RA Manager – Boston Biopharma Ltd

20th December 2021

Time Subject
o Story of diseases & medicines
 Step 1: Discovery & Development
 Step 2: Preclinical Research
 Step 3: Clinical Research
 Step 4: Government review
 Step 5: Post-Marketing-Safety Monitoring
o Departments of the Manufacturing Site
o Definition of Regulatory Affairs
Monday 20th December 2021
08:00 to 09:30 pm UAE Time

o Role of Regulatory Affairs

o CTD /eCTD History
o CTD Triangle
o CTD, NeeS & eCTD definition
o Differences between submission forms
o Flow chart of drug registration in GHC & Gulf countries
o Module 1
o Module 2
o Module 3
 3.2.S Drug Substance
 3.2.P Drug Product
o Module 4
o Module 5
o eCTD
o CTD, NeeS & eCTD criteria
12/20/2021
o Creation of NeeS & eCTD
Story of Diseases & Medicines
Step 1: Discovery & Development

Step 4: Government review

Step 2: Preclinical Research

Step 5: Post-marketing-Safety Monitoring

Step 3: Clinical Research

Step 1: Discovery & Development
Innovator
product

Researchers try to identify Research for a new drug begins in the

the disease laboratory through designing a product to stop
or reverse the effects of the disease
Step 2: Preclinical Research

Innovator
product

Before testing a drug in people, researchers must find out whether it has the potential to cause serious harm (toxicity).
Drugs undergo laboratory & animal testing to answer basic questions about safety.
These studies must provide detailed information on dosing & toxicity levels.
After preclinical testing, researchers review their findings & decide whether the drug should be tested in people.
Step 3: Clinical Research
Step 4: Post-marketing-Safety Monitoring

Innovator
& Generic
products

Drugs are tested on people to make sure they are safe & effective.

• Trials test for safety

• Purpose: safety &
• Purpose: efficacy & • Trials test for & efficacy
dosage
side effects effectiveness & • Study Participants:
• Study Participants:
• Study Participants: monitoring of Several thousand
20 to 100 healthy
several hundred adverse reactions volunteers who
volunteers or people
patients • Study Participants: have the
with the
• Length of Study: 300 to 3,000 patients disease/condition
disease/condition.
several months to • Length of Study: 1 • Post Marketing
• Length of Study:
two years to 4 years Surveillance Trials:
several months
• Approximately 33% • Approximately 25- after a drug or
• Approximately 70%
of drugs move to the 30% of drugs move device has been
of drugs move to the
next phase to the next phase approved for
next phase
consumer sale.
Departments of the Manufacturing Site

Warehouse

Production & Engineering QA QC PhV

RA Marketing

Artwork/Labelling

Medical Affairs
What is the Life cycle of Drug Product?

Business Research &

Supply chain Warehouse
Development Development

Quality Production &

Pharmacovigilance Quality Control
Assurance Engineering

Medical Affairs Methodology &Validation, In process control,

QC Analysis, Microbiology, Process Validation,
Stability study, Packaging Documentation
materials, Raw materials

Artwork/ Regulatory Affairs Marketing

Labelling
Company

Regulatory
Affairs
(RA)
Regulatory
Product Authorities
What is Regulatory Affairs?
Companies Global HA
Link

Regulatory Affairs (RA) is a profession developed:

• by the companies responsible for the discovery, testing, manufacturing & marketing of these
products wanting to ensure that they supply products that are safe & make a worthwhile
contribution to public health.
• from the desire of governments to protect public health by controlling the safety & efficacy
of products in areas including pharmaceuticals, veterinary medicines, medical devices,
pesticides & cosmetics.

RA is the link between Pharma Companies & global health authorities

What is the responsibility of RA ?

• All medicines must have a Marketing Authorization (MA) in order to be put on the market legally
in the country.

• The ultimate purpose of marketing authorization is to ensure that safe, effective, and high-quality
medicines can quickly be made available to citizens.

RA is responsible to compile & submit the registration file of drug product and manufacturing site
“if required” to Health authority, as to grant the MA/GMP certificate.
CTD (Common Technical Document)

is a harmonized format for submission of detailed information on medicines to

regulatory authorities for the purposes of obtaining approval to market a product.

