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Navigating TGA Australia Drug Registration and Compliance · DDReg Knowledge Capsule

• 0:00
  Speaker 1: Imagine spending like a billion dollars in ten whole years
• 0:03
  Speaker 1: developing a miracle.
• 0:04
  Speaker 2: Drug, right, a massive undertaking.
• 0:07
  Speaker 1: Massive, and you successfully navigate the FDA in the US,
• 0:11
  Speaker 1: you get the green light from the EME in Europe,
• 0:15
  Speaker 1: and you are just completely ready to launch in this
• 0:17
  Speaker 1: lucrative new market.
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  Speaker 2: You're popping the champagne.
• 0:20
  Speaker 1: Exactly, and then out of nowhere, your entire rollout is
• 0:24
  Speaker 1: just completely derailed, frozen in its tracks. And why simply
• 0:28
  Speaker 1: because someone on your regulatory team used like the wrong
• 0:31
  Speaker 1: font and structure on a consumer leaflet.
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  Speaker 2: I mean it sounds totally absurd.
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  Speaker 1: It really does, but in the world of Australian drug registration,
• 0:39
  Speaker 1: I mean it actually happens way more often than you'd think.
• 0:42
  Speaker 1: So welcome to DJRA Agnowledge Capsule. Glad to be here today.
• 0:46
  Speaker 1: We are unpacking a comprehensive guide to navigating Australia's Therapeutic
• 0:50
  Speaker 1: Goods Administration or you know the TGA as.
• 0:53
  Speaker 2: We'll call it, right, the TGA.
• 0:54
  Speaker 1: We are looking squarely at their drug registration process today,
• 0:58
  Speaker 1: and I mean whether you are a pharmaceutical executive prepping
• 1:02
  Speaker 1: a massive market entry strategy or maybe a regulatory affairs
• 1:07
  Speaker 1: student mapping out timelines, or you know, just someone who
• 1:09
  Speaker 1: is intensely fascinated by exactly how that life saving medicine
• 1:14
  Speaker 1: actually reaches your local pharmacy.
• 1:16
  Speaker 2: Shelf, because it is fascinating, it really is.
• 1:19
  Speaker 1: So this deep dive is designed specifically for you. Think
• 1:23
  Speaker 1: of this as well, basically your shortcut to understanding a
• 1:26
  Speaker 1: highly unique regulatory maze.
• 1:28
  Speaker 2: Yeah, and to set the baseline here, the Australian regulatory
• 1:32
  Speaker 2: framework under the TGA is actually incredibly.
• 1:34
  Speaker 1: Coherent, really even with the font thing.
• 1:36
  Speaker 2: I know, I know, but it's very logical once you
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  Speaker 2: understand its internal architecture. I mean, it operates with a
• 1:40
  Speaker 2: very high degree of predictability. Okay, and this is a
• 1:43
  Speaker 2: massive but for anyone coming from overseas, it has very
• 1:47
  Speaker 2: distinct jurisdiction specific requirements. You absolutely cannot just take like
• 1:52
  Speaker 2: an FDA submission, slap a new Australian cover page on
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  Speaker 2: it and expect it to just sail through this.
• 1:58
  Speaker 1: The underlying science might be universal.
• 1:59
  Speaker 2: Right, exactly, The science is universal, but the regulatory lens
• 2:04
  Speaker 2: is intensely local.
• 2:06
  Speaker 1: Okay, let's unpack this because before you can even think
• 2:09
  Speaker 1: about submitting a single page of clinical data, you have
• 2:13
  Speaker 1: to know which fundamental regulatory track you belong on in.
• 2:16
  Speaker 2: The first place, right, you have to know where to start.
• 2:18
  Speaker 1: It's the ultimate fork in the road. So when you
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  Speaker 1: look at the AARTG that's the Australian Register of Therapeutic Goods,
• 2:25
  Speaker 1: you're immediately hit with two main classifications. Yes, you have
• 2:28
  Speaker 1: your l entries which stands for listed, in your r entries,
• 2:31
  Speaker 1: which stands for registered. And the difference in the evidentiary
• 2:34
  Speaker 1: burden between these two is just it's staggering.
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  Speaker 2: It really fundamentally comes down to the risk profile. It's
• 2:40
  Speaker 2: about how the TGA handles the burden of proof regarding efficacy.
• 2:45
  Speaker 1: So walk us through the l entries first.
• 2:46
  Speaker 2: Sure, so listed medicines, the l entries are considered lower risk.
• 2:51
  Speaker 2: These are products where the sponsor actually self assesses for
• 2:54
  Speaker 2: quality and safety.
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  Speaker 1: Way self assesses like the Honor system kind of.
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  Speaker 2: Yeah, we are talking about products containing pre approved active ingredients,
• 3:03
  Speaker 2: So complementary medicines, vitamins, sunscreens, things.
• 3:07
  Speaker 1: Like that, Okay, that makes sense.
