Docket:
T-306-11
Citation: 2012
FC 976
Ottawa, Ontario,
August 29, 2012
PRESENT: The
Honourable Mr. Justice Boivin
BETWEEN:
|
|
DUCHESNAY INC.
|
|
|
|
Applicant
|
|
and
|
|
|
THE ATTORNEY GENERAL OF CANADA
THE MINISTER OF HEALTH
|
|
|
|
Respondents
|
|
|
|
|
PUBLIC REASONS
FOR JUDGMENT
(Confidential
Reasons for Judgment issued August 9, 2012)
[1]
This is an application for judicial review of a decision rendered
by the Director General of the Therapeutic Products Directorate (TPD) of Health
Canada (respondent), dated January 21, 2011, whereby a Notice of Deficiency –
Withdrawal (NOD-W) letter was issued in response to a Supplemental New Drug
Submission (SNDS) filed by Duchesnay Inc. (applicant), on April 30, 2009.
[2]
The applicant seeks an order granting the application for judicial
review, quashing the respondent’s decision, and ordering the respondent to
analyze, on an expedited basis, the full contents of the applicant’s SNDS and
to amend the Product Monograph (PM) for the applicant’s drug DICLECTIN®.
Regulatory
Context
[3]
Pursuant to the Food and Drugs Act, RSC, 1985, c F-27
[Act], the respondent, Health Canada, regulates and oversees the drug
submission process in Canada. Drug manufacturers, such as the applicant, are
required to file a New Drug Submission (NDS) pursuant to Section C.08.002 of
the Food and Drug Regulations, CRC, c 870 [Regulations], in order to
have a new drug product approved. Health Canada may then issue a Notice of
Compliance (NOC) for the drug, in accordance with Section C.08.004 of the
Regulations, if the drug is deemed to be safe and effective. Once a NOC is
issued, any changes to the drug that amount to a “significant difference” from
the information or material contained in the NDS must be carried out by way of
a SNDS, as set out in Section C.08.003 of the Regulations. Health Canada may then issue a NOC for the SNDS or choose to issue a Notice of Deficiency (NOD) if
the applicable requirements are not met.
[4]
A comprehensive explanation of a drug’s PM is outlined in the
respondent’s publication Guidance for Industry: Product Monograph (PM
Guidance) (Respondent’s Confidential Record, Volume 1, Tab 3, pp 55-56):
1.2 What
Is a Product Monograph?
A product monograph
is a factual, scientific document on the drug product that, devoid of
promotional material, describes the properties, claims, indications, and
conditions of use for the drug, and that contains any other information that
may be required for optimal, safe, and effective use of the drug. A product
monograph should include appropriate information respecting the name of the
drug, its therapeutic or pharmacologic classification, its actions and/or
clinical pharmacology, and its indications and clinical uses. The monograph
should also include contraindications, warnings, precautions, adverse
reactions, drug interactions and effects on laboratory tests, symptoms and
treatment of overdosage, dosage and administration, storage and stability,
pharmaceutical information, dosage forms, pharmacology, toxicology,
microbiology, special handling instructions, information on clinical trials,
information for the consumer, references, and the dates of the initial printing
and current revision.
1.3
Medical and Scientific Implications
From a medical and
scientific standpoint, the prime objective of a product monograph is to provide
essential information that may be required for the safe and effective use of a
new drug.
As far as the health
professional is concerned, the information provided should be as meaningful and
helpful as possible. However, only those indications and clinical uses that
are based on substantial evidence of efficacy and safety and that are the
subject of a New Drug Submission, or an Abbreviated New Drug Submission, or a
supplement to either submission that has received a Notice of Compliance
pursuant to Section C.08.004 of the Food and Drug Regulations, should be
included in the product monograph. The product monograph is not intended to
serve as a repository of all information currently available on a drug.
Nevertheless, it should be borne in mind that the responsibility of a health
professional, when prescribing a drug, involves all of the relevant facts
relating to that use.
[Emphasis
added]
Factual
Background
[5]
The
factual background of this case is of the utmost importance and a thorough
overview of the facts is accordingly in order.
[6]
The applicant is an innovative pharmaceutical
company based in Quebec that manufactures DICLECTIN®, a medication approved by
the respondent to treat the nausea and vomiting suffered by pregnant women.
DICLECTIN® received a NOC on November 23, 1983.
Studies 02163
and 02191
[7]
In
2004, nearly twenty years after receipt of a NOC, the applicant submitted a
SNDS in order to update the PM with respect to a change in the formulation of
DICLECTIN®. The applicant submitted two bioavailability studies (studies 02163
and 02191) to the respondent in support of the new formulation of the
medication. The studies were conducted by MDS Pharma Services. Study 02163 compared
the administration of DICLECTIN® as a tablet versus as an oral solution and
studied the parameters of each means of administration. Study 02191 consisted
of a food effect study, which looked at how food affected the metabolism of the
drug.
