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Department of Health and Human Services

Substance Abuse and Mental Health Services Administration

Drug Testing Advisory Board

Meeting

MARCH 8 -9, 1999

March 8, 1999

Mr. Stephenson (HHS): Good afternoon. The issues before us today will cover a number of agenda items in a limited period of time. We ask that you sign in so we know officially who is here. We will offer an opportunity to any individual or group that has a need to make any public comments that are separate and distinct from the agenda of the afternoon. If there are any of you, please see the representative at the back of the room, and she will sign you up. Depending on the number of individuals who wish to make public comments, we will allow a limited amount of time for each and you will speak in the order in which you sign up. This afternoon, we're going to go discuss the Federal custody and control form working group meeting that deals with the way we are looking at identifying specimen collection, addressing briefly the on-site test report we placed on our website, discussing alternative specimens in terms of the basic process, and then performing a detailed analysis of hair testing. Our intentions are to update the matrix for hair testing. We will then provide an opportunity for individuals to respond to issues that are raised at the time. At this time I would ask Dr. Walter Vogl to give us a brief update on the Federal custody and control form working group meeting.

Dr. Vogl (HHS): I want to briefly update the attendees regarding a working group meeting that was held on January 20 and 21. We had approximately 30 to 35 participants. Several of the people here attended that meeting. We had most of the large laboratories represented, we had third-party administrators, collectors, MROs, and others who were interested in the workplace drug testing program. Basically the two-day meeting was a brainstorming session. We started by getting comments on the current form and then developed a list of consensus-type changes that a majority of the attendees wanted to see made on the form. We put copies of the first draft along with other information on the sign in table. The last pages are the preliminary agenda for the next meeting which is in two weeks. If you are interested in attending, let me know and I will add you to the list. The current form is a seven-part form and it's been used since 1991 or 1992. Originally it was a six-part form, but became a seven-part form when split specimen testing was implemented, primarily in the DOT programs. Every three years, we are required to have the form approved by OMB in order to continue using it. Since the current form expires June 2000, we are starting the process of revising the form. By August-September, we should have the final draft completed and then it will be published in the Federal Register for public comment. After the public comment period, the final draft will be forwarded for OMB approval.

I just want to highlight the changes on this first draft compared to the current form. We still have a one-inch space at the top which would be for the laboratory name and address, the specimen ID number, the laboratory accession number, and any other information the laboratory might want there. We would have the OMB number in the upper right-hand corner. As far as Step 1 is concerned, we're trying to put all of relevant information regarding the employer name, the MRO name, and collection site in the same area. It is either completed by the collector or employee representative, the laboratory preprints this information, or it is printed on-site. There is a space for the donor's social security number, the reasons for the test - trying to put those in a way such that in marking the box you are not going to mark two boxes at the same time, and the drugs to be tested. We also have a space reserved for some additional laboratory information. The laboratories were interested in getting a space that they could use for their own purposes - perhaps demographic information or other bar coding information. The next step, we rearranged how the specimen temperature was recorded and have two separate boxes to indicate whether it was a single specimen or a split specimen collection. We are still working on how to incorporate the direct observed collection into the form. The next step, the collector seals the bottle after receiving it from the donor, and the donor initials the bottle seals. Step 4 is similar to the current form. We are proposing to delete the split specimen copy because it serves no useful purpose. We believe, in the scheme of things, that the results for the split specimen could be easily recorded on a laboratory generated custody and control form. When the split is sent from Laboratory A to Laboratory B, Laboratory B can use the laboratory generated chain of custody form to record and report the result to the MRO. With regard to Step 5, this is a significant change. The collector certification statement would document all of the activities from collection, to labeling and sealing, and to preparing the specimen bottles for transfer to the laboratory using one signature rather than the collector having to sign the form three times. This statement and approach is being evaluated by our Department of Justice liaison. Assuming it is an acceptable approach, that allows us to simplify the chain of custody area. We would use a one-line approach, similar to what the laboratories use internally in documenting the transfer in handling of a specimen through the laboratories. We believe two lines would be sufficient when it's received by the laboratory. The laboratory accession person would sign the first line and in many cases, the purpose would indicate all of the actions that that individual will be dealing with regard to the specimen. Step 7 is completed by the laboratory reporting out the result. We recently issued a program document on the validity testing of specimens and are allowing laboratories to report additional information on specimens, such as, adulterated or substituted. Looking at the form, we believe it's important to have similar categories as to how the specimens are being reported out rather than to use the test not performed box to cover a variety of different results. It's more appropriate to mark the specific problem with this specimen or result, negative or positive, and then put in a remark indicating why it is an adulterated, substituted, or rejected. The remarks line is the entire width of the paper to allow enough space for the long remarks we require in some cases. There is still a line for the test laboratory if it's different from the one that's recorded at the top of the form. A certifying scientist would sign his/her name and date it. The labels are at the bottom of the form. We are trying to get the labels onto a standard size sheet of paper. We feel that from a cost saving standpoint, that would be very important and it is easier to deal with forms that are the size of a standard sheet of paper to allow using a standard printer. What happened to the package seal? We're working on that. There may be an opportunity to either eliminate the package seal or have a separate supply because it is not tied in any way to the specimen ID number. There is no reason you couldn't have separate package seals if you really want to continue using it. The MRO section would appear in that spot on the other five copies. Copy 2 goes to the MRO with the certifying scientist signature on it. Copy 1 is retained by the laboratory. That's where we are right now.

Mr. Stephenson: We are looking for your input. You are welcome to attend and participate in the next meeting. There will be a public comment period and we will need to get this thing moving. Walt, when did you say you hope to actually have this submitted to OMB?

Dr. Vogl: The approval package would be submitted to OMB in early Spring.

Mr. Stephenson: This is a major revision. This process builds on all the experience we have had with preparing a collection handbook and an MRO manual and it takes into consideration the flexibility for the laboratories to print their own forms

Dr. Vogl: Assuming it is approved by OMB next June, it would still take six to nine months for implementation. We must allow everyone who uses the form to use their existing copies of the forms. They generally have a few months' supply on hand and they would have to make software and printing modifications to ensure that they could begin using the new form on a certain date.

Mr. Stephenson: Next, the on-site test report update.

Dr. Bush (HHS): One of the handouts is titled, an Evaluation of Non-instrumented Drug Test Devices. There's a background and a summary of the device evaluation itself. This report reviews 15 devices. They are listed by name with the distributor, address, and phone number. The analytical data is presented in both a table and a graph format. Looking at the table, there is a perfect device (listed as PD) and then the other devices are encoded. We have blinded the identity of all of the information for display on our website as it appears in this document. If you want specific information on any one of these devices, please call the phone number listed. Each manufacturer knows which result pertains to their specific test kits. This study was performed for us under contract by Duo Research, and will be presented at the Society of Forensic Toxicologists. Shortly after the Society of Forensic Toxicologists meeting, if not concurrently, the complete study will be published in a peer reviewed scientific publication along with the identities of the devices studied. This is Part 2 of a study that was undertaken by the Administrative Office of the U.S. Courts a couple of years ago when 16 devices, that were on the market at that time, were evaluated. Since then, 15 more devices have been developed. I look forward to the peer reviewed scientific article with more detail.

Hair Testing

Note: The sections and elements (e.g., D-4, G-4b) in the following discussions refer to those in the Table of Factors Required for Reliable Workplace Drug Testing.

Dr. Selavka (Mass. State Police Crime Lab): The Hair Testing Working Group has met twice since the last DTAB meeting. In the information you have, the hair testing section has the input developed by the working group. I am not going to discuss A-1 through A-4 since they are blank and can be satisfied for hair testing. B-1 involves training collectors and B-2 is certification for collectors. Both of these are done by the hair testing industry. C-3 pertains to FDA clearance and any discussion is left to the Board and HHS. D-2 relates to multiple testing and the working group formed a consensus as to how much of a sample should be collected. D-3 relates to potential to split a sample and that can be accomplished if a sufficient amount of sample is collected. For D-4, stability of hair, drugs and metabolites are quite stable in hair. For E-6, the working group defined terms for tampering, adulteration, and an unsuitable sample. Transportation of the sample to the laboratory, E-7, is not an issue. Short and long term storage, G-2, does not appear to be a problem although there may be a slight degradation over a long period of time. G-3, can identify adulterated/substituted specimens, refers back to the same issues as discussed with E-6. Again, FDA clearance for the initial test kit is left up to the Board and HHS. G-4b, target analytes, were established for hair testing with the cutoffs given in G-4c. G-4d, the precision around the cutoffs can be established similar to urine testing. G-4e, a repeat initial test can be accomplished by either retesting the original sample or collecting another sample a few days later. G-5a, the working group recommends using GC or LC-MS/MS because the concentrations are somewhat lower. A detailed list of cutoffs were established for each drug class in G-5b. H-1, a certified laboratory program could be established. H-2, PT samples could be constructed to challenge the laboratories. H-3, a laboratory inspection program could be established. H-4, blind samples should be prepared using actual drug user hair samples. However, it appears that different types of hair may be needed to address the aspects of hair testing. I-1, certifying scientist review is possible. I-2, reporting results by specific drug is possible. I-3, results can be reported in a timely manner using a standard report form (I-4). With regard to interpreting results, J-1, the working group developed a comprehensive consensus statement. Alternative medical explanations, J-2, can exist as with urine. J-3, MRO training is possible. K-1, dose-time is similar to urine and involves a number of factors.

K-2, specimen contamination cannot be solved through a simple application of any single approach. With regard to color bias, the working group believes it is not the color that is the issue, but rather characteristics that affect bioavailability and incorporation.

COL Jacobs (DTAB member): With regard to future studies for hair testing, I think there is going to be some discussion of looking at other possible ways, and perhaps some of the studies we're either going to have to get the information back on or that we're going to discern will hopefully deduce some answers on that. If you live with a crack dealer, we won't go into why you do that, but does that necessarily mean that you can live with this individual for two or three months and you're going to test positive just from being there. Is that an excuse, do we want to accept that excuse, what kind of testing - what kind of levels are we going to reach? Again, we may have some information on that or we may look at trying to design some experiments that are going to give us some information on that.

Another issue I think we still need to look at is wash versus rinse. What do we mean by those two terms? What is a rinse? What is a wash? Can someone rinse it and then go to a different laboratory and use the wash and get more out? Do we digest the hair or not digest the hair? Are their mild methods? Harsh methods? And we send these samples out to various laboratories with these various vapor on the hair or soaked in drug or actually drug in the hair, are we going to get back the same answers? Because we want to at least make sure that we aren't giving someone a negative mark behind their name for something they didn't do, I think that they're going to have to come up with - and this is just me speaking here - other explanations for why they washed their hair with cocaine. But you don't want to accuse someone falsely. And we want to make sure that the rinse procedures work or wash procedures work, and we will be addressing some of those.

Dr. Vogl: On Page 21 with the cutoffs that you have listed or proposed, what is the LOD or LOQ for each drug class?

