European regulations require that batch release testing be conducted in Europe for products marketed in the territory. Therefore,
it is important for companies outside Europe to understand how these requirements affect the outsourcing of batch release
testing, including the function of mutual recognition agreements, the role of the Qualified Person, and the extent to which
these requirements apply to clinical trial materials.
One of the many drivers for a company to consider outsourcing is geography—the need to have a particular piece of work conducted
within a specific country or regulatory region.
Companies may first encounter this need if there are potential patent issues surrounding the products they are developing.
In some countries, most notably the US, developmental work is subject to patent restrictions that in other countries would
only apply when the new manufacturer sought material gain, i.e., when it is ready to market a product. A new manufacturer
of a follow-on product would thus wish to conduct any work, outsourced or otherwise, in a country where it would be free from
Later in product development, it may be necessary to conduct clinical trials in specific patient groups or ethnicities, which
may be accomplished most easily by conducting some of the trials in particular countries. It may also be necessary to conduct
clinical trials in a particular country before marketing authorization will be granted in that country.
The final stage where the location of the work can become relevant is in release testing, the quality control testing of each
batch of finished product. This situation is particularly relevant for biological products for which a single manufacturing
site is normally used for global supply, whereas for small-molecule products, multiple manufacturing plants located in local
markets are more common. In the European Union (EU), there is a regulatory requirement that each batch of a finished marketed
product be tested in the EU against the approved product specification. There is no requirement for the product to be manufactured
in the region, but non-EU manufacturing sites are subject to inspection by the EU authorities. For companies with no testing
facilities in the region, the EU marketing of their products will thus require outsourcing to a EU-based facility. The purpose
of this article is to review this requirement and provide guidance to manufacturing companies that need to outsource this
When considering Europe as a market for a pharmaceutical product, one first must define what is meant by Europe. The geographical region and regulatory groupings do not match; whilst the former is fixed, the later is subject to extensions
as the political situation changes.
The top half of Table 1 lists the countries that are currently members of the EU. All legislation passed at the EU level applies
to these countries. For pharmaceutical products, the regulations are administered by the European Medicines Agency (EMEA).
EU legislation is issued in the form of directives from the European Commission (EC) to all member states (countries). Then
each country must implement the directives through its own legal framework within a given time period.
Table 1. Countries of the EU and non-EU members of the European Economic Area
For pharmaceutical products, there are three main directives of relevance to testing requirements:
- Directive 2003/94/EC lays down the principles and guidelines for manufacturing practice for medicinal products for human use
and investigational medicinal products for human use.
- Directive 2001/83/EC is the Community code relating to medicinal products for human use and sets out the requirements and
procedures for obtaining marketing authorization.
- Directive 2004/27/EC amends Directive 2001/83/EC.
Directive 2003/94/EC is supplemented by "The Rules Governing Medicinal Products in the EU, Volume 4, EU Guidelines to Good