e-CFR data is current as of September 3, 2021
EFFECTIVE DATES: Sept. 15, 2021
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Qualifications and aids to interpretation (table definitions and requirements). The following definitions and requirements shall apply to the Table set forth in paragraph (a) of this section and only apply for purposes of this subpart. * * * * *
Smallpox countermeasures injury table. TABLE 2 TO PARAGRAPH (c) | Covered countermeasures under declarations | Serious physical injury (illness, disability, injury, or condition)¹ | Time interval (for first symptom or manifestation of onset of injury after administration or use of covered countermeasure, unless otherwise specified) | |--------------------------------------------|-----------------------------------------|------------------------------------------------------------------------------------------------| | I. Smallpox Vaccines Replication-Deficient | A. Anaphylaxis | A. 0-4 hours. | | | B. Vasovagal Syncope | B. 0-1 hour. | | II. Smallpox Vaccines Replication-Competent| A. Anaphylaxis | A. 0-4 hours. | | | B. Vasovagal Syncope | B. 0-1 hour. | | | C. Significant Local Skin Reaction | C. 1-21 days. | | | D. Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis | D. 4-28 days. | | | E. Inadvertent Autoinoculation | E. 1-21 days. | | | F. Generalized Vaccinia | F. 6-9 days. | | | G. Eczema Vaccinatum | G. 3-21 days. | | | H. Progressive Vaccinia | H. 3-21 days. | | | I. Post-vaccinial Encephalopathy, Encephalitis or Encephalomyelitis (PVEM) | I. 5-14 days. | | | J. Vaccinial Myocarditis, Pericarditis, or Myopericarditis | J. 0-21 days. | III. Vaccinia Immunoglobulin Intravenous (VIGIV) A. Anaphylaxis B. Transfusion-Related Acute Lung Injury (TRALI) A. 0-4 hours. B. 0-72 hours. C. Acute Renal Failure (ARF) C. 0-10 days. D. Drug-Induced Aseptic Meningitis (DIAM) D. Within 48 hours after the first dose and up to 48 hours after the last dose of VIGIV. E. Hemolysis E. 12 hours to 14 days. IV. Cidofovir A. No Condition Covered² A. Not Applicable. V. Tecovirimat A. No Condition Covered² A. Not Applicable. VI. Brincidofovir A. No Condition Covered² A. Not Applicable. VII. Smallpox Infection Diagnostic Testing Devices A. No Condition Covered² A. Not Applicable. ¹Serious physical injury as defined in §110.3(z). Only injuries that warranted hospitalization (whether or not the person was actually hospitalized) or injuries that led to a significant loss of function or disability will be considered serious physical injuries. ²The use of “No condition covered” in this Table 2 reflects that the Secretary evaluated the countermeasure, but at this time does not find compelling, reliable, valid, medical, and scientific evidence to support that any serious injury is presumed to be caused by the associated covered countermeasure. For injuries alleged to be due to covered countermeasures for which there is no associated Table 2 injury, requesters must demonstrate that the injury occurred as the direct result of the administration or use of the covered countermeasure. See §110.20(b) and (c).
Qualifications and aids to interpretation (table definitions and requirements). The following definitions and requirements shall apply to the Table set forth in paragraph (c) of this section and only apply for purposes of this subpart. (1) Anaphylaxis. Anaphylaxis is an acute, severe, and potentially lethal systemic reaction that occurs as a single discrete event with simultaneous involvement of two or more organ systems. Most cases resolve without sequelae. Signs and symptoms begin within minutes to a few hours after exposure. Death, if it occurs, usually results from airway obstruction caused by laryngeal edema or bronchospasm and may be associated with cardiovascular collapse. Other significant clinical signs and symptoms may include the following: Cyanosis, hypotension, bradycardia, tachycardia, arrhythmia, edema of the pharynx and/or trachea and/or larynx with stridor and dyspnea. There are no specific pathological findings to confirm a diagnosis of anaphylaxis. (2) Vasovagal syncope. Vasovagal syncope (also sometimes called neurocardiogenic syncope) means loss of consciousness (fainting) and loss of postural tone caused by a transient decrease in blood flow to the brain occurring after the administration of an injected countermeasure. Vasovagal syncope is usually a benign condition, but may result in falling and injury with significant sequelae. Vasovagal syncope may be preceded by symptoms, such as nausea, lightheadedness, diaphoresis (sweating), and/or pallor. Vasovagal syncope may be associated with transient seizure-like activity, but recovery of orientation and consciousness generally occurs simultaneously. Loss of consciousness resulting from the following conditions will not be considered vasovagal syncope: Organic heart disease, cardiac arrhythmias, transient ischemic attacks, hyperventilation, metabolic conditions, neurological conditions, psychiatric conditions, seizures, trauma, and situational as can occur with urination, defecation, or cough. This list is not complete as other conditions that are not associated with the vaccine also may cause loss of consciousness. Episodes of recurrent syncope occurring after the applicable timeframe are not considered to be sequelae of an episode of syncope meeting the Table 2 requirements. (3) Significant local skin reaction. Significant local skin reaction is an unexpected and extreme response at the vaccination or inoculation site that results in a significant scar that is serious enough to require surgical intervention. The onset of this injury is the initial skin lesion at the vaccination site that generally occurs with replication-competent smallpox vaccinations. Minor