[8]
The
SNDS was approved by the respondent in 2005 and the PM was amended accordingly.
However, the applicant alleges that, shortly after the studies were filed, the
American Food and Drug Administration (FDA) expressed concerns about the
reliability of the studies conducted by MDS Pharma Services. Consequently, the
applicant chose to have the studies independently audited by Bioclinical
Research Solutions, LLC. The applicant contends that the audit revealed serious
problems with the reliability of study 02191 (the food effects study). The
applicant then advised the respondent of the audit and of its intention to redo
the studies in question.
Studies 70294
and 70381
[9]
As
such, in 2008, the applicant commissioned two new bioavailability studies on
DICLECTIN® (studies 70294 and 70381) in order to correct the problems that had
been previously identified and to ensure that the PM contained complete and
up-to-date information. The new studies were conducted by Anapharm, a PharmaNet
company. Essentially, study 70294 was a new food effect study while study
70381 was a single-dose and multi-dose study. The applicant
alleges that the new studies revealed previously unknown pharmacokinetic
properties. The applicant explains that study 70294 revealed that food reduces
the amount of DICLECTIN® that can be used by the body. As well, study 70381
determined that when multiple doses of DICLECTIN® are ingested, the drugs
accumulate in the body and there is significant change in how it is absorbed,
distributed, metabolized and eliminated (ADME process). To ensure these
results, the applicant had the new studies audited for accuracy by Bioclinical
Research Solutions, LLC.
[10]
The
results of the new studies were of some concern for the applicant as it was
well known that instances of “off label dosage” were taking place – where
physicians would prescribe more than the recommended dose of the drug to
patients. The applicant submits that it felt that it was its duty to inform
physicians of the results of the studies – namely those pertaining to dose accumulation
(study 70381) – as the drug was being prescribed to a highly vulnerable
population. For the applicant, the most effective way of sharing this new
information was by way of an amendment to the PM.
[11]
Therefore,
on April 30, 2009, the applicant filed another SNDS with the respondent in
order to correct and update the information included in the PM for DICLECTIN®
that had been approved in 2005. The following changes were sought by the
applicant to the PM: i) remove the pharmacokinetic data from
the old studies; ii) add the pharmacokinetic data from studies 70294 and 70381;
and iii) add the safety information that allegedly arose from the old studies
and the new studies. The applicant affirms that the respondent charged a
fee of $52,900 before it would review the SNDS – although ultimately 75% of
this amount was charged to the applicant ($39,675.00).
[12]
One
year later, the respondent indicated that it was beginning its review of the
applicant’s submission. On April 15, 2010, the respondent’s Division of Biopharmaceutics
Evaluation (DBE2) requested that the applicant complete a Comprehensive Summary
– Bioequivalence (CS:BE) form for the two old studies and the two new studies.
[13]
On
May 14, 2010, the applicant submitted its completed CS:BE forms for the two new
bioavailability studies and advised the respondent that the CS:BE forms were
not necessary for the two old studies because they were not presented in
support of the SNDS.
[14]
A
teleconference was held on May 26, 2010, and the applicant was notified of a pending
NOD decision.
[15]
On
May 31, 2010, the applicant received a NOD from the respondent advising that
its SNDS and the new studies would not be accepted and that the PM would not be
amended. The respondent explained that the “data from studies 70294 and 70381
do not provide any additional relevant pharmacokinetic information further to
that which is already present in the product monograph” (Applicant’s Confidential
Record, Volume 1, Tab 10, p 231).
[16]
On
June 18, 2010, the applicant responded to the NOD (the NOD-Response) and
explained the significance of the information provided by the new
bioavailability studies. The applicant outlined that the new bioavailability
studies were superior to the previous ones as the new studies were able to
measure all of the active metabolites and assessed all of the appropriate
pharmacokinetic parameters.
[17]
On
December 9, 2010, the applicant was informed in an email by the Bureau of
Cardiology, Allergy and Neurological Sciences (BCANS) of Health Canada of the proposed changes to the PM for DICLECTIN® pertaining to some of the
safety-related findings of studies 70294 and 70381.
[18]
On
December 12, 2010, Dr. Cathy Petersen of BCANS participated in a phone
conversation with the applicant and discussed the proposed new wording for the
PM.
[19]
On
December 13, 2010, Dr. Cathy Petersen of BCANS called and informed the
applicant that DBE2 had rejected the new bioavailability studies. The
respondent alleges that Dr. Petersen also advised the applicant that there
would be further rewording changes recommended for the PM.