• 3:09
  Speaker 2: And certain non prescription items. The TGA isn't scrutinizing your
• 3:14
  Speaker 2: clinical trial data before you hit the market for these,
• 3:16
  Speaker 2: they are trusting your self declaration.
• 3:18
  Speaker 1: But they check up on you eventually, right.
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  Speaker 2: It's subject to postmarket audits. But for registered medicines, the
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  Speaker 2: R entries, that is the high risk category, heavy hitters exactly,
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  Speaker 2: prescription medicines, new chemical entities or ncees, biologicals and products
• 3:35
  Speaker 2: seeking new indications.
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  Speaker 1: So for those you can't just self declare.
• 3:39
  Speaker 2: Absolutely not. These require a full, rigorous pre market TGA
• 3:43
  Speaker 2: evaluation and crucially, they want hard evidence of efficacy.
• 3:48
  Speaker 1: You know, I like to think of as like airport security.
• 3:50
  Speaker 2: Oh I like that.
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  Speaker 1: Yeah, So the L pathway the listed goods, that's like
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  Speaker 1: the self declaration express lane. You're carrying harmless items, maybe
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  Speaker 1: some you know, travel sized sunscreen, you declare it and
• 4:01
  Speaker 1: you move through quickly. But the R pathway, the registered goods,
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  Speaker 1: that is the full body scanner. I mean they are
• 4:08
  Speaker 1: searching your luggage, they are swabbing your shoes, and they
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  Speaker 1: want to see literally every single detail of what you
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  Speaker 1: are bringing into the country.
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  Speaker 2: That is a perfect analogy. And just like airport security,
• 4:19
  Speaker 2: if you confidently stride into that self declaration express lane
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  Speaker 2: with the restricted item in your bag.
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  Speaker 1: They don't just politely point you to the other line,
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  Speaker 1: do they.
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  Speaker 2: No, they absolutely do not. They pull you aside, your
• 4:31
  Speaker 2: profile gets flagged, and your journey is delayed indefinitely. Oh wow, Yeah,
• 4:35
  Speaker 2: getting this classification wrong at the very start is a
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  Speaker 2: catastrophic operational.
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  Speaker 1: Error really, just from picking the wrong letter.
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  Speaker 2: Yes, I mean, if you misclassify a product that should
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  Speaker 2: be an R good as an L good or vice versa,
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  Speaker 2: the TGA will just reject the application outright. How it
• 4:52
  Speaker 2: triggers mandatory resubmissions. You lose your spot in the queue
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  Speaker 2: and you potentially invite formal regulatory action.
• 4:58
  Speaker 1: Do you lose time, you lose money.
• 5:00
  Speaker 2: And you hand your competitors a massive market advantage simply
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  Speaker 2: because you misunderstood the fundamental threshold of the AIRTG.
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  Speaker 1: Right. So, let's say we are definitely in that full
• 5:09
  Speaker 1: body scanner lane. We have a complex prescription medicine. It's
• 5:12
  Speaker 1: definitively in our good.
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  Speaker 2: Okay, you're in the R line.
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  Speaker 1: You'd think the path is straightforward from there, But the
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  Speaker 1: TGA actually forces sponsors to choose between multiple evaluation pathways.
• 5:22
  Speaker 2: Right, yeah, they do.
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  Speaker 1: You have to select the correct pathway based on your
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  Speaker 1: specific clinical context and your global approval status. Category one
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  Speaker 1: the standard evaluation that seems to be the default for
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  Speaker 1: anything truly novel.
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  Speaker 2: Yeah. Category one is the heavy lifter. This is the
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  Speaker 2: primary pathway for new chemical entities and medicines with new
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  Speaker 2: indications where there is no comparable overseas approval to.
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  Speaker 1: Rely on, So you're basically starting from scratch with them,
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  Speaker 1: completely from scratch.
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  Speaker 2: Under this pathway, the TGA conducts a full scientific evaluation
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  Speaker 2: of your quality, safety and efficacy data.
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  Speaker 1: And what's the timeline on that?
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  Speaker 2: Well, the TGA advertises a target timeframe for this of
• 6:01
  Speaker 2: two hundred and fifty five working days from acceptance.
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  Speaker 1: Okay, two hundred fifty five working days. It sounds incredibly precise,
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  Speaker 1: you know, almost comforting. It does sound nice on paper, right,
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  Speaker 1: But in practice that clock doesn't tick continuously because when
• 6:14
  Speaker 1: you look at the actual timelines for complex applications, they
• 6:17
  Speaker 1: often stretch out to like eighteen months.
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  Speaker 2: Or more very often. Yes, So what is.
• 6:21
  Speaker 1: Happening internally that balloons a two hundred and fifty five
• 6:24
  Speaker 1: day target into a year and a half long ordeal.
• 6:27
  Speaker 2: It comes down to a mechanism the TGA uses called
• 6:30
  Speaker 2: S thirty one requests.
• 6:31
  Speaker 1: S thirty one requests.
