Regulatory Review of Pharmaceuticals,
Biologics and Medical Devices
2004 Annual Summary of Performance
Message from the Assistant Deputy Minister, Health Products and Food Branch (HPFB)
Help on accessing alternative formats, such as PDF, MP3 and WAV files, can be obtained in the alternate format help section.
 (602 K)
 Our Mission is to help the people of Canada
maintain and improve their health
Health Canada
This publication can also be made available in/on
computer diskette/large print/audio-cassette/braille
upon request.
For further information or to obtain additional copies,
please contact:
Publications
Health Canada
Ottawa, Ontario K1A 0K9
Tel.: (613) 954-5995
Fax: (613) 941-5366
E-Mail : info@hc-sc.gc.ca
© Her Majesty the Queen in Right of Canada, 2005
Cat. H1-9/18-2004
ISBN: 0-662-69159-8
Table of Contents
Executive Summary
Since April 2003, new investments through Health Canada's Therapeutics Access Strategy (TAS) have
lead to substantial improvements in the timeliness and efficiency of Canada's review process for therapeutic
products.
A number of business improvements have been introduced over the last two years. Project management
tools and approaches are being implemented to better coordinate tasks at the various stages of the
review process. International harmonization initiatives, such as the adoption by Health Canada of the
Common Technical Document standard for the filing of drug submissions, have helped reduce the
regulatory burden for manufacturers. Those measures, in addition to investments in internal and
external review capacity, are a few examples of new initiatives that have contributed to recent gains
in regulatory performance.
The most dramatic improvement in Health Canada's regulatory performance has been the reduction
of the review backlog of pharmaceutical submissions by 68% from April 2003 to December 2004
(and by 89% by March 2005). In the biologics area, the backlog was reduced by 23% over the period
April 2003 to December 2004 (but this declined to seven percent by March 2005).
Although there is still much progress to be made, more decisions are being made within internationally
comparable time targets. For example, the proportion of regulatory decisions made within time targets
for new pharmaceutical submissions almost doubled in 2004. Twenty-five percent of regulatory decisions
were made within time targets in 2004, up from 13% in 2003. This is particularly significant
given that a large proportion of submissions processed in 2004 were in backlog.
Market authorization decision times were reduced for specific submission categories, including decreases
in the number of days taken in 2004 to approve brand name priority pharmaceuticals (43% decrease
in 2004 in median market authorization time), as well as generic standards (28% decrease in median
market authorization time).
Performance improvements are also being made in the medical devices area. Despite a significant
increase in the workload of medical device applications (an overall 51% increase in 2004, with the
largest growth occurring for Class II devices), 51% of regulatory decisions were made within target
and average market authorization times improved for Class III and IV devices, decreasing by 11% and
17%, respectively.
Other business improvement activities are underway. They include: streamlining project management
practices; implementing an electronic submission and review system; and developing good guidance and
review practices to enhance the quality of submissions and reviews. This will enable Health Canada to
increase the proportion of submissions meeting time targets, with the goal of reaching internationally
comparable review performance (i.e., 90% of regulatory decisions for new drugs made within time
targets) by 2006 for pharmaceuticals and 2007 for biologics.
This report provides an overview of Health Canada's review performance for pharmaceuticals, biologics
and medical devices. The report also includes a snapshot of other decision-making processes beyond the
regulatory system that ultimately influence access by Canadians to therapeutic products.1
Introduction
This report provides an overview of Health Canada's pre-market regulatory review performance of new
therapeutic products including pharmaceuticals, biologics and medical devices in 20042. This report is
not intended to replace the more detailed quarterly and annual Drug Submission Performance Report.3
| The HPFB strives to maintain a balance between the potential benefits and risks of
all health products. Its highest priority in
determining the balance is public safety. |
The Health Products and Food Branch (HPFB) is a sciencebased
organization within Health Canada that carries out
federal responsibilities for the regulation of therapeutic
products and food. HPFB evaluates and monitors the safety,
efficacy and quality of thousands of human and veterinary
drugs, medical devices, natural health products and other
therapeutic products available to Canadians.
| Health Canada's Therapeutics Access
Strategy is a comprehensive initiative
aimed at helping Canadians maintain and
improve their health by ensuring that
human drugs and other therapeutic
products are safe, of high quality,
therapeutically effective, appropriately
used and accessible in a timely and
cost-effective fashion. |
Before a therapeutic product is authorized for sale in
Canada, the manufacturer must file a submission that
provides the HPFB with substantial scientific evidence of
its safety, efficacy and quality, as required by the Food and
Drugs Act and Regulations. This evidence is reviewed by
skilled scientists to determine whether the potential risks
from the product are acceptable when balanced against
the positive effects for the product's proposed use. If the
product shows satisfactory scientific evidence of safety,
efficacy and quality, the product is granted authorization
for sale in Canada.4
Since 2003, through the Therapeutics Access Strategy, new initiatives have been implemented to
modernize Canada's regulatory system by streamlining the review process, encouraging better quality
incoming submissions and improving the timeliness, efficiency and transparency of the review process.
The Therapeutics Access Strategy is expected to help HPFB reach internationally comparable review
performance by 2006 for new pharmaceutical drugs and by 2007 for new biologic drugs.