[20]
On
December 15, 2010, the Regulatory Project Manager of BCANS sent an email to the
applicant outlining three options: 1) the applicant could receive a Notice of
Deficiency –Withdrawal (NOD-W) with a requirement to file a follow-up
Notifiable Change (NC) to revise the Product Monograph (PM) to include the
updates to safety data identified as a result of the review; 2) the applicant
could remove the updates from the PM pertaining to studies 70294 and 70381, the
SNDS review would proceed for the safety updates and if acceptable, a Notice of
Compliance would be issued for the safety changes; or 3) the applicant could
voluntarily withdraw its SNDS.
[21]
On
December 17, 2010, a teleconference was held in which the respondent provided
the applicant with further clarification of the deficiencies with their
submission. During the teleconference, the applicant indicated that it would
prefer to be issued a NOD-W and requested a detailed explanation of the reasons
supporting the NOD-W.
[22]
On
January 21, 2011, the respondent issued a formal NOD-W to the applicant, which
included the reviewer reports. The NOD-W letter
listed five points which addressed the scientific validity of the new studies.
The letter also outlined that the applicant was entitled to file a Request for
Reconsideration of the respondent’s decision.
[23]
On February 22, 2011, the applicant filed a Request for
Reconsideration pursuant to the Guidance for Industry – Management of Drug
Submissions and the Guidance: Reconsideration of Final Decisions Issued
for Human Drug Submissions. On February 23, 2011, the applicant
filed an application for judicial review with the Federal Court (T-306-11) as
well as an action for damages against the respondent (T-322-11). In accordance with the rules outlined in Guidance:
Reconsideration of Final Decisions Issued for Human Drug Submissions, the
reconsideration process was then terminated in light of the filing of the
notice of application.
[24]
On January 31, 2012, a Confidentiality Order was rendered
by Prothonotary Morneau.
Decision
under review
[25]
The formal NOD-W dated January 21, 2011, issued to the applicant,
stated the following:
In accordance with the Management of
Drug Submissions guidance, Section 5.5.1, this is to notify you that the
Supplemental New Drug Submission for DICLECTIN (doxylamine
succinate/pyridoxine hydrochloride), control number 129701 is
considered withdrawn without prejudice to a refiling.
After review of the information and
material submitted in response to the Notice of Deficiency dated May 31, 2010,
it has been determined that the submission does not comply with the
requirements of the Food and Drug Regulations.
As discussed with the sponsor in a
telephone conversation on January 13, 2010, the NOD-W is based on the
following:
The designs of studies 70294 and 70381
resulted in a large number of deficient subject concentration-time profiles for
the pyridoxine and pyridoxal analytes. These deficiencies are considered to be
serious and pharmacokinetic estimates drawn from these profiles cannot be
considered reliable. In addition, the audit conducted by Bioclinical Research
Solutions, LLC does not demonstrate that the data from studies 02191 and 02163
are in fact unreliable. Therefore, the pharmacokinetic data from studies 02191
and 02163 in the current PM should be retained and the pharmacokinetic data
from studies 70294 and 70381 should not be included in their proposed form.
The sponsor did not submit information
to support the clinical relevance of the findings in the 70381 study and no
clinically relevant changes to the PM were proposed. The proposed changes were
to replace the current studies (02191 and 02163) with the new studies (70294
and 70381). In addition, the PM does not contain information regarding the
clinical importance of any of the pyridoxine metabolites. Rather it states that
the “metabolites including pyridoxal have biologic activity”. However,
regarding study 70381 it is noted that even though methodologically faulty, the
study shows a potential accumulation of doxylamine (and pyridoxine
metabolites), of unknown clinical significance. The sponsor may submit an NC
where mutually agreeable wording could be found for some of the pharmacokinetic
findings from study 70381 that the sponsor wishes to disclose. However, the entire
study cannot be included in the PM, due to methodological deficiencies.
The sponsor’s formal request that the
TPD policy for pyridoxine be updated based on the new data presented has been
noted.
Should you wish to file a Request for
Reconsideration please refer to Health Canada’s Guidance for Industry:
Reconsideration of Final Decisions issued for Human Drug Submissions.
Should you wish to refile this
submission, please refer to the Management of Drug Submissions guidance,
Section 5.7: Refiled Submissions.
The reviewer reports will be provided
following receipt of this Notice, in accordance with Section 6.1 of the
Therapeutic Product Directorate’s guidance on Management of Drug Submissions.
You will find attached a copy of the
reviewer reports.
Issues
[26]
This case raises the following issues:
1)
Is the applicant entitled to submit a new affidavit and evidence
pursuant to Rule 312?
