Author/Editor		Marinko, Petra; Krbavčič, Aleš
Title		Imunogenost interferona: tehnično vrednotenje interferona alfa
Translated title		Immunogenicity of interferon: technical evaluation of interferon alpha
Type		članek
Source		Farm Vestn
Vol. and No.		Letnik 52, št. 2
Publication year		2001
Volume		str. 153-61
Language		slo
Abstract		During long-term treatment of various malignant and viral diseases with interferon-alpha (IFN-alpha) a proportion of patients develop anti-IFN-alpha antibodies for as yet unknown reasons. This article outlines the results of investigations into the production of antibodies to IFN-alpha that were undertaken. The antigenicity might result from the inherent structural properties of IFN-alpha or from the presence of antigenicalIy active derivatives of IFN that are present as a result of the production, purification and storage gracedures employed to manufacture of the cammercial IFN preparations now in use. The technical evaluation of IFN-alpha2a production and storage are described, which gave rise to several recommendations, particularly concerning storage conditions far the commercially available vials. In vials of IFN-alpha2, the presence of IFNalpha-IFN-alpha aggregates and agreggates of IFN with human serum albumin (HSA), the excipient of the dosage form, was demonstrated. Aggregates of IFN-alpha are quite antigenic. As a result of these investigation, further changes in formulation design were implemented. A new injectable solution and HSA free formulation has been developed that has been shown to have fewer imunogenic properties. New forms of pegylated IFN-alpha are also presented in the article.
Summary		Med dolgotrajnim zdravljenjem malignih in virusnih bolezni z interferonom-alfa (IPN-alfa) mnogi pacienti iz doslej ne povsem znanih razlogov razvijejo protitelesa prati IFN-a. Članek daje splošen pregled rezultatov številnih raziskav o razvoju protiteles. Antigenost je lahko posledica strukturnih lastnosti IFN-a ali prisotnosti antigenih derivatov IFN, ki nastanejo med postopki proizvodnje, čiščenja ali med shranjevanjem kornerciatno dostopnih interferonskih farmacevtskih izdelkov. Opisano je tehnično vrednotenje groizvodnje IFN-alfa2a in pogojev shranjevanja, iz česar so izšla številna priporočila za shranjevanje komercalno dostognih vial. V vialah IFN-alfa2 so zaznali agregate IFM-alfa - IFN-alfa in agregate IFN-alfa z ekscipientom - hurnanim serumskim albuminom (HSA). Agregati sa se izkazali za imunogene, Na osnovi rezultatov teh raziskav so razvili nove injektabilne raztopine IFN-alfa2 brez HSA, za katere se je izkazalo, da so manj imunogene. V članku podajamo tudi nove oblike pegiliranega IFN-alfa.
Descriptors		INTERFERON-ALPHA INTERFERON ALFA, RECOMBINANT INTERFERON ALFA-2A SERUM ALBUMIN ANTIBODY FORMATION TECHNOLOGY, PHARMACEUTICAL DRUG STABILITY