Direct and indirect effects of rotavirus vaccination upon childhood hospitalizations in 3 US Counties, 2006-2009.
ABSTRACT Routine rotavirus vaccination of US infants began in 2006. We conducted active, population-based surveillance for rotavirus gastroenteritis hospitalizations in 3 US counties to assess vaccine impact.
Children <36 months old hospitalized with diarrhea and/or vomiting were enrolled from January through June each year during the period 2006-2009 and tested for rotavirus. Age-stratified rates of hospitalization for rotavirus infection were compared with corresponding vaccination coverage among a control group of children with acute respiratory illness. To assess direct and indirect benefits, vaccination coverage rates in the control group were multiplied by vaccine effectiveness estimates to calculate expected reductions in the rate of hospitalization for rotavirus infection. Rotavirus serotypes were compared across years.
Compared with 2006, a significant reduction in rates of hospitalization for rotavirus infection (P < .001) was observed in 2008 among all age groups. There was an 87% reduction in the 6-11-month-old age group (coverage, 77%), a 96% reduction in the 12-23-months-old age group (coverage, 46%), and a 92% reduction in the 24-35-month-old age group (coverage, 1%), which exceeded reductions expected on the basis of coverage and vaccine effectiveness estimates. Age-specific rate reductions were nearly equivalent to those expected on the basis of age-specific vaccine coverage in 2009. Predominant strains varied annually: G1P (91%) in 2006; G1P (45%) and G12P (36%) in 2007; G1P (89%) in 2008; and G3P (43%), G2P (34%), and G9P (27%) in 2009.
Rotavirus vaccination has dramatically decreased rates of hospitalization for rotavirus infection among children in these US counties. In 2008, reductions were prominent among both vaccine-eligible age groups and older, largely unvaccinated children; the latter likely resulted from indirect protection. Although rates among age groups eligible for vaccination remained low in 2009, indirect benefits disappeared.
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ABSTRACT: A 2007 meta-analysis showed probiotics, specifically Lactobacillus rhamnosus GG (LGG), shorten diarrhea from acute gastroenteritis (AGE) by 24 hours and decrease risk of progression beyond 7 days. In 2005, our institution published a guideline recommending consideration of probiotics for patients with AGE, but only 1% of inpatients with AGE were prescribed LGG. The objective of this study was to increase inpatient prescribing of LGG at admission to >90%, for children hospitalized with AGE, within 120 days. This quality improvement study included patients aged 2 months to 18 years admitted to general pediatrics with AGE with diarrhea. Diarrhea was defined as looser or ≥3 stools in the preceding 24 hours. Patients with complex medical conditions or with presumed bacterial gastroenteritis were excluded. Admitting and supervising clinicians were educated on the evidence. We ensured LGG was adequately stocked in our pharmacies and updated an AGE-specific computerized order set to include a default LGG order. Failure identification and mitigation were conducted via daily electronic chart review and e-mail communication. Primary outcome was the percentage of included patients prescribed LGG within 18 hours of admission. Intervention impact was assessed with run charts tracking our primary outcome over time. The prescribing rate increased to 100% within 6 weeks and has been sustained for 7 months. Keys to success were pharmacy collaboration, use of an electronic medical record for a standardized order set, and rapid identification and mitigation of failures. Rapid implementation of evidence-based practices is possible using improvement science methods.PEDIATRICS 03/2013; 131 Suppl 1:S96-S102. · 5.30 Impact Factor
