A Tool for Calculating Test Article Requirements for Toxicology Studies 🧪 — Transcript

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1. 0:00Hey everyone, today we are going to talk about,
2. 0:03how you calculate how much test article or drug or API
3. 0:07that you need for your tox study or your tox program as a whole.
4. 0:12So, typically, I used to use Excel spreadsheets to do this,
5. 0:16it was very tedious, it made my own formulas,
6. 0:20I had, a spreadsheet that I got from Pfizer that had a macro in
7. 0:23it, that that was a little bit easier, it had dropdowns,
8. 0:26But it's just tedious overall,
9. 0:28and so what I did was built this tool that you can basically plug
10. 0:32and play. And you can plug in all the things that you need,
11. 0:36and it will give you either a tutorial, a total for the study that
12. 0:38you need, or an entire total for the program that you need.
13. 0:41So, just a little bit of background about test article requirements for studies,
14. 0:45when it comes to non-clinical development, the biggest rate limiting factor,
15. 0:49by far, is having your test article ready.
16. 0:53In order to have your test article ready,
17. 0:55you need to know how much test article or API you need to support
18. 0:59your tox study or your tox programs.
19. 1:02If you don't know how much you need, then you don't know how much
20. 1:04to make, and then that just puts CMC back a little bit further.
21. 1:08And so if you are running, for example,
22. 1:11a small molecule oncology oral program you
23. 1:16want to run your non-GLP and your GLP studies and get it done within
24. 1:2018 months, which is aggressive but can be doable,
25. 1:24you need to make sure that when you're ready to initiate each tox study
26. 1:27that you have the amount of drug that you need to be able to
27. 1:29initiate those and that you have the right amount of drug that you need.
28. 1:33So, when we go into GLP studies,
29. 1:36we obviously need GMP material or clinical grade material versus
30. 1:40the non-GLP studies which can be a little bit dirtier,
31. 1:43more research grade. So if you're doing different batches of material,
32. 1:47then you need to understand how much API you need in each of those
33. 1:51batches, or if you're doing one full batch,
34. 1:53how much you need in one full batch. So this tool,
35. 1:56it's actually pretty awesome. I built it, I'm super happy with it,
36. 1:59and it basically breaks everything down for you.
37. 2:03So we'll go through it here,
38. 2:14Because they're a lot smaller, volumes,
39. 2:16and so the, the amount that you could potentially waste if you,
40. 2:21for example, a drop gets out, then that's,
41. 2:24makes a pretty big impact on the total. So,
42. 2:26put in your overage, 20 to 30 is recommended.
43. 2:29And then this entire tool goes through by species.
44. 2:31So you have the mouse, you have the associated weight for the males and
45. 2:34females on the mouse, and then the dose volume that is typically associated with
46. 2:38each of the species. These are the dose volumes are also adjustable
47. 2:43within each of the things so within each species you have different types of
48. 2:47studies so if you're gonna run a single dose mouse a seven-day what-have-you
49. 2:51and then you can also add a custom study at the end you can
50. 2:54add a couple of them so that if you're running a three-day or five-day
51. 2:58you can customize it. We also have the rat,
52. 3:01we have the rabbit, the dog, the mini pig,
53. 3:04and the monkey. So we have all the species.
54. 3:07So let's just say we're gonna run a small molecule oral program.
55. 3:12We're gonna run a 14-day non-GLP and we're gonna run a 28-day
56. 3:17GLP in the rat and the dog.
57. 3:20So what we do is come down here, we'll click on the 14 day,
58. 3:23see what it pops up. You can change your dose volume if you want
59. 3:27to, and then you can update your doses depending on what your doses are
60. 3:30gonna be. You know, let's make this,
61. 3:3350 for the purposes of showing you the tool.
62. 3:37Number of doses, 14 days, and it's a daily oral dose,
63. 3:4010 males and 10 females per group.
64. 3:42You can add recovery animals in here as well for the 14-day non-GLP,
65. 3:47we'll keep them out. Dose groups,
66. 3:49exclude and control, so how many treated groups you have,
67. 3:52and then your body weight. If you need to override the body weight,
68. 3:55for example, if you're doing an obese rat study or something,
69. 3:57you can adjust the body weight as well. And then we're gonna click on
70. 4:0028-day rat. Same thing,
71. 4:04we'll say that we had different doses,
72. 4:08we said a little bit of toxicity in the non-GOP,
73. 4:11so we're going to put the doses a little bit lower. Dose volume is
74. 4:14still at 10, 28 doses per animal.
