What is Lean Authoring? Why Lean Authoring? Advantages of Lean Authoring How to apply Lean Authoring Lean Authoring General Lean Authoring Module 3 Real life examples

1. Lean authoring of Module 3
Joyce van Gerven, Regulatory Affairs Manager,
Qdossier B.V., The Netherlands
Lodewijk Venhuizen, Senior Regulatory Affairs
Manager, Crucell Switzerland AG, Switzerland

2. Content
©20140523 2Lean authoring of Module 3
What is Lean Authoring?
•Why Lean Authoring?
•Advantages of Lean Authoring
How to apply Lean Authoring
Lean Authoring General
Lean Authoring Module 3
Real life examples
Questions

3. What is Lean Authoring?

4. Definition of Lean Authoring
©20140523 4Lean authoring of Module 3
Split Content / Context
Naming of documents
Content of documents
Headers and footers

5. Content carrier
(e.g. document)
General aspects 1
Understand the difference
between documenting
information for GMP
versus regulatory dossier
• Better to give a summary of
a validation report than the
report itself that included
references to GMP
documents, like named SOPs
and internal Monographs
Separate content from
context of use
Location of
document
in dossier
or DMS
Cross references
to other content
Branding
within a
content
carrier
Context of use

6. Content & Context - carrot and potato recipes
Manufacturers
Competent
authoritiesDrug
products
Production
process
(active)
substances

7. Content & Context - every item documented
Manufacturers
Competent
authoritiesDrug
products
Production
process
(active)
substances

8. Content & Context – cross references
Manufacturers
Competent
authoritiesDrug
products
Production
process
(active)
substances

9. Content & Context – cross references
Manufacturers
Competent
authoritiesDrug
products
Production
process
(active)
substances

10. Content & Context - Named product in named
country for named submission type
Manufacturers
Competent
authoritiesDrug
products
Production
process
(active)
substances
If you are not the intended recipient of this disk, you
are hereby notified that any disclosure, copying,
distribution or reliance upon the contents of
this disk is strictly prohibited
eCTD on
<INN>
Sequence <…..>
Disk <x> of <n>
<Application Number>
<Type of submission>
Marketing Authorisation Number(s):
<Company logo>
Applicant:
Product Name:
Date Sent:
For technical issues contact
<………@................................>

11. Content & Context - Named product in named
country for named submission type
Manufacturers
Competent
authoritiesDrug
products
Production
process
(active)
substances
If you are not the intended recipient of this disk, you
are hereby notified that any disclosure, copying,
distribution or reliance upon the contents of
this disk is strictly prohibited
eCTD on
<INN>
Sequence <…..>
Disk <x> of <n>
<Application Number>
<Type of submission>
Marketing Authorisation Number(s):
<Company logo>
Applicant:
Product Name:
Date Sent:
For technical issues contact
<………@................................>
If you are not the intended recipient of this disk, you
are hereby notified that any disclosure, copying,
distribution or reliance upon the contents of
this disk is strictly prohibited
eCTD on
<INN>
Sequence <…..>
Disk <x> of <n>
<Application Number>
<Type of submission>
Marketing Authorisation Number(s):
<Company logo>
Applicant:
Product Name:
Date Sent:
For technical issues contact
<………@................................>

12. Lean Authoring?
©20140523 12Lean authoring of Module 3
What do we see in dossiers
• Company names and Logos
• Branding
• Same information at multiple locations
Where to improve
• Mind information that is likely to change over time
• Mind information that is likely to be different between
countries
Definition of detailed / multiple choice
• How lean should you write

13. Why Lean Authoring?
©20140523 13Lean authoring of Module 3
Resulting in poor:
•Retrieval of documents
•Impedes traceability
Resulting in redundant:
•Writing
•Review
•Approval
•Publishing
•Hyperlinking
•QC

14. Advantages of Lean Authoring
©20140523 14Lean authoring of Module 3
Document can be reused across countries
Documents can be reused across products
Improves effective communication and
review process
Improves consistency in messages
•Within and across documents
•Within and across products
•Within and across countries

15. Advantages of Lean Authoring
©20140523 15Lean authoring of Module 3
Eases future updates of documents
Eases future preparation of submissions
Eases retrieval of information in a document
repository and submission
Reduces the chance of rejection by
authorities
Less variations
• Manufacturer’s only described in S2.1 and P3.1
• Manufacturing process not mentioning
manufacturers
• Analytical procedures not mentioning manufacturers

