Consigli pratici per la propria soluzione ectd.

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1 KLever Article Pag 1 di 5 Consigli pratici per la propria soluzione ectd. di Luigi Fabbro, Solution Manager - Klever srl L introduzione del dossier elettronico in formato ectd è ormai alle porte, senza possibilità di ulteriori rinvii. Molte aziende farmaceutiche stanno quindi decidendo come affrontare questa tematica e questo articolo vuole fornire qualche utile spunto per indirizzare il proprio progetto ectd. Obiettivi e Scopo di un progetto ectd Prima di iniziare l implementazione di un progetto ectd è necessario definire in modo chiaro l obiettivo del progetto stesso, necessariamente diverso per ogni azienda. A tal scopo si devono considerare le seguenti caratteristiche aziendali: L organizzazione - Alcune aziende hanno un modello organizzativo che gestisce e controlla centralmente tutte le attività regolatorie mentre altre demandano la responsabilità alle differenti subsidiary internazionali /business unit. Le strategie business - Gli specifici obiettivi di commercializzazione di un prodotto possono richiedere registrazioni centralizzate in EMEA piuttosto che l espansione in USA o Canada. Le risorse disponibili - Le competenze all interno del reparto regolatorio, l infrastruttura IT, le risorse umane e il budget a disposizione. Le specifiche caratteristiche sopradescritte contribuiscono alla definizione dell architettura logica del progetto ectd condizionando: la scelta della piattaforma di publishing centralizzata, dipartimentale singolo utente l adozione (o meno) di una piattaforma di document management a supporto dei processi di creazione dei documenti oggetto del ectd Le componenti del progetto Definiti gli obiettivi e lo scopo di massima, per qualunque progetto ectd è necessario considerare in particolare: - La definizione dei nuovi processi interni per l authoring e l archiviazione dei contenuti - L archivio della documentazione elettronica (con i contenuti per ectd) - Lo strumento di publishing ectd KLever srl Via Argelati 40/A 20143, Milano, Italy info@k-lever.it Tel: Fax:

2 KLever Article Pag 2 di 5 Per affrontare un progetto ectd non è infatti sufficiente acquisire uno strumento di publishing ectd, ma è necessario anche implementare i flussi di lavoro che rendano disponibili i contenuti corretti allo strumento stesso. La definizione di questi processi è naturalmente subordinata alla presenza (o meno) di un archivio di gestione elettronica della documentazione (EDMS) e alle funzionalità dello strumento di publishing ectd selezionato. In altri termini, le piattaforme tecnologiche selezionate possono favorire l implementazione e la mappatura di processi interni piuttosto che vincolare l azienda all applicazione di schemi predeterminati e rigidi. Un aspetto non secondario nell ambito della definizione dei flussi di lavoro è il coordinamento delle attività di consulenti esterni (CRO) che contribuiscono in maniera rilevante al completamente delle attività regolatorie. A fronte di questa analisi che possiamo definire statica, bisogna inoltre considerare anche l estrema dinamicità delle aziende a seguito di acquisizioni, ristrutturazioni e nuove strategie di mercato che possono modificare quelli che sono gli obiettivi iniziali, con l ovvia conseguenza che più l implementazione del progetto è rigida più difficile sarà la sua modifica a fronte di nuovi requisiti. Figura 1 - Soluzione con EDMS e Publishing KLever srl Via Argelati 40/A 20143, Milano, Italy info@k-lever.it Tel: Fax:

3 KLever Article Pag 3 di 5 In base a quanto detto in precedenza l approccio ad un progetto ectd è molto differente fra una multinazionale e un piccola azienda farmaceutica. Gli estremi di un progetto ectd infatti possono infatti variare dall implementazione di una installazione singola dello strumento di publishing ectd, utilizzando file memorizzati sui dischi di rete all implementazione di un ambiente distribuito di più utenti che collaborano alla gestione dei dossier elettronici usando contenuti memorizzati su un sistema di gestione della documentazione elettronica geograficamente distribuito. Soluzioni flessibili In primo luogo l ideale sarebbe individuare soluzioni tecnologiche, sia sul lato della gestione documentale che dello strumento di publishing ectd, che permettano di evolvere facilmente verso implementazioni più complete. L opportunità EDMS Molte aziende vorrebbero inoltre usare il progetto ectd per iniziare l implementazione di un sistema di gestione elettronica della documentazione. La scelta di quale tecnologia EDMS implementare dovrebbe tenere conto di quali altri ambiti funzionali si dovrà implementare l EDMS, tipicamente ambiti GMP (gestione POS e documentazione qualità in produzione) e dell esigenza o meno della convalida del EDMS a fronte di una scelta del EDMS vista al solo supporto della gestione dei dossier e del relativo publishing elettronico. Soluzioni EDMS troppo puntuali potrebbero rivelarsi una criticità nella scelta del EDMS a livello aziendale per gli altri ambiti. I requisiti di uno strumento di publishing ectd Analizziamo i principali requisiti da valutare nella selezione di uno strumento di publishing ectd. Le specifiche ectd Il formato ectd è uno standard ed ogni strumento di publishing ectd dovrebbe essere in grado di soddisfare i requisiti dello standard. Ma le specifiche evolvono nel tempo, in particolare questo avviene per le componenti regionali (modulo 1) e pertanto il fornitore deve: garantire l aggiornamento del software a fronte della modifica delle specifiche permettere l uso delle precedenti versioni per variazioni a dossier già inviati. Import di dossier ectd La possibilità di importare dossier ectd esterni o fare la copia di dossier presenti nel sistema in modo che il dossier importato o copiato possa essere: KLever srl Via Argelati 40/A 20143, Milano, Italy info@k-lever.it Tel: Fax:

4 KLever Article Pag 4 di 5 modificato operando su singoli documenti si possa cambiare il modulo regionale per la registrazione in un altro paese si possa crearne una sequenza successiva La funzione di import permette, per esempio, di affidare ad una CRO la generazione del dossier ectd che, una volta importato nei propri sistemi sarà completato con gli ultimi documenti ed inviati all agenzia. Gestione Link Una delle richieste delle specifiche è poi la presenza di link fra i documenti e questi link fra i documenti si possono fare solo in fase di assemblaggio del dossier, le funzionalità e gli ausili nella gestione dei link è un fattore determinante per la scelta dello strumento. Sarebbe utile inoltre che in fase finale di creazione del dossier ectd eventuali link errati (broken link) non vengano comunque esportati, evitando errori in fase di import nello strumento di review dell agenzia. Le sequenze Supporto evoluto nella gestione delle sequenze del ectd. In particolare la possibilità di: avere una vista cumulativa del dossier, poter raggruppare le diverse sequenze che corrispondono a specifiche attività regolatorie ( ad es. le sequenze della Submission Iniziale, alla Variazione 1A, ) permettere la gestione di submission parallele nel caso si copia un dossier a partire da una determinata sequenza, fare una copia della versione cumulata del dossier e non delle singole sequenze Figura 2 - Raggruppare le sequence ectd in Attività regolatorie KLever srl Via Argelati 40/A 20143, Milano, Italy info@k-lever.it Tel: Fax:

5 KLever Article Pag 5 di 5 Il Teamworking La capacità di gestire il teamworking con una gestione molto dettagliata dei permessi per ogni specifico utente: a. Permette di definire le operazioni consentite a ciascun utente b. Funzioni di lock per indicare che un utente sta lavorando su una parte (modulo o sezione) del dossier c. Un Audit Trail che registra tutte le operazione effettuate nel sistema Integrazione con EDMS L integrazione con un sistema EDMS può essere a diversi livelli e fra i punti più qualificanti si evidenziano: Referenziare i documenti senza doverli copiare su altri archivi Non modificare i documenti nel EDMS (per esempio per settare i link o per configurare alcune opzioni del pdf come richiesto da specifica) Analisi di impatto per verificare quale documento ha una nuova versione dopo il suo assemblaggio nel dossier e poter decidere se aggiornare il documento (il riferimento) o meno Publishing cartaceo Funzioni di publishing cartaceo che permetta la volumizzazione del dossier con la definizione di intestazioni/piè di pagina e copertine per ogni documento. Conclusioni Non è possibile fornire una ricetta unica per la gestione dell ectd valida per tutte le aziende. E certamente possibile identificare la corretta soluzione tecnologica in risposta alla specifica esigenza. Il ruolo del partner tecnologico non deve limitarsi alla fornitura ed all installazione del prodotto di publishing ma deve comprendere la competenza ed il supporto consulenziale necessari per poter avviare un progetto ectd accompagnando l azienda cliente nella fase di Business Process Rengineering necessaria per garantire il successo dell iniziativa. Luigi Fabbro: Laureato in Ingegneria al Politecnico di Milano, è dal 1990 nel mondo IT con incarichi di crescente responsabilità in società multinazionali sia di prodotti che di consulenza. Attualmente in KLever, ha approfondito tematiche nelle aree E-Business, Knowledge Management ed Enterprise Application Integration con l obiettivo di proporre ed individuare soluzioni (prodotti e progetto), partecipando a numerosi progetti SW tecnologicamente innovativi in vari mercati. Dal 2001 ha lavorato prevalentemente nel settore Life Science. Ha svolto incarichi manageriali in area tecnica e di progetto in CTP it Services, Novell, Cambridge Technology Partners, Computer Associates e Platinum Technology. KLever srl Via Argelati 40/A 20143, Milano, Italy info@k-lever.it Tel: Fax:

6 OUR PROFILE For nearly 15 years EXTEDO is a key services and solutions provider in the field of regulatory data and document management for Life Sciences industries and authorities (Pharmaceutical, Crop Science, Chemicals). Based on well-founded expertise and many years of experience EXTEDO provides highly standardized as well as customized solutions in the area of electronic Regulatory Affairs. EXTEDO is a worldwide recognized partner in each of its engaged business activities. EXTEDO s unique market position provides a tremendous amount of inspiring influence on future-oriented new developments in the e-regulatory Affairs sector and economic long term stability. EXTEDO has designed and implemented the EURS system at and at various National Competent Authorities. EXTEDO maintains the open standard CADDY.xml for the electronic submission of Crop Sciences applications to support the mission of the ECPA. EXTEDO being globally represented, services more than 600 Life Sciences organizations in more than 50 countries. Within our focus on the Life Sciences market, we provide services and solutions in the following fields: EXTEDO GmbH Einsteinstrasse Ottobrunn / Germany Phone +49 (89) Telefax +49 (89) info@extedo.com EXTEDO Ltd. Concorde House, Trinity Park, Solihull, Birmingham B37 7UQ / UK Phone +44 (121) info@extedo.co.uk EXTEDO Inc. (North America) 770 E. Market St., STE 115, West Chester, PA / USA Phone +1 (484) Toll-free +1 (877) ESUBMISSIONS Telefax +1 (215) info@extedo.us Internet