2)
Did the respondent err in rejecting the applicant’s SNDS?
3)
Did the respondent commit a breach of procedural fairness?
Relevant
Legislation
[27]
The legislation pertaining to this application consists of Federal
Courts Act, RSC 1985, c F-7, the Federal Courts
Rules, SOR/98-106 (Rules) and the
Regulations. The relevant provisions thereof have been attached to this
judgment as an Appendix.
Standard
of Review
[28]
The parties both agree on the applicable standards of
review. With respect to issue no. 2 before the Court, it is trite law that decisions based on findings of fact are
to be reviewed according to the reasonableness standard (Canada (Citizenship and Immigration) v Khosa, 2009 SCC 12, [2009] 1 S.C.R. 339; Dunsmuir v New
Brunswick,
2009 SCC 9, [2008] 1 S.C.R. 190). Regarding issue no. 3, the
parties agree that the applicable standard of review for questions of
procedural fairness is the standard of correctness (Sanofi Pasteur Ltd v Canada (Attorney General), 2008 FC 286, [2008] FCJ No 352; Hoechst Marion Roussel Canada Inc v
Canada (Attorney General), 2005 FC 1552, [2005] FCJ No 1928).
Issue 1:
Applicant’s Motion Pursuant to Rule 312
[29]
This judicial review was heard on Monday April 23, 2012. On
Wednesday April 18, 2012, the applicant filed a Notice of Motion for leave to
file an affidavit of Sylvie Bergeron including Exhibit A “the transcript of the
examination for discovery of Kimby N. Barton”, dated February 1, 2012, held in
Court file T-322-11, pursuant to Rule 312 of the Rules. Court file
T-322-11 is an action for damages based on the same facts as in file T-306-11.
[30]
This motion was contested by the respondent and was therefore
heard at the beginning of the judicial review hearing on April 23, 2012.
[31]
On the basis of the submissions made by the parties at the
beginning of the hearing, the Court accepted the documents of the applicant
under reserve and also accepted the document from the respondent held in file
T-322-11, entitled “examination for discovery – deposition of Michael Gallo”
dated January 23, 2012, under reserve and under the same conditions. Having had
the opportunity to hear the parties and read the said documents, leave to file
the documents at issue is denied for the following reasons.
[32]
In Atlantic Engraving Ltd v Lapointe
Rosenstein, 2002 FCA 503, [2002] FCJ No 1782 [Lapointe Rosenstein],
the Federal Court of Appeal held that the Court may allow the filing of
additional affidavits when the evidence sought to be adduced :
i.
will serve the interests of justice;
ii.
will assist the Court;
iii.
will not cause substantial or serious prejudice to the
other side;
iv.
was not available prior to the cross-examination of the opponent’s
affidavits.
[33]
The Court observes from the outset, that the examination
for discovery of Ms. Barton was conducted on February 1, 2012, and was held
pursuant to Rule 234 and following of the Rules in a distinct proceeding
(T-322-11). The Court thus agrees with the respondent that granting the
applicant’s motion for the purposes of adducing the said affidavit in the
context of the present proceeding would prejudice its right to confidentiality.
Indeed, to do so, would run counter to the implicit obligation of
confidentiality concerning evidence or information obtained at an examination
for discovery and the interests of justice would not be served by acceding to
the applicant’s motion (see Lac d’Amiante du Québec Ltée v 2858-0702 Québec
Inc., 2001 SCC 51 at paras 60 and 64, [2001] SCJ No 49 [Lac d’Amiante du
Québec Ltée]).
[34]
In fact, examination in the context of an action for
damages (T-322-11) is much broader than examination in the context of a
judicial review and, as such, the applicant is asking the Court to
“cross-pollinate” evidence between the action for damages and the present
judicial review. The applicant was cognizant of this and, moreover,
Prothonotary Morneau explicitly addressed the concern of a potential improper
use of importing the evidence obtained by the applicant in the action for
damages proceeding (T-322-11) into the context of the judicial review
proceeding (T-306-11). In his Reasons for Order and Order in Court file
T-322-11 dated July 22, 2011, Prothonotary Morneau observed the following:
[24] Par ailleurs, le défendeur a
fait valoir à l’audition que si le dossier dans l’action se poursuit et que les
procédures sous la Demande de contrôle judiciaire se poursuivent également, la
demanderesse et son procureur dans l’action auront vraisemblablement accès à
plus d’information et de documents que ce qu’ils pourraient obtenir dans le
cadre de la Demande de contrôle judiciaire. Ceci pourrait faire que la
demanderesse pourrait en quelque sorte importer et se servir dans la Demande de
contrôle judiciaire des éléments d’informations obtenus dans l’action.
