1. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com © Copyright 2005 J. B. Chemicals Pharma Ltd. Electronic Submissions – eCTD Advantages Dr Milind Joshi President – Global Regulatory Management

2. Change is the only universal constant J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pvt. Ltd.

3. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd.  Every regulatory submission is data submission  Dossier structure is complicated  Variety  Quantity  Lack of clarity  Confusing and cumbersome review process  Voluminous data  Diverse data  Multiple expertise needed for complete review  Evolution Data Management and Review

4. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. CTD – Structure  Module 1 is not part of CTD  Contains regional information and prescribing information

5. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. eCTD Modules  Module 1 ( Region specific Information) Environmental Assessment, declarations and forms  Module 2 ( Summaries) -2.3.Quality overall Summary -and Summary of Modules 4 and 5 (e.g. BE Tables)  Module 3 -Drug substance -Drug Product -Appendices -Batch information

6. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. eCTD Modules ( contd..) Module 4  Non-Clinical study report and related data Module 5  Clinical study reports, CRFs, & In –vitro comparative dissolution data, etc.  Bioequivalence studies in ANDA submission  STF (study tagging files) submission  STFs required by Unites states, optional in Europe & Japan

7. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. Data / Dossier Structure Old timesCTDeCTD Administrative / Regional Module 1 Administrative / Regional Module 1 Chemistry Manufacture Control Quality Module 3 Quality Module 3 Non-Clinical / Clinical / BE Non-Clinical Module 4 Non-Clinical Module 4 Clinical/BE Module 5 Clinical/BE Module 5 Summary / Synopsis Summary Module 2 Summary Module 2 No set structureSet structure but without granularity Very definite structure with detailed granularity Xml backbone

8. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. CTD – Common Technical Document  Technical Document – data necessary for proving safety, efficacy and quality of a drug product  CTD – initiative to formalise the technical data  Wide acceptance of the format  Led to discipline in catagorising and presentation of data  Facilitated the review procedure of the huge data  Still many copies of data needed, repeat efforts and confusions unavoidable  Updates in data and version control was cumbersome

9. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. eCTD – Electronic CTD  The format for data compilation remains same  Presentation is electronic and not paper  Undergoing evolution in eCTD for last few years  Initiative for better metadata and data management  Initiative for searchability and faster review  Initiative for better version control and change management

10. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. eCTD  Data that used to be submitted on paper, is submitted on a CD / uploaded on a server  Like guidance for how paper should be, there is guidance for how the files should be  Specific software / application for formation of eCTD  Choice of software / application  Knowledge of not just regulatory requirements but also IT aspects  Not just QbD for product but also Accuracy by Design for data compilation

11. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. eCTD Emergence Paper submission  NeeS  eCTD Late 80’s  2008 for complete transfer at USFDA  Disadvantages of Paper Submission  Exponentially increased number of dossiers any MoH / Regulatory Authority receives in recent times  Need for faster and more efficient review  Need for better searchability, user friendliness and harmonisation

12. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. Disadvantages of Paper Submissions  Voluminous data – difficult to handle  Person dependant for storage and retrieval  Not searchable  Not reusable  Can be lost  Can not be secured  Updates in data is difficult to track  Difficult version control  Eco-friendly (One copy of CTD dossier = 1 tree)

13. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. eCTD  Most far-reaching change in regulatory data management  Needs upgradation and learning at different levels in a company  Constantly changing / evolving hence needs constant training  Management needs to approve the high end software facility or out-sourcing fees  Regulatory officers / executive should learn the detailed requirements – not just pharma-technical but also IT-technical

14. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. CTD & eCTD  Scientific approach  CTD mandatory in the ASEAN, USA, EU & Japan  eCTD ‘must’ for USFDA  Common dossier for all countries with different Module 1 with regional information  Infrastructure created at USFDA for eCTD  Document management capability at USFDA  Version control at USFDA & at user’s end  Paperless  Reduced review time

15. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. Submission Review Tools  Tools provided on an as-is basis with no support from FDA  Support from 3 rd party tools developers to submit and validation of submission prior to FDA submissions.  Adherence to the eCTD specification is critical  Validation of the submission very crucial

16. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. Review Process

17. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. eCTD Requirements  File formats – pdf, xpt, doc, jpg  Doc, xpt and jpg files only allowed in certain modules  Software to have maximum granularity  All pdf files should be searchable / OCRed, vertically oriented  Norms for file naming  Norms for title  Norms for how to write title and file name  Other norms of margins, fonts etc – same as paper compilation  Thorough bookmarking and hyperlinking  No repeatation of data within metadata

18. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. Requirements – Successful eCTD Application  eCTD software ( Good support from vendor )  Quality of HR  IT infrastructure  Understanding of the software & regulatory guidance  Training & updating with current guidance

19. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. eCTD Advantages  Handling of smaller physical form of data compilation like CD  No copies (coloured bound dossiers, field copies etc)  Easily reviewable  Searchable  Life-cycle management of dossiers  Easy updates  Version control  No repetition of data  Maneuverability and easy cross-linking within metadata  Maneuverability and easy cross-linking within data

20. J. B. Chemicals & Pharmaceuticals Ltd. www.jbcpl.com. © Copyright 2005 J. B. Chemicals Pharma Ltd. Thank you !!! milind@jbcpl.com