Status: approvals withdrawn

Organizations involved:

Wyeth/Lederle Labs. – Manuf.; R&D; Tech.

Wyeth – World mark.; Parent

Cross ref: See the Pneumococcal Vaccines entry (#512). See the entry above for Prevnar, which has replaced this as Wyeth’s pneumococcal vaccine; and see the entry below for a similar 23-valent unconjugated vaccine, Pneu-movax 23 (#515), from Merck & Co.

Description: Pneumococcal Vaccine Polyvalent or PNU-Imune 23 is an aqueous mixture of purified capsular polysaccharide antigens obtained from independent culture of 23 types of Streptococcus pneumoniae bacteria.

PNU-Imune 23 is available in package containing five 2.5 mL (5-dose) vials and as a package of five prefilled 0.5 mL Lederject disposable syringes. Each 0.5 mL dose of vaccine contains 25 µg of each type of 23 capsular polysaccharides (using Danish nomenclature – types 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F; using U.S. nomenclature – types 1, 2, 3, 4, 5, 26, 51, 8, 9, 68, 34, 43, 12, 14, 54, 17, 56, 19, 57, 20, 22, 23 and 70) dissolved in isotonic saline solution containing 0.01% thimerosal (mercury derivative; see #939) as an antimicrobial preservative. The vaccine is stored at 2-8˚C (refrigerated).

The major difference between PNU-Imune and a comparable unconjugated vaccine, Pneumovax 23 (from Merck), is that this vaccine contains type 12, while Pneumovax 23 contains type 12F. Otherwise the same types are included in each.

Nomenclature: Pneumococcal Vaccine/Lederle [BIO]; PNU-IMUNE 23 [TR ‘PNU-IMUNE’ is reg. trademark)]; Pneumococcal Vaccine Polyvalent [FDA]; Pneumococcal Vaccine, Polyvalent [FDA former]; Streptococcus pneumoniae capsular polysaccharide vaccine [SY]; PPSV23 [SY]; NDC 0005-2309-31; 0005-2309-33 [NDC]

Manufacture: Each strain of the 23 types of Streptococcus pneumoniae is independently cultured in large fermentation vessels using modified Holt’s media. Cultivation of the pneumococci requires media containing bovine proteins and other macromolecules. These macromolecules and potentially immunogenic substances are not detectable in the final vaccine (at time of 1983 approval). The identity of each inoculum is verified by its reaction with type-specific pneumococcal anti-serum. The bacteria are also examined by this assay and by plate culture after the fermentation run to verify purity and identity of the pneumococcal type. The bacterial capsular polysaccharides are extracted from the culture media by a series of ethanol fractionation/precipitation and ultrafiltration steps, and lyophilized. Final formulation involves mixing of the 23 bulk lyophilized antigen powders, dissolution in saline, addition of thimerosal preservative (0.1%), lyophilization, and packaging.

The product is prepared and tested according to the Pneumococcal Vaccine Guidelines (Jan. 24, 1982) for types 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 12, 14, 18C, 19F and 23F; and according to the license specifications for types 5, 6B, 9V, 10A, 11A, 15B, 17F, 19A, 20, 22F and 33F. Potency, chemical purity, and stability of the vaccine are controlled by physico-chemical characterization of the 23 individual polysaccharides, including determination of molecular size (related to potency) and chemical composition, as well as sterility, general safety, and pyrogenicity tests. Identification of the 23 individual bulk powder components and their presence in the final vaccine are determined by immunoprecipitation methods. Lederle/Wyeth has demonstrated consistency of production for the 23 types of pneumococcal capsular polysaccharides in the vaccine.

FDA class: Biologic PLA

CBER class: Bacterial Antigens and Vaccines

Approvals: Date = 19790815; 1st approval, granted to Lederle Labs. for PNU-IMUNE-14, containng 50 µg of capsular polysaccharide from 14 types of pneumococci

Date = 19830715, PLA supplement; 1st approval of PNU-IMUNE 23, according to CBER/FDA database; The vaccine contains polysaccharide from 23 types of pneumococci with the amount of each antigen decreased from 50 to 25 µg.

Date = 19830721, first approval of PNU-IMUNE 23, according to Wyeth

Date = 19860000; product license revoked under old proper name and reissued under new FDA proper name

Indications: PNU-IMUNE 23 is indicated for immunization against pneumococcal disease caused by those pneumococcal types included in the vaccine.

Status: Until a few years ago, the vaccine was still approved and marketed. Wyeth now offers an improved, more expensive, conjugate vaccine (Prevnar).

In Dec. 2000, CBER/FDA reported that PNU-Imune 23 was being manufactured using bovine-derived material of unknown/undocumented origin, possibly from countries on the official USDA list of countries known to have cattle with BSE. Wyeth/AHP resolved this situation. See the Vaccine Products entry (#400) for further information about BSE/TSE.

In Jan. 2009, CDC issued new recommendations for use of a single dose of the 23-valent vaccine (PPSV23) among adult smokers ages 19-6; and use of a single dose among adults ages 19-64 who are diagnosed with asthma. A second dose is recommended 5 years after the first dose for persons ≥ 2 years who are immunocompromised, have sickle cell disease, or functional or anatomic asplenia.

Tech. transfer: Purified pneumococcal polysaccharide vaccines are disclosed in U.S. patents 4,242,501; 4,221,906; and 4,686,102, assigned to Lederle Labs./American Cyanamid Corp. (now Wyeth). U.S. 4,686,102, “Multivalent pneumococcal vaccine and preparation thereof,” Aug. 11, 1987, and related patents disclose multivalent pneu-mococcal vaccines, and methods of purifying various different types of pneumococcal capsular polysaccharides.

Market: The 2005 Average Wholesale Price (AWP) is $219.62/5-dose vial (no change from 2004) (Red Book, 2005), although the vaccine is no longer available.

The National Immunization Program, Centers for Disease Control and Prevention (CDC), had reported (Dec. 2000) that it purchased the vaccine in bulk for $5.606/dose (contract ended 6/2001).