Science Homework

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

QUAL50950: CTD Approval Process

Module 3: Common Technical Document (CTD) Structure

February 13, 2024

Ms. Shahin Malam

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Agenda

Introduction to CTD

Transition From CTD to eCTD

Overview of eCTD Format

Overview of NDS eCTD Format to Health Canada

Transmission and Validation of eCTD Submissions

Questions

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Evolution of CTD

• Back in the 1980s, the task of transferring regulatory information

to a health authority involved palettes of boxed paper

submissions - a large logistical undertaking that included dense

printing and dedicated regulatory storage departments

• In 1997, the ICH formed the ICH M8 Expert Working

Group/Implementation Working Group

• This group created the CTD, which standardized applications

submitted to regulatory authorities

• In 2003, the original eCTD was adopted by health authorities

and sponsors both in the U.S. and around the world, and eCTD

v3.2.2, the current default version internationally, was

established in 2008

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

The Common Technical Document • ICH - M4: CTD is a joint effort of 3 regulatory agencies: EMA, FDA and Ministry

of Health, Labor and Welfare, Japan

• The agreement to assemble all the Quality, Safety and Efficacy information in a

common format (called CTD - Common Technical Document) has revolutionized

the regulatory review processes, led to harmonized electronic submissions that

enable good review practices.

• The CTD is organized into five modules. Module 1 is region specific and

Modules 2, 3, 4 and 5 are intended to be common for all regions. In July 2003,

the CTD became the mandatory format for new drug applications in the EU and

Japan, and the strongly recommended format of choice for NDAs submitted to

FDA, United States and to NDS’s submitted to Health Canada.

https://www.ich.org/page/ctd

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Benefits of CTD

✓ Reduces time and resources used to compile

applications

✓ Eases preparation of electronic submissions

✓ Facilitates simultaneous review of submissions

✓ Facilitates easier exchange of regulatory information,

thereby ensuring faster availability of new medicines

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Shift From CTD to eCTD

• With the aim of overcoming the challenge of managing huge volumes of

paper-based product data and to enable faster and efficient submissions,

an electronic equivalent of CTD was introduced as eCTD which is now

considered the preferred format

• EMA began accepting eCTD submissions in 2003; In February 2015, the

"EMA announced it would no longer accept paper application forms for

products applying to the centralized procedure beginning July 1, 2015:

• On May 5, 2015, FDA published a final, binding guidance document

requiring certain submissions in eCTD within 24 months.

• In July 2016, Health Canada stated that as of January 1st, 2018, major

regulatory submissions must be filed in eCTD format

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Benefits of eCTD The new standard has proven to have substantial benefits to both health

authorities and industry, some of which include:

✓ More precise submissions

✓ Reduced duplication of submissions because of better organization of

documents

✓ Less storage is required for maintaining the information across multiple

product lifecycles

✓ It is a single application format

✓ It reduces total cost of submission lifecycle process

✓ eCTD is the submission of (mostly) PDF leaf documents, stored in the eCTD

directory structure, crucially accessed through the XML backbone (index.xml)

and with the files integrity guaranteed by the MD5 Checksum.

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 1: Administrative and Prescribing Information (not strictly included in the CTD since documents and format are region specific)

Module 2: Common technical document summaries (summaries of Modules 3-5)

Module 3: Quality

Module 4: Non-Clinical Study Reports

Module 5: Clinical Study Reports

CTD Contains Five Modules

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 1: Administrative Information • FDA: The Comprehensive Table of Contents Headings and

Hierarchy: https://www.fda.gov/media/76444/download

• EMA: EU Module 1 eCTD Specifications Version 3.0.4

https://esubmission.ema.europa.eu/eumodule1/EU%20M1%20eCTD

%20Spec%20v3.0.4.pdf

• Health Canada: Notice - Guidance Document: Creation of the

Canadian Module 1 Backbone https://www.canada.ca/en/health-

canada/services/drugs-health-products/drug-products/applications-

submissions/guidance-documents/ectd/notice-creation-canadian-

module-1-backbone-2012-health-canada-consultation-

document.html#a2

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Mandatory eCTD Human Drug Submissions in Canada

