This document discusses uncertainty in pharmaceutical manufacturing and regulation. It notes that the current US pharmaceutical regulatory system underestimates the inherent complexity of making drugs. Recurring errors, shortages and warning letters serve as reminders that some of our assumptions are incorrect. Pharmaceutical regulatory science has evolved from chaos to continual improvement. The culture of an organization, with an emphasis on quality, anticipation of problems rather than reaction, and measurement to enable anticipation, is important to quality outcomes. Bias and "cognitive dissonance" can prevent admitting mistakes, while "anticipatory thinking" and understanding why certain approaches are taken can help progress quality.

1. Uncertainty
Management in
Chaos: New Prior
Knowledge

2. "Your beliefs are cause
maps that you impose on
the world, after which you
'see' what you have already
imposed." ~ Karl E. Weick
1
2
3
Quality, Cost and Time :: 1, 2 and 3
Current Good Practices, Systems, Management & “Warp speed”

3. Pharmaceutical
Engineering
2005

4. “New” Prior
Knowledge

5. ~ 50 %
Approved but
not marketed?
2019

7. In its 19th century origin, the current US pharmaceutical
regulatory system underestimates the inherent complexity in
making pharmaceutical products. Recurring errors, shortages,
and warning letters serve as a “red flag,” reminding us that
some assumptions we hold as “truths to be self-evident” are
not. From an oxymoron to a discipline, pharmaceutical
regulatory science is unfolding a fascinating journey from
chaos to continual improvement. Ajaz Hussain , CPhI 2019.

8. “It’s a culture first and foremost in a particular manufacturing site
devoted to quality. It’s about the people, it's about anticipating
challenges rather than reacting to them when they occur, it's about
putting in place a model that measures quality in a way that allows you to
anticipate problems rather than identifying them after the fact and having
to respond to them.” Dr. Throckmorton, CDER/FDA, 15 September 2020,

12. HTTPS://WWW.PHARMACEUTICALONLINE.COM/DOC/HOW-TO-BREAK-THE-PHARMACEUTICAL-SIGMA-BARRIER-LIKE-AMGEN-0001

16. The culture of Pharmaceutical Quality: Connecting the Dots. Biopharma Asia 34-38. Issue September/October 2015
The culture of Pharmaceutical Quality Management System. Biopharma Asia November/December 2015
The culture of Pharmaceutical Quality: Personnel Development. Biopharma Asia March/April 2016
Compliance Or Adherence? How To Approach cGMP Regulations In The 21st Century? Pharmaceutical Online. Guest Column | September
22, 2016. https://www.pharmaceuticalonline.com/doc/compliance-or-adherence-how-to-approach-cgmp-regulations-in-the-st-century-0001

19. "Your beliefs are cause
maps that you impose on
the world, after which you
'see' what you have already
imposed." ~ Karl E. Weick

20. Points of view: Human
biases are pervasive and
may have been
evolutionarily selected

21. Lecture @ IMT Mines Albi 14 November 2018

22. Advanced
Pharmaceutical
Engineering

23. “Criticalmass”ofleaderswhocanforeseethe
consequences.

24. A journey to
error prevention
[4]
Leaving the comfort-zone of “FDA Approved and validated so all is good” to detecting,
correcting and preventing errors to arrive at the door of continual improvement.

25. In France Merck AG
Wins Lawsuit on
Levothyroxine Saga
[5]
[6]
[7]
[8]
[9]
[10]
“The Butterfly Effect”

26. Sociotechnical
systems
[11].

27. Clinical &
Social
Pharmacology
“canary in the
coal mine!” [12].

28. Learning from
“but…”
New Prior Knowledge [16]
“Cognitive Dissonance” that prevents admitting
wrongs [17]
“Anticipatory thinking” and sensemaking [18]
Why we do what we do? [19]

29. Previous
notes (2019)
[20]
[21]
[22]

30. Previous notes
(2020)
[23].

31. References and links to related information

32. References and links to related information

33. References and links to related information