Review Performance Reporting Framework for
Pharmaceuticals, Biologics and Medical Devices
This report is organized into five sections that summarize data on regulatory review performance for
new drugs and medical devices5 including: workload, decisions, backlog, timeliness and access to new
drugs in Canada. Definitions of the terms used in the report are provided in Annex A.
I. Workload
Number of Submissions Received Annually for New Drugs and
Medical Devices
In 2004, the number of submissions for new drugs received by HPFB increased by six percent
compared with 2003 (see charts 1-A and B).
Generic standard submissions account for the highest area of growth for pharmaceuticals, increasing
by 27% (from 91 to 116) since 2003. This may be due to an increase in the number of multinational
companies seeking to market generic drugs in Canada.
Submissions for priority biologics grew by 80% (from five to nine).6 Breakthrough therapies include
those used in combination with other drugs that provide significant improvement in health outcomes;
and targeted medicines that are capable of attending to the disease process at multiple sites.
Over 5500 medical device submissions were received in 2004, up by 51% from the previous year
(see chart 1-C). Class II and III medical device submissions increased significantly in 2004, with
Class II medical device submissions more than doubling, growing by 107%; and Class III medical
device submissions increasing by 54%.
The recent increase of medical device submissions is indicative of the degree of technological innovation
within the medical devices industry.
In addition to review of submissions for new drugs and medical devices, the HPFB review workload
includes various other types of submissions that are not covered in this report.7
End-of-Year Workload Status of Submissions for New Drugs and
Medical Devices
This section provides data on the number and composition of new drug and medical device submissions
on hand at the end of the calendar year 2004. Backlog refers to submissions for new drugs or
medical devices which have exceeded their review time performance target without the issuance of a
regulatory decision.
| Since 2004, HPFB has been
receiving submissions for new
drugs in the Common Technical
Document (CTD) format. The
CTD is a common international
format that may be used by
manufacturers to submit
submissions for new drugs to
regulatory authorities. The CTD
format will make it easier for submissions to be filed in
Canada and in other countries
at the same time. |
Through the Therapeutics Access Strategy, many improvements
have been made to more efficiently manage the workload of submissions
for new drugs. Submissions are now managed as 'projects' that are planned and coordinated to meet performance targets.
By December 31, 2004, the end-of-year workload of submissions
for new pharmaceutical drugs included fewer backlogged submissions
compared to previous years (see chart 2-A).
Pharmaceuticals backlog accounted for 19% of the total end-of-year
workload in 2004, the smallest such percentage for the past five years.
The percentage of the end-of-year workload of
submissions for new biologic drugs in backlog
was 51% in 2004, down from 68% in 2003 and
the lowest it has been since 2000, when the
backlog was 47% of the end-of-year workload
(see chart 2-B).
At the end of 2004, 18% of the medical
device submissions workload was in backlog
(see chart 2-C).8 |
Biologics are made from living organisms. Their
processes carry risks related to bacterial or viral
contamination. Due to their complexity, biologics require extensive controls to assure their safety, purity, efficacy and consistency in production.
In addition to the paper based scientific review, the
HPFB conducts a laboratory evaluation of both the product and the key test methods used to control it; and an on-site-evaluation (inspection of the facilities) and personnel involved in production. |
|
 
II. Decisions
Regulatory Decisions Issued for Submissions for New Drugs and
Medical Devices9
Once a submission for a new drug or medical device is accepted for scientific review, it can be subject
to a number of possible decisions. For example, if additional information is required from the manufacturer
to support proper review of the submission, an interim decision may be issued that gives the
manufacturer a specified period of time to provide the necessary information.
In 2004, the majority of regulatory decisions that were issued for submissions for new pharmaceutical
and biologic drugs as well as medical devices were market authorizations (see charts 3-A, B and C).
In 2004, nine percent of pharmaceutical regulatory decisions were pending marketing authorizations.
Many of these submissions from earlier years have since been authorized for sale.10
III. Backlog
Progress in Backlog Reduction of Submissions for New Drugs11
Backlog refers to submissions for new drugs or medical devices which have exceeded their review time
performance target without the issuance of a regulatory decision. The number of submissions in backlog
as well as the "age" of the backlog (i.e. the number of days over target) are important and can be
an indicator of underlying issues such as submission complexity, gaps in internal expertise or available
resources, process inefficiencies, or workload increase.
Backlog is a part of the overall review workload and is constantly changing in composition as submissions fall into backlog and previous backlog is eliminated. Addressing the causes of backlog and
ensuring that it remains at low levels will allow for an increasing number of submissions to be
reviewed within internationally comparable targets.
Business improvements introduced through the Therapeutics Access Strategy have contributed to better
workload management and reduction of backlog. This includes new project management tools and
approaches that improve coordination of tasks at various stages of the review process. In addition,
internal and external regulatory review capacity has been enhanced by hiring additional review staff
and introducing improvements to the contracting procedure to enable acquisition of the right external
scientific expertise at the right time.
Progress has been made in reducing the number of submissions in backlog. As of December 31, 2004,
the accumulated backlog had been reduced by 68% for pharmaceuticals compared to the baseline date
of March 31, 2003 (see chart 4-A).12
Notably, the backlog of brand name standard and supplemental submissions had been significantly
reduced (by 76% and 86%, respectively). Backlog of generic standards remained relatively high.
