Friday, May 18, 2018

Ask CJ: What prior approvals are required for lab work at your company?

From the inbox, a good safety-related question:
We recently had a minor chemical exposure incident here at Random Chemicals Inc., and the safety analysis made its way up to corporate EHS. This prompted some reviews of our lab practices and the powers that be are considering implementation of some kind of approval process for any "new" synthesis procedure. 
They are allowing us to have some feedback into how that would look, so thats nice, but of course the worry is that a lot of red tape just for starting what could be a simple reaction. Do chemists at other companies have similar approval processes? What does it look like when you want to start something new in the lab, just order the chemicals and do it, or does someone have to sign off?  
I suspect that there are bands of chemicals and types of reactions (and sizes) and someone who plans on running a 20 L fluorination probably gets a lot more attention and needs a lot more upper-management approval than someone who is planning on running a 50 mL reaction with some nBuLi. All the Dow items that came post-Sangji seem to have indicated that (for example) large companies require a lot more written procedures and warnings and checks than, say, a typical academic synthesis laboratory.

Readers, what do you think? 


  1. Having worked at a smallish cGMP CRO/CMO, we had a lot of things that we were NOT allowed to use at all and you couldn't even find it on site, not even in our analytical labs, like hexane, benzene, diethyl ether, chloroform, etc., and other things we wanted to avoid, like DCM, NMP, DMAc, DMF, LAH, BuLi, etc. Approval for "bad" solvents and "bad" reagents required proof of exhaustive alternative experiments to our EHS officer of any synthesis in 22L reactors or larger, as well as our strategy for the worst case scenario.

    Conversely, I moved to Global Corporate Chemicals Inc. and we use everything under the sun in our processes except benzene, which was and still is totally shocking to me since corporate are ALWAYS harping about safety. Even new processes we receive from R&D almost always employ diethyl ether and/or hexane and we in manufacturing keep telling them to stop using those two solvents but they refuse to listen. The reason why they refuse? It's because R&D is run by an arm of the company who is physically located at corporate HQ and what they say is the final word and they want new products completed by yesterday by any means possible, whereas manufacturing is run by an on-site arm of the company and we have very little say in R&D/process development since we are not at HQ. It is only a matter of time before the "I told you so" catches us I feel, especially since our house vacuum runs above the autoignition temperature of ether. We usually stick to air venturis for ether, hexane, and halogenated filtrations, but it only takes one person to forget or ignore that SOP.

  2. My last synthesis lab job (within the last couple years, so not ancient history), we had policies with criteria which would trigger a formal safety review. IIRC, criteria included scale of reaction (anything run in a 5 L flask required a team review, we may have had a requirement that over 1 L required chemist and supervisor or another chemist to review) and hazard of reagents. Hazard was triggered by chemicals on some OSHA, EPA, or other lists, anything listed as e.g. a teratogen, mutagen, or sensitizer, and some chemicals that were added due to an incident (POCl3, for instance, as for whatever reason we seemed to have had a cluster on incidents resulting from the reaction leaving the flask during workup, and we decided that everyone would review the proper quench procedure every time.) For the GMP lab, a safety review was part of the batch procedures.

    Although we did have policies (and occasional edicts), more importantly, we tried to have a culture where the chemists knew that what they were doing was potentially hazardous, that they had training to conduct procedures safely and to understand appropriate use of engineering, PPE, and policy controls, and that they were included in developing the safety and chemical hygiene program. It was a small medium company where there was a LOT of pressure to keep work moving, but I really felt good about our safety committee, and the very first words I ever heard my former boss say were along the lines of "I want us to operate safely." Believe that everyone wants everyone else to go home safely, and make that part of your everyday job, and it's not onerous.

    My group (6-8 chemists)would generally meet Monday mornings to talk about the week, and talking about hazards was always a topic, and there would generally often be safety reviews identified or results from reviews fed back to the team. Also, while "new" procedures are possibly deserving of special attention, we'd try to remind ourselves that tried-and-true processes could go wrong, too.

