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Cake day: June 15th, 2023

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  • I work in pharma, regularly writing and filing things with the FDA (and other agencies), and this has been a topic of conversation at work. The good news for people is that the EMA is still a thing in the EU. So, at least the large pharma companies (like the one I work for), are likely to not really change much about their quality control/processes/etc. because we will still need to conform to the EMA guidelines which are typically in line with the current FDA (sometimes more strict, sometimes less so). The real quality concern would be smaller companies that only file for products in the US. They would only need to meet whatever new FDA guidelines come into effect (if they even do, changing stuff like GMP guidance is extremely complicated and time consuming) since the US is their only market.


  • That style does work well for presentations

    I honestly prefer presentations to writing for the reasons you pointed out. I have never been too nervous when it comes to public speaking, and I feel much more able to convey my point through a more conversational style. However, my presentation style (specifically slide design) has had to change a lot over the course of my career.

    When I was in grad school, my preferred method of presentation was to have a slide with a single graph/image/diagram on it and then verbally talk through all the things I wanted to convey for that slide. It allowed me tons of flexibility, kept the slides from becoming cluttered and distracting, and created a more conversational atmosphere as people felt more empowered to ask questions as I was going (this also helps keep the audience engaged).

    However, as I moved into a professional setting, I had a mentor sit me down and tell me how great my presentations were, but they were not really effective in a corporate setting like this one (global company, split across timezones, etc). The simple reason being that the slides I was making were being shared to others who couldn’t make it to my presentation and a good chunk of the actual audience of the presentation only ever got to see the slides, without the benefit of my talking to help them understand. So, this has led me to move more towards including text on my slides. I basically have to ask myself if there is enough information on this slide to understand things without my explaining it, but without anything extra to make it confusing.

    Since the pandemic, I have also had to change things up a bit to make presentations more amenable to presenting via Teams/Zoom. This means things like removing videos, complex animation, or any audio. It just doesn’t work reliably enough through screen sharing and if you can find a way around it, then it makes everybody’s life easier.

    Speaking of tangents, this has been a long one, but I care a lot about effective communication and specifically presentations. So many people are so bad at giving a good presentation, and I find it frustrating personally, when I have to sit through so many.


  • I actually agree with you about math education and math texts. It is really bad at conveying understanding and my math-heavy courses were the toughest for me (E&M in grad school was awful). Too often math textbooks simply present things and leave the proof as an exercise for the reader, or they will lean too far the other way and present formal proofs for everything. Either way is not helpful for developing an intuitive understanding of what is going on.

    The things that helped me develop communication skills the most were simply doing it a lot followed by having some good mentors that I found to be good communicators. My grad school advisor was great at communicating physics and one of my early bosses in industry was an excellent presenter. So, I would often bounce either writing or slides off of them for feedback.


  • I am guilty of writing walls of text as comments, but I try to stick to my lane. You can see my most recent wall of text about freeze dryers as an example. There are a few things that I think need to come together to create a good, high-effort post:

    • Passion - If you don’t care, you aren’t going to spend the time to write about something
    • Knowledge - For some topics this may be less required, but I tend to create walls of text about technical issues. I have a PhD in physics, so that gives me a pretty good foundation of knowledge to work from in this regard
    • Writing Ability - You need to be able to write effectively to make a wall of text worthwhile. This is a skill that gets better the more you do it.

    The other thing I tend to do when writing a high-effort post is I actually proofread it before making it. I try to cut out unneeded tangents, reword things that might be confusing, or supplement things that aren’t motivated enough.

    For me personally, this doesn’t take me too long to do since I have been writing and presenting about extremely technical topics for about two decades at this point. Like I mentioned above, informative writing is a skill that gets better with practice. So, doing it regularly as a significant part of my job as well as providing feedback to others on their writing/presentations, has provided me with tons of practice to improve these things.

    If you want some formal guidance on scientific writing/presentations specifically, two books I have found informative (mostly on presentations) have been:

    • The Craft of Scientific Presentations by Michael Alley
    • slide:ology - The Art and Science of Creating Great Presentations by Nancy Duarte

  • The products I work on are mostly monoclonal antibodies (and the occasional gene therapy product mixed in). So, the types of diseases they are used to treat vary. To be honest, I work on the process/formulation side of the development pipleline and the actual clinical treatment part is pretty much inconsequential to what I do. Some of the past programs I have worked on include treatments for asthma, eczema, multiple myeloma, breast cancer, MS, hemophilia, and tons of others that I don’t remember. Often, when dealing with antibodies, the same medicine can be effective for multiple indications.

