Pfizer blighted by Viracept scare

Despite initial thoughts that Pfizer's version of the drug had not been affected by dangerous levels of ethyl mesylate (EMS) found in the Roche drug as a result of the manufacturing process, Pfizer yesterday dispatched a letter to healthcare professionals informing them of the presence of the impurity in US batches and providing guidance on the way forward. Swiss firm Roche initiated a Europe-wide recall of Viracept in June, after human errors in cleaning practices left excess ethanol in process equipment which reacted with the drug's active ingredient and caused unusually high levels of EMS in the resultant products. However, although the recall itself was triggered by this spike in the level of the toxic compound, it alerted regulators to the fact that EMS is in fact always​ present in the drug albeit at much lower concentrations than detected in the highly contaminated batches. By the beginning of August, Roche had lost marketing authorisation for the HIV drug, and has been forced to assure regulators that it will be compiling registries to keep an eye on Viracept patients stretching right back to when the drug first hit the market in 1998. The crucial point is that although EMS is known to be carcinogenic, mutagenic (harmful to DNA) and teratogenic (harmful to fetuses) through research from animal studies, there is no data on what levels of the compound are harmful to humans. As such, EU regulators have instructed Roche to carry out studies to try and establish just how harmful the compound is before there's a chance of winning back permission to market the drug again in the EU. When in-PharmaTechnologist.com contacted Pfizer following the Roche incident, a representative from the company claimed that Pfizer supplies would be unaffected by the EMS impurities affecting the Roche product. "[EMS] is a potential by-product of the synthetic process,"​ in-PharmaTechnologist.com was told. "However, Pfizer has controls in place to prevent its formation during manufacture."​ Despite these claims, the US Food and Drug Administration (FDA) contacted Pfizer regarding testing of its Viracept product to establish the extent of any EMS impurity in US supplies of the drug. Testing revealed that EMS was indeed present in the Pfizer formulation, though not at the high levels cause by the human errors at Roche's manufacturing site. As a result, the company has liaised with the FDA to establish new specifications to limit the presence of the contaminant in Pfizer-manufactured products, and on measures to protect the HIV patient population currently prescribed the medication. The two organisations have agreed on interim and long-term specifications of EMS in Pfizer-manufactured Viracept, with only product meeting the interim specifications currently being released for patient use in the US. The interim level identified by Pfizer limits the theoretical increased cancer risk over a patient's lifetime to less than 17 cases per 100,000 exposed, with the long-term specification dropping the risk to less than one case per 100,000 exposed. Pfizer has decided on the interim measure to balance the need to maintain supplies of Viracept for patients whilst minimizing patient exposure to the harmful compound. Over in the EU, however, all patients originally prescribed Viracept have been switched to alternative medications. While not following Europe's all-out ban on the drug, in the US Pfizer has made a number of recommendations to physicians with HIV patients currently taking Viracept. EMS is considered particularly harmful to children, with the risk of cancer developing over their lifetime three times greater in patients aged between two and sixteen years. The risk is even higher for infants under two years old, though Viracept has not been approved for use in this age group. Due to the increased risk to pediatric patients, Pfizer has recommended that no children starting HIV treatment be prescribed Viracept until further notice. However, children who are already stable on Viracept should remain on their current course of treatment, according to the FDA/Pfizer evaluation, as the "benefit-risk ratio remains favourable​" for these patients. The teratogenic nature of the toxic compound has led to particular concerns for pregnant women taking the tainted Viracept and the effect it could be having on their unborn children. As such, Pfizer has also made specific recommendations regarding this patient group, though the company was keen to point out that "no significant difference in the prevalence of birth defects between women who used Viracept and those who used other antiretroviral therapy was observed." ​ Pregnant women who need to begin an antiretroviral regime should not be offered Viracept until further notice, according to the company, and any pregnant women currently on the drug should be switched to an alternative therapy. If there are pregnant patients with no alternative treatment options, Pfizer and the FDA assert that the risk-benefit ratio again dictates that these patients should continue taking Viracept. All other patients currently taking Pfizer-manufactured Viracept are being advised to remain on their medication and take as directed by their physician. Pfizer's recommendations regarding Viracept appear somewhat restrained compared to actions taken over in Europe, but the company appears confident that the steps it has taken to limit patient exposure are sufficient. Although the company was unable to respond to queries prior to going to press, it would seem the firm is trying to avoid the fiasco being encountered by Roche over in Europe, which has already cost the Swiss company almost a hundred million Euros. Later this month UK regulators are due to give their verdict on whether Roche's Viracept marketing authorization should be reinstated - Pfizer will surely be keeping a close eye on events over in Europe, and its fingers crossed that it will be spared the rigmarole experienced by its Swiss counterparts.