[25] Ce n’est là toutefois pour
l’instant qu’une hypothèse et, de plus et à tout événement, tous savent très
bien que la demanderesse de même que son procureur sont tenus, entre autres,
par la règle de l’engagement implicite quant aux informations apprises dans un
dossier particulier. Ce serait présumer d’intentions illicites que de faire
échos aux craintes exprimées par la défenderesse.
[35]
The Court further recalls that the Supreme Court of Canada in Lac d’Amiante du Québec Ltée, above, at paragraph 76, cautioned against
relieving a party from the rule of confidentiality as to do so too routinely
“would compromise the usefulness of the rule, if not its very existence.
….”. In the case at bar, the Court remains unconvinced by the argument that the
applicant should be relieved of the obligation of confidentiality in the
interests of justice.
[36]
In addition, the Court recalls that the applicant filed its
Notice of Motion at the eleventh hour. The applicant made this request
forty-three (43) days after it received the transcript and seventy-seven (77)
days after it examined Ms. Barton. The Court further notes that counsel for the
applicant in file T-306-11 also appeared as counsel for the examination for
discovery in file T-322-11 and could thus have made its request much earlier.
At hearing, the applicant failed to prove that the additional evidence could
not have been made available at an earlier date. It follows that the
applicant’s motion is time-barred as it was not filed at the first opportunity.
To accede to such a belated motion would not, in the circumstances, serve the
interests of justice.
[37]
In light of the above and on the basis of the requirements
outlined in Lapointe Rosenstein, above, leave is therefore denied.
Consequently, the applicant’s affidavit of Sylvie Bergeron including Exhibit A
“the transcript of the examination for discovery of Kimby N. Barton” and the
respondent’s document entitled “examination for discovery –
deposition of Michael Gallo” dated January 23, 2012 are to be withdrawn from the Court record.
Issue
2: Did the Respondent err in rejecting the Applicant’s SNDS?
[38]
The
applicant submits that the decision of January 21, 2011 should be set aside
pursuant to subsection 18.1 (4) of the Federal Courts Act on the grounds
that the respondent breached the principle of procedural fairness and based its
decision on erroneous findings of fact.
[39]
The
Court will first address the applicant’s allegation concerning the erroneous
findings of fact.
[40]
In
challenging the respondent’s decision, the applicant has presented to the Court
a myriad of detailed and fact-intensive arguments. However, in essence, the
applicant is seeking to demonstrate that it is entitled to modify the PM.
[41]
As
a preliminary step, it is useful to address the following question: What is a
PM and what is its objective?
[42]
From
a medical and scientific standpoint, Health Canada’s policy on PMs states that
the prime objective of a PM is to provide essential information (not any
information) that may be required for the safe and effective use of a drug. The
information contained in a PM should be as meaningful and helpful as possible.
A PM is a factual and scientific document about a drug product that describes
the properties, claims, indications and conditions of a drug. The policy
further states that a PM is not intended to serve as a repository of all
information currently available on a drug. Moreover, the policy indicates that
“[n]evertheless, it should be borne in mind that the responsibility of a health
professional, when prescribing a drug, involves all the relevant facts relating
to that use” (Respondent’s Confidential Record, Volume 1,
Tab 3, p 56).
[43]
Against
this background, a party seeking to modify a PM will be required to provide
essential and appropriate information for the safe and effective use of the
drug at issue. It stems from the PM Guidance that a PM is not meant to be used
as a means of communicating study results to researchers. Hence, and in
spite of the
fact that raw data might be interesting for research purposes, they are not
essential for a physician.
Relevance and Reliability of
Studies 70294 and 70381
[44]
In
the present circumstances, upon submitting its request to modify the PM, the
applicant was required to demonstrate the clinical relevance of the information
reflecting the efficacy and safety of the drug. The respondent contends that
the applicant filed 44 binders of information in support of its SNDS, with no
narrative, and failed to explain how the findings of the studies had an impact
on the efficacy of the drug.
[45]
It
is well-known that the respondent – Health Canada – has extensive expertise in
assessing what information should be included in the PM and what information
should not. In matters of drug submissions, the jurisprudence of this Court has
shown particular deference towards the respondent (Reddy-Cheminor, Inc. v Canada (Attorney General), 2004 FCA 102, [2004] FCJ No 433; Hospira Healthcare Corp. v Canada
(Attorney General), 2010 FC 213, [2010] FCJ No 405).
