Divya Jaiswal, Business Analyst, HIL Domain Consulting Group, Infosys, Chandigarh, elaborates on how by implementing RPS, FDA will be able to implement a standards-based end-to-end fully electronic receipt, review, distribution and archival environment of its data
Just as electronic common technical document (eCTD) is moving towards v 4.0 in the journey of format for electronic regulatory submissions, the Food and Drug Administration (FDA) is thinking way ahead. The next standard is Regulated Product Submission (RPS), which FDA is planning to implement in order to replace eCTD. By introducing RPS, FDA is planning to work towards implementing a standards-based end-to-end fully electronic receipt, review, distribution and archival environment.
What is RPS?
RPS is a standard proposed by Health Level 7 (HL7), an accredited standards organisation. Presently, the second release of RPS is in progress. This new standard has two distinct benefits above eCTD. First, RPS will launch two-way communication between the submitting organisation and all FDA-regulated product centres within the agency, such as pharmaceuticals, medical devices, veterinary medicines, biologics, radiologics and foods. Second, RPS will allow cross-referencing of previously submitted information and hence will effectively manage the life cycle of submissions.
What changes will RPS bring?
To pharma companies: Organisations will be able to send electronic applications with automated cross-links to earlier submitted data and information. It will save huge time as data has to be submitted only once.
To FDA reviewers: FDA reviewers will get efficient tools to search and analyse data to support their review. It will enable them to retrieve all significant submissions and associated data electronically from their work station.
To FDA: RPS will make FDA capable to handle two-way regulatory correspondence with industry, which will fast track movement towards all-electronic submission and review environment, and will reduce paper submission management systems.
From 2002 eCTD 3.2.x is in place. Although much has been done for its development and implementation, still many restraints are not addressed and will take long procedure to solve these. Few of the issues with current eCTD are:
- It cannot support to other submission structure apart from CTD (e.g. CTAs, paediatric investigational plans, etc.)
- Difficulties to change any existing part (a new DTD version has been required when e.g. a new section is required, an agency changes its name, or new country joins the EU, etc.)
- Lack of ability to spot-on metadata if we get it wrong
- Limited ability to reuse of content across submissions
- Limitations on performance of validation
- RPS will launch two-way communication between the submitting organisation and all FDA-regulated product centres within the agency
Two-way communication: Current structure of eCTD allows submitter to send response to the healthcare authorities but doesn’t allow authorities to send correspondence to submitter. With the help of RPS structure, it will be possible for FDA and other regulatory authorities to send correspondence to submitting organisation/ sponsors.
RPS may be capable to resolve these, but it will involve efforts, time and money. It won’t be so simple to read and understand the XML file, or to review the submission via the folder structure or stylesheet. The eCTD builders will need to be enhanced, and (re)viewing tools used. It is something that won’t be implemented immediately, particularly in Europe, since a lot will need to be done to support its implementation. For example, there will need to be ICH and regional guidance developed and published.
In the US, the FDA is keen to use RPS in other areas where it is responsible for regulation (such as Medical Device submissions), so it could move relatively quickly. However, in Europe, RPS is likely to remain focused on use for human pharmaceuticals, at least in the medium-term.
Moreover, before the standard can be used in the EU and Japan, it will be essential to move the HL7 standard onward to be an international standard via ISO. Though there is much collaborative work on-going between Standards Development Organizations to develop joint standards (eg. ICSR, IDMP), it has become clear that there are strains because of differences in the funding models between organisations.
The implementation also needs to be tied in with the European e-submission roadmap which is going through approval by the European regulators at present. According to the roadmap, a single format for e-submissions at European level (Central/MRP/DCP) is to be implemented from Q1 2018 but this may be extended to National procedures in future. The roadmap also notes that RPS could be used to support veterinary submissions.
RPS Vs eCTD
- Similarity: In many ways RPS is similar to the eCTD. Contentedly, the FDA wants to implement RPS as the next recapitulation of eCTD. RPS and ICH’s eCTD has same concept —the use of a consistent format for regulatory submissions, which includes PDF documents and SAS datasets.
- Dissimilarity: While document contents are same for eCTD and RPS, the internal (extensible markup language (XML) structures differs from each other.
- Milestones and future planning for RPS: At present, the second release of RPS is under development. ICH is planning to direct the third release. The objective behind release three is to have more international requirements. The timelines for HL7 standard to be implemented first at the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) were decided till late 2011, FDA is yet to determine the final date of adaptation of RPS but most probably it will be by 2018. Whenever RPS will be implemented, FDA will offer a training programme for reviewers, including hands-on training classes.
2. https://en.wikipedia.org/ wiki/Regulated_Product_Submissions