[Federal Register Volume 86, Number 155 (Monday, August 16, 2021)]
[Rules and Regulations]
[Pages 45655-45660]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-17216]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Part 110

RIN 0906-AB22


Countermeasures Injury Compensation Program: Smallpox 
Countermeasures Injury Table

AGENCY: Health Resources and Services Administration (HRSA), Department 
of Health and Human Services (HHS).

ACTION: Final rule.

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SUMMARY: HHS is establishing the Smallpox Countermeasures Injury Table 
(Table) as authorized by the Public Readiness and Emergency 
Preparedness Act of 2005 (PREP Act). Through this final rule, the 
Secretary of the U.S. Department of Health and Human Services 
(Secretary) adds the Smallpox Countermeasures Injury Table to the 
agency's regulations. The Table includes a list of covered smallpox 
countermeasures, required time

[[Page 45656]]

intervals for the first symptom or manifestation of onset of injuries, 
and the accompanying Qualifications and Aids to Interpretation (QAI), 
which set forth definitions and other requirements necessary to 
establish Table injuries.

DATES: This rule is effective September 15, 2021.

FOR FURTHER INFORMATION CONTACT: Tamara Overby, Acting Director, 
Division of Injury Compensation Programs, Healthcare Systems Bureau, 
HRSA, 5600 Fishers Lane, 8N146B, Rockville, MD 20857, or by telephone 
(855) 266-2427. This is a toll-free number.

SUPPLEMENTARY INFORMATION: On October 15, 2020, HHS published a notice 
of proposed rulemaking (NPRM) in the Federal Register (85 FR 65311) 
proposing to add the Table for designated covered smallpox 
countermeasures identified in the Smallpox Medical Countermeasures PREP 
Act declaration. The Table includes a list of smallpox countermeasures, 
proposed time intervals for the first symptom or manifestation of onset 
of injury, and Qualifications and Aids to Interpretation which set 
forth the definitions and requirements necessary to establish the Table 
injuries. The NPRM provided a 60-day comment period, and HHS received 
one out-of-scope comment.

I. Background and Purpose

    The PREP Act authorizes the Countermeasures Injury Compensation 
Program (CICP) to provide compensation to certain individuals who 
develop serious physical injuries or to certain survivors of 
individuals who die as a direct result of the administration or use of 
a covered countermeasure identified in a PREP Act declaration.\1\ In 
carrying out the CICP, the PREP Act directs the Secretary to establish, 
through regulation, a Covered Countermeasures Injury Table (Table) 
identifying serious physical injuries that are presumed to be directly 
caused by the administration or use of covered countermeasures 
identified in PREP Act declarations issued by the Secretary. The 
Secretary may only add to a Table injuries that are directly caused by 
the administration or use of the covered countermeasure based on 
``compelling, reliable, valid, medical and scientific evidence.'' \2\ 
The Table informs the public about serious physical injuries known to 
be directly caused by covered countermeasures and creates a rebuttable 
presumption of causation for eligible individuals whose injuries are 
listed on the Table and meet the Table's requirements.
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    \1\ See Department of Defense, Emergency Supplemental 
Appropriation to Address Hurricanes in the Gulf of Mexico, and 
Pandemic Influenza Act of 2006, Part C (Pub. L. 109-148); 42. U.S.C. 
247d-6e.
    \2\ 42 U.S.C. 247d-6e (b)(5)(A).
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    The CICP's regulations, which detail the Program's requirements, 
are found at 42 CFR part 110. The provision at 42 CFR 110.20(a) states 
that individuals must establish that a covered injury occurred to be 
eligible for benefits under the Program. A covered injury is death or a 
serious injury determined by the Secretary to be: (1) An injury meeting 
the requirements of a Table, which is presumed to be the direct result 
of the administration or use of a covered countermeasure unless the 
Secretary determines there is another more likely cause; or (2) an 
injury (or its health complications) that is the direct result of the 
administration or use of a covered countermeasure.\3\ This includes a 
covered countermeasure causing a serious aggravation of a pre-existing 
condition.\4\ In general, 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 are considered 
serious injuries.\5\
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    \3\ 42 CFR 110.3(g).
    \4\ Id.
    \5\ 42 CFR 110.3(z).
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    Individuals with injuries not meeting the requirements of the Table 
may still pursue their claims as non-Table injuries under the 
Program.\6\ In that instance, the requester does not receive the 
presumption of causation for a Table injury and must demonstrate that 
the administration or use of the covered countermeasure directly caused 
the injury.\7\ Proof of a causal association for the non-Table injury 
must be based on compelling, reliable, valid, medical and scientific 
evidence.\8\
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    \6\ 42 CFR 110.20(c).
    \7\ Id.
    \8\ Id.
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II. Summary of the Final Rule

