Transcript Canada`s PMPRB - Moving Forward

Compendium of Policies, Guidelines and
Procedures, June 2009
Implementation: January 1, 2010
Regulatory Affairs and Outreach Branch
Toronto, Ontario
June 17, 2009
Montreal, Quebec
June 18, 2009
Overview
 Introduction
 Guidelines and Procedures
 Scientific Review Process
 Price Tests
 Any Market Review
 “DIP Methodology”
 Re-setting NEAP
 Filing Requirements
Compendium of
Policies, Guidelines and Procedures
 Part A – Legal Framework
New section on legal framework
 Part B – Policies
 New section which sets out Board policies
 Part C – Guidelines and Procedures
 Aligned with price review process
 Schedules
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Modified Terminology for MNE Price
 More transparent

Regulations require reporting of average prices
 New terms:
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Maximum Average Potential Price (MAPP)
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Non-Excessive Average Price (NEAP)
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Introductory price ceiling for all markets: national, pharmacies, hospitals,
wholesalers, and provinces/territories
Based on actual pricing in each market
Maximum Average Potential Price
(MAPP)
 Will publish MAPP for new patented drug products in Summary
Reports
 Will not publish CPI-inflated MAPP
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Domestic Price Comparisons
 New methodology for public prices for comparators identified for
price tests

Clarity and predictability of public prices to be used in price
tests (TCC and RR tests)
 New methodology applies both when comparator sold by same or
different patentee
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Domestic Price Comparisons (cont’d)
 Six price sources will be consulted:
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Association québécoise des pharmaciens propriétaires (AQPP);
IMS Health;
McKesson Canada;
Ontario Drug Benefit (ODB) Programs;
PPS Pharma; and,
Régie de l'assurance maladie du Québec (RAMQ)
 For each comparator identified, lowest public price selected
 Price test conducted using the price identified for each comparator
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New patented drug product XYZ – assume it is a slight or no
improvement and three comparable drug products were
identified as comparators for TCC test
Comparator A
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AQPP
IMS
$2.00
$2.10
Comparator B
$3.50
Comparator C
$0.80
McKesson
$3.20
ODB
PPS
RAMQ
$2.50
$2.00
$3.00
$1.25
TCC test for new patented drug product XYZ
Average transaction
price*
New patented drug
product XYZ
Public price
Comparator A
$2.00 (RAMQ or AQPP)
Comparator B
$3.00 (ODB)
Comparator C
$0.80 (IMS)
* In introductory period, national and market-specific ATPs cannot exceed MAPP. If
TCC test establishes MAPP, in this scenario no ATP can exceed $3.00.
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Publicly Available International Prices
 Patented Medicines Regulations direct patentees to provide
publicly available ex-factory prices when completing Form 2,
Block 5
 Commercially sensitive confidential prices are not to be reported
10
Use of Patented and Non-Patented Drug Products as
Comparators in the Price Tests
 Historical policy and practice
 All pivotal comparators assessed against price tests in Guidelines
 Exclude any comparator, patented or non-patented, being sold at
an excessive price
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Policy on Offsetting Excess Revenues
 Actual price reduction below previous year’s NEAP
 Once excess revenues offset by price reduction, ATP may return
to market-specific NEAP
 VCU required to resolve excess revenues below investigation
criteria after 3 consecutive years
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Example of offset below investigation criteria
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N-NEAP
N-ATP
Sales
Excess
Revenue
Cumulative
Excess
Revenue
Year 1
$10.00
$10.20
100,000 units
$20,000
$20,000
Year 2
$10.20
$10.20
100,000 units
$0
$20,000
Year 3
$10.40
$10.00
100,000 units
-$20,000
$0
Guidelines and Procedures
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Submission Process for New Drug Products
 Filing of Scientific Data
 No explicit regulatory requirement with the exception of Form 1
and product monograph (or information similar to that contained
in product monograph).
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Submission Process for New Drug Products
 Source of Scientific Information
 Patentee Submission
 Research by Drug Information Center (DIC)
 Research by Board Scientific Staff
 Research by Human Drug Advisory (HDAP) Panel members
 Other experts (as required)
 Scientific review does not consider pricing information
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Submission Process for New Drug Products
Scientific Review
DIC
Experts
Patentee
Submission
Board Scientific
Staff
HDAP
Members
HDAP (majority vote)
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Recommendation on Level of Therapeutic Improvement,
Comparators and Dosage Regimens
Products Not Referred to the HDAP
 In general, new patented drug products are referred to HDAP
 However, the following new patented drug products will not be referred to HDAP
unless the patentee files a submission claiming therapeutic improvement:
o
o
o
o
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The new patented drug product represents a new DIN of an existing dosage form of an existing drug
product, or a new DIN of another dosage form of the existing drug product that is comparable to the
existing dosage form as per Schedule 2 and has the same indication or use as the existing DIN; or
The new patented drug product is a combination drug product, the individual components of which are
sold in Canada and have the same indication or use; or
The new patented generic drug product is considered by Health Canada to be bioequivalent to the
reference brand drug product sold in Canada; or
The new patented generic drug product is a licensed version of an existing brand drug product sold in
Canada.
Determining the Primary Indication/Use
 Guidelines did not change;
 Primary indication/use for drug products with multiple indications/use will
be based on the approved indication or use for which the drug product
offers the greatest therapeutic advantage in relation to alternative
therapies;
 Where there is no apparent single approved indication or use for which
the new patented drug product offers the greatest therapeutic advantage,
the approved indication or use representing, potentially, the greatest
proportion of sales will be the basis for recommending its level of
therapeutic improvement; and selection of drug products to be used for
comparison purposes;
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Level of Therapeutic Improvement
 Breakthrough: A breakthrough drug product is the first one to be sold in Canada
that treats effectively a particular illness or addresses effectively a particular
indication.
 Substantial Improvement: A drug product offering substantial improvement is
one that, relative to other drug products sold in Canada, provides substantial
improvement in therapeutic effects.
 Moderate Improvement: A drug product offering moderate improvement is one
that, relative to other drug products sold in Canada, provides moderate
improvement in therapeutic effects.
 Slight or No Improvement: A drug product offering slight or no improvement is
one that, relative to other drug products sold in Canada, provides slight or no
improvement in therapeutic effects.
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Factors Considered in Recommending the Level of
Therapeutic Improvement
 Primary Factors