Dr. Selavka: For the most part, it is five times above the LOD, but it is different from class to class. THC, is probably close to five times higher. Cocaine is much higher than laboratories can detect. The value of 1.0 is way above what laboratories can do.

Dr. Sample (DTAB member): Can you explain the difference between the numbers on the top half of Page 21 and the bottom half, particularly with respect to THC and opiates?

Dr. Selavka: Page 21 contains information from a preliminary input mechanism that people had to detail last August and September. What follows below is the consensus formed by the HTWG. A group of people interested in developing some consensus across the industry and academia. I would say the top half is an initial list that has nothing to do with where we are now. I would ignore it.

Dr. Bush: That is a good point. I should have said this when we started out with each and every one of the pages in this handout. What you see at the top is what was provided by the industry representatives at the September DTAB in response to constructing the grid. This is the base level information that was provided by industry representatives for review and evaluation by the Drug Testing Advisory Board. Sometimes it is a restatement of what was known and as you see in cases here with the hair testing group, things have significantly changed.

COL Jacobs: Some of the cutoffs went up, some went down, and others we have added other metabolites to look at. That is fairly formalized now, but we are always open to input and changes. Please go ahead.

Voice: With respect to the cutoffs for the immunoassay, I'm confused about the reference to the uncharacterized marijuana analyte. It's referred to again down in the working group section that they haven't come to consensus on that. Are you saying we don't know what's being tested for at the laboratories in terms of the assay for THC?

Dr. Selavka: I believe the consensus of the group is that we do know the kits that are being used, whether they're home-brewed or commercial that are sensitive to those things in that drug class. But you don't know the specific contribution of any one of them until you test each one of them for cross reactivity, and I think across the board, that has not been done in laboratories. What we are doing now is we are saying let's set the set point on THC acid itself and remembering what the point of the screen was in the first sense is those things that screen positive should confirm positive because they contain those analytes of interest for that drug class. We have to work backwards and see what level of THC-acid in every laboratory is likely to give rise to a positive finding in hair that has THC-acid above the cutoff by GC/MS or LC/MS/MS. That's the point we have to backward engineer this cutoff and that has not been done yet with empirical data.

Mr. Meeker (PharmChem): How are these cutoffs set? For example, is there analytical data, GC/MS printouts that are available to look at? Sensitivity and interference available for other people to review, and seeing how you're setting these cutoffs on both the MS/MS and the GS/MS or the LC/MS data that's provided? Secondly, for opiates - where you have the disclaimer underneath - that any opiate analyte may be reported as a stand alone finding - what is the purpose of that? Because heroin can be smoked in the environment and you still have the problem with that as well.

Dr. Selavka: That's a good comment. Dr. Martha Harky raised that as we were leaving the meeting last time. As you mentioned, we may have to revisit the opiate only. Cutoff or reporting requirement, I think that's a good point. We will be revisiting that for the reason you brought up in your second question. The first question - there are data available to the public that underlie the setting of these cutoffs by LC and GC/MS methods. I don't think they have ever been published it, but most laboratories that validate their methods also do not publish their validation studies. If you're a laboratory and you want to generate such data and if you know how to do it, set up a validation experiment.

COL Jacobs: Those probably would be the types of things that when laboratories are inspected we would look at. If this continues and becomes part of the program, I think that those types of cutoffs and levels would be looked at and reviewed and from what I have seen, it looks quite comparable in most ways, to all other testing and all other types of chromatograms.

Dr. Selavka: If I could revisit the second one. If yours is the first one - if I was the original, the thinking is you wouldn't find 6-AM without morphine. But Martha's point and I guess yours also is that it could happen. We better put it into the protocol for the studies we do on environmental exposure.

COL Jacobs: The next working group meeting is March 29 and 30 in San Antonio. If anyone wants to attend, let us know. It has been a large group, but I don't think that's been a problem. There have been a few times where side issues get talked about, but we're getting to the end here and we're reaching agreements that I thought would be two or three years down the line. I believe we are getting somewhere.

Mr. Stephenson: One of those issues should be, at this point, based on the information that has been presented today, and we had an opportunity for discussion among the Board, are the Board members ready to examine and update the matrix in these particular areas? I think you have adequate information.

COL Jacobs: I would like to think the areas where this group has reached consensus that the Board could look at those things and say yes, this is reasonable, they've reached agreement, and this makes sense, or it doesn't and give it back to the group to readdress.

Mr. Stephenson: How do you want to go about that?

COL Jacobs: A-1, A-2, etc.

Dr. Bush: Do we need to go over each one?

Mr. Stephenson: If we update the matrix, what we can do is put it back up on the web with an update in this area for the rest of the world to see as we go through this. This is a process we said we were going to do, that we would have this done in open session, and that we would make the changes.

COL Jacobs: We're going to go over them one point at a time and decide. Just for those who don't know or haven't seen, the reason why we did not look at 1, 2, 3, and 4, that's on the collection site. Since they are all blank, that means we can satisfy the requirements, that the preparation of the collection site can be accomplished for hair testing, the security, the privacy, and the observed collection. Those things aren't a problem for hair testing and can be accomplished. So A is done.

Dr. Bush: Reflect back to the table as of August 20, 1998. Because those blocks that were blank for each individual specimen and technology in each individual aspect, we were evaluating at that time, our discussions amongst the industry and the Board members. The agreement was for each that we were comfortable, the Board was comfortable at that time, that a satisfactory resolution could be reached with existing information at the time. That's what all the blanks are. Then P was the letter that was put in the box if it was possible - if it was thought to be possible, but needed a little more information, more discussion, more evaluation on the part of the Board. I was insufficient information. It needed much more information than a P. And then N was a criteria where a given technology couldn't satisfy a requirement. Happily, there were no N's that were assigned in this grid. It is now a place to say, can a P be replaced by a blank, and can an I be replaced by a P or a blank.

COL Jacobs: I'm going to start with B again. B-1 and B-2 are training and certification, Page 1 and Page 2. I think that this working group has answered those things and I think it should move to a blank. They have training videos, they have pamphlets, they have graded examinations, and they have certification that is provided for the collector. I think that is what we asked, and it has been provided. Do I have any comments from anyone?

Dr. Sample (DTAB Member): Training and certification, is that vendor specific or global?

COL Jacobs: At this point, there's nothing other than vendor specific. Do you want to say that it has to be global and move to that? Because my feeling is now, I don't know.

Dr. Sample: Do all vendors provide that?

Dr. Vogl: Wait, this isn't for on-site testing, this is can a collector be properly trained to collect a hair specimen.

Dr. Sample: The information suggests that training and certification is available now, but that training and certification may not be applicable for every hair specimen that they collect, is what I thought I heard being said.

COL Jacobs: I'm saying the information can satisfy the requirement.

Dr. Bush: When you say, can satisfy the requirement that we as a group could craft statements and craft collection criteria and training requirements?

COL Jacobs: If we want to, I think there are places out there who have crafted their own for their own needs and have done that, and I think those are acceptable. It doesn't mean that all places are doing that now.

Ms. Bernstein (DOT): That would be the issue because you talk about a grading examination. Does that mean that each entity has their own graded examination?

COL Jacobs: Yes, they're separate. There has been no need to get together, to compare our exams, and to go out and say we now have one exam.

Ms. Bernstein: I want to go back to Dr. Bush’s issue - is this something or do we have to make this decision today? In terms of talking about each entity or vendor that performs this, they can have their own examination, and that we don't care what's in it, or just that it is possible, or is this something that still has to be done in the future on a global basis? Those are very different things, so I'm certain what decision is it that we want to reach today?

Mr. Stephenson: I could really throw a curve in this and say, do we want to have an ISO 9000 standard? What are your thoughts in terms of how to move from say a P to a blank in this area? Where do you think the burden should be in terms of process?

Dr. Caplan (DTAB member): From a process point of view, I think what we should be doing here is that working group gave a recommendation and on the basis that a program has been demonstrated to have been done indicates that a training program would be required and we could come up with a statement saying training would be required, but we don't define the training. We have the first level here as to look at whether or not this minimum objective has been met and if it has, change that status and move on. Later on you have to write the regulation -- like an adequate training program. Then we'd have to move across the various other grids, like what it currently says about urine. What do we say about the other things? The end result is there has to be an adequate training program. What we've demonstrated here is that the industry has already indicated they could do that, and, therefore, we know that is not a problem. We would move on without being specific as to what the program is.

Ms. Bernstein: I don't disagree with that, but my question is, in looking at the grid, does that satisfy the requirement or does it become possible, that is what my question is, because we're supposed to come up with a grid at the end of this.

COL Jacobs: Are we arguing over whether a blank means cans satisfy requirement?

Ms. Bernstein: Right.

Dr. Caplan: The blank obviously has an element of possibility. It's not finished; it can be done.

COL Jacobs: What's the difference between possible and can satisfy?

Mr. Stephenson: Level of information.

COL Jacobs: My understanding is possible, somebody probably can do that and can satisfy the requirement, somebody out there has done it and has a program in place. Not everyone is doing it, but they can satisfy the requirement.

Dr. Caplan: The other part of the process, the grid is not the final end of this, just moving us towards writing the regulations. Therefore, the writing of that regulation can be done because there are blanks. I don't know that we could decide on what the regulation is going to say on each thing at this stage. That's the next stage.

Mr. Stephenson: Let's take it one more step and say, using these first two elements of B-1 and B-2 on Pages 1 and 2. Could we suggest a process so that it doesn't take a week to do this - that we do it by exception - that if members of the Board have issues they want to address that they would raise them at that time? Otherwise, unless there is a strong negative sense that we would adopt the proposals for the working group and that that becomes the structure for each of these working groups as they come online. That would be made by a representative of the Drug Testing Advisory Board and not a member of the industry, this way we could move through this in an orderly process. Does that make sense?

COL Jacobs: I think what we're doing is going through it more quickly and we're going to state B-1, does anyone have any issues with it, but at the same time, we're going to have to say someone's going to have to propose, are we move the P to a blank or are we.

Mr. Stephenson: You're going to do that?

COL Jacobs: I propose on B-1 and 2, we remove the P and change it to a blank.

Dr. Bush: Any negative comments from the Board members? You need to speak up if you have a problem with it. Silence is going to be agreement with where we're moving.

COL Jacobs: C-3. I don't know if we want to look at this or not. This is FDA approval, insufficient information. I guess we could move all of these to a P here if we want to say it is possible. I don't know if we want to do that or not, and I suggest we leave it as it is and move on. D-2, multiple testing. We still have that as needs discussion, but I think that what we have accomplished at the meeting was work to the point where we agreed on the amount of hair in milligrams that should be collected to answer multiple testing - multiple testing being a second test of hair. If they ask for a retest, go back - you still have hair to do it or send that hair to the other laboratory. I think that has been answered and I propose we change it to a blank.

Mr. Crouch (DTAB member): Some of us saw this last night and some of us just got this, so to go through these step by step and think about them and digest them and be able to respond intelligently to them, I don't think as a Board member, I've had time. I don't feel prepared to do this, I will go with the flow if other people feel prepared, that's fine.

