We are organizing this documentation now, and some suppliers have never done these qualifications before, or, they all planned to work them out on-site while installing. Due to CoVid, et al, that won’t happen and we have to organize all of this on our own. We have an internal GMP team (compliance, QA, etc types), and they keep getting their feathers ruffled when my team suggests that we can work these documents out ourselves. We are looking for examples of these for equipment in the extraction, recovery and purification lines, which I think we could then use as outlines. We would then crawl through our equipment screw-by-screw, process-by-process and work it all out. The IQ’s are easy, the DQ a bit more, with the Operational and Process qualifications to be the main headaches. But those seem hard, not impossible. Any links or examples or pointers?
You should totally be able to do this kind of work yourself. It would probably be helpful to snag someone who does this often - so it can get done quickly - but there’s no reason you cannot get there yourself. This is what I have been doing for the better part of a decade - building facilities and then commissioning/qualification. Here are my tips.
A group that does this work and works in hemp and cannabis. Check me out.
Try to remember that commissioning and qualification exists to meet FDA regulations if you are in the states. Here is an overview from the FDA global taskforce.
So DQ - this is honestly the most important part, but if you already have your equipment, its kind of moot. This is just your verification that what you are ordering from a vendor meets your User Requirements. People often skimp on this and then that leads to issues during OQ most of the time. You can legit just take your URS and add a checklist next to it and check things off. If something is not exact, you just explain why it is equivalent or do a change control to update your URS. I’m linking to some Indian places - they get it right on the documentation side, most of the time. URS Template
IQ - is the easiest. You are really just checking that what you thought was going to arrive actually arrived. While collecting the important bits (serial numbers, motor turning directions, drawings of everything, manuals for everything, etc.). You’ll check for nameplate data, electrical + other utilities connections are functioning, all drawings and documentation. That’s it. IQ Template This template is incredibly thorough. You may or may not need this much information - I try to remind myself that you need about 5 pages for every $250k spent on the equipment and utility. So don’t over do it.
OQ - should actually be really easy also. Sometimes the equipment doesn’t work as intended, but its not crazy sauce here. You should know what you are buying the equipment to do (you have a URS/DQ after all) and you should know that it meets these qualifications on paper (you have your IQ). Now you are going to run tests to prove that it can do the things you said it should be able to do. For instance - if you said it should run at 300 RPM with minimal vibration, test for that. If you say it should run at 5gpm - test for that. If you say it should be able to get things down to -55C in 60 minutes, test for that. Give your self some wiggle room when setting up the tests. Is it -55C +/- 1C? Is it 60 minutes +/- 5 minutes? You probably know what you want to see here - and if you don’t, then you probably need to go back to the DQ and have some more conversations about it. Here is an example for a very specific piece of equipment - its helpful to ask the vendor for this (you always add to what they provide…) that way you understand what they thought their equipment was supposed to be capable of doing.
PQ thoughts - check out the guidance from the FDA, its on Process Validation (which is actually the next step…) but it includes all the bits and pieces you need to perform in PQ to make sure that your process is in control and has limited variability. If you follow all the links - you’ll get to all the guidance and a discussion for the reasoning of why you do each part starting with URS.
Its actually a good presentation and the links take you to some really deep discussions of the regulatory understanding.
But really - I’d consider bringing on a professional C/Q team. CAI is great - I’ve worked with them for years. There are others - almost all of them are working during COVID. On-site, traveling, etc. This is what they do.
You sort of have asked for some document examples in a way that seems to imply you want them to be more specific than I have provided here. Just buy the documentation package from your vendor (for a couple thousand bucks usually…don’t pay more!) and call it good. Flesh it out from there.
Hope this helps.
Let us know how it goes!
Thank you for clearly and precisely putting into words the thoughts we have had for a few weeks now. We are not in USA/CAN so there are some things we need to pay more attention to than others. However, everything you said and linked to was like a checklist to read “Yep, Yep, got-it, Yep, need it, Yep.” So, anyone else reading this, this is gold to get started.
Thank you for the templates and examples! Here is one I found for a cryo chiller that we are going to use as an outline for ours and see how it turns out.824-DQ-IQ-OQ-PQ-Protocol-Mowden-rev-0.pdf (411.3 KB)
We should talk, I’ve been on the hunt for a good GMP consultant
And somehow you didn’t think to call me?