[46]
The
first notice sent to the applicant by the respondent on May 31, 2010 stated
concerns in terms of relevancy of the studies and concluded as follows
(Applicant’s Confidential Record,
Volume 1, Tab 10, p 231):
It is the opinion of the DBE2 that the data from
studies 70294 and 70381 do not provide any additional relevant pharmacokinetic
information further to that which is already present in the product monograph.
[47]
The
applicant disagrees with the respondent’s position and argues that studies 70294
and 70381
presented new and relevant information that necessarily had to be included in
the PM and that the respondent committed an error in finding that the new
studies were not clinically relevant.
[48]
Whilst
the applicant emphasizes that the results of studies 70294 and 70381
dramatically affected the dosage and administration of the drug at issue, the
Court notes that, in the course of the process requesting a modification to the
PM, the applicant made no changes to the Dosage and Administration requirements
in the proposed amended PM (Respondent’s Confidential Record,
Volume 1, Tab 11, p 237).
[49]
More
specifically, there are no suggested changes with respect to the impact of food
(study 70294) or the dosage (study 70381). The Court notes that the concern
about reliability of Study 70294 (food effect) was also communicated by the
respondent to the applicant on May 12, 2010 (Applicant’s Confidential Record,
Volume 1, Tab 10, p 234) and then reiterated on January 21, 2011 (Applicant’s Confidential Record,
Volume 2, Tab 17, p 307). The evidence also shows that a significant proportion
of defects in the first, second and fourth column of the 70294 chart at the
highest measure of concentration mark (Cmax) (Applicant’s Confidential Record,
Volume 2, Tab 17, p 322).
[50]
With
respect to study 70381, the applicant failed to clearly submit and explain to
the respondent the suggested changes in terms of the clinical relevance of the
study. The respondent acknowledges that a typographical error occurred in the
form of a “cut and paste” but the Court agrees that this error is not fatal in
the case at bar given that study 70381 was found to lack clinical relevance. Be
that as it may, even if study 70381 might have been more reliable without the
typographical error, the Court agrees with the respondent that the absence of
any such flaw would not have made the study more relevant for purposes of
including it in the PM.
[51]
While
it may be true that without the typographical error, DBE2
may have conducted a more thorough examination of study 70381 (Applicant’s Confidential Record, Ms. Barton in cross-examination, Tab D, p 403
(page 150 of the transcript)), the reality is that the
generality of the information still stands and no further information was
provided to the Court as to why the numbers with respect to those studies were
relevant – as opposed to possibly reliable – and should be included in the PM.
In these circumstances, the problems
that were identified with the single-dose portion of the study were sufficient
for the respondent to conclude on the study’s relevance and it was not
necessary to consider and analyze the multi-dose portion of the study.
[52]
The
present proceeding being a judicial review, there were no expert witnesses
presented to the Court. Having considered the evidence on record and the
parties’ respective submissions, the arguments of the applicant with respect to
the respondent’s findings on the relevance of both studies (70294
and 70381) have not convinced the Court that the said relevance findings by the
respondent are unreasonable.
Safety Issue
[53]
The
Court recalls that notwithstanding the respondent’s contention that both
studies (70294 and 70381) cannot be included in the PM, it acknowledged during
the process that study 70381 might show potential for accumulation.
[54]
As
the issue of accumulation relates to safety, the respondent conceded that there
might be a concern in this regard and accepted that some of the safety
information that arose from these studies could be included in the PM. In order
to address this concern pertaining to the possible
dose accumulation of the drug as per study 70381, the evidence demonstrates
that the respondent was open and willing to admit statements with respect to
safety in the PM provided that the information could be accurately presented by
the applicant.
[55]
During the hearing before the Court, counsel for the respondent
explained that modifications with respect to safety and more particularly the
recommended wording concerning the possible dose accumulation involve a lower
threshold and can thus be addressed and resolved more rapidly.
[56]
In this case, this information concerning possible safety changes
was in fact communicated to the applicant prior to the decision being rendered.
The respondent further indicated that, assuming acceptable modifications, it
would issue a Notice of Compliance (NOC) (Applicant’s Confidential Record, Volume 2, Tab 14, p 299).
[57]
However, it seems that the applicant nonetheless insisted that the
entire study (or studies) be included in the PM. In that respect, the evidence
demonstrates that the applicant did not follow up on the respondent’s suggestion and recommendation. Indeed, the applicant did
not submit a proposed statement or suggest appropriate wording regarding the
dosage recommendation provided to the physicians (Applicant’s Confidential Record, Volume 2, Tab 14, p 299 and Tab 17, p
307). In other words, the applicant ignored
the respondent’s offer to provide more specific and relevant information with
respect to the issue of safety and failed to make changes to the Dosage and
Administration requirements in the proposed amended PM. In these circumstances,
the Court cannot accept the applicant’s contention that the
respondent’s rejection of the SNDS means that physicians will continue to
prescribe DICLECTIN® ignorant of how the new study results might affect a
vulnerable portion of the population. The applicant simply remained inflexible
in the face of the respondent’s recommendation in this regard and the
respondent cannot be faulted for the applicant’s failure to follow-up on the
recommendation.