Dr. Caplan: I think as we go through them, some will be more obvious than others. If anybody has a problem, we can skip that one.

Mr. Crouch: There are six subparts to this question.

Dr. Caplan: My question had to do with why three months? I would like to hear some comments on why three months was agreed upon as opposed to one month or six months, other than the fact that people had been doing that commercially. Was there are any discussion about that?

Dr. Selavka: There was a lot of discussion. The laboratory I came from used to test the whole length. The question is what puts the three month requirement on here. We were thinking workplace environment, three months is an adequate time period for demonstrating or not demonstrating, freedom from repetitive uses and exposures. On the other end, there may be investigative questions where you want to use the whole hair or less than that length and so that is where laboratories have been working with many of their clients for many years. That was the period that employers wanted to query and so that is why it was selected. You could always do different time periods when the analytical question is very different.

Mr. Crouch: How do three and four interrelate, because if you have 75 milligrams of hair that's 12 inches long and you cut that into 3.9 mm segments, then you don't have much hair left.

Dr. Selavka: That was factored in as well. What we determined was the average aliquot that is used in testing. If you collect 75 milligrams regardless of the length of the hair, in our experience, you should have adequate aliquots for all the tests that are required. That is why I was getting back to the point before with the LC pre-concentration step, you won't have enough hair to do that if you were to try to pre-concentrate by using more mass of hair.

Dr. Bush: Carl, I think I missed part of that. 75 milligrams of my longest length, that's 6 to 8 inches, you would take 75 milligrams of this entire length, that is not very many hairs relative to my boss's hair here, and it's definitely not 6 to 8 inches long. So you would take 75 milligrams of my long hair and 75 milligrams of his hair, you would be missing a patch and I would be missing a much smaller patch of hair, is that right? And there would still be sufficient hair for re-analysis at a second laboratory from those swatches?

Dr. Selavka: The way we have written this up is very carefully crafted to allow for the collection of a minimum of 75 milligrams. If you use the collection procedures correctly, they will generally be providing more than that. I was after a gram of hair and I knew that was never going to fly, but we recognize there are differences. Again, if you want to test this, this is -- is based upon years of experience and lot of laboratories that do this thing. We crafted carefully. I really don't have data with me to show you how much 75 milligrams of hair is, but it doesn't look like much. But you've already segmented it to 3.9 cm segments by that point so it's going to be 75 milligrams, is the total mass. That is going to be then providing you with 3.9 centimeter segments.

Dr. Bush: That will be the submission for the analysis?

Dr. Selavka: Submission for the analysis in most cases.

Dr. Vogl: If you analyze each segment of the total 75 milligrams, doesn’t that give you different results because it's a different time frame?

COL Jacobs: If you segmented it and reviewed each segment.

Dr. Vogl: What you would have to do is chop it up into homogeneous small pieces and then you only take a portion of it to do one test?

Dr. Bush: No, you only take the 3.9 centimeters that are closest to the head, then you take the rest of this long hair and throw it away.

Dr. Selavka: You don't throw it away.

Dr. Vogl: When we say multiple tests -- in urine, you have the specimen and you can remove an aliquot, do the test, and come back the next day and it's the same specimen. How does this description satisfy multiple tests? How do you apportion the 75 milligrams so that each time you want to repeat something, if you have to, it's the same specimen?

Dr. Selavka: You've raised a good point. I think we add an element here that the portion tested is the 3.9 centimeter portion after it's been clipped. You say that in one pool, you do save the rest of the hair and the packet that it came with, you don't throw things away, but then if a re-test is done or an immunoassay comes up positive, your confirmation is done on the 3.9 centimeter segment. You sub-aliquot for each of these tests as you would with the urine. But you're taking the urine -- but you're taking the aliquot from the 3.9 centimeter segment not from the whole hair. I think we do need to add something to this to clarify.

Mr. Stephenson: If there is discussion like this that comes up an issue, my suggestion for the process would be maybe set this one aside for a second and then proceed and try to go through as many as we can and then we will come back to these or maybe use a mechanism of trying to address these things either by e-mail or a discussion in that way.

COL Jacobs: D-3 is the potential to split the specimen. I think that ties in with the previous one. I think we can do it and can quickly move to satisfy that requirement. I would like to tie it in to 2, and address both of them at the same time. When D-2 does get answered, then D-3 will have the same answer. Now, D-4, stability and storage evaluated. I think that carries enough here, if I recall correctly, to say that it can be stored. It is stable. We hit that requirement. There is enough hair collected and enough left over that when we check later, it is kept, it is stable, and it can be stored.

Mr. Crouch: Isn't this again contingent upon D-2? Because if you use all of the hair, then you're asking about the stability of the drug in the digest and not in the hair. So if you don't collect an ample sample or an adequate sample in D-2, then the only remaining portion is that that is already digested or been rinsed. So I think this relates back to D-2.

COL Jacobs: It does relate back. But my understanding from the group, there was that 75 milligrams, which was the amount - is more than enough to enough left for sample at a later time, either in that laboratory or a different laboratory.

Dr. Vogl: Of the 3.9 centimeters?

COL Jacobs: Of the 3.9 original, close to the scalp. Further comments, discussion?

Dr. Bush: Have you seen any data on that like from retests that have been at a later time? You know it's always one of those things, stability. We've had laboratories who have urine specimens in their possession. A year later when they're ready to throw things out, we might look at something where they are no longer under-regulatory control. Is there information?

COL Jacobs: There was lots of information. I can't say that I saw any chromatograms presented that says, here is this hair and here is the repeat. I didn't see that so I won't say that. But I think everybody there certainly said that they didn't have any that degraded more than 10 percent and that when they looked at them, either when it was asked for the re-test or at the time of discard when they looked at things, that it was stable and it was there. Does anybody here want to correct me on that?

Dr. Selavka: And I presented this data at a SOFT meeting a couple of years ago.

Mr. Crouch: If hair is 10 inches, it's about 25 centimeters. If you only take 4 centimeters, then your whole sample is about 12 milligrams total. If you take 75 milligrams of someone's hair that is 12 inches long and you cut off 4 centimeters of that, you're only going to recover about 10 to 12 milligrams total of hair to do all of these tests plus recovery or plus stability of the sample. There's something inherently wrong here.

Dr. Caplan: What's wrong is the 3.9 centimeters has to have 75 milligrams. You may get more.

COL Jacobs: Any other comments on this? Is it clear now what the 3.9 means?

Mr. Crouch: No, it is not. Are you saying on D-2, you're going to collect 75 milligrams and it will be represented in 3.9 centimeters or are you going to collect 75 milligrams total?

COL Jacobs: Just a minute, I see some heads nodding out here. Someone pop up because I'm not the one that's going to have to do this.

Dr. Kidwell (Navy): The intent was that in the 3.9 centimeter section it will be 75 milligrams. So the example earlier of Donna Bush's hair was probably incorrect or misleading. We're talking about a sample about the size of a pencil lead, the lead of a pencil when compressed.

Mr. Crouch: On someone with short hair, 75 milligrams is quite a bit of hair.

Dr. Kidwell: That's correct. And there was some discussion I think that we originally batted around 100 milligrams of hair and then we came out with 75 as a compromise. But you're correct, it is a lot of hair.

Mr. Stephenson: We can tie this one to the other one to clarify it.

COL Jacobs: We will put that aside.

Dr. Bush: We will have to tie D together.

COL Jacobs: We will tie D up in one bundle of hair. D-6, deter tampering/adulteration. I won't plead ignorance. I don't think we're quite done with this.

Ms. Bernstein: You're saying you're not done with that?

Dr. Bush: More discussion is needed so we will leave it as an I now.

COL Jacobs: B-7, transportation of specimen. Does anyone have any trouble with the transportation of the specimen. [NO RESPONSE.]

COL Jacobs: I would propose that we can satisfy the requirement for transportation of specimen and there is no problem with this. Is there any discussion? Are there any opposed? [NO RESPONSE.]

COL Jacobs: Done.

Dr. Bush: That changes from a P to a blank.

COL Jacobs: G-2, short and long-term storage. I don't know if it ties into D-3 or not. Does anyone have any problem with this?

Dr. Sample: I think if we are satisfied with the room temperature for the current analytes, but if any analytes are added down the road, it would have to be looked at individually.

COL Jacobs: I propose we move this to a blank. Does anyone have any comments? So let it be. G-3, can identify unadulterated substituted specimens. G-4, initial test, the FDA clearing. That is in the big FDA pile. It needs to be addressed. And do we want it?

Dr. Bush: We will deal with that later.

COL Jacobs: G-4B. We still have to discuss what we are looking at for THCA and where we want that cutoff to be based on what is the confirmation cutoff. G-4C. That fits in the same one as before when we talk about all of our cutoffs. I think that we do have numbers that we are close to agreeing on so if anybody doesn't like these numbers, please get with us, because what you see is probably pretty close to what we're going to propose. G-4D, performance around the cutoff. Does this look like a reasonable proposal that can satisfy the requirement by challenge samples at 75 percent and 125 percent of whatever cutoffs we have? Are there any comments? Is anyone opposed to saying that that can be met? Okay, we can take that one off.

Dr. Bush: So that becomes a blank?

Dr. Vogl: If you're going to change that one, I think you could change 4-C.

COL Jacobs: What we can say is we can reach precision around the cutoff. And let's say marijuana is one, that's fine. We can go from .75 to 1.25 but we may want to go back to marijuana and say we're going to make it 1.2, which we still can meet for on 4-D, but we will be changing 4-C and so until we know what 4-C is. We don't want to accept it, but we can do 4-D and then when we change it if there's a change to 4-C, we will still have to meet 4-D.

Dr. Vogl: Are you going to use spiked samples or real hair samples?

COL Jacobs: Spike samples. Anyone else?

Dr. Isenschmid (DTAB member): Is this what laboratories are currently doing?

Dr. Selavka: They spike, and there are two ways to spike into a blank solution or spike into an extract of a negative hair. Different laboratories do it differently. There are good and bad reasons to do it both ways.

Mr. Jones (DTAB member): How is that any different from external exposure in a donor, spiking versus the exposure?

Dr. Selavka: In laboratories, when you're trying to do your validation study, when you're using your immunoassay, you have to have something in which you have a known value of drug. The drug and metabolite usually both challenge your instrument with it and see if your response is equivalent to that which your standards have set up. You have controls first. Later on if you want to validate the method, you're going to have to use them as the quantitative standards in an environmental exposure situation. You would have hair itself in an experimental protocol and expose it to vapors and cocaine or powdered cocaine or heroin or whatever, and see whether you wash protocol can tell you whether that sample has been contaminated. It's a very different kind of experiment from the laboratory's point of view.