Division 8 - Prescription and non-Prescription (Human Drugs only) – including Administrative (i.e. NDS, ANDS) and Labelling ONLY regulatory activities

Division 8 - Post-market Vigilance Data (Human Drugs only)

Drug Master Files (Human Drugs only)

Regulatory activities for medical device applications and veterinary drugs remain out of scope for filing in eCTD

format; they must be filed in “non-eCTD electronic-only” via zip folders

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Health Canada NDS: Module 1 https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/ectd/notice-creation-canadian-module-1-backbone-2012-health-

canada-consultation-document.html

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 2 eCTD Folder Structure

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 3 eCTD Folder Structure

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 4 eCTD Folder Structure

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 5 eCTD Folder Structure

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Transmission of Electronic Data to Health Canada

• All regulatory transactions in eCTD format must be sent via the

Common Electronic Submissions Gateway (CESG), with the

exception of those exceeding 10 gigabytes (GB) in size which

would require:

• Universal Serial Bus (USB) 2.0 or 3.0 drive

• Portable External Hard Drive with USB 2.0 or 3.0 interfaces

• Either would need to be sent to HC with a hardcopy cover

letter

• Prior to using the CESG for sending transactions, sponsors

must register as a trading partner

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

eCTD Software

• Specialized software is needed in order to compile documents

into eCTD format for submission

• This usually involves software that allows both publishing and

viewing of the eCTD submission

• Almost 15 years after its last update, eCTD’s latest version has

been finalized and is being rolled out internationally

• eCTD v4.0 offers significant advancements in the way that

sponsors and regulatory bodies handle submissions, and

adapting to these improvements will be mandatory across all

major regulatory authorities by 2028 (earlier, in many regions).

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Validation of eCTD Submission • Validation checks are needed to ensure compliance with eCTD

specifications – submission may be rejected if not done correctly

• Validation is an important processing component and should be

done on all eCTD submissions regardless of the method of

submission

• Validate all eCTD submissions prior to sending to Health Canada

• Health Canada also performs additional validation checks for

both eCTD and non-eCTD submissions once a submission is

received

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

CTD Prototype Project – NDS Assigned: Feb 13, 2024 Due: March 5, 2024

Weight: 25% of Final Grade As discussed in class, the ICH M4: The Common Technical Document is an agreement to assemble

all the Quality, Safety and Efficacy information in a common format (called CTD - Common Technical Document). The CTD has revolutionised the regulatory review processes and led to harmonized electronic submissions that enable good review practices. For industries, it has eliminated the need to reformat information for submissions to the different ICH regulatory authorities. In Canada, most submissions to Health Canada must be submitted in the CTD format. As a regulatory affairs project manager for a small start up biotechnology company, you have been asked to prepare a new drug submission (NDS) through the regular (non accelerated) pathway for a new oncology product named “Sheridanumab”. You have been tasked with preparing all Module 1 and 2 documents. The remaining Modules will be prepared by other colleagues.

1. Create a prototype of your NDS submission for Modules 1 and 2, listing all relevant documents that you would need to file and what CTD section it would go in. Please organize your Modules using the following format:

2. List all guidance document(s) you used to determine how to build your prototype.

3. Why is it important that the NDS be submitted in CTD format?

General Instructions: • The Prototype project should follow the APA format with font size 12 and 1.5 spacing, Times New Roman. • A title page should be included in addition to the page limit. The title page should contain information such as Student Name, Student ID, Prototype title, course code etc.

