Global Regulatory Landscape for COVID-19 & Overview Regulatory Pathways

1. Global Regulatory Pathways for
COVID-19 Therapies and Vaccines
June 2020
Mridula Shukla
Global Lead, Regulatory Affairs
ALL INFORMATION IN THIS PRESENTATION IS BASED ON PUBLIC SOURCES ONLY.

2. 1
COVID-19 Vaccines and Therapy Options
Source: Public Source, including “Looking Forward: COVID-19 Treatments, Vaccines, and Distribution” (PRA Health).
GAO publications. https://www.gao.gov/assets/710/707152.pdf
• Vaccines protect people from disease by triggering an immune system to produce
antibodies that will fight the pathogen attacking the body. In the case of COVID-19,
the pathogen is the virus SARS-CoV-2
• Illustrated below are three different mechanisms to prompt the body to produce
antibodies
• Effective therapies for COVID-19 can reduce morbidity, mortality, and infectivity
• Researchers are actively investigating therapeutics that could potentially be effective
in combatting the disease, including some already existing antiviral drugs
• Some strategies currently under investigation include:
o Antivirals
o Immunotherapies
o Symptom reduction therapies
Vaccines
Therapies

3. 2
Key Challenges to Vaccine and Therapy Development
• Expensive Research, Discovery and Testing:
Significant development and regulatory costs
prior to approval
• Time Consuming: ~12-18 months, even in
expedited scenarios
• Extensive Regulatory Approval Processes
• Mass Manufacturing and Distribution
constraints
• Safety profile for ‘at-risk’ population
• Virus Mutation: RNA viruses can mutate and
potentially reduce or eliminate a vaccine’s
effectiveness
• Quality and Compliance Assurance during the
drug/vaccine life cycle
• Risk from accelerated process: accelerating
development could increase risk of adverse
effects, since less time would be allocated to
proving safety and effectiveness
• Supply Constraints: Increasing export
restrictions, dependence on imported supplies,
and competition for materials may constrain
access to supplies
Source: Public Sources, GAO publications. https://www.gao.gov/assets/710/707152.pdf

4. 3
Significant Ongoing Research on COVID-19 Treatments and Vaccines
Source: Milken Institute as of 5/28/2020. https://milkeninstitute.org/covid-19-tracker
145
vaccines
in development
224
treatments
in consideration
85
135
139
9 1
TREATMENT
VACCINE
Stage of Development
Pre-clinical Clinical Phase I Phase II
Treatments
and Vaccines
by types
Milken Institute Data

5. Global Regulatory Response to COVID-19 &
Overview Regulatory Pathways

6. 5
New Regulatory Paradigm to meet the COVID challenge
• Under normal
circumstances, the entire
process typically takes 10
to 15 years, with more
than 65 percent of
candidates failing,
according to an MIT study
• New regulatory
environment requires
significant flexibility to
speed to ensure timely
approval of safe treatments
and vaccines
Source: Public Sources, GAO publications. https://www.gao.gov/assets/710/707152.pdf

7. 6
US FDA Announcements since COVID-19 pandemic
FDA Will Facilitate Biological Product Development Against COVID-19
• Converted its in-person meetings scheduled through April 30, 2020 to
teleconferences
• Extended the response due date for medical device marketing applications that
relate to biological products and are subject to CBER review
• Automatic 60-day extension for certain on hold applications or near term
response due
• Paused certain lot release activities and has ceased to receive biological product
samples in physical form until further notice
• FDA has developed a procedure to provide interested healthcare providers
with emergency use of investigational convalescent plasma
Highlights of CBER
Measures (March 27,
2020)
Enacted on March 6, 2020, appropriated $61 million to FDA
• Objective: to prevent, prepare for, and respond to coronavirus, domestically or
internationally, including the development of necessary medical
countermeasures and vaccines, advanced manufacturing for medical products,
the monitoring of medical product supply chains, and related administrative
activities
Coronavirus
Preparedness and
Response Supplemental
Appropriations Act
(March 6, 2020)
Source: Public Sources.

