Case Studies

Challenge

• Client planned to initiate a Phase 3 clinical trial and was evaluating several design options to support global registrations.
• The proposed product was a rare disease treatment, a borderline biotech with advanced medicinal therapy (ATMP) and a high-tech drug-device combination.

Solution

• A scientific advice briefing package was authored, leveraging the company’s available data and desired areas of clarification.
• The briefing was processed via EMA’s IRIS system, a standard procedure.
• Note 1: Option of seeking EMA Service desk guidance was considered but dismissed due to the stage of product development, type, and extent of questions, as well as the nature of the product and its potential classification.
• Note 2: EMA Orphan designation and PIP applications were recommended to the client.

Benefits

• Time and resource efficiency on the client’s side for the authoring of an extensive scientific advice briefing package.
• Leveraging the option of free EMA scientific advice for high-tech medical device-drug combination products resulted in a beneficial cost optimization for the development project and informed classification of the product.
• Adjusting the Phase 3 clinical trial design to global key health authorities’ feedback, including EMA, enabled the client’s goal of global registration with only one Phase 3 study.

Challenge

• Client had a biotech product for an unmet medical need in Phase 3 development and was considering the best approach for initial registrations in Europe.
• The aim was to submit marketing authorisations applications (MAA) the quickest possible way in EU, UK, and Switzerland.
• Based on regulatory strategy, client was planning to optimise late steps of the Phase 3 data generation to support the most optimal MAA filing.

Solution

• Pre-submission briefing package were authored, and a pre-submission meeting was organised with EMA to inform them on the program R&D and clinical status, target product profile, and estimated timelines. Option of conditional marketing authorisations was discussed as an option with conditions and flexibility outlined.
• Based on the discussion with the EMA, an international procedure (IRP) with EMA was suggested for the UK and a pre-submission meeting with MHRA was organised.
• Flexibilities as well as potential submission in parallel to EMA’s ongoing assessment was discussed.
• In parallel, a similar approach was suggested to Swissmedic for Switzerland, leveraging EMA as the reference and supported by a local regulatory Marketing Authorisation holder. A strategy that client could partner with A-REG on in the future.

* Marketing Authorisation holder in Switzerland can be only a legal entity having its legal seat based in Switzerland.

Benefits

• Time and resource efficiency for the client’s pre-submission meeting briefing package and for the health authority’s interactions with the organisation.
• Conditional Marketing Authorisation option allowed for parallel submission of the MAA during the completion of the Phase 3 clinical trial, enabling initiation of the assessment while additional data were still being generated.
• Reliance route for UK and Switzerland offered time savings during the regulatory assessment timeline for both countries as well as regulatory dossier content alignment, supporting flexibility for future commercial deliveries.

Challenge

• Client has been planning to file parallel applications for initial marketing authorisation (MA), including WHO for a biotech product addressing an unmet medical need.
• The Health Authorities (HA) were requesting regular updates and progress reports.
• There was a frequent exchange of information among the HAs and ongoing parallel communication was critical for all involved HAs.

Solution

• Preparation of a comprehensive data package detailing current status, extent of data available and timing of future inputs.
• Offered several HAs a joint meeting where information was shared and discussed/via Q&A session, to support the eventual joint assessment.
• Organised a shared EMA, TGA and WHO virtual meeting with the client (including several pre and rehearsal meetings, debrief meeting and meeting minutes).

Benefits

• Time and resource efficiency on client’s side (1 HA meeting instead of 3, 1 meeting minutes).
• HAs heard the same information at the same time and had opportunity to ask questions and hear the responses to questions asked by a different HA.
• WHO confirmed their assessment will be based on EMA, while TGA didn’t comment whether they planned to follow EMA via reliance route, similar to WHO, but confirmed the dossier for EMA/WHO and TGA would be different due to different requirements for batch release.

Challenge

• Client planned to add a new alternative finished product (DP) manufacturer, that manufactures the product packed in a different container closure system, essentially a new presentation format.
• Commercial DP deliveries were planned from the new manufacturer as soon as possible.
• For the EMA region as well all countries, that were following the EMA reliance route in their assessment.

Solution

• Preparation of regulatory strategy including its validation with Health Authorities:
• EU (EMA): Type II variation
• UK (MHRA): line extension (new PLGB number) with limited content, referencing to previously submitted data, hybrid DP procedure parallel to EMA assessment.
• Singapore (HSA): MIIv2 (major) variation including complete current dossier baselining (+ complete line extension (Taiwan (TFDA), PMF process complete (GMP certification) and major variation submission with complete data package in parallel to EMA assessment, using EMA as reference HA.
• Significant contribution to preparation of CMC data package covering all CTD documents (complete new 3.2.P folder of the CTD).
• Authoring of QOS (Module 2.3 of the CTD), complete Module 1 including labelling and co-authoring data package required for the GMP certification or confirmation in Taiwan and other countries.

Benefits

• Time and resource efficiency on client’s side and manufacturing site’s side.
• Maximal utilisation of regulatory reliance route, using EMA as a reference.
• As a result of a reliance procedure approach, minimum CMC documents differed in data package for each of the HAs, this provided flexibility in manufacturing and batch release of commercial goods as batches could be processed in identical ways for all markets up until the packaging step.
• At the same time optimisation of the time-to-market by negotiating with HAs the assessment in parallel to EMA.