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  Speaker 2: Yeah, so under section thirty one of the Therapeutic Goods Act.
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  Speaker 2: The TGA can issue formal requests for more information or clarification.
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  Speaker 2: And here is the kicker. When the issue in S
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  Speaker 2: thirty one, the two hundred and fifty five day evaluation
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  Speaker 2: clock literally stops.
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  Speaker 1: Wait, it just pauses.
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  Speaker 2: It entirely freezes.
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  Speaker 1: So if you are a sponsor, you might be on
• 6:51
  Speaker 1: day two hundred thinking, you know, you are coasting toward
• 6:54
  Speaker 1: the finish line, and suddenly the TGA hits a pause
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  Speaker 1: button because they found some anomaly in your stability data.
• 7:00
  Speaker 2: That is precisely what happens. And an S thirty one
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  Speaker 2: isn't usually a simple you know, please clarify this sentence
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  Speaker 2: on page four kind of request.
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  Speaker 1: I mean guessing it's a bit more involved.
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  Speaker 2: Oh, definitely. It often involves deep technical queries related to
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  Speaker 2: quality control, manufacturing processes, or even complex statistical modeling in
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  Speaker 2: your clinical trials.
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  Speaker 1: Wow, so the whole company has to pivot to answer this.
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  Speaker 2: Yeah, the internal scramble at a pharmaceutical company when an
• 7:26
  Speaker 2: S thirty one lands is intense. You might have to
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  Speaker 2: pull data from manufacturing sites in three different countries, run
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  Speaker 2: new stability assays, or have your biostatisticians completely recut the
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  Speaker 2: clinical data, and.
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  Speaker 1: The clock just stays pause that whole time.
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  Speaker 2: The clock stays paused until the TGA is fully satisfied
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  Speaker 2: with your response. This is exactly why complex biologicals or
• 7:46
  Speaker 2: fixed dose combinations routinely exceed that idealized timeline.
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  Speaker 1: Okay, so if category one is the heavy lifter, then
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  Speaker 1: category two, the abridged evaluation feels a bit more manageable.
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  Speaker 2: I guess it is a bit narrower.
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  Speaker 1: Yeah, it shares that same two hundred and fifty five
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  Speaker 1: data target, but it's restricted to modifications of already registered medicines.
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  Speaker 1: But the pathways that really jump out to me are
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  Speaker 1: the accelerated options.
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  Speaker 2: Ah yes, Priority review and provisional registration right.
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  Speaker 1: Because these are designed for patients who simply don't have
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  Speaker 1: eighteen months to wait.
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  Speaker 2: Priority review is an incredibly powerful tool. I mean, it
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  Speaker 2: cuts the TGA's target time frame down tow one hundred
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  Speaker 2: and fifty working days. That's a huge difference, it is,
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  Speaker 2: but the threshold to qualify is exceptionally high. Your medicine
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  Speaker 2: must address a serious or life threatening condition.
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  Speaker 1: Okay, that makes sense, and you have to prove.
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  Speaker 2: It offers a substantial clinical improvement over whatever therapies currently
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  Speaker 2: exist in Australia.
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  Speaker 1: So you can't just be like slightly better.
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  Speaker 2: No, absolutely not. You have to represent a major paradigm
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  Speaker 2: shift in treatment.
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  Speaker 1: And what about provisional registration.
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  Speaker 2: Provisional registration aligns more with international models for early access.
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  Speaker 2: It basically offers a time limited registration, typically a one
• 8:57
  Speaker 2: year window, that.
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  Speaker 1: Can be renewed based on what kind of data.
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  Speaker 2: Based on promising but perhaps incomplete clinical data.
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  Speaker 1: So they are essentially saying, look, the early data looks phenomenal.
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  Speaker 1: Patients are dying, so we're going to let you sell
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  Speaker 1: it for a year, but you owe us the final data.
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  Speaker 2: Exactly. You still need robust phase three trial data eventually,
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  Speaker 2: but you are fulfilling mandatory post market commitments to gather
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  Speaker 2: the rest of it while the drug is already out
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  Speaker 2: there in the wild.
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  Speaker 1: Right. So it allows patients to access life saving drugs earlier,
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  Speaker 1: but it places an immense ongoing burden on the sponsor
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  Speaker 1: to rigorously collect and submit that confirmatory data.
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  Speaker 2: Correct, you can't just launch it and forget it.
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  Speaker 1: Okay, I'm with you on the novel pathways and the
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  Speaker 1: expedited pathways. But there is another option, Category three, the
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  Speaker 1: verification pathway.
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  Speaker 2: Yes. Category three.
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  Speaker 1: Now this applies when a drug is already approved by
• 9:47
  Speaker 1: a comparable overseas regulator, right, specifically the USFDA, the EMA
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  Speaker 1: in Europe, Health Canada, or Japan's PMDA.
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  Speaker 2: That's right, those specific agencies.
