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Question Based Development to Quality by Design to Continued Process
Verification
Ajaz S. Hussain, Ph.D.
Insight Advice & Solutions LLCNational Institute for Pharmaceutical
in a state of control (the validated state) during
commercial manufacture…PV Guidance 2011
An ongoing program to collect and analyze product and process data that relate to product quality must be established (§ 211.180(e)). The data collected should include relevant process trends and quality of incoming materials or components, in-process material, and finished products. The data should be statistically trended and reviewed by trained personnel. The information collected should verify that the quality attributes are being appropriately controlled throughout the process.
• 14. What is the rationale for selecting this manufacturing process for the drug product?
• 15. What is the potential risk of each process step to impact the drug product CQAs and how is the risk level justified?
• 16. For each of the potentially high risk manufacturing unit operations:
• a) What input material attributes and process parameters were selected for study and what are the justifications for the selection?
• b) What process development studies were conducted? Provide a summary table listing batch size, process parameter ranges, equipment type and estimated use of capacity.
• c) What process parameters and material attributes were identified as critical and how do they impact the drug product CQAs?
• d) How were the process parameters adjusted across lab, pilot/registration and commercial scale? What are the justifications for any changes?
• 17. If applicable, what online/at-line/in-line monitoring technologies are proposed for routine commercial production that allows for real-time process monitoring and control? Provide a summary of how each technology was developed.
Using Process Capability To Ensure Pharmaceutical Product Qualityby Lawrence X. Yu, Daniel Y. Peng, Robert Lionberger, Alex Viehmann and Karthik IyerThis article introduces the definition and calculation of process capability, illustrates their use in the pharmaceutical industry, and describes the relationship of process capability with production batch failure rate. The use of process capability in product development, process scale up and qualification, and commercial production is also described.
French Revolution, we look to a future that will bring us
everything or nothing, depending
on the public trust”
The Nation Needs a Comprehensive Pharmaceutical Engineering Education and Research System
“A recent re-examination by the US Food and Drug Administration of the current pharmaceutical quality decision-making system raised fundamental questions about its efficiency and its continuing effectiveness to address the increasing complexity of pharmaceutical systems.”
“….low success rate for identifying the root cause of deviations and out-of-specification observations as well as the predominant focus on end-product testing—often based on an inadequate statistical consideration of inherent variability and static process conditions— which, some argue, evolved to facilitate regulatory document expectations for “process validation.”
“Generics is all about file first and figure out later” State
of QbD Implementation Report to FDA June 2010, Ted Fuhr, Mckinsey& Company
“It would also mean the FDA had no power to deny tentative
approval to an application that clearly could never win final approval -
an applicant could state in its ANDA that it planned to manufacture a generic drug in an outhouse behind the applicant's house using a child's chemistry set.“ U.S. District Judge Beryl Howell (March 11, 2015)
“The key to good decision‐making is not knowledge, it is understanding. We are swimming in the former. We are desperately lacking in the latter” ‐ Malcolm Gladwell
What will it take to ensure that your QbD program delivers
(a) confidence in the CQA’s?
(b) provides a ‘stable’ and ‘in control’ process?
(c) reduces the risk of development failure?
(d) reduce risk of GMP noncompliance?
To remain true to ‘first do no harm’ we, the legitimate pharmaceutical community, have inherited, and accepted, a culture of quality that demands that our intention, our awareness and our skills deliver ‘quality by design’ with continued vigilance to detect, correct and to prevent errors that have caused, or have the potential to cause, harm to the patients we serve. We also recognize the limitations of our pharmacovigilance.
We must more clearly recognize that CAPA is not ‘continual improvement’ and that we must strengthen our culture of quality to deliver continual improvement in our ability to assure quality, reduce costs and enhance confidence in what we do. Ajaz S. Hussain, Ph.D., Mumbai, 24 March 2015
9. Into a blind darkness they enter who follow after the Ignorance, they as if into a greater darkness who devote themselves to the Knowledge alone.
10. Other, verily, it is said, is that which comes by the Knowledge, other that which comes by the Ignorance; this is the lore we have received from the wise who revealed That to our understanding.
11. He who knows That as both in one, the Knowledge and the Ignorance, by the Ignorance crosses beyond death and by the Knowledge enjoys Immortality
Isha Upanishad: Knowledge and Ignorance, Verses 9 – 11
VIDYA AND AVIDYA
VOLUME 17 THE COMPLETE WORKS OF SRI AUROBINDO (2003)
The problem of reductionism: - it works for small, not for big steps - it misses the whole - it misses the meaning - in the end, it undercuts itself.Systems approach……
Note. I have take a different point of view from that of Dharm P. S. Bhawuk, Science of Culture and Culture of Science: Worldview and Choice of Conceptual Models & Methodology. The Social Engineer. Vol. 11, No. 2, July, 2008.
Practicing to improve (awareness of) our intentions is our wisdom tradition, and is reflected in our laws, in US, India and around the globe…