    Through this final rule, the Secretary adds the Smallpox 
Countermeasures Injury Table to subpart K of 42 CFR part 110. The Table 
established in this final rule is limited to smallpox covered 
countermeasures identified in the Secretary's PREP Act Declaration for 
Smallpox Medical Countermeasures.\9\
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    \9\ 80 FR 76546 (Dec. 9, 2015).
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    The Smallpox Countermeasures Injury Table lists several smallpox 
covered countermeasures and serious physical injuries that, based on 
compelling, reliable, valid, medical and scientific evidence, are 
directly caused by the administration or use of the associated covered 
countermeasures. The Table provides the serious injuries associated 
with a specific countermeasure and the time interval within which the 
first symptom or manifestation of onset of injury must appear. The QAI, 
which accompany the Table, are definitions included to further explain 
the requirements for each covered injury and the level of severity 
necessary to qualify as a Table injury. The Secretary will stay 
informed of updates in the scientific and medical field concerning 
potential new information about causal associations between injuries 
and covered countermeasures and update the Table as needed.
    In accordance with 42 CFR 110.42(f), in addition to the standard 
filing deadline, with the publication of this new Table, certain 
eligible requesters have one year from the effective date of the 
publication of the Table to file claims for injuries that meet the 
Table's requirements. Individuals who sustained injuries that are not 
included on the Table or that do not meet all of the requirements for a 
Table injury, but who may prove causation of the injury through other 
means, are not eligible for the additional one-year filing deadline 
based on the Table's publication. Because the new Table would not 
enable such individuals to establish a Table injury, they would be 
subject to the standard filing deadline in 42 CFR 100.42(a) (i.e., one 
year from the date of administration or use of the covered 
countermeasure).
    In this final rule, the Secretary has made the following change 
from what was proposed in the NPRM for the purposes of clarity.
    a. Changed paragraph (d)(6) by adding a comma after ``pustules)'' 
and before ``generally'' to the second sentence. The revised sentence 
states, ``The rash or lesions, characterized by multiple blisters 
(vesicles or pustules), generally evolve in a similar sequence or 
manner as the original vaccination site.
    b. Changed paragraph (d)(9) by adding ``to'' after ``attributed'' 
and before ``it'' to the seventh sentence. The revised sentence states, 
``Symptoms that occur before 5 days or more than 14 days after 
receiving the smallpox vaccine should not be attributed to it.''

III. Comments and Responses

    The NPRM set forth a 60-day public comment period, which ended on 
December 14, 2020. During the comment period, HHS received one comment 
that was not relevant to the NPRM. As noted above, the only

[[Page 45657]]

changes made to the final rule are to paragraphs (d)(6) and (9) for 
clarity.

IV. Regulatory Impact Analysis

    HHS examined the impact of this final rule as required by Executive 
Order 12866 on Regulatory Planning and Review (September 30, 1993), 
Executive Order 13563 on Improving Regulation and Regulatory Review 
(January 18, 2011), the Congressional Review Act (5 U.S.C. 804(2)), the 
Regulatory Flexibility Act (RFA) (September 19, 1980, Pub. L. 96-354), 
section 202 of the Unfunded Mandates Reform Act of 1995 (March 2, 1995; 
Pub. L. 104-4), section 654(c) of the Treasury and General Government 
Appropriations Act of 1999, and Executive Order 13132 on Federalism 
(August 4, 1999).

Executive Orders 12866 and 13563

    Executive Order 12866 requires all regulations reflect 
consideration of alternatives, costs, benefits, incentives, equity, and 
available information. Regulations must meet certain standards, such as 
avoiding an unnecessary burden. Regulations that are ``significant'' 
because of cost, adverse effects on the economy, inconsistency with 
other agency actions, effects on the budget, or novel legal or policy 
issues, require special analysis. In 2011, President Obama supplemented 
and reaffirmed Executive Order 12866.
    Executive Order 13563 provides that, to the extent feasible and 
permitted by law, the public must be given a meaningful opportunity to 
comment on any proposed regulations, with at least a 60-day comment 
period. In addition, to the extent feasible and permitted by law, 
agencies must provide timely online access to both proposed and final 
rules of the rulemaking docket on https://www.regulations.gov/, 
including relevant scientific and technical findings, in an open format 
that can be searched and downloaded. Federal agencies must consider 
approaches to maintain the freedom of choice and flexibility, including 
disclosure of relevant information to the public. Objective scientific 
evidence guides regulations and should be easy to understand, 
consistent, and written in plain language. Furthermore, Federal 
agencies must attempt to coordinate, simplify, and harmonize 
regulations to reduce costs and promote certainty for the public.

Summary of Impacts

    In this final rule, the Secretary establishes a Table identifying 
serious physical injuries that are presumed to result from the 
administration or use of certain covered countermeasures, required 
definitions of those injuries, and the time interval in which the onset 
of the first symptom or manifestation of each injury must manifest for 
the presumption of causation to apply. The Table establishes a 
presumption of causation for requesters meeting the Table's 
requirements and relieves requesters of the burden of demonstrating 
causation. However, this presumption is rebuttable if, based on the 
Secretary's review of the evidence, a source other than the 
countermeasure is found to be the more likely cause of the injury. The 
publication of this Table may afford some requesters a new filing 
deadline.
    The Secretary has determined that minimal staff and funding 
resources are required to implement the provisions included in this 
final rule. Therefore, in accordance with the Regulatory Flexibility 
Act of 1980 (RFA) and the Small Business Regulatory Enforcement 
Fairness Act of 1996, which amended the RFA, the Secretary certifies 
that this final rule will not have a significant impact on a 
substantial number of small entities.
    The Secretary has determined that this final rule does not meet the 
criteria for an ``economically significant'' regulatory action as 
defined by Executive Order 12866 and would have no major effect on the 
economy or Federal expenditures. The Secretary also has determined that 
this final rule is not a ``major rule'' within the meaning of the 
statute providing for Congressional Review of Agency Rulemaking, 5 
U.S.C. 801. The Office of Information and Regulatory Affairs within the 
Office of Management and Budget has determined that this rule is not a 
``significant regulatory action'' within the meaning of section 3(f) of 
the Executive order.

