are ever likely to have. primates and rabbits were considered the best models for human disease. as regards vaccine effectiveness, "the committee finds that the available evidence from studies with humans and animals, coupled with reasonable assumptions of analogy, show that ava as licensed is an effective vaccine for the protection of humans against anthrax, including inhalational anthrax, caused by all known or plausible engineered strains of b. anthracis." with regard to safety, "the committee found no evidence that people face an increased risk of experiencing life-threatening or permanently disabling adverse events immediately after receiving ava, when compared with the general population. nor did it find any convincing evidence that people face elevated risk of developing adverse health effects over the longer term, although data are limited in this regard (as they are for all vaccines)." side effects of ava were found to be "comparable to those observed with other vaccines regularly administered to adults". the committee concluded that ava is "safe and efficacious" for pre-exposure prevention of inhalational anthrax. it also asserted that a new and improved anthrax vaccine might have greater assurance of consistency than ava and recommended licensure of a new vaccine requiring fewer doses and producing fewer local reactions. in the months after the october 2001 anthrax letters attacks, washington and new york area mail sorters were advised to receive prophylactic vaccination with ava. owing to the controversy surrounding the administration of the vaccine to military personnel, however, some 6,000 us postal service employees balked at this, preferring to take their chances with the risks of residual anthrax spores in the workplace. bioport changed its name to emergent biosolutions in 2004. injunctions and fda re-reviews (2004-2006) despite the positive iom assessment, mandatory vaccinations of military personnel were halted due to an injunction which was put into place on october 27, 2004. the injunction cast questions about numerous substantive challenges regarding the anthrax vaccine in footnote #10, yet the procedural findings centered on fda procedural issues, stating that additional public comment should have been sought before the fda issued its final rule declaring the vaccine safe and effective on 30 december 2003. the fda's incomplete rulemaking from 1985 effectively rendered the anthrax vaccine program illegal. the basis was the never finalized fda proposed rule. in that rulemaking the fda published, but never finalized, a licensing rule for the anthrax vaccine in the federal register, which included an expert review panel's findings. those findings included the fact that the "anthrax vaccine efficacy against inhalation anthrax is not well documented," and that "no meaningful assessment of its value against inhalation anthrax is possible due to its low incidence," and that "the vaccine manufactured by the michigan department of public health has not been employed in a controlled field trial." on december 15, 2005, the fda re-issued a final rule & order on the license status of the anthrax vaccine. after reviewing the extensive scientific evidence and carefully considering comments from the public, the fda again determined that the vaccine is appropriately licensed for the prevention of anthrax, regardless of the route of exposure. also in 2005, the george w. bush administration established a policy to ensure that the strategic national stockpile retains a current unexpired inventory of 60 million doses of ava. (the us gao reports that 4 million doses of the inventory will expire every year, requiring vaccine destruction services.) these would be used for pre- or post-exposure vaccination — of emergency first responders (police, firefighters), federal responders, medical practitioners, and private citizens — in the event of a bioterrorist anthrax attack. reinstatement of the avip (2006-2016) on october 16, 2006, the dod announced the reinstatement of mandatory anthrax vaccinations for more than 200,000 troops and defense contractors. (another lawsuit was filed by the same attorneys as before, challenging the basis of the vaccine's license on scientific grounds.) the reinstated policy required vaccinations for most military units and civilian contractors assigned to homeland bioterrorism defense or deployed in iraq, afghanistan or south korea. a modification of previous policy allowed military personnel no longer deployed to higher threat areas to receive follow up doses and booster shots on a voluntary basis. as of june 2008, over 8 million doses of ava had been administered to over 2 million us military personnel as part of the avip. in december 2008, the fda approved the new biothrax im formulation for intramuscular injections thus reducing the immunization schedule from a total of 6 shots to 5 shots (see below). on february 12, 2009, emergent biosolutions announced that the drugs controller general of india (dgci) had approved licensing of biothrax for distribution by biological e. of hyderabad. in 2011, biothrax was approved for sale in singapore by the singapore health sciences authority. building 55 approval (2016) the fda approved the company's license (officially called a supplemental biologics license application, or sbla) to manufacture biothrax in a large building in lansing, michigan known as "building 55." according to homeland preparedness news, "the use of building 55 to manufacture biothrax could expand manufacturing capacity to an estimated 20 to 25 million doses annually." the us federal government has a goal to stockpile 75 million doses of anthrax vaccines. the new facility and its capacity will help emergent meet the government's security needs. emergent worked with the biomedical advanced research and development authority (barda) within the office of the assistant secretary for preparedness and response in the united states department of health and human services on the project. the facility's value is estimated at $104 million, according to yahoo finance. administration vaccination schedule vaccination with emergent biosolutions biothrax ava and biothrax im intramuscular injections in the deltoid is given at 0 and 4 weeks, with three vaccinations at 6, 12, and 18 months, followed by annual boosters. as of 11 december 2008, the new biothrax im for intramuscular injections in the deltoid was approved by the us fda which changes the immunity initialization sequence from 6 to 5 shots given at 0 and 4 weeks and then at 6, 12, and 18 months, followed by annual boosters. this prolonged