Protecting the Frontline in Biodefense Research The Special Immunizations Program (2011) / Chapter Skim
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4 Regulations and Other Guidance Pertaining to the Development and Use of Vaccines in the Special Immunizations Program
4 Regulations and Other Guidance Pertaining to the Development and Use of Vaccines in the Special Immunizations Program
Pages 77-94
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From page 77... ...
The SIP pro gram is designed to serve a small population of laboratory workers and others with potential occupational exposures to highly hazardous pathogens. Even with a potential expansion of the SIP to meet the needs of additional users from the growing community of researchers working on countermeasures against pathogens for which the civilian population may be at risk of exposure, and the incorporation into the SIP of new vaccines against additional pathogens and toxins, the SIP could only continue to serve a relatively small population of lab workers who would benefit from immunization.
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From page 78... ...
Most of the vaccines included in the SIP are directed against pathogens that are now identified as Select Agents (42 CFR Part 72; 42 CFR Part 73; 7 CFR Part 331; 9 CFR Part 121) , which can cause life-threatening and/or fatal illness in exposed laboratory workers.
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From page 79... ...
are available for use by the military or for emergency use in civilians via the Strategic National Stockpile approval pathway, wherein safety and efficacy (primarily immunogenicity) data were obtained in fairly large, randomized clinical trials, supplemented by post-marketing (Phase 4)
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From page 80... ...
that have been studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments. Such an approval is based on adequate and well-controlled clinical trials estab lishing that the biological product has an effect on a surrogate endpoint that is reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical benefit (21 CFR § 601.41)
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From page 81... ...
) The third licensure pathway that is applicable to vaccines utilized under the SIP is known simply as "the Animal Rule." This rule was promulgated in 2002 and designed to permit approval of drugs and biologics (including vaccines)
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From page 82... ...
licensure, there is a fourth mechanism -- Emergency Use Authorization (EUA) -- that may enable potential recipients to receive an in vestigational SIP vaccine outside of an IND protocol.
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From page 83... ...
2. Based on the totality of scientific evidence available, including data from adequate and well-controlled clinical trials, if available, it is reasonable to believe that the product may be effective in diagnos ing, treating, or preventing (a)
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From page 84... ...
, which may someday provide sufficient evidence of risk/ benefit to enable an EUA for a specific vaccine to be used by military personnel and/or civilians should a public health emergency be declared. 4.3 ADMINISTRATION OF SIP VACCINES UNDER AN INVESTIGATIONAL NEW DRUG APPLICATION FDA regulations 21 CFR Part 312 (drugs)
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From page 85... ...
-- submitted for experimental drugs (including vaccines) already showing promise in clinical testing for serious or life-threatening conditions, either in an ongoing clinical trial under an existing IND or in instances where all clinical trials have been com pleted and the sponsor is actively pursuing marketing approval.
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From page 86... ...
For such instances, FDA issued a final rule on August 13, 2009, to facilitate the availability of drugs (including vaccines) to patients with serious diseases or conditions when there is no comparable or satisfactory alternative therapy in a program known as "expanded access to investigational drugs for treatment use." Among other provisions, the final rule authorizes shipment of the vaccine for a specified use (21 CFR § 312.36)
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From page 87... ...
is either being investigated in a controlled clinical trial under an IND designed to support a market ing application, or all clinical trials of the vaccine have already been completed. • The sponsor is actively pursuing marketing approval with due diligence.
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From page 88... ...
Although a centralized approach to manage these INDs has a number of important advantages -- including detailed knowledge of each IND dossier, complete and careful documentation of adverse event and immunogenicity data, and timely revisions of regulatory documents such as appropriately updated Investigator's Brochures -- the requirement that vaccinees must, in nearly all instances, travel to USAMRIID to be vaccinated has appeared to impede participation in the program severely. Therefore, the committee believes that the utilization of other IND mechanisms such as investigator-initiated INDs or treatment INDs held by investigators at other government or academic institutions should be strongly considered, contingent on a continuing strong commitment for complete and standardized data and fulfillment of responsibilities under the IND collection.
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From page 89... ...
In addition to these regulations, FDA published a guidance document in 2008 (FDA 2008) that is intended to provide pharmaceutical manufacturers with further financial incentives to develop drugs (including vaccines)
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From page 90... ...
of the current investigational SIP vaccines, would likely consist of either accelerated approval (if a suitable antibody correlate is available) or full approval under the Animal Rule.
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From page 91... ...
Joint development programs between these and U.S.based entities might also be a means to accelerate development of additional vaccines of interest to the SIP. Teams of vaccine development experts might also be assembled to carry out on-site reviews, patterned after successful "due diligence" approaches carried out by large pharmaceutical companies and ven ture capital groups for merger and acquisition and/or in-licensing opportunities for SIP portfolio expansion.
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From page 92... ...
. Therefore, if an Orphan Drug Designation is pursued as an ancillary regulatory mechanism, attention must be given to the potential concern among SIP vaccine recipients that assurances regarding the safety of the product may be less robust than those for vaccines given to the general population.
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From page 93... ...
If expression of those genes consistently resulted in, for example, the generation of recombinant viral capsid protein antigens critical to a protective immune response, then the clinical profile of one vaccine might be easily bridged to another, without the need for extensive clinical testing of each recombinant vaccine individually. Experience gained with such a platform could also be leveraged for other pathogens that might be of greater commercial interest, and thus provide a continuous "warm base" for the manufacture of large batches to be used commercially as well as smaller batches to be used as "orphan vac cines" for the SIP or other biodefense purposes.
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From page 94... ...
Efforts undertaken by FDA and others should continue to advance this area in the future, and the committee endorsed these goals. 4.6 FINDINGS AND CONCLUSIONS ON REGULATORY PATHWAYS APPLICABLE TO THE SIP • Finding 8: There are provisions within existing FDA regulations that could apply to the SIP and, in particular, that could be used to enable the administration of additional SIP immunizations and/or to enable the use within the SIP of additional IND vaccines (both domestic and foreign)
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