Qualified Person Release of IMP's Imported from Outside the EU: A Business Benefit?

In May 2004 EC Directive 2001/20/EC came into force, impacting the way clinical trials are controlled.  This article focuses on one part of that directive, the duties of the Qualified Person (QP) when releasing product that has been manufactured outside of the EU.  The directive requirements are as laid down in Article 13 of the directive.  Annex 13 of Volume 4, Good Manufacturing Practices gives the QP a more detailed view of how to comply with the directive.

When a medicinal product destined for a clinical trial is manufactured outside the EU the QP needs to establish that the facility and practices at that facility meets, as a minimum, the GMP requirements of the EU.  The QP also needs to ensure that each batch manufactured is assessed for compliance with the authorisation for the clinical trial.  How is this best achieved?

Normally this would be done via an audit of the facility and then remote review of the batch documentation pertaining to individual batches.  However, this is a simplistic view and the intricacies of how this is effectively achieved can provide some interesting debate.  Some questions that might arise:

Who should audit?  The QP?  What if the QP is not an experienced auditor?

What if the audit, as is likely, raises compliance issues indicating that the facility is not in total compliance with EU. GMP rules?

If the supply of product is to carry on over a period of time how often should an audit take place?

How does the QP deal with change within the supplier's facility?

How does an MRA with the country involved affect the duties of the QP?

How much responsibility does the QP have for decisions made by the supplier on individual batch issues?

In the author's opinion an audit and routine batch review is not enough to enable the QP to effectively carry out his/her duties.  It is also not necessarily going to give the business benefit that could result from a more structured approach.  The following is suggested as a competent, realistic and effective means of ensuring that the QP batch release adds real business benefit:

The QP must have personal knowledge of the facility and the key staff employed at that facility, essentially a sound working relationship should be developed and maintained.  Where non-compliances are identified, the QP must risk assess the situation and be comfortable with the corrective action plan to address the non-conformance.  This plan must be monitored.  Where an MRA exists, Annex 13 indicates that the responsibility of the QP to control and have continuous knowledge of the activities within the facility is reduced.  It is the author's opinion that such personal knowledge of the facility, and detailed overview of their activities, is just as important.  A Technical Agreement should be in place between the individual companies that, in particular, must give direction on how change is controlled between both companies and who is responsible for individual activities.

For individual batch review, the QP should not restrict his/her activities to the routine manufacturing and testing documentation.  In particular, deviations and/or OOS reports must be thoroughly investigated.  The transport conditions should also be considered and 'Quality Systems' information, such as audit reports, validation status, stability data and Annual Product Reviews should be available and referred to where appropriate.

The use of the QP for batch release can give real business benefit, if the procedures and practices developed enable a good working relationship between the individual parties and a review that readily establishes that the batches released not only meet the basic requirements of the directive, but also ensures that appropriate proactive activity is undertaken, leading to reduced issues, greater confidence and ultimately less risk to the clinical trial.
 

Author: Alan Smith

Download this article 

For further information, please Contact Us.