Lean authoring of module 3

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

2Lean authoring of Module 3

Content

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What is Lean Authoring?• Why Lean Authoring?• Advantages of Lean AuthoringHow to apply Lean AuthoringLean Authoring GeneralLean Authoring Module 3Real life examplesQuestions

What is Lean Authoring?

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Definition of Lean Authoring

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Split Content / ContextNaming of documentsContent of documentsHeaders and footers

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 MonographsSeparate 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

Content & Context - carrot and potato recipes

Manufacturers

CompetentauthoritiesDrug

products

Productionprocess

(active)substances

Content & Context - every item documented

Manufacturers

CompetentauthoritiesDrug

products

Productionprocess

(active)substances

Content & Context – cross references

Manufacturers

CompetentauthoritiesDrug

products

Productionprocess

(active)substances

Content & Context – cross references

Manufacturers

CompetentauthoritiesDrug

products

Productionprocess

(active)substances

Content & Context - Named product in named country for named submission type

Manufacturers

CompetentauthoritiesDrug

products

Productionprocess

(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 <………@................................>

Content & Context - Named product in named country for named submission type

Manufacturers

CompetentauthoritiesDrug

products

Productionprocess

(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 <………@................................>

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Lean Authoring?

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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

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Why Lean Authoring?

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Resulting in poor:• Retrieval of documents• Impedes traceabilityResulting in redundant:

• Writing• Review• Approval• Publishing• Hyperlinking• QC

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Advantages of Lean Authoring

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Document can be reused across countriesDocuments can be reused across productsImproves effective communication and review processImproves consistency in messages

• Within and across documents• Within and across products• Within and across countries

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Advantages of Lean Authoring

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Eases future updates of documentsEases future preparation of submissionsEases retrieval of information in a document repository and submissionReduces the chance of rejection by authoritiesLess variations

• Manufacturer’s only described in S2.1 and P3.1• Manufacturing process not mentioning manufacturers• Analytical procedures not mentioning manufacturers

How to apply Lean Authoring

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What is important for dossier preparation?

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Which marketing license to be obtainedWhich claims to be supportedWhich documents to be used• Content• Identification• Format• Header• Cross referencesHow to communicate?• Verbally• Written

• eMail• Meeting minutes• Project plans• Document management systems (trackability, traceability)

Content Plan/

Preparation planner

•ToC•Dossier planning

•Submission planning

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from Qdossier

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from Qdossier

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Dossier Plan Lifecycle

Lean Authoring

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Lean Authoring

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Provide information only once in a dossier only in one documentProvide it at the correct (or most appropriate) locationBe conciseUse the same terms; prevent use of synonymsRefer to the data provided elsewhere rather than repeat

It is neit

her a nove

lla

nor a scie

ntific art

icle

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Lean Authoring – RulesConsistency

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All information in the dossier needs to be consistent

• The less repetition, the smaller the risk for inconsistenciesRe-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)

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Lean authoring – RulesCross references

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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

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Lean authoring – General

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Apply default Word numbering:

• 4.4 Lyophilisation and stabilisationInstead of

3.2.S.2.2.4.4 Lyophilisation and stabilisation

• Figure 1 Manufacturing process flow diagramInstead 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

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Lean authoring – Text

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Words that should be avoided:• In order• Assume• New/Old• Possibly• PleaseWhat else should be avoided

• Long sentences• Sentences starting with

• With this variation/submission …• …we (the company) shows• We (the company) would like to …

Lean authoring Module 3

Real life examples

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ProEasy to navigate when using eCTD .xml or NeeS ToCOnly small document to revise for variationBetter reusability of documents between products

ConDifficult to navigate when using Windows ExplorerLarge document to revise for variation all content might be reviewed again

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Pros and cons of high document granularity

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Granularity and appearance of documents

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Per document• Corresponding to the content plan

One doc per section

Multiple docs per section

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Single vs. Multiple Granularity

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3.2.P.8.1 Stability Summary and ConclusionLorem 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 CommitmentNam 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 DataLorem 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

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Appearance of documents

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Document-specific headers, so:• NOT Uniform across a dossier!• NOT Referencing the dossier!

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Appearance of documents

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Not this

But this

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Appearance of documents

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Proper styles• Heading numbering not including CTD section #• Table/figure numbering not including section #

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Lifecycle example

0000Pilot Scale

Initial stability

0001Pilot Scale

Extension stability

Long-term 12 M stability data

0010Commercial scale

Initial stability

0011Commercial 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

DELETE

Short-termstability data

Short-termstability data

Short-term stability data

commercial scale

Short-term stability data

commercial scale

REPLACE

NEWREPLACE

REPLACE

CollaborationCrucell and Qdossier

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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

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What could Qdossier do?

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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)

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CRO’s and Client’s agreements

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Delivery of a clear source data packageGood agreements in who is doing whatGoal settingManage the internal teams for review of the documentsKnowledge of the content

• Check that nothing is missing• No changes introduced, even minor

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Challenges and solutions

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Understanding of the content for Q-Dossier• Questions on content• New definitions Tracker of the questions and answers

• GAP analysisMeetings

• Kick off• Life meetings (F2F)• Weekly TC

Questions ?

41Lean authoring of Module 3

Rolling out at Crucell

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Experience with HA• Documents used for submission• Feedback HA

Next steps other vaccines Crucell• Project started on lean and eCTD• Experience will be used

Questions?