Guidance for Submission

Version 1.0.1

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Document Control
Version Date Author Comments
1.0 Prepared on: 30.10.2018 EXTEDO
Approved on: 5/3/2019

1.0.1 Revised & Amended by Maha Jaghbeer

Registration department:
Ahlam Abd Alaziz
on 4/4/2019
Bayan Hyasat

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 Table of Contents
1..........Introduction...................................................................................................5
2..........Scope……………...........................................................................................6
3..........Registration Process......................................................................................7
4..........Structure and Content of Submission.......................................................11
4.1.........Structure and Content of Submission:.....................................................................11
4.2.........Module 1: Regional Administrative Information...................................................11
5..........Presentation of the Product File.................................................................12
5.1.........Softcopy Requirements:............................................................................................12
5.2.........Number of copies:......................................................................................................12
5.3.........Media:.........................................................................................................................12
5.3.1........System compatibility:..........................................................................................12
5.4.........Security:......................................................................................................................12
5.4.1........Password protection:...........................................................................................13
5.4.2........Virus protection:..................................................................................................13
6..........Document Requirements............................................................................14
6.1.........Legibility and Size:....................................................................................................14
6.2.........Language:...................................................................................................................14
6.3.........Authentication:...........................................................................................................14
7..........Inquiries.......................................................................................................15
8..........Renewal........................................................................................................16
9..........Variations.....................................................................................................17
10.......Baseline:.......................................................................................................18
Appendix A: JO Module 1 Administrative Information...................................19
Appendix B: Data Requirements.........................................................................21
Appendix C: Module Common Technical Documents Summaries..................22
Appendix D: Module 3 Quality............................................................................24
Appendix E: Module 4 Nonclinical Study Reports.............................................35
Appendix F: Module 5 – Clinical Study Reports................................................36
Appendix G: File Formats....................................................................................37

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Appendix H: ICH Common Technical Document..............................................40
Appendix I: References.........................................................................................43
Appendix J: Renewal Requirements....................................................................44
Appendix K: Baseline Requirements...................................................................47
Appendix L: BE/ comparative dissolution checklists.........................................48
Appendix M: Abbreviations and Acronyms.......................................................49

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1. Introduction

The Registration Department in the Jordan Food & Drug Authority (JFDA) has developed this
document, "Guidance for Submission" to assist applicants and industry in the preparation and
submission of drug applications for new Marketing Authorization (MA) as well as renewals and
variations to existing products to the JFDA. The guidance provides an outline of the way the
Framework will be managed with respect to drug applications by the JFDA.

It is intended to provide clarification to applicants of the way in which the Registration

Department in the JFDA manage information and material submitted in accordance with the
Regulatory framework for Drug Approvals (version 1.0). Also, it provides assistance to comply
with the requirements of filing and maintenance of their application.

Industry representatives, as well as the staff of the JFDA responsible for the drug application
management, will follow this guidance and operational directions in various areas, including the
handling of application information, procedure related to drug assessment, clarification and
performance target of drug assessments.

To maintain its consistency and enhanced transparency, this guidance will be updated regularly
to reflect the current practices in regulatory sciences. It is expected that this guidance and any
amendments to it will create efficiency in the drug application management and reduce the
number of clarification requests.

It should be noted that the JFDA has the right to request any information and data within the
context of this guidance in order to assess adequately the safety, efficacy and quality of any
medicinal products available in the Hashemite Kingdom of Jordan. The JFDA is committed to
ensuring that such requests are justifiable and decisions are clearly documented.

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2. Scope
This guidance document applies to all submission types:
 New submission (MA)
 Generics
 Originators
 New drugs
 Vitamins
 Biologics
 Radiopharmaceuticals
 Herbal medicines
 Renewal
 Variation
 Baseline

All submitted information and material will be screened to ensure that it is complete and of
suitable quality to be reviewed. The same management principles will be applied consistently to
all submission types.
This guidance document covers the preparation and filling requirements for submissions in
electronic format (eCTD). It is based on the ICH CTD and the eCTD Specifications, JO M1
Specification & electronic JFDA Drug Workflow System [REGULATORY APPROVAL
FRAMEWORK] .

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3. Registration Process

Important Note:

•All days mentioned throughout this document are Calendar 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 eJDWS system. Once
application form is completed, a reference number will be assigned to the application once
submitted to facilitate the communication with the JFDA. 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 2 days before the appointment. The applicant can reschedule a week before
the chosen appointment. If it is missed, the applicant has to book a new appointment again.
(Refer to new submission procedure steps in eJDWS).

Figure 1 A “Drug Application” includes the application form, the product file and the drug
sample

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2. Acceptance of Drug Application

Figure 2 Registration Process Flow

Upon receipt of the drug application in the appointment day, a checklist for ‘Phase I Validation’/
Screening will be used to verify that the information and materials provided are complete.
If the applicant did not attend for an appointment; the screener can cancel the application after 30
minutes from appointment time by using No Show button

A. Invalid Submission:
Resubmit the file within 30 days which will be calculated through eJDWS, and the
content of the CD will not be screened
B. Valid Submission Without Deficiencies:
If application is complete it will be officially received & will proceed to the next step –
assessment.
C. Valid Submission With Deficiencies:

• If deficiencies are identified a deficiency letter will be generated and given to the
applicant stating the deficiencies. The applicant will have a period of 30 days to
complete the requirements and the drug application will not be queued.
Otherwise, JFDA will securely dispose of the product file or extend the deadline
for another 30 days by RA Manager Approval.
• If the applicant fails to provide the requested information within 30 days, the drug
application will be rejected.

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3. Phase II Validation
(Refer to eJDWS)
The technical content of the CD will be validated to ensure that all information provided are
according to the requirements of the guidelines (phase II validation) If any information is
missing or incorrect, the applicant will be notified electronically by the inquiry. - The applicant
will be given an opportunity to complete the file within inquiry due date. Otherwise, the file 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 within inquiry due date.