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ABSTRACT: Rotavirus gastroenteritis is a vaccine-preventable disease that confers a high medical and economic burden in more developed countries and can be fatal in less developed countries. Two vaccines with high efficacy and good safety profiles were approved and made available in Europe in 2006. We present an overview of the status of rotavirus vaccination in Europe. We discuss the drivers (including high effectiveness and effect of universal rotavirus vaccination) and barriers (including low awareness of disease burden, perception of unfavourable cost-effectiveness, and potential safety concerns) to the implementation of universal rotavirus vaccination in Europe. By February, 2014, national universal rotavirus vaccination had been implemented in Belgium, Luxembourg, Austria, Finland, Greece, Luxembourg, Norway, and the UK. Four other German states have issued recommendations and reimbursement is provided by sickness funds. Other countries were at various stages of recommending or implementing universal rotavirus vaccination.The Lancet Infectious Diseases 05/2014; 14(5):416-425. · 19.45 Impact Factor
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ABSTRACT: Acute gastroenteritis (AGE) is a very common reason for pediatric consultations. Various expert committees have issued guidelines for its management, based on systematic use of an oral rehydration solution (ORS), early appropriate nutrition (most recent previous diet), and avoiding routine treatment with medication. The aim of the study was to assess the application of these guidelines by pediatricians in outpatient practice for mild to moderate AGE. A secondary objective was to question pediatricians about their practices for vaccination against rotavirus. In June 2012, e-mail requests were sent to 1187 pediatricians in private practice, asking them to complete an anonymous questionnaire online at the website of the French Association of Pediatricians in Outpatient Practice. A total of 641 (54%) responses could be analyzed. Nearly all the pediatricians recommended early resumption of nutrition after administration of ORS. Depending on the child's age, 16 to 23% reported they would recommend resuming feeding with lactose-free milk, and 80% would advise an antidiarrhea diet for children older than 6months. The drugs prescribed most often were, in decreasing order, racecadotril (acetorphan), diosmectite, and probiotics. Although 90% of the pediatricians prescribed vaccination against rotavirus, 65% estimated that it was performed in more than half of all children. This study of the management of moderate acute gastroenteritis shows variable adhesion to guidelines by pediatricians treating outpatients. Although ORS, maintenance of breastfeeding, and early nutrition after ORS are now widely applied, the type of nutrition recommended often failed to meet guidelines. Drug prescription is still too frequent. Anti-rotavirus vaccine is prescribed often but is administered much less frequently.Archives de Pédiatrie 08/2013; · 0.41 Impact Factor
R E V I E W A R T I C L E
The Impact of Anti-infective Drug Shortages on
Hospitals in the United States: Trends and
Milena M. Griffith,1,2,3Alan E. Gross,1,2,3Sarah H. Sutton,3,4Maureen K. Bolon,3,4John S. Esterly,2,3,5Jean A. Patel,2,3
Michael J. Postelnick,2,3Teresa R. Zembower,3,4and Marc H. Scheetz1,2,3
1Department of Pharmacy Practice, Midwestern University Chicago College of Pharmacy, Downers Grove, Illinois;2Department of Pharmacy and
3Antimicrobial Stewardship Program, Northwestern Memorial Hospital,4Division of Infectious Diseases, Department of Medicine, Northwestern
University Feinberg School of Medicine, and5Department of Pharmacy Practice, Chicago State University College of Pharmacy, Illinois
(See the Editorial Commentary by Leviton, on pages 692–3.)
Anti-infective shortages pose significant logistical and clinical challenges to hospitals and may be considered
a public health emergency. Anti-infectives often represent irreplaceable life-saving treatments. Furthermore,
few new agents are available to treat increasingly prevalent multidrug-resistant pathogens. Frequent anti-
infective shortages have substantially altered patient care and may lead to inferior patient outcomes. Because
many of the shortages stem from problems with manufacturing and distribution, federal legislation has been
introduced but not yet enacted to provide oversight for the adequate supply of critical medications. At the
local level, hospitals should develop strategies to anticipate the impact and extent of shortages, to identify
therapeutic alternatives, and to mitigate potential adverse outcomes. Here we describe the scope of recent anti-
infective shortages in the United States and explore the reasons for inadequate drug supply.
