Download - Pros and cons of eCTD baseline submissions
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
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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
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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
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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
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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