Biopharmaceutical Manufacturing: The Challenge of Global Regulatory Compliance

This article provides an overview of regulatory issues facing companies that seek to market their biopharmaceutical agents globally, including a trend toward harmonization of requirements as well as the differences in rules concerning applications, GMP standards, and communication with reviewers.
Jun 02, 2008
Volume 32, Issue 6

Suk-Heui Park
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 market.

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 for manufacturers.

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 review.

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 process.

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.

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