have just to give you an idea. Those are basically the biggest hurdles that you'll reach when you come into PMRA for submission. So I will just try to clarify where stumbling blocks often are in order to help you to put the best package together.

         So essentially for the biopesticide registration in Canada, our main goal is to facilitate risk reduction through improved access to biopesticides. I'd just like to mention that under PMRA's current policy, we consider biopesticides to be microbials as well as semiochemicals. We do not currently consider biochemicals to fall under the biopesticides. So biochemicals are generally regulated just as a regular chemical submission with PMRA.

         I've also got a slide with definitions which you've all seen earlier, so I don't think I'll spend too much time on that.

         Now we have something called categories at PMRA, categories of submissions. I'll try to just go over the two main categories that you're going to be dealing with biopesticides.

         Category A submissions are new technical active ingredients that have never been seen before in Canada and their associated end-use product. And obviously, for a microbial, it would be a new microbial pest control agent and its associated end-use product.

         They are generally major new use products. And if you were to come just alone to PMRA, they would have an 18-month time line. So the benefit, obviously, with the joint review is that you get a 12-month time line. And again, that's a 12-month review, and this is an 18-month review. The review process begins once we've actually gone through the screen and ensured that the product is reviewable. And I'll get into that a bit more.

         Now the other thing that Wendy had spoken about a bit, and there was a question as well with the user-requested minor use registration program. That's generally useful for products that are registered in another OECD country. Obviously, the U.S. is generally the primary one. But any other OECD country as long as it's been registered within the last five years in another country, we would consider that to come in as a minor use. And obviously biopesticides would fall under that category if it's a minor use which most of them would be, and you would be getting a 12-month time line. So it does reduce the time line under that program as well.

         It's also important to note that we do not have any cost recovery fees for microbials or semiochemicals. Currently, under our regulation, we do have fees for the review of data. And microbials and semiochemicals have been exempted from those fees.

         There is one fee, and it is $262. That's for the label review, but that's the only fee that you have. So you will not be charged for the review of any of the data.

         Now the other category that biopesticides could fall under would be Category B submissions. And these are submissions generally to amend a currently registered product, a currently registered biopesticide, or to register a product that represents a change to the use pattern of the active ingredients within a given use site category. And Category B submissions have a 12-month time line.

         Yes?

         AUDIENCE MEMBER: Lisa, would other semiochemical registration -- pheromones?

         MS. LANGE: They would also be treated as a biopesticide and would come in through this program.

         AUDIENCE MEMBER: As a Category A?

         MS. LANGE: As a category A. If it is a new active, yes, it would be considered a Category A.

         AUDIENCE MEMBER: When you say pheromones in Category A, you mean all semiochemicals?

         MS. LANGE: All semiochemicals, yes. Sorry.

         Okay. So as I guess has been stressed often today, getting started the first thing is a presubmission process. We find that is very important to have companies come in, especially for companies who aren't familiar with the regulatory process. As you can tell, it can be quite onerous. There's a lot of information that is required. And in order to get the best package together, we do recommend that you come in and have a presubmission consultation. It's not required, but it certainly will help.

         This will ensure that you have a good package. And obviously, we will be able to help you understand our process and how to fill out forms and that kind of thing. And also to make sure that all the data required will be there. And if there are any waivers that you were planning to put in, it's a good idea to let us know what those waivers would be. And we can help you sort of make sure that you put in a proper waiver that will be acceptable.

         And I have on the slide that we would request the information package 45 days prior to the meeting. I have actually spoken with our section who deals with the presubmission consultation. And at this point, they're actually handling them in about 15 to 30 days. So if you came to us, probably two to three weeks ahead of time with the package, that would be enough time for us to put together a meeting and have you come in.

         And for the presubmission consultation package, similar information as what was mentioned earlier. We require a cover letter requesting the presubmission consultation and a draft label as well as a list of the contents that are contained in the product, the active ingredient and any formulants, a short summary of available data such as efficacy, environment, health and any waivers that you would be requesting. And it's a particularly important for the nonpheromone, nonmicrobial products if you want to come in to have a presubmission consultation.

         As well for microbials, we require identity of the organism and survival parameter, manufacturing method, potential health or environmental issues. And for semiochemicals, relevant chemistry information and manufacturing methods.

