The European Commission has backed recommendations by the European Medicines Agency (EMEA), which suggested the suspension just weeks after manufacturer Roche initiated an EU-wide recall of the drug following the discovery of elevated ethyl mesylate levels in Viracept tablets. The suspension has been ordered because of "concerns that the quality of the product and therefore its safety in normal conditions of use can not be guaranteed at present," according to a European Commission statement. It has now been almost two months since the original cases of increased levels of contaminant were discovered and reported by Roche. In that time it has emerged that not only was the company well aware that the compound was present in the drug, but that adequate research to identify just how toxic the chemical is to humans has never really been carried out. A human error in cleaning processes at Roche's manufacturing plant in Switzerland was the original cause of the spike in ethyl mesylate levels. The mistake resulted in a large quantity of ethanol remaining in processing equipment, which reacted with the drug's active ingredient and caused the unusually high levels of the genotoxic compound in the final Viracept product. Although ethyl mesylate is a known genotoxic substance (harmful to DNA) and can cause cancer or harm unborn children if used during pregnancy, the precise level at which the compound is harmful to humans remains unknown. Despite this, Roche has continued to manufacture Viracept since it was granted marketing authorisation in 1998, knowing that this harmful compound would be present, albeit to a much lesser extent than the tainted batches that prompted the June recall. When in-PharmaTechnologist.com tackled Roche representatives on this point, they insisted the ethyl mesylate was present only in trace levels in the drug, and that the company had adequately "followed regulatory processes." However, regulatory authorities are now reeling the company in, with Roche having to deal with the consequences of the contaminant that has been present for the last ten years. All patients that were being prescribed Viracept have now been transferred onto alternative medication, and the company has ceased manufacture of the drug until the authorities are satisfied that the company's manufacturing processes have been amended satisfactorily and the risk of harm to patients minimised. "We are in discussions with authorities to find a new way of production that will eliminate the errors," a spokesperson for Roche told in-PharmaTechnologist.com. "We are aiming for the removal of any trace [of the contaminant], but our investigations will show how the new process will work…the work is ongoing." According to the spokesperson, the company understands the problem that causes the contamination, and said that it is "not a huge challenge" to solve it - which begs the question as to why the apparently simple solution wasn't implemented from the start. Roche hopes to be able to manufacture the drug again by September/October, with authorisation to market the drug hoped to be returned in the weeks or months following recommencement of manufacturing activities. However, Roche also has a number of other commitments before Viracept will be allowed back on the market. How much damage has been done? Due to the unknown factors relating to the ultimate toxicity of the ethyl mesylate compound, the authorities have demanded that toxicological studies be carried out to establish more accurately precisely what levels of the contaminant are dangerous to humans. Roche has already submitted proposals for three such studies to the European authorities in response to this requirement, two of which are due to have started in recent weeks. Until the results of this research on ethyl mesylate are available, the Committee for Medicinal Products for Human Use in the UK (CHMP) has proposed an interim limit of 0.6 parts per million, in line with scientific consensus on genotoxic impurities and available data on the compound. In its September meeting the CHMP will discuss the possibility of recommending the lift of the marketing authorisation suspension. However, as well as the scientific research, Roche now also has to establish patient registries of every patient worldwide who may have been exposed to the highly contaminated batches of the drug that were distributed from March this year until the time of the recall. A second registry is also being established to include every woman who took the drug during pregnancy and every child to have taken the drug or been exposed in the womb, stretching right back to when the drug first hit the EU market in 1998. Every single one of these patients will be followed up every six months for a minimum of five years. The recall has already cost Roche CHF115m (€70m). Despite efforts to reassure former Viracept patients, the damage may have already been done. With all patients already switched to alternative treatments, and trust in the medication understandably somewhat battered by the contamination incident, just how many patients will be happy to return to Viracept is a matter of speculation. "It's a decision to be made between patients and physicians," said the Roche spokesperson. "Viracept was a very important treatment for the patients, we think many will return." Whether Roche's confidence in Viracept's former patients is matched by the patients' confidence in the drug itself will be seen when - and if - the drug appears back on the market. Pfizer emerges unscathed The Roche contamination and recall has not affected patients in the US, Canada or Japan, as Pfizer is responsible for manufacturing the Viracept supplied to these countries. In a previous interview a Pfizer spokesperson told in-PharmaTechnologist.com that the company was aware that ethyl mesylate is a potential by-product of the synthetic manufacturing process, but that the company "has controls in place to prevent its formation during manufacture." It would seem, therefore, that Pfizer's preventative measures have spared the company the nightmare that Roche (and its Viracept patients) are currently experiencing. Unfortunately, Pfizer's product has not been approved in the EU and as such cannot be provided as a substitute to Roche's Viracept patients on this side of the Atlantic.