16. How to apply Lean Authoring

17. What is important for dossier preparation?
©20140523 17Lean authoring of Module 3
Which marketing license to be obtained
Which claims to be supported
Which documents to be used
• Content
• Identification
• Format
• Header
• Cross references
How to communicate?
• Verbally
• Written
• eMail
• Meeting minutes
• Project plans
• Document management systems (trackability, traceability)

18. ©20140523 Lean authoring of Module 3 18
from Qdossier

19. ©20140523 Lean authoring of Module 3 19
from Qdossier

20. ©20140523 Lean authoring of Module 3 20
Dossier Plan Lifecycle

21. Lean Authoring

22. Lean Authoring
©20140523 22Lean authoring of Module 3
Provide information only once in a dossier
 only in one document
Provide it at the correct (or most
appropriate) location
Be concise
Use the same terms; prevent use of
synonyms
Refer to the data provided elsewhere
rather than repeat

23. Lean Authoring – Rules
Consistency
©20140523 23Lean authoring of Module 3
All information in the dossier needs to be
consistent
•The less repetition, the smaller the risk for
inconsistencies
Re-use documents across products to
•Reduce the risk of inconsistencies and
compliance issues
•Increase the possibility for grouping and work
sharing across products (only EU)

24. Lean authoring – Rules
Cross references
©20140523 24Lean authoring of Module 3
Cross-references to other products in time
independent documents to justify the
quality, safety or efficacy.
• Not advisable, don’t do it
• It puts your product at risk when something unforeseen
happens to the referenced product

25. Lean authoring – General
©20140523 25Lean authoring of Module 3
Apply default Word numbering:
• 4.4 Lyophilisation and stabilisation
Instead of
3.2.S.2.2.4.4 Lyophilisation and stabilisation
• Figure 1 Manufacturing process flow diagram
Instead of
Figure 3.2.S.2.2-1 Manufacturing process flow diagram
• Apply default Word References
• Tables and figures references in text using cross-references

26. Lean authoring – Text
©20140523 26Lean authoring of Module 3
Words that should be avoided:
• In order
• Assume
• New/Old
• Possibly
• Please
What else should be avoided
• Long sentences
• Sentences starting with
• With this variation/submission …
• …we (the company) shows
• We (the company) would like to …

27. Lean authoring Module 3
Real life examples

28. Pro
Easy to navigate
when using eCTD
.xml or NeeS ToC
Only small document
to revise for variation
Better reusability of
documents between
products
Con
Difficult to navigate
when using Windows
Explorer
Large document to
revise for variation 
all content might be
reviewed again
©20140523 Lean authoring of Module 3 28
Pros and cons of high document granularity

29. Granularity and appearance of documents
©20140523 29Lean authoring of Module 3
Per document
•Corresponding to the content plan
One doc per section 
Multiple docs per section 

30. Single vs. Multiple Granularity
©20140523 30Lean authoring of Module 3
3.2.P.8.1 Stability Summary and Conclusion
Lorem ipsum dolor sit amet, consectetuer adipiscing elit, sed
diam nonummy nibh euismod tincidunt ut laoreet dolore magna
aliquam erat volutpat. Ut wisi enim ad minim veniam, quis
nostrud exerci tation ullamcorper suscipit lobortis nisl ut aliquip
ex ea commodo consequat. Duis autem vel eum iriure dolor in
hendrerit in vulputate velit esse molestie consequat, vel illum
dolore eu feugiat nulla facilisis at vero eros et accumsan et iusto
odio dignissim qui
3.2.P.8.2 Post-Approval Stability Protocol and Stability
Commitment
Nam liber tempor cum soluta nobis eleifend option congue nihil
imperdiet doming id quod mazim placerat facer possim assum.
Typi non habent claritatem insitam; est usus legentis in iis qui
facit eorum claritatem. Investigationes demonstraverunt lectores
legere me lius quod ii legunt saepius. Claritas est etiam processus
dynamicus, qui sequitur mutationem consuetudium lectorum.
Mirum est notare quam littera gothica, quam nunc putamus
parum claram, anteposuerit litterarum formas humanitatis per
seacula quarta decima et quinta decima. Eodem modo typi, qui
nunc nobis videntur parum clari, fiant sollemnes in futurum.
3.2.P.8.3 Stability Data
Lorem ipsum dolor sit amet, consectetuer adipiscing elit, sed
diam nonummy nibh euismod tincidunt ut laoreet dolore magna
aliquam erat volutpat. Ut wisi enim ad minim veniam, quis
nostrud exerci tation ullamcorper suscipit lobortis nisl ut aliquip
ex ea commodo consequat. Duis autem vel eum iriure
Lorem ipsum dolor sit amet, consectetuer adipiscing
elit, sed diam nonummy nibh euismod tincidunt ut
laoreet dolore magna aliquam erat volutpat. Ut wisi
enim ad minim veniam, quis nostrud exerci tation
ullamcorper suscipit lobortis nisl ut aliquip ex ea
commodo consequat. Duis autem vel eum iriure dolor in
hendrerit in vulputate velit esse molestie consequat, vel
illum dolore eu feugiat nulla facilisis at vero eros et
accumsan et iusto odio dignissim qui
Nam liber tempor cum soluta nobis eleifend option congue
nihil imperdiet doming id quod mazim placerat facer
possim assum. Typi non habent claritatem insitam; est usus
legentis in iis qui facit eorum claritatem. Investigationes
demonstraverunt lectores legere me lius quod ii legunt
saepius. Claritas est etiam processus dynamicus, qui
sequitur mutationem consuetudium lectorum. Mirum est
notare quam littera gothica, quam nunc putamus parum
claram, anteposuerit litterarum formas humanitatis per
seacula quarta decima et quinta decima. Eodem modo
Lorem ipsum dolor sit amet, consectetuer adipiscing
elit, sed diam nonummy nibh euismod tincidunt ut
laoreet dolore magna aliquam erat volutpat. Ut wisi
enim ad minim veniam, quis nostrud exerci tation
ullamcorper suscipit lobortis nisl ut aliquip ex ea
commodo consequat. Duis autem vel eum iriure