         We find this really is a critical step, the presubmission stage as mentioned to make sure that the package is complete and that all the information that we're going to require is there. We find with the biopesticides but also with general submissions, any kind of submission that comes in the door, often the packages are pretty shaky. They come in, companies haven't put together necessarily all the information that's required. It would be as simple as some of the forms aren't properly filled out. It might be a case of some data missing that's required or a waiver that's not been properly constructed. So it really is to your benefit to take the time to come to us and have a presubmission consultation. Otherwise, you'll lose a lot of time.

         Sharlene has mentioned as well in the EPA a similar thing. You'll spend a lot of time going through loops of the screen, having deficiencies identified and coming back to you. It just increases the time lines. So it's definitely useful to come in for that.

         Now, to set up a presubmission consultation, we actually have a section within our submission management -- I'm sorry. They've changed names. Submission consultation and Documentation Division, I believe is the division now. Anyway, there's a section which is called the presubmission consultation coordination section. And Stephane Lavigne is currently the acting head of that section so you can contact him directly at the phone number or by e-mail. As well, you can always feel free to get in touch with me directly. I know that Stephane is fairly overworked with the chemicals because he deals with the chemicals as well. So you can always get in touch with me. Ultimately, he would still be involved, but it might speed things up.

         I guess I don't have my contact information here. So I'll tell you, you can reach me at (613) 736-3760. And my e-mail is the same as Stephanes. It would be lisa_lange; and that's L-a-n-g-e.

         So once you've gone through the presubmission package, it's up to you to now apply for your submission to PMRA. And we require a cover letter with the purpose of your submission. All the forms, including application form, the application fee form, which you just have to put in the $262 label fee. It's marked under the Category A box. And the specification form, if it's appropriate. A draft label. And any documentation, including letters of confirmation of source, et cetera.

         We also require an index for the submitted data and studies, and the actual data and studies and any foreign reviews if they're applicable. If you do have foreign reviews, we do find them useful. Obviously because we deal so closely with EPA, if you have any DERs from EPA, we're happy to accept them. But we will also accept other OECD country reviews.

         They do certainly help the process if you have them, if you've been registered in any other country.

         And it's important to note as well, that any incomplete submissions will not go forward, so this would be the step where we would actually write a letter of deficiency. It would go back to you. You'll be given 45 days. Once it comes again, there's a 45-day time line for us to do the screen so that we can finally move forward. But this is where we can sort of get into this loop.

         Obviously, if there's any simple clarifications, we avoid writing a letter. We'll try to phone and ask for something by fax if that can be done. But if there are enough deficiencies, we have to kind of stop the clock and start over again. So this where things tend to get tied up.

         This slide is a little bit incorrect. It should just say data requirements established during a presubmission consultation. We're not talking about joint stuff. I'm sorry. I messed up the slide on that. But in any event, if you have come in for a presubmission consultation, any of the data requirements that were established will be good for 24 months once you come in.

         Now we have these things in Canada called DACOs, data codes. It's our numbering systems similar to, I believe, the MRID system in the U.S.

         Now I did just want to briefly mention our differences in data requirements for the pheromones. If it's a straight-chained lepidopteran pheromone or a non-straight chain. So I put up the definition. I won't bother reading it because I'm sure you all can read. But we do different requirements for straight-chains versus nonstraight-chained.

         So the data requirements for straight chained lepidopteran pheromones include index, the label, the product chemistry for both the technical and the end use. Toxicology for both the technical and end use, exposure metabolism as well as value efficacy and any foreign reviews if applicable.

         And for the non-SCLPs, we require parts zero to six, which are mentioned in the first slide. As well as seven, food feed and/or tobacco residue, environmental chemistry and fate, environmental toxicology; and, of course, there's always value if you have foreign reviews.

         Now I know that Catherine Adcock will be discussing a bit more in detail the data requirements tomorrow, so I don't think we need to go into detail. But these are just the basic requirements.

         The DACO numbering applies to studies, screening forms, waiver requests, and previously submitted studies and foreign reviews. So basically, everything falls under a DACO number of some kind.

         And as for the microbials, we require a data index, label, product characterization and analysis, human health and safely, exposure, metabolism, environmental fate, toxicology and the value and foreign reviews if they're applicable. And, again, all of this will be discussed in the presubmission consultation so you'll understand where the required data is and where it might be conditional and what conditions would apply.