The total backlog of submissions for new biologic drugs was reduced by 23% as of December 31, 2004
compared to the baseline date of March 31, 2003 (see chart 4-B). Supplemental biologics accounted
for the greatest reduction in backlog, with 33% of the backlog eliminated. However, the number of
priority biologics in backlog increased from seven to 11 submissions, (or 57%).
IV. Timeliness
Performance for Review of Submissions for New Drugs and
Medical Devices
Performance targets differ by the type of submission. Different classes of therapeutic products have
different target times for completion of reviews. For example, target review times are significantly
shorter for all classes of medical devices than for other therapeutic products. HPFB's goal is to meet
90% of review performance targets for new drugs by 2006 for pharmaceuticals and 2007 for biologics.
Review Performance Targets for First Decision Concerning Market
Authorization13
| Submission for New Drug |
Target Times |
| (Pharmaceutical and Biologic) |
(Calendar days)* |
| Brand Name Priority/Priority Biologic |
180 or 120 or 200** |
| Brand Name Standard/Standard Biologic |
180 or 300 |
| Brand Name Supplemental/Supplemental Biologic |
180 or 300 |
| Generic Standard |
180 |
| Generic Supplemental |
180 or 300 |
| |
|
| Medical Device Application |
Target Times |
| |
(Calendar days) |
| Class II |
15 |
| Class III |
75 |
| Class IV |
90 |
| Class II, III and IV Amendment Applications are the same as above |
|
*Performance targets do not include processing or screening of submissions for new drugs.
**Target times vary depending on the submission class.
Charts 5-A, B and C provide performance information on all review decisions for submissions for
new drugs and medical devices, including authorizations, pending authorizations, refusals and interim
decisions.
In 2004, the proportion of regulatory decisions made within time targets for new pharmaceutical drugs
almost doubled to 25% compared with 13% in 2003 (see chart 5-A).14 Of the 359 decisions issued, 90
were within target in 2004 compared with 39 within target for the 304 decisions issued in 2003. This is
a significant achievement given that a large proportion of submissions processed in 2004 were in backlog.
Compared with all five years, 2004 had the highest number of review decisions issued for biologics
(totalling 78); 32% more compared with the second highest number (59 decisions issued in 2002
and 2003).
In 2004, 13% of biologic review decisions were made within performance targets compared with 17%
in 2003 (see chart 5-B). The drop in performance may have been influenced by the progress made in
reducing backlog submissions, resulting in fewer decisions made on time, but more decisions made
overall.
In 2004, 51% of review decisions for medical device submissions were made within target
(see chart 5-C)15. Work on new initiatives is continuing to help better manage the workload so
that an increasing number of decisions will be made within performance targets.
Market Authorization Times
This section provides data about all new drug products and medical devices authorized for sale in
Canada. In measuring Canada's time to market authorization, HPFB includes the time from receipt
of a submission to authorization, including the company time required to respond to any questions
or requests for additional information, as well as the time taken to improve deficient submissions. In
many cases, more than one review cycle is required before a new therapeutic product is authorized for
market access16. Market authorization times are different from review performance target times since
the time taken for scientific review is one component of the overall process that is considered in
determining time to authorization.
With fewer submissions in backlog and a greater number of submissions meeting performance targets,
average and median authorization times can be expected to decrease in the year to come.16 Market authorization times are not directly comparable between countries since they reflect different processes and
procedures and each country varies in its approach. These differences include legislation, operational procedures,
performance targets and approaches that are used to track, count and report on performance.
Table 1-A: Market Authorization Times for Pharmaceuticals from 2002-2004
| |
Brand Name Priority |
Brand Name Standard |
Brand Name Supplemental |
| Year |
Number Approved |
Average Days |
Median Days |
Number Approved |
Average Days |
Median Days |
Number Approved |
Average Days |
Median Days |
| 2002 |
9 |
322 |
286 |
24 |
741 |
671 |
68 |
429 |
402 |
| 2003 |
6 |
366 |
382 |
29 |
707 |
688 |
110 |
496 |
433 |
| 2004 |
5 |
217 |
217 |
36 |
876 |
736 |
101 |
404 |
374 |
| |
Generic Standard |
Generic Supplemental |
| Year |
Number
Approved |
Average
Days |
Median
Days |
Number
Approved |
Average
Days |
Median
Days |
| 2002 |
57 |
517 |
489 |
4 |
490 |
379 |
| 2003 |
57 |
551 |
512 |
10 |
569 |
410 |
| 2004 |
83 |
436 |
369 |
10 |
379 |
328 |
In 2004, Brand Name Standard submissions had a 24% increase in average market authorization times
since 2003. This may be a result of the clearance of many backlogged submissions in 2003 and 2004.
Since 2002, all other average market authorization times for pharmaceutical new drug submissions
improved, with the greatest decline observed for Brand Name Priority drugs, decreasing by 41%
since 2003.