CTD Section Document(s)/Forms you would provide in the section*

1.0.1 Cover Letter etc.

<<Continue this table as you see fit>>

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Questions

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

QUAL50950: CTD Approval Process

Module 3: Common Technical Document (CTD) Structure

February 13, 2024

Ms. Shahin Malam

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Agenda

Introduction to CTD

Transition From CTD to eCTD

Overview of eCTD Format

Overview of NDS eCTD Format to Health Canada

Transmission and Validation of eCTD Submissions

Questions

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Evolution of CTD

• Back in the 1980s, the task of transferring regulatory information

to a health authority involved palettes of boxed paper

submissions - a large logistical undertaking that included dense

printing and dedicated regulatory storage departments

• In 1997, the ICH formed the ICH M8 Expert Working

Group/Implementation Working Group

• This group created the CTD, which standardized applications

submitted to regulatory authorities

• In 2003, the original eCTD was adopted by health authorities

and sponsors both in the U.S. and around the world, and eCTD

v3.2.2, the current default version internationally, was

established in 2008

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

The Common Technical Document • ICH - M4: CTD is a joint effort of 3 regulatory agencies: EMA, FDA and Ministry

of Health, Labor and Welfare, Japan

• The agreement to assemble all the Quality, Safety and Efficacy information in a

common format (called CTD - Common Technical Document) has revolutionized

the regulatory review processes, led to harmonized electronic submissions that

enable good review practices.

• The CTD is organized into five modules. Module 1 is region specific and

Modules 2, 3, 4 and 5 are intended to be common for all regions. In July 2003,

the CTD became the mandatory format for new drug applications in the EU and

Japan, and the strongly recommended format of choice for NDAs submitted to

FDA, United States and to NDS’s submitted to Health Canada.

https://www.ich.org/page/ctd

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Benefits of CTD

✓ Reduces time and resources used to compile

applications

✓ Eases preparation of electronic submissions

✓ Facilitates simultaneous review of submissions

✓ Facilitates easier exchange of regulatory information,

thereby ensuring faster availability of new medicines

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Shift From CTD to eCTD

• With the aim of overcoming the challenge of managing huge volumes of

paper-based product data and to enable faster and efficient submissions,

an electronic equivalent of CTD was introduced as eCTD which is now

considered the preferred format

• EMA began accepting eCTD submissions in 2003; In February 2015, the

"EMA announced it would no longer accept paper application forms for

products applying to the centralized procedure beginning July 1, 2015:

• On May 5, 2015, FDA published a final, binding guidance document

requiring certain submissions in eCTD within 24 months.

• In July 2016, Health Canada stated that as of January 1st, 2018, major

regulatory submissions must be filed in eCTD format

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Benefits of eCTD The new standard has proven to have substantial benefits to both health

authorities and industry, some of which include:

✓ More precise submissions

✓ Reduced duplication of submissions because of better organization of

documents

✓ Less storage is required for maintaining the information across multiple

product lifecycles

✓ It is a single application format

✓ It reduces total cost of submission lifecycle process

✓ eCTD is the submission of (mostly) PDF leaf documents, stored in the eCTD

directory structure, crucially accessed through the XML backbone (index.xml)

and with the files integrity guaranteed by the MD5 Checksum.

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 1: Administrative and Prescribing Information (not strictly included in the CTD since documents and format are region specific)

Module 2: Common technical document summaries (summaries of Modules 3-5)

Module 3: Quality

Module 4: Non-Clinical Study Reports

Module 5: Clinical Study Reports

CTD Contains Five Modules

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 1: Administrative Information • FDA: The Comprehensive Table of Contents Headings and

Hierarchy: https://www.fda.gov/media/76444/download

• EMA: EU Module 1 eCTD Specifications Version 3.0.4

https://esubmission.ema.europa.eu/eumodule1/EU%20M1%20eCTD

%20Spec%20v3.0.4.pdf

• Health Canada: Notice - Guidance Document: Creation of the

Canadian Module 1 Backbone https://www.canada.ca/en/health-

canada/services/drugs-health-products/drug-products/applications-

submissions/guidance-documents/ectd/notice-creation-canadian-

module-1-backbone-2012-health-canada-consultation-

document.html#a2

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Mandatory eCTD Human Drug Submissions in Canada