31. Appearance of documents
©20140523 31Lean authoring of Module 3
Document-specific headers, so:
•NOT Uniform across a dossier!
•NOT Referencing the dossier!

32. Appearance of documents
©20140523 32Lean authoring of Module 3
Not this
But this

33. Appearance of documents
©20140523 33Lean authoring of Module 3
Proper styles
•Heading numbering not including CTD section #
•Table/figure numbering not including section #

34. ©20140523 Lean authoring of Module 3 34
Lifecycle example
0000
Pilot Scale
Initial stability
0001
Pilot Scale
Extension stability
Long-term 12 M
stability data
0010
Commercial scale
Initial stability
0011
Commercial Scale
Extension stability
Long-term 24 M
stability data
Current
View
Long-term 12 M
stability data
Long-term 24 M
stability data
Long-term 12 M
stability data
commercial scale
Long-term 12 M
stability data
commercial scale
Long-term 24 M
stability data
commercial scale
Long-term 24 M
stability data
commercial scale
Short-term
stability data
Short-term
stability data
Short-term
stability data
commercial scale
Short-term
stability data
commercial scale

35. Collaboration
Crucell and Qdossier

36. ©20140523 36Lean authoring of Module 3
Set up of new dossier for influenza vaccine
Inherited dossier Baseline dossier (to go)
No strict separation DS/DP Defined the DS and DP
Usage of (translated) SOPs Summaries and general description
Local documents No local documents, but summaries
Usage of Brandname throughout dossier Use generic name
Inconsistent naming Naming convention introduced (DS; DP)
Master files/ full dossiers suppliers Make list of important parameters (summary)
Long text Shorter text, summaries, translations
QOS QOS rewritten

37. What could Qdossier do?
©20140523 37Lean authoring of Module 3
Place the information at the correct dossier section
• Crucell and Qdossier understanding of the content
• Repetition of information in DS and DP
Summarise lengthy dossier sections (content)
• Creation of new (e)CTD documents
• Ease the upload into the company’s ‘documentation’ system
Overview of all Documents
• Important having the overview of documents from the old dossier to
the new dossier
• Creation of the Content Plan (ToC, etc)

38. CRO’s and Client’s agreements
©20140523 38Lean authoring of Module 3
Delivery of a clear source data package
Good agreements in who is doing what
Goal setting
Manage the internal teams for review of
the documents
Knowledge of the content
•Check that nothing is missing
•No changes introduced, even minor

39. Challenges and solutions
©20140523 39Lean authoring of Module 3
Understanding of the content for Q-Dossier
•Questions on content
•New definitions
Tracker of the questions and answers
•GAP analysis
Meetings
•Kick off
•Life meetings (F2F)
•Weekly TC

40. Questions ?

41. Rolling out at Crucell
©20140523 41Lean authoring of Module 3
Experience with HA
• Documents used for submission
• Feedback HA
Next steps other vaccines Crucell
• Project started on lean and eCTD
• Experience will be used

42. Questions?