Table 1-B: Market Authorization Times for Biologics from 2002-2004
| |
Priority Biologic |
Standard Biologic |
Supplemental Biologic |
| Year |
Number Approved |
Average Days |
Median Days |
Number Approved |
Average Days |
Median Days |
Number Approved |
Average Days |
Median Days |
| 2002 |
5 |
751 |
688 |
7 |
951 |
957 |
39 |
405 |
399 |
| 2003 |
5 |
894 |
958 |
7 |
928 |
876 |
33 |
527 |
404 |
| 2004 |
6 |
874 |
915 |
8 |
1,033 |
1,019 |
54 |
478 |
493 |
Average market authorization times for Standard Biologics increased by 11% in 2004. Although
the authorization time in 2004 was higher than that of 2002, the area of greatest improvement was
Supplemental Biologics, with a reduction in average days to authorization by nine percent compared
to 2003. Priority Biologics had a 16% increase in average authorization times in 2004 compared to
2002 with a slight improvement between 2003 and 2004 by two percent.
Table 1-C: Market Authorization Times for Medical Devices from 2002-2004
| |
Class II |
Class II |
Class IV |
| Year |
Number Approved |
Average Days |
Median Days |
Number Approved |
Average Days |
Median Days |
Number Approved |
Average Days |
Median Days |
| 2002 |
1,725 |
12 |
8 |
455 |
101 |
75 |
106 |
161 |
136 |
| 2003 |
1,478 |
21 |
13 |
554 |
104 |
91 |
111 |
178 |
132 |
| 2004 |
2,745 |
29 |
25 |
613 |
93 |
84 |
106 |
148 |
136 |
| |
Amendment Applications (Class II, III and IV) |
| Year |
Number Approved |
Average Days |
Median Days |
| 2002 |
1,082 |
8 (Class II) 60 (Class III) 115 (Class IV) |
4 (Class II) 33 (Class III) 45 (Class IV) |
| 2003 |
1,099 |
7 (Class II) 79 (Class III) 110 (Class IV) |
4 (Class II) 56 (Class III) 103 (Class IV) |
| 2004 |
1,044 |
18 (Class II) 67 (Class III) 69 (Class IV) |
19 (Class II) 68 (Class III) 85 (Class IV) |
Class II authorization times increased by 38% in 2004 compared with 2003. This may be due to the
increase in workload of this class of devices by 107% (almost 1600 more submissions compared to
2003).
Market authorization times for medical devices improved in 2004 for Class III and IV devices when
compared with 2002 and 2003. Since 2003, time to authorization decreased, on average, by 11% for
Class III and 17% for Class IV.
V. Access to New Drugs
The time it takes for the public to have access to new therapeutic products in Canada is determined
by many factors, including:
- Global marketing strategies of individual manufacturers, which influence where and when they
file their regulatory submissions; and whether and when they will market launch their product in
Canada following a market authorization decision.
- The length of time HPFB takes to review a submission and authorize sale of the product.17
- Decisions taken by other bodies including pricing decisions by the Patented Medicine
Prices Review Board (PMPRB).18
- Formulary listing recommendations by the Common Drug Review (CDR).
- Formulary listing decisions taken by federal, provincial and territorial drug plans and privately
financed drug plans.19
Table 2 displays key decisions that influence access to new drugs in Canada. The drugs listed in
table 2 are those which have been subject to a formulary listing recommendation by the CDR between
January 2004 and April 2005. The CDR does not review generic or over-the-counter drug products,
medicines for use in hospitals, blood products, or vaccines. Hence, this table does not include every
drug which received a market authorization since the fall of 2003.20
Table 2: Access to New Drugs in Canada
Submissions
for New Drugs |
Health Canada
a. Filing Date
b. Approval
Date |
Market
Notification
Date |
PMPRB Price Decision
a. Date of first sale
b. Under PMPRB
jurisdiction
c. Status |
Common Drug Review
a. Filing
b. Recommendation
and Decision Date |
United States
Food and Drug
Administration (FDA)
a. Filing Date
b. Approval Date |
1. Adderall XR - for
treatment of Attention
Deficit Hyperactivity
Disorder (ADHD). |
a. Dec 29 2000
b. Jan 23 2004 |
Jan 30 2004 |
a. Jul 2002
b. Apr 13 2004
c. Under review |
a. Apr 13 2004
b. Not to be listed on
Nov 24 200421 |
a. Oct 3 2000
b. Oct 11 2001 |
2. Avodart - for treatment
of symptomatic Benign
Prostatic Hyperplasia
(BPH) in men with
enlarged prostates. |
a. Dec 3 2001
b. Jul 22 2003 |
Nov 14 2003 |
a. Jan 7 2004
b. Jan 7 2004
c. Within Guidelines,
Nov 2004 |
a. Aug 24 2004
b. For listing on
Jan 20 2005 |
a. Dec 21 2000
b. Nov 20 2001 |
| 3. AXERT - for the acute
treatment of migraine
headache in adults. |
a. Sep 17 2001
b. Sep 29 2003 |
Dec 8 2003 |
a. Jan 9 2004
b. Jan 9 2004
c. Within Guidelines,
Sep 2004 |
a. Dec 24 2003
b. For listing on
