Integrating EU and US regulation

Pharmaceutical Technology Europe interviews Sylvia M. Findlay, Programme Leader at Frost & Sullivan. The company has recently released a report entitled Drug Approval Process in Europe — An Outlook and believes that integration of the EU and US drug approval process is a necessity.

Q1: The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is working to develop a standard set of regulatory processes for Europe, the US and Japan. Do you know anything about the progress that has been made so far?
Information Sharing Agreements have been formulated by the FDA to enhance better dialogue among various regulators. Important information about pending approvals, post-marketing surveillance and enforcement actions concerning products and facilities in Australia, Canada, Mexicoa, Japan and EMEA are being shared with the FDA.

The drug regulatory systems in all three regions share the same fundamental concerns for the safety, efficacy, and quality of drug products. The ICH Common Technical Document allows data in the same format to be submitted to drug review authorities in all three ICH regions.

Medical Dictionary for Regulatory Activities (MedDRA) is a new international medical terminology designed to improve the electronic transmission of regulatory information and data worldwide.

Q2: What are the main barriers to the formation of an integrated drug approval process and how do you think these can be overcome?
There lies an imminent requirement to create an interface among industry, academia, healthcare providers and stakeholders to facilitate data transfer on drug safety. Clinical trial design and evaluation for both the EU and the US should be made consistent, which can be enabled by continuous dialogue between the regulatory agencies. The consistency check should be done even among the EU countries; for example, there is currently no harmonization on regulatory approvals for non-medicine human cell and tissue-based products.

ICH has made some progress in this area and is working towards an integrated regulatory system.

Q3: Can you provide a brief overview of some of the differences between the EU and US approval processes for drugs and biosimilars?
Some of the differences between the drug approval processes in EU and the US are highlighted in the table.

Q4: And some of the differences regarding parallel trading?
As there are differing drug approval systems in Europe and the US, the impacts on the market are also varied. Lower price inflation is also seen in Europe compared with the US.

Parallel trading has gained significant weight in the European pharmaceuticals industry and its value is estimated at approximately 2–% of the total European pharmaceutical sales. The US drug industry has witnessed parallel trading in the past and it is a very potential country for parallel traders. With the Pharmaceutical Market Access and Drug Safety Act (S.334), parallel trading has been legalized between US and Australia, New Zealand, Canada, the EU, Japan and Switzerland. The US has to keep a close eye on parallel trading to ensure it does not replicate the EU scenario.

Q5: The EU has pioneered the creation of a regulatory pathway for biosimilars. Can you tell us more about this?
Europe has pioneered in charting out a regulatory pathway for biosimilars as European countries reviewed the pharmaceutical legislation so as to support the adoption of biosimilars. In 2003, the EU amended the secondary legislation governing the marketing authorizations for biosimilars and in 2005 the EMEA issued a general guideline for biosimilars covering the whole range of biotechnology drugs such as vaccines, blood derivatives, gene and cell therapy.

Biosimilars are mandated to undergo the centralized procedure for marketing authorization, but the reference product used for the comparability studies should be authorised in the EU and a high standard for quality assessment is demanded by the new legislation. The marketing authorization holder should consider which indication ought to be studied while developing a biosimilar, but the Committee for Human Medicinal Products (CHMP) will provide scientific advice towards biosimilar development. The CHMP has been developing a set of guidelines towards the comparability issues regarding the quality (EMEA/CHMP/49348/05), pre-clinical and clinical features (EMEA/CHMP/42832/05) of the drug.

Q6: What problems stem from the gap between European regulatory authorities and national pricing authorities?
The regulatory framework in Europe was quite diverse, but efforts have been made to harmonize regulatory procedures among the member states. This was partly achieved with the introduction of centralized procedure and mutual recognition procedures, but a major gap still lies between regulatory authorities and the national pricing authorities. Although the centralized procedure authorizes the sale of drugs in all member states, pharmaceuticals companies still have to file for price or reimbursement approvals, which has a major impact on the launch timing of new drugs as well as influencing parallel trade.

Q7: How likely is it that an integrated transatlantic regulation will be formed?
The FDA is working with the ICH to bring in integrated transatlantic regulation. There has already been good progress on this front, especially with the introduction of the common technical document, and several guidelines on quality, safety and efficacy have also been issued by the ICH in the EU, the US and Japan to enhance the integration. I think the formation of a common transatlantic regulation is quite near and this will provide immense benefits to the medical community as well as the pharma industry.

Q8: How likely is it that an EU-wide synchronized approval process across all member states will be formed?
The European Commission should establish clear guidelines for implementing the clinical trial design and incorporating any specific national law. Europe-wide harmonization would enable faster approval process and reduce delays in drug launches.

Q9: Why is globalization vital for the future of the pharma industry?
As the pharmaceutical industry moves towards globalization, regulatory convergence is critical. Transatlantic regulatory convergence will have immense benefits such as faster technology transfer, reduced regulatory expenditures, the harmonization of patent laws and pausing the regulatory approval of unsafe drugs. This will ensure a faster approval process and enable new drugs to reach the entire medical community faster.