A 45-year-old man with a medical history significant for
human immunodeficiency virus (HIV)/AIDS was
admitted to the medical intensive care unit with acute
respiratory failure requiring intubation, after 4 days of
shortness of breath, fever, and productive cough. Em-
piric therapy for community-acquired pneumonia and
Pneumocystis jiroveci pneumonia was started. Because of
the national shortage of intravenous sulfamethoxazole-
trimethoprim, the local pharmacy stock was depleted, so
the patient began treatment with the oral formulation.
When his condition failed to improve, the Antimicro-
bial Stewardship Program contacted the manufacturer,
and, 72 hours after initiation of therapy, an emergency
supply of intravenous sulfamethoxazole-trimethoprim
was obtained through a compassionate use program.
Anti-infectives frequently represent irreplaceable life-
saving treatments, particularly for hospitalized patients.
Access to these medications is jeopardized by the in-
creasing frequency of drug shortages. Anti-infectives
represent 13% of the 193 currently unavailable medi-
cations asofFebruary2011.Compounding thisissue
is the dramatic reduction in the approval of new anti-
infective agents by the United States Food and Drug
Administration (FDA) [2, 3]. Meanwhile, anti-infective
resistance escalates. These factors have converged to
create a public health emergency.
The Center for Drug Evaluation and Research
(CDER) Drug Shortage Program of the FDA defines
a drug shortage as ‘‘a situation in which the total supply
of all clinically interchangeable versions of an FDA-
regulated drug is inadequate to meet the current or
projected demand at the user level’’ . Anti-infectives
present significant challenges in the realm of drug
shortages. First, lack of drug availability will delay
treatment or require the use of nonpreferred therapies
Received 4 August 2011; accepted 6 October 2011.
Correspondence: Marc Scheetz, PharmD, MSc, Department of Pharmacy
Practice, Midwestern University Chicago College of Pharmacy, 555 31st St,
Downers Grove, IL, 60515 (firstname.lastname@example.org).
Clinical Infectious Diseases
? The Author 2012. Published by Oxford University Press on behalf of the
Infectious Diseases Society of America. All rights reserved. For Permissions,
please e-mail: email@example.com.
d CID 2012:54 (1 March)
d Griffith et al
Embargoed until 12.01am EST January 20th 2012
a growingproportionof infectedpatients in acute carehospitals,
a single anti-infective agent may represent an irreplaceable
therapeutic option . Thus, a tenuous supply of anti-infective
agents may result in delays of effective therapy, suboptimal
therapeutic selections, and incorrect substitutions . Here
we describe the scope and impact of recent anti-infective
shortages in the United States and explore the multiple reasons
for inadequate drug supply.
SCOPE AND IMPACT OF ANTI-INFECTIVE
Clinicalchallenges withdrug shortagesas illustratedin the former
case are unfortunately becoming all too common. According to
a survey conducted in 1999 by the Infectious Diseases Society of
America Emerging Infections Network, ?82% of respondents
reported a need to alter therapy due to a shortage of an anti-
infective agent. This survey also identified common disease states
for which the therapy alterations occurred, including sepsis, en-
docarditis, meningitis, and neurosyphilis . In the years
that have followed this survey, the difficulties that shortages
present remain disturbingly persistent. Drug shortages also
have a large economic burden. A 2011 survey conducted by
Kaakeh et al found that the labor costs associated with drug
shortages in the United States were estimated at $216 million
Not only have anti-infective shortages continued to occur
with increasing frequency, new anti-infective approvals from
the FDA have slowed [2, 3]. To evaluate trends in anti-infective
shortages, we performed analysis using available data.
compiled from national databases (Figure 1) [1, 13]. Each drug
formulation was included once from 2005 to 2010, with current
shortages receiving priority and resolved shortages classified
according to the first year of shortage. If resolution occurred
during the time period, the shortage of the drug was classified as
resolved. Topical and systemic anti-infectives including anti-
bacterials, antifungals, and antivirals were reviewed. Vaccines
were excluded from the analysis because they represent pre-
ventative agents rather than direct treatment. New molecular
anti-infective entities were determined by searching the FDA
drug approvals Web site for new approvals from January 2005
through December 2010 . One limitation of this analysis is
that recent shortages were less likely to be resolved when the
data were collected. Despite this, shortages increased linearly
the time of data collection .