5. Testing

All drug products will be subjected to appropriate testing according to the type of the application
and dosage form according to lab testing bylaw.

6. 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.

7. Pricing

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

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8. Stop-clock

The stop-clock starts whenever JFDA issues an Inquiry Form. Inquiries may be raised at any
time from the Phase II Validation/ Assessment. The stop-clock ends whenever JFDA receives
complete and acceptable responses from the applicant.
If the applicant faces difficulties in responding to inquiries within the specified time, applicant
should contact JFDA as soon as possible. A drug application will be considered rejected if the
stop-clock time exceeds the JFDA deadline.

9. JFDA Decision

The final decision is made based on the outcome of JFDA'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 30 days against the JFDA decision.

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4. Structure and Content of Submission
4.1 Structure and Content of Submission:

The JFDA will require all applicants to submit their applications in accordance to the JO M1
specifications & ICH Electronic Common Technical Document (eCTD) format. For more
information on the eCTD, please refer to appendices A-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 eCTD 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.

4.2 Module 1: Regional Administrative Information

This module includes the required regional information specific to Jordan, such as administrative
information and certificates. For more information, please refer to appendix A.

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5. Presentation of the Product File
A softcopy (electronic-based) of the product file shall be submitted by the applicant. The
softcopy shall be eCTD.

5.1 Softcopy Requirements:

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 application number
• The company name (MAH)
• The product Trade name
• The active substance name (INN Name)
• The sequence number(s) of the submissions contained on the CD/DVD (e.g. 0002)

5.2 Number of copies:

Applicants should submit one softcopy
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.

5.3 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 JFDA will not accept any hardware (laptops, desktops, thumb drives, hard drive,
floppy discs, etc.) from applicants in connection with the electronic submission.

5.3.1 System compatibility:

The electronic submission (as provided) must be directly readable and usable on JFDA hardware
and software.

5.4 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 to the JFDA,
security and submission integrity is the sole responsibility of the JFDA. In this respect, it should

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be noted that the JFDA 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 JFDA.

5.4.1 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 JFDA.
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 JFDA maintain the integrity of
the submitted files.

5.4.2 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 JFDA, a similar internal virus check will be performed. If a
virus is detected it can constitute grounds for refusal of the electronic submission.

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6. Document Requirements

6.1 Legibility and Size:

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

6.3 Authentication:
Authentication – also known as legalization – refers to the process whereby the origins of a
document are attested. Authentications of documents are made to JFDA by the Health authority
and the Ministry of Foreign affairs or concerned party in the country of origin, in addition to the
Jordan Embassy or Consulate where the document was issued. For more details, please refer to
appendix A.

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7. Inquiries

An applicant may receive an inquiry from eJDWS system. When the answers are ready,
applicant shall do the following:
1. in eJDWS:
a. Respond electronically to eJDWS inbox to close the inquiry by uploading validation
report of the new follow up submitted sequence according to the due date specified
through eJDWS (Reason: to stop the clock)
2. In the softcopy:
a. Provide JFDA with the following:
i. Section 1.9 in module 1: should include a document (letter) which lists the inquiries
(questions) with the corresponding narrative text response for each question. This
section will not be used for supporting technical documentation which will be
included to the relevant modules. Each question should be followed by the name of
section, page number and a hyperlink where the answer can be found in the
concerned module.
ii. Relevant section(s) added in the right place of the submission

b. Prepare a CD/DVD including the above document(s) in the form of:

i. eCTD submission: follow the guideline “JO eCTD M1 Specifications” published in
the website.

Taking into account, the labelling of the CD as mentioned in page 11 of this guidance.

Note:
• Only full answers of the inquiries are accepted.

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8. Renewal
An applicant shall submit a renewal request every five years – on drug products that have already
received a marketing authorization from the JFDA – at least three months before the certificate
expires (4 years and nine months after approval) according to appendix J through the following
steps:
1. In eJDWS:

a. Choose the required drug under “Old Products” section and press ‘Renewal’ button
b. Complete the form and submit it electronically
c. Save a copy of the application form (for preparing the softcopy)

2. In the softcopy:

Prepare a CD/DVD including the required document according to appendix J in the form of:

a. eCTD submission: follow the guideline “JO M1 Specifications” published in the

website.

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9. Variations
An applicant can submit a variation request – on drug products that have already received a
marketing authorization from the JFDA – through the following steps:
1. In eJDWS:

a. Choose the required drug under “old 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)

2. In the softcopy:

Prepare a CD/DVD including the required document (according to PAC requirements) in the
form of:

b. eCTD submission: follow the guideline “JO M1 Specifications” published in

the website.

Notes:

• The requirements of variation are available in the JFDA's website.

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10. Baseline:
A baseline submission is the resubmission of currently valid documents to start
the eCTD lifecycle for the submission submitted not in eCTD format.
Submission of a baseline shall be before starting a new regulatory activity or
after the end of a regulatory activity.

The compiled baseline submission is a submission of the current status of the

dossier, i.e. currently valid documents that have already been provided to JFDA
and already approved.

The baseline should be clearly stated in the cover letter of the “baseline eCTD
sequence” that the content of the previously submitted dossier has not been
changed, only the format. There is no need for the JFDA Drug Directorate to
assess baseline submissions and hyperlinks between documents are not
necessary. The submission unit ‘reformat’ should be used in the envelope for
the baseline sequence and submission type should be “none”.

The baseline submission sequence for registered product files should be

submitted as sequence (0000). However, in some cases e.g. renewals and
variations submitted as eCTD, the submission of the baseline can happen in a
higher sequence of the submission life cycle. The baseline should always be a
separate submission and should never include any changes of the documents or
content of the application.