scarring or minor local reactions do not constitute a Table 2 injury. A robust take, defined as an area of redness at the vaccination site that exceeds 7.5 cm in diameter with associated swelling, warmth and pain, is generally considered an expected response to the vaccination or inoculation. A robust take, in itself, does not constitute a Table 2 injury, even when the redness and swelling involves the entire upper arm with associated enlargement and tenderness of the glands (lymph nodes) in the underarm (axilla). (4) Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN). SJS/TEN is a spectrum of acute hypersensitivity reactions that affects skin, mucous membranes, and sometimes, internal organs (systemic toxicity) associated with the use or administration of replication-competent smallpox vaccines. For purposes of Table 2, both skin and mucous membrane rash or lesions must be present. Rash or lesion distribution must be widespread. Rash must not have a symmetric acral distribution (affecting arms, hands, legs or feet). Two or more mucosal sites must be involved. Mucosal lesions generally manifest as painful lesions in sites, such as the mouth or eyes. Skin rash or lesions in SJS/TEN usually consist of red or purple raised areas (erythematous macules), blisters, and ulcerations. (5) Inadvertent autoinoculation (IA). IA is the spread of vaccinia virus from an existing vaccination site to a second location usually by scratching the vaccination site and subsequently spreading the virus, which produces a new vaccinal lesion on the same person who received the vaccination. IA is the most common adverse event associated with the replication-competent smallpox vaccine. (6) Generalized vaccinia (GV). GV is a vaccinal infection that occurs from the spread of vaccinia from an existing vaccination or inoculation site, with the use or administration of a replication-competent smallpox vaccine, to otherwise normal skin, resulting in multiple new areas of vaccinal rash or lesions. The vaccinia is believed to be spread through the blood. The rash or lesions, characterized by multiple blisters (vesicles or pustules), generally evolve in a similar sequence or manner as the original vaccination site. (7) Eczema vaccinatum (EV). EV is the transmission or the spread of vaccinia virus from a vaccination site, after the use or administration of a replication-competent smallpox vaccine, to skin that has been affected by, or is currently affected with, eczema or atopic dermatitis. EV is characterized by lesions that include multiple blisters (vesicles or pustules), which generally evolve in a similar sequence or manner as the original vaccination site. The lesions may come together to form larger lesions. Lesions may also spread to patches of skin that have never been involved with eczema or atopic dermatitis. The new lesions, if cultured, will be positive for vaccinia virus. A person with EV may (8) Progressive vaccinia (PV). PV is the failure to initiate the healing process in an initial vaccination or inoculation site, after the use or administration of a replication-competent smallpox vaccine, by 21 days after exposure to vaccinia, with progressive ulceration or necrosis at the vaccination site leading to a large destructive ulcer. PV is seen in people who are immunocompromised (have an impaired immune system) and is characterized by a complete or near complete lack of inflammation or absence of inflammatory cells in the dermis of the skin at the vaccination site. The diagnosis of PV may be made before 21 days after exposure, especially in a known immunocompromised individual who develops a lesion at the vaccination site. PV may spread through the blood to any location in the body. No one who experiences a significant healing process of the vaccination site within 21 days after receipt of the replication-competent smallpox vaccine or exposure to vaccinia has PV. (9) Post-vaccinial encephalopathy, encephalitis, and encephalomyelitis (PVEM). PVEM is a spectrum of overlapping conditions that includes post-vaccinial encephalopathy, encephalitis, and encephalomyelitis, and, for the purposes of Table 2, is treated as one injury. For the purposes of Table 2, PVEM is an autoimmune central nervous system injury that occurs after the use or administration of a replication-competent smallpox vaccine. In rare cases, the vaccinia virus is isolated from the central nervous system. Manifestations usually occur abruptly and may include fever, vomiting, loss of appetite (anorexia), headache, general malaise, impaired consciousness, confusion, disorientation, delirium, drowsiness, seizures, language difficulties (aphasia), coma, muscular incoordination (ataxia), urinary incontinence, urinary retention, and clinical signs consistent with inflammation of the spinal cord (myelitis), such as paralysis or meningismus (meningeal irritation). Long-term central nervous system impairments, such as paralysis, seizure disorders, or developmental delays are known to occur as sequelae of the acute PVEM. No clinical criteria, radiographic findings, or laboratory tests are specific for the diagnosis of PVEM. Symptoms that occur before 5 days or more than 14 days after receiving the smallpox vaccine should not be attributed to it. In addition, encephalopathy caused by an infection, a toxin, a metabolic disturbance, a structural lesion, a genetic disorder, or trauma would not meet the Table 2 definition. (10) Vaccinial myocarditis, pericarditis, or myopericarditis (MP). For purposes of Table 2, MP is vaccinial myocarditis, pericarditis, or myopericarditis. Vaccinial myocarditis is defined as an inflammation of the heart muscle (myocardium) because of receiving the replication-competent smallpox vaccine. Vaccinial