Unfunded Mandates Reform Act of 1995

    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $158 million, using the most current (2020) Implicit 
Price Deflator for the Gross Domestic Product. This final rule would 
not result in an expenditure in any year that meets or exceeds this 
amount.

Executive Order 13132--Federalism

    The Secretary also reviewed this final rule in accordance with 
Executive Order 13132 regarding federalism and has determined that it 
does not have ``federalism implications.'' This final rule will not 
``have substantial direct effects on the states, or on the relationship 
between the national government and the states, or on the distribution 
of power and responsibilities among the various levels of government.''

Paperwork Reduction Act of 1995

    This final rule has no information collection requirements.

List of Subjects in 42 CFR Part 110

    Biologics, Immunization.

    Dated: August 9, 2021.
Xavier Becerra,
Secretary, Department of Health and Human Services.

PART 110--COUNTERMEASURES INJURY COMPENSATION PROGRAM

0
1. The authority citation for part 110 continues to read as follows:

    Authority:  42 U.S.C. 247d-6e.


0
2. Amend Sec.  110.100 by revising paragraph (b) introductory text and 
paragraph (c) and adding paragraph (d) to read as follows:


Sec.  110.100   Injury Tables.

* * * * *
    (b) 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.
* * * * *
    (c) Smallpox countermeasures injury table.

[[Page 45658]]



                        Table 2 to Paragraph (c)
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                                                      Time interval (for
                                                       first symptom or
                                                       manifestation of
                                   Serious physical     onset of injury
  Covered countermeasures under    injury (illness,          after
          declarations                disability,      administration or
                                      injury, or        use of covered
                                    condition) \1\      countermeasure,
                                                       unless otherwise
                                                          specified)
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I. Smallpox Vaccines Replication- A. Anaphylaxis....  A. 0-4 hours.
 Deficient.                       B. Vasovagal        B. 0-1 hour.
                                   Syncope.
II. Smallpox Vaccines             A. Anaphylaxis....  A. 0-4 hours.
 Replication-Competent.           B. Vasovagal        B. 0-1 hour.
                                   Syncope.
                                  C. Significant      C. 1-21 days.
                                   Local Skin
                                   Reaction.
                                  D. Stevens-Johnson  D. 4-28 days.
                                   Syndrome/Toxic
                                   Epidermal
                                   Necrolysis.
                                  E. Inadvertent      E. 1-21 days.
                                   Autoinoculation.
                                  F. Generalized      F. 6-9 days.
                                   Vaccinia.
                                  G. Eczema           G. 3-21 days.
                                   Vaccinatum.
                                  H. Progressive      H. 3-21 days.
                                   Vaccinia.
                                  I. Post-vaccinial   I. 5-14 days.
                                   Encephalopathy,
                                   Encephalitis or
                                   Encephalomyelitis
                                   (PVEM).
                                  J. Vaccinial        J. 0-21 days.
                                   Myocarditis,
                                   Pericarditis, or
                                   Myopericarditis
                                   (MP).
III. Vaccinia Immunoglobulin      A. Anaphylaxis....  A. 0-4 hours.
 Intravenous (VIGIV).             B. Transfusion-     B. 0-72 hours.
                                   Related Acute
                                   Lung Injury
                                   (TRALI).
                                  C. Acute Renal      C. 0-10 days.
                                   Failure (ARF).
                                  D. Drug-Induced     D. Within 48 hours
                                   Aseptic             after the first
                                   Meningitis (DIAM).  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     A. Not Applicable.
                                   Covered \2\.
V. Tecovirimat..................  A. No Condition     A. Not Applicable.
                                   Covered \2\.
VI. Brincidofovir...............  A. No Condition     A. Not Applicable.
                                   Covered \2\.
VII. Smallpox Infection           A. No Condition     A. Not Applicable.
 Diagnostic Testing Devices.       Covered \2\.
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\1\ Serious physical injury as defined in Sec.   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.
\2\ The 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 Sec.   110.20(b) and (c).

    (d) 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).

[[Page 45659]]

    (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 vaccinial 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 vaccinial 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 vaccinial 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 become severely ill with signs and symptoms 
that involve the whole body (systemic illness), such as fever, malaise, 
or enlarged glands (lymph nodes).
    (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

[[Page 45660]]

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.
    (ii) 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 blood stream, 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.

[FR Doc. 2021-17216 Filed 8-13-21; 8:45 am]
BILLING CODE 4165-15-P