This document discusses Canada's orphan drug regulatory framework. It begins by defining orphan drugs as treatments for rare diseases affecting fewer than 5 in 10,000 people. It outlines challenges in developing and accessing orphan drugs, including small patient populations that make clinical trials difficult. Health Canada is proposing a framework to improve orphan drug availability through an accelerated review pathway, early advice to sponsors, transparency throughout the drug life cycle, and collaboration with international regulators and health technology assessment bodies. The key components of the framework include orphan drug designation, written regulatory advice, modernized market authorization applications, post-market oversight, and transparency.

1. Canada’s
Orphan
Drug
Regulatory
Framework:
What
Health
Canada
is
doing
now
and
what
is
yet
to
come
Canadian
Expert
Pa.ents
in
Health
Technology
Conference
November
7,
2016
Liz
Anne
Gillham-­‐Eisen
Health
Products
and
Food
Branch

2. Orphan
drugs
Orphan
drugs
are
used
to
treat
rare
diseases
which:
• are
life-­‐threatening,
seriously
debilita.ng
or
both
serious
and
chronic
in
nature
• affect
a
rela.vely
small
number
of
pa.ents
(less
than
5
in
10
000,
but
typically
closer
to
1
in
100
000)
• are
oRen
gene.cally
based,
onset
at
birth
or
early
childhood,
lead
to
a
shortened
life-­‐
span
• reduce
quality
of
life
and
place
significant
challenges
on
pa.ents,
caregivers
and
the
healthcare
system
• are
difficult
to
study
because
of
the
small
pa.ent
popula.on
2

3. Challenges:
Limited
pa?ent
popula?ons
and
treatments
3
There are more than 7,000 rare diseases
Rare diseases affect 1 in 12, or nearly 3 million Canadians
Diagnosis is challenging and can take years
Once diagnosed, there is likely no treatment available, or limited treatments for the patient

4. Challenges
–
Orphan
drug
development
and
pa?ent
access
4
Orphan
drugs
are
challenging
to
develop:
Small
pa.ent
popula.ons
make
it
difficult
to
conduct
clinical
trials,
especially
in
na.ons
without
large
pa.ent
popula.ons
LiXle
is
oRen
known
about
the
rare
disease
Researchers
and
drug
sponsors,
in
the
past,
did
not
have
incen.ves
to
invest
in
developing
drugs
for
rare
diseases
Once
developed
and
approved:
Orphan
drugs
are
oRen
costly
Pa.ents
across
Canada
may
not
have
equal
access
to
approved
orphan
drugs

5. An
Orphan
Drug
Framework
for
Canada
A
Regulatory
Framework
for
Drugs
for
Rare
Diseases
(Orphan
Drugs)
proposed
to
-­‐
• channel
orphan
drugs
into
a
federal
regulatory
pathway
designed
to
improve
market
availability
in
Canada
• draw
on
new
post-­‐market
and
transparency
powers
from
Vanessa’s
Law
• reflect
Canada’s
legisla.ve
and
regulatory
context,
while
aligning
where
possible
with
other
interna.onal
regulators’
orphan
drug
frameworks
• encourage
the
genera.on
of
knowledge
regarding
rare
diseases
in
drug
development
through
an
open
and
transparent
regulatory
environment
and
the
provision
of
advice
to
companies
developing
orphan
drugs
• allow
for
accelerated
market
authoriza.on
5

6. Life-­‐cycle
Approach
What
is
known
about
the
poten?al/actual
benefits,
harms
and
uncertain?es
associated
with
a
drug
changes
over
?me
Current:
Limited
point-­‐in-­‐,me
oversight
based
on
applica.ons
for
clinical
trials
and
marke.ng
authoriza.ons.
Future:
Expanded
and
con,nuous
oversight
beginning
at
early
development
stage
with
medical
plausibility
and
encompassing
a
greater
ability
to
define
post-­‐approval
informa.on
gathering.
Transparency
throughout
the
life
cycle
More
collabora.on
with
other
health
system
partners,
such
as
HTA
Agencies
6

7. Key
Components
of
the
Framework
Defini?on
Orphan
drugs
are
used
to
treat
rare
diseases
which:
• are
life-­‐threatening,
seriously
debilita.ng
or
both
serious
and
chronic
in
nature
• affect
a
rela.vely
small
number
of
pa.ents
(less
than
5
in
10
000)
Orphan
drug
designa?on
cer?ficate
• publicly
iden.fy
medically
plausible
orphan
drugs
to
enable
early
considera.on
of
medically
plausible
drugs
by
payers
for
purposes
of
improving
pa.ent
access
Regulator’s
Advice
• wriXen
regulator’s
advice
for
clinical
trials,
the
poten.al
balance
of
pre-­‐
and
post-­‐
market
evidence
requirements,
and
the
development
of
post-­‐market
plans
• joint
advice
where
possible
with
interna.onal
regulators
and
HTA
bodies