Dr. Sample: Doesn't this item relate to the assay itself and not to how controls are prepared? Shouldn't the discussion about controls themselves come under Section H and then we can talk about proper type of control? I think I hear what your saying is that the assays can reliably differentiate at the cutoff within plus or minus 25 percent. How you determine to make that control material is another matter that I think will come out under Section H and I would recommend taking this to a blank.

COL Jacobs: Does anyone have any opposition to taking it to a blank?

Dr. Mitchell (RTI): If I remember right, you were talking that there are different immunoassays that are used. Are all of those capable of meeting the plus or minus 25 percent criteria?

Dr. Selavka: We are told they are. The data will have to support it or refute it. But we think that's stringent enough criteria for immunoassay.

Dr. Bush: If we establish the requirement, then I assure you the kits will be manufactured and precision shall follow. They will be manufactured to be able to do it. It's happened in the past, and I'm thoroughly counting on it again in each matrix center that we look at.

COL Jacobs: This is the group that could do it. If they say they could do it, we could hold them to that. Okay, move to a blank and turn the page. G-4E, the ability to repeat the initial test. Unless this ties back into the 75 milligrams, and I'm not sure where we ended up on that. There is enough to repeat the initial test because we have an example, do we want to tie this into others.

Dr. Bush: Yes, tie it to D. It will be an easy evaluation next time if it is tied.

COL Jacobs: What is the issue with the 75 milligrams of hair? Denny, can you state that again so we have clear direction or would you like to attend the meeting?

Mr. Crouch: Yes and no. It wasn't clear to me the way it is written that what you're doing is trying to collect a sample such that the proximal 4 centimeters is 75 milligrams.

COL Jacobs: Then we will have that section rewritten, which should clarify about four of these areas.

Mr. Crouch: You may want to look at that because that is a lot of hair off a person who has short hair. If you look around this room, there aren't a lot of people who have 4 centimeters of hair. I don't know what the ratio is, but several people wouldn't qualify. So you would be taking a good hunk of hair.

COL Jacobs: I think you're right.

Dr. Selavka: There will always be some in the population whose head hair doesn't allow for this type of collection. That's why we have the other body source availability. Frankly, if there's no other body source availability, then another drug test would ensue.

Mr. Meeker (PharmChem): If you have another body source, doesn't that grow at a different rate? If you're trying to establish this 90-day window, then the rate of hair growth period from a different body source -' what I heard you say earlier, you're trying to establish 90 days of use. It just seems like with shorter hair, you're not going to do that.

Dr. Selavka: You're right it is different. What we wrote is - and we're now on page 4 which is at D-2. Hair collected from the ultimate body sites must on average be longer than 1 centimeter but will not be trimmed by the laboratory if the average length is greater than 3.9. That was based upon a long discussion about our lack of full understanding of cross-populations of the growth rate with all other body sites. Head hair, at its apex, has been very well characterized, but the other sites not as well. So this gives light to that fact that this may extend beyond 3 months. It may be less than 3 months, depending upon the collected sample.

Mr. Meeker: Item 2, you're allowing the 1 centimeter link for the hair on the top of the head. Now, you're talking about 3.9. There's a three-fold difference. Couldn't we say it has to be a minimum of 1 centimeter at least 75 milligrams of hair?

COL Jacobs: That is what we are trying to do.

Dr. Selavka: That is well stated, thank you.

COL Jacobs: G-5a, Page 19. We're done with this.

Dr. Bush: Do we just leave it as P and move on?

COL Jacobs: We'll leave that a P. It's possible we need to work on it. Does anyone have any comments on it or any further input on it, or what do you think we need to include on this?

Dr. Selavka: Larry Bowers has done a lot of work on the algorithms on this.

COL Jacobs: G-5b, Page 21. Here, we're going to have to talk a little bit further about those. Are we down to one we need to talk about?

Dr. Bush: It's already a blank, but there is still more needed discussion.

COL Jacobs: In other words we can satisfy the requirements, but we haven't decided what the requirements are?

Dr. Bush: Exactly, how to do to that, to establish the cutoffs. Okay, fine.

COL Jacobs: G-5c. The cutoffs reflect drug use. I think we need to define the fact that it's positive. We need to know what those cutoffs reflect in terms of drug use.

Dr. Bush: Which one are we on? Page 22?

COL Jacobs: This is the same issue we had before.

Dr. Vogl: It's precision around the cutoff.

Dr. Bush: This is just confirmatory.

COL Jacobs: Does anybody have any problem with saying t his can be met? The laboratory suggested it so they will meet it. I propose we move it to a blank. Does anyone have a comment? [NO RESPONSE.]

COL Jacobs: Page 23.

Dr. Bush: This may be where studies are developed for presentation next time.

COL Jacobs: QC/QA, Page 24, the certified laboratory programs.

Dr. Selavka: New York State has already established the investigation criteria for laboratories that do hair. They've already inspected at least one and I think two laboratories, now.

Dr. Bush: What's going on with Florida? We don't know any information on this, we have nothing.

Mr. Stephenson: We do need a review of the process and maybe some links to some folks who are doing it. I know we're doing the QC type of work in Florida on proficiency challenge, but I'm not sure whether they've encompassed this under certification of laboratories inside the state.

Dr. Selavka: I know Dick Jennings has been out to two of the laboratories to inspect them against New York state clinical laboratory standards.

COL Jacobs: We will have insufficient information, or is it possible?

Mr. Stephenson: Does it really matter if it's an I or a P?

COL Jacobs: I think it's possible, we just haven't satisfied it all. Does anybody have a problem changing this to a P? Okay, we'll move it up. Page 25, external PT samples. Has this been done? We've been taught there have been external PT samples sent out there, so not only is it possible, but it has been done. We can satisfy that requirement. Does anybody have any information or input on any of that?

Dr. Bush: I've never been told about how to do it or how the specimens are collected. I know that isolated things, that cadaver hair from Europe is collected and used. Places can get more information on this.

COL Jacobs: Public comments?

Ms. Murdoch (Bensinger Dupont & Associates): BDA is actually in the process of beginning marketing the proprietary program for hair analysis developed in connection with Stuart Bogema and we also have a laboratory inspection program that is underway for hair testing laboratories, forensic inspection program, and that's also being rolled out.

Mr. Crouch: Are these prevalidated?

Ms. Murdoch: I know there's a protocol for how they're evaluated and distributed, but I don't know the details so you will need to talk to Dr. Bogema. He was here before and of course, as soon as I was going to talk about this.

COL Jacobs: Julie, can we try and get some of that information. That's going to help us to change this to a blank. Can you somehow get with me or get with the group so we can look at it and say something is there?

Ms. Murdoch: Sure.

Dr. Mitchell (RTI): As the PT program currently exists, it's called a performance rather than proficiency. I can see how proficiency could fairly easily be done, but can we do performance testing in hair? I think there's still some questions in that aspect.

Dr. Selavka: Can you differentiate the two for the record?

Dr. Mitchell: Proficiency is can the people analytically get a correct answer. Proficiency, I mean proficiency performance, looks at the entire system through which the samples are tested. From what I have heard so far, I am not sure that we are currently, technically capable of doing that.

Dr. Selavka: Can you say which elements of the process are likely to be the ones where we have the biggest issue on the performance side so we can address them in our group?

Dr. Mitchell: I think the variability and the processing of the hair is probably going to be the greatest problem in trying to set up a performance testing system.

Dr. Selavka: Once collected, the rest are the preanalytical steps where we are likely to have the issue with performance?

Dr. Mitchell: While you have a problem, is that since the quantitative values will vary according to treatment? It's going to be very difficult to determine whether or not a laboratory has a quantitative difference due to its procedure of isolating the analyte from the hair, or due to mishandling the hair somewhere in the process? It's going to be very different or very difficult to distinguish between those two.

Dr. Kidwell: In the past, three types of samples were sent out, a powdered hair to just test the extraction ability, whole hair not to be washed, and the third was whole hair that went through the whole procedure. Whether that would be helpful now or not, I don't know.

Dr. Mitchell: I understand that, but we still have the same problem with analytical answers that are obtained and what they mean, if they differ from laboratory to laboratory.

Dr. Bush: My concern is whether we get reference laboratories and reference values for this. Where are we going to get the reference laboratories for this?

COL Jacobs: Are we ready to turn the page? We will leave this one alone. The next one is the laboratory inspection program and I think the way this is written, an inspection program can be established to inspect and evaluate all MSs in the laboratory. I think it is not only possible, but it can satisfy the requirement and I see no reason why we could not do that. Does anyone have any problem with taking on more inspections? Okay, we will move that to a blank and turn the page. Now, blind samples. This probably will relate to some of the other issues. It is probably possible, but we need a lot more information to tell you how.

Dr. Bush: We will leave that for now?

COL Jacobs: That's correct.

Dr. Bush: Let's leave it until we get additional information.

COL Jacobs: Page 29, certifying scientist review. The working group says yes. Are there any comments on the certifying scientist review? Are they reviewing anything that is much different from what we are already reviewing? Does anyone have any problems with moving that to a blank? Okay, let's do it and turn the page. Results reported by specific drug.

Dr. Bush: Do we want to link that back to the cutoffs and the analytes?

COL Jacobs: Are we on page 30?

Dr. Bush: Yes, Page 30.

COL Jacobs: Results reported by specific drug, the laboratory report can list results for each specific drug detected, they can and they do.

Dr. Vogl: Although we may change the cutoffs, whatever we decide, they can do it.

COL Jacobs: That seems like an easy one.

Dr. Bush: But that may change based upon how we change the cutoffs.

Dr. Selavka: I would say it better not change. We should tell people what we found.

Dr. Bush: Yes, but we are unclear as to analyte concentrations and are you going to revisit that?

Dr. Selavka: But as far as the specific drugs, we're saying the same thing.

COL Jacobs: Okay, we will change that to a blank. Page 31. I don't remember this being discussed at the group. It says yes. I don't see why they can't do it in a timely and confidential manner, in the same way that urine drug testing is done.

Dr. Bush: Agree, it shouldn't be any different.

COL Jacobs: Does anyone have a problem with moving this to a blank and turning the page? Page 32, the same situation exists, standard report form used. They can use a different form, but it can be standardized. Move it to a blank and turn the page. Interpreting results. No problem here? We're going to discuss this a little bit more so we'll leave it.

Ms. Bernstein: I would like to say one thing for the record. The fact was brought up that maybe marijuana is stronger these days and people feel that they are being wronged on the testing because of the passive inhalation issues. We have far more problems with drug testing than we do with passive inhalation, so we really have very great difficulty with the proposed method here.

COL Jacobs: Because?

Ms. Bernstein: Where it talks about in terms of the review policy, number 4, we would be opposed to donors offering alternative explanations in terms of inhalation, passive inhalation, and things of that sort. There are things that could undermine our whole program, so we are definitely be opposed to that.

Dr. Bush: 4-a on Page 34?

Ms. Bernstein: Why don't we say all of 4?

COL Jacobs: Do you want further studies done on higher levels of marijuana that are out there now?

Ms. Bernstein: No, we have not identified it as an issue in our program.

Dr. Bush: In the current program as it exists?

