Safe and Effective Medicines for Children Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act (2012) / Chapter Skim
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3 Policy Framework for BPCA and PREA
3 Policy Framework for BPCA and PREA
Pages 63-88
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From page 63... ...
In application, when it requests or requires pediatric studies of specific products, FDA considers what age ranges are appropriate given the medical condition to be studied, the research questions and procedures, and, possibly, the characteristics of the drug in question. This chapter begins with a brief overview of the regulatory context for BPCA and PREA, including definitions of key terms, procedures govern 63
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From page 64... ...
The discussion of PREA includes a short comparison of differences in requirements for pediatric drug studies between the United States and Europe. The chapter concludes with some suggestions for policy makers as they consider the reauthorization of BPCA and PREA in 2012.1 Chapter 4 describes another part of the regulatory framework for pediatric studies -- regulations concerning the protection of human participants in research.
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From page 65... ...
These discussions may, for example, make clear that PREA requirements will be waived because the condition being studied is not diagnosed in children. Alternatively, FDA may signal to sponsors that pediatric studies will be required, and it may encourage them to start planning for those studies and to be ready to begin them as early as possible taking safety into account (see discussion of the pediatric plan below)
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From page 66... ...
Under the FDC Act, sponsors of original and supplemental applications must provide substantial evidence of a product's safety and effectiveness for its intended use. As described in the statute, substantial evidence means evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the label ing or proposed labeling thereof.
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From page 67... ...
. Labeling Requirements The sponsor technically owns and holds copyright to a product's labeling information, and it normally proposes and participates in labeling changes subject to close FDA oversight.
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To monitor and learn more about drug safety in actual use, FDA uses two general strategies. The first strategy for postmarket safety monitoring involves the periodic reporting of new safety information to FDA.
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From page 69... ...
. These required safety investigations may involve pediatric studies but are separate from any requirements under PREA.
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From page 70... ...
as a reward for having performed pediatric studies as specified in a written request from FDA. The core incentive is a 6-month period of pediatric exclusivity that is awarded if the Secretary of Health and Human Services (through delegation to FDA)
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From page 71... ...
The law does not require that studies demonstrate that a drug is safe and effective for the specified pediatric use. Indeed, in some cases, pediatric studies have yielded important negative findings and labeling changes that warn that a drug or biologic is not safe and should not be administered in specific pediatric settings.
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From page 72... ...
New conditions of use NDA FDA may accept and review a 3 years + exclusivity (protects an follow-on application during 6 months innovator's new conditions the 3-year period but may of use for a previously not formally approve that approved active moiety application for the protected when clinical research was conditions of use until 3 years required to be performed to after the innovator's new achieve the new approval, conditions were approved e.g., FDA approves a new indication for use, potentially including a pediatric indication, or certain other changes) Orphan drug exclusivity NDA, BLA FDA may accept and review 7 years + (covers drugs and biologics a competitor application 6 months for rare diseases)
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From page 73... ...
The agency is permitted up to 180 days to make its determination whether pediatric exclusivity has been earned. As a result, sponsors now must complete and submit their reports on pediatric studies more than a year before the scheduled expiration of underlying patent and market exclusivity.
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From page 74... ...
.5 Written Requests FDA's written request for a pediatric study is a critical component of BPCA that determines when and how a product will become eligible for pediatric exclusivity. FDA may issue a written request at any time (i.e., it need not be linked to an NDA, BLA, or supplement)
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From page 75... ...
Drug sponsors may submit to FDA a Proposed Pediatric Study Request that outlines their ideas for pediatric studies. FDA may modify or reject the proposal.
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From page 76... ...
Requests for Studies of Off-Patent Products As mentioned in Chapter 1, BPCA created a role for the National Institutes of Health (NIH) in supporting pediatric drug studies for both onpatent and off-patent drugs.6 For drugs that are off-patent, BPCA directed NIH to create a list of pediatric therapeutic priorities and to propose written requests for studies to FDA.
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From page 77... ...
. PEDIATRIC RESEARCH EQUITY ACT FDA promulgated its Pediatric Rule -- the predecessor of PREA -- in 1998.
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From page 78... ...
The Pediatric Plan PREA refers to but does not define the term pediatric plan. In draft guidance for industry on compliance with PREA, FDA describes a pediatric plan as a statement of intent submitted by the applicant outlining the pediatric studies (e.g., pharmacokinetics/pharmacodynamics, safety, efficacy)
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From page 79... ...
As described below, EMA requires determination of a specific plan for pediatric studies shortly after Phase I studies with adults are completed. Deferral of Pediatric Assessments FDA is authorized, on its own initiative or upon the request of an applicant, to defer the submission of required pediatric assessments for completion at some time after the drug or biologic is approved for marketing.
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From page 80... ...
(In years past, approval letters were often not specific about the rationales for a waiver or deferral.) FDAAA specified that if FDA grants a waiver on the basis of evidence that a drug or biologic would be ineffective or unsafe in TABLE 3-2 Reasons for Waiver of Pediatric Assessment Requirements Authorized Under PREA with Examples from Recent NDA or BLA Approvals Reason for Waiver Example Necessary studies are impossible or highly FDA waived the pediatric study requirement impracticable (because, for example, the for gabapentin (Gralise)
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From page 81... ...
. Relationship to European Requirements for Pediatric Studies As noted in Chapter 1 and above, the laws and policies administered by FDA differ from those of the EMA as they relate to requirements for pediatric drug studies.
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From page 82... ...
will not be accepted for filing. As described earlier, FDA encourages discussions of plans for pediatric studies relevant to PREA requirements by the end of Phase II of clinical development.
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From page 83... ...
. Communication does not, however, mean that pediatric drug development programs will have identical pediatric study protocols.
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From page 84... ...
As specific examples, the PeRC • reviews all written requests under BPCA before they are issued; • may review the findings of studies submitted in response to such requests and make recommendations about the granting of exclusivity; • consults with review divisions on pediatric plans and assessments under PREA and reviews requests for waivers or deferrals; and • consults on the tracking and public availability of information about pediatric studies and labeling changes. PUBLIC ACCESS TO INFORMATION Congress has increasingly required FDA to provide public access to information concerning the application of BPCA or PREA.
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From page 85... ...
BPCA FDA must make available to the public a summary of the medical and clinical (2002) pharmacology reviews of pediatric studies conducted for an NDA supplement.
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From page 86... ...
Changes have also incorporated more pediatric expertise into the review of requests and requirements for pediatric studies and the findings of the studies submitted in response. As the 2012 reauthorization of BPCA and PREA is debated, one question is whether both policies should now be made permanent (i.e., not be subject to further time-limited extensions)
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From page 87... ...
A requirement for earlier submission should, however, encourage the timely planning, conduct, and submission of pediatric studies. The next chapter reviews policies for the protection of child participants in research and discusses ethical issues in pediatric studies conducted under BPCA and PREA.
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Key Terms
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