Smallpox Preparedness and Response Updates from FDA
- July 17, 2018: Drug Trial Snapshot: TPOXX - TPOXX is a drug for the treatment of smallpox disease. Drug Trials Snapshots provide consumers with information about who participated in clinical trials that supported the FDA approval of new drugs. Also see Therapeutics below
- July 13, 2018: FDA approves the first drug with an indication for the treatment of smallpox - TPOXX was approved under the FDA’s Animal Rule, which allows findings from adequate and well-controlled animal efficacy studies to serve as the basis of an FDA approval when it is not feasible or ethical to conduct efficacy trials in humans.
- July 10, 2018: FDA issued a draft guidance for industry, Smallpox (Variola Virus) Infection: Developing Drugs for Treatment or Prevention (PDF, 120 KB), to assist sponsors in all phases of development of antiviral drugs for the treatment or prevention of smallpox (Variola virus) infection. Also see Guidance for industry below
- Variola virus is the causative agent of smallpox.
- Smallpox was declared eradicated in 1980 by the World Health Organization, with no known cases of naturally occurring smallpox having occurred since 1977. The last outbreak of smallpox in the United States occurred in 1949.
- While there is no known immediate, direct threat of a biological attack using smallpox (i.e., an intentional release of Variola virus), concerns over the possible use of Variola virus in a biological attack have led to increased preparedness efforts.
- Transmission:Smallpox can be transmitted person-to-person via inhalation of virus-containing airborne droplets of saliva from an infected person. Transmission can also occur via contact with material from the smallpox pustules or crusted scabs, or through materials such as bedding or clothing that has been in contact with the pustules or scabs.
- Prevention: Smallpox can be prevented by vaccination with smallpox vaccine. The vaccine does not contain the smallpox virus and cannot give you smallpox. Also see Vaccines below
- Treatment: Treatment of patients with smallpox generally involves supportive care. TPOXX (tecovirimat) is approved for the treatment of smallpox. Also see Therapeutics below
FDA plays a critical role in protecting the United States from chemical, biological, radiological, nuclear (CBRN), and emerging infectious disease threats.
FDA's roles in smallpox preparedness and response include:
- Facilitating the development and availability of medical countermeasures (MCMs) that can be used to diagnose, prevent, or treat smallpox. Also see Medical countermeasures and Guidance for industry below, and What are medical countermeasures?
- Working with medical product sponsors to clarify regulatory and data requirements necessary to rapidly advance development of MCMs essential to supporting response efforts.
- Protecting the safety of the nation’s blood supply and human cells, tissues, and cellular/tissue-based products for transplantation. Also see Guidance for industry below
- Enabling access to investigational MCMs—when necessary—through an appropriate regulatory mechanism such as under an Emergency Use Authorization (EUA) or under expanded access when the clinical circumstances warrant.
- Protecting consumers against fraudulent products - Unfortunately, during emergency situations, fraudulent products claiming to prevent, treat or cure conditions associated with the emergency almost always appear for sale. The FDA monitors for fraudulent products and false product claims related to CBRN and emerging infectious disease threats and takes appropriate action to protect consumers. Also see Consumer protection below
Vaccination against smallpox before contact with the Variola virus can protect you from getting sick. Vaccination within 7 days of being exposed to Variola virus may provide protection from disease and, if you still get smallpox, may reduce the severity of disease. Currently, smallpox vaccine is not available to the general public because smallpox has been eradicated, and the virus no longer exists in nature.
The Strategic National Stockpile (SNS) currently contains three smallpox vaccines:
- ACAM2000 (Smallpox [Vaccinia] Vaccine, Live) is a replication-competent vaccinia virus vaccine, indicated for active immunization against smallpox disease in persons determined to be at high risk for smallpox infection. This is the only licensed smallpox vaccine in the United States. Also see ACAM2000 (Smallpox Vaccine) Questions and Answers
- Imvamune (MVA-BN) is an investigational, replication-deficient smallpox vaccine. In a smallpox emergency, Imvamune could potentially be made available under an Investigational New Drug Application (IND) or an EUA for persons with certain immune deficiencies or conditions (such as persons with a diagnosis of HIV or atopic dermatitis).
