Principles of Vaccine Licensure, Approval, and Recommendations for Use.

The licensure and recommendation processes for vaccines are complex. In the United States, vaccines are licensed for the civilian and military populations on the basis of review of Biologics License Applications submitted to the Food and Drug Administration (FDA) by vaccine manufacturers. For FDA-licensed vaccines, the product label includes indications, contraindications, and precautions for each vaccine. Package inserts do not include recommendations for vaccine use from the Advisory Committee on Immunization Practices (ACIP). The ACIP is chartered as a federal advisory committee to provide expert external advice and guidance to the director of the Centers for Disease Control and Prevention on the use of vaccines and related agents for control of vaccine preventable diseases in the civilian and military populations of the United States. As an external advisory committee to the Centers for Disease Control and Prevention, the ACIP has no regulatory authority but the committee does have responsibility for approving vaccines to be covered under the Vaccines for Children program. To implement ACIP vaccine recommendations in the public and private sectors, a collaboration of federal, state, and local governments as well as private organizations dealing with public health, vaccine supply, vaccine administration, vaccine finance, outcomes monitoring, public perception, and public trust and support must work together. Issues including vaccine misinformation, declining community immunity (herd protection), and need for risk communication add stress to this complex and fragile system. This study describes the functions of and interactions between FDA and ACIP.

Licensure, Approval, and Uptake of Vaccines in the United States.

Immunization is one of the most effective public and private preventive health interventions, resulting in significant reductions in vaccine-preventable diseases and in substantial cost savings to the US healthcare system. Vaccine licensure, development of recommendations for use, and implementation of those recommendations leading to uptake, community protection, and effect on disease burden represent a complex system that requires collaboration in the areas of basic science, public health, vaccine delivery, outcome monitoring, and public perception. The Advisory Committee on Immunization Practices (ACIP) sets standards for immunization delivery for both public and private vaccine providers, and state immunization programs can use these ACIP recommendations to develop school immunization requirements.

Discrepancies Between US Food and Drug Administration Vaccine Licensure Indications and Advisory Committee on Immunization Practices Recommendations: Provider Knowledge and Attitudes.

PURPOSE: In the United States, the Center for Biologics Evaluation and Research at the US Food and Drug Administration (FDA) is responsible for licensure of vaccines. The Advisory Committee on Immunization Practices (ACIP) is a federal advisory committee that provides guidance to the Centers for Disease Control and Prevention (CDC) on use of vaccines. Discrepancies between FDA licensure indications and ACIP/CDC vaccine recommendations exist, challenging health care providers. The objectives of this study were: (1) to categorize differences between FDA vaccine licensure indications and ACIP/CDC vaccine recommendations for vaccines; and (2) to assess knowledge, attitudes, and practices of pediatricians, family physicians, and obstetrician-gynecologists regarding their understanding of differences. METHODS: Information was extracted from FDAvaccine package inserts, and corresponding information was collected for ACIP/CDC vaccine recommendations (2000-2014) for vaccines in the childhood and adult immunization schedules. Surveys regarding knowledge of discrepancies were distributed electronically to members of the Georgia chapters of the American Academy of Pediatrics (GA-AAP) and the American Academy of Family Physicians (GA-AAFP), and the national American College of Obstetricians and Gynecologists (ACOG) in 2014. FINDINGS: Differences were identified in 20 instances: differences in age group indications were identified in 6, in dosing administration schedules in 4, and in immunocompromised hosts and pregnant women in 10. We received 145 (8.5%) responses from GA-AAP, 237 (9.5%) from GA-AAFP, and 869 (1.5%) from national ACOG members. A total of 105 (72%) GA-AAP respondents reported that they follow AAP recommendations and 168 (71%) GA-AAFP respondents follow ACIP recommendations. GA-AAP and GA-AAFP respondents generally were not aware of data the FDA considers for vaccine licensure or data that pharmaceutical company representatives are permitted to discuss. Respondents remain current with vaccine recommendations through review of materials from professional organizations, the CDC, and package inserts; Continuing Medical Education; and information from pharmaceutical representatives. A total of 780 (90%) ACOG respondents had no concerns regarding routinely recommended reduced diphtheria toxoid and acellular pertussis vaccines (n = 730 [84%]) and influenza during pregnancy vaccines (n = 852 [98%]) to pregnant patients. However, these findings must be interpreted within the context of a low overall ACOG survey response rate. IMPLICATIONS: Education regarding existence of and reasons for discrepancies between FDA licensure of and ACIP/CDC recommendations for vaccines and reasons for these differences could optimize immunization delivery.

Understanding FDA-Approved Labeling and CDC Recommendations for Use of Vaccines.

