U.S. and EU regulatory requirements are also important aspects to keep in mind when planning for a clinical trial. In the U.S., the FDA, DEA, and state agencies provide guidelines, while in the EU, Annex 13, the EMEA, and other specific country requirements are the guidelines.
Regulations require that the preparation of all materials meet GMP and GCP requirements, Dr. Urban explains. Sutterlin notes that the clinical supply contractor should be flexible and have a full set of standard operating procedures (SOPs) in place. In addition, clinical supply contractors should be able to provide guidance when selecting packaging components.
Some companies lock themselves into obscure components at the stability phase of a product's life cycle, which translates into long lead times due to custom manufacturing requirements. Most companies like to review all the necessary SOP documentation, which is currently paper and will probably become electronic in the future, Dr. Urban notes.
According to Maroevich, the most important regulatory requirements are the complete segregation and traceability of all drug lots during preparation and 100% accountability for all materials and labels.
The most significant recent change in regulations is the May 2004 EU Clinical Trial Directive. One important component of the directive requires that a Qualified Person (QP) certify that investigational materials manufactured and packaged outside of the EU are GMP compliant before use in EU countries.
The review may also include an audit of the facilities that performed the manufacturing and packaging. The directive is on top of existing export and import regulations and taxes. The directive is important because so many trials are global, explains Halquist.
In addition, he says that there are nearly 400 virtual companies with supplies not only coming from the U.S., but from all over the globe including India, Japan, and Australia.
Maroevich reports that advice from the April 2005 Pacific Region Clinical Support Discussion Group recommends getting a QP involved as early as possible. Late contacting of QPs results in rushing of the clinical trial preparation process.