- Aventis Pasteur Smallpox Vaccine (APSV) is an investigational, replication-competent vaccinia virus vaccine. In a smallpox emergency, APSV could potentially be made available under an IND or EUA for use in circumstances where ACAM2000 is depleted or not readily available.
Replication-competent vaccinia virus vaccines are generally safe and effective, but some people do experience side effects and adverse reactions. Severe adverse reactions are more common in people who are being vaccinated for the first time and among young children (≤5 years of age). Vaccinia Immune Globulin Intravenous (Human) (VIGIV) is indicated for the treatment and/or modification of certain conditions that are complications resulting from smallpox vaccination with replication-competent vaccinia virus vaccines.
Also see related information about smallpox vaccines, from FDA’s Center for Biologics Evaluation and Research (CBER), and Smallpox Vaccines and Medical Management of Adverse Reactions (information for clinicians) from CDC.
The Strategic National Stockpile (SNS) currently contains two smallpox therapeutics:
- TPOXX (tecovirimat) is indicated for the treatment of smallpox. This is the only approved smallpox therapeutic in the United States.
- Cidofovir is an investigational therapeutic for the treatment of smallpox. Cidofovir has not been tested in people with smallpox, and thus it is not known whether a person with smallpox would benefit from treatment with Cidofovir. In a smallpox emergency, Cidofovir could potentially be made available under an IND or EUA for the treatment of smallpox if the circumstances warrant.
Also see Medical Management of Adverse Reactions from CDC, which includes information for clinicians on how to obtain VIGIV and antivirals.
Diagnosis of initial cases of smallpox in a smallpox emergency would likely be based on clinical diagnosis confirmed by follow-up laboratory testing. Laboratory diagnostic testing for Variola virus would occur in a CDC Laboratory Response Network (LRN) laboratory using specialized diagnostic tests and protocols for Variola virus.
Cleared Variola virus diagnostic tests:
- Draft Guidance for Industry: Smallpox (Variola Virus) Infection: Developing Drugs for Treatment or Prevention (July 2018) - This draft guidance addresses nonclinical development, key study design considerations for animal efficacy studies to support potential new drug application (NDA)/biologics license application (BLA) submissions under the Animal Rule, and considerations for obtaining a human safety database. This draft guidance revises the draft guidance for industry entitled Smallpox (Variola) Infection: Developing Drugs for Treatment or Prevention issued on November 23, 2007.
- Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) (PDF, 502 KB) (August 2007) – see Vaccinia, page 6
- Guidance for Industry: Recommendations for Deferral of Donors and Quarantine and Retrieval of Blood and Blood Products in Recent Recipients of Smallpox Vaccine (Vaccinia Virus) and Certain Contacts of Smallpox Vaccine Recipients (December 2002)
- May 1, 2018: The Antimicrobial Drugs Advisory Committee met to discuss the new drug application (NDA) 208627 for TPOXX (tecovirimat), sponsored by SIGA Technologies Inc., for the proposed indication of the treatment of smallpox disease caused by Variola virus in adults and pediatric patients. Meeting materials, including briefing information and minutes are available.
Unfortunately, during outbreak situations, fraudulent products claiming to prevent, treat or cure a disease almost always appear. The FDA monitors for fraudulent products and false product claims related to smallpox and takes appropriate action to protect consumers.
Fraudulent product updates and warning letters
- FDA acts to remove unproven, potentially harmful treatment used in ‘stem cell’ centers targeting vulnerable patients - Vaccinia Virus Vaccine (Live) seized after being used inappropriately in vulnerable cancer patients (August 28, 2017)
- Smallpox information from CDC (includes information for clinicians, laboratory personnel, public health planners, and vaccinators)
- Smallpox information from the National Institutes of Health
- Smallpox information from the World Health Organization
- About Emergency Use Authorization
- Animal Rule information
- The FDA's Drug Review Process: Ensuring Drugs Are Safe and Effective
Consumers and general information: contact FDA
You may also call 1-888-INFO-FDA / (1-888-463-6332)
Report a fraudulent smallpox product
Includes options for phone and online reporting