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  Speaker 1: And the target here is one hundred and seventy five
• 10:00
  Speaker 1: working days. But honestly, I have to ask if the
• 10:03
  Speaker 1: FDAs already spend a year and millions of dollars tearing
• 10:06
  Speaker 1: the drug's data apart and finally gave it the green light.
• 10:09
  Speaker 2: I know where you're going with this.
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  Speaker 1: I mean, why on earth does the PGA need one
• 10:12
  Speaker 1: hundred and seventy five working days? Isn't this just a
• 10:15
  Speaker 1: bureaucratic rubber stamp.
• 10:16
  Speaker 2: It is absolutely not a rubber stamp, and honestly, assuming
• 10:20
  Speaker 2: it is one of the most dangerous, costly mistakes a
• 10:23
  Speaker 2: sponsor can.
• 10:24
  Speaker 1: Make, really because it feels redundant.
• 10:26
  Speaker 2: I get why it feels that way, But the TGA
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  Speaker 2: views its sovereign responsibility to the Australian public very very seriously.
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  Speaker 2: They do not simply accept an overseas decision wholesale.
• 10:37
  Speaker 1: So what are they doing for one hundred and seventy
• 10:38
  Speaker 1: five days? Then?
• 10:39
  Speaker 2: In a Category three verification, the TGA is scrutinizing the
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  Speaker 2: Overseas Regulator's evaluation report, but they are scrutinizing it specifically
• 10:47
  Speaker 2: against the proposed Australian population, local standards of care and
• 10:51
  Speaker 2: local labeling requirements.
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  Speaker 1: Okay, so they aren't rereading the raw clinical data completely
• 10:56
  Speaker 1: from scratch. They are basically auditing the FDA's home work.
• 11:00
  Speaker 2: Yes, they are auditing the f SIZE homework to ensure
• 11:02
  Speaker 2: it applies perfectly to the Australian context. I see, if
• 11:05
  Speaker 2: your proposed indication in Australia differs even slightly from what
• 11:09
  Speaker 2: the FDA approved, Say you want a broader age range
• 11:13
  Speaker 2: or maybe a slightly different dosing regimen.
• 11:15
  Speaker 1: The TGA will catch that.
• 11:16
  Speaker 2: Oh, they will catch it, and they will reject the
• 11:18
  Speaker 2: verification pathway and heavily question your clinical data. They are
• 11:21
  Speaker 2: verifying that the overseas assessment perfectly aligns with Australian clinical realities.
• 11:26
  Speaker 2: It is a rigorous scientific audit, not a passive sign off.
• 11:30
  Speaker 1: That actually makes a lot of sense. They trust the
• 11:33
  Speaker 1: FDA's math, but they're going to make sure the variables
• 11:35
  Speaker 1: apply to their specific equations exactly. So if the TGA
• 11:39
  Speaker 1: is fiercely independent and refuses to just rubber stamp and
• 11:42
  Speaker 1: FDA approval. How do they handle real time global collaborations
• 11:47
  Speaker 1: because there is a major mechanism for this called the
• 11:50
  Speaker 1: excess Consortium.
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  Speaker 2: Yes, the axcess concern.
• 11:53
  Speaker 1: How does egcess actually work without stepping on Australia's sovereign toes?
• 11:57
  Speaker 2: Well, the Excess Consortion is a fascinating piece of regulatory innovation.
• 12:01
  Speaker 2: It is a coalition made up of regulatory agencies from Australia, Canada, Singapore,
• 12:06
  Speaker 2: Switzerland and the UK acting as an associate member post Brexit.
• 12:10
  Speaker 1: Okay, so a fairly tight group.
• 12:12
  Speaker 2: Yeah, And the goal is to conduct joint reviews of
• 12:14
  Speaker 2: new medicines submitted in parallel across these jurisdictions to speed
• 12:18
  Speaker 2: up access and really share the regulatory workload.
• 12:20
  Speaker 1: You know. It feels like a highly efficient international university
• 12:23
  Speaker 1: study group.
• 12:24
  Speaker 2: Study group.
• 12:24
  Speaker 1: Yeah, Like you have five brilliant students and instead of
• 12:27
  Speaker 1: everyone reading the exact same thousand page textbook completely in isolation,
• 12:32
  Speaker 1: they split up the heavy reading and the scientific assessments.
• 12:36
  Speaker 2: Right, divide and conquer exactly.
• 12:38
  Speaker 1: So Switzerland takes the toxicology, Canada looks at the manufacturing
• 12:42
  Speaker 1: Australia dives into the clinical efficacy, they share their notes,
• 12:46
  Speaker 1: they discuss the findings, and I'm guessing this is the
• 12:49
  Speaker 1: crucial part to maintain that sovereignty. Each student still ultimately
• 12:54
  Speaker 1: writes and submits their own independent final paper.
• 12:58
  Speaker 2: That captures the dynamic perfectly. Work sharing under access means
• 13:02
  Speaker 2: the TGA will rely heavily on a scientific assessment conducted
• 13:05
  Speaker 2: by say swissmetic or.
