Professional Documents
Culture Documents
US and EU Expedited Pathways
US and EU Expedited Pathways
Expedited Pathways
Agenda
• United States
– Defining “serious” and “unmet need”
– Fast Track designation
– Breakthrough therapy designation
– Accelerated Approval
– Accelerated Approval – the “Animal Rule”
– Priority Review
• Priority Review Vouchers
– 21st Century Cures Provisions
• Regenerative Medicine Advanced Therapy (RMAT)
• Limited Population Pathways for Antibiotics (LPAD)
– Exclusivity Provisions
Agenda
• Europe
– Accelerated Assessment
– Conditional Approval
– Exceptional Circumstances
– PRIME
– Adaptive Pathways
BACKGROUND:
FOUR FDA PROGRAMS FOR EXPEDITED REVIEW
• The intention is to directly attempt to meet unmet medical needs for treating serious/life threatening
conditions
• Four programs created by the FDA intended to improve speed to market and expedite drug
development and review of drugs
• We want to get the drug to the patient sooner
• FDA Refences: Section 506 with 3 subsections for detailed review 506(a), 506(b), 506(c)
FDA 21 CFR 312.80
establishes procedures to expedite the development, evaluation, and marketing of new therapies
intended to treat persons with life-threatening and severely-debilitating illnesses, especially where no
satisfactory alternative therapy exists
Breakthrough
Fast Track Accelerated Priority
Therapy
Designation Approval Review
Designation
“Serious” defined
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“Serious” defined
• A drug must be intended to have an effect on a serious condition or a serious aspect of a
condition, such as a direct effect on a serious manifestation or symptom of a condition or
other intended effects, including the following:
– A diagnostic product intended to improve diagnosis or detection
of a serious condition in a way that would lead to improved
outcomes
– A product intended to mitigate or prevent a serious treatment-
related side effect (e.g., serious infections in patients receiving
immunosuppressive therapy)
– A product intended to avoid or diminish a serious adverse event
associated with available therapy for a serious condition (e.g.,
product that is less cardiotoxic than available cancer therapy)
– A product intended to prevent a serious condition or reduce the
likelihood that the condition will progress to a more serious
condition or a more advanced stage of disease
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Unmet Medical Need
Reference Section 506(b) of the FD&C Act, Section 506(a) of the 21 CFR 314, subpart H Prescription Drug User Fee
as added by section 112 of the FD&C Act, as added by 21 CFR part 601, subpart Act of 1992
Food and Drug Administration section 902 of FDASIA E
Modernization Act of 1997 Section 506(c) of the
(FDAMA) and amended by FD&C Act as amended by
section 901 of the Food and section 901 of FDASIA
Drug Administration Safety and
Innovation Act of 2012 (FDASIA
Qualifying A drug that is intended to treat a A drug that is intended to A drug that treats a An application (original or
Criteria serious condition AND treat a serious condition serious condition AND efficacy supplement) for a
nonclinical or clinical data AND preliminary clinical generally provides a drug that treats a serious
demonstrate the potential to evidence indicates that meaningful advantage condition AND, if approved,
address unmet medical need OR the drug may demonstrate over available therapies would provide a significant
A drug that has been designated substantial improvement AND demonstrates an improvement in safety or
as a qualified infectious disease on a clinically significant effect on a surrogate effectiveness OR
product. endpoint(s) over available endpoint that is Any supplement that
therapy reasonably likely to proposes a labeling change
predict clinical benefit or pursuant to a report on a
on a clinical endpoint that pediatric study under 505Ab
can be measured earlier OR
than irreversible morbidity An application for a drug that
These designations and pathways or mortality (IMM) that is has been designated as a
are independent of each other. reasonably likely to qualified infectious disease
predict an effect on IMM product OR
or other clinical benefit Any application or
(i.e., an intermediate supplement for a drug
clinical endpoint). submitted with a priority
review voucher.
US Expedited Pathways - Continued
Program Name Fast Track BTD Accelerated Priority Review
Approval
When to Submit With IND or After With IND of after The sponsor should With original BLA, NDA
Request Ideally, no later than the pre- Ideally no later than the ordinarily discuss the or efficacy supplement.
