CFR Subpart H

CFR Subpart H
in effect

21 C.F.R. § 640.80 Albumin (Human).

(a) Proper name and definition. The proper name of the product shall be Albumin (Human). The product is defined as a sterile solution of the albumin derived from human plasma. (b) Source material. The source material of Albumin (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§ 640.1 through 640.5, or Source Plasma prepared as prescribed in §§ 640.60 through 640.76. (c) Additives in source material. Source material shall not contain an additive unless it is shown that the processing method yields a final product free of the additive to such extent that the continued safety, purity, potency, and effectiveness of the final product will not be adversely affected.

21 C.F.R. § 640.81 Processing.

(a) Date of manufacture. The date of manufacture shall be the date of final sterile filtration of a uniform pool of bulk solution. (b) Processing method. The processing method shall not affect the integrity of the product, and shall have been shown to yield consistently a product which is safe for intravenous injection. (c) Microbial contamination. All processing steps shall be conducted in a manner to minimize the risk of contamination from microorganisms, pyrogens, or other impurities. Preservatives to inhibit growth of microorganisms shall not be used during processing. (d) Storage of bulk fraction. Bulk concentrate to be held more than 1 week prior to further processing shall be stored in clearly identified closed vessels at a temperature of −5 °C or colder. Any other bulk form of the product, exclusive of the sterile bulk solution, to be held more than 1 week prior to further processing shall be stored in clearly identified closed vessels at a temperature of 5 °C or colder. Any bulk fraction to be held one week or less prior to further processing shall be stored in clearly identified closed vessels at a temperature of 5 °C or colder. (e) Heat treatment. Heating of the final containers of Albumin (Human) shall begin within 24 hours after completion of filling. Heat treatment shall be conducted so that the solution is heated continuously for not less than 10, or more than 11 hours, at an attained temperature of 60±0.5 °C. (f) Stabilizer. Either 0.08±0.016 millimole sodium caprylate, or 0.08±0.016 millimole sodium acetyltryptophanate and 0.08±0.016 millimole sodium caprylate per gram of protein shall be present as a stabilizer(s). Calculations of the stabilizer concentration may employ the labeled value for the protein concentration of the product as referred to in § 640.84(d). (g) Incubation. All final containers of Albumin (Human) shall be incubated at 20 to 35 °C for at least 14 days following the heat treatment prescribed in paragraph (e) of this section. At the end of this incubation period, each final container shall be examined and all containers showing any indication of turbidity or microbial contamination shall not be issued. The contents of turbid final containers shall be examined microscopically and tested for sterility. If growth occurs, organisms shall be identified as to genus, and the material from such containers shall not be used for further manufacturing.

21 C.F.R. § 640.82 Tests on final product.

Tests shall be performed on the final product to determine that it meets the following standards: (a) Protein concentration. Final product shall conform to one of the following concentrations: 4.0 ±0.25 percent; 5.0 ±0.30 percent; 20.0 ±1.2 percent; and 25.0 ±1.5 percent solution of protein. (b) Protein composition. At least 96 percent of the total protein in the final product shall be albumin, as determined by a method that has been approved for each manufacturer by the Director, Center for Biologics Evaluation and Research, Food and Drug Administration. (c) pH. The pH shall be 6.9 ±0.5 when measured in a solution of the final product diluted to a concentration of 1 percent protein with 0.15 molar sodium chloride. (d) Sodium concentration. The sodium concentration of the final product shall be 130 to 160 milliequivalents per liter. (e) Potassium concentration. The potassium concentration of the final product shall not exceed 2 milliequivalents per liter. (f) Heat stability. A final container sample of Albumin (Human) shall remain unchanged, as determined by visual inspection, after heating at 57 °C for 50 hours, when compared to its control consisting of a sample, from the same lot, which has not undergone this heating.

21 C.F.R. § 640.83 General requirements.

(a) Preservative. The final product shall not contain a preservative. (b) Storage of bulk solution. After all processing steps have been completed, the sterile bulk solution shall be stored in a manner that will ensure the continued sterility of the product, and at a temperature that shall not exceed the recommended storage temperature of the final product prescribed in § 610.53 of this chapter.

21 C.F.R. § 640.84 Labeling.

In addition to the labeling requirements of §§ 610.60, 610.61, and 610.62 of this chapter, the container and package labels shall contain the following information: (a) The osmotic equivalent in terms of plasma, and the sodium concentration in terms of a value or a range in milliequivalents per liter; (b) The cautionary statement placed in a prominent position on the label, “Do Not Use if Turbid. Do Not Begin Administration More Than 4 Hours After the Container Has Been Entered.”; (c) The need for additional fluids when 20 percent or 25 percent albumin is administered to a patient with marked dehydration; (d) The protein concentration, expressed as a 4 percent, 5 percent, 20 percent, or 25 percent solution.

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