7 Submission Management Electronic Submission Management solutions from EXTEDO support all current standards like CTD, ectd, PIM, SPL, CADDY and CADDY.xml including the new standard regarding Study Tagged Files. EXTEDO s Submission Management Systems can be integrated into standard Document Management Systems as well as Company Internal Systems via common available API s. Products: ectdmanager Suite, RLPmanager, DOCmanager, DRAmanager, EURS is Yours, PlantOS.xml, GECCO The Pharmacovigilance solution from EXTEDO is developed as a standardized software solution, especially for the classification, creation, review, submission and maintenance of ICSR, PSUR and SUSAR reports to the EMEA and the National Competent Authorities. This solution has been designed to be fully functional with elementary SW. EXTEDO s standardized software solution is a high-quality and functional product for the straightforward Drug Safety/ Pharmacovigilance Management based on the MedDRA and E2B standards. Products: PcVmanager Pharmacovigilance Management Project Management The smooth technical and process integration of turn-key solutions at Life Sciences companies requires highly specialized and dedicated services. For Life Sciences organizations it is primarily not economic to maintain the specific subject niche competence for analysis, design, integration, training and support in-house. The support of a technologically and thematically highly specialised Subject Matter Expert of a certain degree is required. EXTEDO is the specialist in the area of design, development and integration of its pioneering electronic Regulatory Affairs solutions. Software Engineers, Business Consultants, Project Manager and Managing Consultants are committed to actively progress our client specific projects at its specific phases and of different sizes. Document Management EXTEDO s value added Document Management solutions are generally based on all leading DMS from vendors like CSC, d.velop, Documentum, FileNet, IBM, Lascom, Microsoft, NextDocs, Open Text, Optimal Systems, Qumas, Saperion and others. Within extensive national and international projects regarding the installation and integration of DMS inside regulatory departments EXTEDO has acquired a well-founded expertise and recognition. Products: DOCvalidator, DMSconnect, minidms Labeling Management The Labeling Management solution from EXTEDO provides native authoring for PIM and SPL labeling information. The solution is fully integrated with ectdmanager and some Translation Memory Systems like TRADOS. Finalized PIM and SPL submissions are added when appropriate to the ectd with a single and simple drag and drop operation. EXTEDO s standardized software solution offers benefits like rule sets for editing QRD templates, managing of country specific translations, support of general translation process, validation, export and publishing of the submission as well as import of reviewed submissions from the authorities. EXTEDO s services framework is based on: Project Management Software Engineering Computer & Software Validation Business Consulting System Integration Regulatory Solution Training EXTEDO s services are processed based on a many years best practices model which is represented within a certified Quality Management System. Products: PLmanager

8 ectd - The Concept The ectd (electronic Common Technical Document) is part of the ICH (International Conference on Harmonization) initiative to provide a common format for the pharmaceutical industry for agency transfer of dossier applications that is acceptable across the ICH regions of the United States, Japan, and the European Union. This initiative is part of the primary ICH goal to facilitate the more economical use of human, animal, and material resources, and the elimination of unnecessary delay in the global development and approval of new medicines. The ectd specification is an international standard for submitting electronic dossiers. It specifies the format and the structure of an electronic submission. E X T E D O s e C T D m a n a g e r S u i t e Electronic and Paper Publishing All in One Solution! ectdmanager is an off-the-shelf scalable all-in-one electronic submission management system for ectd and non-ectd electronic and paper submissions. It provides the functions of building, viewing, validating and publishing (electronic and paper) and enables the easy-to-use compilation of compliant submissions based on CTD, ectd, IMPD and other submission structures. Important features include: Business process excellence Intuitive and ergonomic user interface