Interferon alfa-n3 (human leukocyte derived)

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 × 10 8 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., >/= 10 9 infectious units per milliliter. The manufacturing process yielded a cumulative reduction of >/= 10 14 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 10 8 reduction in the titer of hepatitis B virus as determined by HBsAg assay, and a 10 9 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.

Alferon N Injection is indicated for the intralesional treatment of refractory or recurring external condylomata acuminata in patients 18 years of age or older (See DOSAGE AND ADMINISTRATION ).

The physician should select patients for treatment with Alferon N Injection after consideration of a number of factors: the locations and sizes of the lesions, past treatment and response thereto, and the patient's ability to comply with the treatment regimen. Alferon N Injection is particularly useful for patients who have not responded satisfactorily to other treatment modalities, e.g., podophyllin resin, surgery, laser or cryotherapy.

There have been no studies with this product in adolescents. This product is not recommended for use in patients less than 18 years of age.

The recommended dose of Alferon N Injection for the treatment of condylomata acuminata is 0.05 ml (250,000 IU) per wart. Alferon N Injection should be administered twice weekly for up to 8 weeks. The maximum recommended dose per treatment session is 0.5 ml (2.5 million IU). Alferon N Injection [Interferon alfa-n3 (human leukocyte derived)] should be injected into the base of each wart, preferably using a 30 gauge needle. For large warts, Alferon N Injection may be injected at several points around the periphery of the wart, using a total dose of 0.05 ml per wart.

The minimum effective dose of Alferon N Injection for the treatment of condylomata acuminata has not been established. Moderate to severe adverse experiences may require modification of the dosage regimen or, in some cases, termination of therapy with Alferon N Injection.

Genital warts usually begin to disappear after several weeks of treatment with Alferon N Injection. Treatment should continue for a maximum of 8 weeks. In clinical trials with Alferon N Injection, many patients who had partial resolution of warts during treatment experienced further resolution of their warts after cessation of treatment. Of the patients who had complete resolution of warts due to treatment, half the patients had complete resolution of warts by the end of the treatment and half had complete resolution of warts during the 3 months after cessation of treatment. Thus, it is recommended that no further therapy (Alferon N Injection or conventional therapy) be administered for 3 months after the initial 8-week course of treatment unless the warts enlarge or new warts appear. Studies to determine the safety and efficacy of a second course of treatment with Alferon N Injection have not been conducted.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Injectable Solution: Each vial contains 1 ml of Alferon N Injection. Each ml of Alferon N Injection contains 5 million IU of Interferon alfa-n3, 3.3 mg of phenol, and 1 mg of Albumin (Human) in a pH 7.4 phosphate-buffered saline solution (8.0 mg/ml sodium chloride, 1.74 mg/ml sodium phosphate dibasic, 0.20 mg/ml potassium phosphate monobasic, and 0.20 mg/ml potassium chloride). One vial per box. (NDC 54746-001-01).

STORAGE

Alferon N Injection [Interferon alfa-n3 (human leukocyte derived)] should be stored at 2° to 8°C (36° to 46°F). Do not freeze. Do not shake.

CAUTION: FEDERAL (U.S.A.) LAW PROHIBITS DISPENSING WITHOUT PRESCRIPTION.

1. Friedman-Kien, AE; Eron, LJ; Conant, M; et al., JAMA 1988; 259:  533-538.
2. Kirby, P; (editorial comment), JAMA 1988; 259:  570-572.
3. Friedman-Kien, AE; Plasse, TF; et al., Papilloma Viruses: Molecular and Clinical Aspects [Howley, PM, Broker, TR (eds)], New York, Alan R. Liss, Inc.; 1986; 217-233.
4. Geffen, JR; Klein, RJ; Friedman-Kien, AE; J. Infect. Dis. 1984; 150:  612-615.
5. Kauppila, A; et al., Int. J. Cancer 1982; 29:  291-294.
6. Trown, PW; et al., Cancer 1986; 57 (Suppl):  1648-1656.
7. Schafer, TW; et al., Science 1972; 176:  1326-1327.

Manufactured and Distributed by:

Interferon Sciences, Inc.

783 Jersey Avenue

New Brunswick, NJ 08901-3660

U.S. Lic. No. 930

Copyright © 1989, 1990, 1997, 2000 Interferon Sciences, Inc.

New Brunswick, NJ 08901-3660.

All rights reserved.

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