Quality by Design (QbD) is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. QbD principles are heavily integrated throughout the ICH Quality Guidances, starting with ICH Q8 on Pharmaceutical Development.
Sponsors of investigational new drugs are encouraged to adopt the following basic approach:
- Define what quality looks like and establish a Quality Target Product Profile (QTTP)
- Define what product attributes ensure product quality and establish Critical Quality Attributes (CQAs)
- Define how you’ll measure those quality attributes and establish an Analytical Target Profile (ATP)
- Define how you’ll manufacture to consistently achieve your quality attributes and establish a Design Space.
QbD done right culminates in a Design Space with...
- The minimum number of variables to control which are necessary to assure drug product quality
- This creates the most economical manufacturing process possible that is well characterized and controllable.
QbD done poorly culminates in a Design Space with...
More than the minimum number of variables to control to assure drug product quality
This creates a manufacturing process with waste and superfluous variables that obfuscate true process understanding and control
The manufacturing platform you choose comes with a default Design Space!
Developers of cell & gene therapies essentially have two choices when it comes to platforms for drug product manufacturing: G-Rex or Mechanized Bioreactors.
A comparison table below shows that virtually identical design spaces, with the exception that Mechanized Bioreactors require strict control over variables that are related to the movement of fluid.
Must Strictly Control [X] to Assure Drug Product Quality | G-Rex | Mechanized Bioreactor |
Number & nature of cells seeded for culture | Yes | Yes |
Reagent Concentration, Volumes, & Temperature | Yes | Yes |
Cell Culture Media Formulation | Yes | Yes |
Length & cycle time of Unit Operation(s) | Yes | Yes |
Hold time between Unit Operation(s) | Yes | Yes |
Cell Culture Environment (temperature, % CO2 & O2, Humidity, etc.) | Yes | Yes |
Media Flow Rate | N/A | Yes |
Cell Culture Vessel Agitation Rate | N/A | Yes |
Sheer Force | N/A | Yes |
Instruments Used (IQ/OQ/PQ and Calibration Procedures) | Yes | Yes |
Formulation Conditions | Yes | Yes |
Implications of Design Space...
It is not hyperbole that the implications of choosing a platform that must or must not strictly control variables related to the movement of fluid is the difference between choosing scalability, flexibility, commercial viability, and company vitality.
...in development
Core Development Criteria | G-Rex | Mechanized Bioreactor |
Can develop design space at small or pilot scale? | Yes | No |
Can time/cost efficiently set up multivariate experiments to understand CQAs & CPPs? | Yes | No |
Can time/cost efficiently determine Proven Acceptable Ranges (PARs) | Yes | No |
Can time/cost efficiently perform comparability studies & drive continuous improvement | Yes | No |
Can time/cost efficiently validate commercial processes | Yes | No |
Can time/cost efficiently drive post-approval product lifecycle management | Yes | No |
...in manufacturing
G-Rex’s simplified design space…
Mechanized Bioreactor’s design space…
It's choice, not chance, that determines your destiny
The G-Rex is the most scalable, flexible, adaptable, versatile, and commercially viable platform for developers of cell & gene therapies. Your success or failure begins with choices you make early. Choose wisely.