         So for the organization of the submission package, we require within the envelope to come in a covering letter, the forms, the fee of $262, and any documentation. We also require three hard copies of the label and an electronic copy of both the label and the index. In the binders, we require the data parts, the screens, the waiver requests, foreign reviews, comprehensive summary. They should be labeled on the spine as well as on the front. And a table of contents should also be included within each binder.

         The summary binder would have the index and the label and the summary of all of the data that's being submitted as well as MSDS. And Binder 2 would have product characterization and chemistry if applicable. And there should be only be one part per binder. So if you multiple data parts, you should have multiple binders.

         Now we've mentioned the screening process that we have. So once a submission comes in, it goes into our submission screening section. And essentially what they do is they want to ensure that the submission is organized and formatted correctly. And similar things that you've heard earlier today from both the joint review process as well as the EPA system.

         We want to ensure that all the information is organized and is complete and is accurate, and that all the information that's required is addressed. And any early identification of deficiencies, will be noted at this time.

         The screening occurs within the first 45 days that the submission is here. And again, if there's any deficiencies, after 45 days you would be notified of them.

         So once it comes into screening, anything that was established during the preconsultation requirement is what we're expecting to see. We will assign a submission number to that. And it is a unique number so each technical and each end-use product will have its own number. And that's the best way to refer to anything when you are getting in touch with us. If you have questions, if you can use the submission number that definitely helps us.

         And, of course, the screen also involves a detailed screen of the nondata components, the draft label, and the index. And we also check for the presence or absence of required supporting data.

         So if there are any deficiencies identified, a letter of screening deficiency will be sent. You will be advised of any deficiencies. And you are given 45 days to reply. Obviously, you can reply faster. But once it comes in, it's going to go through our 45-day process again. This is always the place where you're going to lose time. So if your submission comes in perfectly, it will go right into preliminary review after this. But often, unfortunately, there is a loop. But as I mentioned, if we can address things through a fax or phone calls, we will do that if it's a simple deficiency just to speed up the process.

         So the label, we require both electronically and a paper copy. And for information of what needs to be on the label you can look at the handbook and the PCP Regulations. The registration handbook is available on our web site under the publications part of it. You'll notice if you go to our web site on the left-hand side there's a sort of drop table with a whole bunch of different links. And one of them is for publications. And you can find the registration handbook under there.

         And, also, we check -- there's different requirements. The label has to have a primary panel and a secondary panel. I'll just briefly mention the primary panel includes information such as the name of the product, the registration number, the classification, whether it's domestic, commercial, the net contents, the guarantee of the active ingredient, and any symbols, and the requirement to read the label before using.

         The secondary panel would include information such as directions for use, any precautionary statements, any kind of notice to user, that kind of thing, would be on the secondary panel.

         So moving into Category B submissions, basically, the same type of information is required. You're required to provide a covering letter, all of the forms, of course, the draft label, and documentation, as well as an index for the submitted data, the actual date, and foreign reviews if applicable. And again, if any of this is incomplete, you will not move forward. There would be a deficiency loop.

         Now examples of Category B submissions would include things such as changes to the product chemistry, the technical changes to the product chemistry in end-use or manufacturing-use products, changes to the labeling, extension or conversion of a temporary registration, as well as a new product or use that's not something that we haven't seen before, just an expansion of something existing.

         So the requirements for the category B biopesticides, of course, depend on the purpose of the submission in relation to currently registered products. And a presubmission consultation is, again, suggested; it's not required, but it does help.

         Now, I do want to talk a little bit about common deficiencies that we find in the screening process. Some of them are fairly simple, straightforward things that just get missed. Other things are more important. But it is key to the submission, so I have a few slides. You can take these home with you; and, hopefully, they will help you when you are putting in a submission.

         Often we'll find that indices are not submitted or are formatted incorrectly, data requirements are not adequately addressed, material safety data sheets not submitted, labels will be missing or it would have incorrect information. Not all labeling components are submitted electronically, labels not formatted properly; chemistry data not organized or labeled according to the Canadian data code; submission format organization does not follow proper criteria; incorrect data code used to identify the study; request for data waivers do not include adequate scientific rationale; and, of course, generally, this would be discussed in the presubmission consultation. If you are going to be putting in a waiver, we suggest that you let us know what the waiver is and we can make sure that it's -- as Sharlene had mentioned, you have to give us a sound scientific rationale. We're pretty open to waivers, but they have to be scientific and make sense.