8. Key
Components
of
the
Framework
Market
Authoriza?on
Applica?ons
• modernized
licensing
structure
and
possibility
for
abbreviated
pathway
for
ultra-­‐rare
orphan
drugs
• ability
to
issue
terms
and
condi.ons
on
a
market
authoriza.on
• post-­‐authoriza.on
plan
to
characterize,
monitor
and
con.nue
to
iden.fy,
assess
and
manage
the
harms
and
benefits
associated
with
the
orphan
drug
– includes:
enhanced
post-­‐market
surveillance
procedures,
regular
monitoring
of
terms
and
condi.ons
of
market
authoriza.on,
risk
management
plan,
confirmatory
studies,
etc.
Transparency
• Transparency
throughout
the
life-­‐cycle
of
the
drug
to
communicate
applica.ons
under
review
and
regulatory
review
decisions.
Pa?ent
Involvement
• Collec.on
and
considera.on
of
public
input
into
the
review
of
submissions
for
orphan
drugs.
8

9. Regulatory
Openness
and
Transparency
• To
help
Canadians
beXer
understand
how
and
why
decisions
are
made:
– Submissions
Under
Review
• hXp://www.healthycanadians.gc.ca/drugs-­‐products-­‐medicaments-­‐produits/
authorizing-­‐manufacturing-­‐autorisa.on-­‐fabrica.on/review-­‐approvals-­‐evalua.on-­‐
approba.ons/submissions-­‐under-­‐review-­‐presenta.ons-­‐cours-­‐examen-­‐eng.php
– Drug
and
Health
Products
Register
• hXps://hpr-­‐rps.hres.ca/
– Regulatory
Decision
Summary
(RDS)
–
purpose
and
reason
• hXp://www.hc-­‐sc.gc.ca/dhp-­‐mps/prodpharma/rds-­‐sdr/drug-­‐med/index-­‐eng.ph
– Summary
Basis
of
Decision
(SBD)
–
more
technical
than
RDS
• hXp://www.hc-­‐sc.gc.ca/dhp-­‐mps/prodpharma/sbd-­‐smd/drug-­‐med/index-­‐eng.php
– Summary
Safety
Reviews
• hXp://www.hc-­‐sc.gc.ca/dhp-­‐mps/medeff/reviews-­‐examens/ssr-­‐rei-­‐eng.ph
– Stakeholder
Registry
• hXp://www.hc-­‐sc.gc.ca/ahc-­‐asc/public-­‐consult/stakeholder-­‐intervenants/index-­‐
eng.php
9

10. Pa?ent
Involvement:
Exploring
opportuni?es
• Pa.ent
input
can
add
value
to
the
evalua.on
of
human
drugs,
such
as
contribu.ng
to
benefit/risk
assessment
• Current
approach
considered
“ad-­‐hoc”.
Pa.ents
as
part
of
expert
commiXees
or
panels;
part
of
specific
issues,
and
rou.nely
as
part
of
policy
and
regulatory
development.
Health
Canada
is
currently
exploring
and
examining
the
most
effec.ve
ways
to
involve
pa.ents
in
the
review
process
• Not
a
ques.on
of
“if”
but
a
ques.on
of
“how”
• Consulta.on
with
pa.ents,
pa.ent
groups,
caregivers
and
health
care
providers
cri.cal
for
the
design
of
any
program(s)
10

11. Pa?ent
Involvement
Pilot
Project
• Pa.ent
Involvement
pilot
project
launched
in
2014
• Orphan
drugs
context
was
considered
a
good
star.ng
point
• Pilot
was
intended
to
be
a
simula.on
of
how
input
could
be
obtained
and
used
to
help
inform
Health
Canada’s
benefit/risk
assessment
• Two
drugs
were
involved
in
the
pilot
(one
biologic
and
one
pharmaceu.cal)
• Input
was
sought
through
online
ques.onnaires
designed
to
gather
the
perspec.ves
of
pa.ents,
caregivers,
pa.ent
groups
and
health
care
professionals.
Ques.ons
related
to
quality
of
life,
experience
with
other
therapies,
unmet
need,
and
risk
tolerance.
• Results
–
more
experience
is
needed;
reviewer
and
pa.ent
group
training
would
be
useful,
.ming
of
request
for,
and
receipt
of
input
is
important,
considera.on
should
be
given
to
establishing
criteria
for
when
to
request
pa.ent
input
that
would
be
of
most
value
to
both
reviewers
and
pa.ents.

