Since the early 1990s, there has been an increasing focus on moving many of the regulatory review aspects of new drug approvals to an electronic medium.
The evolution of technology resulting in more affordable high-powered processing coupled with a global adoption of an electronic communications platform – the internet – has resulted in a near-exponential increase in the number of ‘e’ initiatives driven by both regulators and industry.
Early efforts were innovative yet uncoordinated – in other words, the FDA developed its own strategy while other countries such as Germany came up with other plans.
The initial response from industry was one of cautious optimism. It wasn’t until the FDA announced that it would accept an all-electronic submission as THE submission that companies began to truly pursue the necessary technology solutions to aid in the construction of electronic NDA (eNDA) submissions.
Meanwhile, other regulatory authorities were less aggressive about implementing environments for the acceptance and review of electronic submissions.
Further complicating the situation is that most, if not all, of these countries would need to change their laws in order to allow an all-electronic submission to be the official (archivable) submission of record. In nearly every European country, a paper copy of a new drug application is still officially required, even if the authority has the desire and the capacity to accept and review an electronic submission.
Harmonisation – almost
More recently, The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) launched a project to bring together the regulatory authorities of Europe, Japan and the USA and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of product registration (see box story The ICH parties).
While the ICH has been facilitating the development of a number of initiatives aimed at harmonising many approval-related activities, the activity around developing a new drug application format that can be used – and re-used – for several regulatory authorities has been one of great interest and speculation.
Having already reached consensus on the organisation and structure of a new drug application in the common technical document (CTD) specification, focus has now quickly turned to the development of an electronic packaging of the format – resulting in the electronic CTD or eCTD.
While the CTD specification defined what information was required in the submission and its logical organisation, the eCTD defined the technical aspects of delivery.
What’s widely believed to be the most complex aspect of the eCTD is its requisite inclusion of highly technical backbone files – essentially XML files that represent a ‘packing list’ of the content files being delivered in each instance (or sequence) of a multi-part submission.
In addition to identifying the contents of a submission package, these files must also indicate the action being taken with each file – is a file being added to already submitted files? Is it replacing an already-submitted file? Should a previously submitted file be withdrawn from the review process?
Broadly, this concept is called the ‘lifecycle operation’ for the file (Fig. 1).
Today and the future
Today, many companies are beginning to consider the business process implications of implementing the eCTD. Over three-quarters of the companies recently surveyed in the 2005 Liquent Regulatory Trends Survey indicated that they intend to implement the use of the eCTD format in the next two years (see page 33). Tempering this transition is the industry’s concern about the willingness and ability for agencies around the world to accept the eCTD-formatted submission without also requiring paper by its side.
Yet there are other changes afoot that may be diverting focus from the eCTD. Expected to be implemented shortly, the FDA will begin requiring that product labelling information be submitted in a new format. The structured product labelling (SPL) format is an XML-based specification that introduces a significant new challenge for sponsors and manufacturers.
The EMEA region has a similar initiative, expected to become ‘highly recommended’, in its product information management (PIM) standard. PIM is also an XML-based specification designed to streamline the submission and review of product information in the multi-lingual European environment.
Many companies, while aware of these new formats, have some level of scepticism about how aggressive these authorities will be about accepting – and possibly mandating – these new formats. The impact to business processes that support labelling content development and submission will be significantly impacted by these new standards.
There are more organisations and initiatives at work ‘electronifying’ the drug approval process. The Clinical Data Interchange Standards Consortium(CDISC) has been busy working on its study data tabulation model (SDTM) – another XML format.
Announced in July 2005 as the FDA standard format for clinical trial submission data, it is expected to lead to efficiencies in clinical research and reviews of regulatory submission by FDA. CDISC has also been developing the structured clinical trial protocol (SCTP) XML standard. This standard is being developed to support the SDTM standard as well as to support study tracking databases and the sponsor’s development of the clinical trial protocol documentation.
All of this activity shares an ultimate and common goal: to streamline the submission and review (and ideally approval) of the key information used by regulatory authorities in the new drug approval process.
By applying a more structured approach to the collection, management and exchange of this information, reviewing authorities are better able to focus on the right information – and more of it – by working within a framework that is well organised and consistent. Sponsors can also see benefits by being better able to create and identify.