Baseline submission composed of the currently valid documents that have

already been provided to JFDA and already approved, summary of
documentation list in addition to payment receipt, refer to appendix K

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 Appendix A: JO Module 1 Administrative Information
Section Requirements Remarks 1 2 3 4 d
HC
1.0 Cover letter    
1.2 Application Form Taken as PDF  
from eJDWS

1.3 Product Information

1.3.1 Summary of Product Characteristics (SPC) and a
Comparison
1.3.2 Labeling Inner label

1.3.3 Patient information leaflet (PIL)

1.3.3.1 Arabic leaflet Mandatory for
OTC products

1.3.3.2 English leaflet and Comparison For generics:

comparison with
the originator + the
originator leaflet.

1.3.4 Artwork (Mock-ups) Outer carton

1.3.5 Samples
1.4 Information on the experts
1.4.1 Quality
1.4.2 Non-Clinical
1.4.3 Clinical
1.5 Environmental Risk Assessment Only one
subsection is
applicable

1.5.1 Non-Genetically Modified Organism (Non-GMO)

1.5.2 GMO
1.6 Pharmacovigilance
1.6.1 Pharmacovigilance System 
1.6.2 Risk Management Plan 
1.7 Certificates and Documents
1.7.1 Manufacturing Sites Documents g c b 

e
1.7.2 CPP or Free-sales  

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 1.7.3 Certificate of analysis – Drug Substance & f f f
Finished Product

1.7.4 Certificate of analysis – Excipients

1.7.5 Declaration of Ingredients from Human origin   
1.7.6 Pork-content declaration   
1.7.7 Certificate of suitability for TSE
1.7.8 The diluents and coloring agents in the product   
1.7.9 formula
Data Protection
1.7.10 Letter of access or acknowledgment to DMF If applicable
1.8 Pricing
1.8.1 Price certificate     
1.8.2 Other documents related   

1.9 Responses to questions

Additional data
1: Company original paper (not a
photocopy)
2: Signature of authorized person
3: Company official stamp
4: Authentication
e.g. World wide
registration status
e.g. Plasma
master file
approval from
COO
a) Originator Only (SPC from Health Authority)
b) Certificates only
c) Site Master File only
d) Hard-copy
e) Not required for local manufactures
f) Only for Finished Product
g) JFDA accreditation letter or: Accreditation
requirements:
- GMP/ ML for finished product manufacturer
- CPPs from reference countries to substitute
inspection).
- SMF( section 3.2.A)

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 Appendix B: Data Requirements
The data requirements for each application will differ, depending on the drug
submission type. However, all the required data should be in accordance with the CTD
structure.

Please refer to the following documents published in the website:

 Drug registration and re-registration criteria

 Natural product registration criteria
 Biosimilar product registration criteria
 Bioequivalence studies regulations
 Post-approval changes regulations (PAC)

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 Appendix C: Module Common Technical Documents Summaries
Contains summaries (the Quality Overall Summary, the Non-clinical Overview / Summaries, and
the Clinical Overview / Summaries).
Should include sufficient information from each module to provide the reviewer with an
overview of all the CTD Modules and should also emphasis critical key parameters of the
product and provide, for instance, justification in cases where guidelines were not followed.

Module 2.2 Introduction:

Should include its pharmacological class, mode of action and the proposed clinical use.

Module 2.3 Quality Overall Summary:

The following points should be taken into considerations:
 The Quality Overall Summary (QOS) is a summary that follows the scope and the outline
of the Body of Data in Module 3.
 The QOS should not include information, data or justification that was not already
included in Module 3 or in other parts of the CTD.

 The QOS should include sufficient information from each section to provide the Quality
reviewer with an overview of Module 3, the QOS should also emphasis critical key
parameters of the product and provide, for instance, justification in cases where
guidelines were not followed.
 For Generics: Sections Required only: 2.3 Quality Overall Summaries and 2.5 Clinical
Overview (the written summary (BE report or Synopsis) of the bioequivalence has to be
part of the Clinical Overview .
(Non-clinical and Clinical Summaries can be provided, but they are only mandatory if
new additional studies have been provided within the documentation).

Module 2.4 Nonclinical Overview:

The interpretation of the data, the clinical relevance of the findings, cross-linking with the quality
aspects of the pharmaceutical, and the implications of the nonclinical findings for the safe use of
the pharmaceutical (i.e., as applicable to labeling) should be addressed in the Nonclinical
Overview.

Module 2.5 Clinical Overview:

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The Clinical Overview is intended to provide a critical analysis of the clinical data in the
Electronic Common Technical Document, it will necessarily refer to application data provided in
the comprehensive Clinical Summary, the Clinical Overview should provide a succinct
discussion and interpretation of these studies together with any other relevant information.
Module 2.6 Nonclinical Summary
The primary purpose of the Nonclinical Written and Tabulated Summaries should be to provide a
comprehensive, factual synopsis of the nonclinical data.
Module 2.7 Clinical Summary
The Clinical Summary should provide a detailed factual summarization of the clinical
information in the eCTD.

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 Appendix D: Module 3 Quality
3.2 Body of Data
3.2.S Drug Substance

The information on the drug substance can be submitted in the following order:
1. Valid European Certificate of Suitability (CEP) with all appendices (copy for drug substance
manufacturer/s.
The Drug Substance sections should refer to the Certificate of Suitability in the relevant
sections in Module 3.2.S ,the Certificates of Suitability are deemed to replace the data of the
corresponding sections (S.2.2, S.2.3, S.2.4 and S.2.6) and therefore in principle no further
additional information is necessary except concerning technical characteristics of the
substance where not covered by the Certificate of Suitability (e.g. when the Certificate of
Suitability does not describe a specific technical grade, information and data for the re-test
period).