Advanced features for Life Cycle Management and Control Compliance with 21 CFR Part 11 Management, submission component display, paper publishing and Report Management: Ability to start without using a Document Management System and grow to integrate with your DMS Advanced audit trail Powerful Hyperlinking capabilities: cross links powerful management of hyperlinks resolution of external hyperlink hyperlink to bookmarks automated text to hyperlink functionality according to certain technical writing standards handling of named destinations Clone submissions Easily reuse submissions for another region Sophisticated replication facilitates collaborative working in globally distributed workgroups Integrated validation procedure and tracking functionalities for ectds Management and generation of Study Tagging Files ectdmanager optionally incorporates a sophisticated replication mechanism that provides globally distributed workgroup users with simultaneous access to a submission. This also reduces network traffic and delay. ectdmanager can be easily integrated into document management systems such as: EMC Documentum Content Manager FCG First Doc, FCG First Point IBM Score Microsoft Sharepoint OpenText Livelink QUMAS DocCompliance and others ectdmanager has a powerful hyperlinking engine that automatically handles the detection, notification and correction of broken hyperlinks and many other features. Plus an integrated validation function (at no extra cost) ensures compliance of the generated submission to ICH and regional specifications. Application Benefits Working with ectdmanager ensures a fast and accurate generation and life cycle management of your submission (electronic and paper). Your main advantages for using ectdmanager are: process efficiency cost reduction and faster time to market These advantages are reached by: improved submission quality reduced preparation and update time for original applications, variations, amendments, etc. fast access to documents and ectd status for everyone involved in the project reduction of paper and lower logistics overhead support of parallel work locally and worldwide sophisticated management of hyperlinks Life Cycle Management of Pharmaceutical Submissions ectdmanager s visual structure editor provides users with the ability to build and review submissions without knowledge of XML technology. Structural elements can be easily added, edited and deleted. Documents can be scanned, copied, moved or imported by drag-and-drop from the file system or from most DMS. Hyperlinks and comments can be set at any time during submission compilation. Once an ectd-based dossier has been approved by the agency, its post approval maintenance life cycle starts. ectdmanager provides unique visual and contextual aids to ensure rapid response and accuracy. Documentum is a trademark of Documentum, a division of EMC Corporation; DocCompliance is a trademark of QUMAS; Livelink is a trademark of OpenText. All other trademarks, trade names and service marks are the properties of their respective owners. Submission Management / ectdmanager

9 DRAmanager Drug Regulatory Activity Management The management of various parallel product specific registration and approval tasks in different regions or countries at the same time represents a challenging task for Regulatory Affairs departments. Keeping a controlled overview of all dedicated product specific information and registration processes at the FDA, EMEA or other National Competent Authorities represents a major success driver within the today s Regulatory Affairs business. Based on many years of experience driven by EXTEDO s wide client base the DRAmanager has been designed and developed since 2006 to provide a common view for the accurate and efficient management of Drug Regulatory Activities. The DRAmanager has been implemented from the perspective of Pharmaceutical organizations which are engaged in multiple international drug development and approval processes. E X T E D O s D R A m a n a g e r EXTEDO developed the DRAmanager Suite as a standardized and open software solution, especially for the management of product specific information and associated regulatory tasks. An integrated workflow engine notifies dedicated users about deadlines and open tasks which are supposed to be processed in order to keep the registered products compliant from a submission, labeling as well as a drug safety perspective. The DRAmanager has especially been designed to be fully functional on elementary hard- and software requirements. EXTEDO s standardized software solution DRAmanager is a high-quality and functional product for the straight forward management of drug regulatory activities. The Concept of EXTEDO s DRAmanager DRAmanager is the implementation of an overall system architecture which complies with all regulatory activities and much more. It ensures the fast and smooth functioning of creating and maintaining drug product information and associated activities in accordance with the EMEA, FDA and National Competent Authorities. Important features include: Living drug products which adequately associates registration activities and status information Automated task processing and integrated workflow management component Parallel work supported: in-house and international Intuitive