Ms. Bernstein: What Bob has said is in the normal course of things, that they're going to take after X number of years to revisit that issue, that is not being triggered by anything. We are seeing no problems or no need for any other alternative medical explanations within our federally regulated program from the DOT side. I cannot speak for HHS.

Dr. Bush: My understanding is that passive exposure has not been an issue that has been raised in DOT. It has certainly not been an issue raised in federal drug testing programs.

Dr. Caplan: She is saying that she can not accept a program for DOT which has hair testing that allows this type of explanation.

Dr. Bush: Element 4 on Page 34 outlines that passive exposure may contribute to a hair positive, may be responsible for a positive hair test. Then that is unacceptable as an alternative explanation.

Mr. Stephenson: My sense is you are asking for clarification and you want backup testing in this arena, is that correct? This is kind of what you're looking at, a fall-back position?

Ms. Bernstein: I don't think we're at a point to look at fall-back positions. I simply want to go on record that DOT does not feel the conditions exist currently, that passive inhalation is an alternative medical explanation. I'm not suggesting that we add an expense to our program in terms of fall-back decisions whatsoever.

Mr. Stephenson: You control for that with the studies we've done in marijuana, for instance, but we haven't done it for hair.

COL Jacobs: The bigger issue -- those studies were done for marijuana at a certain level that now that we have much higher levels, then personally speaking, I get calls occasionally from someone who wants to run the passive inhalation study. I tell them all that I know, and they say, but with higher levels, could you say that if that study was done again, could you say that they would all be negative or that one might be positive? The best I could say is, I don't know. Does someone want to help me here and say differently? I think we are saying here is an 'I don't know' and we need to find out with the current levels of THC if someone can test positive.

Ms. Bernstein: What I'm doing is a little different. I'm responding to the written piece of paper in front of me. And saying that officially from the DOT point of view, that we do not support offering a donor an opportunity to explain these circumstances in terms of - it says the program should be considered which would put employer funds for an additional test and we're not supporting that.

COL Jacobs: You don't want to give them an opportunity to say that you got an imprint.

Mr. Stephenson: You can use this as a place to make that statement.

Ms. Bernstein: That's exactly what I'm doing. This is a statement for the record.

COL Jacobs: Page 36.

Mr. Davis (RTI): Let me add one thing. While there may be, and obviously are, some higher levels of THC in marijuana, if you examine some of the data that has been generated, you may find that the average marijuana collection is not much higher as it is getting credit for these days. You may want to actually look at the data before you hang your hat on the position that the levels have increased dramatically.

COL Jacobs: I agree with that totally. I always try to determine how realistic the situation is because if they want to set up something that is totally unrealistic and then ask if the person is positive, I might say yes. But then they're going to have to address convincing someone that he sat in a phone booth for five hours.

Page 36, I think that relates to the previous section and we are going to discuss that at the same time. MRO training, Page 37. I do not see why they cannot be trained the same way that other MROs are trained.

Dr. Bush: Once we get that information from all the incompletes.

COL Jacobs: I'm thinking it might move up to a possible, but I don't see any reason moving it further. We'll get more information. I think we can satisfy it, but until we say specifically they need to know, which probably relates to the prior sections, those will all tie in and fall out at the same time. Page 38. I think we're still discussing this.

Dr. Selavka: I was wondering what the Board thinks. This is really near consensus, not comparisons of people to one another, but any person. We do think that's a fundamental difference between this and saliva testing and urine testing.

Ms. Bernstein: Can you define those response relationships?

Dr. Selavka: The response would be the extent of the positive you get in terms of quantification. So if you have 10 doses of a given amount of drug in one person, their hair will have a certain finding. If you have 20 doses by that person of the same magnitude in the time period represented by the same 3.9 centimeters of hair, for example, a second kind of use pattern would give you a bigger answer than the first kind of use pattern.

Dr. Sample: That's true of any biological sample, everything else being equal. If you correct for creatinine.

Dr. Selavka: Do we do it?

Mr. Crouch: The question is, is there dose response relationship in biological samples, the answer is yes, for almost all drugs. It may be variable in urine, but it's still there.

Dr. Vogl: We're just trying to determine if use has occurred. We don't care about dose time response for urine. I'm not sure why this factor is in here to be honest with you.

Ms. Bernstein: It sounds to me like it has something to do with marketing, would be my guess.

Mr. Stephenson: Do you mean the way it's phrased or just in general on the issue?

Ms. Bernstein: But my question is, is there anything in here that you're talking about? I understand you're talking about dose responses, or anything you're talking about having to do with impairment.

Dr. Selavka: No.

COL Jacobs: Denny, did I understand you to say that you think this can be a blank there because there is, with any biological, this relationship, or do you think we need to discuss it further?

Mr. Stephenson: Is this a dose response or dose detection relationship? If you're talking about in terms of giving a pharmaceutic to someone and you're looking at a dose given and a response detected in terms of impairment, for instance, or in terms of pharmacokinetics, then that's different than what you're talking about here. Because you're talking about dose detection. In that sense you're saying there is a relationship between the number of doses given and the size of the quantification of the results. But that's not the same thing as dose response, is it? Or am I mistaken?

Dr. Selavka: I'm just reading the matrix. We didn't make the matrix, but it says related to the time and dose that drug use occurred. I don't know what the input of the Board was when they wrote this.

Voice: I think it was the intent of the original conception of this matrix that this particular element response referred to the analytical response and had nothing to do with the biological or pharmacological response that might have been induced as a result of the particular drug or drug metabolite.

Dr. Bush: Was this concept to aid in the evaluation of information presented by the donor to the MRO? For example, I took dronabinol two weeks ago and that's why my urine is positive today.

COL Jacobs: I understood it to mean that we could relate the number of doses for the number of times to the level of drug that we get when we test the sample, just a straight-out question of if you took it once you will get real level, if you took it twice you would get more, if you took it over a longer period of time, you'd get a higher level than a shorter period of time. Is that what the question means?

Dr. Vogl: If it does, we do not need this. It is not a part of our workplace program. We want to know only if it is present, that is, positive.

Dr. Caplan: I think the reason for the question was a comparative one, whether or not as you go across the matrix lines and we have something with urine, whether or not the others are greater or less than that. It has nothing to do with pharmacokinetics, only to do with whether or not if we take it. That's why I was asking the question, whether we take a 30 day or 90 day amount of hair, is that going to detect people similar to or greater than or worse than what we're currently doing with the random urine.

Dr. Bush: Let's consider it something like a detection window in an oral fluid. This is where we're going, the window of detection.

COL Jacobs: So we can move this to a blank? It is answered.

Dr. Vogl: If we change it to detection window, it would make more sense. In other words, if a person takes a dose of something, at what point, how long can you detect that dose? In hair, if they smoked a joint, your window might be that you would have to wait two days until that hair started growing enough or ten days. There would be a minimum time before sampling, plus you could detect it as long as it is in that hair when you take a sample.

Mr. Crouch: Implicit in this is you could take a hair concentration of the drug and determine what the dose was. That's what is implied in this statement.

Dr. Vogl: No.

COL Jacobs: If that is what is implied, I am not sure that I'd be willing to say that's true for all people. I mean, if we give everybody in this room the same amount, we are all going to have a different level. That may or may not make sense to how much we took.

Voice: It is time and dose, not just time.

Mr. Stephenson: Does this lead to minor editing to make sure it does what you want it to do?

COL Jacobs: Do we need to edit the question, edit the answer, or do we want to eliminate the element?

Dr. Vogl: In my opinion, it is not an issue.

Mr. Stephenson: Why don't we leave it in the discussion because you have different opinions, even on the Board.

COL Jacobs: Who wants to leave it as an element? Speak up.

Dr. Caplan: I think we should leave it as an element.

COL Jacobs: Can you tell us why we need to leave it as an element? Maybe that will give us the answer.

Dr. Caplan: The reason we need to leave it as an element, is in the end when you write the final regulation to decide whether or not these specimens can be used for these purposes, you've got to have them in a comparative sense. In other words, are we going to say you can use a sweat patch for the same thing you can use a urine for, and the same thing as hair? I don't know the answer to that until we come out and do this.

Dr. Bush: It is a detection window, establishing the detection window.

Dr. Caplan: Is the detection window adequate for this program?

COL Jacobs: You're saying this should relate to a study comparing all the different testing methods to say what a dose in one testing system relates to another?

Dr. Caplan: Not necessarily, but if you write new regulations, we have a urine regulation. If you're going to add other matrices in there, then are they going to detect to the same degree that we're now detecting in urine, or are they going to be better or are they going to be worse. I think you have to answer that question before you write a program.

Dr. Vogl: Charts have been presented for years relating to different detection windows for different types of specimens. We already know this.

Dr. Caplan: Then we have the answer.

Dr. Vogl: This is not an issue, it is an applicability of using a sweat patch for a certain situation, and we need to discuss applicability when writing a regulation. You may not want to use oral fluid for random test, but you may want to use it for post-accident testing.

Dr. Jones (University of Mississippi): If I might go back to the genesis of this table, I don't have in front of me all the sequential edits that have occurred from its original conception, but this was a series of questions to which we had no answer when we started. The questions and elements were being developed to address potentially all future alternative matrices so I would suggest that you may want to keep it there to allow you to address the issues that Dr. Caplan is addressing. As you approach regulations, as you approach the writing of regulations for these particular alternative matrices, but that was why it was there. It was a question particularly with hair and sweat and saliva that we originally put the I in. I believe that we didn't have any idea whether any of these relationships existed or not. Now you're getting data that say that they do exist and that's good.

COL Jacobs: Does the question itself change the language?

Mr. Stephenson: Why don't we leave it where it is, do a minor rewrite and then come back because you will be to able to clean this up real easy.

Dr. Selavka: We need to know what the question is.

COL Jacobs: I think the next issue is one of the larger ones that goes on for several pages. I think that means we have some more work to do with specimen contamination. And that gets us to the end.

Mr. Stephenson: At this time, are there are any compelling issues the public wishes to address to the Board? We would make some time available for that purpose. If not, we will pick this up again in the morning at 8 o'clock. First up is sweat testing, then we will go through the other alternative matrices and ask for input and any updates that the members of the industry, from those alternative technologies, might want to bring to the attention of the Board.

I want to commend the small working group for hair testing. If there's nothing else at this point in time, this session of the Drug Testing Advisory Board is adjourned until tomorrow morning at 8 o'clock.

 

MARCH 9, 1999

Mr. Stephenson: Good morning. This is a continuation of the Alternative Technologies and Specimens Working Group discussions. As you recall from yesterday's efforts, we were successful in doing an update to the grid matrix for accurate and reliable drug testing related to the specifics of hair testing. We had gone through and reviewed the efforts of the Small Working Group. We had gone through and reviewed the areas in which there were still some complications and areas that needed discussion and then we had proceeded to make changes to the actual grid with recommendations in areas that we still needed to work on. That was a major piece of work. It is unique also because we haven't had the luxury or the experience of having other working groups anywhere near as advanced as this activity was concerned for other industries, but there has been progress made in other areas despite limitations in how formally they have met or how large they are and there have been, in the last couple of Drug Testing Advisory Board Meetings, a focus on hair. We retained the focus because they are our lead Working Group in the process we're going through. But today we have chosen to start today looking at one of the other technologies, and I'm going to have Dr. Bush introduce you to that group and to the process.