         The table of contents may not be included. Sometimes in the binders tabs separating studies are not labeled or labeled incorrectly; and, therefore, things get lost. When the packages come in, sometimes there are multiple, multiple binders and it's really easy for things to get lost if they're not labeled properly. So though it might sound obvious to you, generally, when a binder comes in it's split up and sent off to each of the different divisions that are handling whether it's environment or health or efficacy. And some parts go to multiple different divisions. So it's easy for things to get lost. And there's certainly been cases where we've had things that we know the data is in and we don't know where it is, and it takes us a long time to find it. So just ensure that you do label everything properly so we don't loose it.

         And, of course, the response to a letter of deficiencies might not be formatted correctly if the DACO number isn't listed or insufficient copies are submitted. And, of course, if you do not respond within 45 days, the submission would be withdrawn. Obviously, if there is a problem, you can let us know that it's coming in. We're not going to just kick it out the door on day 45. But if we haven't heard anything, you know, we'll often give you a fee days grace. But if nothing comes in, we're going to assume that you're just not going to reply to the response. So I would caution. Try to get it in on time. And if you can't, let us know so that we're expecting it.

         And, obviously, a specification form and application form, if they're missing or incorrectly filled in, that would also trigger a deficiency, as well as if there is no Canadian agent.

         And the last slide I think for the deficiencies, insufficient copies of data or information, missing or ineligible pages, consolidated response to all the deficiencies is not addressed. So only part of the deficiencies are addressed and not all. If we don't have all the deficiencies addressed, it still won't count. We need everything. And, of course, a letter of conformation of source and supply.

         So most of these deficiencies can easily be avoided if information is properly read. And, obviously, if you have questions and don't understand the deficiencies, you should get in touch with us. We want to make sure that the applications go forward as well. We really do want to encourage biopesticides.

         So even though you've been given a lot of information which might sound like we're working against you, that's not true. We have requirements that we have to meet, but we do try to work with you. So, please, if you do have deficiencies that don't seem to make sense or if you're putting in a package and you can't understand something, just pick up the phone and call us. We're a pretty happy bunch. And although we have a lot of work -- it's much easier for us to talk to you on the phone ahead of time than to spend time writing letters and everything. That really slows down everything for us as well. We don't like sending those letters out any more than you are happy to receive them, if you can believe it.

         So once we've moved past the screening process, we do a preliminary review as well. And this is done by the science divisions to ensure the information we have is reviewable. We want to make sure that the data requirements have been addressed, and that all waivers are scientifically sound.

         If there is a deficiency during the preliminary review, you're given 90 days to reply because often there's a bit more information that's required than just during the screen.

         Again, though, if it's something that seems fairly basic, perhaps we're just missing something, we don't make a connection, or something is unclear, we will get in touch with by phone and then fax a letter, something quick to you, and ask for you to reply back.

         If we do fax, we normally give you two weeks to reply. And again, that will speed things up because we don't have to stop the clock and start over again. But that would only happen when there are simple clarifications that we need. Obviously, if some data part is missing and it's obvious that it's not there, we would actually have to send the letter. Sometimes little things go missing, and we'll try to call and confirm.

         So, once you've moved past preliminary evaluation and preliminary review, you move into full data review. This is where the clock generally will start -- the preliminary review in here will include the 12 months or 18 months. So this would be 18 months for the biopesticide that's come in alone to Canada.

         They are assigned at this point to the evaluation divisions, and the evaluators will complete the review and draft evaluation reports and data evaluation record.

         So then we move on to the regulatory decision, which is, hopefully, the last part. Final review would be completed and a risk assessment is conducted. At this point if a regulatory document is going to be released for public comment, this would be put together. It would either be a regulatory note or a proposed regulatory decision document.

         The final label review will be conducted at this point. And a certificate of registration would be issued. Now, it might also be a temporary registration depending on the conditions. A temporary registration is the same as a conditional registration with the EPA. There would be some outstanding data that's required, but it is not deemed to be a safety issue and we can grant a one-year registration in order to allow you to develop data in that time.

         Now, Wendy had mentioned a little bit about this earlier. We are currently updating our regulatory directive on pheromones. It's going to incorporate information that came out of the 1999 OECD Workshop that was held in Ottawa, in which EPA was involved as well.

         And we are hoping to publish it early next year. It's about that far from being approved. Then it has to go for translation. So we're hoping it should come out sometime early in 2002. And when it does come out, it will come out as a proposal. And the proposal period -- when a proposal goes out, we have a 60-day comment period. So, obviously, if any of you have any comments, we would appreciate those.

