- How should I go about vetting the capabilities of a process chemist vs a regular bench scale chemist?
- Are they actually as different as I imagine?
- Where might I find toll manufacturers that have good reputations with small-mid size batches (1-10 kg at first)?
Wednesday, April 3, 2013
Process Wednesday: how to choose a scale-up partner?
From a respected reader, a very interesting set of questions about kilo-scale chemistry:
I'm a relatively new process chemist, but I have some ideas, naturally. (I invite readers with more experience than I to chime in.) I confess that after my very short stint in a large pharma environment, I've spent my time working on the other side of this question, i.e. we're the people trying to get the business of people like my respected reader. So that colors my thoughts about these questions (I'm just trying to air my biases here.)
I've sat here for 30 minutes trying to come up with a good definition, but I should just rely on our mentor-by-literature, Dr. Neal Anderson, who says that "[t]he role of process R&D is to ensure that high-quality material is produced in a timely fashion to fill the needs of developing a compound."
Perhaps I reveal my cognitive biases, but I don't think it's a coincidence that "high quality" is first in Dr. Anderson's definition. I believe that "process chemists" spend much more time as analytical chemists, worrying about quality and specifications than typical bench-scale chemists. While we spend most of our time thinking about the how and the how much, it is the question of how good? that I feel I worry most about. (...because if it's not good enough, you can't sell it!)
All of this to say that there are a variety of means to judge process chemists and contract manufacturing organizations: by their experience levels, by their publication records, patents, etc. It's nice when they've performed large-scale chemistry before (their answer to "What's the largest reaction you've routinely run?"), or had their processes scaled past the kilo laboratory into a plant. On 1 kilogram scale, you can pull off a variety of kludgey tricks (column chromatography, etc.) that you can't really perform on 100 kilogram scale. Questions about their largest reactor size or batch size (and when they used it last!) and their drying capabilities might be helpful in determining whether or not they are used to handling kilogram quantities of material.
But while all of the above is helpful, I believe the question "What are your specifications?" and "What assays do you use?" will come much sooner from an experienced process chemist.* **
(As for finding good toll manufacturers for 1-10 kilogram scale, that's a difficult question. Naturally, I'm going to encourage you to look in the Western world (though I don't doubt there are bargains to be had overseas!). There are, of course, the larger companies -- the AMRIs and the Cambridge Majors. Informex and other similar fine chemical manufacturing conferences are good places to talk to representatives from smaller companies. There are some relevant publications -- I'm thinking of Contract Pharma in particular, here. Here's that recent thread at In the Pipeline about small-scale API manufacture, with a lot of good recommendations.)
Readers, I've blathered on quite a bit. I'm doubtlessly wrong -- please tell me where.
*Naturally, "how much do you need?", "when do you want it?" and "how much can you pay?" are questions that you'll get asked, too.
**We haven't talked about the essential need for a dedicated, well-resourced analytical/quality control department. Another post, maybe.