CTD Dossier Preparation - Pharmaceutical Export Promotion ...

1 CTD Dossier PreparationK. Srikantha ReddyK. Srikantha AffairsMedreich LimitedMedreich Dossier PreparationCTD Dossier Preparation CTD (Common Technical Document) contains 5 modules Module1 Module 1 Module 2 Module 3 Module 4 Module 5 DMFDrug Master File (DMF) is a submission to theFood and Drug Administration (FDA) that maybeusedtoprovideconfidentialdetailedbe usedtoprovideconfidentialdetailedinforma tion about facilities, processes, orarticles used in the manufacturing, processing,packagingandstoringofoneormor ehumanpackaging,andstoringofoneormorehum andrugs. The information contained in the DMFmay be used to support following,InvestigationalNewDrugApplicat ion(IND) InvestigationalNewDrugApplication(IND), New Drug Application (NDA), Abbreviated New Drug Application (ANDA), Export : An Abbreviated New Drug Application (ANDA)is an application for a generic druglfitiliddi tiapprovalfor an existinglicensedmedication orapproved drug.

2 The ANDA contains data which when submittedto FDA's Center For drug Evaluation andResearch (CDER), Office of Generic Drugs,provides for the review and ultimate approvalpppof a generic drug product. Once approved, anapplicant may manufacture and market thegenericdrugproducttoprovideasafe,gene ricdrugproducttoprovideasafe,effective, low cost alternative to the 1 ( EU)Module-1: Administrative Information and Prescribing Information 10 Cover Letter Cover Letter Comprehensive Table of Content Application Form 13 Pd t Ifti Product Information SPC s, Labelling and Packaging Mock-Up Specimen Consultation with target patient group 135 SPC s already approved in the Member SPC s already approved in the Member states Braille Module - Information about the Experts Specific Requirements for different pqtypes of applications Environmental Risk Assessment Information relating to Orphan Market gpExclusivity Information relating to Pharmacovigilance Information relating to Clinical Trials Information relating to Pediatrics Response to Queries Additional Data Module - 2 Module - 2.

3 CTD Summary 21 Tbl f C t t (Ch i ) Table of Content (Comprehensive) Introduction (general introduction to the Pharmaceutical , including its pharmacology class, d f ti d d lii l ) mode of action, and proposed clinical use) Quality Overall Summary Non-clinical Overview Clinical Overview Non-clinical Written and Tabulated Summaries Clinical summary y Module - Non-clinical Overview General Aspects Ge e a spects Content and Structural Format Clinical Overview Product Development of Content Rationale Overview of Biopharmaceutics 253 Overview of Clinical Pharmacology Overview of Clinical Pharmacology Overview of Efficacy Overview of Safety Overview of Safety Benefits and Risks Conclusions Literature References Module - Non-clinical Written and Tabulated Summaries Pharmacology 262 Phki ti Pharmacokinetics Toxicology 27 Clinical summary Clinical summary Biopharmaceutic Studies and Associated Analytical Methods Clinical Pharmacology Studies

4 Clinical Efficacy 274 Cli i l S f t Clinical Safety Literature References 276 Synopses of Individual Studies Synopses of Individual Studies Module - 3 Module 3: Quality Table of Contents Body of Data y Drug Substance General Information Nomenclature Structure 32S13 General Properties General Properties Module Manufacture Manufacturer Details Module 3 Description of Manufacturing Process and Process Controls 32S23 Control of Materials Control of Materials Controls of Critical Steps and Intermediates 32S25 P V lid ti d / E lti Process Validation and /or Evaluation Manufacturing Process Development Characterisation Elucidation of structure and other Characteristics Impurities 33puModule -3 Control of Drug Substance Module 3 Specification of Drug Substance Analytical Procedures Validation of Analytical Procedures

5 Validation of Analytical Procedures Batch Analyses Justification of Specification 32S5 Reference Standards or Materials Reference Standards or Materials Container Closure System Stability Stability Summary and Conclusions Post-approval Stability Protocol and Stability Commitment Stability Commitment Stability Data Module - Product Description and Composition of the Drug Product 32P2 Phti l D lt Pharmaceutical Development Components of Drug Product 32P22 Drug Product Drug Product Manufacturing Process Development p Container Closure System Microbiological Attributes Compatibility Module -332P3 Mft Module Manufacture Manufacturer 32P32 Batch Formula Batch Formula Description of Manufacturing Processand Process Controls Controls of Critical Steps and Intermediates 32P35 Process Validation and /or Evaluation Process Validation and /or Evaluation Module -332P4 Control of Excipients Module Control of Excipients Specifications 32P42 Analytical Procedures Analytical Procedures Validation of Analytical Procedures Procedures Justification of Specifications 32P45 Excipients of Human or Animal Excipients of Human or Animal Origin Novel Excipients Novel Excipients Module -332P5 Ctl f D Pdt Module Control of Drug Product Specification of Drug Product 32P52 Analytical Procedures Analytical Procedures Validation of Analytical Procedures Batch Analyses Batch Analyses Characterisation of Impurities Justification of Specification Reference Standards or Materials