GMP is where I got started!
DQs are hard in the cannabis industry at a small-commercial scale. I’ve found this to be the case especially with material of construction and material traceability.
Additional issue at this level is heat transfer fluids, believe it or not. Basically, at higher temperatures most if not all of the heating circulator manufacturers specify a toxic heat transfer fluid that won’t be acceptable for incidental product contact as required somewhere in ICH.
I need to ask this question off the bat.
Are you looking to qualify to Pharma (CFR 210/211) or Dietary Supplement (CFR 111) or Food grade (CFR 110)?
The obvious problem you might face is equipment compliance to 316SS contract wetting parts for Pharma compared to 304SS acceptable to dietary/food.
Which territory are you producing for? If Europe then requirements for Pharma might be critical…
I love that work that this community does. Any way I can help, just let me know.
We’re in Latin America and going for the full-pharma, local and then eventually EU, so preparing for both.
I cannot tell you how many times we’ve discussed which line can be 304, 316, 316L, contact critical points, etc. And then scheduling which certified welder works where… Yeah, Pharma GMP is a challenge.
For our chillers we are using pure ethanol. And that we had to argue to allow to be industrial grade, not pharma… And the chillers are in another room, so not even air is the same.
Materials are a pain. We have to sand down and repaint our grinder stand because they don’t like the enamel paint.
Traceability is actually one area where we aren’t too concerned… We have a full ERP system (like Oracle/SAP) and experienced people on the team, so… We know implementing it is the daily struggle, but right now we have good resources thrown at traceability that will sort it out. Plus we don’t have to track by the individual plant down here, Batches rule all.
Very interested to know if you have had any luck with finding suitable 21 CFR Part 11 system support or is the QA team taking a practical approach to the computerized system risk approach?
It has been a roller-coaster choosing the IT, but we have and the proof will be in the pudding… in a few months. We are installing a fully integrated Enterprise Resource Planning system with some customized bells and whistles. But, an ERP system is a great segue into CFR 21 & GMP Certification. You have accounting, inventory, HR, maintenance, training, CRM, etc that are all interconnected and thus contain many control points. If you take a manufacturing model that most industries use (make it when they order it) then you can setup your Bill of Materials to control everything you do. So, a client orders 10,000 bottles of tincture and that whole process begins the traceability. Does the Warehouse Inventory module say we have 10,000 bottles, 498L MCT oil, 1.2L 80% Distillate, 0.8L Peppermint oil in-stock? And they are only in-stock if: They have been approved through the Supplier Module after all the Assessment work the Procurement Team and QA did and signed off by the Warehouse Manager, with the eDocs and Scanned docs all stored and eSigned (which not only date stamps, but can include a picture and GPS coordinates with SMS verification for security), after QC has matched our internal HPLC results with the official 3rd party results for anything needing a COA or Quarantine Control to be entered into the system and Inventory. Then the system is also a stop-check for label requirements and Stability Testing and the like. ONLY THEN will the system spit-out a work-order to then go make it. And that is after we’ve extracted (which has it’s own rules similar to above) and purified and and and…
Basically, a good ERP system by design is an interconnected one-thing-is-connected-to-everything. If one link is missing, it’s not like the chain is broken, it never existed because it can’t without that link. So that in and of itself offers the platform for traceability and control that makes Pharma GMP happy. Now adjust and customize for the cannabis industry, add a barcode scanner here and there, have extra eDocs created and eSigned and build your system. Then, CFR 21 validation is honestly just a hack-a-thon by your QA team. “Does clicking here allow anyone to do something we don’t want? Compliance/Non-Compliance/ Non-Compliance Number, Responsible Person, Action Taken, Signed, Dated” For every Critical Point. And we are all used to having different Access Rights and buttons shading out and all that, so building the rules around who can do what is integrated right there at Login/Password.
That is a long way of saying that a unified ERP system is my choice to comply with CFR 21 and the intricacies of the cannabis industry. Presently I think most people are choosing a ‘normal’ GMP system like InstantGMP! and Vulcan mind-melding it with a METRC system AND THEN ALSO getting Quickbooks, ZoHo Inventory, eSignature software, SalesForce, etc etc. AND THEN ALSO having to validate each and every one of those.
