EU mulls GMPs for investigational drugs

07/01/2002

By Chris Anderson

BRUSSELS, Belgium- A recent proposal by the European Commission would require that all investigational new drugs (INDs) meet the same good manufacturing practice (GMP) requirements as authorized medicinal products.

Notable changes for INDs-limited production pharmaceutical products used in clinical trials-would affect certain production methods, product sampling, data retention and validation processes.

"The proposed change ensures that medicinal products for clinical trials are manufactured according to GMP, as is the case for other products," says Per Haugard, an EU Commission spokesperson. "Patients in clinical trials should not be treated with substandard products."

However, due to the nature and limited production of INDs, some of the GMP requirements will need to be adapted, notes Haugaard.

In particular, according to the draft proposal, process validation may not always be possible as it is with pharmaceuticals in wide distribution. "In many cases, it's impossible to require process validation as INDs are often made in just one batch," says Fred Blumenschein, chief of case management and guidance with the Center for Drug Evaluation and Research, Rockville, MD.

In these cases, "provisional production parameters and in-process controls may be deduced from experiences with analogues and from earlier development work," according to the proposal, which will be included as a clause in last years' Clinical Trials Directive 2001/20.

The changes for INDs are not expected to add significant cost to companies preparing an IND. Nevertheless, it would specifically require manufacturers or importers to notify European Commission authorities of any changes to the IND's production methods, as well as record details in GMP documentation.

Other specific changes would require the retention of samples from each batch of bulk formulated product for at least two years; validation of production processes such as sterilization to show that the process had performed as intended; and a system for recording and reviewing complaints; as well as establishing an effective recall process.

Complaints about product defects would need to be investigated, including any comparator products used in the trial, in which case the manufacturer of the comparator product must also be informed of the complaint.

While the changes for INDs are few, the EU says that they are important in assuring the quality of INDs and protecting the people involved in the clinical trial phase of new drugs.