2- If the Certificate of Suitability (CEP) is not available all the Drug Substance sections in
Module 3.2.S should be full-filled and a valid copy of GMP certificate (for drug substance
manufacturer/s) should be included in section (3.2.R).
The information from the Open Part of the DMF should be provided in drug application.
Information in sections (S.2.2, S.2.3, S.2.4 and S.2.6) may not be available to the holder of
the drug product, they will be in the closed part of the DMF which will be available from the
drug substance supplier, so the supplier of the drug substance can send a Drug Master File
(closed part of the DMF) directly to authority.

3.2.S.1 General Information (name of the active ingredient, manufacturer)

Information on the nomenclature of the drug substance (INN), chemical name, USAN…),
Structure (structural formula, molecular formula).
General properties: A list should be provided of physicochemical and other relevant
properties of the drug substance, including biological activity for biotech, should be
specified.
For Biotech:
The schematic amino acid sequence indicating glycosylation sites or other posttranslational
modifications and relative molecular mass should be provided, as appropriate.

3.2.S.2 Manufacture (name of the active ingredient, manufacturer)

3.2.S.2.1 Manufacture name, address.
The name, address, and responsibility of each manufacturer should be provided.
Name should comply with (CEP or GMP certificate provided).

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3.2.S.2.2 Description of Manufacturing Process& process controls.
The description of the drug substance manufacturing process represents the applicant’s
commitment for the manufacture of the drug substance. Information should be provided to
adequately describe the manufacturing process (flow diagram) and process controls.
For Biotech:
Information should be provided on the manufacturing process, which typically starts with a
vial(s) of the cell bank, and includes cell culture, harvest(s), purification and modification
reactions, filling, storage and shipping conditions.
Batch(es) and scale definition:
An explanation of the batch numbering system, including information regarding any pooling
of harvests or intermediates and batch size or scale should be provided.

Cell culture and harvest:

A flow diagram should be provided that illustrates the manufacturing route from the original
inoculums (e.g. cells contained in one or more vials(s) of the Working Cell Bank up to the
last harvesting operation. The diagram should include all steps (i.e., unit operations) and
intermediates. Relevant information for each stage, such as population doubling levels, cell
concentration, volumes, pH, cultivation times, holding times, and temperature, should be
included. Critical steps and critical intermediates for which specifications are established (as
mentioned in 3.2.S.2.4) should be identified.
A description of each process step in the flow diagram should be provided, information
should be included on, for example, scale, culture media and other additives (details provided
in 3.2.S.2.3); major equipment (details provided in 3.2.A.1); and process controls, including
in-process tests and operational parameters, process steps, equipment and intermediates with
acceptance criteria (details provided in 3.2.S.2.4). Information on procedures used to transfer
material between steps, equipment, areas, and buildings, as appropriate, and shipping and
storage conditions should be provided. (Details on shipping and storage provided in
3.2.S.2.4.)

Purification and modification reactions

A flow diagram should be provided that illustrates the purification steps (i.e., unit operations)
from the crude harvest(s) up to the step preceding filling of the drug substance. All steps and
intermediates and relevant information for each stage (e.g., volumes, pH, critical processing
time, holding times, temperatures and elution profiles and selection of fraction, storage of
intermediate, if applicable) should be included. Critical steps for which specifications are
established as mentioned in 3.2.S.2.4 should be identified.
A description of each process step (as identified in the flow diagram) should be provided.
The description should include information on, for example, scale, buffers and other reagents
(details provided in 3.2.S.2.3, major equipment (details provided in 3.2.A.1), and materials.
For materials such as membranes and chromatography resins, information for conditions of
use and reuse also should be provided. (Equipment details in 3.2.A.1; validation studies for
the reuse and regeneration of columns and membranes in 3.2.S.2.5.) The description should
include process controls (including in-process tests and operational parameters) with
acceptance criteria for process steps, equipment and intermediates. (Details in 3.2.S.2.4.).

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Reprocessing procedures with criteria for reprocessing of any intermediate or the drug
substance should be described. (Details should be given in 3.2.S.2.5.).
Information on procedures used to transfer material between steps, equipment, areas, and
buildings, as appropriate, and shipping and storage conditions should be provided (details on
shipping and storage provided in 3.2.S.2.4.).

Filling, storage and transportation (shipping)

A description of the filling procedure for the drug substance, process controls (including in-
process tests and operational parameters), and acceptance criteria should be provided.
(Details in 3.2.S.2.4.) The container closure system(s) used for storage of the drug substance
(details in 3.2.S.6.) and storage and shipping conditions for the drug substance should be
described.

3.2.S.2.3 Control of Materials.

Materials used in the manufacture of the drug substance (e.g., raw materials, starting
materials, solvents, reagents, catalysts) should be listed identifying where each material is
used in the process. Information on the quality and control of these materials should be
provided.
For Biotech:
 Control of Source and Starting Materials of Biological Origin
 Source, history, and generation of the cell substrate
 Cell banking system, characterization , and testing

3.2.S.2.4 Control of Critical Steps& intermediates.

Critical Steps: Tests and acceptance criteria (with justification including experimental data)
performed at critical steps identified in 3.2.S.2.2 of the manufacturing process to ensure that
the process is controlled should be provided.
Intermediates: Information on the quality and control of intermediates isolated during the
process should be provided.

3.2.S.2.5 Process Validation

Process validation and/or evaluation studies for aseptic processing and sterilization should be
included.
For Biotech:
Sufficient information should be provided on validation and evaluation studies to
demonstrate that the manufacturing process (including reprocessing steps) is suitable for its
intended purpose and to substantiate selection of critical process controls (operational
parameters and in-process tests) and their limits for critical manufacturing steps (e.g., cell
culture, harvesting, purification, and modification).
The plan for conducting the study should be described and the results, analysis and
conclusions from the executed study(ies) should be provided. The analytical procedures and
corresponding validation should be cross-referenced (e.g., 3.2.S.2.4, 3.2.S.4.3) or provided as
part of justifying the selection of critical process controls and acceptance criteria

3.2.S.2.6 Manufacturing Process Development.

