How many FDA approved Inactivated vaccine are there?

Introduction to Inactivated Vaccines
Inactivated vaccines represent one of the most traditional and well‐established approaches in immunization. In these vaccines, the pathogen is “killed” or chemically inactivated so that it cannot replicate or cause disease, yet its antigenic surface proteins remain intact to stimulate the body’s immune response. Over the decades, such vaccines have been used to prevent a variety of infectious diseases. Their production is based on solid scientific rationale and numerous clinical studies, and they are an essential component of public health programs worldwide.

Definition and Characteristics
An inactivated vaccine is produced by subjecting the pathogen—usually a virus—to physical or chemical treatments such as heat, formaldehyde, or β-propiolactone, which eliminate its replicative capacity while preserving the conformation of key antigens. The fundamental characteristics include:
- The vaccine contains the entire pathogen or selected purified antigens from the pathogen.
- The inactivation process is designed to ensure complete loss of infectivity without compromising the antigenic structure required for immune recognition.
- These vaccines do not replicate in the host and thus offer a high level of safety even in populations with weakened immune systems.
- Production methods demand rigorous quality control measures so that the inactivation is complete and the immunogenic epitopes of the pathogen are retained.

Advantages and Disadvantages
Inactivated vaccines have several advantages that have underpinned their long history of use:
- Safety: Because the pathogen has been inactivated, there is no risk of the vaccine-associated infection, even in immunocompromised individuals.
- Stability: The process of inactivation often leads to vaccines with robust stability profiles that do not require extreme storage conditions, compared with more delicate live vaccines.
- Ease of Production: Many inactivated vaccines can be produced using well-established manufacturing methods; facilities that have been used historically for vaccine production can often be retooled to produce inactivated vaccines, thereby shortening development timelines in times of public health emergencies.

However, these vaccines also have limitations:
- Immunogenicity: As they do not replicate within the host, inactivated vaccines generally induce a lower magnitude of immune response compared to live attenuated vaccines. This sometimes necessitates the use of booster doses or adjuvants to reach and maintain protective immunity.
- Antigenic Integrity Concerns: The inactivation process itself must be perfectly calibrated to avoid denaturation or crosslinking of proteins that are critical for eliciting a protective immune response. Failure to optimize these parameters may render the vaccine less effective.
- Multiple Doses: Often, multiple immunizations (a primary series and booster shots) are required to achieve long-term protection.

FDA Approval Process for Vaccines
The pathway for any vaccine—including inactivated vaccines—being approved by the Food and Drug Administration (FDA) follows a strict, multi‐phase process designed to rigorously assess the vaccine’s safety, immunogenicity, and overall efficacy before it is authorized for public use.

Overview of the Approval Process
The FDA approval pathway for vaccines encompasses several key stages. First, a vaccine candidate undergoes preclinical testing in vitro and in animal models to establish both safety and potential efficacy. Following promising pre‐clinical data, the vaccine enters a series of clinical trials classified into Phase I, Phase II, and Phase III:
- Phase I: Small groups of healthy volunteers receive the vaccine to determine its safety profile and to establish an initial understanding of its immunogenicity.
- Phase II: Larger cohorts are enrolled to refine the dosing schedule, continue the safety evaluation, and gain more detailed immunological data.
- Phase III: These pivotal studies involve thousands of participants to firmly establish the vaccine’s effectiveness in preventing the disease as well as to further monitor for less common adverse events.
Once these stages yield robust evidence of safety and efficacy, the vaccine manufacturer compiles a comprehensive regulatory dossier. This dossier is reviewed by the FDA’s expert panels, and if the evidence meets all established standards, the vaccine is approved, often by the FDA’s Center for Biologics Evaluation and Research (CBER).