Increased efficacy
Reduction in incidence or grade of important adverse reactions
 The primary factors will be given the greatest weight. Primary
factors will be considered in order to assess if the new patented
drug product is a breakthrough, or represents substantial,
moderate or slight/no improvement relative to other drug products
available in Canada
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Factors Considered in Recommending the Level of
Therapeutic Improvement
 Secondary Factors

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Route of administration
Patient convenience
Compliance improvements leading to improved therapeutic efficacy
Caregiver convenience
Time required to achieve the optimal therapeutic effect
Duration of the usual treatment course
Success rate
Percentage of affected population treated effectively
Disability avoidance/savings
 Secondary factors will then be considered. These secondary factors could result in the level of
therapeutic improvement being assessed at up to the level of moderate therapeutic improvement.
 Note: factors such as the mechanism of action; a new chemical entity and a different
pharmacokinetic profile will generally not be taken into consideration, unless the impact of these
factors results in either increased efficacy and/or a reduction in the incidence or grade of important
adverse reactions.
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Methodology for the Evaluation of the Level of
Therapeutic Improvement
 An evidence-based approach will be used
 Hierarchy of evidence from the Oxford Centre for
Evidence-Based Medicine (see Schedule 1 in the
Compendium)
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Selection of Comparators
 HDAP uses the World Health Organization (WHO) Collaborating
Centre for Drug Statistics Methodology’s Anatomical Therapeutic
Chemical (ATC) Classification System
 Products will typically be those identified at the 4th sub-class level
 HDAP may also choose from the next higher sub-class or another
sub-class
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Selection of Comparators
Will be
reviewed
by HDAP
Level of Therapeutic
Improvement
Comparators
Breakthrough
None
Substantial
Improvement
Drug products over
which is it
substantial improvement
Moderate
Improvement
Drug products over
which is it
moderate improvement
Slight/No
Improvement
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Comparable drug products
-if no comparable drug products:
“superior” drug products
Selection of Comparators
Level of
Therapeutic
Improvement
Will not be
reviewed by
HDAP unless
company
makes
submission
claiming
therapeutic
improvement
-Same active ingredient
-Same indication/use
-Same or comparable
dosage form
-Same or different dosage
regimen
Combination
Drug Products
Generic Bioequivalent
Generic Licensee
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Comparator
-Same active ingredient
-Same indication/use
-Same or comparable
dosage form
Each of the
component
parts
Brand name
drug product
Comparable Dosage Regimens
 Guidelines did not change
 Will normally not be higher than the maximum of the usual
recommended dosage in the Product Monograph
 The most appropriate strength of the drug product will be chosen
for a particular dosage regimen
 Course of treatment will be applicable to acute indications
 A per-day regimen (based on maintenance dose) will be applicable
to chronic situations
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OTC and Veterinary Drug Products
 Upon receipt of a complaint, the PMPRB will undertake the
scientific review of the patented OTC or veterinary drug product in
the same manner as is undertaken for all other patented drug
products
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Submission Process for New Drug Products
 Communication of Results
 Following HDAP meeting (approximately 1 – 2 weeks after
meeting)
 Board Staff proceed to price review
 Patentees have opportunity to re-submit
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Introductory Price Tests
 Price premium aligned with degree of therapeutic improvement:
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Breakthrough – Median of International Price Comparison (MIPC)
Substantial Improvement – Higher of top of Therapeutic Class Comparison
(TCC) test and the MIPC
Moderate Improvement – Higher of mid-point between top of TCC test and
the MIPC, and top of TCC test