• 13:07
  Speaker 1: Health Canada, which says a ton of time.
• 13:09
  Speaker 2: It prevents massive duplication of effort globally. But the consortium
• 13:14
  Speaker 2: doesn't produce a single binding regulatory decision, right. The TGA
• 13:18
  Speaker 2: still makes its own independent determination on whether to approve
• 13:21
  Speaker 2: the drug for Australia based on that shared assessment.
• 13:24
  Speaker 1: So operationally, what does this actually look like for a sponsor?
• 13:28
  Speaker 1: Because I assume you can't just check a box on
• 13:29
  Speaker 1: a form and say, hey, let's do the access pathway.
• 13:32
  Speaker 2: No, definitely not. I mean, the strategic value is immense
• 13:35
  Speaker 2: because you can massively reduce your total regulatory burden across
• 13:39
  Speaker 2: multiple markets simultaneously.
• 13:41
  Speaker 1: Which is the dream, right, But.
• 13:43
  Speaker 2: It requires meticulous agonizing, presubmission planning agonizing. Truly, you have
• 13:49
  Speaker 2: to submit your dossier to all participating agencies in parallel
• 13:53
  Speaker 2: at the exact same time.
• 13:54
  Speaker 1: Oh wow, that sounds like a logistical nightmare.
• 13:57
  Speaker 2: It is. You have to interact with TGA months in
• 13:59
  Speaker 2: advance to determine if they are going to act as
• 14:02
  Speaker 2: the lead assessor for a particular module or a co assessor.
• 14:05
  Speaker 1: And why does that matter so much?
• 14:07
  Speaker 2: Because that completely dictates the documentation you produce and the
• 14:11
  Speaker 2: specific timelines you are beholden to. I mean, if Canada
• 14:15
  Speaker 2: is the lead on clinical data, you have to ensure
• 14:17
  Speaker 2: your data meets Canadian expectations, knowing the TGA is essentially
• 14:21
  Speaker 2: reading over their shoulder.
• 14:22
  Speaker 1: Okay, yeah, you can't just stumble into the xass pathway.
• 14:26
  Speaker 1: It requires deep global strategic alignment absolutely. So even with
• 14:30
  Speaker 1: a global study group, you still have to pass local.
• 14:32
  Speaker 2: Exams every single time.
• 14:34
  Speaker 1: And this is where so many companies trip up navigating
• 14:37
  Speaker 1: the Australian specifics because even if you utilize global work
• 14:41
  Speaker 1: sharing or you come in with a shiny new FDA approval,
• 14:46
  Speaker 1: your submission will absolutely fail if it doesn't cater to
• 14:49
  Speaker 1: highly localized requirements.
• 14:50
  Speaker 2: Oh without a doubt.
• 14:52
  Speaker 1: So submissions to the TGA use the standard ICCHM for
• 14:55
  Speaker 1: CTD format that's the common technical document used globally. Everyone's
• 15:00
  Speaker 1: speaks that language. But Australia demands strict local layers on
• 15:03
  Speaker 1: top of that, don't they.
• 15:04
  Speaker 2: They do the core science and the CTD is universal,
• 15:07
  Speaker 2: but the application is entirely local. For instance, the product
• 15:11
  Speaker 2: information the PI and the consumer medicine information the CMI
• 15:15
  Speaker 2: leaflets in the box exactly the documents that doctors and
• 15:18
  Speaker 2: patients actually read. These must flawlessly follow the TGA specific templates,
• 15:22
  Speaker 2: style guides, and structural requirements.
• 15:25
  Speaker 1: And earlier we talked about a billion dollar drug being
• 15:27
  Speaker 1: derailed by a formatting error. Are global pharmaceutical companies really
• 15:31
  Speaker 1: messing up something as basic as formatting frequently? Yes.
• 15:36
  Speaker 2: Sponsors often treat the PI and CMI as mere formatting exercises,
• 15:41
  Speaker 2: almost like drafting a marketing burchure at the very end
• 15:43
  Speaker 2: of the process, which an afterthoughts exactly, they assume that
• 15:47
  Speaker 2: if the European leaflet was fine, they can just translate
• 15:50
  Speaker 2: the spelling to Australian English and submit it.
• 15:52
  Speaker 1: But the TGA doesn't like that, not at all.
• 15:55
  Speaker 2: These are foundational regulatory documents, deviating from the TGA's expations
• 16:00
  Speaker 2: for structure, language and content is literally one of the
• 16:04
  Speaker 2: most common sources of deficiency responses and S thirty one.
• 16:08
  Speaker 1: Requests just because of the layout.
• 16:10
  Speaker 2: Yep, it is a totally unforced error driven by regulatory arrogance.
• 16:15
  Speaker 1: It's just wild to think about. You have these brilliant
• 16:17
  Speaker 1: scientists who mapped the human genome, but the application gets
• 16:22
  Speaker 1: stalled because someone didn't use the mandatory heading structure in
• 16:24
  Speaker 1: a word document.
