This document discusses knowledge management strategies for empowering operations and ensuring compliance. It begins with definitions of knowledge and an overview of how technical knowledge management works, including storyboarding, video capture, project organization, and publishing libraries and standard operating procedures. The agenda then covers setting up single-use and stainless steel bioreactors, differences in setup times, and how the single-use ecosystem changes personnel and logistics. Compliance data on inspection observations is presented showing that standard operating procedures and training are frequently cited issues. A case study demonstrates minimizing process variability using a knowledge management platform. Lessons learned questions how to ensure standard operating procedures are fully understood and how resources like experts, mentoring, and on-the-job training can improve

1. Empowering Operations and Perfecting Compliance
Technical Knowledge Management

2. Bespoken
Instructions

3. Learning pathway
Knowledge definition*
The psychological result of perception,
learning and reasoning
• Something you have observed
• That you have interpreted and stored
• That you can apply to future situations
*Webster

4. How we work
Storyboard
• Transfer the full actual instructions into a synopsis of operations
• Customer project team approval
Capture
• Video capture on-site
• Selection of key steps
Project
• Organize the procedure relevant information
• Project Mediabooks
Libraries
• Released Mediabooks
• SOPs, Specimens, Warnings & Symbols Publishing
• Simplifying update and revision exercise

5. Agenda
1.
Single Use Ecosystem
2.
Shop floor Set Up & Operations
3.
Compliance
4.
Case Study
5.
Lessons Learnt and Conclusion

6. Single Use Last Decade Journey
Application focussed

7. Supply chain and packaging
expertise
Leachables Extractables

8. Single Use Last Decade Journey
Single Use in production are pre-fabricated Units

9. On-The-Job: Successful model…
IKEA
could never achieve such a lowcost position if
customers did not agree to take on some of the
tasks usually performed by manufacturers and
retailers, such as delivering furniture to their
homes and assembling it.
Jérôme Barthélemy: (Excerpts) FALL 2006 MIT SLOAN
MANAGEMENT REVIEW
Single Use is changing personnel daily life

10. Instructions at point-of-use
Yet know-how and knowledge do not fully
stand out from SOPs

11. Agenda
1.
Single Use Ecosystem
2.
Shop floor Set Up & Operations
3.
Compliance
4.
Case Study
5.
Lessons Learnt and Conclusion

12. Set up a 50L Bioreactor
S.U versus 50L Bio preparation S.S

13. 50L Bio Single Use - courtesy of Crucell B.V.

14. CIP - SIP
50L Bio Stainless Steel

15. Benchmark activities with Mediabooks
• Single Use activities
• Stainless Steel
– Deliver at point of use,
– Gaskets/ Seals
– Unpacking and check
– Valves & Air Filters connections
– Installation
– Sensors
– Inflation
– SIP CIP
– Sensors and fluids
connections
– Run
– Run

16. Single-Use
Stainless Steel
1000L Bioreators Set up comparison time wise
Courtesy of Sartorius Stedim biotech

17. The Last Mile:
•
Activities Changed
•
Skill Sets Changed
•
Logistic Changed
•
Risks Changed
•
Labor more complex
Successfull Single Use implementation requires to cope with
a Shopfloor ECOSYSTEM change

18. Agenda
1.
Single Use Ecosystem
2.
Shop floor Set Up & Operations
3.
Compliance
4.
Case Study
5.
Lessons Learnt and Conclusion

19. Compliance
CDER Enforcement Actions
Top 20 483s FY 2012
44% SOP related
11% Training related 1200
1000
275
800
258
237
286
228
258
239
600
Biologics
400
649
572
498
2007
2008
200
594
746
758
787
2010
2011
2012
0
2006
2009
2006 – 2012 : number of 483’s issued
Drugs