12. Finding the right balance
Who best to
provide input?
When most
feasible and
useful to
collect?
What other
information
could be
collected?
Most
effective and
best format/s:
summaries?
Other?
How best
to use the
input?
Accountability
Routine collection or
establish criteria for
when most
valuable?
Meaningful
data and
timeliness
of reviews

13. Vanessa’s
Law
• Overall
policy
objec.ves
are
to:
– Provide
a
range
of
pre-­‐
and
post-­‐market
regulatory
tools
that
enable
the
safety
oversight
of
therapeu.c
products
throughout
their
lifecycle;
and
– Promote
greater
confidence
in
the
oversight
of
therapeu.c
products
by
increasing
transparency.
• Vanessa’s
Law
amends
the
Food
and
Drugs
Act
improving
Health
Canada’s
ability
to:
– collect
post-­‐market
safety
informa.on
– take
appropriate
ac.on
when
a
serious
risk
to
health
is
iden.fied
• These
amendments
are
par.cularly
important
in
the
rare
disease
context
where
oRen
.mes:
– many
of
the
pa.ents
impacted
are
vulnerable
paediatric
popula.ons
– informa.on
on
the
drug
and
the
disease
is
some.mes
limited
13

14. Vanessa’s
Law
• June
18,
2016:
No.ce
of
Intent
that
Health
Canada
plans
to
bring
forward
regulatory
amendments
to
implement
key
authori.es
under
Vanessa’s
Law
Coming
soon
•
Two
regulatory
packages
are
under
development:
– Authori.es
to
implement
a
lifecycle
approach
to
regula.ng
drugs
(“Vanessa’s
Law
Lifecycle
Authori.es”)
– Recall
of
drugs
and
medical
devices
Coming
later
• Analysis
con.nues
on
the
other
Vanessa’s
Law
authori.es
(terms
and
condi.ons
for
market
authoriza.ons,
repor.ng
of
adverse
reac.ons,
and
disclosure
of
clinical
trial
informa.on)

15. Current
availability
of
Orphan
Drugs
in
Canada
• Patented
Medicine
Prices
Review
Board's
(PMPRB)
Orphan
Drug
Launch
Monitor,
published
in
2016:
– analyzes
the
interna.onal
approval
of
designated
orphan
drugs
and
assesses
their
availability
in
Canada
– focuses
on
a
number
of
select
orphan
drugs
reported
at
the
ac.ve-­‐
substance
level
and
iden.fied
based
on
the
following
criteria:
1. drugs
that
received
orphan
designa.on
and
approval
in
the
US
and/or
EU
over
the
last
decade
(2005–2014),
and
2. drugs
that
only
have
orphan
indica.ons
– includes
Canada
and
the
seven
PMPRB
interna.onal
comparator
countries
(PMPRB7):
France,
Germany,
Italy,
Sweden,
Switzerland,
the
United
Kingdom
(UK)
and
the
US
15

16. The
PMPRB
analysis
reveals
the
following
key
points:
16
Many orphan drugs available in PMPRB7 countries are approved for
use in Canada
Health Canada approved 9 of the top 10 select orphan drugs
Orphan drugs not available in Canada represent a small share of the
international market: some were accessed through the Special Access
Program, while others were approved by Health Canada in 2015

17. Access
to
drugs
as
a
priority
Minister
of
Health
mandate
leXer
(2015)
• “…improve
access
to
necessary
prescrip.on
medicines”
HPFB
priori.es
–
new
Strategic
Plan
Research &
development
Health Canada review /
authorization
Patented Medicine
Prices Review Board
(PMPRB)
Health Technology
Assessment
Provincial/Territorial
Drug Plans
pan-Canadian
Pharmaceu?cal
Alliance
(pCPA)
Hospitals
Patient
Access
Innova.on
and
access
to
drugs
-­‐
What
role
can
the
regulator
play?
Private Plans

18. Where do we go from here?
• Improving
research,
approval,
and
access
• Many
of
the
tools
considered
for
orphan
drugs
can
also
be
considered
in
the
context
of
all
drugs
• Work
is
ongoing
to
explore
and
examine
most
effec.ve
ways
to
involve
pa.ents
in
the
review
process
• Life
cycle
approach
and
increasing
transparency
• Con.nue
collabora.ons
interna.onally
to
promote
convergence,
and
enhance
collabora.ons
among
key
Canadian
stakeholders
across
the
lifecycle
of
a
drug

19.
Thank
You/Merci!
19