Comprehensive
Summaries: Bioequivalence forms (CS:BE forms)
[58]
A
further argument made by the applicant, in support of its contention that the
respondent erred, is that the respondent failed to review its
CS:BE forms before rejecting the SNDS. The applicant states that upon receiving
the NOD on May 31, 2010, it learned of a memorandum dated May 12, 2010 wherein
DBE2 outlined that it had already rejected the new studies two days before the
applicant had submitted its CS:BE forms (May 14, 2010). The
applicant asserts that DBE2 made no efforts to contact the applicant before it
issued the May 12, 2010 memorandum in order to advise that the forms, and the
extensive work required to complete them, were no longer necessary. The
applicant also alleges that the respondent erred by requesting the applicant to
submit the CS:BE forms as studies 70294 and 70381 dealt with bioavailability
rather than bioequivalence.
[59]
In
this regard,
the Court observes that CS:BE forms – which follow a particular template
provided by Health Canada – provide a summary of the submission and hence do
not include new information. The CS:BE forms were requested from the applicant
as per standard procedure. The respondent explains
that the
only difference between a bioequivalence and a bioavailability assessment is
that bioequivalence compares two situations, whereas bioavailability only
examines one. In the end, however, both amount to the same exercise. Ms. Kimby
Barton’s explanation in her affidavit on this point are apposite (Respondent’s Confidential
Record, p 10, at paras 51-53):
51. A CS:BE aids reviewers in
their assessment of pivotal comparative bioavailability studies. A comparative
bioavailability study is considered to be pivotal if the results from the study
are used to support the safety and efficacy of the drug product.
52. Since a completed CS:BE is a
summary, it does not include any new information. It is, however, a useful
tool. By summarizing information found in multiple documents, and directing
reviewers to where documents can be found within the drug submission, a CS:BE
helps reviewers provide consistent and timely evaluation.
53. The CS:BE is not an official
requirement. However, if a submission includes one or more pivotal comparative
bioavailability study(ies), completed CS:BEs are usually included in the
documents provided by the sponsor at the time of filing. If CS:BEs are not
provided at the time of filing, it is standard practice for Health Canada to request that the sponsors complete a CS:BE for each pivotal comparative
bioavailability study. This request is made proactively prior to the file being
reviewed in detail, to avoid further delays in the review process should such a
summary be of assistance.
[60]
A
further issue
before the Court was whether the respondent took into account the applicant’s
CS:BE forms before issuing the NOD on May 31, 2010. On this issue, the Court
agrees with the respondent to the effect that the new studies were deficient and
did not demonstrate clinical relevance and, this fact alone was sufficient to
dismiss the submission. Ms. Barton also explained in her affidavit that, in
some cases, the CS:BE will not have any impact on the decision because of the
significant deficiency (Respondent’s Confidential Record, p 10, para 54):
54. In some cases, however, a decision about a submission is made
by a reviewer without having to refer to the CSBEs provided by the sponsor. In
particular, if there is a significant enough deficiency in the submission, the
review stops, and the CS:BEs provided by the sponsor may not be used.
[61]
Therefore,
in light of the above and considering the deficiencies identified
with the data provided by the new studies (70294 and
70381), the Court is of the view that the respondent did not commit a
reviewable error in rejecting the applicant’s SNDS. The Court finds that the
respondent’s decision was a reasonable one.
[62]
The Court now turns to the issue of procedural fairness.
Issue 3: Did the Respondent Commit a Breach of Procedural Fairness?
[63]
The
applicant maintains that the respondent breached its duty of fairness in the
circumstances (Baker v Canada (Minister of Citizenship and Immigration), [1999] SCJ No 39, [1999] 2 S.C.R. 817 [Baker]. For
the reasons that follow, the Court is of the view that there was no such breach
committed by the respondent.
[64]
The Court is of the view that that the decision-making process in
the case at bar is more akin to an administrative process than a judicial
process. Therefore, the degree of fairness owed in the present case is lower
than the degree of fairness owed in the context of a judicial proceeding (Canadian Pharmaceutical Technologies International (C.P.T.) In. v Canada (Attorney General), 2009 FC 244, [2009] FCJ No 435 [C.P.T.];
Apotex In. v Canada (Minister of Health), 2009 FC 452, [2009] FCJ No
577).