Criteria for Vaccine Approval
The criteria for FDA approval are stringent and include multiple layers of evaluation:
- Safety: All inactivated vaccines must demonstrate a high safety profile. This is particularly important since the target populations often include infants, the elderly, or immunocompromised individuals for whom adverse reactions must be minimized.
- Efficacy/Immunogenicity: The vaccine must elicit a sufficient immune response—usually measured by antibody titers and sometimes by T-cell responses—that correlates with protection against the disease. In many cases, surrogates such as seroconversion rates or neutralizing antibody levels are used as benchmarks.
- Manufacturing Consistency: Robust processes and quality control measures must be demonstrated to ensure that every batch of vaccine is identical in its antigenic properties and overall quality. This is critically important for inactivated vaccines, where the inactivation process itself introduces variables that must be strictly controlled.
- Stability and Storage: The vaccine must be shown to maintain stability and effectiveness under recommended storage conditions. This also encompasses considerations about transportation and shelf-life.
- Risk–Benefit Analysis: The overall benefits of vaccination must outweigh any potential risks, a determination that is based on data collected across clinical studies and post-marketing surveillance.

List of FDA Approved Inactivated Vaccines
Assessing the number of inactivated vaccines that are approved by the FDA requires a close look at the specific products that have been licensed based on their mode of action and manufacturing process. In our review of the synapse-derived references and regulatory documents, several key vaccine products emerged as examples of inactivated formulations that have received FDA approval.

Current Approved Vaccines
Based on the synapse and other reliable sources, several leading examples of FDA-approved inactivated vaccines include:

1. Influenza Inactivated Vaccines
The influenza vaccines represent one of the largest groups of inactivated vaccines approved by the FDA. Multiple influenza formulations are produced by different manufacturers such as GlaxoSmithKline and Sanofi Pasteur. For instance, products like Fluarix and Fluzone—approved by FDA_CBER—are formulated as inactivated vaccines that use chemically inactivated influenza viruses to prevent seasonal influenza. Although there are various brands and formulations, when considered as a category, they represent the cornerstone of seasonal influenza immunization.

2. Inactivated Polio Vaccine (IPV)
The inactivated polio vaccine was first licensed in the United States in the 1950s and remains one of the classical examples of an inactivated vaccine. Commercial products such as IPOL, manufactured by Sanofi Pasteur, are used in the routine immunization schedule to protect against poliovirus. The IPV is a proven public health success story and one of the original inactivated vaccine formulations approved by the FDA.

3. Inactivated Hepatitis A Vaccines
Hepatitis A vaccines, such as Havrix and Vaqta, are produced using chemically inactivated hepatitis A virus. These vaccines are highly effective and demonstrate the versatility of inactivation technology in protecting against viral hepatitis. Both products have been thoroughly evaluated and approved by the FDA, offering safe prophylaxis against hepatitis A infection.

4. Japanese Encephalitis Vaccine (Ixiaro)
Ixiaro, which is developed by Pfizer Japan, Inc. and subsequently approved by FDA_CBER, is an inactivated vaccine formulation used to prevent Japanese encephalitis. It is produced using an inactivated virus that induces robust immunity among travelers and residents in endemic regions. Ixiaro’s licensing by the FDA underscores the application of inactivation methods for arboviral diseases.

5. Rabies Vaccines
Inactivated rabies vaccines such as Imovax Rabies and Human Diploid Cell Vaccine (HDCV) are widely accepted as the standard of care in post-exposure prophylaxis for rabies. Although rabies vaccines have undergone several generations, the modern inactivated formulations are known for their safety profile and consistent efficacy, having been approved by the FDA for many decades.

6. Combination Vaccines with Inactivated Components
There are also several combination vaccines that include inactivated components—these include acellular pertussis vaccines and IPV-containing formulations such as Kinrix and Pediarix, which target multiple pathogens simultaneously. These products are typically licensed as combination products, but the inactivated components (for example, the inactivated poliovirus in IPV as well as inactivated toxoids in DTaP formulations) play a critical role in protection. FDA_CBER has reviewed and approved these products, ensuring that each inactivated component meets the relevant standards.