75. 4:17Now that we're in the GLP, we're gonna have five males and five female
76. 4:22recovery animals. We're still gonna have three dose groups.
77. 4:25Just a note as well, if you have more than three treated groups,
78. 4:28you just add the button and you'll get another dose group
79. 4:33in here to be able to add that. And if you put it back
80. 4:35down, it'll go back down to three. So it goes up to five dose
81. 4:38groups. And then if we want to go and do a 14-day dog,
82. 4:43Let's say, you know, we're going to do the same,
83. 4:45we'll do 130, 10,
84. 4:4814 doses per animal, three males,
85. 4:50three females, no recovery groups or no resistance.
86. 4:53Yep, no recovery animals. And then three dose groups within the GLP dog.
87. 4:58Let's say we had some toxicity. So we're going to go down now.
88. 5:01We'll say we'll do 50 and we'll do 25.
89. 5:0428 days,
90. 5:07so four males and four females is a GLP study.
91. 5:10So we're going to have two males and females per recovery group.
92. 5:14And we're gonna do three dose groups. Body weight looks good.
93. 5:17So once you're all set with this. You know what,
94. 5:20let's add on a Latin square safety farm study as well,
95. 5:24because that's always important. Five dose animals per group because we're going to have
96. 5:28the TK dose. We're going to do one male and one female per group.
97. 5:33Three dose groups, excluding the control.
98. 5:35That all looks good. So we're going to go all the way down here.
99. 5:38We're going to hit calculate. This is the beauty of the tool.
100. 5:43You have your total for the program.
101. 5:45So this includes everything, all five studies.
102. 5:48What you would need for that if you were going to make one batch
103. 5:51and then it breaks it down in between each study.
104. 5:53So how much you would need for the 14 day, the 28 day and
105. 5:57then the CV study. So if you were making different batches,
106. 6:00if you were making your research batch for the 14 days,
107. 6:02then you would have that. Then you can calculate what you would need for
108. 6:05the GLP studies. You can also see here,
109. 6:08it has the compliance text, non-GLP,
110. 6:11GLP, and so then at the bottom you can see that it has a
111. 6:13summary API by study and it breaks it all down into each one and
112. 6:17then puts the total here. So if we wanted to do a custom study,
113. 6:21say we're going to add a full 14 day or,
114. 6:25you know, let's say we're going to add, yeah, 14 day monkey study,
115. 6:28just for kicks. We can add, click add.
116. 6:31It'll add as many custom studies as you want.
117. 6:34Click on it and it'll pop up and it's the same thing as before.
118. 6:37You can adjust the doses, per animal. So how many doses that you're going
119. 6:40to do at 14 dose, adjust the dose volume.
120. 6:44You can adjust the doses themselves, the dose levels,
121. 6:46and then the animals per group and how many groups,
122. 6:49and then you can even adjust if it's going to be a GOP or
123. 6:51a non-GOP. And then if you calculate,
124. 6:54hit calculate again, you can see that it added the custom study in.
125. 6:58And the great thing here is that you can put in 14 day.
126. 7:02Non-GOP NHP. And what it'll do is it'll
127. 7:06update it here and show you exactly which one that is.
128. 7:09So you can keep everything together. And then if you want to,
129. 7:11you could always print this page as well, call it a day,
130. 7:14send it out. so like I said, this is a great tool. Use it,
131. 7:17bookmark it, share it. it's really awesome.
132. 7:19I will link it, to the video so that you know where to go
133. 7:23to, to get it. And if you need any help or anything,
134. 7:28Non-Clinical Academy, that's where my online courses are.
135. 7:31We go to a bigger deep dive into this stuff within the course.
136. 7:35And Toxic Strategy is where all my consulting information is.
137. 7:38But LinkedIn as well. feel free to reach out anytime.
138. 7:41you can DM me anything you need, but I hope you guys enjoy this
139. 7:45tool. It's definitely made it a world easier for myself.
140. 7:47and we'll have more to come. Thanks.