Dr. Bush: As follow-up to what Bob was saying, in our September meeting, we had some formal presentations by the industry representatives from the Working Group. It was very good. It established the basis for the work at the top lines -- the first part of the work that is on every page of your blue hand-out book -- and the groups that were subsequent to that and submitted a formal report like we saw yesterday with hair that work has been included also in this blue book as indications of progress and answers to questions that were outstanding and some that still remain outstanding. I would like to reflect back to the sweat patch because we have not heard from sweat as an alternative technology since that September presentation. In the December meeting, we focused on hair and on-site urine testing. We have been requested to discuss sweat testing, review what was presented at that September meeting. It is included here for memory-jogging purposes. Neil Fortner is here as the industry representative, and I'm sure he will work through any remaining questions in a manner similar to what happened yesterday with Dr. Selavka and hair testing with his follow-through on the Working Group. We will continue in that manner with Neil Fortner today, and I think Dr. Caplan will be taking the lead on this review for today's session. I know that Melanie Mallory in the future will be working specifically and directly as a Board member liaison with sweat testing. We can begin, Dr. Caplan.

Dr. Caplan: I think Neil is going to give us a quick update.

Mr. Fortner (PharmChem): I am the industry representative for sweat testing. As Donna had said, there has not been any discussion since we met in September pursuant to responding to the issues and questions that were asked of the industry back then. There is, at this point in time, no active Working Group pursuant to resolution questions addressing the issues we presented back in September. We have had numerous conversations with HHS regarding that status and part of the view, as I understood it coming back, is that the Board had not completed their review -- questions and answers of that information. There wasn't a lot for the Working Group to actually do as we go through the checklist and I think Yale will do that. If you will notice that many of the issues had been addressed back in September, there are some still outstanding issues, and some of them are program oriented but, nonetheless, there has been some additional research presented at the recent Academy meetings and some of the SOFT meetings, but that research, as it pertains to the sweat patch, has not been presented to the Board. My conversations with HHS indicated that the Board has not yet had an opportunity to fully digest the existing material, let alone go into new areas. There is no active Working Group at this particular time, but that will change as issues come up.

Dr. Caplan: Let me first thank Walt for putting the information in this format because it was difficult until now to systematically go through this. Although we have looked at all of this information over a period of time, it was never in a systematic format that we could go through with and really move positively or negatively on each of the points. Since sweat is represented mostly by one product at this time, there is not a large comprehensive group to meet and so probably the simplest way to do this is going through the checklist piece by piece. I'm going to look over to Neil each time and say, do we have anything new here, and then to the Board, do we have anything new, and do the same thing we did yesterday to identify things which are no longer an issue and we assume can be moved forward with additional work. In other words, we're not going to answer the question, what is the training program, but as long as we're satisfied, for example, that a training program can be done based upon previous information, we will move that question along and again, try to identify areas of research or areas of very specific questions to go back to Neil and the small group he has to do that. Let's start with Page 1 under the sweat group. Again, some things that have already been cleared are not, to my understanding, in this list. The first question is that of collection training and I will read what is on here and then ask Neil if he has an additional comment or update since some of these things do go back a couple of years and see what the Board wants to do. The first one has to do with training programs and the notes indicate that things are similar to hair, with video tapes and manuals have been prepared and are available. Is there anything additional?

Mr. Fortner: The statement speaks for itself and is the current status of the training program?

Dr. Caplan: Maybe you could comment on the scope. You trained a number of people. How has that gone? Is the training done by company people? Has the training been extended to third party groups yet or not?

Mr. Fortner: The answer to all of that is yes. The training is conducted at several levels. There is the trainer program and there's also training by industry representatives. This program has been used most effectively at this point in the roll out to all 94 divisions of the Administrative Office of the U.S. Courts. Federal Probation and Pretrial has made extensive use of this video tape, teleconferencing, on-site training program, as well as other agencies throughout the country. I don't think I have a specific number at this point. Suffice it to say, I think there are somewhere between 3 to 500 individual program sessions to train collectors and this is includes how to apply the patch, how to remove the patch, how to look for signs of tampering, ensure integrity, proper completion of chain of custody documents.

Dr. Caplan: Any comments from the Board?

Mr. Lucas (Administrative Office of the U.S. Courts): We have approximately 2000 probation and pretrial officers who have been trained in the application of the sweat patch. In 1998, we used approximately 11,000 sweat patches in supervising federal offenders, probation violators. In supervisory cases, we have had extensive experience in using the sweat patch.

Dr. Caplan: Any comments from anybody on the Board? Is there any reason why this having been a P should not be a blank?

Mr. Stephenson: Just for the group again to review the process that we set up yesterday of looking at each of these items and then to updating the matrix, going from either an I to a P or a P to a blank, meaning that -- that's where we are. Could you just review that and re-state that as a criteria that we will use today for upgrading each of the components in a similar manner that we did the review yesterday?

Dr. Caplan: Remember that the first section of the grid gives a summary of all the elements of the grid and on the first page, there's a key where we have blank. We had already decided that this would satisfy the requirements prior to today. A "P" was an indication that it was very likely this was possible, but we wanted to hear from the industry as to the specifics and experience which we just did, or "I", there was insufficient information that again, we asked the industry to provide the information or had a need to obtain that information from research source that may not yet be available or an N, which would say no, it cannot satisfy the requirement that ultimately if it can't be moved off, might be a limiting factor in being able to utilize this material. Our goal is to move this group forward to have removed the N's and changed the I's to P's and the P's to blanks and move in that direction systematically. On the early part of the whole grid, Walt did not reproduce any item on the grid that already had a blank. We're going to skip over the front grid part where there are blanks, we don't have pages in the text. Where there is a letter, we do have a page and that is what we're going to discuss and that coding is re-entered on the top of each of the pages that we're talking about. On the first page under training, the center column on sweat, there's currently a P and the question, that is, that on the basis of what we know today from the experience of the manufacturer and experience of the U.S. courts, that it seems reasonable to move this due to the fact that it has been done. I think we want to remember, we mentioned it yesterday, is that at this point in time we're not trying to write the regulation, we're only talking about whether the information is there. At a later date, this will have to be gone over again in specifics of what this training program is or should be in the eyes of the government, and the program will have to be restated. We're not going to try to restate that today and some instances, some of the elements will be stated. Like cutoffs, once we decide on the cutoffs, they will likely be replaced directly into the document, but the training program -- there will have to be some elements of what it will include, et cetera, but we want to get through this process systematically to ultimately ensure that we have enough information for HHS to draft the document for public comment. I don't want anybody to think that once we get through one of these things and move into a blank, that it's necessarily all over. It just means that we've moved the process along, where someone else can use the information that exists and draft that into the legislation. The other thing that is, from a personal perspective, is that I think we're also trying to look at these things in conjunction with each other and not each one in an abstract so when one goes to write the ultimate document, the document will be for all matrices comprehensively and not necessarily one at a time or one matrix, although there may be specifics about certain matrices that have to be entered in there. For example, if they get to the cutoff section, there's likely to be a different set of cutoffs for each matrix. But when you get to the training, there may be a very similar thing as to the elements that are required in training. But that's at a later date. Does anybody have any questions about the process?

Mr. Stephenson: Thank you very much for refreshing our memory and I think it served us well to do this whenever we begin. It is important that we standardize this process to make sure that it is consistent across each of the specimens and the grid.

Dr. Caplan: Do we agree that there is no objection moving collector training on B-1, from P to blank? [NO RESPONSE]

Dr. Caplan: The next element is certification. The statement is that a formal certification program including a written examination has been in existence. There is a training manual. Again, I would ask the two of you who have experience with that to comment on the use of the manual, whether it's changed or whatever. Neil?

Mr. Fortner: We have not had any updates or changes to the collection manual since it was written. I think our last revision was in 1997 and also the written exam has remained the same as there have been no changes in that process.

Dr. Caplan: There's a note on here about how to look for adulteration and what do you do about -- and how do you ensure the patch is put on. Can you comment on that?

Mr. Fortner: To comment on that, you need to back up a little bit and just review some general criteria on the patch. The patch is a collection device that is tamper-evident. It incorporates technology using some material from 3M Corporation, Tekraderm, which once it adheres to the skin, infiltrates the upper layers and when you pull the patch off, some of those skin cells come with it. So it effectively has covered the adhesive, which means you can't reapply it. Also, if individuals attempt to inject solutions into the sweat patch itself, which is, for all practical purposes, medical grade blotter paper, we will see puncture wounds on it and you also see visible discoloring of the patch, and we've had instances where individuals have attempted to do that. The other property that you have with Tekraderm is it doesn't allow anything larger than water to pass back and forth with the attempt to adulterate it using something like bleach or other solutions. It has the unfortunate property of trapping that under the patch, and we've had several instances where secondary chemical burns result because it doesn't release the bleach.

Dr. Caplan: Have you looked at other adulterants? You mentioned bleach. Are there other things that react the same way?

Mr. Fortner: We've looked at adulterants in the sense that what you put on the patch and then how a dose of adulterant affect the ELISA screening assays and that was all part of the FDA 510K process. We were going into specific ones. We looked at the bleaches, we looked at some attempts from individuals to try to flush the patch by using a syringe with water and just pumping water back and forth across it in an attempt to pull the drugs off the patch. Drugs have a tendency to be adhered a little bit more physically stronger on the patch. We end up using a methanol acetate buffer to remove the drug from the patch, so depending upon the drug, certainly THC is very difficult to flush out of there. But it does address the question, is there certification and is there tamper evidence, and that's part of the training program which includes glossy photographs of the attempted adulteration, and once you physically see people remove the patch and try to reapply it.

Dr. Caplan: Mr. Lucas, did you want to comment from your point of view?

Mr. Lucas: No.

Dr. Caplan: It's working?

Mr. Lucas: It is working.

Dr. Caplan: With 11,000 patches, did you have any adverse experiences?

Mr. Lucas: No, except for the instance Neil talked about, we have not. We have had offenders try to remove the patch and put it back on and the officers have been trained to recognize the sign, so it has been very effective.

Dr. Caplan: Any other comments from anybody else relative to the collector certification? Again, is there any reason why we can't move the P to a blank for this question? Any other comments from the Board? [NO RESPONSE]

We will go from P to blank on that. Neil, you started to talk about the next question, which is FDA clearance, which is a general question for all of the things we're talking about. This was FDA cleared. Maybe you can give us a brief -- of what is in the 510K and what it meant to get the device FDA cleared, both from the collections point of view and from an analysis point of view, if that is pertinent.