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A description and discussion should be provided of the significant changes made to the
manufacturing process and/or manufacturing site of the drug substance used in producing
nonclinical, clinical, scale-up, pilot, and, if available, production scale batches.
For Biotech:
The description of change(s) made to the manufacture of drug substance batches used in
support of the marketing application (e.g., nonclinical or clinical studies) should include.
Testing used to assess the impact of manufacturing changes on the drug substance(s) and the
corresponding drug product(s) can also include nonclinical and clinical studies. Cross-
reference to the location of these studies in other modules of the submission should be
included.

3.2.S.3 Characterization (name of the active ingredient, manufacturer)

3.2.S.3.1 Elucidation of Structure and other Characteristics.
Confirmation of structure based on e.g., synthetic route and spectral analyses should be
provided. Information such as the potential for isomerism, the identification of
stereochemistry, or the potential for forming polymorphs should also be included.
For Biotech:
For desired product and product-related substances, details should be provided on primary,
secondary and higher-order structure, post-translational forms (e.g., glycoforms), biological
activity, purity, and immunochemical properties, when relevant.

3.2.S.3.2 Impurities
Specify impurity profile.

3.2.S.4 Control of Drug Substance (name of the active ingredient, manufacturer):

3.2.S.4.1 Specification (name, manufacturer)
The specification for the drug substance should be provided.
(if pharmacopoeial a copy of the monograph should be included).

3.2.S.4.2 Analytical Procedures (name, manufacturer)

The analytical procedures used for testing the drug substance should be provided.

3.2.S.4.3 Validation of Analytical Procedures (name, manufacturer)

Analytical validation information, including experimental data for the analytical procedures
used for testing the drug substance, should be provided.
Verification used for Pharmacopoeial methods.
Validation used for Non-Pharmacopoeial methods.

3.2.S.4.4 Batch Analyses (name, manufacturer)

Description of batches and results of batch analyses should be provided.

3.2.S.4.5 Justification of Specification (name, manufacturer)

Justification for the drug substance specification should be provided.
(if pharmacopoeial a copy of the monograph should be included).

3.2.S.5 Reference Standards or Materials(name of the active ingredient, manufacturer)

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 Standard name and its manufacturer (provide COA of API reference standard).

3.2.S.6 Container Closure System (name of the active ingredient, manufacturer)

Mention the type of the container, closure.

3.2.S.7 Stability (name of the active ingredient, manufacturer)

Results of the stability studies (e.g., forced degradation studies and stress conditions)
should be presented in an appropriate format such as tabular, graphical, or narrative.
Conclusions with respect to storage conditions and retest date or shelf-life, as appropriate.
Include stability data minimum of: 6 months at accelerated conditions and 12 months at long
term conditions for three batches.

3.2.P DRUG PRODUCT (NAME OF THE FINISHED PRODUCT,

DOSAGE FORM)

3.2.P.1 Description and Composition of the Drug Product (name of the finished
product, dosage form)
A description of the drug product and its composition should be provided.
List of all components of the dosage form, and their amount on a per-unit basis (including
overages, if any) the function of the components, and a reference to their quality standards
(e.g. compendia monographs or manufacturer’s specifications)

REFERENCE
UNIT FORMULA Percentage
NAMES OF INGREDIENTS FUNCTION TO
formula
STANDARDS
ACTIVE SUBSTANCE

EXCIPIENTS

3.2.P.2 Pharmaceutical Development (name of the finished product, dosage form)

This section should contain information on the development studies conducted to establish
the dosage form, the formulation, manufacturing process, container closure system,
microbiological attribute, usage instructions.

3.2.P.2.1 Components of the Drug Product (name of the finished product, dosage form)
3.2.P.2.1.1 Drug Substance (name of the finished product, dosage form)
The compatibility of the drug substance with Excipients should be justified.
Physicochemical characteristics for Drug Substance that can influence the performance of the
drug product should be discussed (e.g., water content, solubility, particle size distribution or
polymorphic form).

3.2.P.2.1.2 Excipients (name of the finished product, dosage form)

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The functions of Excipients, their concentration and their characteristics that can influence
the drug product performance should be discussed for each Excipient.

3.2.P.2.2 Drug Product (name of the finished product, dosage form):

3.2.P.2.2.1 Formulation Development (name of the finished product, dosage form)
A brief summary describing the development of the drug product, including pre formulation
studies or justification if not needed.

3.2.P.2.2.2 Overages (name of the finished product, dosage form)

Any overages in the formulation should be justified.

3.2.P.2.2.3 Physicochemical and Biological Properties (name of the finished product,

dosage form)
Parameters relevant to the performance of the drug product, such as pH, ionic strength,
dissolution, redispersion, reconstitution, particle size distribution, aggregation,
polymorphism, rheological properties, biological activity or potency, and/or immunological
activity, to be addressed if needed.

3.2.P.2.3 Manufacturing Process Development (name of the finished product, dosage

form)
 Specify the critical steps of Manufacturing
 Any differences between pivotal clinical batches and the production batches should
be mentioned with its justification (ex: scaling up from pilot to production).

3.2.P.2.4 Container Closure System (name of the finished product, dosage form)
The suitability of the container closure system (described in 3.2.P.7) used for the storage,
transportation (shipping) and use of the drug product should be discussed. e.g., choice of
materials, protection from moisture and light, compatibility of the materials of construction
with the dosage form (including sorption to container and leaching) safety of materials of
construction, and performance (such as reproducibility of the dose delivery from the device
when presented as part of the drug product).

