Implementing Regulatory Information Management (RIM) systems
- One project was the implementation of a next major version of an existing shell on top of Documentum® at global headquarters of a Tier 2 pharmaceutical company a couple of years ago.
- Another project concerned the configuration of Documentum® at global Headquarters to manage regulatory documents for eCTDs for the eCTD accepting countries for a Tier 1 biological-pharmaceutical company.
- Another project was a Circular Information Management implementation using a single tool for the data, document and dossier management at global headquarters, regional hubs and local affiliates of a Tier 1 pharmaceutical company. This program focused, though not limited to regulatory affairs.
- For the eDMS major version project, the company had already decided to go for a next major version of the existing shell. However, they wanted to take the opportunity to reduce the rework on documents to prevent country-specific documents and to accommodate for inability to clone master dossiers to country-specific eCTD sequences.
The main challenges were to create awareness about the ‘less = more’ principle and visualize how more dossiers could be created with less documents and how more transparency could be achieved in less time.
- The Documentum® configuration project initiated by the time eCTDs became mandatory for the Centralized Procedure in the EU. At that time this company had only submitted paper dossiers or digitalized paper dossiers. Guidance on eCTD lifecycle management was available, but the technical operations ‘new, append, replace and delete’ were difficult to comprehend and what impact it has on document granularity and future transparency of the eCTD lifecycle. Moreover, in general, the RA professionals were very much focused on the submissions that had to go out now and could not clearly see how a product lifecycle could be reflected in a dossier lifecycle.
- The implementation of a comprehensive eDMS, RIM and publishing tool was to be rolled out globally. The most challenging was the alignment of country-specific differences in dossier format and disharmonized regulatory follow up for an identical change. Though ICH harmonizes the CTD format, it does not touch on:
- what is considered a pharmaceutical product, drug substance, medical device, cosmetic or food supplement
- whether or not multiple dosage forms, strengths and packaging is registered under a single number or multiple numbers
- what is considered a major, moderate or minor change, or even does not have regulatory impact
- whether in SAP, a change in color results in a different product ID, whereas in the eCTD it remains within the same lifecycle with the same marketing authorization numbers.
- whether changes could be submitted together, separate in parallel or sequential
- significantly different review and approval times by health authorities
- whether different changes to be made to obtain approval; sometimes even contradictory (e.g. about definition of substance and corresponding values for strength; different interpretation of active and excipient)
- significantly different implementation times following approval by health authorities
Considering the complexity listed above, the biggest challenge was to ensure that the software vendor understood all touch points and impacts of the features they applied within their software to fulfill the needs of the business people.
Description of the projects
- To counteract the challenge about awareness, Qdossier worked with a team of representatives from global Regulatory Affairs. We applied the principles to separate content from context. To allow the team members to see the reasons for separating content from context, Qdossier developed a dossier content plan to define document granularity, document naming (using fixed and variable parts) and document header information. Herewith the team could envisage how dossiers could be structured to define the context of documents. They also could comprehend how what content documents should have and that the context does not have to be within the document, but how that could be deduced from the dossier (e.g. cover letter and application form).
Subsequently, the document granularity and related mandatory metadata fields were configured accordingly in eDMS. A set of Qdossier document templates were developed to reflect each individual document type listed in the content plan and assigned to correlating document types in the shell.
Subsequently, we zoomed in on the use of document templates (page layout, headings and headers), authoring styles (factual and direct as compared to gobbledygook) and proper use of MS-Word features. We also trained the authors on document authoring to implement a lean, active authoring style, omitting obvious references and repetition of information, is so much easier to comprehend. The team also understood that documents should describe content; no context, as the latter was deduced from the dossier’s Module 1 documents.
