recombinant products.

[Guest guest]

Dear Group:

As a follow up to the Hep. B discussions........

I was alerted to the article [copied below] in the BMJ regarding recombinant

products by our friend " Nurse " . Here is an exerpt from her email to

me:

"

Dear Liz,

Hi. Have you seen this letter to the editor of the BMJ regarding

recombinant products. The point is made, as you have made, that recombinant

products arent REALLY synthetic but grown on biologic cultures which could

transmit viruses and prions. He is referring to recombinant factor VIII for

hemophiliacs but this could apply , obviously , to all recombinant

products.....vaccines etc......

Once again this makes me think of Merck's Recombivax ( recombinant hep b

vaccine) which was (is still ? ) manufactured and filled in the UK.

Were they using UK albumin to grow this vaccine? Probably. Especially that

made before the ban. "

Hope this helps someone Liz.

http://www.bmj.com/cgi/content/full/316/7141/1385

Recombinant factor VIII may not abolish risk of new variant CJD from

factor VIII

EDITORBarbara and Flanagan report the precautionary measures against new

variant Creutzfeldt-Jakob disease that have been announced by the UK

Department of Health.1 Unfortunately, the secretary of state announced

the outcome of the NHS review of the provision of factor VIII for

patients with haemophilia at the same time. The rationale for endorsing

the use of recombinant factor VIII in children has thus become linked to

concerns over new variant Creutzfeldt-Jakob.

Recombinant factor VIII is a biologically derived product produced by

cell culture, not a synthetic product as stated in the announcement from

the Department of Health. This is an important distinction because the

word synthetic may be taken to imply that recombinant products do not

carry a risk of transmitting infectious agents.

Recombinant factor VIII typically has a total protein content that is

greater than or equivalent to that contained in some high purity

plasma-derived factor VIII. This protein has the potential to be a

source of infectiona recognised problem for all recombinant products.2

Seroconversion for virus has been reported in haemophilic patients

receiving recombinant factor VIII.3 All currently available recombinant

and most commercial plasma-derived factor VIII products contain human

plasma protein (often as stabiliser) obtained from donors in the United

States. To date, new variant Creutzfeldt-Jakob has not occurred in this

population. It is therefore difficult to differentiate between

recombinant factor VIII and factor VIII derived from US plasma in terms

of the risk of transmission of the disease from human protein. The risk

is different, however, when the content of other animal protein is

considered. The final product specifications for recombinant products

restrict the amout of hamster, murine, and (in one case) bovine protein

as well as potentially oncogenic DNA residues. The presence of these

contaminants may carry its own risk.

There is strong concern that the aetiological agent of transmissible

spongiform encephalopathies can jump between animal species.4

Transmission of contamination from animal-derived starting materials is

possible. Fragments of retrovirus-like particles, presumably derived

from hamster culture cells, have been detected in one recombinant factor

VIII.5 Finally, the complexity of the manufacturing process for

recombinant products has periodically interfered with their

availability, and total reliance on them may be inappropriate for many

patients.

The statement from the Department of Health is misleading, and the

advice given to clinicians regarding prescribing of such products is

suspect in the context of new variant Creutzfeldt-Jakob disease. Yet

again, political expediency has precipitated the reaction to this

threat, this time to appease vocal and perhaps misinformed groups

calling for recombinant factor VIII products.

J P Betts, International technical affairs director. 

Grupo Grifols, Cambridge CB4 4GP

*J P Betts works for Grupo Grifols, a Spanish company producing a range

of products from plasma fractionation, including factor VIII, albumin,

and immunoglobulins. One of the group's other companies manufactures a

recombinant blood product.

------------------------------------------------------------------------

1.Barbara J, Flanagan P. Blood transfusion risk: protecting against the

unknown. BMJ 1998; 316: 717-718[Full Text]. (7 March.) 2.Committee on

Proprietary Medicinal Products. Note for guidance: production and

quality control of medicinal products derived by recombinant DNA

technology. Brussels: CPMP , 1994(III/3477/92; revision 1994.) 3.

Aygoren-Pursun E, Scharrar I. A multicenter pharmacosurveillance study

for the evaluation of the efficacy and safety of recombinant factor VIII

in the treatment of patients with hemophilia A. Thromb Haemostas 1997;

78: 1352-1356[Medline].4.Bruce ME, Will RG, Ironside JW, McConnell I,

Drummond D, Suttie A, et al. Transmissions to mice indicate that `new

variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501

[Medline].5.Arnold D. Virus safety considerations for recombinant factor

VIII (recombinant factor viii, Kogenate). Hemophilia 1995; 1(suppl 2):

22-23.