The impact of these shortages is probably realized in delays
to effective therapy, suboptimal therapeutic selections, and
incorrect substitutions. Clearly, both suboptimal therapy and
delay of active anti-infective therapy can lead to worse patient
outcomes [5–8, 14].
The potential for anti-infective shortages to lead to sub-
optimal therapy exists in the setting of multiple therapeutic
options, particularly when medical evidence clearly defines
a hierarchy of treatment alternatives. This was realized in the
treatment of neurosyphilis from 1999 to 2000, during which
intravenous penicillin G was voluntarily recalled owing to reg-
ulatory concerns from the FDA . Intravenous penicillin G is
well established as the drug of choice for neurosyphilis ;
during the shortage practitioners were forced to use alterna-
tive agents that lacked robust efficacy data, such as ceftriaxone
[17, 18].Acyclovir has been recommended as first-line treatment
for herpes encephalitis since 1986, when a morbidity and mor-
tality benefit over vidarabine was shown in a randomized trial
. During the most recent shortage of the intravenous
formulation , clinicians may have been forced to use an
alternative agent. Sulfamethoxazole-trimethoprim has been the
first-line treatment for P. jiroveci pneumonia since the 1980s,
when a survival benefit over pentamidine was shown in a pro-
spective trial [20, 21]. The current shortage of the intravenous
formulation mayresultin adverse outcomesforpatientswith
severe disease. Two very recent anti-infective shortages include
isoniazid  and streptomycin . Isoniazid has shown efficacy
in placebo-controlled  and comparative antitubercular trials
against Mycobacterium tuberculosis and has been a mainstay of
treatment since the 1960s . Owing to the anecdotal nature
of second-line therapies, streptomycin has been a keystone in
the treatment of gentamicin-resistant enterococcal infections
[25, 26]. Given the potential for worse outcomes with second-line
therapies, further research regarding the clinical impact of drug
shortages on patient outcomes should be conducted.
In the event of a drug shortage, an ineffective alternate agent
involvedin deciding onthebest substitute. Alternatively,timeto
active therapy may be delayed if therapy is not readily available.
Although to date there are limited data regarding patient out-
comes specifically in the setting of shortages, the literature does
provide insight into the impact of inactive and delayed active
therapy in general. Increased mortality has been seen after
delays in appropriate anti-infective therapy for patients with
bacterial sepsis , bloodstream infections [6, 7, 28–30],
nosocomial pneumonia , ventilator-associated pneumonia
, and community-acquired pneumonia .
Thus, timely and appropriate anti-infective therapy has
been demonstrated to be critical for multiple disease states.
Complicating the problem is the fact that very few antimi-
crobial options exist in many cases due to increasing drug
resistance. Multiple bacterial pathogens have now earned the
status of multidrug resistant (MDR), extremely drug resistant
(XDR), or pandrug-resistant (PDR) . Hence, multidrug
Anti-infective Drug Shortages
d CID 2012:54 (1 March)
2010, with current shortages receiving priority and resolved shortages classified according to the first year of shortage. If resolution occurred during the
time period, the drug was classified as resolved. Topical and systemic anti-infectives including antibacterials, antifungals, and antivirals were reviewed.
Vaccines were excluded from the analysis. New molecular anti-infective entities were determined by searching the Food and Drug Administration drug
approvals Web site.
Trends in anti-infective drug shortages and new molecular anti-infective entities. Each drug formulation was included once from 2005 to
d CID 2012:54 (1 March)
d Griffith et al
resistance is becoming a frequent occurrence in today’s noso-
comial setting . The compilation of clinically significant anti-
infective shortages presented in Table 1 represents agents that are
often the best or the only option to treat these multidrug-resistant
Unavailable products broadly affect the treatment and pre-
vention of infectious diseases and are not limited to anti-infective
shortages. It is important to note that vaccine shortages have
a rich and unfortunate history and have important public health
implications. Since the year 2000, there have been shortages
for several vaccine-preventable diseases including varicella,
hepatitis B, Haemophilus influenza, meningitis, and influenza
[40–42]. Recent examples of vaccine shortages have occurred
with the herpes zoster and yellow fever vaccines .