May 27 2004 |
a. Dec 17 1999
b. May 7 2001 |
| 4. Ciprodex - for treatment
of ear infections: acute
otitis media with otorrhea
through tympanostomy
tubes in pediatric patients
aged six months and older
and for acute otitis externa
in pediatric and adult
patients aged one year
and older. |
a. Nov 22 2002
b. May 10 2004 |
May 13 2004 |
Not under PMPRB
jurisdiction |
a. Jun 11 2004
b. Not to be listed on
Jan 26 2005 |
a. Sep 23 2002
b. Jul 18 2003 |
| 5. Combigan Ophthalmic
Solution - for treatment
of glaucoma/ocular
hypertension. |
a. Jul 18 2002
b. Dec 9 2003 |
Dec 11 2003 |
a. Dec 9 2003
b. Dec 9 2003
c. Within Guidelines,
Sep 2004 |
a. Dec 15 2003
b. For listing on
May 27 2004 |
Information not
available on FDA
website |
| 6. Evra - to prevent
pregnancy. |
a. Apr 2 2001
b. Aug 20 2002 |
Oct 24 2002 |
a. Oct 2002
b. Oct 2002
c. Voluntary Compliance
Undertaking, Feb 2005 |
a. Dec 19 2003
b. Not to be listed on
Jun 23 2004 |
a. Dec 21 2000
b. Nov 20 2001 |
7. Fabrazyme - for use as a
long-term enzyme replacement
therapy in patients
with Fabry disease. |
a. Aug 7 2000
b. Jan 23 2004 |
Apr 8 2004 -
for DIN
02248966
Sep 17 2004 -
for DIN
02248965 |
Not under PMPRB
jurisdiction |
a. Feb 24 2004
b. Not to be listed on
Nov 24 200422 |
a. Jun 2000
b. Apr 24 2003 |
| 8. Forteo - for treatment of
osteoporosis. |
a. Nov 16 2001
b. Jun 3 2004 |
Jul 15 2004 |
a. Jul 15 2004
b. Aug 17 2004
c. Under review |
a. Jun 28 2004
b. Not to be listed on
Dec 22 2004 |
a. Nov 29 2000
b. Nov 26 2002 |
| 9. Gynazole.1 - for local
treatment of vulvovaginal
infections caused by
Candida albicans. |
a. Jul 30 2001
b. Dec 23 2003 |
Apr 20 2004 |
a. Apr 27 2004
b. Apr 27 2004
c. Within Guidelines,
Nov 2004 |
a. Jun 30 2004
b. Not to be listed on
Jan 26 2005 |
a. Information not
available on FDA
website
b. Feb 7 1997 |
| 10. Humira - for adult
patients with moderately
to severely active rheumatoid
arthritis who have
had an inadequate
response to one or more
disease-modifying antirheumatic
drugs. |
a. May 15 2002
b. Sep 24 2004 |
Sep 24 2004 |
a. Sep 29 2004
b. Sep 29 2004
c. Within Guidelines,
Mar 2005 |
a. Sep 24 2004
b. For listing on
Feb 11 2005 |
a. Information not
available on FDA
website
b. Dec 31 2002 |
| 11. Iressa - for the treatment
of patients with locally
advanced or metastatic
non-small cell lung
cancer after failure of
prior platinum-based and
docetaxel chemotherapy. |
a. Nov 25 2002
b. Dec 17 2003 |
Dec 17 2003 |
a. Dec 17 2003
b. Dec 17 2003
c. Within Guidelines,
Oct 2004 |
a. Dec 22 2003
b. Not to be listed on
Jun 23 2004 |
a. Aug 2 2002
b. May 5 2003 |
12. Neulasta - reduction in
the duration of neutropenia
and the incidence of
febrile neutropenia in
patients treated with cytotoxic chemotherapy
for malignancy (with
the exception of chronic
myeloid leukaemia and myelodysplastic
syndromes). |
a. Jun 28 2001
b. Mar 12 2004 |
Mar 12 2004 |
a. Apr 12 2004
b. Apr 12 2004
c. Under review |
a. Mar 29 2004
b. To be listed on
Oct 27 2004 |
a. Information not
available on FDA
website
b. Jan 31 2002 |
| 13. Pegasys RBV - for treatment
of adults with
chronic hepatitis C who
have compensated liver
disease and who have not
been previously treated
with interferon alfa 2. |
a. Aug 20 2002
b. May 10 2004 |
May 26 2004 |
a. May 26 2004
b. May 26 2004
c. Under review |
a. May 14 2004
b. To be listed on
Oct 14 2004 |
a. Jun 3 2002
b. Dec 3 2002 |
| 14. Relpax - for the acute
treatment of migraine
with or without aura
in adults. |
a. Mar 21 2003
b. Aug 5 2004 |
Oct 13 2004
|
a. Nov 1 2004
b. Nov 1 2004
c. Within Guidelines,
Mar 2005 |
a. Sep 21 2004
b. Not to be listed on
Mar 23 2005 |
a. Oct 27 1998
b. Dec 26 2002 |
| 15. Remodulin - for the
treatment of pulmonary
arterial hypertension
(PAH). |
a. Dec 17 2001
b. Oct 4 2002 |
Apr 30 2004 |
a. Oct 7 2004
b. Oct 7 2004
c. Within Guidelines,
Mar 2005 |
a. Jul 14 2004
b. Not to be listed on
Nov 17 2004 |
a. Oct 16 2000
withdrawn
Jul 5 2001
Re-filed:
Aug 9 2001
b. May 21 2002 |
| 16. Replagal - for long-term
enzyme replacement
therapy in patients with
Fabry Disease. |
a. Sep 10 2000
b. Feb 6 2004 |
Mar 18 2004 |
Not under PMPRB
jurisdiction |
a. Feb 19 2004
b. Not to be listed on
Nov 24 2004 |
a. Jun 16 2000
b. Information not
available on FDA
website |
17. Reyataz - for the treatment
of HIV-1 infection
in combination with
other anti-retroviral
agents. |
a. Mar 21 2003
b. Dec 5 2003 |
Jan 9 2004 |
a. Jan 2004
b. Nov 2 2004
c. Under review |
a. Dec 16 2003
b. To be listed on
May 27 2004 |
a. Dec 20 2002
b. Jun 20 2003 |
| 18. Sensipar - for the
treatment of secondary
hyperparathyroidism in
patients with Chronic
Kidney Disease. |