Adherence to recommendations for the use of licensed vaccines ensures maximum individual and societal benefits from the national immunization program. The US Food and Drug Administration (FDA) licenses a vaccine once it determines that data submitted by the manufacturer reveal that the vaccine is safe and effective for its intended use. For each US-licensed vaccine, the FDA-approved prescribing information contains detailed information for health care providers to ensure safe and effective use. Centers for Disease Control and Prevention recommendations for the use of a licensed vaccine often are based on additional considerations, such as disease epidemiology, public acceptance, vaccine supply, and cost. Our objective in this article is to explain the reasons for the differences between FDA-approved prescribing information and Centers for Disease Control and Prevention recommendations for vaccine use.

Protecting the Community Through Child Vaccination.

The direct impact of vaccines on children is well described, but the major public health impact of indirect protection provided to the community by vaccines is underappreciated. Community protection occurs when vaccinated persons block the chain of transmission, protecting undervaccinated or unvaccinated susceptible community members by preventing exposure and limiting the spread of the pathogen through the community. Substantial declines in disease incidence have occurred shortly after implementing new childhood vaccines, including declines among vaccine-ineligible children, adolescents, and adults. Protection of susceptible community members depends on maintaining high vaccination rates. Improved recognition of community protection will strengthen childhood vaccination strategies that will protect our communities into the future.

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea.

These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea.

These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.

FDA licensure of and ACIP recommendations for vaccines.

Many healthcare providers are not familiar with the Food and Drug Administration (FDA) vaccine licensure process, the Advisory Committee on Immunization Practices (ACIP) vaccine recommendation process, and how FDA vaccine licensure and ACIP recommendations are related. Vaccines for use in the United States military and civilian populations are licensed by the FDA by several potential pathways but use of licensed vaccines in the civilian population should be based on recommendations made by the ACIP. In performing these distinct activities, FDA and ACIP function under different mandates. In this article, we discuss whether the FDA licensure pathways used to approve a vaccine impacts ACIP recommendation categories for vaccines licensed from 2006 to 2016.

Policy making for vaccine use as a driver of vaccine innovation and development in the developed world.

In the past 200years, vaccines have had unmistakable impacts on public health including declines in morbidity and mortality, most markedly in economically-developed countries. Highly engineered vaccines including vaccines for conditions other than infectious diseases are expected to dominate future vaccine development. We examine immunization vaccine policy as a driver of vaccine innovation and development. The pathways to recommendation for use of licensed vaccines in the US, UK, Canada and Australia have been similar, including: expert review of disease epidemiology, disease burden and severity; vaccine immunogenicity, efficacy and safety; programmatic feasibility; public demand; and increasingly cost-effectiveness. Other attributes particularly important in development of future vaccines are likely to include: duration of immunity for improved vaccines such as pertussis; a greater emphasis on optimizing community protection rather than direct protection only; programmatic implementation, feasibility, improvements (as in the case of development of a universal influenza vaccine); public concerns/confidence/fears related to outbreak pathogens like Ebola and Zika virus; and major societal burden for combating hard to treat diseases like HIV and antimicrobial resistant pathogens. Driving innovation and production of future vaccines faces enormous economic hurdles as available approaches, technologies and regulatory pathways become more complex. As such, cost-mitigating strategies and focused, aligned efforts (by governments, private organizations, and private-public partnerships) will likely be needed to continue to spur major advances in vaccine technologies and development.

Lessons learned from making and implementing vaccine recommendations in the U.S.

After publication of certain vaccine recommendations made by the Advisory Committee on Immunization Practices, several unexpected events have occurred during implementation of these recommendations. These have included changes in recommendations following adverse events involved with a particular vaccine and the conferral of community protection as an offshoot of vaccination of a specific population. Vaccine shortages and hesitancy have also been proven impediments to full implementation, and vaccine recommendations have not gone unaffected by either public perception of a vaccine or by cost considerations.

Lessons Learned From Making and Implementing Vaccine Recommendations in the U.S.

After publication of certain vaccine recommendations made by the Advisory Committee on Immunization Practices, several unexpected events have occurred during implementation of these recommendations. These have included changes in recommendations following adverse events involved with a particular vaccine and the conferral of community protection as an offshoot of vaccination of a specific population. Vaccine shortages and hesitancy have also been proven impediments to full implementation, and vaccine recommendations have not gone unaffected by either public perception of a vaccine or by cost considerations.

The history of the United States Advisory Committee on Immunization Practices (ACIP).

The United States Advisory Committee on Immunization Practices (ACIP) is a federal advisory committee that develops written recommendations for use of vaccines licensed by the Food and Drug Administration (FDA) for the U.S. civilian population. Vaccine development and disease outbreaks contributed to the need for a systematized, science-based, formal mechanism for establishing national immunization policy in this country. Formed in 1964, the ACIP was charged with this role. The committee has undergone significant changes in structure and operational activities during its 50-year history. The ACIP works closely with many liaison organizations to develop its immunization recommendations, which are harmonized among key professional medical societies. ACIP vaccine recommendations form two immunization schedules, which are updated annually: (1) the childhood and adolescent immunization schedule and (2) the adult immunization schedule. Today, once ACIP recommendations are adopted by the Director of the Centers for Disease Control and Prevention and the Secretary of the Department of Health and Human Services, these recommendations are published in Morbidity and Mortality Weekly Report (MMWR), become official policy, and are incorporated into the appropriate immunization schedule.

