SummaryThe last year has been a turbulent one in regulatory terms, with a raft of legislative changes as patient safety and global standardisation have risen up the agenda. Joel Finkle & Gillian King of CSC assess the changes.
In the US, the FDA is pursuing an electronic submissions strategy fairly aggressively, though favouring phased migration. The goal is mandatory eCTD submission, driven by the Food and Drug Administration Safety and Innovation Act (FDASIA). This also includes the acceptance of electronic submissions for devices. Under the FDASIA, all New Drug Applications (NDAs) must be filed electronically by 2015; all Investigational New Drug Applications (INDs) by 2016.
The FDA has also been developing guidance for Module 1 version 2, which enables the submission of promotional materials in electronic format and grouped submissions, permitting companies to use one submission sequence to update multiple applications.
The biggest difference is version 2’s structure. Instead of a complex XML format, there will simply be one element that identifies where forms go, another for promotional materials, and a keyword to pinpoint the kind of promotional material or the particular form being sent – much the same as eCTD 4.The use of controlled vocabularies is another major change to Module 1 and should mean fewer software upgrades.
In Europe, patient safety is high on the agenda. As of July 2012, it has been mandatory to provide EudraVigilance Medicinal Product Dictionary (EVMPD) data for every product authorised for sale in the EU. After initial uproar, the unrest around this not insignificant demand has largely subsided. The main outstanding concern is around data updates. Any changes to data have to be submitted within 15 working days and companies are seeking clarification on what this means in practice.
Further changes concern clinical trials. Currently companies must get approval from each EU country in which they conduct a clinical trial, and from both the national authority and ethics committees. The EMA wants to harmonise the process to facilitate centralised approval, though details have yet to be issued.
Meanwhile health authorities’ lack of specific approval or timely will imply tacit approval. There are some worries about the planned introduction of a European portal however, due to a dearth of practical information.
With patients a top priority, the European health authorities have developed strict guidelines to control anything a patient reads - on a product’s packaging, in the accompanying leaflet or in promotional material. The goal is harmonisation across European agencies but translation issues remain a problem.
The European Commission has issued a directive on medical devices in the wake of the scandal over breast implants. Changes are to include stricter rules on (1) how devices are to be made, sold and distributed; (2) the conduct of clinical trials and the production of evidence; and (3) pharmacovigilance reporting. However, the guidelines are not expected to be adopted by the EU until 2014 and will not come into effect until 2015-2019.
In Japan, the eCTD is still not mandatory in Japan but the Pharmaceuticals and Medical Devices Agency (PDMA) now plans to shorten the review process, inspiring new interest among smaller organisations. Larger pharma companies have already been using the eCTD for 3-5 years. Patient safety is also prevalent priority in the country. As of April 2013 companies filing approval applications for new drugs and follow-on biologics will be required to develop a risk management plan.
The International Conference on Harmonisation (ICH) has been developing IDMP standards aimed at improving the consistency in product terminology and the exchange of product information across its members, though nothing is expected before late 2014/early 2015.
The approved standard will be based on technology used for Structured Product Labeling. The goal, in part, is to improve visibility of where products are sold and used in case adverse events or product recalls occur, This is achieved through the use of ID numbers.
The eCTD 4 is finally in a tentative standard and it is hoped that initial implementation in at least one region -- likely the US -- will take place by 2015 following ISO approval.
With all of these changes afoot, and more to come, companies will need to pay ever greater heed to how they manage their processes and to their efficiency in handling submissions.