nvCJD Donor Plasma Product Market Withdrawal Is "Prudent" - EMEA

Medicinal products derived from blood or plasma of donors believed to have new variant Creutzfeldt-Jakob Disease should be withdrawn from the market, the European Medicines Evaluation Agency Committee on Proprietary Medicinal Products recommended Feb. 25.

Although CPMP maintained that "transmission of nvCJD by medicinal products derived from human blood or plasma is very unlikely," the group suggested that "as a precautionary measure," it would be "prudent to withdraw batches of plasma-derived medicinal products from the market if the donor to a plasma pool is subsequently strongly suspected or confirmed" of having the disease.

The committee said recalls are warranted because "it is now recognized that nvCJD has different characteristics [than] sporadic, familial and iatrogenic CJD."

CPMP's recommendation also applies to medicinal products for which a plasma-derived product was employed as an excipient. CPMP noted that "since a recall involving albumin used as an excipient has the potential to cause major supply difficulties for essential products, manufacturers should avoid using, as an excipient, albumin derived from countries where a number of cases of nvCJD have occurred."

The document encourages manufacturers to develop substitutes for plasma-derived albumin for excipient use "although it is recognized that this can be difficult and requires a long-term approach."

Although CPMP recommended recalls in the defined cases, it recognizes that there may be instances where a recall would not be in the best interests of the public health. "Consequences for essential medicinal products where alternatives are not available will need careful consideration by national authorities," CPMP stated. For example, "case-by-case consideration" should occur "where plasma-derived products have been used in the manufacture of other medicinal products."

For sporadic, familiar and iatrogenic CJD, CPMP repeated that "recall of plasma-derived products is not justified where a donor later is confirmed as having CJD." The group noted that "there is no evidence" that these CJD variants "are transmitted via blood transfusion or via plasma-derived products."

FDA does not make a distinction between CJD and nvCJD; no cases of nvCJD have been observed in North America. FDA has asked for recalls of plasma derivatives if the source blood is CJD-implicated. A product can be exempt from recall if it is life- or health-sustaining and there is no alternative product.

FDA's Transmissible Spongiform Encephalopathies Advisory Committee concluded in October that albumin should be exempt from recalls of plasma-derived products because it is less likely to carry the infectious agent causing CJD ("The Pink Sheet" Oct. 13, 1997, T&G-3). FDA also is considering a blood product recall exemption for donors who have received single-donor dura mater grafts ("The Pink Sheet" March 2, p. 28).

Explaining the differences between nvCJD and other forms of the disease, CPMP said that abnormal cellular protein associated with TSEs "has been observed in samples of tonsil and spleen taken at necropsy in nvCJD cases but not in other CJD cases."

The finding "may indicate an increased level of infectivity associated with the lymphoid system in nvCJD cases," CPMP maintained. Therefore, "there may be an increased risk of infectivity being present in blood."

New variant CJD strikes teens and young adults who "usually...present with psychiatric or sensory disturbances," CPMP noted. Clinical signs later "evolve into a more typical picture of CJD." The clinical phase of nvCJD "may be more than a year" compared to "a relatively fast clinical course and an average age of onset of 65 years" for other forms.

According to CPMP, 24 cases of nvCJD have been identified in the EU - 23 in the U.K. and one in France. "Although the incidence does not appear to be rising, it is considered too early to predict the future trend for nvCJD." Cases of nvCJD were first identified in 1996.

The U.K. Medicines Control Agency said that the Committee on Safety of Medicines "will undertake a risk assessment for medicinal products containing components derived from pooled human plasma."

CSM recommended "an extension of blood product recalls to include donors subsequently identified as being strongly suspected of having nvCJD." Previously, MCA only initiated recalls in confirmed cases of nvCJD.