Postmarketing Study Commitment Trends for New Drugs: An Analysis of NMEs Approved in 2008
Given that the FDA Amendments Act of 2007 (FDAAA) took effect in late March 2008, the 2008 class of approved NMEs offered an early glimpse into how anxiously the FDA would wield its newly found powers regarding postmarketing requirements and risk evaluation and mitigation strategies (REMS).
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Multi-country Regulatory Filings
Allison Gillespie, Senior Consultant, PAREXEL Consulting
Manuela Kohler,
Director, Service Line Leader, PAREXEL Consulting
The current global economic climate is generating tremendous pressure on bio/pharmaceutical companies to maximize the value of their assets. Sponsors with novel therapies need to speed up time-to-market and introduce their products in multiple countries as quickly as possible. Companies with established products want to increase their sales by expanding into additional markets to offset impending patent expirations.
A proactive multi-country regulatory filing strategy helps any pharmaceutical company get the most from its product portfolio by accelerating global product introductions while avoiding regulatory pitfalls. By understanding the differences in regulatory processes for countries around the world, and taking advantage of the Common Technical Document (CTD) defined by the International Conference on Harmonisation (ICH), bio/pharmaceutical companies can significantly improve the speed and efficiency of preparing multi-country submissions while reducing regulatory delays.
Leveraging the CTD
The CTD is the key to leveraging the benefits of multi-country filings. Based on ICH guidelines, the CTD provides a standardized structure for regulatory submissions that is acceptable to all ICH members – the European Union, Japan, and the United States. Other countries that accept the CTD for regulatory submissions include Australia, New Zealand, Canada, India, and China. Other countries have also elected to accept the CTD for regulatory submissions, including Turkey, Serbia, Croatia, Bosnia-Herzegovina, Ukraine, and Kazakhstan.
Although the CTD makes multi-country filing easier, regulatory submissions in the EU, the US, and elsewhere in the world continue to have significant differences, and documents must be adapted to local requirements. The fact that a product has been approved in one country or region does not guarantee its approval in other countries. At the same time, regulatory approval of a pharmaceutical product in a major market will often improve its chances for acceptance in other countries.
Developing an effective multi-country submissions strategy
The appropriate multi-country strategy depends on a variety of factors, such as:
- The product indication and the location of potential patients
- Pricing and reimbursement issues
- The size and resources of the sponsor
- Whether the product is a novel therapy or an established treatment expanding into new markets
- Analysis of market penetration and market share potential, as well as the current market leader
- Manufacturing capacity and distribution logistics
The order and timing of multi-country filings can have a significant effect on whether a submission is reviewed and approved quickly, or is subject to delays. Although every situation is unique, the following are examples of sound strategic approaches for three common multi-country filing scenarios:
- Mid-sized and large multinational bio/pharmaceutical companies with new products – It is often advantageous for major bio/pharmaceutical companies to submit their initial marketing authorization applications in the US and the EU in parallel to maximize their return on investment. These applications would typically be followed by a “second wave” of applications in other important markets such as Canada, Australia, New Zealand, China, and India. The key to this strategy is to develop a strong core dossier that can then be adapted to accommodate the differing requirements of the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). Consultation with regulatory specialists regarding the submission in “second wave” countries accepting the ICH CTD format is also important early in the process.
- Small companies with novel therapies – Smaller bio/pharmaceutical companies usually seek initial regulatory approval for their products in their home countries, then use the approved dossier as the basis for applications elsewhere. Smaller companies can also benefit from outside medical and regulatory expertise with local knowledge of region-specific requirements, standard therapeutic-area practices, and existing reference products to help them formulate successful submissions.
- Mid-sized and larger companies with products that are already established in the EU, seeking to expand their markets – Pharmaceutical companies with a portfolio of approved products in the EU can leverage their existing approvals to expand into non-EU European countries such as Croatia, Serbia, Ukraine, and Russia. Recent dossiers in CTD format can be used for submission to these countries, although some local-language translations and country-specific documents are required. Experience has shown that local presence and established relationships with regulatory authorities are also essential for market success in these countries.
The importance of local knowledge
In all of these scenarios, local knowledge of regulatory differences is crucial to the success of any multi-country submissions strategy. Familiarity with these differences in advance of preparing a submission can mean the difference between a smooth review process and significant delays or failures. Below are a few examples that illustrate the importance of understanding and anticipating unique local situations:
Australia – A non-Australian company wishing to register a new medicinal product in Australia must have a locally-registered sponsor. Australia also offers an abridged submission process for products that have already been approved and marketed in other “acceptable” countries, with a review timeframe that is 20 weeks shorter than the standard process.
New Zealand – A shortened review process is also offered by New Zealand for products that have been approved and marketed in the US, Canada, Australia, the EU (centralized procedure), or the United Kingdom. The product must be identical in all aspects to the approved product. The Extended Abbreviated Process is completed within 135 days, instead of an average of 450 days, and offers the sponsor significant savings on fees.
Malaysia – Only local companies can submit an application for drug registration. Foreign companies with no local presence in Malaysia must designate a locally established legal entity to be the Market Authorization Holder (MAH). In addition, the country’s National Pharmaceutical Control Bureau (BPFK) only accepts web-based, on-line submissions.
Succeeding with multi-national filings
A proactive multi-country regulatory filing strategy helps any size bio/pharmaceutical company accomplish both of those goals by increasing global sales, reducing regulatory submission costs, and lowering the risk of regulatory delays or failures. To succeed with multinational registrations, a sponsor must:
- Identify key target markets for submissions
- Understand important regional differences
- Find the right local resources to avoid regulatory pitfalls
- Create a robust CTD
- Develop a submissions strategy that leverages the CTD to secure regulatory approvals in the shortest possible time
A strategic multi-country approach will maximize the return on product investments while also bringing important therapies to patients who need them around the world – a desirable outcome in any economic environment.
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