How to create a validated ectd submission based on the new guidelines and specification - Part 1

Transcription

1 How to create a validated ectd submission based on the new guidelines and specification - Part ectd MCC Validation Criteria Michael Gessert Product Manager Global Review & Validation Dr. Gerhard Neurauter Director Regulatory Competence Center 14/15. February 2013

2 Agenda Why do we need validation criteria? Requirement on validation criteria Compliance, Content, Technical and Business Validation MCC Val. Crit. overview (how many, explain tabel, screenshoots) Validation Criteria as a group (PDF, XML, File&Folder etc..) Severities Required tools to run the validation Change Request and Update of Val. Crit. 2

3 Why do we need validation criteria 3

4 The reason for validation criteria In the past, there was a variety of interpretation, how a valid Submission should look like All vendors of compilation / validation tools and agencies had a different interpretation Which is still ongoing to get synchronized in Europe ETICS by ICH was established ETICS (electronic transfer and interchange of submission) project was established to create test submissions to give all involved parties the chance test, enhance quality and harmonies their interpretation to avoid different compilation / validation results Goal: Handle violations with the same severity on all tools 4

5 The reason for validation criteria The Problem is in building not in validation ectdmanager s intelligence is representing, all those years of experience to create, exchange and compile worldwide valid submissions The best Specification can only be the platform to build the technical validator: there is always room for interpretation Q&A EXTEDO was chosen a the most experienced partner to develop & establish MCCs Validation Criteria 5

6 The reason for validation criteria Different numbering system in DTDs and Validation sets 1.4 old = Validation set new = validation set 3.1 Changes in the interpretation, validation criteria, tracking, consequences, severity of errors and different transition periods Nees as an in-between solution lots of troubles (for both parties: Industry & Agencies) Based on this experience, for example, there is no NeeS in Switzerland 6

7 Validation criteria in other ectd regions M1 regional part: A variety of national validation criteria M2-M5: ICH There is no dedicated validation criteria from ICH, BUT: national different interpretation of the ICH specification EU -> History of validation criteria 2008/Q3 2013/Q4 y: EU validation rules for DTD 1.0, DTD 1.2, DTD 1.2.1, DTD 1.3, DTD1,4, DTD 1.4 new, DTD 1.5 7

8 Validation Criteria Requirements 8

9 Requirement on Validation Criteria Theoretical requirements Unique in formulation Unique in interpretation No double definition of rules Clearly explained Not in contradiction to itself, to other rules or the ICH specification Must not allow cascading errors 9

10 Requirement on Validation Criteria Requirements from daily experience Changes in Specification Changes in ICH specification which needs to be reflected in national requirements Lack of harmonization (vendors, interpretation, tools) Quality of dossiers needs to be improved Desire to automate the validation process 10

11 Requirement on Val. Crit. - Severities What is a severity? (e.g. EMA) The weight of a criteria Makes a submission accept or reject 11

12 Requirement on Val. Crit. - Severities History Severity In the past, severities were driven to be as granular as possible to provide as much details as possible As a result there was lot of confusion and interpretation at Industry, vendors and on Agency side EU-History: started with A-B-C as a result some agencies in EU accepted a submission others rejected the same submission, due to different interpretation of the rules and severities (no A s, only 2 B s or only 5 B s no better only B s of category PDF???) EU today: Pass/ Fail warning (Best practice) only fail is strong enough to reject and even one fail is enough to reject ) USA: high med low CA: error, warning, ignore CH: A-B-C in changing process to P/F 12

13 Compliance-,Technical- and Business or Content Validation 13

14 Compliance-,Technical- and Business or Content Validation What is a Compliance Check? Since the title of this presentation is 2.22 ectd MCC Validation Criteria nothing to add at the moment 14

15 Compliance-,Technical- and Business or Content Validation What is a technical validation? Using a validation tool to run a validation of a submission against MCC validation criteria Automated, machine readable & executable tests Checking technical details e.g. version of PDF files, identity of files (checksum), formal checks on XML files Backbone files Lifecycle checks Naming restrictions File size 15

16 Compliance-,Technical- and Business or Content Validation What is a technical validation NOT? NO content (pharmaceutical know how) is checked NO check if content is complete NO check if all documents are provided What is a technical valid ectd submission? NOT a valid application (= content proofed) Can contain only 1 document (e.g. application letter) and provide no more content documents 16

17 Compliance-,Technical- and Business or Content Validation What is a content validation / review? Since the title of this presentation is 2.22 ectd MCC Validation Criteria nothing to add at the moment 17

18 MCC Validation Criteria Overview 18

19 MCC Val. Crit. overview MCC Validation Criteria Is an Excel file (2 22 _ectd_validation_criteria_vx.x) Criteria are providing a list of 27 pass / fail criteria 12 best practice criteria On counting numbered 19

20 MCC Val. Crit. overview MCC Validation Criteria are providing information about Creteria Categories (Checksum DTD - File Reference - Files/folders - index.xml - Modified File Security - Sequence Number - Util Folder - xlink:href XML - ID Attribute Leaf PDF - PDF initial view) Description on the validation criterion (Provides text to describe what is tested) Severities (pass/fail best practice) 20

21 MCC Val. Crit. overview MCC Validation Criteria are providing information about File & Folder Structure Trough M1 to M5 Meta information about folders Multiple Optional Required Folders Expected Names 21

22 Validation Criteria as a group 22

23 Validation Criteria as a group Criteria Categories/Groups For P/F criteria Checksum md 5 checksum e.g of the technical files DTD File Reference Files/folders use of naming index.xml Modified File Security Sequence Number must be 4-digit number ( ) Util Folder location & naming of the technical files xlink:href XML format of a XML file well formed 23

24 Validation Criteria as a group Criteria Categories For BP Criteria Files/folders naming ID Attribute Leaf only appears, where allowed PDF version control Modified File Lifecycle PDF initial view which viewing mode is active if a PDF is opened Checksum 24

25 Required tools 25

26 Required tools Compliation Tool (for building an ectdsubmission) Manual building as an option? Easy to install easy to use providing structures Takes care for naming and PDF versions Always provides latest regulatory updates Good to have one tool for all submission formats (paper NeeS - ectd) Provides validation options.. e.g. ectdmanager 26

27 Required tools Validation Tool Easy to install easy to use Provides easy to use GUI / Interface Provides always latest regulatory updates Creates validation reports Reviewing Tool Easy to install easy to use Supports the review process Supports the communication to applicants Must protect customer documents (not changing by e.g. PDF annotation) Speeds up the process giving feedback to Industry If a company is using all tools they should use only 1 source of validation criteria to avoid inconsistency: Validating with different tools must provide same results 27

28 Change Request and Update of Validation Criteria 28

29 Change Request and Update of Validation Criteria Validation Criteria are always a living process (see EU development) Applicants and Agencies will always find issues to enhance conditions / criteria, during the living of an actual version of validation criteria This gives you (Industry & Agency) the chance to adjust the world of ectd to your requirements See ectd as a living process to live it, yo need a communication channel (Agency - Industry) Comites to exchange experience and work out developments Industry Industry Agency - Industry CR option update for ValCrit possibel & M1 spec 29

30 Danke Baie Dankie Ngiyathokoza Ke a leboha Ke a leboga Siyabonga Inkomu Ndo livhuwa Ro livhuwa Enkosi Ngiyabonga Thank You