Case Studies

Converting a 505(b)(2) NDA from the United States into a European MAA

published 16 Nov 2020

Project based on:

Preparation and coordination of a hybrid marketing authorisation application in 12 EU countries for a topical product authorised in the United States via the 505(b)(2) pathway.

Company Description:

A small pharmaceutical company based in the United States, focused on development of products for pain relief.

Support required/Problem statement:

The client had no regulatory or commercial presence or representation in the EU, therefore needed a complete regulatory service package including:

  • project management;
  • gathering of intelligence;
  • preclinical, clinical, CMC and procedural due diligence and technical consultancy;
  • strategy setting;
  • protocol review;
  • coordination of scientific advice meetings;
  • MAA preparation, eCTD publication and submission;
  • DCP management;
  • communication with competent authorities.


Scope/added complexity:

The scope of the project was to to convert the US NDA into a submission-ready package for the EU and to manage the marketing authorisation application procedure through to completion.

The project was complicated by various factors:

  • This was an inherently complex topical product for which US and EU regulatory requirements differed significantly.
  • The various stakeholders were located across three continents, with the sponsor in the US, the manufacturer in Asia and the importation/batch release site, QPPV and regulatory services in the EU. This required sensitivity with regard to cultural differences and approaches.
  • The client had limited knowledge of European regulatory affairs and scenarios and needed/welcomed guidance on all matters, even logistical arrangements such as selection of hotels for agency meetings etc.

As the client had no legal presence in the EU, RRL stood in as temporary MAH, requiring three-way technical agreements to be set up between sponsor, RRL, and batch release and pharmacovigilance service providers.

Method:

The project was managed through one point person at RRL – a senior consultant – who coordinated with the sponsor’s core team, and organised contributions by other RRL consultants and subcontractors as and when required. The point person met the client core team via teleconference at least once a week, with frequent additional ad hoc meetings. RRL staff also had occasional face to face meetings with members of the core team.

The first step in tackling the project was preclinical, clinical and CMC due diligence of the US NDA, followed by technical consultancy to guide the client in dealing with the identified gaps. This process took 2.5 years and several other aspects of the project were tackled simultaneously as outlined below. The technical consultancy included extensive guidance, input into all preclinical, clinical and CMC protocols and review of all reports.

A regulatory strategy was devised, first for scientific advice and later to pin down the target countries for a DCP and select the preferred RMS. Strategy setting also involved freedom of information submissions in the UK.

Scientific advice meetings were organised in three countries. This involved submission of applications; briefing book preparation; logistical coordination of the meeting itself (accommodation, mock meeting, preparation and delivery of the presentation during the scientific advice meeting proper, post mortem, compilation of minutes).

Agreements were set up with the importation and batch release site as well as the pharmacovigilance service provider. RRL contributed significantly to compilation of the RMP.

Finally, RRL compiled the MAA (Modules 1-5) and managed all aspects of the DCP, including all communication with competent authorities and technical assistance with responses to deficiency letters.

In the later stages of the project, RRL assisted the client during discussions between the client and potential commercial partners in Europe.

Activities to date/Issues resolved:

The project has been completed and the client has expressed the wish of working with RRL for future projects in Europe.

Additional Information:

Reporting to: VP Global R&D

Duration of contact: 2015-2019