• 16:25
  Speaker 2: It happens all the time.
• 16:27
  Speaker 1: But moving beyond the paperwork, the clinical data extrapolation is
• 16:30
  Speaker 1: where the science actually gets tested.
• 16:32
  Speaker 2: Yes, the extrapolation.
• 16:33
  Speaker 1: Let's say a sponsor runs a massive, wildly successful Phase
• 16:38
  Speaker 1: three clinical trial overseas, great efficacy, incredible safety profile. Why
• 16:44
  Speaker 1: might the TGA flag that pristine clinical data when they
• 16:48
  Speaker 1: try to register the drug in Australia.
• 16:50
  Speaker 2: This touches on an incredibly important aspect of modern pharmacology,
• 16:54
  Speaker 2: demographics and extrapolation. The TGA expects sponsors to account for
• 16:58
  Speaker 2: Australian epidemial and local standards of care.
• 17:01
  Speaker 1: Okay, so who's actually in the trial.
• 17:03
  Speaker 2: Matters exactly If your massive successful clinical trial program didn't
• 17:08
  Speaker 2: include any Australian participants, say it was studied primarily in
• 17:11
  Speaker 2: East Asian or entirely within North American populations. The TGA
• 17:16
  Speaker 2: is not just going to take your word for it
• 17:17
  Speaker 2: that the drug will behave exactly the same way in
• 17:19
  Speaker 2: the Australian demographic.
• 17:21
  Speaker 1: Because you can't just assume a human as a human
• 17:22
  Speaker 1: as a human. When it comes to complex drugs, we're
• 17:24
  Speaker 1: talking about things like genetic markers for drug metabolism. Right.
• 17:27
  Speaker 2: Absolutely, pharmacogenomics play a massive role. Different populations metabolized drugs
• 17:32
  Speaker 2: at different rates, but it's also about environmental factors and comorbidities.
• 17:37
  Speaker 2: For example, Australia has unique epidemiological profiles like incredibly high
• 17:42
  Speaker 2: rates of melanoma and specific skin cancers due to UV exposure.
• 17:46
  Speaker 1: Right the ozone hole and all that exactly.
• 17:48
  Speaker 2: So if you are bringing a new oncology drug to
• 17:51
  Speaker 2: market and your trials didn't account for the baseline health
• 17:55
  Speaker 2: or specific standard of care treatments that Australian patients receive,
• 17:58
  Speaker 2: you have a problem.
• 17:59
  Speaker 1: You can't just gloss over.
• 18:00
  Speaker 2: That, No, you have to provide rigorous scientific justification for
• 18:04
  Speaker 2: extrapolating your overseas safety and efficacy data to the Australian public.
• 18:09
  Speaker 1: And this leads directly into another massive local requirement. The
• 18:13
  Speaker 1: Risk Management Plan or RMP, and specifically the Australian specific
• 18:17
  Speaker 1: annex the ASAA. Yes, while the TGA draws heavily from
• 18:21
  Speaker 1: the European RMP structure, the ASA is entirely bespoke to Australia, right.
• 18:26
  Speaker 2: It is so. The RMP outlines how you will identify,
• 18:29
  Speaker 2: characterize and minimize the risks of your drug once it
• 18:32
  Speaker 2: is in the real world. The ASA adapts that global
• 18:35
  Speaker 2: plan strictly to the Australian context. It has to detail
• 18:39
  Speaker 2: pharmacovigilance activities specific to the Australian healthcare system, local risk
• 18:43
  Speaker 2: minimization measures like maybe specific training programs for Australian doctors,
• 18:48
  Speaker 2: and any post market commitments made directly to the TGA
• 18:52
  Speaker 2: makes sense.
• 18:53
  Speaker 1: We also need to talk about manufacturing, because having a
• 18:56
  Speaker 1: great drug is pretty useless if the TGA doesn't trust
• 18:59
  Speaker 1: the factory making That is a very true. There is
• 19:01
  Speaker 1: a heavy emphasis on GMP good manufacturing practice compliance, and
• 19:06
  Speaker 1: the TGA conducts overseas manufacturing assessments or omes. What happens
• 19:12
  Speaker 1: if a sponsor doesn't take this seriously early.
• 19:14
  Speaker 2: Enough, well, the delays can be catastrophic.
• 19:18
  Speaker 1: Catastrophic.
• 19:18
  Speaker 2: Oh yeah, let's say you are manufacturing your drug in
• 19:21
  Speaker 2: this beautiful, state of the art facility in Switzerland. You
• 19:24
  Speaker 2: might assume the TGA will just not an.
• 19:25
  Speaker 1: Accept it, right, I think so at Switzerland.