Slight/No Improvement – Top of TCC test
Introductory Price Tests
Level of Therapeutic
Improvement
Comparators
Intro Price
Tests
Breakthrough
None
MIPC
Substantial
Improvement
Drug products over
which it is
substantial improvement
Higher of:
Top TCC test and MIPC
- Higher of:
Mid point and Top TCC test
Moderate
Improvement
Drug products over
which it is
moderate improvement
Comparable drug
products
Slight/No
Improvement
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-if no comparable drug
products: “superior”
drug products
Top TCC test / MIPC
- If cannot derive dosage regimen
or price of comparator(s) is
excessive
MIPC
Top TCC test
- Lower of:
Bottom TCC test and MIPC
- If cannot derive dosage regimen
or price of comparator(s) is
excessive
MIPC
Introductory Price Test
Level of
Therapeutic
Improvement
-Same active ingredient
-Same indication/use
-Same or comparable dosage
form
-Same or different dosage
regimen
Combination Drug
Products
Generic Bioequivalent
Generic Licensee
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Comparator
-Same active ingredient
-Same indication/use
-Same or comparable
dosage form
Each of the
component
parts
Brand name
drug product
Intro Price
Test
-RR test if same dosage
regimen
-TCC test if different dosage
regimen
TCC test (sum of each
of the component parts)
RR test
Reasonable Relationship (RR) Test
 Clarify language
 Change to test 2:
 will also conduct if slope zero
 addresses situation where only negative y-intercepts
 Test 3:
 Maintain pricing for new lower strength at price of existing
higher strength
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Highest International Price Comparison
(HIPC) Test
 For all patentees, HIPC test conducted:
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At national level
For pharmacy and hospital customer classes
For each province and territory
 HIPC test not applied to wholesaler class of customer
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International Therapeutic Class Comparison
(ITCC) Test
 Not pivotal price test – for information only
 Focus on median price
 Two methods:
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
Straight Class Approach
Ratio Approach
 Only generics of companies selling in Canada included
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Investigation Criteria
 N-ATP or any MS-ATP of a new patented drug product exceeds
MAPP during introductory period by more than 5%
 N-ATP of an existing patented drug product exceeds N-NEAP by
more than 5%
 Excess revenues (calculated at national level) for a new or existing
patented drug product are $50,000 or more
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Any Market Price Review
 Intent of statute - ensure prices not excessive in “any market” or
“relevant market”
 At introduction:

Both national and “market-specific” ATPs will be investigated if trigger criteria
 After introduction:
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Monitor National ATP
Review specific markets only if national ATP triggers investigation criteria
 Submarkets:
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Pharmacies, hospitals, wholesalers
Provinces/Territories
 Excess revenue calculated at national level
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Any Market Review – Introductory Period
Assume top of TCC test is $12.00 and HIPC test is $15.00
N-ATP
Year 1
$10.80
W-ATP
$11.00
P-ATP
H-ATP
$11.40
$10.00
MAPP
$12.00
Assume top of TCC test is $12.00 and HIPC test is $10.00
N-ATP
Year 1
$10.00
W-ATP
$11.00*
P-ATP
$10.00
H-ATP
$9.00
MAPP
$10.00
*HIPC test not applied to Wholesaler class of customer, price not excessive
Any Market Review – Existing
(based on second example on previous slide)
Year 1
N-ATP
MAPP
$10.00
$10.00
N-ATP
Year 2
$10.20
W-ATP
MAPP
P-ATP
MAPP
H-ATP
MAPP
$11.00
$12.00 $10.00
$10.00
$9.00
$10.00
N-NEAP W-ATP
W-NEAP P-ATP
P-NEAP
H-ATP
H-NEAP
$11.22 $10.38
$10.20
$9.00
$9.18
$10.40
$9.18
$9.18
$10.20
$11.22
N-ATP = N-NEAP, no review at level of markets
Year 3
$10.47
$10.40
$11.44
$11.44 $10.80
N-ATP > N-NEAP, triggers investigation criteria, review at level of markets
Price in Pharmacy appears to exceed Guidelines. Price must be reduced in
Pharmacy. Excess Revenues calculated based on N-ATP and N-NEAP.
“DIP Methodology”
 If price increase due solely to end or reduction of a benefit,
patentee not held to allowable CPI increases
 Type of Benefit:

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Must conform to ss. 4(4) or 4(5) of the Regulations – “price reduction given
as a promotion or in the form of rebates, discounts, refunds, free goods, free
services, gifts or any other benefits of a like nature”
“DIP Methodology”
Evidence of Benefit
 Form of evidence (e.g., agreement/contract, data requirements) not
specified to allow flexibility given newness of DIP methodology
 However,
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Need to demonstrate that recipient was aware that it was receiving a benefit
not offered to all customers
Need to identify type and value of benefits and when/how it was offered
Provide evidence of termination/reduction of benefits
Need to identify whether recipient is still receiving other benefits
“DIP Methodology”
 Price

If evidence of benefit, ATP of market could increase to highest NEAP of
another market
 Rationale:
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Remove disincentives to offering benefits
“DIP Methodology”
N-ATP
Year 1
$10.00
N-ATP
MAPP
$12.00
N-NEAP
W-ATP
$10.00
W-ATP
MAPP
$12.00
W-NEAP
P-ATP
$10.00
P-ATP
MAPP
$12.00
P-NEAP
Year 2
$8.10
$10.20
$10.20
$10.20
$6.00
$10.20
Year 3
$8.20
$8.20
$10.40
$10.40
$6.00
$6.20
Year 4
$10.60
$8.40
$10.60
$10.60
$10.60
$6.40
N-ATP > N-NEAP, triggers investigation criteria, review at level of markets
Price in Pharmacy appears to exceed Guidelines. Evidence required to
invoke DIP Methodology provided. Price in Pharmacy not excessive as it is
same as W-NEAP.
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Re-setting the NEAP
 Interim MIPC if too few comparator countries; may be reviewed
when sold in 5 countries or after 3 years
 Recognition of possible “cost of making and marketing”

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e.g., once NOC obtained after drug product first sold as Investigational New
Drug, through Clinical Trial Application, or under the Special Access
Programme (SAP)
Filing Requirements
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Form 1 - Medicine Identification Sheet (electronic format
including Product Monograph)
Information
Timing
Identity of the drug Earliest of:
product, patentee
Seven (7) days after the date of
and patent(s)
the first NOC issued
Seven (7) days after date of first
sale in Canada
Updating
Within thirty (30) days after any
information on
modification of information
identity of the drug
product/patentee
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Patent Act Regs
80(1)(a)
80(2)a)
3(1)
3(2)
3(3)
3(4)
FORM 2 - Information on the Identity and Prices of the
Medicine (electronic format)
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Information
Timing
Patent Act Regs
- Price & sales data for the
drug product sold to each
class of customer (H, P, W,
O) by province/territory in
Canada
- Publicly available exfactory price sold to each
class of customer in
Canada and 7 countries
listed in Regulations
- When a drug product is
80(1)(b)
first offered for sale in
80(2)(b)
Canada, no later than thirty
(30) days after the first day
of sales
-Each year:
On or before July 30 (Jan. 1
to June 30 reporting period)
On or before Jan. 30 (July 1
to Dec. 31 reporting period)
4(1)(e)
4(2)
&(3)
4(1)(f)
Where to find Forms on PMPRB Web site
48
Reporting Process
 Form 2 Block 4 and Block 5 templates specific to each company are sent
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49
by PMPRB to patentee approximately 45 days before reporting deadline
Failure to File (FTF):
 Letter advising patentee of FTF
 7 days to file missing information
 Board Order
Data submitted by patentee goes through PMPRB electronic verification
system
Error report generated
Compliance Status reports sent approximately 45 days after reporting
deadline
Upcoming regulatory filing: a gentle reminder
 Form 2 reporting January-June 2009 data due on or before July 30, 2009
 Don’t forget cover sheet i.e. Block 1, 2, 3 and electronic signature
 Block 4 and 5
Strength/unit, dosage form: Follow the template
 DIN, strength/unit, dosage form must be the same on both Blocks
 Pack size: pay attention to the unit in strength/unit to determine the pack size
 Block 5
 Generic name: beware of spelling mistakes
 Ex-factory price for Canada must be reported too
 Ex-factory price for other countries must be in national currency of the country
 Never comment directly on Forms: include a separate document (word or email)
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Communication with Board Staff
 Query to PMPRB Staff
 Guidelines: Ginette Tognet
Tel: (613) 954-8297
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
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
E-mail: [email protected]
Scientific and Introductory price reviews: Catherine Lombardo
Tel: (613) 952-7620
E-mail: [email protected]
Filing Form 1 and 2: Beatrice Mullington
Tel: (613) 952-2924
E-mail: [email protected]
Investigation: Senior Regulatory Officer assigned to it
Form 3: Lokanadha Cheruvu
Tel: (613) 954-9812
E-mail: [email protected]
 All other questions: 1-877-861-2350
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[email protected]