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DLRC has recently supported a client in the resolution of unexpected quality issues during the registration of a novel analgesic formulation.
The application to register this formulation was submitted part way through the stability programme for the product. During the assessment process, out of specification stability results were detected at both different time points and stability conditions.
To resolve this issue, Carl from DLRC provided regulatory and project management support to the client by leading the investigation into the potential root cause of the out of specification results. This involved liaising directly with, and managing third party manufacturing sites and analytical laboratories.
Once the root cause and the required corrective actions had been identified, Carl from DLRC successfully negotiated a resolution of the issues with the Regulatory Agencies on behalf of the client. The out of specification results were notified, a justification made as to why the out of specification results had no adverse impact on the safety and efficacy profile of the proposed formulation, and corrective actions proposed.
After the negotiations with the Regulatory Agencies, Carl from DLRC prepared a formal report to explain to the Regulatory Agencies the reason for the out of specification results and why the corrective actions resolved the issues. Amended CMC sections of the Marketing Authorisation were prepared by DLRC based on data from third party sources. These documents were then combined as part of a grouped variation package required to amend a Marketing Authorisation.Once the documentation was finalised, it was published by Laura from DLRC using specialist software to ensure a technically valid submission. All corrective actions were approved without any requests for information (RFI) being received and with no negative impact on the Marketing Authorisation approval.
DLRC has supported a centralised Marketing Authorisation Application (MAA) for a novel formulation of an oncology drug. The clinical development programme was almost completed when we joined the team (2015) but the study reports were still being finalised. We provided support for multiple agency meetings including authoring of a number of supporting and briefing documents and delivery of presentations to the Regulators. We also provided feedback on the Clinical Study Reports helping to ensure consistency with the proposed labelling as well as scientific accuracy.
DLRC oversaw the finalisation of the CMC sections of the dossier ensuring consistency of formatting and correct document granularity. We were actively involved in the review of the summaries and overviews in Module 2 and provided feedback to authors to help ensure compliance with the relevant guidelines. Once all of the documents were finalised we ensured that they were all appropriately hyperlinked and used our specialist software to publish a technically valid eCTD sequence. This was transmitted to the European Medicines Agency using their eSubmission Gateway, meaning that the dossier was submitted to concerned parties in parallel. The dossier was successfully validated and the assessment clock started on schedule. DLRC applied scientific and regulatory expertise together with effective project management to ensure that this application was submitted on time and then validated by EMA. DLRC continues to support the application.
If you would like more information about Marketing Authorisation Application (MAA) Filing Support or would like assistance with an MAA Filing, please contact our trusted and resourceful team: Email DLRC or call +44 (0)1462 372 472
DLRC has supported a development programme for a first in class oncology drug in a haematology indication. The entry into humans (EIH) study was in progress when we joined the team (2012) and we have since supported the European Programme that has taken the molecule through a second phase 1b study in a new indication to the start of the Phase 3 programme. Not for the first time, we have been successful in in using the Voluntary Harmonisation Procedure for the Phase 3 study in Europe. There have been complexities including a reformulation of the drug product requiring a bioavailability study and additional work to determine the dose to take forward in development.
During this time we have lead the team through national scientific advice in two EU countries and three CHMP scientific advice/protocol assistance requests. Orphan designation was required and following a submission that progressed without any issues at validation, it was granted at Day 30 of the procedure. A Paediatric Investigation Plan was required because the lead indication was not included on the list of class waivers.
We managed the writing of the PIP application, the response to request for modification at Day 60 including a clarification meeting, and conclusion of the procedure according to the required timeline of the team. DLRC continues to support the programme.
Our client is developing a first in class molecule for a paediatric indication of high unmet medical need. Following a conventional Phase 1 program in adult volunteers, the drug was to be tested in the target paediatric patient population which included infants and toddlers. DLRC supported the client in obtaining national scientific advice in the UK and France on the proposed first in paediatric study design allowing for subsequent timely CTA approvals in key EU countries.
The client also wanted to ensure that key aspects of the development program were acceptable in both the EU and US. In the absence of regulatory precedence or guidance for the disease area, DLRC proposed and managed a parallel FDA/CHMP scientific advice procedure during which alignment on the regulatory position of FDA and CHMP was obtained.
Following this successful advice procedure, DLRC worked with the client's development team to advise on and manage the preparation of a Paediatric Investigation Plan (PIP) application. The PIP procedure was completed on schedule, prior to the initiation of Phase 2.
As a result of the successful collaboration on this project, DRLC was contracted to provide EU regulatory support for two of the company's other early phase projects.