Dr Milind Joshi President Global Regulatory Management Electronic

Change is the only universal constant www. jbcpl. com. © Copyright 2005 J. B.

Data Management and Review § 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 www. jbcpl. com. © Copyright 2005 J. B. Chemicals Pharma Ltd. J. B. Chemicals & Pharmaceuticals Ltd.

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

e. CTD 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 www. jbcpl. com. © Copyright 2005 J. B. Chemicals Pharma Ltd. J. B. Chemicals & Pharmaceuticals Ltd.

e. CTD 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 www. jbcpl. com. © Copyright 2005 J. B. Chemicals Pharma Ltd. J. B. Chemicals & Pharmaceuticals Ltd.

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

e. CTD – Electronic CTD § § § The format for data compilation remains same Presentation is electronic and not paper Undergoing evolution in e. CTD 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 www. jbcpl. com. © Copyright 2005 J. B. Chemicals Pharma Ltd. J. B. Chemicals & Pharmaceuticals Ltd.

e. CTD § 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 formation of e. CTD § Choice of software / application § Knowledge of not just regulatory requirements but also IT aspects § Not just Qb. D for product but also Accuracy by Design for data compilation www. jbcpl. com. © Copyright 2005 J. B. Chemicals Pharma Ltd. J. B. Chemicals & Pharmaceuticals Ltd.

e. CTD Emergence Paper submission Nee. S e. CTD Late 80’s 2008 for complete transfer at USFDA § Disadvantages of Paper Submission § Exponentially increased number of dossiers any Mo. H / Regulatory Authority receives in recent times § Need for faster and more efficient review § Need for better searchability, user friendliness and harmonisation www. jbcpl. com. © Copyright 2005 J. B. Chemicals Pharma Ltd. J. B. Chemicals & Pharmaceuticals 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) www. jbcpl. com. © Copyright 2005 J. B. Chemicals Pharma Ltd. J. B. Chemicals & Pharmaceuticals Ltd.

e. CTD § 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 www. jbcpl. com. © Copyright 2005 J. B. Chemicals Pharma Ltd. J. B. Chemicals & Pharmaceuticals Ltd.

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

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

e. CTD 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 www. jbcpl. com. © Copyright 2005 J. B. Chemicals Pharma Ltd. J. B. Chemicals & Pharmaceuticals Ltd.

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

e. CTD 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 www. jbcpl. com. © Copyright 2005 J. B. Chemicals Pharma Ltd. J. B. Chemicals & Pharmaceuticals Ltd.