NeeS (Non-eCTD electronic Submissions)

is based on electronic Tables of Content, bookmarks & hypertext links. eCTD folder structure is used.

eCTD (Electronic Common Technical Document)

is the electronic version of CTD.
CTD is a joint effort of 3 regulatory agencies:

1.European Medicines Agency (EMA- Europe)

+
2. Food and Drug Administration (FDA - USA)
+
3. Ministry of Health of Japan (MHLW)

=
CTD is maintained by
International Council on Harmonisation “ICH”
of technical requirements for registration of
pharmaceuticals for human use.
The CTD is organized into five modules.
Module 1 is region specific.
Modules 2, 3, 4 and 5 are intended to be common for all regions.
Criteria CTD NeeS eCTD
Type Paper Electronic Electronic

Compiled on any Documents

Need special software to
Compilation program then printed generated in PDF
create xml backbone
as hard copy format

TOC/ Hard copy/ Xml file, hyperlink,

Hyperlink in pdf
navigation tabs/volumes bookmarks

Submission Hard copy in volumes CD CD

Flow chart of drug registration in GHC & Gulf countries

1. Receipt of application

Receipt & Validation Procedures

Marketing
2. Accepted for Review Authorization
Approval

Queuing for review

Registration Rejection
3. Process of Scientific Review
Decision

Sample
6. Reply from Company
Quality Safety Efficacy
analysis

Parallel review

5. Questions from HA
4.1 Registration Dept 4.2 QC Laboratory to company
Module 1
“Regional Administrative Information”

• This module should contain documents specific to each region specified by the relevant regulatory authorities.
1.1 Cover Letter
1.2 Application form
1.3 Product information
1.3.1 Summary of product Characteristics (SmPC)
1.3.2 Labeling
1.3.3 Patient information Leaflet (PIL)
1.3.4 Artwork (Mock-ups)
1.4 Certificates (Price certificate, CPP, GMP, COS, LOA, Alcohol and pork free declaration, COA of API & FP… etc)
1.5 Environmental Risk Assessment
1.6 Pharmacovigilance
1.7 Information on the Experts
1.7.1 Quality
1.7.2 Non-clinical
1.7.3 Clinical
Module 2
“All summaries / overviews”

2.1 ToC “m2-m5”

2.2 Introduction
2.3 Quality Overall Summary
2.4 Non-Clinical Overview
2.5 Clinical Overview
2.6 Non-Clinical Written & Tabulated Summaries
Pharmacology
Pharmacokinetics
Toxicology
2.7 Clinical Summary
Biopharmaceutic studies & associated analytical methods
Clinical pharmacology studies
Clinical efficacy
Clinical safety
Literature references
Synopses of individual studies
•M3 is composed of 2 main parts;
 3.2.S (Substance)
 3.2.P (Product) & some regional information

•M3 includes CMC (Chemistry, Manufacturing & Controls) details.

•Sequence is done in numbering style,

so first section is 3.1 (TOC), followed by 3.2.S & 3.2.P, then appendices.
• The following table summarizes the contents of 3.2.S & 3.2.P

Contents 3.2.S 3.2.P

General 3.2.P.1
3.2.S.1
Information/Description (Description
(General Information)
&Composition &Composition )
Development -- 3.2.P.2
Manufacture 3.2.S.2 3.2.P.3
Characterization/ 3.2.S.3 3.2.P.4
Excipients control (Characterization) (Excipients control)
Product Control 3.2.S.4 3.2.P.5
Reference Standards 3.2.S.5 3.2.P.6
Container Closure system 3.2.S.6 3.2.P.7
Stability 3.2.S.7 3.2.P.8
Module 3 Quality: Chemistry, Manufacturing & Controls (CMC)

3.1 Table of content (Module 3)

3.2 Body of Data
3.2 .S Drug Substance
3.2.S.1 General Information
(Nomenclature , Structure &General Properties)

3.2.S.2 Manufacture

3.2.S.3 Characterization
3.2.S.4 Control of Drug Substance
(Specification, Analytical procedures, Validation of Analytical
procedures, Batch Analysis & Justification of Specification )