REASONS FOR ANTI-INFECTIVE SHORTAGES
As manufacturers are not legally required to supply reasons for
drug shortages, discerning causality can be difficult [10, 44]. At
their discretion, manufacturers may offer reasons for the short-
age. The American Society of Health-System Pharmacists and
FDA drug shortage Web sites publish reasons for shortages;
Table 1. Illustrative Examples of Anti-infective Drug Shortages
Date of Onset of
Most Recent Shortage Impact
Acyclovir injectionManufacturing issuesFebruary 2009 Only therapy recommended for HSV/VZV
encephalitis [19, 34]
Amikacin injectionRaw material shortage;
July 2010Potential aminoglycoside of choice for
neutropenic hypotension and pneumonia
based on local susceptibilities and patient
factors [35, 36]
Among limited alternatives for atypical
mycobacterial infections or
multidrug-resistant tuberculosis 
First-line agent for patients with b-lactam
allergy who required gram-negative
b-lactam coverage [35, 36]
Empiric therapy selection in many
national guidelines for a variety
of infections [35, 36]
Aztreonam injectionRaw material shortage August 2008
Ciprofloxacin injectionRaw material shortage;
noncompliance with GMPs
August 2009 Ophthalmia neonatorum prophylaxis; all
alternatives have less evidence or higher
incidence of adverse effects 
Foscarnet injectionManufacturing issuesJuly 2010Recommended alternative for
ganciclovir-intolerant patients or
ganciclovir-resistant viruses 
Ganciclovir capsulesManufacturing issuesMay 2009 Minimal
Mupirocin ointmentIncreased demand January 2005
Recommended drug for Staphylococcus
aureus decontamination before surgical
Isoniazid tablets Increased demand;
September 2011First-line treatment of active and latent
Penicillin G injection Single-source manufacturer;
noncompliance with GMPs
January 2007First-line agent for neurosyphilis 
January 2005First-line anti-infective for many serious
nosocomial infections [35, 36]
Polymyxin B injectionIncreased demandJanuary 2008Often last-line therapy for serious
gram-negative infections 
Streptomycin injectionNone givenSeptember 2011Recommended for gentamicin resistant
enterococcal endocarditis 
Manufacturing issuesMay 2010First-line treatment for Pneumocystis jiroveci
pneumonia and Stenotrophomonas
maltophilia infections 
Table current as of 28 September 2011.
Abbreviations: GMP, good manufacturing practice; HSV, herpes simplex virus; VZV, varicella-zoster virus.
Anti-infective Drug Shortages
d CID 2012:54 (1 March)
however, these reports originate from voluntary information
provided by manufacturers [4, 44].
Contemporary Examples of Anti-infective Shortages
Anti-infective shortages occur for a variety of reasons that can be
distilled to problems caused by decreased supply or increased
demand (Table 1) . Examples of reasons for decreased supply
include issues related to procuring raw materials, processing,
distributing, regulatory compliance, and market forces. Increased
demandmay be due to epidemics, new therapeutic indications, or
perceived shortages. A survey of manufacturer reasons for drug
shortages conductedin 2000foundthat the mostcommon reason
was shortage of raw material, followed by regulatory issues and
to product quality (54%), capacity issues (21%), manufacturers
halting production (11%), and other reasons (14%) .