BLA or pre-NDA meeting end of phase 2 meeting possibility of
accelerated approval
with the review division
during development,
supporting, for
example, the use of the
planned endpoint as a
basis for approval and
discussing the
confirmatory trials,
which should usually be
already underway at the
time of approval.
Timeline to Within 60 calendar days of Within 60 days of Not specified Within 60 calendar days
Agency Response receipt of the request receipt of the request of receipt of original
BLA, NDA or efficacy
supplement.
Features Actions to expedite Intensive guidance on Approval based on an Shorter clock for review
development and review efficient drug effect on a surrogate of marketing
Rolling review development endpoint or an applications (6 months
Organizational intermediate clinical compared to 10-month
commitment endpoint that is standard review).
Rolling review reasonably likely to
Other actions to predict a drug’s clinical
expedite review benefit.
US Expedited Pathways - Continued
Program Name Fast Track BTD Accelerated Fast Track
Approval Designation
Additional Designation may be Designation may be Promotional materials Designation will be
Considerations rescinded if it no longer rescinded if it no longer Confirmatory trials to assigned at the time of
meets the qualifying meets the qualifying verify and describe the original BLA, NDA or
criteria for fast tract. criteria for BTD anticipated effect on efficacy supplement
IMM or other clinical filling.
benefit
Subject to expedited
withdrawal
Fast Track Designation
Breakthrough Therapy Designation
Accelerated Approval
Animal Rule
• Accelerated Approval – Animal Efficacy Rule:
21 CFR Part 314 Subpart I (NDA) / 21 CFR Part
601 Subpart H (BLA) - Approval of new drugs
when human efficacy studies are not ethical or
feasible. Products have been studied for their
safety and efficacy in ameliorating or preventing
serious or life-threatening conditions caused by
exposure to lethal or permanently disabling toxic
biological, chemical, radiological, or nuclear
substances.
Priority Review
What is a Priority Review Voucher (PRV)?
• PRV program is a regulatory incentive program
administered by the FDA to promote drug
development for certain unmet medical needs.
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Priority Review Vouchers
Tropical Disease Priority Pediatric Rare Disease Medical Countermeasures
Review Voucher Priority Review Voucher
Date established 2007 (FDAAA) 2012 (FDASIA) 2016 21st Century Cures
Criteria Section 1102 of FDAAA Specifically targets the need Encouraging Treatments for
authorizes FDA to award for additional therapies for Agents that Present a
priority review vouchers to rare pediatric subsets of National Security Threat
sponsors of certain tropical other diseases. [Section 3086].
disease product applications
that meet the criteria Section 908 of FDASIA The Act creates a new
specified by the Act. A defines a "rare pediatric priority review voucher
priority review voucher may disease" as one which program for “material threat
be used by the sponsor who "primarily affects individuals medical countermeasures.”
obtains it or another aged from birth to 18 years, The Act defines the term to
sponsor to obtain a priority including age groups often be drugs or vaccines
review for a different called neonates, infants, intended to treat biological,
application. A priority review children and adolescents," chemical, radiological, or
voucher may be transferred and is a rare disease nuclear agents that present
from the sponsor who according to federal statute a national security threat, or
obtains it to another (200,000 persons in the US to treat harm from a
sponsor. or fewer). condition that may be
caused by administering a
drug or biological product
against such an agent.
Priority Review Vouchers
Tropical Disease Priority Pediatric Rare Disease Medical Countermeasures
Review Voucher Priority Review Voucher
Outcomes Upon marketing approval of Upon marketing approval of The Secretary shall award a
a NDA, BLA or supplement, a NDA, BLA or supplement, priority review voucher to
the FDA grants a voucher for the FDA grants a voucher the sponsor of a material
priority review to be used for priority review to be threat medical
with a product of its choice used with a product of its countermeasure application
or sold to another developer choice or sold to another upon approval by FDA
developer
Permanent Will sunset (expire) in 2020 The program is scheduled to
and will need to be sunset (expire) on October
reauthorized by Congress 1, 2023.
21st Century Cures - Incentives
Signed in to law December 2016. Legislative package
which promotes biomedical innovation.