    I've heard stories of e.g. grad students having to chase down PI's to get a sign off before starting a reaction, and that's not the way to do it. Certainly not in a professional environment.

    1. Should have also said, if someone felt a safety review was appropriate even if it didn't meet formal criteria, we'd do it.

  3. When I was working in new product development and process research, there were certain classes of reactions that had safety guidelines that people had to sign on to before doing these. If you wanted to do something new, you needed approval from your manager and an EHS review where you went through possible hazards, and controls. Also, all reactions needed to be listed on a white-board in the front of the lab, along with SDSs of all the reagents being used in a magazine rack next to it (if they existed). We also had a pretty good safety culture, involving "behavior-based safety" where a coworker would observe you doing labwork for a short period of time with a checklist of things to look out for. They could often make suggestions that I hadn't considered.

  4. The line "this experiment is similar to a past one and requires no further review" was pretty much a standard header in my lab notebook at a past big company job, and was largely true. In most cases, we were making minor tweaks to processes that had already been beaten to death, and trying a genuinely new experiment did require a hazard review.

    What I'm seeing more of recently is a push to require a review of the business need for lab work. At smaller companies, it's been a problem that salespeople try to circumvent the process to request lab work, and ask me for a "favor" that ends up taking my time away from a problem more important to the business.

    1. Off-books work is a frustrating aspect of working at small companies, agreed.

      "Did you talk to the boss"
      "um, no"

  5. I do not feel the company I work for is large, it is not even in the C&EN top 50 chemical companies. However, the site I work at has around 400 employees. I think it is more the site, than the company that sets the mood for how safety is implemented. The site I work at was designed to run dangerous materials and that culture has remained over the decades and company take overs. Safety is taken seriously but the list of things we cannot use is short and changes based on the dollars that is offered to make it. I do not mean to say that that the company has a mercenary attitude, it is just that if you can do something safely you can probably handle other unsafe things.
    I have heard at other sites in the company they must jump large hurdles with EH&S just to get what we would find to be mundane materials. I have not seen that to be the case while I have been here. For me it seems like we are in an academic setting, but I am in R&D so my experience may not be normal.

  6. Large corporation here, r&d site in Europe. Every experiment non-identical to previous ones = safety assessment countersigned by any other member of the team (up to 30 min work). If it involves highly toxic chemicals, or if non standard safety measures have to be taken, the risk assessment has to be approved by the manager (up to one day of delay) or even by safety officer (1-3 days).

  7. Where I am (UK pharma site) only a few chemicals need special permission, including cyanide, Cr(VI), benzene, DCE, extreme sensitizers like p-phenylenediamine. I think some chemicals are banned outright but the only one I can think of right now is CCl4. There's much more oversight for the scaleup team than med chemists, of course.

  8. I work at mid-size petrochemicals company. We have numerous SOPs for standard lab activities (using syringes, metal alkyls, hot oil baths, inert-gas/vacuum lines, etc.), but to cover new reactions and new chemicals we have an online management of change system for laboratory work. This is meant to cover scale up of reactions, entirely new reactions, and creation and purchase of new chemicals. So, if you are doing something that fits this criteria (and there's a whole policy around what does and doesn't trigger this type of review), you fill out the online form. Depending on the risk/hazard assessment it gets sent for various levels of approval (technically qualified individual, management, EH&S). Approval from all required levels has to be obtained before you can proceed with the lab work or procurement of new chemicals.

    A lot of the chemistry we do is very similar on a day to day basis, so we aren't stuck in these, and they get through pretty quick when you do have to do these reviews. Also, we can group numerous similar chemicals together. So, if I'm planning on making several iterations of the same thing but with various functional groups we can write one management of change for all of them. Given what we'd have to do at our PSM facilities, this is rather straight forward and not as arduous as you might think.