Problems with supply can occur at many steps throughout
the manufacturing process. Unavailable raw materials or bulk
items have been the suggested reason behind the shortages for
gentamicin, vancomycin, amikacin, aztreonam, and ciprofloxacin
[44, 47]. Noncompliance with current good manufacturing pra-
ctices or other regulations may result in FDA enforcement
actions and temporary halting of manufacturing. The FDA has
cited regulation infraction or noncompliance with current good
manufacturing practices as the cause of shortages of penicillin G
sodium and potassium injections, ticarcillin-clavulanate, and
ciprofloxacin [44, 47]. Product contamination due to impurities
or manufacturing delays has also led to shortages. Many anti-
infectives are sterile injectable products, which are at a higher risk
of contamination than oral medications and thus more likely
to become unavailable owing to sterility concerns. In addition,
manufacturing equipment issues or lack of excipients may lead
to production delays. Contamination or manufacturer delay
has resulted in shortages for piperacillin-tazobactam, foscarnet,
Changes in product formulation may delay production, resulting
in a shortage, as in the case of piperacillin-tazobactam. The
product was reformulated to contain edetate disodium dihydrate
and sodium citrate, which allowed for increased compatibility
with other concomitantly administered intravenous agents while
leaving dosing and administration unchanged [44, 47].
Corporate business decisions may contribute to drug short-
ages by decreasing or limiting supply of a drug. Manufacturers
may cease production of a drug due to availability of therapeutic
alternatives, reallocation of their resources, or other financial
reasons . A recent example may be the case of injectable
minocycline in 2005; the same year tigecycline, a competing tet-
racycline, was approved for use. The company (then Wyeth
Pharmaceuticals) halted the production of injectable minocycline
, presumably to preferentially market tigecycline. This deci-
sion is concerning as minocycline may represent the most active
compound in the tetracycline class for some clones of multidrug-
resistant Acinetobacter baumannii [50, 51], an emerging nosoco-
providing injectable minocycline but unfortunately has priced it
similarly to tigecycline and notably higher than the previously
available injectable minocycline product.
There are further examples of manufacturer decisions to halt
production of medications that have affected the supply on the
market and decreased the number of manufacturers producing
a product. Examples of manufacturers voluntarily ending pro-
duction of medications include ticarcillin, kanamycin, cefoxitin,
loracarbef, cefotetan, spectinomycin, and erythromycin ophthal-
mic ointment [44, 47]. The impact of any shortage may be
compounded if the product is only available from a single source,
such as with sulfamethoxazole-trimethoprim . Although all
name-brand medications will have a single-source manufacturer
when they are under patent protection, generics may also be
Single-source manufacturers negatively affect consumers when
they increase the price of a generic product when few alternatives
are available. Examples of agents affected by these price increases
include ritonavir , oxacillin , and penicillin G .
Stockpiling and poor inventory practices may result in an
artificial shortage [54, 55]. Artificial shortages, or the mal-
distribution of product, decrease available supply for purchase
and may occur when institutions buy in excess of their needed
inventory in response to speculation of impending shortage
[54, 55]. A shortage of ciprofloxacin, for example, was at-
tributed to consumer hoarding after the Bacillus anthracis
exposures in 2001 .
Changes in therapeutic indications may increase product
demand, resulting in a shortage. Higher demand for a medica-
tion may have many causes, such as an epidemic, an emerging
infectious disease, a new FDA-approved indication, a new un-
labeled use, or market factors. Increased demand has caused
shortages of ganciclovir, mupirocin, streptomycin, erythromycin
tazobactam [44, 47].
Shortages are often due to a myriad of reasons, and
manufacturers often offer no explanation. Because manu-
facturers declined to provide reasons for shortages in the case
of cefotaxime, rifabutin, minocycline, cefazolin, cefepime,
and tobramycin [44, 47], the reasons for shortages of these
products remain unknown.
An unfortunate by-product of the frequency and financial
impact of drug shortages has been the creation of the ‘‘gray
market.’’ Although little documentation of the gray market
exists in medical literature, it is a well-known entity to those
involved in purchasing pharmaceuticals, with many institutions
reporting daily solicitations from gray market vendors [57, 58].