a. Nov 14 2003
b. Aug 9 2004 |
Sep 16 2004 |
Not under PMPRB
jurisdiction |
a. Aug 20 2004
b. Not to be listed on
Mar 23 2005 |
a. Sep 5 2003
b. Mar 8 2004 |
| 19. Teveten Plus - for
treatment of mild to
moderate essential hypertension
in patients for
whom combination
therapy is appropriate. |
a. Feb 22 2001
b. Jun 8 2004 |
Jul 6 2004 |
a. Jul 6 2004
b. Jul 6 2004
c. Within Guidelines,
Mar 2005 |
a. Jul 8 2004
b. To be listed on
Dec 15 2004 |
a. Aug 30 2000
b. Nov 1 2001 |
| 20. Viread - for treatment
of HIV-1 infection in
combination with other
anti-retroviral agents in
adults who have experienced
virologic failure
on other regimens. |
a. Dec 28 2001
b. Mar 18 2003 |
Mar 15 2004 |
a. Mar 15 2004
b. Mar 15 2004
c. Advance Ruling
Certificate, Jun 3 2004 |
a. Feb 23 2004
b. Not to be listed on
Aug 25 2004 |
a. Apr 30 2001
b. Oct 26 2001 |
| 21. VFEND - for treatment
of invasive aspergillosis. |
a. Sep 3 2003
b. Aug 20 2004 |
Nov 12 2004 |
a. Nov 15 2004
b. Nov 15 2004
c. Within Guidelines,
Mar 2005 |
a. Oct 25 2004
b. To be listed on
Apr 14 2005 |
a. Nov 17 2000
b. May 24 2002 |
| 22. Zavesca - for treatment
of adults with mild
to moderate Type 1
Gaucher disease for
whom enzyme replacement
therapy is not a
therapeutic option. |
a. Aug 27 2003
b. Mar 31 2004 |
May 26 2004 |
a. May 26 2004
b. May 26 2004
c. Within Guidelines,
Nov 2004 |
a. May 13 2004
b. Not to be listed on
Nov 24 2004 |
a. Apr 20 2001
b. Jul 31 2003 |
Annex A: Definitions
These plain language definitions are intended for general understanding and are not necessarily the formal definitions used by Health Canada or those that appear in the legislation or regulations.
1. Therapeutic Product Types
The following therapeutic product types are described in this report.
- Pharmaceuticals: drugs that are mostly synthetic products that are made from chemicals.
Pharmaceuticals include prescription and non-prescription drugs such as antibiotics, disinfectants,
as well as low risk products such as sunscreens, antiperspirants and toothpaste.
- Biologics: drugs that are made from biological starting material, including those produced using
recombinant DNA procedures. They include vaccines, blood and blood products and many
hormonal products such as insulin. Radiopharmaceuticals (drugs that contain radioactive components)
are included as part of this product group in this report as they are regulated by the same
program within the HPFB.
- Medical Devices: any article or instrument used in the diagnosis, treatment, mitigation, or
prevention of a disease, disorder, or abnormal physical state and in restoring, correcting, or
modifying organic functions in humans or animals. Devices range from band-aids to pacemakers
and also include those used in the prevention, diagnosis and care of pregnancy.
2. Submissions for New Drugs and Medical Devices
The focus of this report is on submissions for new drugs and medical devices. Definitions are provided below.
- Submission for New Drugs: include the following submission types for pharmaceuticals and biologics, where 'brand name' and 'generic' refers to pharmaceuticals.
(a) Priority (Brand Name or Biologic): submissions for products intended for the treatment, prevention,
or diagnosis of serious, life-threatening, or severely debilitating illnesses or conditions where:
no product is presently marketed in Canada or; the new product represents a significant increase in
efficacy and/or significant decrease in risk such that the overall benefit/risk profile is improved over
existing therapies. Submissions granted priority review status are subject to the same quality, safety
and efficacy requirements as non-priority submissions - with shorter performance target times. In
this report, priority includes the Notice of Compliance with Conditions submission type (refer to
Regulatory Decision Types below for more information).
(b) Standard (Brand Name or Biologic): a submission that contains scientific information about the
product's safety, efficacy and quality and is typically 100 to 800 binders of data. It includes: the
results of both the pre-clinical and clinical studies; details regarding the production of the drug;
its packaging and labelling; information regarding therapeutic claims; conditions for use; and
side effects.
(c) Supplemental (Brand Name, Generic, or Biologic): submissions to support proposed changes to
already authorized products. Such changes might include: changes to the dosage form or strength
of the drug product; labelling; recommended route of administration; and expanded indications
(claims or conditions of use) for the drug product.