New Chemical Entity 5 years • Granted to a drug that contains no active moiety
that has been approved by FDA under section 505(b)
• Runs from time of NDA approval
• Bars FDA from accepting for review any ANDA or
505(b)(2) application for a drug containing the same
active moiety for: - five years if an ANDA or 505(b)(2)
does not contain a paragraph IV certification to a
listed patent - four years if an ANDA or 505(b)(2) is
submitted containing a paragraph IV certification to
a listed patent
Drug - New Indication/ new population/ new dosage 3 years • New clinical studies in humans, conducted by
form/Rx-to-OTC switches sponsor and essential for approval
Orphan drug 7 years marketing exclusivity • Blocks competitors from obtaining FDA approval
even if they have generated their own data
• Applies only to the indication for which the product
is approved
Biologic 12 years (4 years data and 12 • 12 year marketing exclusivity for new biological
year marketing) structures – but if application is filed by same
sponsor or manufacturer of the Pioneer product (or
a licensor, predecessor in interest or a related party),
the changed biological structure must also result in a
(1) change in indications, route of administration,
dosing schedule, dosing form, delivery system,
delivery device or strength or (2) change in safety,
purity or potency
First interchangeable biosimilar 12 months • First follow-on product that is deemed by FDA to be
interchangeable
First biosimilar No exclusivity provided • No follow on exclusivity for same biological structure
New indication for an approved biologic No exclusivity provided • “Evergreening” not in scope
EU Expedited Pathways
Program Accelerated Conditional Exceptional PRIME Adaptive
Name Assessment Approval Circumstances Pathways
Nature of Designation Designation Designation Designation Designation
Program
Reference Recital 33 of Regulation (EC) (EC) No 507/2006 Article 14 (8) of Recital 33 and Article Recital 33 and Article
No 726/20041 Regulation (EC) No 14(9) of Regulation 14(9) of Regulation
726/2004 (EC) No 726/2004 (EC) No 726/2004,
Qualifying A justification including the Limited to products to The applicant can show The scheme aims to Based on 3 principles:
Criteria major benefits expected should treat: that he is unable to support medicinal 1. Iterative
be submitted. The following list 1. seriously debilitating provide comprehensive products of major public development. This is
of key items would normally be diseases of life- data on the efficacy and health interest and in either:
addressed in a justification for a threatening diseases safety under normal particular from the - a. staggered approval
request for accelerated 2. to be used in conditions of use, viewpoint of therapeutic from an initial restricted
assessment: emergency situations because: innovation (i.e. those patient population in
- The unmet needs and the 3. Orphan Medicinal - The indications for which fulfil the which the benefit
available methods of prevention, Products which the product in accelerated outweighs the risk, to
diagnosis or treatment. Must demonstrate: question is intended are assessment criteria). increasingly wider
- The extent to which the The risk-benefit balance encountered so rarely Criteria: populations (expansion
medicinal product is expected to of the product is that the applicant Addresses an unmet of the indication); or
have major impact on medical positive cannot reasonably be medical need - b. confirmation of the
practice, its major added value, It is likely that the expected to provide potential to address to a benefit/risk balance of a
and/or how it addresses the applicant will be able to comprehensive significant extent the product authorized
greater unmet needs. provide comprehensive evidence, or unmet medical need for under Conditional
- A brief outline of the main data - In the present state of maintaining and Marketing Authorization
available evidence (e.g., number Fulfilment of unmet scientific knowledge, improving the health of with early or surrogate
of clinical trials, key results) on medical need comprehensive the Community, endpoint
which the applicant bases its The benefits to public information cannot be 2. Gathering of
claim of major public health health of the immediate provided, or evidence thorough real-
interest. availability outweigh the - It would be contrary to life data to supplement
risks inherent in the fact generally accepted clinical trial date
that additional data are principles of medical 3. Involvement of
still required ethics to collect such patients and health
information, a technology assessment
marketing authorization (HTA) bodies in the
may be granted subject discussion of the
to certain obligations product development
design
EU Expedited Pathways - Continued
Accelerated Conditional Exceptional PRIME Adaptive
Assessment Approval Circumstances Pathways
When to submit As early as possible but Submitted as a Recommended that Can be submitted at At a point in
Request prior to the submission component of the appropriateness is the time of proof of development when
of the MAA but at least Letter of Intent to discussed at the pre- concept (Phase III) the principles can be
10 days before the start Submit (4 – 6 submission meeting. for larger pharma or applied to the
of the procedure. months) prior to the Justification should proof of principle for development
submission of the be included as part of SMEs. program.
MAA. Module 1.