Alferon N Injection (Interferon Alfa-N3) - Description

DESCRIPTION

Alferon N Injection® [Interferon alfa-n3 (human leukocyte derived)] is a sterile aqueous formulation of purified, natural, human interferon alpha proteins for use by injection. Alferon N Injection® consists of interferon alpha proteins comprising approximately 166 amino acids ranging in molecular weights from 16,000 to 27,000 daltons. The specific activity of Interferon alfa-n3 is approximately equal to, or greater than, 2 × 10⁸ IU/mg of protein.

Alferon N Injection® is manufactured from pooled units of human leukocytes which have been induced by incomplete infection with a murine virus (Sendai virus) to produce Interferon alfa-n3. The manufacturing process includes immunoaffinity chromatography with a murine monoclonal antibody, acidification (pH 2) for 5 days at 4°C, and gel filtration chromatography.

Since Alferon N Injection® is manufactured using source leukocytes, human donor screening is performed to minimize the risk that the leukocytes could contain infectious agents. In addition, the manufacturing process contains steps which have been shown to inactivate known viruses. There has been no evidence of infection transmission to recipients in clinical trials (See WARNINGS).

The Alferon N Injection® manufacturing process was evaluated for quantitative removal or inactivation of model pathogenic viruses. The viruses were deliberately added to the leukocytes in amounts far exceeding those present in contaminated blood, i.e., >/= 10⁹ infectious units per milliliter. The manufacturing process yielded a cumulative reduction of >/= 10¹⁴ of infectious HIV-1, i.e., >/= 10^6.5 removal by acid inactivation and >/= 10^7.9 removal by the purification process. In the validation studies, there was 10⁸ reduction in the titer of hepatitis B virus as determined by HBsAg assay, and a 10⁹ reduction in the infectious titer of herpes simplex virus-1 (HSV-1). Cultivation of Alferon N Injection® [Interferon alfa-n3 (human leukocyte derived)] Purified Drug Concentrate with human indicator cells, i.e., MRC-5 cells, peripheral blood leukocytes in the presence of Cyclosporin A, and fetal cord blood cells, did not detect the presence of infectious viruses.

As part of a validation study, Alferon N Injection® was examined for the presence of the following viruses; Sendai virus (SV), HlV-1, HTLV-l, HBV, HSV-1, CMV, and EBV. Alferon N Injection® contained no detectable quantities of these viruses. In addition, other studies, i.e., Polymerase Chain Reaction (PCR) and Dot Blot Hybridization (DBH), have shown no detectable genetic material from these viruses in Alferon N Injection®. The sensitivity of the PCR was 10 copies for HlV-1 (env gene probe) and 10 copies for HBV (S/P gene probe). The sensitivity of the DBH was 1 pg for EBV, < 10 pg for CMV, < 10 pg for HSV-1, and < 2 pg for SV. Furthermore, sera from 105 patients treated with Alferon N Injection® (95 with condylomata acuminata and 10 with cancer) were tested for antibody to HlV-1 and HlV p24 antigen. There was no evidence to suggest transmission of HlV-1 by Alferon N Injection®. Sera from 135 patients with condylomata acuminata treated with Alferon N Injection® were tested to determine abnormal SGOT laboratory values. There was no evidence to suggest transmission of hepatitis by Alferon N Injection® based on both SGOT results and patient data collected during clinical trials.

Alferon N Injection® has been extensively purified using immunoaffinity chromatography with a murine monoclonal antibody, acidification (pH 2) for 5 days at 4°C, and gel filtration chromatography. Alferon N Injection® has been subjected to the acid treatment for five days during its manufacture in order to reduce the risk of viral transmission. Subsequent analyses of the Alferon N Injection® [Interferon alfa-n3 (human leukocyte derived)] Purified Drug Concentrate confirm the absence of detectable infectious or non-infectious viral particles.

The leukocyte nutrient medium contains the antibiotic neomycin sulfate at a concentration of 35 mg/L; however, neomycin sulfate is not detectable in the final product, i.e., < 0.64 µg/ml.

Murine immunoglobulin (IgG) is detected in the Alferon N Injection® Purified Drug Concentrate at levels below 0.15% of the Interferon alfa-n3 protein. This equates to levels less than 8 ng of murine IgG per million of IU Interferon alfa-n3 (range of 0.9 to 5.6 ng typically found).

Alferon N Injection® is available in an injectable solution containing 5 million IU Interferon alfa-n3 per vial for intralesional injection. The solution is clear and colorless. Each milliliter (ml) contains five million IU of Interferon alfa-n3 in phosphate-buffered saline (8.0 mg sodium chloride, 1.74 mg sodium phosphate dibasic, 0.20 mg potassium phosphate monobasic, and 0.20 mg potassium chloride) containing 3.3 mg phenol as a preservative and 1 mg Albumin (Human) as a stabilizer.