         What will generally happen is our publications coordinator sends an e-mail out. You might all be familiar with it. But they'll send out an e-mail and let you know it's on the web site and you can just find it on the web site under the publications. You just go to regulatory proposals, and you will find it there.

         We, also, recently published a regulatory directive on microbials which updated the previous proposal that had been out for quite a few years. So that was published in March 2001. And, again, this can be found on our web site.

         Other relevant documents that you would find useful. And these often are ones that you would find for chemicals as well as the biopesticides. We have the Management of Submissions Policy, which explains the different types of categories of submissions that we have at PMRA. It also explains the whole submission process, the different levels, the screen, and the preliminary review, the review. And it actually even has a little flow chart which shows you the different loops that you can go through. So that can be found on the web.

         We also have Regulatory Proposal 98-02 for organizing and formatting a complete submission for pest control products. And I believe that's actually going to be published very shortly as a directive. I don't think there are many changes from what's currently in the proposal.

         And we also have directive 98-05, which is the chemical pesticide research permit guidelines. And as mentioned earlier, we do have the user-requested minor use registration program and the user requested minor use label expansion program. We have two directives for those that you can find as well as the registration handbook.

         And I think -- did we ever get around to doing CDs with all -- so in the proceedings, you will get, actually, all of these documents on CD. But you can find them very easily on the PMRA web sites.

         I think that's it. Do you have any questions?

         AUDIENCE MEMBER: The address on the web site, please?

         MS. LANGE: Wendy actually had it in her presentation. But it's www.hc-sc -- it's for Health Canada -- and then slash PMRA. But Wendy's last page of her presentation has it as well just in case you didn't get it jotted down properly.

         MR. LIBMAN: I'd like to ask my annual question to you to and Wendy. I guess Wendy is not here right now.

         MS. LANGE: Yes, she managed to sneak out already.

         MR. LIBMAN: That's very smart of her. She knew this question was coming.

         Why and when are you going to put biochemicals in the category of biopesticides in Canada or why not?

         MS. LANGE: I'm not sure. I know that we had tried to pilot a few and nothing much has really happened. There was a few that have come in and haven't really -- they started to come in as presub and they haven't actually applied for submission yet. So we're certainly hoping to pilot some, but we just haven't had a whole lot come in the door.

         I think it's a kind of thing we have to learn as we go. And obviously with the contacts we've made with EPA, that is going to help things out. But at this point, I don't know of a program starting immediately. I don't see that happening in the near future. I think that's the most I can say.

         Yeah, that's what I mentioned. We're looking for pilots, so we're happy if you have something coming in. But like I said, any of the pilots that we've started haven't succeeded to a submission. And it's not necessarily because they couldn't do it, but there are some companies, I think, just lost interest.

         MR. LIBMAN: You're looking for a pilot biochemical for the U.S. So something that's not registered in the U.S. right now.

         MS. LANGE: Yes.

         MR. LIBMAN: Thank you.

         MS. LANGE: We would certainly be happy to consider something like that.

         AUDIENCE MEMBER: I have a follow-up comment to what the gentleman here just said. We're in the process of getting a biopesticide through the regulatory process here and it's something that I know the Pacific Northwest and the potatoes in the Red River Valley would be interested. And of course, those are neighbors to the Canadian provinces. So I've been getting questions from my Canadian colleagues in the company, well, what are you going to do next? And I said, Well, right now I don't know. Just as a follow up.

         MS. LANGE: So is it currently in the process in the States?

         AUDIENCE MEMBER: It's currently in the process here in the States, yes.

         MS. LANGE: Okay. Well, the best way would be probably be to go through URMUR program with us once you're registered, that's the user-requested minor use. Assuming it's a minor use. I'm guessing it would be.

         AUDIENCE MEMBER: Is potatoes a minor use in Canada?

         MS. LANGE: No.

         AUDIENCE MEMBER: Okay.

         MS. LANGE: If it's potatoes, no, then it wouldn't fall under. It would have to -- but certainly, you could submit the DERs that you get from EPA. And if it's still in the process, we can certainly consider it as a workshare, possibly, depending on how far along.

         Okay. Probably not, then.

         AUDIENCE MEMBER: Well, I'm giving you a heads up.

         MS. LANGE: Okay. Great. Thanks. That's it