Assignment of GMP

Student name : Abdulrahman Abdulaziz Aldossari

Student ID : 437050091

Section : 189

Registration stages:
All days mentioned throughout this document are WORKING days (subject to

change).

All Applications will be subjected to the following procedures:

1. Online Filing of Application

The applicant shall fill up the appropriate application form in the SDR system. Once

completed, application form cannot be submitted unless the payment is received by

SADAD. A reference number will be assigned to the application once submitted to

facilitate the communication with the SFDA. Then, the applicant will be given an

opportunity to book an appointment to hand over the drug application (figure 1). An

automatic reminder will be sent 3 days before the appointment. The applicant can

reschedule 3 weeks before the chosen appointment. If it is missed, the applicant has to

book a new appointment again by requesting a completion appointment by email

(sdr.drug@sfda.gov.sa).

2-Acceptance of Drug Application

Upon receipt of the drug application in the appointment day, a checklist for ‘Phase I

Validation’ will be used to verify that the information and materials provided are

complete.

Drug application Without Deficiencies:

The applicant will be notified of the acceptability by printing an Acknowledgement

Letter. Then, the drug application will be forwarded to the product manager for

further processing and assessment. Once these applications are accepted, they will be

assessed in the order in which they are received.

Drug application With Deficiencies:

If deficiencies are identified, an Acknowledgment Letter stating the deficiencies will

be issued. The applicant will be required to submit the requested information within

90 days from the date of the letter.

*The applicant shall send an e-mail to the Drug sector (sdr.drug@sfda.gov.sa)

requesting an appointment to complete the deficiencies.

*If the applicant has provided the requested information within

90 days, the application will be accepted and the drug application will be forwarded to

the product manager for further processing and assessment.

*If the applicant has provided the requested information within 90 days, but it was

found to be still incomplete, the applicant can complete the missing within the rest of

the 90 days.
*If the applicant fails to provide the requested information within 90 days, the drug

application will be rejected.

3-Phase II Validation

After accepting the drug application from the applicant, the submitted information and

material will be validated to ensure that it has suitable quality to be assessed.

However, if deficiencies are identified, the applicant will be

asked to submit the required information, and it will follow one of the following

cases:

 If the applicant has provided the requested information within

90 days, the product file will be forwarded for further processing and assessment. The

applicant will be notified by e- mail.

 If the applicant has provided the requested information within 90 days but it

was found to be still incomplete, SFDA will study the case and may extend the

period for another maximum 30 days. The applicant will be notified by e-mail.

 If the applicant fails to provide the requested information within 90 days, the

drug application will be rejected.

4. Assessment of Application
All applications will be assessed in terms of quality, safety and efficacy – as needed –

depending on the type of the product.

If issues are identified during the assessment, these issues will be resolved through

electronic Inquiry Forms. Although there is no limitation of inquiries, it is expected

that these issues be resolved by two to three inquiries. Responses to inquiries are

required within 90 days.

5. Pricing

The pricing will be calculated according to the pricing rules outlined in the pricing

guideline.

6. Testing

All drug products will be subjected to appropriate testing according to the type of the

application and dosage form. Moreover, the applicant is requested to deliver the

samples to SFDA headquarters as part of the drug application. There will be no direct

contact between the applicant and SFDA’s laboratory.

7. Inspection

The inspection department will communicate with the applicant to decide the

appropriate time for inspection – if needed, depending on the schedules of the

inspectors. After the inspection is done, an inspection report will be written and a

copy of this report will be sent to the applicant. In case of deficiencies, further details

will follow.
 8. Stop-clock

The stop-clock starts whenever SFDA issues an Inquiry Form. Inquiries may be raised

at any time from the Phase II Validation to SFDA decision. The stop-clock ends

whenever SFDA receives complete and acceptable responses from the applicant.

If the applicant faces difficulties in responding to inquiries within the specified time,

applicant should contact SFDA as soon as possible. A drug application will be

considered rejected if the stop-clock time exceeds the SFDA deadline.