MS-Word features applied properly, results in eCTD-ready documents upon rendering to PDF. This prevented or reduced the need for post-finalization publishing. The correct document granularity and naming, allowed to produce standalone documents that were reused without rework for multiple purposes. At the same time, these standalone documents could be finalized independently from other documents; so less effort on the critical path. The existing integration between the previous version and their eCTD building tool was easily applied on the new version. Now the ‘where used’ function could easily show in which dossiers a selected document has been (re)used and for what purpose.
- For the Tier 1 company, Qdossier applied a similar approach as described above. However, in this case it was just on top of Out of the Box Documentum® without any configuration. Qdossier’s templates are being delivered in a folder structure, somewhat like the ICH CTD structure, but modified to separate content from context. Herein, we have distinguished
- what was specific for the finished product, substance, excipient or packaging material
- what was managed by the various disciplines (e.g. regulatory affairs, labeling, chemical-pharmaceutical development and production, nonclinical development and clinical development, pharmacovigilance)
- what are time independent documents and what are time dependent documents (latter being clinical overviews, response documents and investigator brochures)
This folder structure has been configured at plain Documentum®. The metadata as defined by the content plan has been configured in the eDMS accordingly. Together with the team we developed dictionaries for finished products, substances, manufacturers, countries, packaging materials, etc.. Those pick lists must be used when creating a document. The mandatory properties were dependent on the document type and limited to a minimum, considering the content only.Once the configuration was done and product documentation was created to a finer document granularity and proper naming, the company wanted to create baseline submissions for their most complex product. Though this was a time consuming effort, the transparency gained was enormous. Soon all other colleagues wanted to have baselines for their products too. It resulted in baseline dossiers for all their centrally registered products. Unfortunately, the EMA considered that the baseline was to be considered a Type II variation, because of the total amount of typo corrections, removal of outdated information and harmonization across sections. Subsequently, the company did not submit the other baselines, but used these as starting materials for any future variations.
- The global company, rolling out the eDMS, RIM and eCTD building features globally, organized various meetings with various stakeholders from different disciplines and different locations. The meetings concerned introduction,- configuration-, migration-, training-, and implementation meetings with the software vendor they had selected. At a certain stage, Qdossier was hired to liaise between the vendor and the company. The vendor knew exactly what features the tool could do; individual business people knew exactly what they wanted. Qdossier was able to bridge the gap between those two fields of expertise. In some of the cases it was just to provide clarifications of what a sender was messaging. In general, it was very important that people started thinking in electronic processes, rather than paper processes (or digitalized paper processes). By providing appealing examples, Qdossier was able to influence the way the tool should follow the Best Practice existing process or the way existing processes could be revised to follow Best Practice electronic processes. By investigating why individual countries have established certain rules and structures of dossiers, how different definitions of a product were applied, we worked towards common denominators. In general this was obtained through finer granularity and separating content from context.
- Benefits for the customer upgrading to the next version of the shell on top of Documentum® were that far less documents needed to be created; less time spent on publishing; transparency within the eDMS and ability to take advantage of the ‘where used’ feature within the eDMS (pointing to multiple named dossiers and sequences).
- Benefits for the customer configuring Documentum® from scratch were similar to the ones above. In addition, in the eDMS, there is a comprehensive starting point for all future variations. The company established future proof eCTD lifecycles in a way that a ‘current view’ within of the eCTD represents only documents that represent the currently proposed and registered product. Therefore, the current view could be cloned for any new countries/regions, requiring primarily replacement of country-specific Module 1 documents. Considering the Brexit, this company is ready to create a current view from their eCTDs and submit that as Sequence 0000 to the MHRA.
- Benefits provided by Qdossier for the customer rolling out an comprehensive global tool, were primarily bringing together the business people and software engineers and develop common denominators to describe marketing licenses, products and regulatory procedures across. Subsequently a lean business process could be described to fulfill the majority of business needs (if not all) and the software engineers were able to deliver solutions facilitating the process through predefined workflows. After the Go-Live date the tool was embraced by the users and they are more than happy to share their experiences.
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