(d) Generic Standard: submissions that demonstrate that the proposed generic product is as safe and
efficacious and manufactured to the same quality standards as the brand name product. Typically
between 10 and 20 binders of data, the submission includes scientific information that shows how
the generic product performs compared with the brand name product, as well as details regarding
production, packaging and labelling.
- Medical Device Submissions: includes the application types listed below.
(a) Medical Device Applications: medical devices are categorized into four classes based on the classification
rules of the Medical Devices Regulations. Class I devices present the lowest potential risk
(e.g. thermometers) and do not require a medical device licence for their sale in Canada. Class II,
III and IV devices range from low, moderate, to high risk, respectively and manufacturers must
obtain a medical device licence before their products can be legally sold in Canada. As the class
of the device increases, more data is required from the manufacturer in support of safety and
effectiveness of the device.
(b) Medical Device Amendment Applications: changes to a licensed medical device (Class II, III,
or IV) - such as a change in design, indications, or additions/deletions of identifiers.
3. Regulatory Decision Types
For this report, four decision types are provided, including: market authorizations; pending market
authorizations; interim decisions; and refusals. Further detail on each decision type is outlined below.
- Market Authorizations: apply to submissions for new drugs and medical devices that have been
authorized for sale in Canada.
(a) Notice of Compliance: if, at the completion of a review of a submission for a new drug, HPFB
concludes that the benefits outweigh the risks and that the risks can be mitigated and/or managed,
the product is issued a Notice of Compliance (NOC). This allows the manufacturer to sell the
product in Canada.
(b) Notice of Compliance with Conditions (NOC/c): may be granted to provide earlier market
access to potentially life-saving drugs. Eligibility is restricted to drugs intended for the treatment,
prevention, or diagnosis of serious, life-threatening, or severely debilitating illnesses or conditions
where promising clinical evidence indicates that the product provides an effective treatment where:
no alternative therapy is available on the Canadian market; or the new product represents a significant
improvement in the benefit/risk profile over existing products. An NOC/c provides the manufacturer
authorization to market a drug with the condition that it undertakes additional studies to
confirm the clinical benefit. Conditions associated with approval allow HPFB to monitor the safety
and effectiveness of the drug through enhanced post-market surveillance.
(c) Medical Device Licence: upon completion of a medical device application review, HPFB concludes
that the evidence exists to support the safety and effectiveness of the device as required by
the regulations, a Medical Device Licence is issued, allowing the manufacturer to sell the device
in Canada.
(d) Medical Device Licence with Conditions: HPFB may issue a Medical Device Licence with
Conditions when there is reasonable assurance that the device is safe and effective, but where
supplemental information would further support this conclusion. Such information must be
submitted within a prescribed timeframe.
- Pending Market Authorizations: apply to those submissions for new drugs that have been provided
with an 'issuable' NOC but are not yet authorized for sale due to outstanding regulatory issues that require
resolution. Examples of situations where a "pending market authorization" would be issued include submissions
where an NOC cannot be issued due to the Patented Medicine (Notice of Compliance) Regulations or
submissions where changes are required to existing Food and Drug Regulations to change the drug status from
prescription to non-prescription.
(a) Issuable NOC (Patent): HPFB may issue an NOC that is on hold due to Patent Regulations.
(b) Issuable NOC (Rx to OTC): HPFB may issue an NOC that is on hold due to a change in status
of the drug from prescription to over-the-counter.
- Interim Decisions: apply to submissions for new drugs and medical devices that contain deficiencies
and are deficient vis a vis the regulatory requirements for market authorization. These regulatory decisions
(described below) have provided the manufacturer with a notice of the information required and a time
period in which to respond with the missing documentation.
(a) Notice of Deficiency: If a major deficiency is detected that prevents completion of the scientific
review of a submission for a new drug, HPFB can issue a Notice of Deficiency (NOD). The
manufacturer is provided with a specified period in which to respond with the required information.
(b) Notice of Non-Compliance: If, upon completion of the new drug review, the submission is found
to be deficient vis a vis the requirements of the Food and Drugs Act and Regulations, a Notice of
Non-Compliance (NON) may be issued. This notice outlines all the outstanding issues and requests
for information that HPFB has about the submission. The manufacturer has a specified period in
which to respond with the required information.
(c) Additional Information Letter: If, during the course of the scientific review of a medical device
application, there remains insufficient information to determine whether the device meets the safety
and effectiveness requirements, an Additional Information Letter may be issued, providing the
manufacturer with a specified period in which to respond with the required information.
- Refusals: are final decisions where the manufacturer has been provided with the opportunity to improve
the submission or application but has been unable to satisfy the requirements of the Food and Drugs Act and
Regulations. In the case of a refusal, a manufacturer may re-file a new application at a future time, without
prejudice. Refusal decision types are outlined below.
(a) Notice of Deficiency Withdrawal Letter: May be issued if the manufacturer fails to submit the
requested information in response to a NOD within the required time period, or the response
contains unsolicited information, is incomplete or deficient.
(b) Notice of Non-Compliance Withdrawal Letter: May be issued if the manufacturer fails to submit
the requested information in response to a NON within the required time period, or the response
contains unsolicited information, is incomplete or deficient.
