Pros & cons of eCTD baseline submissions

What is a baseline submission?

Single eCTD submission capturing all the appropriate information thatreflects what has been submittedoAll modulesoModule 3 only (32S, 32P, 32A and/or 32R)

Corresponds to approved marketing license of a drugMerges per eCTDs per strength to single eCTD lifecycle

20110920 2Pros & cons of baseline submissions

Content of a baseline

Module 1Cover letter (state content has not changed, only its format)

Module 2Integrated overviews and summaries for Quality, Nonclinical and

Clinical or a clear combination of thoseCumulative list of all clinical trialsIndividual study synopses

Module 4 + 5 All study reports as is

20110920 Pros & cons of baseline submissions 3

Content of a baseline

Module 3No chronological cumulative presentation, but a “current view”Hyperlinks not necessaryDo notoExclude any information form original dossier (unless updated by

a regulatory process)o Include any information not submitted before in the original

dossierDocument granularity that fits best

with the lifecycle of documents

20110920 Pros & cons of baseline submissions 4

Granularity!?

Document granularity Module 3

Coursest and finest granularity defined by ICH M4 on organisation of Module 3

Determine granularity based on likelihood of:Future changesReusability across productsReusability across regions

Apply meaningful names for now, here and the future

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Subsequent sequences should matchgranularity of the previous sequences

Granularity and future?

Only replace or delete whole documents, not sections or pages in eCTDe.g. single 32P33 vs. Formulation, filling, packaging and labelling

Mention information only once and in a single documente.g. Batch numbering in 32P33 only and not repeated in 32P54

Do not mention the reason for submitting a documente.g. Do not mention “to support the change of.....”

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Granularity and regional difference

Additional specifications beyond the Ph.Eur. in a subset of countriesS41 Specifications Ph.Eur. Vs. S41 Specifications polymorphism

Different level of detail in a limited number of documentse.g. Details around control of critical steps, whereas the remainder

is identical

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Granularity and reuse across products

Separate content from contextDrug substance documentation not refering to the context of useAnalytical procedures across substances and productsP1 Description and composition vs. Container descriptionP4 Compendial combined vs. Compendial individualP7 Container material information, rather usage

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How to define the granularity?

By use of an ToC outline capturing granularity and naming

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Analytical procedure “Test C by Method D” is not product specific and can be reused across products

When to be created and submitted?

At start of an eCTD lifecycle for an existing dossier0000=Baseline0001=Major variation or renewal

During the eCTD lifecycle

20110920 10Pros & cons of baseline submissions

Submission type: reformat

Pros of baseline submissions

Ability to remove repeating and therefore redundant information, such asScale at other sections than S22 and P33Manufacturer names at other sections than S21, P31 and A1Buildings at other sections than A1

Ability to create content in context in appropriate sectionsManufacturing process development and Pharmaceutical

development

Ability to apply specific information at relevant sections onlyIn text and in header and footer20110920 Pros & cons of baseline submissions 11

Pros of baseline submissions 2

Ability to start a clear lifecycle and audit trail

Ability to create documents for reuse across products, e.g.Filling, packaging and labelling processesSelection and justifications for excipientsSuitability of containerExcipientsAnalytical procedures (and Quality by design)Container closure systemsFacilities and equipment

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Pros of baseline submissions 3

Greatly improves the review processWithin the companyFor agencies

Improves transparencyWhat document has been submitted where?What products are supported by a document?

EU agencies encourage/recommend baseline submissions; US accepts these

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Cons of baseline submissions

Time consuming (up to 15 days)Requires limited content knowledge and advanced Word

knowledge

Insufficiencies and incompliance becomes apparent; e.g.Lack of validation because it got approved before it was requiredLack of stability data because it was OK at time of registration

Inability toAdd more recent though never submitted informationCorrect erroneous informationRemove out-dated though never replaced information20110920 Pros & cons of baseline submissions 14

To be co

rrected

with var

iations

Thank you

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