From the synapse data provided, specific drug application numbers approved by FDA_CBER that contain inactivated components include:
- 125731_001 (Prevnar 20): Although primarily a pneumococcal conjugate vaccine, it is manufactured using processes that include chemical inactivation of bacterial components, contributing to its safe immunogenic profile.
- 125525_001 (Quadracel): As a combination vaccine that includes inactivated pertussis components along with diphtheria, tetanus, and IPV, Quadracel is an example of how inactivated vaccine technology is integrated into larger immunization products.
- 125260_001 (Kinrix): This vaccine, which is also a combination product containing an inactivated polio component along with other antigens, has been approved by FDA_CBER.
- 103907_001 (Pediarix): Another combination pediatric vaccine that includes inactivated viral components and is FDA approved.

When these and the standalone categories are tallied, it becomes evident that the FDA has approved a diverse range of inactivated vaccines that belong to different product lines, with each category containing several formulations. If one were to consider each licensed formulation for influenza, poliovirus, hepatitis A, Japanese encephalitis, rabies, and combination vaccines containing inactivated elements separately, the overall number of FDA-approved inactivated vaccine products in the United States is estimated to be in the range of 20–25 unique product formulations. This estimate takes into account that many seasonal influenza vaccines alone are produced in multiple formulations by various manufacturers; however, as a category, they represent one major group of inactivated vaccines.

Historical Approvals and Changes
Historically, inactivated vaccines have been among the first vaccines to be developed and approved by the FDA. The inactivated polio vaccine (IPV), licensed in the 1950s, set the stage for subsequent developments in the field. Since then, the evolution of vaccine technology has seen a significant increase in both the number and variety of inactivated vaccines approved by the FDA. For example:
- 1950s and 1960s: The introduction of IPV and later hepatitis A vaccines were major milestones in the development of inactivated vaccines.
- 1970s–1990s: Inactivated vaccines continued to be refined with the incorporation of improved inactivation methods (such as the use of β-propiolactone) and more rigorous quality control protocols. During this period, the FDA reviewed and approved a number of inactivated influenza vaccines that became integral to annual immunization programs.
- 2000s to Present: With the advent of combination vaccines, many products now include inactivated components (e.g., DTaP-IPV combinations) that provide broad protection against several pathogens in a single shot. Modern regulatory filings have also highlighted the importance of consistency in the inactivation process, resulting in enhanced manufacturing procedures and more stable vaccine products.

In summary, the inactivated vaccine category has expanded considerably over the past several decades. From the early days of IPV to the current generation of seasonal influenza vaccines, hepatitis A vaccines, and vaccines like Ixiaro and rabies vaccines, the number of FDA-approved products has grown. When considering both standalone inactivated vaccines and those presented as part of combination formulations, the current total is estimated to be around 20–25 distinct product formulations approved by the FDA, reflecting the evolution and diversification of vaccine technologies over time.

Impact and Usage of Inactivated Vaccines
The widespread use of inactivated vaccines has had a profound impact on public health, and their continued evolution has ensured that they remain a cornerstone in the prevention of infectious diseases.

Public Health Impact
Inactivated vaccines have dramatically reduced the incidence and severity of many life‐threatening diseases. Some of the most notable impacts include:
- Polio Eradication Efforts: The IPV has contributed significantly to the near-eradication of poliomyelitis in many regions, a public health triumph achieved through decades of extensive immunization campaigns.
- Seasonal Influenza Prevention: Inactivated influenza vaccines are administered annually to millions of individuals worldwide, reducing hospitalizations, disease severity, and mortality associated with seasonal epidemics. Their adaptability to circulating strains makes them a critical tool for public health.
- Protection Against Hepatitis A and Japanese Encephalitis: The introduction of inactivated hepatitis A vaccines has led to marked reductions in disease outbreaks and complications related to hepatitis A. Ixiaro, an inactivated Japanese encephalitis vaccine, has improved the protection of travelers and residents in endemic areas, thereby reducing the burden of encephalitis.
- Rabies Post-Exposure Prophylaxis: The availability of safe, inactivated rabies vaccines means that prompt vaccination after exposure can almost invariably prevent the onset of rabies—a disease that was once almost universally fatal.

These vaccines have not only saved lives but also generated significant economic benefits by reducing the need for costly treatments and hospitalizations. The maturation of manufacturing processes and the rigorous evaluation protocols mandated by the FDA have ensured that safety concerns remain minimal, thereby reinforcing public trust in immunization programs.

Usage in Various Diseases
Inactivated vaccines are used against a wide array of pathogens:
- Respiratory Pathogens: Influenza vaccines are perhaps the most commonly used inactivated vaccines, administered annually to high-risk populations.
- Enteric Pathogens: Hepatitis A vaccines are used in both routine immunizations and outbreak situations; the technology also extends to other inactivated enteric vaccines.
- Neurotropic Viruses: Japanese encephalitis vaccines such as Ixiaro are critical in regions where arboviral diseases are endemic, reducing the incidence of severe neurological diseases.
- Rabies: Inactivated rabies vaccines are used worldwide as part of post-exposure prophylaxis protocols.
- Combination Products: Many combination vaccines, such as those that protect against diphtheria, tetanus, pertussis, and polio, rely on inactivated components to provide broad-spectrum protection. This synergy in modern combination vaccines illustrates how inactivated vaccine technology can be integrated to serve multiple public health needs in a single formulation.

Furthermore, the evolution of inactivated vaccine technology has fostered improvements in global vaccine coverage. Enhanced manufacturing protocols, improvements in quality control, and the incorporation of modern adjuvants have contributed to more effective and longer-lasting formulations that align with dynamic public health requirements. In situations where cold chain maintenance is challenging, vaccine formulations have been optimized to provide stability and sustained immunogenicity even under less-than-ideal conditions.

Conclusion
In answering the question, "How many FDA approved Inactivated vaccine are there?" it is essential to consider the complexity of the modern vaccine landscape. The synapse sources and accompanying regulatory documentation do not provide a singular, explicit numerical count. However, by synthesizing the evidence from multiple references and considering the various categories and formulations approved by the FDA, we can draw several key conclusions:

1. In the context of standalone inactivated vaccines—such as the inactivated polio vaccine, hepatitis A vaccines, Japanese encephalitis vaccine (Ixiaro), and rabies vaccines—there are a minimum of approximately 5 principal vaccine types.
2. The influenza vaccines, which as a category are among the most widely used inactivated vaccines, exist in multiple formulations produced by different manufacturers. This increases the overall count when each formulation is considered individually.
3. When combination vaccines that include inactivated components (such as those containing IPV, acellular pertussis, and diphtheria and tetanus toxoids) are included in the tally, a broader perspective indicates that there are roughly 20–25 distinct product formulations across all indications that have been approved by the FDA.
4. The historical development of inactivated vaccines demonstrates a gradual increase in product diversity as manufacturing techniques have improved and regulatory standards have evolved. Early vaccines like the IPV set the precedent, and subsequent advancements have led to the robust portfolio of inactivated vaccines in current use.

From a general-specific-general perspective, inactivated vaccines started as a few pioneering products in the mid-20th century and have now expanded into a wide range of formulations that are critical to public health. Specifically, the evidence suggests that while there is no single “magic number” provided in the available synapse sources, an estimated 20–25 unique formulations—including both standalone vaccines and combination products—are approved by the FDA. In a general sense, this diversity underscores the importance and impact of inactivated vaccine technology in the United States’ immunization programs.

In conclusion, while the exact number depends on how one categorizes the products (by vaccine type or by individual product variations), a detailed examination of FDA regulatory approvals, scientific publications, and synapse reference data leads us to estimate that there are roughly 20–25 FDA-approved inactivated vaccine formulations available to protect against different pathogens and diseases. This robust portfolio reflects decades of incremental improvements, rigorous regulatory oversight, and extensive public health benefits resulting from the development and widespread use of inactivated vaccines.