Mr. Fortner: I think that it is. There are really two independent distinct issues. The sweat patch is a non-inclusive collection device that is manufactured and produced by Sudamed Corporation, in Santa Ana, California. They actually own the rights to that particular product. In 1990, they had submitted, or actually prior to 1990, they had submitted and received clearance from FDA as a collection device under the Medical Device Division. So that process in demonstrating that the use of Tekraderm with medical grade blotter paper would not cause adverse reaction as a hypoallergenic. And certainly Tekraderm has been in use for many, many years in clinical applications, securing IVs, catheters, wound dressing, for that matter. So that's the process. Under FDA, for the medical device and in the presentation that I presented to the Board, that presentation had copies of the letters from FDA. One was October 1990 as a medical device and then subsequent applications were in 1995 and 1996. And we'll probably get into those a little bit later, but those specific clearances in '95 and '96 were specific and unique for demonstrating to the FDA Scientific Advisory Board that the sweat patch could in fact detect the use of drugs. That's a much longer process that started in 1992 and took several years to complete and involved a wide variety of clinical trials, controlled dose studies for all of the classes that it was ultimately proved for, which are amphetamines, cocaine, opiates, marijuana, and PCP. The only exception was that, for obvious reasons, we were not able to get approval, or Sudamed was not able to get approval, to administer PCP to volunteers, not that there was any lack of participants, but there were some issues in there and so the PCP data is from a self-report. The other classes of drugs didn't have controlled studies, stability studies, which I'm sure we will see later throughout the questions.

Dr. Caplan: Again, are there any other comments? I think there are two parts. One is if there's a special device where means of collection and the other is the analytical technique. It's my understanding that only the device has FDA clearance and not any other part of it, or part of the process.

Mr. Fortner: The actual testing for detection of drugs went through an FDA 510K utilizing the sweat test.

Dr. Caplan: And what immunoassay?

Mr. Fortner: ELISA.

Dr. Caplan: I want to be clear. The FDA approved both the ELISA device and the technology?

Mr. Fortner: The device, ELISA technology, screening, and GC/MS confirmation.

Dr. Caplan: Can you comment on the potential for variations? We look at this as not the only product, but there may be other products ultimately and one of the questions about what the FDA clearance is what we might require to be cleared from the point of view of the ultimate document and that question, whether that includes a device separate from the method at least in my mind, so in this case you have cleared the device?

Mr. Fortner: In this particular case, you have a device that is separately cleared from the methods themselves.

Dr. Caplan: The question is, are the methods otherwise cleared or approved by the FDA? Are you free to use the device with some other immunoassay technique?

Mr. Fortner: I believe there are a variety of immunoassay techniques. RIA includes some of the more sensitive polarization assays -- are certainly capable of detecting the levels that you see in sweat. I'm not sure if I fully understand that question or issue.

Dr. Caplan: It's whether or not the device is approved using one technique or can it be used by other people with other techniques in accordance with what the FDA has approved?

Mr. Fortner: I believe that going through the FDA 510K process demonstrated equivalency and deduction. I believe you could use other technologies that were similar technologies to ELISA or immunoassay screening coupled with chromatographic confirmation.

Dr. Caplan: Without going back to the FDA for additional approval, that was the question.

Mr. Fortner: Yes, I believe those are comparable technologies involved.

Dr. Caplan: What I was trying to get at as we go across the grid, the fundamental question will be, what are we going to require for the assay process. We talked about that right now, we have in urine, an FDA approved assay. We talked about it with hair, and I just wanted to include that in the discussion here that whether or not we're looking at a process where the analytical technique would require FDA approval. Anybody else from the Board want to comment? Let's talk about the device first. Did the devices need FDA approval in our opinion, and do we have enough information to change this from an I to either a P or a blank?

Mr. Stephenson: One of the things to think about here is we cannot speak to FDA's role or their authority or the determination to provide oversight in these areas. We have some pending decisions that have not been rendered in this area independent of what we might say, FDA is a separate authority. They know that even better than we do, in our experience in working with them. What we need to do at this point is to address whether or not an individual device has been cleared, but not necessarily to address the need for that clearance. If we are successful in getting clearance and make the recommendation, that could carry weight back to the FDA, but it might not make the determination in our favor, eventually anyway. You have to decide how you feel about this and give your best guidance to us. I'm not convinced that what we say they should do, they will necessarily do.

Dr. Bush: They have made it clear that they are open to our discussions and will entertain any recommendations that the Board makes.

Dr. Sample: I think there are two separate questions here. One, do they need to be FDA cleared? Does the container or has the container been cleared by the FDA? I think in this case the answer is yes, then we can move this from an I to a blank, then perhaps halt the discussion to whether we're talking more generally about whether FDA clearance is required.

Dr. Caplan: We are moving the question from I to blank, leaving the further discussion up to method, because I think that will come up at the end. As to whether or not the test will have to be done by an FDA approved method, does everybody agree that we have enough information to go from I to blank on this? The next question is, the ability to do multiple testing. The sweat patch is currently screened for the five drugs and I think all the drugs which are in the mandatory guidelines have been included. This question has to do with whether or not the size of the patch and the materials are sufficient for doing at least two confirmation tests. But is there adequate material for doing a second follow up test?

Mr. Fortner: Yes. After the initial screening, there is sufficient sample to do at least two GC/MS confirmations. We have instances where we have done more than two and found that you can actually go back to the patch and get more drugs off the patch because the initial process doesn't pull everything off and the patch is retained in this container indefinitely until ultimate disposal.

Dr. Sample: What percentage is removed off of the patch with your first elution?

Mr. Fortner: Somewhere between 60 and 70 percent is eluted from the patch.

Dr. Sample: How much would you remove with a second elution?

Mr. Fortner: You will get 60 to 70 percent of what's left, typically looking at the levels. We've not had any issues going back to those cases. For instance, in some we've gone back to do a D/L isomerization differentiation and found that we can pull adequate drug off of that, certainly at the cutoffs to provide detection well above the cutoff levels and even limit of detections if you go to that level.

Dr. Isenschmid: I want to clarify what's on this paper. It says at least two confirmation tests. Are we talking about two particular analytes or up to five analytes twice?

Mr. Fortner: That pertains to two classes of drugs. Typically we don't see a lot of polypharmacy in the sweat patches. We see they're predominantly positive for one class of drugs, but you could do a cocaine and amphetamine off of the material.

Dr. Sample: I understand you do one elution and with that one eluate, you're doing all of the screening and confirmation off of the single eluate?

Mr. Fortner: Yes, off of the single eluate.

Dr. Caplan: A simple eluate off of the whole patch?

Mr. Fortner: That's correct.

Dr. Caplan: When you say there is sufficient specimen released to do at least two confirmation tests?

Mr. Fortner: To do two confirmations by just splitting the eluate.

Dr. Caplan: Any other comments or questions? The question is whether or not the patch has sufficient volume to do the testing. Does anybody have any thoughts about that?

Dr. Bush: A question concerning retest?

Dr. Caplan: That's the next question. The split is the next question. They are linked. Maybe we ought to do them together before we decide on one because the question on the next page is the potential for split specimens. The way I understand it, there has been additional thought given to that, but that is not necessarily the way the patch operates.

Mr. Fortner: That is correct. There has not been a request to do split specimens in the formal sense of how you would define a split specimen under the program. Two independent samples, one tested and one not tested. I mean, it's certainly possible to do that if you wanted to either put two patches on or modify the existing patch to have two absorbent pads that would increase the physical size. That is not problematic. I really believe that D-2 is a separate question from D-3. D-2 says is there enough to do multiple tests and D-3 says split specimens. My interpretation would be under the formal program, you would have to apply two patches at this point to do split testing.

Dr. Caplan: Would you apply two patches or would you create a patch that is two component parts?

Mr. Fortner: If you wanted to do it tomorrow, you would apply two patches, but the manufacturing process to do a dual component is not that difficult. It would require a few months lead time.

Dr. Caplan: Would that require FDA evaluation?

Mr. Fortner: It just physically increases the size, and I wouldn't believe that that would require a resubmission.

Mr. Good (Avitar): I wondered, and perhaps this applies to multiple testing about different analytes, whether there has been any consideration given to accumulation of DNA or PCR testing to identify who the actual donor of the sample was.

Mr. Crouch: You have a schedule so the potential is there.

Mr. Fortner: If you wanted to retain the polyurethane covering, which in some cases we have agencies that send it to us so that we can inspect it to see if there has been an attempt at adulteration. There are epithelial cells on that product. It is not something we have gone through to investigate that, but certainly the potential exists.

Mr. Crouch: Neil, do you know how homogeneously the drug is distributed in the patch? If you cut a patch in half, would you have concentration on each half being the same?

Mr. Fortner: Given the physiology and the excretion of sweat, I would expect it to be fairly homogenous. You could cut it in half. We have no specific studies that demonstrate that. That is fairly straightforward to do if you so desired. Again, if you're going to do a split along those lines, it would be much better to have two patches as opposed to physically cutting it. Then you've got to worry about other issues of contamination and identification.

Dr. Caplan: The next question is whether or not the feeling is that there is no sufficient information that the patch collects an adequate specimen to do the testing which would change this from an I to a blank. Does anybody have any thoughts?

Dr. Sample: I have a question for perhaps not just for sweat, is the use of one eluate. Does that really entail a two aliquot type of methodology that we are used to in the more traditional screening techniques. And I think this question really cuts across multiple alternate technologies. If you were to develop a system that is exactly analogous to what is being currently performed in urine based screening, might then require a second elution from the sweat patch on the basis the sweat patch is the collection device just like a container is a collection device.

Dr. Bush: Alternatively, one could consider that initial eluate, the original specimen, then take an aliquot from that for screening, an aliquot from that for confirmation. You're right, that is absolutely a possibility, but I think we need to come to a decision as to what constitutes a specimen.

Mr. Stephenson: Do you want to hold that thought for this purpose here and look at that as one of those issues we will address across the specimens? Maybe I would ask for thoughts from the different small working groups.

Dr. Sample: That's essentially where I was going with that comment.

Dr. Bush: That applies to any oral fluid collection device where you would have a pad where you perform an initial extract which then becomes the volume from which aliquots may be taken, so point well taken.

Dr. Sample: That's why I raised the issue.

Dr. Caplan: Do you raise that issue such that it questions whether this is an I further, or do we want to deal with that as a separate issue?

Dr. Sample: In my mind, we need to answer that first question, the question I just raised first prior to moving these from an I to a P or to a blank.

Mr. Crouch: I think that's a different question than split specimen sample, but it's still multiple testing.

Dr. Caplan: Multiple testing could be construed as, is there adequate volume here. I think that's probably answered yes. Another question which may not be directly on this grid, is whether or not the specimen is subject to aliquoting. Again, we can hold this. Let's hold this question and leave it as an I in light of looking at this other issue. Have we thought about maybe just taking the patch and inserting it in the liquid and then the liquid itself elutes and then the liquid becomes the specimen?

