How to integrate Raw Material Variation into QbD Risk Assessment
It’s Not the Development Scientists’ Fault!
As an R&D scientist, I experienced the pressure of tight development timelines. I wanted my verification, qualification or validation lots to pass the first time so we can meet our milestones (= and to get a positive annual performance review).
To achieve this, I tried to eliminate variation by carefully controlling the experiment environment – such as securing a big stash of raw materials from a single lot. Then I relegated the raw material variation worries to my manufacturing colleagues. Ah, My job is done!
You’ve done this too. (Shh…)
We know this comes back to haunt you. Manufacturing environments are full of variations. I should include these variations during our development so I can design a more robust process. And yes, this takes more thought, time and work – which I don’t have.
Unless we change our KPI (key performance indicators) for R&D, this behavior of rushing will not go away. Currently, there is little incentive for the R&D scientist to spend more time on characterization studies – when you are pressured for time.
This is where Quality by Design comes in.
3 months later…
You receive an email from a clinical manufacturing colleague. Qualification lot just failed. They want to talk to the process development person. As the first reaction, where do you point your fingers at? Raw material variation, of course!
Raw material variability
Currently, how do we deal with raw material variability in the biopharmaceutical industry? This was the main theme at Biopharmaceutical Process and Quality Consortium 2015 in Lowell, MA.
During the 2-day summit, speakers shared their challenges and ideas on how we should approach raw material variability on topics such as:
- Challenges of raw material variability in biopharmaceutical industry
- Industry Practices and Path-forward
- Technologies and methodologies of process control
- Process Analytical Technology in the Biopharmaceutical industry
- Quality by Design in the Biopharmaceutical industry
- Continuous bioprocessing infrastructure (Upstream and downstream)
- Systems technology for continuous bioprocessing
- Current practices and progress within the industry
My good friend and colleague, Prof. SK Yoon, was the co-chair host. He invited me to share how we – the QbDWorks community – were approaching raw material variability.
During a coffee break, he confessed that he struggled with securing speakers under the theme of raw material variability. This is surprising. Don’t we all have a story or two on how variation in raw material affected our drug production lots?
It turns out that drug companies aren’t so eager to share their failures with the public. So I suggested we – as a community – start building a public database of failures from raw material variability so that the industry can learn from each other and prevent common mistakes.
We already have a hard time dealing with drug shortages. We should collaborate more. United we stand, divided we fall.
Now let’s go to the presentation.
How to integrate Raw Materials into QbD Risk Assessment
At which stage, do we integrate raw materials variability?
I always emphasize the importance of design space in QbD. What goes in design space becomes high priority and highly visible.
If raw material variation causes my process so much trouble, shouldn’t we integrate the variability earlier – at the development phase?
Here’s the presentation from BPQC 2015. Share your practices on how you deal with raw material variation.
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