6 Container Closure System Module -3 Module Stability Stability Summary and Cli Conclusions Post-approval Stability Protocol and Stability Protocol and Stability Commitment 32P83 Stability Data Stability Data Module - 3 Facilities and Equipment Adventitious Agents Safety Evaluation 32A3 Novel Excipients Novel Excipients Information/ Requirements Process Validation and or Evaluation Medical Device Restricted part of DMF 32R4 Mdiil dt tii i i Medicinal products containing or using in the manufacturing process materials of animal and / or human origin. List of Literature References Module -4 Module - 4: Non-clinical Study Reports Module Table of contents Study Reports 421 Pharmacology Pharmacology Primary Pharmacodynamic Secondary Pharmacodynamic 423 Sft hl Safety pharmacology Pharmacodynamic drug interactions Module - Pharmacokinetics Analytical Methods and validation Reports 4222 Absorption Absorption Distribution Metabolism Excretion Pharmacokinetic Drug Interactions Other Pharmacokinetic studies Module - Toxicology 4231 Single-dose toxicity Single-dose toxicity Repeat-dose toxicity Genotoxicity y Carcinogenicity

7 Reproductive and developmental tiit toxicity Local tolerance 4237 Other toxicity studies Other toxicity studies Literature References Mdl 5 Cli i l St d Rt Module - 5 Module - 5: Clinical Study Reports Table of Contents Tabular Listings of All Clinical Studies Clinical Study Reports Bioavailability (BA) study Reports Comparative BA and Comparative BA and Bioequivalence study reports In-vitro In-vivo Correlation study reports reports Reports of Bioanalytical and Analytical methods 5321 Plasma Protein Binding Study Plasma Protein Binding Study Reports Reports of Hepatic metabolism and Drug Interaction Studies and Drug Interaction Studies Reports of Studies Using human Biomaterials 5331 H lth S bj t PK d I iti l Module - 5 Healthy Subject PK and Initial Tolerability study reports Patient PK and Initial Tolerability ystudy reports.

8 Intrinsic Factor PK study reports 5334 E t i i F t PK t d t Extrinsic Factor PK study reports Population PK study reports 5341 Healthy subject PD and PK/PD Healthy subject PD and PK/PD study reports Patient PD and PK/PD study reports Study reports of controlled clinical studies studies Module - 5 Study reports of Uncontrolled clinical studies studies Reports of Analyses of data from more than one study Other clinical study reports Reports of Post-Marketing Ei Experience Case report forms and Individual patient listings patient listings List of Key Literature References eCTDeCTD(Version )(Version ) Srikantha ReddyK. Srikantha ReddySr. ManagerSr. Manager--Regulatory AffairsRegulatory AffairsMedreich LimitedMedreich LimitedMedreich LimitedMedreich eCTD electronic Common Technical Document The eCTD is the electronic equivalent to the CTD The eCTD is the electronic equivalent to the CTD.

9 Regulatory Perspective TheeCTDisdefinedas an interface for industry toagency transfer of regulatory information while atthesametimetakinginto consideration thegfacilitation of the creation, review, lifecyclemanagementandarchivaloftheelect ronicsubmission submission. Common structure for Modules 2 through 5 Agency specific requirements for Modules 1 eCTD Technical Perspective Structured set of common folders structure Structured set of common folders structure containing PDFs and SAS files (Statistical Analysis Software) on a CD/DVD (Can also be submitted through Agency web portals) The eCTD backbone is an XML file (Extensible M kL)tithttf thMarkup Language) representing the structure of the submission, it includes links to files and other metadata such as check sum information. The schema for the XML is very rigid. PDF hyperlinkseCTD Granularity of files submitted is small (there are no longer issues of creating large volumes of PDFs).

10 Increased potential for reusing the same submission content across agency submissions. The standard, and many of the modules have been agreed upon by the main worldwide agencies. Once a submission is sent in eCTD format all future submissions for the application should be in eCTD it tP t 11 Cli t El ti Opportunity to use Part 11 Compliant Electronic Signatures. Use only file formats specified in the guidance Use only file formats specified in the guidanceeCTDB enefitseCTDB enefits Easy to distribute and review More efficient use of resources, less cost and stress to the organization Highly organized electronic table of contents Searchable Self-validating Integrated document and life-cycle management Cross submission integration Living documentLiving document New, replace, append & deleteHow it is different to Paper/Document CTDHow it is different to Paper/Document CTD Overall Table of contents provided in XML (Extensible Markup Language) Utility files to enable technical conformance and iiviewing Submission Folders, XML and Utility Files are created tti ll ifCTD b ildidautomatically if an eCTD builder is used.