9. SFDA Decision

The final decision is made based on the outcome of SFDA's assessment, pricing,

testing and inspection. The decision can be one of the following:

*Approval: when the drug application has satisfied the registration requirements for

quality, safety and efficacy.

*More information is needed: when the drug application has minor deficiencies.

*Rejection: when the drug application has not satisfied the registration requirements.

10-Appeal Process

The applicant will have the right to appeal within 60 calendar days against the SFDA

decision. The relevant guidance will be published.

Structure and Content of Submission:

The SFDA will require all applicants to submit their applications in accordance to the

ICH Common Technical Document (CTD) format. For more information on the CTD,

please refer to appendix E.

The dossier requirements for each application will differ, depending on the type of

application. For more details refer to appendix B.

It is important to remember that the CTD provides a format for an MAA and does not

indicate the content of a dossier and which studies should be performed. Regional

and national requirements may affect the content of the dossier; therefore, the dossier

will not necessarily be identical for all regions.

Relevant guidelines are updated and published in the Drug Sector website, such as

Stability guideline, should be followed in providing the information or studies.

Module 1: Regional Administrative Information

This module includes the required regional information specific to GCC, such as

administrative information and certificates.

Presentation of the Product File

A softcopy (electronic-based) of the product file shall be submitted by the applicant

along with a hardcopy (paper-based) of selected documents of Module 1 ONLY1. The

softcopy shall be either:

eCTD2, or an electronic version of the product file in NeeS3 format (appendix C)

Hardcopy and Softcopy Requirements:

For the hardcopy (selected documents of Module 1), it should be bound into one

volume (flat file). The flat file specifications:

A4 lightweight flat file

Clear front and opaque back cover with removable title strip, and with a two-hole flat

bar filing mechanism

Label: should contain information:

Reference number (generated from SDR system)

Company name

Product trade name

Product Generic name

Date of submission (DD/MM/YYYY)

Type of submission (e.g. initial, renew or variation)

For the softcopy) electronic-based), each CD or DVD and its hard-plastic cover

submitted should include the following label information, clearly presented and

printed on the media with the font of 12 Times New Roman (or equivalent):

 The reference number

 The company name

 The product Trade name

 The Generic name

 The submission type of each submission(s) contained on the CD/DVD (e.g.

initial)
  The sequence number(s) of the submissions contained on the CD/DVD (

Number of copies:

Applicants should submit:

a) THREE softcopies full submission

b) and ONE hardcopy of selected documents of Module 1 for all

drug submission types.

The submitted copies should be identical. The submission shall be in ONE media only

(CD or DVD) i.e. if the submission size was above 750MB then the applicant has to

use a DVD.

Media:

The electronic submission may only be submitted in CD or DVD (single or dual

layer). The disc must not be bootable or have auto-start programs.

Currently both CD-ROM and DVD ISO 9660 are considered an acceptable media

standard.

However, the SFDA will not accept any hardware (laptops, desktops, thumb drives,

hard drive, floppy discs, etc.) from applicants in connection with the electronic

submission.

System compatibility:

The electronic submission (as provided) must be directly readable and usable on

SFDA hardware and software.

Although it is the policy of the SFDA to maintain desktop configurations and IT

infrastructure in line with common office standards, the electronic information

provided in the submission must not only be readable on the latest operating system,

but support a reasonable number of backward versions of windows operating systems.

Security:

There are various aspects related to security. The physical security of the submission

during transportation/transmission is the responsibility of the applicant. Once

received within the SFDA, security and submission integrity are the sole

responsibility of the SFDA. In this respect, it should be noted that the SFDA will take

appropriate measures to prevent loss, unauthorized duplication and/or access or theft

of regulatory information presented both on paper and electronic media that are

distributed throughout the SFDA.

Password protection:

One-time security settings or password protection of electronic submissions for

security purposes is not acceptable during transportation/transmission from the

applicant to the SFDA.

Applicants should also not include any file level security settings or password

protection for individual files in the electronic submission.