History and evolution of the advisory committee on immunization practices--United States, 1964-2014.

The Advisory Committee on Immunization Practices (ACIP) is chartered as a federal advisory committee to provide expert external advice to CDC and the Secretary of the U.S. Department of Health and Human Services (DHHS) on the use of vaccines in the civilian population of the United States. This report summarizes the evolution of ACIP over the 50 years since its establishment in 1964 by the Surgeon General of the U.S. Public Health Service (USPHS).

The Red Book through the ages.

The first edition of the Red Book was published in 1938. Since then, there have been numerous advances in the fields of infectious diseases and public health that have decreased morbidity and mortality of infants, children, and adolescents. Over the years, emerging pathogens and disease complexes have been described, sophisticated diagnostic techniques developed, advances in antimicrobial therapy have occurred, and immunizations have been implemented to prevent previously deadly diseases. Of the 18 diseases or organisms in the 1938 edition, 13 are now vaccine-preventable. Since inception of the Red Book, the aims of the editors have been to keep pace with these innovations and to continue to inform the medical community. These goals have made the Red Book a fundamental resource for pediatricians and other health care professionals in terms of guiding diagnosis, therapy, and prevention of infectious diseases. The list of 18 diseases or organisms originally described in the 1938 Red Book has expanded to include over 160 diseases or organisms in the 2012 edition. The pace of biomedical discovery, as well as the amount of information available and the number of methods for its delivery, will continue to accelerate in the future. Integration of information into future editions of the Red Book will ensure that practitioners continue to rely on the Red Book in its various electronic formats for clinical guidance and support.

Vaccines in the pipeline: the path from development to use in the United States.

New vaccines in the United States go through a complex process on their path from development to the domestic market involving an intricate partnership of public and private agencies and organizations. This process includes licensure by the US Food and Drug Administration, the development of recommendations by the Advisory Committee on Immunization Practices, and safety oversight post-licensure. This article examines the roles of the US Food and Drug Administration and the Centers for Disease Control and Prevention as well as certain professional organizations in governing the testing, marketing, and usage of new vaccines. Vaccines currently in development to treat numerous infectious and noninfectious diseases are also examined and compared with frameworks of domestic vaccine development prioritization, past and present, as assessed by the Institute of Medicine.

How to communicate with vaccine-hesitant parents.

Development of safe and effective vaccines is one the greatest medical triumphs. However, despite high immunization rates in the United States, 85% of health care providers (HCPs) will have a parent refuse a vaccine for his or her child each year. HCPs have the greatest influence on a parent's decision to vaccinate his or her child. To effectively communicate with vaccine-hesitant parents, HCPs must first understand the concerns of parents regarding immunization and understand influences that can lead to misinformation about the safety and effectiveness of vaccines. HCPs should establish an open, nonconfrontational dialogue with vaccine-hesitant parents at an early stage and provide unambiguous, easily comprehensible answers about known vaccine adverse events and provide accurate information about vaccination. Personal stories and visual images of patients and parents affected by vaccine-preventable diseases and reports of disease outbreaks serve as useful reminders of the need to maintain high immunization rates. Ongoing dialogue including provider recommendations may successfully reassure vaccine-hesitant parents that immunization is the best and safest option for their child.

Immunization programs for infants, children, adolescents, and adults: clinical practice guidelines by the Infectious Diseases Society of America.

Evidence-based guidelines for immunization of infants, children, adolescents, and adults have been prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). These updated guidelines replace the previous immunization guidelines published in 2002. These guidelines are prepared for health care professionals who care for either immunocompetent or immunocompromised people of all ages. Since 2002, the capacity to prevent more infectious diseases has increased markedly for several reasons: new vaccines have been licensed (human papillomavirus vaccine; live, attenuated influenza vaccine; meningococcal conjugate vaccine; rotavirus vaccine; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis [Tdap] vaccine; and zoster vaccine), new combination vaccines have become available (measles, mumps, rubella and varicella vaccine; tetanus, diphtheria, and pertussis and inactivated polio vaccine; and tetanus, diphtheria, and pertussis and inactivated polio/Haemophilus influenzae type b vaccine), hepatitis A vaccines are now recommended universally for young children, influenza vaccines are recommended annually for all children aged 6 months through 18 years and for adults aged > or = 50 years, and a second dose of varicella vaccine has been added to the routine childhood and adolescent immunization schedule. Many of these changes have resulted in expansion of the adolescent and adult immunization schedules. In addition, increased emphasis has been placed on removing barriers to immunization, eliminating racial/ethnic disparities, addressing vaccine safety issues, financing recommended vaccines, and immunizing specific groups, including health care providers, immunocompromised people, pregnant women, international travelers, and internationally adopted children. This document includes 46 standards that, if followed, should lead to optimal disease prevention through vaccination in multiple population groups while maintaining high levels of safety.