user interface with an improved learning curve Advanced features for the creation, re-use, tracking and printing of drug product information Distinguished Audit Trail The company s portfolio can be mapped in the repository with their all concerned data (product name, dosage form, composition, presentation). The system is also supported by MedDRA database for selection of the appropriate indication. This data collection can be reuse country by country, with adding relevant information about the actions done in those regions. All the submitted documents, answers for the questions and reactions from the Health Authority can be followed. Advanced Drug Activity Management via DRAmanager Once a drug product has been created within DRAmanager the product-specific life cycle and all associated regulatory activities at the certain markets can be controlled. Agency-specific questions, deficiency and approval data can be referenced and processed by the RA Manager. Easy support and overview of open tasks can be maintained efficiently. Drug specific processes and deadlines within the scope of the product can be managed in an accurate and very efficient manner. The concerned departments can be easily informed about the up-to-date knowledge with the help of reports containing regulatory status, deadlines, and the approved production-related packaging or quality requirements. The DRAmanager has been designed as a client/server architecture allowing multiple users access to one labeling document simultaneously. Drug product files can be edited and processed at different sites and imported on a central site via a corporate network. If wanted, DRAmanager can be easily integrated into document management systems such as EMC Documentum Content Manager Microsoft Sharepoint QUMAS DocCompliance FCG First Doc NextDocs DM OpenText Livelink IBM Score and others to share data sources or link to certain content objects. Documentum is a trademark of Documentum, a division of EMC Corporation; DocCompliance is a trademark of QUMAS; Livelink is a trademark of OpenText. All other trademarks, trade names and service marks are the properties of their respective owners. Submission Management / DRAmanager

10 EURS is Yours ectd Specification With the ectd Specification and the regional Module 1 Specifications an exchange standard has been established that defines how regulatory information shall be passed from industry to regulatory authorities. The ectd specifies the format and the structure of an electronic submission. To generate electronic drug applications the pharmaceutical industry uses special compilation software. Actually, both industry and authorities have a vital interest to guarantee that a submission meets all requirements of the ectd specification refined by regional requirements and officially authorized Q&A documents. EXTEDO provides EURS is Yours to regulatory authorities as well as applicants. EURS is Yours EURS is Yours is a multifunctional software solution that serves as an overall ectd validation and as retrieval software as well. It reports whether a submitted ectd-based application conforms the official interpretation of the ectd format. Furthermore it provides access to submissions allowing the user to search, view, annotate or print certain regulatory documents. EXTEDO designed and implemented EURS is Yours as a standardised software solution to cover the EURS specifications and the extensions to these specifications that have been gained by hands-on experience with ectd dossiers in close cooperation with various regulatory authorities. EURS is Yours is especially designed for the validation, acceptance, import, review and maintenance requirements of the EMEA and associated national competent authorities (NCAs). It operates with basic hard- and software and can be integrated in any information system, keeping full functionality. EURS is Yours is independently controlled by EMEA and NCAs. It will be regularly updated in the light of changes in the ICH ectd Specification and/or EU Module 1 Specification, ICH-developments and further experience gained by the agency and authorities in the context of the EMEA driven ectd Implementation Group. Benefits EURS is Yours runs on various types of IT infrastructures (standalone, groupware) and provides an intuitive and configurable user interface, configurable validation requirements to verify ectd compliance, a very fast and accurate import procedure into a standard ectd repository, extremely fast and easy-to-use search functions based on full text, TOC entries, annotations or ectd-based attributes, easy-to-use application to improve electronic reviewing processes with an integrated, context-sensitive online-help. From the authority s point of view the most important features of EURS is Yours are that it accesses submissions fast and smoothly and that it covers the entire life cycle management of a drug product. This results in further benefits like support of parallel work (inhouse and international), advanced features for validation, import, display, search and printing, extensive audit trail, powerful navigating tools (hyperlinks, private and public comments, enhanced search). Life Cycle Management of Pharmaceutical Submissions Once an ectd submission has been imported within EURS is Yours by the agency its drug approval maintenance life cycle starts. Added, Deleted, Appended or Replaced documents, i.e. every version-related change of the dossier, are visualised by self-explanatory icons. Submissions can be organized by certain Regulatory Activities which are representing the overall regulatory status of a drug product. EURS is Yours allows different users access to one dossier simultaneously. Optionally a sophisticated caching mechanism (Central Repository) can be implemented especially for using EURS is Yours in internationally distributed workgroup communities. This reduces network traffic and waiting periods. If wanted, EURS is Yours can optionally be integrated into state-of-the-art document management systems by using standard interfaces. Submission Management / EURS is Yours