• 19:28
  Speaker 2: But if the TGA does not have a mutual recognition
• 19:30
  Speaker 2: agreement covering that specific type of product, they will demand
• 19:33
  Speaker 2: an OMA. This means TGA inspectors either need to comprehensively
• 19:37
  Speaker 2: audit the paperwork of the overseas regulator or literally physically
• 19:42
  Speaker 2: inspect the site themselves to ensure it meets Australian GMP standards.
• 19:46
  Speaker 1: And I can imagine setting up an international factory inspection
• 19:49
  Speaker 1: isn't exactly something you do over a weekend, not at all.
• 19:52
  Speaker 2: It takes months to organize and execute. If you wait
• 19:55
  Speaker 2: until you are submitting your main clinical dossier to initiate
• 19:59
  Speaker 2: the process, you're essentially pausing your own launch.
• 20:03
  Speaker 1: So your clinical data might be completely approved, but you
• 20:06
  Speaker 1: can't launch.
• 20:07
  Speaker 2: Right You won't be legally allowed to supply the drug
• 20:09
  Speaker 2: because the manufacturing site doesn't have TGA clearance. These assessments
• 20:13
  Speaker 2: must be initiated well before you even submit your main dossier.
• 20:17
  Speaker 1: Okay, so let's say the sponsor navigates all of this perfectly.
• 20:20
  Speaker 2: Okay, best case scenario.
• 20:21
  Speaker 1: Right, they nail the ARTG classication, they pick the exact
• 20:24
  Speaker 1: right pathway. Maybe they even ace the ACESS consortium. They
• 20:29
  Speaker 1: format the PI flawlessly, their ASA accounts for local demographics,
• 20:33
  Speaker 1: the GMP clearance is pristine, and they finally get the
• 20:36
  Speaker 1: drug registered. The champagne corks pop.
• 20:39
  Speaker 2: The race is one yeah, not even close.
• 20:42
  Speaker 1: No.
• 20:42
  Speaker 2: No. Getting the drug registered isn't the finish line. It
• 20:46
  Speaker 2: is merely the starting gun for a rigorous, ongoing phase
• 20:49
  Speaker 2: of compliance and pharmacovigilance. Oh right, Registration in the RTG
• 20:54
  Speaker 2: is not a terminal milestone. It opens up a lifelong
• 20:58
  Speaker 2: set of operational obligations.
• 21:00
  Speaker 1: The post approval reality. The timelines for adverse event reporting
• 21:04
  Speaker 1: once you are on the market are incredibly intense.
• 21:07
  Speaker 2: They're very strict.
• 21:08
  Speaker 1: Like, if there is a fatal or life threatening reaction
• 21:10
  Speaker 1: associated with your drug from the Australian market, you have
• 21:14
  Speaker 1: exactly fifteen calendar days to report it to the TGA.
• 21:17
  Speaker 1: That's right, And for other serious unexpected reactions you have
• 21:20
  Speaker 1: thirty calendar days. Managing that kind of data flow across
• 21:23
  Speaker 1: a global company just must be an operational nightmare.
• 21:26
  Speaker 2: It requires immense infrastructure and It is not just about
• 21:29
  Speaker 2: reacting to bad news or waiting for an email to
• 21:32
  Speaker 2: come in. I want you hunting for it exactly. The
• 21:34
  Speaker 2: TGA expects proactive signal detection. If a sponsor is just
• 21:38
  Speaker 2: running a passive system basically waiting for a doctor to
• 21:40
  Speaker 2: call a one eight hundred number with the complaint, they
• 21:43
  Speaker 2: are facing massive regulatory risks. The TGA actively participates in
• 21:48
  Speaker 2: international safety data sharing networks. They are proactively looking for
• 21:52
  Speaker 2: safety signals globally, and they fully expect you, the sponsor,
• 21:57
  Speaker 2: to be doing exactly the same thing and porting those
• 22:00
  Speaker 2: signals back to them.
• 22:02
  Speaker 1: This directly connects to the daily workflow for you, the listener,
• 22:05
  Speaker 1: whether you are managing this process, building the strategy, or
• 22:08
  Speaker 1: just studying it. Because when you look at the most
• 22:11
  Speaker 1: common delays in pitfalls, the biggest enemies in TGA registration
• 22:15
  Speaker 1: aren't unpredictable scientific.
• 22:17
  Speaker 2: Disasters, No, they rarely are.
• 22:19
  Speaker 1: It's not that the drugs suddenly stopped working. The biggest
• 22:22
  Speaker 1: hurdles are almost entirely self inflicted wounds.
• 22:25
  Speaker 2: That is the absolute most critical takeaway here. The science
• 22:29
  Speaker 2: is rarely the reason of submission stalls. It is almost
• 22:32
  Speaker 2: always the strategy and the execution right.
• 22:34
  Speaker 1: It's things like inadequate presubmission planning where sponsors just didn't
• 22:38
  Speaker 1: read the current guidance or didn't engage with the TGA
• 22:41
  Speaker 1: early enough, or.
• 22:42
  Speaker 2: Those GMP clearance gaps.