Applicants should allow printing, annotations to the documents, and selection of text

and graphics. The Internal security and access control processes in the SFDA

maintain the integrity of the submitted files.

Virus protection:

The applicant is responsible for checking the submission for viruses. Checking must

be performed with an up-to-date and well-recognized Anti- virus application.

After receipt of the submission at the SFDA, a similar internal virus check will

be performed. If a virus is detected it can constitute grounds for refusal of the

electronic submission.
 6 Document Requirements

Legibility and Size:

All documents should be legible. The page size, including tables, shall be uniform.

Page divider/tab:

A page divider or tab (with the header of the section printed) should be used to

separate selected section in module.

Language:

Information and documents supporting a drug application – such as certificates and

approval letters– must be either in Arabic or English. If documents are neither in

Arabic nor English, a translation to English (from an authorized translation office)

and authentication from the Saudi Embassy in the COO are required.
Authentication:

Authentication – also known as legalization – refers to the process whereby the

origins of a document are attested. Authentications of documents are made to SFDA

by the Health authority and/or the Ministry of Foreign affairs in the country of origin,

in addition to the Saudi Arabia Embassy or Consulate where the document was

issued. For more details, please refer to appendix A.

Inquiries-7

An applicant may receive an inquiry from SDR system , when the answer are ready

: applicant shall do the following

:In SDR

Respond electronically to SDR inbox to close the inquiry (Reason: to stop the clock)

:Note

.No hardcopy is required with the submission

.Only full answers of the inquiries are accepted

:drug registration

:Saudi drug registration (SDR) system*

The Saudi drug registration (SDR) system is an electronic system which aim to

facilitate the registration of medicinal, herbal and health products for both

human & veterinary use. The SDR will allow the registered establishments in

Drug establishment National Registry (DENR) to use the system in new

.application, renewal and variation of their products

:First

Log in to the web site:

http://sdr.sfda.gov.sa

Click on:

Create New Applications

Choose the application

according to the type of

drug:

a. Human Drugs *

b. Veterinary Drugs

c. Herbal & Health

Product

:Second

1-Type of

Application:

Select the type of

application:

1. New Drug*
2. Generic

3. Biological

4. Radiopharmaceutical

Then complete the

required information (trade name, product strength, dosage form, name, address etc.).

After you complete the

required information

.Click on save icon

Note: In filling out the application

form it is not required to be in order.

Third:

2-Application Details:

2.A: Names and ATC

Code.

-Active Substance:

Fill in the fields and then

click on add icon.

-Excipient:

Fill in the fields and then

click on add icon.

-ATC Code:

Click on:
And search for the drug

After you complete the

required information

Click on save icon.

2.B: Product Information:

2.C: Contact Information:

2.D: Manufacturers:

2.E: Certificate of a

pharmaceutical Product:

2.F: Animal Source

Material: If any component of the

product contain any

animal source material,

complete the required

information.

3.Scientific Advice:

4‐ Pediatric Development Program:

5 Application Status:

Select the application

status, then complete

the required information

6- Fee Due Statement:

7- Scheduling:

After choose the

meeting from the

schedule the time of the

meeting it will appear in

the bottom of this page

, click twice on the time

then click on print icon, Acrobat (PDF) file, print

After printing click on

scheduling icon for

confirm the meeting

-Documents required for registration:

CTD Structure for Human Drugs Submission

*Regional Administrative Information

Cover letter R

Comprehensive table of content R

Application Form R

Labeling R

Artwork (Mock-ups) R

Samples R

GMP Certificate R

CPP or Free-sales R

Certificate of analysis – Drug Substance / R

Finished Product

Certificate of analysis – Excipients R

Alcohol-free declaration R

Pork- free declaration R

 Certificate of suitability for TSE R

Responses to questions R

Nomenclature R

Structure R

General Properties R

Manufacturer(s) R

Control of Drug Substance R

Analytical Procedures R

Description and Composition of the Drug R

Product

Stability Summary and Conclusions R

Stability Data R

*Common Technical Document Summaries:

-Quality Overall Summary

-Drug substance

-General Information

-Manufacture

-Characterization

-Control of Drug Substance

-Reference Standards or Materials

-Container/Closure System

-Stability

-Drug Product

-Description and Composition of the Drug Product

-Pharmaceutical Development

-Manufacture

-Control of Excipients

-Control of Drug Product

-Reference Standards or Materials

-Container/Closure System

-Appendices

-Facilities and Equipment

-Adventitious Agents Safety Evaluation

- Novel Excipients

-Regional Information

-Nonclinical Overview

-Clinical Overview

-Product Development Rationale

-Overview of Biopharmaceutics

-Overview of Clinical Pharmacology

-Overview of Efficacy

-Overview of Safety

-Benefits and Risks Conclusions

-References

-Non-Clinical Written and Tabulated Summaries

-Pharmacology Written Summary

-Brief Summary

-Primary Pharmacodynamics

-Secondary Pharmacodynamics
-Safety Pharmacology

What's New in the Data Requirements for Human Drugs Submission?

The following table shows the updated sections:

Module 1

1.7 Certificates and documents 1.7.3 Certificate of analysis – drug substance/finished

product

1.7.10 Letter of access or acknowledgment to DMF

Module 3

3.2 Body of data

3.2.S Drug substance

1. Certificate of Suitability (CEP)

2. Drug Master File (DMF)

*Manufacture

*Process Validation and/or Evaluation

*Characterization

*Impurities

*Control of Drug Substance

*Analytical Procedures

*Validation of Analytical Procedures

*Batch Analyses

*Reference Standards or Materials

*Stability Summary and Conclusions

*Drug product

*Manufacture
*Process Validation and/or Evaluation

*Control of Drug Product

*Analytical Procedures

*Validation of Analytical Procedures

*Batch Analyses

*Reference Standards or Materials

*Stability

-Common Technical Document (CTD)

The Common Technical Document is an internationally agreed format for the

preparation of a marketing authorization (MA) that is to be submitted to the

regulatory authorities in the three ICH regions (USA, EU and Japan) and in some

other countries and regions. The CTD provides a common format for the preparation

of a well-structured dossier. It uses a modular framework described in ICH Topic

M417. This guidance document should be read in conjunction with the most recent

version of the ICH CTD guidance documents.

It is important to remember that the CTD provides a format for an MAA and does not

indicate the content of a dossier and which studies should be performed. Regional

and national requirements may affect the content of the dossier; therefore, the dossier

will not necessarily be identical for all regions.

The CTD is applicable for all types of products (new chemical entities, biologicals,

herbals etc.)
The CTD is organized into five modules (figure 4). Module 1 is region specific.

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

Module 1: Administrative Information and prescribing Information

Module 2: Common Technical Document Summaries

Module 3: Quality

Module 4: Non-Clinical Study Reports

Module 5: Clinical Study Reports

• The CTD was agreed upon in November 2000, in San Diego,

USA.

• The purpose of this Common Technical Document (CTD) is to

provide a harmonized structure and format for new product

applications (marketing authorization).

• The use of the CTD format is mandatory as from 1 July 2003

in the European Union.

• The ICH Steering Committee adopted a new codification

system for ICH Guidelines (Nov 2005)

*The focus of the is to provide a common format for the

preparation of a well-structured submission according to the

modular framework described in the ICH guidelines of the

Common Technical Document for Registration for Human Use

(ICH Topic M4).

• The CTD guidance indicates where and how available

information is to be presented.

• The CTD is not intended to indicate what studies are actually

required (Authorities can ask for specific types of data).