11 PlantOS.xml Suite To meet the requirements of EU, US and Canadian authorities the crop sciences industry has to use different standards and different technologies. A common worldwide understanding of how to submit pesticide registration application documents would facilitate the interchange of dossiers between industry and the competent authorities. More recently, an additional standard CADDY.xml has been developed and authorized by the European Commission. It will allow a better integration with the internal information system of regulatory authorities. CADDY.xml is aligned with future developments at OECD level, which go in the direction of xml-based submission templates, and will facilitate broader exchange of regulatory dossiers also in regions and countries where CADDY is not used. EXTEDO s off-the-shelf Submission Management System PlantOS.xml is the implementation of CADDY.xml and much more. It is a high-quality and functional product for the straightforward assembly and compilation of compliant electronic dossiers based on the standards: CADDY.xml (EU) PDF-submissions (USA) e-index (CAN) and still paper PlantOS.xml The PlantOS.xml system is an internationally applicable software solution for publishing electronic and paper-based submissions based on one single process. The general dossier structure is based on regional format templates which can be interpreted by PlantOS.xml. The benefits of PlantOS.xml include: Improved dossier quality Reduced preparation and update time for new submissions, supplementals, amendments, etc. Fast access to documents for everyone who has access to the electronic dossier Shorter approval times which means reduced time to market Less paper quantity and lower logistics overhead Advanced archiving capabilities PlantOS.xml is the implementation of CADDY.xml, US based PDF-submissions and Canadian e-index. It ensures the fast and smooth functioning of a submission with the following additional benefits: Generation of PDF-submissions and the xml-based e-index Living dossier Parallel work supported: in-house and worldwide Intuitive user interface Supports e- and p-publishing in one controlled process Powerful navigating tools: links, private and public comments, bookmarks Life Cycle Management of Crop Sciences Submissions Structural elements can be edited, added and deleted and documents can be copied, moved or imported by drag and drop from other dossiers (DMS). Links, comments and highlights can be set at any time during compilation since documents are referenced relative to a structure element. Once an electronic dossier has been approved by the agency, its Post Approval Maintenance Life Cycle starts which is comprehensively supported by PlantOS.xml. The following icons visualize any version related change of the dossier: Document was added to the currently selected submission. It is of regulatory relevance. Document has been re-assigned by the applicant. Document has been replaced by a new document. The new document is now relevant. PlantOS.xml has been designed as a client/server architecture allowing different users access to one dossier simultaneously. EXTEDO s PlantOS.xml can easily be integrated into state of the art document management systems such as EMC Documentum Content Manager Within a short time: FCG First Doc, FCG First Point IBM Score Microsoft Sharepoint OpenText Livelink QUMAS DocCompliance and others PlantOS.xml view The PlantOS.xml Suite is improved by a set of specific added value products. PlantOS.view represents the read-only application to fully access the dossier-specific submission and associated attributes. The entire retrieval capabilities are supported by PlantOS.view as well. Documentum is a trademark of Documentum, a division of EMC Corporation; DocCompliance is a trademark of QUMAS; Livelink is a trademark of OpenText. All other trademarks, trade names and service marks are the properties of their respective owners. Submission Management / PlantOS.xml

12 Automated Document Compliance Check Globally oriented organizations as well as small to medium-sized companies have mostly established corporate documentation standards and guidelines which are used within product development, technical documentation and regulatory submission management. Most documents are written based on such standardized templates. Even today, technical writing and reporting are still rather manual tasks. Therefore, it can happen that document formats are changed and thus do not correspondend with specific templates and documentation guidelines. The greater the number of authors, the higher the risk of violating the standard. Inconsistencies within the technical documentation may lead to non-compliance with the format-specific requirements and may for instance cause delays in the submission publishing and reviewing process. DOCvalidator We Take A Step Beyond EXTEDO s DOCvalidator is an application that reports formatting errors with documents (MS Word + PDF). It enables your organization to verify the compliance of documents against a set of predefined corporate formatting standards. From the collection of document specifications the following list provides an initial overview of the test, which specifications are executed and reported: Document Level (margins, page numbering, header and footer, section breaks, macros, hyperlinks, template name) Chapter Level (text alignment, headings) Character Level (font type, character size and colour, page and table numbering) DOCvalidator can be configured to meet your specific documentation standards. Your Advantage Working with DOCvalidator ensures a reliable and smooth integration of legacy as well as newly created documents into high-level publishing processes. Your main advantages from using DOCvalidator are Process efficiency from a regional as well as global product documentation perspective Cost efficiency based on the accurate automation of a time consuming management process Shorter time to market based on a reliable quality ensured document release process These key advantages are reached by: an improved document quality a reduced publishing time being delayed by insufficient document formats a semi automated document compliance check with regard to corporate or regulatory guidelines DOCvalidator checks both Word and PDF documents. It can verify the compliance of legacy documents or externally created documents which have to be integrated into company specific document management and publishing processes. DOCvalidator can optionally be used together with the DMS Documentum, IBM SCORE, CSC firstdoc etc. to verify the compliance of documents with regard to specific life cycle states. The concept is to state only those documents EFFECTIVE that match the corporate formatting standards. Based on the fact that the Regulatory Agencies are strongly moving forward to an electronic only process, the overall quality assurance of electronic documents becomes a crucial success driver with regard to long-term archival and Regulatory Compliance. Document Management / DOCvalidator

13 Adverse Event Management The Concept of PcVmanager The electronic reporting of SUSARs (Suspected Unexpected Serious Adverse Reactions) and ICSR s (Individual Case Safety Reports) to EMEA and National Competent Authorities represents a major task in pre- and post-authorisation of a medicinal product. The E2B Specification is an international standard for creating and submitting electronic case safety reports across the entire life cycle of associated drug products. The E2B specifies the format and the structure of an electronic case safety report. The benefits of the PcVmanager include: Ability to work with standardized gateway supporting the required encryption protocols AS2/AS1, etc. Integrated Workflow Engine and Task View Full Scalability (start small in a local environment) 21 CFR 11 compliant Based on the ICH initiative a standard called E2B has been implemented by Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 according to the EudraVigilance project to provide a common format for an electronic and efficient adverse event reporting. PcVmanager has been implemented from the perspective of the Pharmaceutical Industry to enable its users to classify, create, review, submit and maintain adverse event reports. PcVmanager is supported by an embedded Workflow Management and Reporting Component. EXTEDO s PcVmanager EXTEDO developed the PcVmanager as a standardized software solution, especially for the life cycle management of mandatory SUSAR and ICSR reports to the EMEA and the National Competent Authorities as well as all reported SAE s for an overall safety re-evaluation. The PcVmanager has been designed to be fully functional with elementary hard- and software. EXTEDO s standardized software solution PcVmanager is a high-quality and functional product for the straightforward drug safety management based on the E2B and MedDRA standards. Runs on various types of IT-infrastructures (standalone, groupware, DMS based, via the web) Customizable validation requirements to import E2B-XML files Very fast and easy search functions based on case report data or MedDRA codes Easy to learn and easy to use application to improve business processes PcVmanager is the implementation of the E2B specification and much more. It ensures the fast and smooth functioning of creating and assessing reported adverse events and to adequately cover the regulatory requested case safety report and drug safety management: Fully compliant with the regulations, directives and the general guidance related to electronic reporting of adverse event reporting Support of SUSAR, ICSR, CIOMS I Reports, CIOMS Line Listings and Tabulated Summaries as well as MedWatch Reports Adverse Event Management availability of all E2B specified fields case tracking / history comments case validation check additional attachments for cases like CIOMS I, , etc. versioning of cases Extensive Reporting Capabilities Integrated MedDRA Browser Integrated E2B gateway for direct Submission to the EudraVigilance Clinical Trial Module (EVCTM), the EudraVigilance Post-Authorisation Module (EVPM), national regulatory authorities and global trading partners gateway Adverse Event Reporting via E2B Once an adverse event report has been created, verified and validated it can be submitted to any competent agency, and/or business partners via: an E2B compliant gateway [EudraVigilance gateway] XML import to EVPOST an system as XML-file or document attachment Paper based reports [electronically and/or printed] as CIOMS I Form as MedWatch Form Drug-specific adverse events can be managed in a very accurate and efficient manner. The following icons visualize the type of drug safety report: SUSAR (Suspected Unexpected Serious Adverse Reaction) ICSR (Individual Case Safety Report) The PcVmanager has been designed as a client/server architecture allowing multiple users to access one adverse event report simultaneously. Case Reports can be reviewed at different sites and imported on a central site via a corporate network based on the E2B Specification. If wanted, PcVmanager can easily be integrated into state of the art document management systems such as DOCUMENTUM, Livelink, Qumas, SCORE or others and connected to company specific databases. Pharmacovigilance Management / PcVmanager

14 PLmanager Product Labeling Management Improved B2G communication via PIM in the EU The creation, management, translation and submission of Labeling information for research and development or esubmission processes to the FDA, EMEA or other National Competent Authorities based on the regional Labeling standards SPL (Structured Product Labeling), PIM (Product Information Management) or beyond - represent a business critical regulatory task within the drug approval and maintenance process. Based on the regional initiatives driven by the FDA and the EMEA new standards called SPL (FDA) and PIM (EU) have been implemented to provide a common electronic format for the accurate and efficient management of drug specific labeling documents. The PLmanager has been implemented from the perspective of the Pharmaceutical organizations which are engaged in international drug development, approval and maintenance processes. E X T E D O s P L m a n a g e r EXTEDO developed the PLmanager Suite as a standardized and open software solution, especially for the creation, review, translation, maintenance and submission of electronic labeling documents e.g. Company Core Data Sheets (CCDS), SPL and PIM files and more, to the support internal as well as an integrated translation and drug approval process with EMEA and the FDA. The PLmanager has especially been designed to be fully functional on elementary hard- and software requirements. EXTEDO s standardized software solution PLmanager is a high-quality and functional product for the straight forward Product Labeling management process. The Concept of EXTEDO s PLmanager The PIM (DES) and SPL specifications are an international standard for creating and submitting electronic labeling documents across the entire life cycle of associated drug products. PIM (DES) and SPL specify the format and the structure of an electronic labeling document. The benefits of the PLmanager include: Runs on various types of IT-infrastructures (standalone, groupware, DMS based) Full support of all DES versions from 2.2 up to the newest one Full support of SPL Different users with simultaneous access Integrated validation mechanism according to the DES and SPL Integrated annotation and translation management Provides the interface of external translation tools (like SDL/Trados) Accurate and efficient management of labeling templates Easy to learn and easy to use application to improve business processes Once an electronic labeling document has been created, validated and submitted to any agency the product specific life cycle starts. Agency specific annotations can be imported and processed by the sponsor. Easy support and overview of open translation tasks can be maintained efficiently. Drug specific changes within the scope of the product can be managed in an accurate and very efficient manner. The following common sense icons visualize the status of any type of the designated labeling documents: Mandatory elements have not been edited yet Translations are still open to be completed Language specific labeling has been completed The PLmanager has been designed as a client/server architecture allowing different users access to one labeling document simultaneously. Labeling files can be reviewed at different sites and imported on a central site via a corporate network. If wanted, PLmanager can easily be integrated into state of the art document management systems such as EMC Documentum Content Manager FCG First Doc, FCG First Point IBM Score Microsoft Sharepoint OpenText Livelink QUMAS DocCompliance and others Documentum is a trademark of Documentum, a division of EMC Corporation; DocCompliance is a trademark of QUMAS; Livelink is a trademark of OpenText. All other trademarks, trade names and service marks are the properties of their respective owners. Labeling Management / PLmanager