In the gray market, intermediary distribution companies
d CID 2012:54 (1 March)
d Griffith et al
purchase large quantities of medications at discounted prices
and resell the product at inflated prices during a shortage. Of
concern, little regulation exists, and these drugs may have been
improperly handled, counterfeited, or recalled . During
a shortage, these medications are offered by gray market
wholesalers to pharmacies for the purpose of procuring a large
resold at up to 5 times the normal price . Medications that
are bought from the gray market owing to shortage are not
guaranteed to be unadulterated. Counterfeit anti-infectives that
may besoldin the gray market posea threattopublic healthand
may result in poor patient outcomes . Unfortunately this
process continues despite increased scrutiny from the FDA .
Role of Federal Oversight
The FDA lacks authority to require companies to manufacture
a product or to produce a certain amount of a product. Instead,
this agency passively monitors drug shortages and relies on in-
formation provided by manufacturers and reports of shortages
. Under the Food, Drug, and Cosmetic Act, 21 USC Section
506(c), a company is required to notify the FDA 6 months
before ending production of a ‘‘medically necessary’’ drug if it is
the only manufacturer of that product .
Animportant function oftheFDA is toprovide notification if
FDA-approved medications exist as foreign-marketed products.
These preparations may be available for importation into the
United States. Notification of this possibility may occur via
electronic communication from the FDA Current Drug Short-
ages Web page . Foscarnet is an example of an anti-infective
approved for importation from the United Kingdom .
Because of the currently constrained role of federal oversight,
an enhanced role for the FDA was proposed in November 2010
at a meeting of several national associations, including the
American Society of Anesthesiologists, the American Society of
Clinical Oncology, American Society of Health-System Phar-
macists, and the Institute for Safe Medication Practices. A plan
intended to reduce patient harm and minimize interruptions in
patient care was devised to address the growing number of drug
shortages . The panel recommended expanding the role of
the FDA, requiring manufacturers to provide between 9 and 12
months of notification for market withdrawals. The proposed
plan broadens the definition of ‘‘medically necessary’’ to in-
clude any medication for which interruptions in manufacturing
would decrease the current supply to the point that it would not
be able to meet demand. Other suggestions from this group in-
cluded improving distribution options for drugs in limited supply
and requiring manufacturing redundancies as part of the FDA
approval process in order to limit single-source products .
As a first step to address these suggestions, a US Senate bill
(S 296, Preserving Access to Life-Saving Medications Act) was
introduced in February 2011 and was referred to the Committee
on Health, Education, Labor, and Pensions. This bill would
amend the Food, Drug, and Cosmetic Act by requiring manu-
facturers of prescription drugs to notify the FDA 6 months
before halting or interrupting production or any manufacturing
changes that could potentially lead to a shortage [64–66]. Un-
planned interruptions would require manufacturers to notify
the FDA immediately. If a manufacturer failed an inspection,
placed on inspections that are likely to result in a drug shortage.
The FDA would penalize noncompliance and partner with
manufacturers to prevent drug shortages . Furthermore, the
FDA would identify drugs susceptible to shortage by assessing
the following factors: the number of manufacturers, the sources
of raw material or active pharmaceutical ingredients, the supply
chain characteristics, and the availability of therapeutic alter-
natives. Any actions taken to address drug shortages would be
reported by the Secretary of Health and Human Services to
Congress on an annual basis . At the end of June 2011,
a similar House of Representatives bill (HR 2245, Preserving
Access to Life-Saving Medications Act of 2011), was introduced
Health Subcommittee . We support such efforts to amend
the Federal Food, Drug, and Cosmetic Act.
Anti-infective drug shortages continue to pose significant prob-
lems for clinicians and are a rapidly evolving public health
to patients unable to receive specific anti-infectives. Enhanced
oversight by governmental agencies may be necessary to identify
and correct shortages of these life-saving anti-infectives. Bills such
as the Preserving Access to Life-Saving Medications Act could
provide the FDA with the appropriate authority to minimize the
impact of drug shortages.
Potential conflicts of interest.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
All authors: No reported conflicts.
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