Status: FDA approval withdrawn

Organizations involved:

BioPort Corp. – Former

Emergent Biosolutions Inc. – Parent; Former

Michigan Biologics Products Institute – Former

SmithKline Beecham Corp. – Former

Cross ref: See Rabies Vaccine Products (entry #525).

Description: Rabies Vaccine Adsorbed (RVA) is an aqueous formulation of rabies virus cultured in diploid fetal rhesus lung (FRhL-2) cells, inactivated with beta-propiolactone (BPL), and adsorbed on aluminum phosphate adjuvant. The vaccine is prepared from the Kissling strain of Challenge Virus Standard (CVS) rabies virus adapted to fetal rhesus lung diploid cell culture. The inactivated virus is concentrated by adsorption onto aluminum phosphate adjuvant. The vaccine is effective for pre- and post-exposure indications:, and is administered intramuscularly (not intradermally). BioPort’s Rabies Vaccine is the only human rabies vaccine approved for manufacture in the U.S. and the only rabies vaccine approved in the U.S. in liquid formulation (because it is adsorbed to aluminum phosphate) rather than being a lyophilized powder.

RVA is a suspension containing 2.5 international units (IU) or more of rabies antigen per 1.0 mL dose, no more than 2.0 mg aluminum phosphate/mL, with 0.01% sodium ethyl-mer-curithiosalicylate (thimerosal; see #939) as an antimicrobial preservative. The solution has a light pink color due to the use of phenol red as a pH indicator. The vaccine is packaged in single-dose, rubber stoppered vials containing a full dose of 1.0 mL after withdrawal. The dating period is two years when stored at 2-8˚C (refrigerated).

Nomenclature: Rabies Vaccine/BioPort [BIO]; Rabies Vaccine Adsorbed [FDA]; RVA [SY]

Companies.: RVA was approved for manufacture by BioPort Corp. (Lansing, MI: formerly Michigan Biologics Products Institute; before that, Michigan Department of Public Health), CBER/FDA est. no. 0099. BioPort is now a subsidiary of Emergent Biosolutions Inc. RVA was formerly marketed world-wide by SmithKline Beecham plc (SKB; now GlaxoSmithKline plc). In recent years, RVA was marketed only within the State of Michigan by BioPort Corp. With BioPort now concentrating on manufacture and development of bioterrorist/biological warfare defense vaccines, particularly anthrax, the company is no longer manufacturing RVA.

FDA class: Biologic PLA

CBER class: Viral And Rickettsial Vaccines

Approvals: Date = 19880318; first approval, PLA ref. no. 80-0218 and ELA ref. no. 83-0296; granted to Michigan Department of Public Health

Date = 19981112; approval revoked and granted (reissued) to new owner, BioPort Corp.

Indications: [portion of the "INDICATIONS AND USAGE” section of product insert/labeling]:

Rabies Vaccine Adsorbed is indicated for immunization against rabies in the following circumstances: primary pre-exposure immunization which is intended to induce immunity before exposure to the virus; preexposure booster immunization which is intended to augment or reinforce the level of immunity induced by previous immunization against rabies; or post-exposure prophylaxis which is given to persons who, in the judgement of the treating physician, may have been exposed to rabies. Each circumstance requires a different schedule of injections...[truncated].

Status: With BioPort now concentrating on anthrax and other biodefense vaccines, RVA is no longer being manufactured. FDA approval was recently revoked (not on recent lists of approved biologics).

BioPort reported in Jan. 1999 that RVA was being manufactured but only distributed within the State of Michigan (intrastate commerce, not explicitly subject to FDA regulation).

In Aug. 2000, it was reported that Bioport had allegedly lost the “master manuals” for manufacture of RVA. This was disclosed through a royalties dispute with several former State of Michigan employees. There has been no subsequent confirmation of this reported in the media.

In Dec. 2000, CBER/FDA reported that RVA 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. See the Vaccine Products entry (#400) for further information about BSE.

Medical: Pre-exposure vaccination involved three 1.0 mL intramuscular injections at 0, 7 and 21 or 28 days. Booster vaccination involved a single 1.0 mL injection. Post-exposure prophylaxis for previously unvaccinated persons involved administration of rabies immune globulin, 20 IU per kg body weight, and five 1.0 mL injections of vaccine on days 0, 7, 14 and 28.