3.2.P.2.5 Microbiological Attributes (name of the finished product, dosage form)

Where appropriate, the microbiological attributes of the dosage form should be discussed,
including, for example, the rationale for not performing microbial limits testing for non-
sterile products and the selection and effectiveness of preservative systems in products
containing antimicrobial preservatives.
For sterile products, the integrity of the container closure system to prevent microbial
contamination should be addressed.

3.2.P.2.6 Compatibility (name of the finished product, dosage form)

 The compatibility of the drug product with:
 The reconstitution diluent(s) or
 Dosage devices (e.g., precipitation of drug substance in solution, sorption on injection
vessels, stability)

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3.2.P.3 Manufacture (name of the finished product, dosage form)
3.2.P.3.1 Manufacturer(s) (name of the finished product, dosage form)
The name, address, and responsibility of Finished product manufacturer, including
contractors, and each proposed production site or facility involved in manufacturing and
testing should be provided.

3.2.P.3.2 Batch Formula (name of the finished product, dosage form)

A batch formula should be provided that includes a list of all components of the dosage form
to be used in the manufacturing process and their amounts on a per batch basis.

3.2.P.3.3 Description of Manufacturing Process and Process Controls (name, dosage

form)
A flow diagram should be presented giving the steps of the process and showing where
materials enter the process.
The critical steps and points at which process controls, intermediate tests or final product
controls are conducted should be identified.
A narrative description of the manufacturing process, including packaging, that represents
the sequence of steps undertaken and the scale of production should also be provided.
Equipment should, at least, be identified by type (e.g., tumble blender, in-line homogeniser)
and working capacity, where relevant.
Steps in the process should have the appropriate process parameters identified, such as time,
temperature, or PH. Associated numeric values can be presented as an expected range.
Numeric ranges for critical steps should be justified in Section 3.2.P.3.4. In certain cases,
environmental conditions (e.g., low humidity for an effervescent product) should be stated.

3.2.P.3.4 Controls of Critical Steps and Intermediates (name of the finished product,
dosage form)
Critical Steps: Tests and acceptance criteria should be provided (with justification, including
experimental data) performed at the critical steps identified in 3.2.P.3.3 of the manufacturing
process, to ensure that the process is controlled.
Intermediates: Information on the quality and control of intermediates isolated during the
process should be provided.

3.2.P.3.5 Process Validation and/or Evaluation (name of the finished product, dosage
form).
Process validation protocol (should outline the formal studies planned for the production
scale batches) or / and Process Validation Report should be provided. (Which include
Description, documentation, and results of the validation studies for critical steps or critical
assays used in the manufacturing process).

Validation of the sterilization process or aseptic processing or filling should be provided.

3.2.P.4 Control of Excipients (name of the finished product, dosage form)

3.2.P.4.1 Specifications (name of the finished product, dosage form)
The specifications for excipients should be provided.
(if compendial provide the monographs).

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3.2.P.4.2 Analytical Procedures (name of the finished product, dosage form)
The analytical procedures used for testing the excipients should be provided (if compendial
provide the monographs).
Also provide Certificate of Analysis of each excipient.

3.2.P.4.3 Validation of Analytical Procedures (name of the finished product, dosage

form)
For Pharmacopoeial Excipients (Not Applicable).
For non-compendial excipients, Analytical validation information, including experimental
data, for the analytical procedures used for testing the excipients should be provided, where
appropriate.

3.2.P.4.4 Justification of Specifications (name of the finished product, dosage form)

For Pharmacopoeial Excipients (Not Applicable).
For non-compendial excipients, Justification for the proposed excipient specifications should
be provided, where appropriate.

3.2.P.4.5 Excipients of Human or Animal Origin (name of the finished product, dosage
form)
For excipients of human or animal origin, EDQM certificate of TSE/BSE free certificates or
certificate from health authorities should be provided.
3.2.P.4.6 Novel Excipients (name of the finished product, dosage form)
If included in the drug formula (full details if used for the first time in a drug product.)

3.2.P.5 Control of Drug Product (name of the finished product, dosage form)
3.2.P.5.1 Specification(s) (name of the finished product, dosage form)
The specification for the drug product should be provided.

METHOD &
PARAMETER SPECIFICATIONS
REFERENCE

3.2.P.5.2 Analytical Procedures (name of the finished product, dosage form)

The analytical procedures (Method of Analysis) used for testing the drug product should be
provided.

3.2.P.5.3 Validation of Analytical Procedures (name of the finished product, dosage

form)
 Validation of method of analysis, including experimental data, for the analytical
procedures used for testing the drug product, should be provided (Assay, impurities,
dissolution.)

Note: if the analytical procedures used in the control of the drug product are Pharmacopoeial
then verification is required which include:

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  System suitability (tailing factor, resolution, stability of solution, theoretical plates, …)
Selectivity including spiking (to prove resolution from excipients), stress conditions
testing and purity of the peak (the method used to prove the purity of the peak should be
stated).
 Linearity and Accuracy

3.2.P.5.4 Batch Analyses (name of the finished product, dosage form)

A description of batches and results of batch analyses should be provided,
Description of batches as the following:

Results of batch analyses:

DRUG NAME BATCH MANUFACTURIN MANUFACTURING PACKAGE BATCH SIZE &TYPE
& CONC. NO. G DATE SITE TYPE (Pilot, Production)

Results of batch analyses

Test Parameters
BATCH NO. BATCH NO. BATCH NO.
Acceptance criteria

Results Results Results

A copy of the original analysis certificates for all these batches are included at the end of Part
3.2.P as regional information (3-2-R).

3.2.P.5.5 Characterization of Impurities (name of the finished product, dosage form)

Information on the characterization of impurities should be provided, it could be referred to
Module 3, Drug substance section "3.2.S.3.2 Impurities".

3.2.P.5.6 Justification of Specification(s) (name of the finished product, dosage form)

Justification for the proposed drug product specification should be provided (if not
compendial).

