If you are applying QbD for Vaccines, this presentation will be helpful. Dr. Hyun Sung Kim presented a summary of A-VAX case study at KOBIA 2014. Dr. HS Kim (HS from hereon) is the Quality Director at Green Cross, Korea. I share my notes with you.
As with any case study, I’d like to remind the QbD community to use it as an example and not as a reference manual. Many of us will agree that there are different and better ways to conduct risk assessments and execute design space studies. Yet these fictitious case studies are still valuable to the QbD community because real examples are unavailable due to confidentiality.
So Let’s dive into the A-VAX case study
HS began with an interesting question that many folks may struggle with when conducting QbD risk assessment.
Q) How do we distinguish CQA versus CPP? Isn’t this like a Chicken or an Egg problem?
Here is how HS explained it:
My response would be similar, CQA’s are usually what operators check for on the SOP’s.
CPP’s are what the operators control using knobs or procedures.
In other words, CQA’s are results and CPP’s are control factors. When using transfer function, Y=f(X), CQA’s are Y’s and CPP’s are X’s. Please check out this Video (Framework for Scientists).
With the definitions clarified, the presentation covered:
- Process Validation
- Survey of CPP and CQA
- TPP, CQA and PRA
- Control Strategy
with an emphasis on the Control Strategy section.
Since the workshop was sponsored by Ministry of Food Drug and Safety (Korean FDA), some slides are in Korean. If you have any questions, please let me know.
A-VAX follows the typical QbD framework:
Target Product Profile – Critical Quality Attributes – Critical Process Parameters – Risk Assessment – Design Space – Control Strategy – Lifecycle Management
The presentation emphasized the Control Strategy section so I’ll share a few highlights.
Please refer to the original slides for CQA, CPP and Design Space section.
The process of AVAX is as follows:
Here is how the team derived the Process Parameters. Fishbone or Ishikawa is a good tool as a first step. I do recommend using a detailed process map for a higher resolution map of process parameters so that you can specifically associate process parameters with each process. This is a crucial step before design space studies.
As a QbD facilitator, the QTPP-CQA-CPP gathering process is very time consuming. To solve this pain, I developed the Lean QbD Risk Assessment process, Lean QbD software has templates of QTPP-CQA-CPP. In addition process parameters are already associated with each process.
For A-VAX, Here are the Target Product Profiles that leads to QTPP. I do appreciate the humor and creativity of the authors (i.e. horrificus-confirmed cooties).
The results of risk assessment is shown below. Please note that the team iterated risk assessment over time (Initial – Triage 1 – Triage 2). This is commendable.
However, RPN’s (Risk Priority Number) remain unchanged.
RPN (risk priority number) should have changed over the iterations, if design space studies were done. As the team gathered more information, risk profiles are likely to change.
Following is a summary of the CQA-CPP relationship for Drug Substance.
And this is the CQA – CPP relationship table for the Drug Product.
The diagram below further explains the overview of the QbD framework for A-VAX. Again the authors mention the “iterative” approach to risk assessment as more data become available. RPN’s don’t change but the number of “critical” attributes has decreased.
Here is how the authors outline Control Strategy for A-VAX.
This is a summary of drug substances, intermediate conjugated bulks, final drug product and their specifications.
The control strategy covers both the product and the process.
And finally the outcome of the Control Strategy, including the Tests associated with each CQA is presented below. This is important yet commonly overlooked. Have a test associated with the control strategy.
Summary: A-VAX Control Strategy for both Product and Process
A-Vax study details the overall process of how they applied the QbD framework for a vaccine product. Please read the full document and the presentation for further information.
The Full A-VAX Case Study:
Check out the A-VAX template for the Lean QbD – the tool that helps streamline QbD risk assessment and control strategy. If you’d like to be informed, please subscribe to our email below – or better yet, contact me.