:Variations
An applicant can submit a variation request – on drug products that have already

:received a marketing authorization from the SFDA – through the following steps

:In SDR8

a-Choose the required drug under “Registered Products” section and press ‘Variation’

.button

b-Complete the form and submit it electronically

c-Save a copy of the application form (for preparing the softcopy)

:In the softcopy

:Prepare a CD/DVD including the required document in the form of

.a-Nee S submission: follow the instructions in appendix C of this guidance

b- M1 “GCC guideline the follow submission: eCTD

.published in website

:Variation Requirements
- An application for Variation to a Marketing Authorization should always be

submitted (please refer to latest edition of the framework).

- Applicants should present a summary of the intended change in tabular form in

which the current state/situation and the situation after the intended change are

compared to outline the scope of the change in a transparent manner.

-A justification for the introduction of the change should always follow.

- Some documents such as certificate of analysis (COA), specification sheet, and

approval letters from the country of origin …etc. should be submitted when relevant.

- It is important to note that the authority reserves the right to request any additional

information and data not specifically described in this document, in order to assess

adequately the safety, efficacy and quality of drug products. Authority is committed to

ensuring that such requests are justifiable and decisions are clearly documented.

-Applicants should be aware that deficient documentation can lead to rejection of the

application. In addition, submitting redundant or irrelevant information may delay

approval procedures.

Types of Variations:
The variation or post-marketing changes can be classified into two categories:

A. Minor variations:

Type IA: Such minor variations do not require prior approval before implementation

(“Do and Tell” procedure). Type IAIN variations should be submitted immediately,

within 14 days following implementation. Other type IA variations, however, can be

compiled in a single variation application, to be submitted to the SFDA no later than

January 31st of each year. The variation application for every product should clearly

indicate:

- All IA variations that have been implemented during the previous year.

- Date of implementation of each variation.

- Code of each variation, based on this guideline, and a proof that the conditions of

such variations have been met.

- All the corresponding documentation listed in this guideline for each variation.

Type IB: Such minor variations must be submitted to the authority by the Marketing

Authorization Holder (MAH) before implementation, but do not require a formal

approval. However, the MAH must wait a period of time (please refer to latest edition

of the framework) to ensure that the application is deemed acceptable before

implementing the change (“Tell, Wait and Do” procedure).

B. Major variations:

 Type II: Such major variations, which may have a significant impact on the

Quality, Safety or Efficacy of a medicinal product and require prior approval before

implementation.

In order to facilitate the classification of variation or post-market changes, examples

and appendices listed below are explicitly define the various types of changes:

- Appendix 1; example of some major changes and most minor changes; which are

classified by the type of change. When the conditions are not met, the change may

classify as either a major change or may make a new application is necessary.

- Appendix 2 list the types of changes that make a new application necessary.

- Appendix 3 Requirements for addition/change to an API supplier

* I. Administrative Changes

* II. Quality Changes

*Safety, Efficacy, Pharmacovigilance Changes: Change in the summary of

product characteristics, labeling and patient information leaflet of a

generic/hybrid/biosimilar medicinal product following assessment of the same

change for the reference product. Change(s) to therapeutic indication(s).

* PMF/VAMF
Examples for changes that make a new application necessary include but are not
limited to the following:

1. Changes to the API, for example:

- Change of the API to a different API;

- Inclusion of an additional API in a multi-component product;

- Removal of one API from a multi-component product;

- Change in the dose of one or more APIs.

2. Changes to the pharmaceutical form/dosage form, for example:

- Change from an immediate-release product to a slow- or delayed-release dosage

form and vice versa;

-Change from a liquid to a powder for reconstitution, or vice versa.

-A change from multi-dose to single-dose or vice-versa (both for addition or

replacement).

3. Changes to the strength.

4. A change or addition of route of administration.

5. The addition or replacement of measuring or administration device being an

integrated part of the primary packaging that results in a change to the strength,
pharmaceutical form or route of administration of the product.

6. Other changes specific to veterinary medicinal products to be administered to food-

producing animals; change or addition of target species.

Reference: SFDA
https://www.sfda.gov.sa/ar/regulations?keys=&regulation_type=All&date%5Bmin
%5D=&date%5Bmax%5D=&tags=2
THANKS FOR EVERYTHING DR. SAFAR