3.2.P.6 Reference Standards or Materials (name of the finished product, dosage form)
Refer to Module 3, section "3.2.S.5 Reference Standards or Materials".

3.2.P.7 Container Closure System (name of the finished product, dosage form)
A description of the container closure systems should be provided
(and critical dimensions, with drawings where appropriate), along with specification and
Method of Analysis (Where appropriate).

For non-functional secondary packaging components (e.g., those that neither provide
additional protection nor serve to deliver the product), only a brief description should be
provided.

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For functional secondary packaging components, additional information should be provided.

3.2.P.8 Stability (name of the finished product, dosage form)

3.2.P.8.1 Stability Summary and Conclusion (name of the finished product, dosage
form)
The types of studies conducted (Accelerated, Long term…), protocols used, and the results of
the studies should be summarized.
The summary should include, conclusions with respect to storage conditions (labeling
statement) and shelf-life that will be applied on the product indented to be marketed in our
country. and, if applicable, in-use storage conditions and shelf life.

Provide Special stability tests for different dosage forms (e.g. inverted stability study,…) if
applicable.

Summarize Forced degradation studies and stress condition (i.e. Photo stability studies) if
applicable.

3.2.P.8.2 Post-approval Stability Protocol and Stability Commitment (name of the

finished product, dosage form)
The post-approval stability protocol and stability commitment should be provided:
1. To Complete Real Stability Data (to cover shelf life) on pilot batches (if not completed at
time of submission) and Real Stability Data on production batches (if not submitted with
file) once they are available as annual report.
2. Ongoing stability (Real data as annual report).

3.2.P.8.3 Stability Data (name of the finished product, dosage form)

Results of the stability studies should be presented for 3 batches:
Accelerated (40 ± 2 °C / 75 % RH ± 5 %) minimum time period at submission (6 months)
Long term (30 ± 2 °C / 65 % RH ± 5 % Zone IV a) minimum time period at submission
(12 months) with a commitment to cover the shelf life once available.
Provide Supportive stability data (if available).

For biosimilars: the quality sections (should include comparative studies with reference
drug, beside his own) in section 3.2.R (or according to international practice).

3.2.R:
 Certificate of Analysis for drug substance from supplier/s
& from Drug Product manufacturer.
(COA should be Stamped & Signed, or electronic signature).

 Valid certificate of suitability [CEP] from EDQM for drug substance [from each supplier]
(copy).
 Valid GMP certificate for drug substance manufacturer(copy)[ from each manufacturer ]
Only if CEP is not available (note that in this case all drug substance sections will be
required).
 Raw data and chromatograms for stability study.

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 Summary of production & Quality control protocol.
 PMF

3.2.A
SMF

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 Appendix E: Module 4 Nonclinical Study Reports
4.1 TABLE OF CONTENTS
A Table of Contents should be provided that lists all of the Nonclinical Study Reports and gives
the location of each study report in the Common Technical Document.
4.2 STUDY REPORTS
The study reports should be presented in the following order
4.2.1Pharmacology
4.2.2Pharmacokinetics
4.2.3Toxicology
4.3 LITERATURE REFERENCES

For Generic: Module 4 (Not applicable ).Literature References may be included.

For the biosimilars: non-clinical studies are required in section (to be specified later according
to international practice).

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 Appendix F: Module 5 – Clinical Study Reports
5.1 TABLE OF CONTENTS
A table of contents for the study reports should be provided.

5.2 Tabular Listing of All Clinical Studies

5.3 Clinical Study Reports

5.3.1 Reports of Biopharmaceutic Studies

5.3.1.1 Bioavailability (BA) Study Reports

5.3.1.2 Comparative BA and Bioequivalence (BE) Study Reports:

For Generic: Provide Bioequivalence Study report (format & content submitted according to the
data specified in BE registration criteria) which includes:
 Table of content of BE (BE checklist appendix L)
 BE Additional requirements in appendix L
 Summary report
 In-vitro testing
 In-vivo study design
 Assay methodology Validation
 Pharmacokinetic Parameters of BE
 Statistical Analysis
 Appendices (for Detailed Analysis)

5.3.1.3 In vitro-In vivo Correlation Study Reports

5.3.1.4 Reports of Bioanalytical and Analytical Methods for Human Studies

For Generic: Summary Bioequivalence tables:
 Reanalysis of Study Samples
 Summary of Standard Curve and QC Data for Bioequivalence Sample Analyses
 SOPs Dealing with Bioanalytical Repeats of Study Samples

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5.3.2 Reports of Studies Pertinent to Pharmacokinetics using Human Biomaterials
For Generic: Not Applicable

5.3.3 Reports of Human Pharmacokinetic (PK) Studies

For Generic: Should be provided, if BE study not submitted (Justified)

5.3.4 Reports of Human Pharmacodynamic (PD) Studies

For Generic: Should be provided, if BE study not submitted (Justified)

5.3.5 Reports of Efficacy and Safety Studies

For Generic: Not Applicable

5.3.6 Reports of Post-Marketing Experience

Risk management Plan (where appropriate).
PSUR to be submitted after product placed in the market of the country of origin.

5.3.7 Case Report Forms and Individual Patient Listings

For Generic: Not Applicable

5.4 Literature References

For originator drugs: only the Literatures Pertinent to the Claimed Indication(s) are required.
For Generic: Optional, the Literature References for the originator drug (Pertinent to the
Claimed Indication(s)) should be included in case where originator drug is not registered in
Jordan.

For biosimilars: the clinical studies (comparative) are required in section (to be specified later
according to international practice).

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 Appendix G: File Formats

General requirements:
Generally, the relevant information must be structured according to the requirements of the
Common Technical Document (CTD). The following files formats are accepted:
• PDF
• For graphics: Joint Photographic Experts Group (JPEG), Portable Network Graphics
(PNG), Scalable Vector Graphics (SVG) or Graphic Interchange Format (GIF).

