BioWorld International Correspondent

BRUSSELS, Belgium - The European Medicines Agency has released draft guidance on virus safety evaluation of biotechnological medicines for clinical trials. The declared aim is to allow a harmonized approach throughout the EU for both sponsors and regulators - since an agreement would ease multi-center studies that involve different countries in the European Union.

The draft sets out criteria for viral safety evaluation studies, especially validation studies, required before and during clinical development. It also suggests the extent to which manufacturers should be able to refer to in-house experience concerning virus safety evaluation, and outlines the nature of the risk assessment that should form part of the safety evaluation.

The guidance will apply to investigational products prepared from cells cultivated in vitro from characterized cell banks of human or animal origin. It covers monoclonal antibodies and recombinant DNA-derived products, including recombinant subunit vaccines, but does not apply to products that contain recombinant viruses such as vaccines or gene therapy products using viral vectors; it doesn't cover products derived from hybridoma cells grown in vivo, either. Material to be used solely for nonclinical testing also is excluded.

Testing of the master cell bank for viral contaminants should be performed prior to the initiation of a Phase I trial, the draft indicated, and any change in the production process that results in an extension of the in vitro cell age would require reassessment of end-of-production cells. Validation would be required for steps considered effective in inactivating or removing viruses during processing. And since the potential remains for contamination with a virus originally present in the cells or arising from materials of biological origin that have been used during cultivation of the production cells, the process normally should be evaluated for the inactivation or removal of enveloped viruses or retroviruses and small non-enveloped viruses.

Comments are being sought before the end of 2006 on the draft, which was compiled by the agency's biotechnology working party over the course of this year.

New European Fears On GM Contamination

European public opinion is being given yet another demonstration of the weakness of controls on biotechnology by the latest in a series of industry errors, as news emerges in Europe that rice imports from the U.S. have for years been contaminated by an unauthorized GM strain.

The European Commission announced Aug. 21 that U.S. Agriculture Secretary Mike Johanns had informed it late on Aug. 18 about the detection of trace amounts of non-authorized genetically modified rice in samples taken on the U.S. market from commercial long grain rice.

The source of the contamination is Bayer AG's experimental GM rice, LLRICE601, which is engineered to withstand application of the herbicide glufosinate. Bayer said the GM rice "is present in some samples of commercial rice seed at low levels" even though field testing ended five years ago. Bayer informed the U.S. Department of Agriculture of the contamination July 31.

European Union officials promised immediate and urgent action to seek "more and specific information, in particular in relation to the risk assessment and to the detection method" from the U.S. authorities.

"As in the past, the European Commission will ensure that unauthorized GM products do not reach the EU citizen," according to a formal EU statement. EU experts also were scheduled to meet the company representatives on Aug. 21 to obtain further information, and the EU stated that "based on this information, a decision on further actions, if necessary, will be taken."

Opponents of biotechnology are rushing to exploit the opportunity. Friends of the Earth Europe pointed out that Europe is faced with the possibility of illegal and unauthorized GM crops being imported from the U.S. - for the second time in 18 months, following Syngenta's admission last year that it had been selling an experimental and illegal GM maize variety to U.S. farmers for four years. Maize exports to Europe were contaminated with the Syngenta maize, and the EU authorities put in place emergency measures that still are in place to prevent the import of contaminated maize.

Now critics of EU policy are calling for a ban on the €70 million (US$77 million) of U.S. rice that Europe imports every year - in line with the decision taken by Japan over the weekend. They claim that the rice has not been approved for human consumption anywhere in the world and has not undergone any official assessments to determine its health or environmental impact.

Adrian Bebb, GM food campaigner for Friends of the Earth Europe, said: "This is a complete scandal. The biotech industry has failed once again to control its experiments, and lax regulations in the U.S. have allowed consumers worldwide to be put at risk. The European Union must immediately suspend U.S. rice imports until consumers can be guaranteed protection from untested and illegal foods."

Critics also are calling for an investigation in the U.S. and Europe into the full extent of the contamination and for Bayer to release all the necessary information into the public domain on the safety testing and detection methods for LLRICE601.

The U.S. announcement stated that conventional long-grain rice on the market has been contaminated by the GM rice grown at experimental test sites between 1998 and 2001, but it did not reveal how widespread the contamination is or how the contamination occurred.

The EU insisted it acted appropriately.

"We are treating this with the utmost priority," spokeswoman Antonia Mochan told BioWorld International. She said the principal task was to obtain the risk assessment on the rice, to be able to evaluate the U.S. authorities' reassurance that the presence of those traces do not pose safety concerns in food, feed and the environment.

She added that the case was not exactly the same as the Syngenta maize, in which the GM protein was not authorized.

The GM protein in the Bayer rice is authorized for use in oilseed rape and maize, Mochan pointed out. "As soon as we have the necessary information, our reaction will be appropriate and proportionate," she said.