initialization sequence is required with annual booster shots, because the anthrax vaccine's primary ingredient, the anthrax protective antigen, can impair the life-cycle of the human immune system's memory b-cells and memory t-cells, through inducing the production of immunoglobulin g (igg) which sequesters furin. the loss of memory b-cells leads to declining concentrations of igg which can sequester apa, and therefore declining tolerance to the presence of anthrax bacteria. there is the potential that other memory b-cell populations will be adversely affected as well. furin is the protein activator for pro-parathyroid hormone, transforming growth factor beta 1, von willebrand factor, pro-albumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, gonadotropin, and nerve growth factor. furin is also essential to maintain peripheral immune tolerance by creating memory t-cells and suppressor t-cells. based on a retrospective cohort study of female military members inoculated during pregnancy, there may be a small risk of birth defect for inoculation during first trimester. however, the difference between the vaccinated and unvaccinated control groups was not large enough to be conclusive. the approved us fda package insert for ava contains the following notice: pregnant women should not be vaccinated against anthrax unless the potential benefits of vaccination have been determined to outweigh the potential risk to the fetus. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this product, the patient should be apprised of the potential hazard to the fetus. contraindications the approved us fda package insert for ava contains the following notice: severe allergic reaction (e.g., anaphylaxis) after a previous dose of biothrax. administer with caution to patients with a possible history of latex sensitivity because the vial stopper contains dry natural rubber and may cause allergic reactions. adverse reactions there have been no long-term sequelae of the known adverse events (local or systemic reactions) and no pattern of frequently reported serious adverse events for ava. the approved fda package insert for ava contains the following notice: "the most common (>10%) local (injection-site) adverse reactions observed in clinical studies were tenderness, pain, erythema and arm motion limitation. the most common (>5%) systemic adverse reactions were muscle aches, fatigue and headache." also, "serious allergic reactions, including anaphylactic shock, have been observed during post-marketing surveillance in individuals receiving biothrax". drug interactions the approved us fda package insert for ava contains the following notice: immunosuppressive therapies may diminish the immune response to biothrax. post-exposure vaccination some studies show that use of antibiotics effective against anthrax plus administration of ava is the most beneficial approach for purposes of post-exposure prophylaxis. this practice has been endorsed by the advisory committee on immunization practices (acip), the johns hopkins working group on civilian biodefense, and the 2002 institute of medicine report on the vaccine. however, ava is not licensed for post-exposure prophylaxis for inhalational anthrax or for use in a 3-dose regimen. any such use, therefore, would be on an off-label or ind (officially experimental) basis. "... the safety and efficacy of biothrax for post-exposure setting have not been established.". controversy in the united states although many individuals have expressed health concerns after receiving anthrax vaccine, a congressionally directed study by the institute of medicine (part of the national academy of sciences) concluded that this anthrax vaccine is as safe as other vaccines. the academy considered more than a dozen studies using various scientific designs, and heard personally from many concerned us military service members. development of a replacement vaccine while effective in protecting against anthrax, the licensed vaccine schedule is not very efficient, involving a cumbersome five (previously six) dose injection series. typically, five injections are given over a period of 18 months in order to induce a protective immune system response. in addition, in 2004 the us department of health and human services contracted with vaxgen inc. to supply up to 75 million doses of a recombinant anthrax vaccine, for $877 million. to be acceptable to hhs, this vaccine was to be protective against anthrax in three doses or less. on december 19, 2006, hhs voided the contract, because of stability problems with the vaccine, and a failure to start a phase 2 clinical trial on time. in may 2008, emergent biosolutions, the maryland-based successor to bioport, both controlled by former lebanese banker faud el hibri, acquired rights to vaxgen's patents and processes. on 30 october 2012, the us national institute of allergy and infectious diseases agreed to provide $6.5 million to the united kingdom's health protection agency for initial work on a potential future anthrax vaccine that could be delivered through the nasal passage instead of via a needle. the hpa has long produced the uk's avp anthrax vaccine. research is being continuously done to develop and test new improved candidate anthrax vaccines. the primary immunogen of acellular existing vaccines, i.e., protective antigen (pa), is highly thermolabile due to inherent structural and chemical instability. various endeavors are underway to thermostabilize pa molecule by solvent engineering and genetic engineering approaches to generate a thermostable anthrax vaccine formulation without compromising on the immunogenicity and its protective potential. the generation of a thermostable anthrax vaccine would minimize the current cold chain requirement for its storage and transport. anthrax vaccines which would be amenable to other modes of administration such as oral, nasal, skin patch etc., are also being experimented. human genome sciences announced in 2007, the development of a new anthrax neutralizing monoclonal antibody with the trademark name of 'abthrax'. the vaccine sensitizes the human immune system to the presence of the anthrax toxin factor. in 2008, hgs reported on testing on 400 human volunteers given abthrax. in 2009, hgs announced that they had made first delivery of 20,000 doses of abthrax to the united states department of defense. currently three anthrax antitoxin antibodies, namely, anthrax immune globulin intravenous or 'aigiv' (polyclonal), 'obiltoxaximab' or 'anthim' (monoclonal), and 'raxibacumab' or 'abthrax' (monoclonal) are approved for the treatment of inhalation anthrax.