• 22:43
  Speaker 1: Exactly where a manufacturing site's paperwork just expires mid review
• 22:47
  Speaker 1: and suddenly the whole application holds.
• 22:49
  Speaker 2: And that formatting arrogance we talked.
• 22:50
  Speaker 1: About, yes, ignoring the PI and CMI templates because you
• 22:55
  Speaker 1: thought you knew better. And perhaps most dangerously, it's treating
• 22:59
  Speaker 1: that Australians specific annex the ASA as a static afterthought document.
• 23:04
  Speaker 2: Oh. Absolutely, treating the ASA as a static box sticking
• 23:08
  Speaker 2: exercise is a guaranteed way to encounter regulatory friction. The
• 23:12
  Speaker 2: TGA reviews ASA updates.
• 23:14
  Speaker 1: Constantly, so it's not a one and done.
• 23:16
  Speaker 2: No, it is meant to be a dynamic, living document
• 23:19
  Speaker 2: that evolves as you gather real world safety data from
• 23:22
  Speaker 2: the Australian population. When sponsors fail to integrate it into
• 23:26
  Speaker 2: their ongoing daily pharmacovigilance planning, they face massive roadblocks when
• 23:30
  Speaker 2: they try to renew their registration or add a new
• 23:33
  Speaker 2: indication later on.
• 23:35
  Speaker 1: So if we pull all of this together, the core
• 23:36
  Speaker 1: message of this deep dive is really about respect.
• 23:39
  Speaker 2: Respect.
• 23:39
  Speaker 1: Yes, success in the TGA framework rewards careful preparation, incredibly
• 23:44
  Speaker 1: accurate documentation, and choosing your valuation pathway with a clear,
• 23:48
  Speaker 1: defensible strategic rationale. You just have to respect the sovereign
• 23:51
  Speaker 1: requirements of the Australian system, even if your drug is
• 23:55
  Speaker 1: a blockbuster hit literally everywhere else in the world.
• 23:57
  Speaker 2: Precisely, the entire art architecture of the TGA is design
• 24:01
  Speaker 2: to protect public health first and foremost.
• 24:04
  Speaker 1: Right.
• 24:04
  Speaker 2: And while we've spent this time talking about the mechanics
• 24:07
  Speaker 2: of pathways, S thirty one requests and formatting templates, I
• 24:11
  Speaker 2: want to leave you with a final thought about the
• 24:13
  Speaker 2: tension at the very heart of this system.
• 24:15
  Speaker 1: Okay, what is that?
• 24:16
  Speaker 2: Well, earlier we discussed provisional registration, that pathway that grants
• 24:21
  Speaker 2: one year of early access for patients with unmet life
• 24:25
  Speaker 2: threatening needs while the sponsor continues to gather post market
• 24:29
  Speaker 2: phase three data.
• 24:30
  Speaker 1: Right, and it sounds like a perfect solution, you know,
• 24:32
  Speaker 1: get the drug to the people who need it right now,
• 24:35
  Speaker 1: prove it works entirely later.
• 24:36
  Speaker 2: But consider the profound ethical dilemma it creates for the regulator. Oh,
• 24:41
  Speaker 2: I see what happens to the Australian patients who come
• 24:44
  Speaker 2: to rely on that life saving medication, whose symptoms are
• 24:47
  Speaker 2: successfully managed by it for a year. If the sponsor's
• 24:49
  Speaker 2: post market data ultimately fails to support full registration when
• 24:53
  Speaker 2: that window.
• 24:53
  Speaker 1: Expires, Wow, that's a nightmare scenario.
• 24:57
  Speaker 2: It is the regulator is forced into an agoni position.
• 25:01
  Speaker 2: Do you pull a drug that individuals are relying on
• 25:04
  Speaker 2: or do you permanently approve a drug that officially failed
• 25:07
  Speaker 2: its final evidentiary burden?
• 25:09
  Speaker 1: That is tough.
• 25:09
  Speaker 2: That immense tension balancing early access against the demand for
• 25:13
  Speaker 2: absolute scientific certainty is exactly why the initial evaluation process,
• 25:18
  Speaker 2: regardless of the pathway you take, is so unforgivingly rigorous.
• 25:22
  Speaker 1: That is a heavy lingering question to end on, but
• 25:25
  Speaker 1: a vital one because it really reminds us that behind
• 25:28
  Speaker 1: every common technical document and every formatting template, there are
• 25:32
  Speaker 1: actual patients waiting for answers. It's not just paperwork, it's
• 25:35
  Speaker 1: people's lives at the end of that maze. Truly, Well,
• 25:38
  Speaker 1: thank you for joining us on this deep dive. Keep
• 25:41
  Speaker 1: questioning the systems, keep exploring the mechanisms behind the medicines,
• 25:44
  Speaker 1: and the next time you think about taking a shortcut
• 25:46
  Speaker 1: through that regulatory full body scanner. Remember the alarms you
• 25:50
  Speaker 1: might trigger until next time.