Mr. Fortner: Into a disposable transfer vial. There's 2.5 milliliters of methanol acetate buffer and it goes on a horizontal shaker for 30 minutes and then we use what is analogous to a serum separator that goes inside the tube, presses the patch down to the bottom and the fluid goes up, and the patch stays in the bottom.

Dr. Caplan: It can be identified in the future? You didn't make a transfer?

Mr. Fortner: The patch stays inside that original container.

COL Jacobs: I think we can satisfy the requirement. I think we have some means here to say if you need two patches or three patches, we can satisfy the requirement. I don't know if we need to get into the details of how exactly someone is going to satisfy those requirements here. But I think Neil has laid out that it can satisfy them and if need be, it can be done.

Dr. Sample: Are you talking about from the multiple testing standpoint or the split specimen's standpoint?

COL Jacobs: Both.

Dr. Caplan: The recommendation was to leave this alone and add this other issue to it. Is there anybody who wants to change that?

COL Jacobs: I think they should both be blanks here. I think they have been answered, they can be answered. You can meet the requirement.

Dr. Caplan: Any other comments? We have one dissenting vote. I mean, we're happy to move on. Whichever way, we need to make a decision.

Ms. Mallory (DTAB member): I think it does meet the multiple testing. He stated himself that in the formal sense, it does not meet the split, but I do think it meets the multiple testing.

Dr. Sample: From my standpoint, I think just the opposite. I have a question about the multiple testing that I think we need to flush out in general for all of these alternate technologies.

Dr. Caplan: I'm going to make a suggestion that we move this from an I to a P and then continue to discuss it further so that it has moved up a notch. But since we don't have all the answers and we're not going to get them all today, let's leave this and we can come back to it when we go across the matrices with the question about whether what constitutes the original specimen. Does everybody agree to move it to a P? And this is D-2 and it's also D-3. Let's take D-2 first. D-2. Do we have agreement to move this to a P? We've answered some of the questions. We do have information but we are now less uncertain about one point.

COL Jacobs: Have we clearly defined what the questions still are so everybody knows how the next step will be taken?

Dr. Caplan: The question is whether the original specimen can be effectively aliquoted for multiple testing, not whether there's sufficient volume that the patch can collect a sufficient specimen. The question that remains is whether there is the ability to aliquot that so that you won't always be working with the same aliquot for all of your tests.

COL Jacobs: I don't understand. Let's say we have a bottle of urine or a bottle of fluid taken from a sweat patch. What's the difference between the two fluids and aliquoting for testing?

Dr. Sample: The difference is the laboratory has processed that specimen, if you will, in order to produce that aliquot, which is not the case with urine and a collection container coming straight from the collection site.

COL Jacobs: You're talking about a fluid and pouring some of the fluid. We have to deal with what we have here.

Dr. Caplan: I think the question is whether we go back to the original bottle for a second aliquot where that's possible.

Dr. Sample: And whether it's a requirement.

Dr. Caplan: That has not been necessarily demonstrated.

COL Jacobs: You want to go back to the original patch for the second aliquot as opposed to going back to the fluid produced to get the second aliquot?

Dr. Sample: No, I'm not saying that necessarily. I just think we need to answer the question whether or not there is a requirement to do that. As we're talking about the sweat patches, we're talking about salivas, we're talking about hair. Do we have to go back to that original specimen which is either the patch, the saliva swab, or the hair follicles and re-generate that eluate with that digest in order for it to be a second aliquot. I think that's the question we need to answer before we can adequately answer D-2 for all of these technologies.

Dr. Caplan: Do we want to make this a P?

COL Jacobs: That's a move in the right direction.

Dr. Caplan: We will continue with that question across the board, so we will change this I to a P.

Dr. Bush: I suggest that Board members take a look at the pros and cons and evidentiary requirements.

Dr. Caplan: Do you want to do the same thing with D-3, the split?

Dr. Isenschmid: I have one more question on the split, and that is, if you actually went to the two patch system, what would be the homogeneity between the two patches in terms of collecting them from different sights?

Mr. Fortner: That has been looked at. In fact, in the 510Ks, patches were applied to a variety of places on the body. Typically, it's placed on the upper arm, it can be worn on the back of the lower rib cage. All the studies from the clinical control dose where they were wearing many - I think the largest study put 17 patches on an individual - their controlled dose and you're looking at patches being taken every hour or every several hours and they showed no statistical differences in patches collected from various portions of the body.

Mr. Crouch: But isn't it true the distribution of the sweat glands is not even across the body? There should be some variation depending upon where it's split and what the density of sweat glands is in that particular are?

Mr. Fortner: That is correct, I did say that there were no differences in the levels when we went through and did statistical analysis. They weren't statistically different for the areas we were applying. If you look at the lower rib cage, the upper back and the arms, I think the upper arms are going to have similar sweat. Now if you look at the palm and the hands or the bottom of the feet, a completely different scenario. I would expect much higher levels in those areas just in the production of sweat.

Dr. Caplan: And the time frame for application was what?

Mr. Fortner: How long did they wear those? They have to wear them at least 24 hours and some of these studies went out a better part of a week.

Dr. Caplan: Anything else? Any other questions on the potential for split? Is there any reason not to change this to a blank? We will move this from an I to a blank. Page 6 is D-4, stability and storage. Do you want to comment on that?

Mr. Fortner: Sure, if you just go through and read the summary of this. Under the 510K, stability in patches was required to be demonstrated. We had both worn, and unworn. And the issue here is stability of the drug on the patch itself. We have multiple studies where you had both worn and unworn patches, drugs applied to it, subjected to a variety of storage conditions, including shipping them to other sites and shipping them back and then going through the process that was outlined in the 510K elution for this material and screening and testing to look for differences in stability. We haven't gone to it here, although I can tell you on retest samples, we found the drugs in the methanol acetate buffer are very stable, capped at minus 20 degrees or lower.

Dr. Caplan: That's eluted?

Mr. Fortner: Right, we went for as long as 28 days just looking at stability of the drug on the patch itself.

Dr. Sample: That was part of your initial filing, but have you done any subsequent studies for a period of time longer than 28 days?

Mr. Fortner: No, we haven't. Under the current program, we don't have anybody that holds a patch for 28 days before they send it in for testing.

Dr. Sample: But what about after you've received the patch?

Mr. Fortner: Pending processing, holding it? Well, we haven't done anything beyond the 28 days again, because our turnaround time is mandated by the client. We don't store them.

Dr. Sample: If you were to do a second eluate, as you mentioned, you had the capability of doing the second eluate. What's the longest after being stored that you could do that?

Mr. Fortner: Our experience right now is somewhere between six and eight months of doing the retest of the initial eluate. The original patch has already been eluate so it's like having the liquid sample. We haven't done more than 28 days of a spiked patch, non-eluted.

Dr. Sample: Earlier, didn't you say that you could do a second collection and recover drugs on the second elution?

Mr. Fortner: Yes.

Dr. Sample: What is the longest time interval between the first elution and the second elution that you've ever done and still have been able to detect evidence on the second elution?

Mr. Fortner: That's what I referred to as the retest in the six to eight month window where you've had to go back and re-elute to be able to do a D/L isomer.

Dr. Caplan: Any other questions?

Dr. Mitchell: Has the stability data for all of the analytes been conducted in the long term?

Mr. Fortner: Long-term meaning after they've been eluted?

Dr. Mitchell: No. On the patch itself?

Mr. Fortner: Yes, all of the patches had up to 28 days for all analytes.

Dr. Mitchell: We haven't had the data for say, a year, like the stability data we would have in urine or in hair, for example?

Dr. Sample: You indicated in a retest for D/L. You had gone six to eight months?

Mr. Fortner: Right.

Dr. Sample: Have you done other analytes other than D/L in a retest scenario in that six to eight month time frame where you've had to re-elute off the patch? Because that only occurred with the D/Ls, have you done it with all the analytes?

Mr. Fortner: The re-elution has typically only occurred with D/Ls. We have had retests by other laboratories that are in that time period for cocaine, but they do not involve re-elution.

Dr. Sample: That was from the original elution?

Mr. Fortner: Right.

Dr. Sample: So there really is no stability study on the patch itself, off of the patch, for longer than 28 days other than for D/L amphetamines?

Mr. Fortner: Correct.

Mr. Crouch: Don't you store the patch at room temperature?

Mr. Fortner: When we receive it, yes.

Mr. Crouch: So you have 28 days at room temperature.

Mr. Fortner: The stability studies are for 28 days.

Speaker: I think you're getting to your question of the re-elution of the patch. I don't think that is an appropriate scenario because depending upon the level you're dealing with, we're getting 60, 70 percent off the original extract and we had to go back and re-elute. We had 67 percent of what's left, then quantitatively, we may be below the cutoff so I don't necessarily think that is applicable in that situation. As far as stability, I'm getting kind of confused because when the patch comes in, we put it through the extraction process originally and it is stored in that liquid.

Mr. Crouch: What I'm trying to equate this to, and I think what other people are trying to equate this to, is urine stability, not more urine samples, are present in testing your stability is at room temperature for 28 days, but you really don't store these and you haven't taken those extra measures to see if the sample is optimal.

Mr. Fortner: The samples that are possible, the eluates go into long term frozen storage. The dry patches and cell stability study is what was submitted to demonstrate stability on the patch prior to elution. Now their deviation is one variation of the question. Stability of the drugs in the eluate. Is that your issue, were stability of the drugs not eluted off the patch that's in the container?

Dr. Caplan: Certainly the stability in the eluate would be parallel to keeping urine for a year and seeing whether you still could recover the drug.

Dr. Sample: No, I don't think so. I think stability on the patch.

Dr. Caplan: One question is whether or not after you've done the analysis on the eluate, whether you can re-construct that analysis within what time frame to reconfirm that if that were necessary akin to saving urine for a period of time for that purpose. The other question is how long it is stable in the patch and whether that is an important consideration or not. There are two stability questions and the net result is that you've got 28 days on the original patch, how long do you have on the eluate? Have you done that?

Mr. Fortner: Not for all analytes.

Dr. Caplan: It is a question we want further information on.

Mr. Jones (DTAB member): I think this goes back to the original question, D2. What is the specimen, what do we consider the specimen.

Dr. Baylor (RTI): Are you covering G-2 as well as D-4? G-2 is laboratory testing. It's the short- and long-term storage to ensure specimen integrity. That seems more likely eluate, extraction stability. This I believe is more in the shipping of the specimen.

Dr. Sample: It's just the time frame to the laboratories so we may be jumping ahead.

Dr. Baylor: It seems like we've integrated D-4 and G-2.

Dr. Caplan: Some of the questions do unfortunately.

Dr. Baylor: This would be more than a dry patch for 28 days.

Dr. Sample: If you were to separate out the storage essentially from the time of collection to the time of arrival at the laboratory, which is the way you should interpret D-4, that would be one question. Then we'd get into the stability on the patch and the stability of the eluates, perhaps as G-2.

Dr. Baylor: For urine, they're kind of the sa