20. Top 20 Inspectional Observations
Training related 483 citations :
DRUGS
FY
2006
2007
2008
2009
2010
2011
2012
2012
DRUGS
FY
2006
483 FY citations analysis
rank freq rank freq rank freq rank freq rank freq rank rank Freq
freq
Freq
483 FY citations analysis
rank
freq
Training-operations, GMPs, written procedures21 CFR 211.25(a)
8 59.00
65.00
8
21
60.008 79.00 5 92.00 8 65.00
Training-operations, GMPs, written procedures 9 60.00CFR 211.25(a) 8 48.00 109 49.00
GMP Training Frequency
21 CFR 211.25(a)
23 38.00CFR18 41.00 24 27.00 27 31.00 16 48.00 18 49.00 13 54.00
54.00
21
211.25(a)
13
23 38.00
GMP Training Frequency
Training, Education, Experience overall
21 CFR 211.25(a)
62 16.00CFR48 19.00 108 8.00 31 27.00 20 44.00 25 38.00 19 44.00
44.00
19
21
211.25(a)
62 16.00
Training, Education, Experience overall
97
21 108 8.00
77 13.00
Supervisor Training/Education/Experience
Supervisor Training/Education/Experience 21 CFR 211.25(b)
77 13.00CFR 211.25(b)118 5.00 124 6.00 81 12.00 76 14.00 97 9.00
9.00
60.00
60.00
100.00
48.00
49.00
171.00
141.00163.00
163.00
# # Total Training top 20
Total Training citations citations top 20
4.75% 11.52%
versus citations top 20
versus sum sum citations top 20
4.75%
8.22%
4.97%
3.93%
8.73%11.31%
11.31%
it Procedures not in writing, fully followed
21 CFR 211.22(d)
1 127.00
1 150.00
1 112.00
1 157.00
1 165.00 1 201.00 1 169.00
Absence of Three citations are now in the top 20 7showing improvement6is89.00
Written Procedures
21 CFR 211.100(a)
5 83.00
62.00
7 52.00
6 75.00
2 128.00
required 3 116.00
Written procedures not established/followed 21 CFR 211.67(b) translate 10 52.00
43.00
9 64.00
80.00
How to ensure the training 10 54.00 into less9 deviation and 7more 7 89.00 7 73.00
SOPs not followed / documented
21 CFR
6 82.00
5 72.00
5 58.00
4 81.00
2 115.00 6 89.00 10 64.00
efficient processes? 211.100(b)
346.00
336.00
265.00
377.00
449.00
507.00
422.00
# Total SOPs out of top 10 citations
«Retrain is not doing better»
42.51%
43.75%
43.09%
45.53%
46.72%
46.99%
44.70%
FDA White Paper: March 2011
citations How To Reduce Human Error By Managing Human Factors White Paper
TOP 10
814
768
615
828
961
1079 944.00
Top 20
1264
1216
966
1247
1485
1616
1441

21. Top 10 Inspectional Observations –
SOP related 483 citations
2006
Procedures not in
21 CFR 211.22(d)
Responsibilities of
1 127
writing/ fully followed quality control unit
Absence of Written
Production and
21 CFR 211.100(a)
5
83
Process Controls
Procedures
Written procedures
21 CFR 211.67(b)
Cleaning and
not established/
10 54
Maintenance
followed
Production and
SOPs not followed /
21 CFR 211.100(b)
6
82
Process Controls
documented
346
# Total SOPs related out of top 10 citations
42.51%
•
•
2007
2008
2009
2010
2011
2012
1
150
1
112
1
157
1
165
1
201 1 169
7
62
7
52
6
75
6
89
2
128 3 116
10
52
9
43
9
64
7
80
7
89
5
72
5
58
4
81
2
115
6
89 10 64
336
43.75%
265
43.09%
377
45.53%
449
46.72%
SOPs: can they kill 2 birds …..Documentation and Training?
Yet the instruction is of essence and must be documented.
How to ensure the instructions pertained in SOPs are fully
understood and performed on a daily basis?
Augment ownership of operations?
507
46.99%
7
73
422
44.70%

22. Agenda
1.
Single Use Ecosystem
2.
Shop floor Set Up & Operations
3.
Compliance
4.
Case Study
5.
Lessons Learnt and Conclusion

23. Minimizing variability in process operations
using knowledge management platform
Herman van Herk
Scientist USP
Vaccine Process and Analytical Development
Archimedesweg 4-6
PO Box 2048
2301 CA Leiden
The Netherlands
Tel: +31 (0)71 519 9197
Email: hvanher@its.jnj.com

24. Agenda
1.
Single Use Ecosystem
2.
Shop floor Set Up & Operations
3.
Compliance
4.
Case Study
5.
Lessons Learnt and Conclusion

25. Lessons Learnt and Questions
1. SOPs :
Must be followed
Sole training material?
2. Classrooms – Hands-on
Training efficacy? Lectures or Visual
3. Resources:
– Experts / Trainers availability
– Mentoring & Learn-by-peers
– On-the-Job

26. • Manage Technical Assets differently
Flip the class room
Back to the roots

27. The Edtech experience illustration
http://youtu.be/gM95HHI4gLk?t=5m40s
Salman Khan’s Talk at TED.com (excerpts)

28. Conclusion
Compliance & Cost control
First Hand Reference Tutorials
Efficient documentation process
Less deviations
Expandable
Coordination
Irrespective of language
“Watch it and do it”
Empower Personnel: Move from “certainty” to “routine dexterity”

29. Thank you
Expandable and language free