    The finished vials, post-lyophilization, sealing, labeling, and packaging, are sent to infusion clinics. There, clinicians will add water to the vials to reconstitute the drugs and then administer them to patients via IV (usually).


  • Watching TC do a video about something I do professionally has been a bit of a trip. For context, I work with freeze dryers (we call them lyophilizers) in pharmaceuticals rather than foods. I help design the lyophilization cycles for biologics and gene therapy products that get preserved through freeze drying. Until this video, I had no idea that people used these instruments for at-home food preservation (which is kind of insane imo).

    The instruments that I work with are typically a much larger version of the bench-scale machine that he is using (usually one of the LyoStar line). However, I have used smaller, bench-scale units as well for some quick and dirty work. I included some pictures at the end behind a spoiler tag. Happy to answer any questions people have.

    Some differences in how I use lyophilizers in a scientific setting as opposed to a home-use food setting:

    • Typically, we only lyo products that are already filled in vials as opposed to a full tray like he’s done.
    • We don’t pre-freeze our products before they go into the lyophilizer. Instead we refrigerate the shelf that the vials are sitting on to freeze the contents before we proceed to the drying steps.
    • Speaking of the shelves, in our instrument, the shelves can move up and down. This is used to compress the vials after the cycle is completely done, fully seating the vial stoppers and sealing them before we open up the main door.
    • Also speaking about stoppering the vials, we typically allow some nitrogen into the chamber before sealing up the vials, at a pressure moderately less than atmospheric pressure. This helps keep the vial sealed until it is properly crimped with a seal.
    • When it comes to drying, we do it in two stages. The primary drying step is when our product is kept cold, but put under vacuum. This removes most of the water, but not enough for our purposes. The secondary drying step is when the product is heated while the vacuum is maintained. This removes the rest of the water. We typically shoot for a residual moisture of <1% for a good cycle.
    • He talks about how long the process takes. I have worked on processes that take from 1-5 days. Typically, the lyophilizer is limited with how much liquid can be removed per unit time. This limit is determined by the geometry of the vent that connects the main chamber with your vials, and the chamber containing the condenser. Also, if you try to dry too quickly, it can damage the product you are trying to preserve.
    • He has some discussion at the end about the end of the cycle and the progress bar. What the instrument is doing is comparing the vapor pressure in the chamber using two different sensors. One of those is sensitive to the vapor pressure of water vapor, and the other is not. So, when things are fully dried out, those two are going to read the same pressure. While drying is still occurring, the sensor that detects water vapor will read a higher pressure. So, the instrument will continue to extend drying until those two pressures are the same.
    Some Pictures

    Benchtop lyophilizer that I have experience using. You can see some vials lined up inside the door. I have never used the bottle connections hanging off the side:

    One of the trays of vials that is loaded before going into the lyophilizer. The vials that are partially stoppered in the middle of the tray actually contain the drug. All the vials without stoppers are empty and simply there to help hold things in place as well as distribute heat predictably through the tray. The stoppered vials in the corners are there to help distribute the weight as the shelves compress to fully seat the stoppers.

    Here are a small number of vials that I ran on a benchtop unit without any spacer vials or the tray. I would never do this for any reason other than to take a picture like this. This is a good view of what a partially stoppered vial looks like. It allows a path for water vapor to escape out the top of the vial.

    Finally, here is a vial post-lyophilization. The liquid has turned into a solid, white cake at the bottom of the vial. This is because most lyophilization formulations include sugars that provide structure for the cake and keep it porous. The sugars provide protection against freeze/thaw stress for the molecule of interest as well. The porosity of the cake allows for quick and easy reconstitution by adding water, usually in <30 seconds or so.


  • The fraud surrounding Alzheimer’s research continues… Not too long ago the fraud was related to amyloid (archive version). That article was even written by the same author and features many of the same investigators.

    I work in Pharma R&D (on the manufacturing side) and the company I work for has run trials for Alzheimer’s products based on research that has since been found to be fraudulent. As a published scientist myself, I would like to think that this level of manipulation and fabrication is the exception rather than the rule. However, I do think it is worth asking at this point what it is about Alzheimer’s research in particular that has led to this being so prevalent and, more importantly, so impactful. Basically, how did it go so far before anything was caught?

    I suspect at least part of the answer is due to the large influx of money into the field. Researchers were tripping over themselves to earn those grants and then, once they had them, produce results to keep them. I am not in academia, so I don’t have great insight into the NIH, NIA or their processes, but this should be a wake up call to put up a certain amount of guard rails.