3.2.S.5 Reference Standards

3.2.S.6 Container Closure System

3.2.S.7 Stability
Module 3 Quality: Chemistry, Manufacturing & Controls (CMC)

3.2.P Drug Product

3.2.P.1 Description and Composition of the Drug Product

3.2.P.2 Pharmaceutical Development

3.2.P.3 Manufacturer

3.2.P.4 Control of Excipients

3.2.P.5 Control of Drug Product (Specification, Analytical

procedures, Validation of Analytical procedures, etc. )

3.2.P.6 Reference Standards

3.2.P.7 Container Closure System

3.2.P.8 Stability
Module 3 Quality: Chemistry, Manufacturing & Controls (CMC)
3.2 A Appendices
3.2 A1 Facility & Equipment's

3.2 A2 Advertising agents safety evaluation

3.2 A3 Excipients

3.2 R Regional Information

3.2.R.1 Production documents
3.2.R.1.1 Executed production documents
3.2.R.1.2 Master production documents

3.2.R.2 Raw data and chromatograms for stability study & for validation

3.3 Literature References

Module 4
“Non-Clinical Study reports”

• The pre-clinical studies will cover the information related to the

pharmacology, pharmacokinetics & toxicology testing.

• This module is not required for generic submission.

Module 5
“Clinical Study Reports”

The module contains 4 sections:

5.1 Table of Content (Not required in eCTD)
5.2 Tabular Listing of All Clinical Studies
5.3 Clinical Study Reports
5.4 Literature References
What is eCTD?

 eCTD is an interface for industry to agency transfer of regulatory information.

 eCTD is composed of:

 Directory structure
 Content files
 XML eCTD instance
eCTD software

Using a friendly eCTD creation tool

(e.g. eCTDmanager)
CTD, NeeS & eCTD criteria

• PDF Version should be 5.0 or higher.

• Print area for pages should fit on a sheet of A4

and letter (8.5” X 11”) paper.

• Sufficient margin (at least 2.5 cm) on the left

side of each page should be provided to avoid
obscuring information.

• Header and footer information can appear

within these margins.
CTD, NeeS & eCTD criteria
• Fonts & Font Size
Times New Roman, Arial, Courier and Fonts supported in the
Acrobat set itself.
12- point font size
• Use of Color fonts
Black font color is recommended. Blue color can be used for
hypertext link.
• Page Orientation
Page Should be properly oriented so that all portrait pages are
presented in portrait and all landscape pages are presented in
landscape.
• Headers and Footers
Unique header or footer that identifies its subject matter.
CTD, NeeS & eCTD criteria

• Source of Electronic Document

 Scanning should be avoided where possible.
 Document Should be generated from electronic source documents
and not from scanned material, except where access to the source
electronic file is unavailable or where a signature is called for.
 All scanned documents should be OCR. (Optical Character
Recognition).

• Methods for creating PDF documents and Images

It is recommended that scanning be undertaken at a resolution of 300
dpi (dots per inch) to balance legibility and file size.
CTD, NeeS & eCTD criteria

• Folder & file Naming Conventions

Only lower case letters should be used in all file and
directory names.
Name is a token composed of the following characters.
Letters “a” to “z”
Digits “0” to “9”
Hyphens “-”
Security
No security settings or password protection for PDF files
should be included.
Creation of NeeS & eCTD

Create 5 folders and name them as m1, m2, m3, m4 and m5 respectively.

Note
TOC is in the main folder of the drug submission.
Creation of NeeS & eCTD
Folders should be named as follows in m1:
Creation of NeeS & eCTD
Folders should be named as follows in m2:
Creation of NeeS & eCTD
Folders should be named as follows in m3:
Creation of NeeS & eCTD
Folders should be named as follows in m3:
Creation of NeeS & eCTD
Folders should be named as follows in m3:
Creation of NeeS & eCTD
Folders should be named as follows in m3:
Creation of NeeS & eCTD

DP Name – DP Manufacturer

Screenshot
of the folder structure of m3

DS Name – DS Manufacturer
Creation of NeeS & eCTD

Screenshot
of the folder structure of m4
Creation of NeeS & eCTD
Screenshot
of the folder structure of m5
📥e-mail : ( [email protected] )

📱 Mobile no.: 002 01005044453

🌍 LinkedIn account: