In recent years, biopharmaceutical companies have joined Big Pharma in expanding their businesses into global markets. In
the process, many of these companies have found that navigating disparate regulatory requirements can be confusing, time consuming,
and risky. A lack of understanding about a particular regulatory agency's requirements for processes or facilities can lead
to excessive delays in market authorization, thereby affecting a product's opportunity for success in a highly competitive
Nonetheless, regulatory agencies from the United States, Europe, and Japan are making visible efforts to collaborate and coordinate
their requirements for processes and manufacturing facilities. This harmonization of rules means the process of global regulatory
compliance has become somewhat easier than it was just five years ago. The adoption of unified guidelines as well as increased
collaboration with industry in major economic markets have eliminated many duplicative and dissimilar testing requirements
Even so, key differences in the regulatory review process require that pharmaceutical companies seeking to market products
in several countries take a truly global approach to regulatory issues, build a strong working knowledge of the countries
and their regulators, and adequately prepare for the rigorous process of submitting applications and undergoing regulatory
Moving toward harmonized regulatory requirements
The process of harmonizing global regulatory requirements began more than 15 years ago, when industry groups and regulatory
authorities in the US, Western Europe, and Japan formed the International Conference on Harmonization of Technical Requirements
for the Registration of Pharmaceuticals for Human Use (ICH). This industry–regulatory consortium seeks to accelerate global development of new medicines as well as decrease research
and development costs by eliminating duplicative or contradictory requirements among various regulators while maintaining
standards on quality, safety, and efficacy. The rationale for ICH is that more efficient use of research time and money could
make life-saving medications available to consumers more quickly and reduce overall healthcare costs (1).
Through ICH, regulators and industry experts discuss scientific and technical aspects of the development and manufacture of
medicinal products and agree on scientific and quality standards for clinical, laboratory, and manufacturing practices. Between
1990 and 2004, six ICH conferences were held, leading to the release of dozens of technical guidelines, common vocabularies,
and specifications for a common marketing authorization application (2).
The US Food and Drug Administration, European Medicines Agency (EMEA), and Japanese Ministry of Health, Labor, and Welfare (MHLW) now rely on ICH technical guidelines when ensuring pharmaceutical companies comply with quality standards.
But complete harmonization cannot happen overnight, or even within 15 years. Differences in governmental structures, cultural
norms, and business environments lead to distinct interpretations in and implementation of international guidelines. In addition,
there is often a lag between the publication of ICH guidelines and the adoption by individual countries because of the time
it can take for each governmental body to put the change through its own review and approval process.
Consequently, regional differences still exist in how individual countries go about ensuring compliance with current good
manufacturing practices (CGMPs), and those distinctions can influence costs and the speed with which a company obtains marketing
approval. Differences in regulatory requirements can be complex and affect nearly every aspect of the marketing authorization
Submitting new drug applications to multiple regulatory agencies
Despite increased coordination among FDA, EMEA, and MHLW in recent years, differences in each agency's submission requirements warrant that companies closely monitor
all three agencies for changing rules and requirements, particularly concerning the information that must be included as part
of the submission and the need for local partners. For small biopharmaceutical companies, submitting multiple new drug applications
while simultaneously seeking to expand business overseas can be an overwhelming task to handle alone.