[65]
More particularly, the Court notes that the process in the
circumstances is a flexible one. For instance, the fact that a sponsor may
re-file following a negative decision and request a reconsideration is
reflective of a process that is administrative. The applicant also acknowledges
that there was no legal obligation on the part of the respondent to meet with
the applicant and that an oral hearing was not required to be conducted
(Transcript, p 38, lines 6-7 & 21-23).
[66]
The Court’s review of the record and evidence leads it to conclude
that an adequate review of the applicant’s submission was conducted by the
respondent. This review revealed several fatal deficiencies in the applicant’s
submission and it was thus reasonable for the respondent to bring its review of
the submission to an end.
[67]
The applicant nonetheless alleges that the respondent failed to
conduct a comprehensive review. Yet, the evidence demonstrates that the issues raised by the applicant in its NOD-Response (June 18, 2010) were
identified and addressed by the respondent (see Applicant’s Confidential Record, Volume 2, Tab 14 (email dated December 15, 2010);
Respondent’s Confidential Record, Volume 2,
Tab 22 (email dated December 17, 2011); Applicant’s Confidential Record, Volume 2, Tab 17 (Notice of Deficiency –
Withdrawal Letter (NOD-W dated January 21, 2011)). Hence, the Court
cannot agree with the applicant that there was a failure to provide reasons. In
fact, reasons were given in the NOD by the respondent and the applicant was
given an opportunity to respond in writing. The applicant’s response was
considered and the respondent confirmed its original decision in the NOD-W.
[68]
Also,
the Court cannot agree with the applicant that the respondent added concerns in
its NOD-W; rather, the NOD-W merely responded to each of the points made by the
applicant in its NOD-Response and included the reviewer reports. Further,
the Court observes that the respondent responded to the
applicant’s request and the applicant was provided with opportunities to
communicate with the respondent – including a teleconference (Applicant’s Confidential Record, Volume1, Tab C (Affidavit of Michael Gallo), p 18,
para 63; Applicant’s Confidential Record,
Volume 1, Tab 9, pp 226-227). In this case, the decision-making
process has to be viewed in a continuum and, as it was unfolding, the
respondent answered the applicant’s concerns as
and when they were expressed.
[69]
The
Court likewise rejects the argument that the process was not entirely
transparent and points to the review conducted by Dr. Zoltan
Gombos of BCANS (Applicant’s Confidential Record, Volume 2, Tab 17, p 327). The
research conducted by Dr. Gombos merely demonstrates that the respondent
took an additional step and performed a literature and a web site search to
verify whether there would be any mention of clinical relevance. Nothing of
significance was found.
[70]
Finally, there is the issue of the Reconsideration process.
This mechanism was explicitly created to allow for reconsideration
of a decision and provides a party with further opportunity to respond to
concerns about the studies outlined in the NOD-W. While the applicant submitted
a request for reconsideration it also concurrently filed an application for
judicial review before the Court. In doing so, the applicant chose to terminate
the Reconsideration process. Pursuant to the Guidance for Industry:
Reconsideration of Final Decisions Issued for Human Drug Submissions “[i]f,
at any time during the Reconsideration process, the sponsor files a Notice of
Application to the Federal Court to resolve the matter, the Directorate will
terminate the Reconsideration process” (Respondent’s Confidential Record, Volume 2, Tab 24, pp 387 & 392).
[71]
The applicant emphasized that the Director General issued both the
NOD and the NOD-W, which gave the applicant cause to doubt that there would be
any meaningful review during the Reconsideration process given that it was also
to be carried out by the Director General. Again, the Court cannot accept the
applicant’s argument in this regard as it was in no way precluded from
raising this concern during the Reconsideration process.
[72]
After
reviewing the evidence and hearing the parties, the Court finds that the
respondent’s decision, when read as a whole and in its proper context, is
reasonable and that the respondent did not commit a breach of procedural
fairness (Baker, above; Newfoundland and
Labrador Nurses' Union v Newfoundland and Labrador (Treasury Board), 2011 SCC 62 at paras 16, 20, 22 and 23, [2011] 3 S.C.R. 708).
[73]
The Court’s
intervention is accordingly not warranted. The application for judicial review
will be dismissed.
POSTCRIPT:
[1]
These
Reasons for Judgment are un-redacted from Confidential Reasons for Judgment
which were issued on
August 9, 2012
pursuant to the Court's Direction dated August
9, 2012. Pursuant
to the letter dated August 15, 2012 sent by the applicant and the letter dated
August 16, 2012 sent
by the respondent,
the references to the "Applicant's Record" and the
"Respondent's Record" have been corrected to read "Applicant's
Confidential Record" and "Respondent's Confidential Record".
“Richard Boivin”
Email this Content