(c) Refusal Letter: May be issued if the manufacturer fails to submit the requested information in
response to an Additional Information Letter within the required time period, or the response
contains unsolicited information, is incomplete or deficient.
Annex B: The Role of the Patented Medicine Prices
Review Board and the Common Drug
Review
Price Review - The Patented Medicine Prices Review Board
The Patented Medicine Prices Review Board (PMPRB) is an independent quasi-judicial administrative
agency, responsible for regulating the prices that patentees charge, the "factory-gate" price for prescription
and non-prescription patented drugs sold in Canada to wholesalers, hospitals, or pharmacies for
human and veterinary use, to ensure that they are not excessive. The PMPRB regulates the price of
each patented drug product, including each strength of each dosage form of each patented medicine
sold in Canada.
Under the Patented Medicines Regulations, patentees are required to file price and sales information
twice a year for each strength of each dosage form of each patented medicine sold in Canada for price
regulation purposes. Patentees are also required to file research and development expenditures once a
year for reporting purposes. Manufacturers must inform the PMPRB of their intention to sell a new
patented medicine but are not required to obtain approval of the price before they do so.
Common Drug Review - The Canadian Coordinating Office for Health
Technology Assessment
The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) is Canada's health
technology agency whose goal it is to increase access to and use of evidence as a basis for informed
decisions about technology use in Canada's publically funded health care system.
Since September 2002, CCOHTA's mandate was expanded to include the Common Drug Review
(CDR), a single process to assess new drugs for potential coverage by participating federal, provincial and
territorial drug benefit plans. CCOHTA develops evidence-based clinical and pharmacoeconomic reviews
which are used by the Canadian Expert Drug Advisory Committee, an independent advisory body of
professionals in drug therapy and evaluation, as the basis for its formulary listing recommendations to the
participating drug plans. Federal, provincial and territorial governments continue to make final formulary
listing decisions, taking into account recommendations provided by CDR.
1 For more information on progress, refer to 'Regulation and Beyond: Progress on Health Canada's Therapeutics Access
Strategy', available at
http://www.hc-sc.gc.ca/hcs-sss/pubs/care-soins/2005-therap-strateg/index_e.html
2 See Annex A for definitions of pharmaceuticals, biologics and medical devices.
3 The Drug Submission Performance Report uses different definitions and terminology to outline performance statistics and
is therefore not directly comparable. For more information refer to
http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/docs/perform-rendement/index_e.html
4 Cost-effectiveness considerations are examined by organizations outside of HPFB (refer to Section V: Access to New Drugs
in Canada).
5 For consistency and to simplify terminology, medical device applications are referred to as 'submissions' throughout
the report.
6 Compared to other therapeutic products, a high proportion of biologics are designated as priority submissions.
7 Other submission types not included in this report are Clinical Trial Applications, Investigational Testing Applications
(for medical devices), Notifiable Changes, Drug Identification Number Applications and Faxback Amendment
Applications (for medical devices).
8 Data on medical devices workload prior to 2004 is not available.
9 See Annex A, for definitions of regulatory decisions for submissions for new drugs and medical devices.
10 Note: Pending Market Authorizations are counted once; those that have subsequently been approved for sale are not
counted again as Market Authorizations.
11 Backlog information for medical devices is not included since baseline data is not available. Backlog data for medical
devices will be provided in future editions of this report.
12 As of March 31, 2005, 89% of the pharmaceuticals backlog and seven percent of the biologics backlog had been eliminated.
13 For further information on performance targets, refer to The Guidance for Industry on the Management of Drug
Submissions and The Management of Applications for Medical Device Licenses and Investigational Testing Authorizations
available at
http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/mgmt-gest/index_e.html and
http://www.hc-sc.gc.ca/dhp-mps/md-im/applic-demande/pol/mdlapp_demhim_pol_e.html respectively.
14 Cancellations are excluded from charts 5-A, B and C.
15 Data for medical devices covers the third and fourth quarter (last six months) and not the full year of 2004. Validated
data on medical devices review performance prior to 2004 is not available.
16 Market authorization times are not directly comparable between countries since they reflect different processes and procedures and each country varies in its approach. These differences include legislation, operational procedures, performance targets and approaches that are used to track, count and report on performance.
17 Note that HPFB has mechanisms in place such as the Special Access Program, that enable interim access to new drugs or
medical devices. For more information, refer to: http://www.hc-sc.gc.ca/dhp-mps/acces/index_e.html.
18 More details on the role of the PMPRB and CDR are provided in Annex B.
19 Federal, provincial and territorial governments manage drug formularies and assess the drugs for which reimbursement
from government plans is available. In some cases, drugs have a restricted status limiting coverage to particular types of
patients or situations.
20 CDR commenced during the fall of 2003.
21 Adderall XR was resubmitted to CDR for review and subsequently withdrawn as it was suspended from the Canadian
market on Feb 9, 2005. Adderall XR returned to the Canadian market in August 2005 following recommendations
made by an independent New Drug Committee appointed by Health Canada. For more information, refer to
http://www.hc-sc.gc.ca/ahc-asc/media/nr-cp/2005/2005_92_e.html
22 Fabrazyme was resubmitted to CDR for review and recommended not to be listed on May 18 2005.
|