What makes those multi-software choices easier is that you probably have legacy system in place that you want to continue to use somehow. So you piece-meal different systems together and all that while working every day. With ERP system implementation, you semi-sorta-gotta do it all-in, even if that means shutting down or completely rebuilding certain parts. But that in-and-of-itself is what CFR 21 wants you to show. So…
Take a look at this simple list: GxP Module - TotalLab
If thinking about how to do that with multiple IT systems, it looks daunting. But when it is all inside one-system, a lot of those concerns are dealt with already.
Looks like your team has given this aspect of the buildout solid consideration. Glad to see the mention of product stability testing data. Have you seen some interesting results from the stability testing evaluations?
There you go, poking the weak spots…
Trying to figure the Stability Testing part out is very difficult. Different Zones I to IVb, Internal process stability tests, general batch testing… yeah, lots of those issues to work through. We haven’t actually begun producing yet, so, a lot is theoretical. I’m still trying to decide which product to start this all with, and how we will apply that to each successive product we develop. Fun stuff.
Yes and no, you really need a system to be GAMP5 compliant if you’re going to use it as your main QA Hold system. That does mainly just entail QA validation of clicks and functions, but it also requires time stamps for everything, audit trail for every user login and click and additional validation if it is attached to any other data acquiring hardware (scales, etc)
The last pharma company I was at was making $100MM per year and just barely beginning to break through into GAMP5 stuff.
You guys seem to be really thorough in your approach and clearly you’re not scared to invest capital if you’ve gotten an ERP system!
One bridge to cross at a time… But, again, I think you’d be surprised at what they can do.
And there are many ERP systems out there besides SAP/Oracle. Go with a smaller one that is for a manufacturing industry, then pay for customization. I calculated that Year 1 implementation would be roughly 20% more cost than METRC + GMP off-the-shelfs, but by Year 2 it drops to 1/3rd the cost since the licensing fees are normal; i.e. they don’t have the ‘green tax’ added to everything in this industry.
I am really enjoying the direction this thread is heading in, looking forward to seeing this project and discussion developing. I know you mentioned you are in Latin America and projects on the continent are very interesting. Have always felt it a pity that Argentina is the only PIC/S member country in South America, but hoping Columbia, Uruguay, Brazil and others will come along as medical regulations harmonize globally.
Besides those already contributing to this thread I suspect the following @elchemy @CollectiveObjective @Dirteagle @broken_glassware @GreenMachine_Consult and @JimmyIRL would make for great contributors
Excelent thread and worth a million bucks litteraly.
I worked with several extraction companies in Eu but it seemed that a pharma GMP for API from BDS is is really still a rarity in EU besides GW and Bedrocan.( People were looking st me like wtf is this guy complicatiing things were cooking oil!) Cosmetics are more frequent and food grade is still top dog.
Seems GMP will be booming in EU if CBD goes back to the narcotics division, but for now everyone is making food grade, natural cosmetics and such
Im an agronomic conusltant for cannabis GAP and GACP for cannabis cultivaiton, and also a part of a small analytics company(4 pharmaguys and me an agronomist) who do CBX+ TERPs and Residual solvents in different cannabis relat3d edibles, extraxts cosmetics.
Let me just say its the wild wild west over here, never saw a residual free extract ( IPA <50ppm, or EtoH >5000ppm, beside GMP materials ofc), and the products are selling in stores like hot cakes. One sample had 100k ppm IPA i mean shame on you producer!!
Not to mention claims of 99.7% isolate test is more of a fullspectrum first pass slopy cromatography ( this was stipulated because of 0.03thc, 0.09 cbg and some 0.04 cbc to top of the cbdv in a supposed excelent first grade isolate)
Not to mention market claimed best price FS oil, thats just isolate and MCT and a collorant…
What I want to say is that GMP should be a guidance tool to anyone who wants to be really safe and sure that they arent causing a small % of the users harm. My friends say Generate More Paper, and justify your work well. I say its been a great experience working with GMP people and it fills me with hope that its reaching cannabis industries around the world.
At least my gammy’s will buy some clean product from the farmacy now, since she has been vary of my home kitchen :))
I thank you for your information it has been a great review of the past endeavors with serious companies
Sorry to drop in if you need some help getting the biomass into GMP i could try and help…
Otherwise imma sit quiet and let the pharma guys talk