8. 7
US FDA Announcements since COVID-19 pandemic (cont’d)
Public Private Partnership announced on April 17, 2020
• Select Public Partners: FDA, NIH, FNIH, BARDA, EMA, CDC, VA, DoD
• Select Private Partners: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eisai,
Eli Lilly, Evotec, Gilead, GlaxoSmithKline, Johnson & Johnson, KSQ Therapeutics,
Merck, Novartis, Pfizer, Roche, Sanofi, Takeda, Vir etc.
• Key Working Groups: Preclinical, Therapeutic Clinical, Clinical Trial Capacity,
Vaccines
Accelerating COVID-19
Therapeutic
Interventions and
Vaccines (ACTIV)
Coronavirus Treatment Acceleration Program (CTAP) which includes following
advantages:
• Dedicated staff includes senior management
• FDA generally responds within a day
• Ultra-rapid input based on product’s scientific merits, stage of development, and
possible priority potential
• Protocol review within 24 hrs, in some cases
• Review Single patient expanded access requests around-the-clock and usually
within 3 hrs
• FDA to collaborate with applicants and other regulatory agencies to expedite
assessments and to transfer manufacturing to alternative or new sites to avoid
supply disruption
Coronavirus Treatment
Acceleration Program
(CTAP)
Source: Public Sources.

9. 8
Summary of Expedited Regulatory Pathways for COIVD-19
United States
Source: https://www.natlawreview.com/article/fast-track-covid-19-drug-and-vaccine-approval-united-states-and-europe
Off-Label Use of an
Approved Product
• Healthcare providers can typically decide whether to prescribe an existing
approved drug “off-label” without FDA oversight, subject to the provider’s
assessment of the potential benefits versus the risks for the patient, prevailing
professional standards of practice and potential liability considerations
Emergency Use
Authorization
• FDA may use its Emergency Use Authorization (EUA) authority to permit the use of
unapproved medical products, or the off-label use of approved medical products,
to diagnose, treat or prevent serious or life-threatening diseases
• On 4 February 2020, the Secretary of Health and Human Services made the
determination with respect to COVID-19 for authorization of emergency use
Investigational New Drug
Applications and Rapid
Scientific Advice
• FDA is expediting the provision of pre-IND feedback and the review of INDs for
sponsors seeking to develop COVID-19 vaccines.
• Expedited Pre-IND meeting by allowing the submission of Pre-IND meeting request
and Briefing package together and reducing the review timeline (30 days Vs 60
days)
Expanded Access
Program
• Under the National Expanded Access Treatment Protocol, the FDA has authorized
expanded access for use of COVID-19 convalescent plasma for patients with
serious or immediately life-threatening COVID-19 who are not eligible to
participate in randomized controlled trials
Coronavirus Treatment
Acceleration Program
• Special emergency program intended to expedite the development and approval
of possible therapies for COVID-19 (not available to vaccine developers)
• Under this program, FDA will provide rapid interactive input on product
development plans and/or study protocols

10. 9
# Rapid Review Procedures Key features (refer to EMA publication for details)
1 Rapid scientific advice • No pre-specified submission deadlines to submit submission dossier (initial contact: 2019-
ncov@ema.europa.eu )
• Flexibility regarding the type and extent of the briefing dossier (case-by-case basis)
• This scientific advice is free of charge (EMA/134143/2020)
• The total review time reduced to 20 days (vs regular 40/70 days)
2 Rapid agreement of a
pediatric investigation
plan (PIP) and rapid
compliance check
• No pre-specified submission deadlines
• Possibility of a focused scientific documentation (case-by-base basis)
• Total evaluation time for a PIP reduced to a minimum of 20 days (compared to 120 days)
• Following PDCO opinion, the EMA decision will be adopted within 2 days (vs 10 days)
• Discuss the plan with international regulators during the evaluation (global perspective)
• The timelines for a compliance check can be reduced to 4 days if necessary
3 Rolling review • Rolling reviews are conducted under the EMA emerging health threats plan and requires
specific agreement by the COVID-ETF
4 Marketing authorization • Applications for a marketing authorization will be treated in an expedited manner
• Option to contact EMA Product Lead and provide explanation/justification for for a shorter
review timetable ad hoc given COVID-19 pandemic
5 Extension of indication
and extension of
marketing authorization
• Above support available to already authorized products that are being developed
(repurposed) for treatment or prevention of COVID-19
6 Compassionate Use • Certain unauthorized medicinal products may be made available at national level through
compassionate use programs
7 Other considerations • The Priority medicines (PRIME) scheme could be considered by developers to receive
enhanced support
• Expedited review under PRIME may take a maximum of 150 days (vs 210 days)
Source: EMA initiatives for acceleration of development support and evaluation procedures for COVID-19 treatments and vaccines, May 4, 2020
https://www.ema.europa.eu/en/documents/other/ema-initiatives-acceleration-development-support-evaluation-procedures-covid-19-treatments-vaccines_en.pdf
Summary of Expedited Regulatory Pathways for COIVD-19
Europe

11. Thank you
Contact for Feedback or Questions:
Mridula Shukla
Global Lead, Regulatory Affairs
https://www.linkedin.com/in/shuklamridula/
ALL INFORMATION IN THIS PRESENTATION IS BASED ON PUBLIC SOURCES
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