pericarditis is defined as an inflammation of the covering of the heart (pericardium) because of receiving the smallpox vaccine. Vaccinial myopericarditis is defined as an inflammation of both the heart muscle and its covering because of receiving the smallpox vaccine. The inflammation associated with MP may range in severity from very mild (subclinical) to life threatening. In many mild cases, myocarditis is diagnosed solely by transient electrocardiographic (EKG) abnormalities (e.g., ST segment and T wave changes), increased cardiac enzymes, or mild echocardiographic abnormalities. Arrhythmias, abnormal heart sounds, heart failure, and death may occur in more severe cases. Pericarditis generally manifests with chest pain, abnormal heart sounds (pericardial friction rub), EKG abnormalities (e.g., ST segment and T wave changes), and/or increased fluid accumulation around the heart. A Table 2 injury of MP requires sufficient evidence in the medical records of the occurrence of acute MP. (11) Transfusion-related acute lung injury (TRALI). TRALI is defined as the onset of respiratory distress within 6 hours in non-critically ill patients, and 72 hours in critically ill patients, after receipt of blood products containing plasma, in this case, VIGIV. The relative level of illness will be determined on a case-by-case basis after reviewing the medical records and the medical history. The respiratory distress is the result of receiving a plasma containing transfusion (VIGIV) and subsequently developing pulmonary edema, respiratory distress, and hypoxia. TRALI occurs as the result of an antibody response in the host to the donor antibodies within the plasma product. Pulmonary edema is non-cardiac in nature and does not occur more than 72 hours after receiving VIGIV. Pulmonary edema occurring more than 72 hours after receiving a blood product containing plasma (VIGIV) or associated with cardiac dysfunction is not TRALI and is excluded as a countermeasure-related injury. TRALI has been identified as a major cause of mortality in those individual receiving plasma-containing transfusions. A Table 2 injury for TRALI has occurred in a recipient if there is sufficient evidence in the medical record of an occurrence of TRALI and the pulmonary edema is not caused by cardiac dysfunction or other causes and occurs within 72 of receiving a blood product containing plasma, in this case VIGIV. (12) Acute renal failure (ARF). ARF is the sudden loss of the kidneys' ability to perform their main function of eliminating excess fluids and electrolytes (salts), as well as waste material from the blood. ARF, which is also called acute kidney injury, develops rapidly over a few hours or a few days. ARF can be fatal and requires intensive treatment; however, ARF may be reversible. ARF may cause permanent loss of kidney function, or end-stage renal disease necessitating dialysis or transplant. A Table 2 injury for ARF has occurred if there is sufficient evidence in the medical record of an occurrence of ARF within the identified timeframe and the individual received the associated countermeasure (VIGIV). (13) Drug-induced aseptic meningitis (DIAM). (i) DIAM is an inflammation of the meninges (linings of the brain) that is not caused by a bacteria or virus, but is caused by a drug or medication. The symptoms of meningitis include severe headache, nuchal (neck) rigidity, drowsiness, fever, photophobia (light sensitivity), painful eye movements, nausea, and vomiting. Discontinuation of the medication leads to a resolution of the symptoms. DIAM is thought to occur because of an immunological hypersensitivity reaction to a specific medication. In the case of immunoglobulins, DIAM may be precipitated by the immunologically active components within the plasma or because of the stabilizers used within the product. The symptoms of DIAM may reoccur with another exposure to the offending agent.
A Table 2 injury for DIAM has occurred in a recipient if there is sufficient evidence in the medical record of an occurrence of DIAM within the identified timeframe and the individual received the associated countermeasure (VIGIV). DIAM occurring in the absence of the use of VIGIV, or DIAM occurring with the use of VIGIV outside the established timeframe of onset, which is any time after the first dose and up to 48 hours after the last dose of this medication, is not a Table 2 injury. (14) Hemolysis. Hemolysis is the physical breakdown of red blood cells (RBCs) either through natural attrition or as caused by external factors. The RBC's function is to transport oxygen throughout the body in the hemoglobin contained within the RBC. Additionally, the RBCs contain the majority of the body's potassium stores. With hemolysis, the body is unable to transport oxygen effectively, and the person develops hypoxia. Additionally, the rapid breakdown of the cell releases large amounts of potassium into the bloodstream, which can cause abnormal heart rhythms and cardiac arrest. In severe cases of hemolysis, a blood transfusion may be required to correct the resulting anemia. A Table 2 injury for hemolysis has occurred if there is sufficient evidence in the medical record of an occurrence of hemolysis, and the patient received the associated countermeasure (VIGIV). Hemolysis occurring in the absence of the use of VIGIV and outside of the timeframe of 12 hours to 14 days after receiving VIGIV is not a Table 2 injury. Hemolysis occurring from a more likely alternative diagnosis, such as infections, toxins, poisons, hemodialysis, or medications, is not a Table 2 injury. This list of conditions that can cause hemolysis, not associated with VIGIV, is not exhaustive, and all additional diagnoses within the medical documentation will be evaluated.