Division 8 - Prescription and non-Prescription (Human Drugs only) – including Administrative (i.e. NDS, ANDS) and Labelling ONLY regulatory activities

Division 8 - Post-market Vigilance Data (Human Drugs only)

Drug Master Files (Human Drugs only)

Regulatory activities for medical device applications and veterinary drugs remain out of scope for filing in eCTD

format; they must be filed in “non-eCTD electronic-only” via zip folders

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Health Canada NDS: Module 1 https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/ectd/notice-creation-canadian-module-1-backbone-2012-health-

canada-consultation-document.html

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 2 eCTD Folder Structure

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 3 eCTD Folder Structure

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 4 eCTD Folder Structure

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Module 5 eCTD Folder Structure

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Transmission of Electronic Data to Health Canada

• All regulatory transactions in eCTD format must be sent via the

Common Electronic Submissions Gateway (CESG), with the

exception of those exceeding 10 gigabytes (GB) in size which

would require:

• Universal Serial Bus (USB) 2.0 or 3.0 drive

• Portable External Hard Drive with USB 2.0 or 3.0 interfaces

• Either would need to be sent to HC with a hardcopy cover

letter

• Prior to using the CESG for sending transactions, sponsors

must register as a trading partner

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

eCTD Software

• Specialized software is needed in order to compile documents

into eCTD format for submission

• This usually involves software that allows both publishing and

viewing of the eCTD submission

• Almost 15 years after its last update, eCTD’s latest version has

been finalized and is being rolled out internationally

• eCTD v4.0 offers significant advancements in the way that

sponsors and regulatory bodies handle submissions, and

adapting to these improvements will be mandatory across all

major regulatory authorities by 2028 (earlier, in many regions).

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Validation of eCTD Submission • Validation checks are needed to ensure compliance with eCTD

specifications – submission may be rejected if not done correctly

• Validation is an important processing component and should be

done on all eCTD submissions regardless of the method of

submission

• Validate all eCTD submissions prior to sending to Health Canada

• Health Canada also performs additional validation checks for

both eCTD and non-eCTD submissions once a submission is

received

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

CTD Prototype Project – NDS Assigned: Feb 13, 2024 Due: March 5, 2024

Weight: 25% of Final Grade As discussed in class, the ICH M4: The Common Technical Document is an agreement to assemble

all the Quality, Safety and Efficacy information in a common format (called CTD - Common Technical Document). The CTD has revolutionised the regulatory review processes and led to harmonized electronic submissions that enable good review practices. For industries, it has eliminated the need to reformat information for submissions to the different ICH regulatory authorities. In Canada, most submissions to Health Canada must be submitted in the CTD format. As a regulatory affairs project manager for a small start up biotechnology company, you have been asked to prepare a new drug submission (NDS) through the regular (non accelerated) pathway for a new oncology product named “Sheridanumab”. You have been tasked with preparing all Module 1 and 2 documents. The remaining Modules will be prepared by other colleagues.

1. Create a prototype of your NDS submission for Modules 1 and 2, listing all relevant documents that you would need to file and what CTD section it would go in. Please organize your Modules using the following format:

2. List all guidance document(s) you used to determine how to build your prototype.

3. Why is it important that the NDS be submitted in CTD format?

General Instructions: • The Prototype project should follow the APA format with font size 12 and 1.5 spacing, Times New Roman. • A title page should be included in addition to the page limit. The title page should contain information such as Student Name, Student ID, Prototype title, course code etc.

CTD Section Document(s)/Forms you would provide in the section*

1.0.1 Cover Letter etc.

<<Continue this table as you see fit>>

To add slide numbers, choose Insert>Header & Footer, check the Slide number option, then click on Apply to All.

Questions