1.2.1.1_Overview of Clinical Trials in Canada_Tanya Ramsamy_e

8/13/2019 1.2.1.1_Overview of Clinical Trials in Canada_Tanya Ramsamy_e

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Helping the people

of Canada maintain and

improve their health

Aider les Canadiens et

les Canadiennes maintenir

et amliorer leur sant

Overview of Clinical Trials in Canada

International Regulatory Forum, 2013

Tanya Ramsamy, PhD,Office of Clinical Trials

Therapeutic Products Directorate

Health Products and Food Branch

Health Canada

ust22, 2007


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Objectives

Overarching principles

Regulatory framework (focus on drugs)

Comparative bioavailability (BE) trials for generics

Organizational structures

CTA statistics


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New population

New route of administration

New disease indications

Exploring

other

applications

Drug Molecule Life as Seen by Regulator

Impact of genericsLarger scaleSmall scale Commercial scale

Years since atent first filed b innovator4 8 12 16 20 24

Continuous monitoring and assessment of safety

Phase

I

Phase

II

Phase

III

1st

Regulat

ory

approv

al

1st

Gen

erics

Non-clinical testing


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Data integrity

Ethics review

Regulations

Trial has

Scientific merit

Protection of

Clinical trial

subjects


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Health Products

AndFood Branch

Therapeutic

Products

Directorate

Biologicsand Genetic

Therapies

Directorate

Natural Health

Products

Directorate

Pharmaceuticals

Medical devices

Biologics

Radiopharmaceuticals

Natural Health

Products

HPFB

Inspectorate


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FOOD AND DRUGS ACT

Food and Drug Regulat ionsPART C: DRUGS

Division 1

Division 1A: Establishment Licences

Division 2: Good Manufacturing Practices

Division 3Division 4

Division 5: Drugs for Clinical Trials Involving Human Subjects

Division 6

Division 7

Division 8

Division 9

Medical Devices Regulat ions

Natural Health Products Regu lat ions(Part 4)


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Division 5: Drugs for Clinical Trials

Involving Human Subjects In effect since September 1st, 2001

Two overarching objectives:

strengthen protections for human research

subjects

increase R & D investment in clinical trials in

Canada


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Division 5 (Contd)

Applies to the sale of a drug for the purposes ofclinical testing in or on humans, independent of

who is sponsoring the trial

Include several definitions

Requirements for authorization of a clinical trial

Clinical trial application (CTA)


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Division 5 (Contd)

Post-authorization requirements

Gives the Minister clear authority to reject,

suspend or cancel the authorization of aclinical trial

Good Clinical Practice (GCP) & inspection


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CTAs are required for

Phase I, II, and III clinical trials

Comparative bioavailability (bioequivalence) trialsfor generics

Study of a product outside the parameters of themarketing authorization

E.g., change in: indication, patient population, dosage

regimen, route of administration


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CTAs are not required for

Phase IV trials (investigations on-label)

But:

REB approval is required

GCP must be observed

record-keeping is required


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Authorization Requirements

Clinical Trial Application (CTA):Attestation

protocol

informed consent form

investigators brochure

chemistry & manufacturing information

2-day turnaround request for additionalinformation

30-day review default period


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Authorization Requirements (Contd)

REB refusals, if any, must be reported

Sponsor must specify the QualifiedInvestigator(s) and trial site(s)

REB approval at each trial site

Changes to the protocol or chemistry &manufacturing that impact on safety must be

filed as an amendment (CTA-A)


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Post-authorization Requirements

Changes that do not impact on safety are filedas CTA-Notifications

Labelling

Record-keeping (25 years) Reporting of serious unexpected adverse drug

reactions

Premature discontinuation of clinical trial

Submission of information and/or samples


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Comparative Bioavailability (BE) Trials

Same regulatory requirements as for other trials

Product monograph may be submitted in lieu of IB

Some different quality requirements, specified in

guidance 7-day administrative review target for studies in healthy

volunteers

The majority of studies are not intended to supportregistration of the generic drug in Canada

Review of comparative bioavailability studies focuses onsafety of clinical trial subjects (usually healthy volunteers)


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Safety Considerations in BE Trials Include:

Study design, choice of dose, and pharmacodynamics

The contraindications, warnings and precautions for the drug

Tuberculosis screening

Pregnancy testing Hb and hematocrit check if total blood volume > 500 mL

Intravenous catheter for multiple blood draws, if appropriate

The risks related to the drug are listed in the informedconsent form and acceptable contraceptive methods are

defined


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Inspection Program

Conducted by the HPFBI, with authority undersection 23 of the Food and Drugs Act

Inspections conducted against requirements of

Division 5 and generally accepted principles ofGCP

Sites chosen at discretion of HC or if complaintsarise

Sites may or may not be forewarned of theplanned inspection


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Pre-CTA Meetings

Present relevant data, clarify requirements,discuss concerns, and resolve potential issues


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Clinical Trials for Natural Health

Products (NHP)

Part 4 of the Natural Health Products Regulations

In effect June 2003August 2012: Office of Clinical Trials authorizes

CTA of NHP for conditions of use not appropriate

for self-care (exception: hormones and probiotics)


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Part 4 NHP Regulations

Authorization requirements are similar for drugsand NHP except:

Request for additional information is not limited to

2 days

No 30-day review default period(CT for NHPs cannot start until a NOA is issued)

CTAInvestigators Brochure must include

preclinical and clinical information if any

REBone member knowledgeable incomplementary or alternative health care

Quality requirements


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Guidance Documents for CTAs for drugs

Guidance for Clinical Trial SponsorsClinical Trial Applications

Quality (Chemistry and Manufacturing) Guidance: Clinical TrialApplications (CTAs) for Pharmaceuticals

Various quality guidance documents for biologics

Requirements for tuberculosis screening Inclusion of women in clinical trials

Standards for clinical trials in type 2 diabetes in Canada

Submission of pharmacogenomic information

Various ICH guidelines Registration and disclosure of clinical trials

Guidance documents from other regulators (e.g., FDA, EMEA)


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0

500

1000

1500

2000

2500

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Number

ofCTAs

Year

Biologics/Radiopharmaceuticals

Bioequivalence

Pharmaceuticals


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References

Division 5 Regulations http://laws.justice.gc.ca/en/F-27/C.R.C.-c.870/

Guidance for Clinical Trial

Sponsors

http://www.hc-sc.gc.ca/dhp-

mps/prodpharma/applic-demande/guide-

ld/clini/ctdcta_ctddec-eng.php

Quality (Chemistry and

Manufacturing) Guidance:

Clinical Trial Applications

(CTAs) for Pharmaceuticals


mps/prodpharma/applic-demande/guide-

ld/clini/qual_cta_dec-eng.php

Quality requirements for

biologics and

radiopharmaceuticals


mps/brgtherap/applic-

demande/guides/qualit/index-eng.php
http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.phphttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.php


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Thank you for your attention!

Questions?