Portable Document Format:

PDF is an open, de facto, published format created by Adobe Systems Incorporated
(http://www.adobe.com). It is not necessary to use a product from Adobe or from any specific
company to produce PDF documents. PDF is accepted as a standard for documents defined in
this specification. The following recommendations support the creation of PDF files that
agencies can review effectively. To ensure that PDF files can be accessed efficiently, PDF files
should be no larger than 100 megabytes. Optimize PDF files for fast web view.
The following points can be made in relation to PDF files:
• Files must be legible with PDF version 1.4 or higher
• PDF files produced from an electronic source document are highly preferred over
PDF files produced from scanned paper, since those 'electronic' PDF files provide the
maximum functionality to the reviewers in terms of search and print capabilities, and
copy and paste functionality. The overviews/summaries in the CTD Module 2 should
always be generated from an electronic source document.
• If scanning is unavoidable, readability and file size must be balanced; the following
is recommended: resolution 300 dpi (photographs up to 600 dpi), avoid gray scale or
color where possible, use only lossless compression techniques.
• If colors other than black are used, the colored pages must be tested on a black and
white printer for acceptable reproduction and legibility prior to submission.
• Print area for pages must fit on an A4 sheet of paper; margins must allow binding in
multi-ring binders without affecting readability.
• Landscape-oriented tables must automatically appear in landscape on screen.

Text Searchable Files:

Applicants are requested to ensure that all submissions contain the maximum amount of text
searchable content. Documents with searchable text will aid the assessor, or any other user, in
searching for specific terms and also in copying and pasting information into another document,
such as an assessment report. JFDA recognizes that not all documents need to be text searchable.

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This appendix provides some guidance about what must be text searchable and the ways to
ensure that files are created appropriately.

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Documents that must always be text searchable:
The PDF should be produced wherever possible from a text source, such as MS Word, but if
sourced from a scanned original then they must be OCR’d.
• Key administrative documents in Module 1 including, the cover letter, application
form, SPC, labeling and PIL documents
• The main body of text of Risk Management Plans
• Any document in Module 2 of the submission (QOS, Nonclinical Overview and
Summaries, Clinical Overview and Summaries).
• The main body of text in any reports, methods, analytical procedures, etc. supplied in
Module 3 of the submission
• The main body of text and main tables in modules 4 and 5.
Documents that do not need to be text searchable:
The PDF should be produced wherever possible from a text source, such as MS Word, but if
sourced from a scanned original then there is no need for OCR.
• Any original Certificate of Pharmaceutical Product
• Any original Certificate that confirm that the product is free from BSE/TSE
• Any original GMP certificate
• Any original certificate of analysis
• Any manufacturer’s licenses
• Any certificates of suitability
• Any Manufacturing Authorization
• Any literature references sourced from journals, periodicals and books (except when
these are used in a bibliographic application so support the main claims of the
application).
• Any page with a signature that does not contain other information key to the
understanding of the submission
• Applicants should consider providing signatures on separate pages from key text in
reports, overviews, etc.

Use of Electronic Signatures:

The use of advanced electronic signatures (digital signatures) will be crucial in achieving pure
electronic communication between the pharmaceutical industry and regulatory agencies,
particularly for authentication of electronic submissions and documents contained therein.

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 Appendix H: ICH Common Technical Document
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 M4 (http://www.ich.org/). 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 3Figure 3). 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

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Figure 3: Diagrammatic representation of the organization of the ICH CTD

eCTD
The eCTD is defined as an interface for industry to agency transfer of regulatory information
while at the same time taking into consideration the facilitation of the creation, review, lifecycle
management and archival of the electronic submission.
The eCTD is an electronic version of the CTD. The structure, folder and file names correspond
to those of the CTD. As a submission format, however, it contains additional technical
components which enable the lifecycle of individual files in the application, and the lifecycle of
the product itself, to be managed.
An eCTD has the following components: Folder structure, Contents (files) and XML backbone.

The folder structure has a hierarchical organization reflecting that of the CTD, and it holds the
scientific and technical contents of the eCTD (divided into many files which are the same as
those in the non-eCTDs, usually in PDF format).
The XML backbone is recognizable as ‘index.xml’ at the root level of the submission folder of
an eCTD and provides two useful functions:

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• It provides a hyperlinked table of contents of the entire submission when viewed in a
web browser with a suitable style sheet
• It provides descriptive information (‘metadata’) on the files that make up the actual
contents of the eCTD.

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 Appendix I: References
JFDA Reference Documents:

 Regulatory Framework for Drug Approvals (eJDWS)

 JO Module 1 Specifications
The latest versions of JFDA's guidance documents are available on the website at the
following address:
http://www.jfda.jo

ICH Reference Documents:

M4: The Common Technical Document

 Organization of The Common Technical Document for the Registration of

Pharmaceuticals for Human Use

 Implementation Working Group – Questions & Answers (R3)

 Electronic Common Technical Document Specification (version 3.2)
 The Common Technical Document for The Registration of Pharmaceuticals for
Human Use: Quality – M4Q(R1)

 The Common Technical Document for The Registration of Pharmaceuticals for

Human Use: Safety – M4S(R2)

 The Common Technical Document for The Registration of Pharmaceuticals for

Human Use: Efficacy – M4E(R1)
These documents and more are found at the ICH website at the following address:
http://www.ich.org/

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 Appendix J: Renewal Requirements

J1: First Renewal

Section Description Remarks
1.0 Cover letter CL from applicant
requesting re-registration in
addition to
Cover letter from MAH
requesting re-registration
1.2 Application Forms
1.3 Product Information
1.3.1 Summary of Product Characteristics (SPC) and Legalized SmPC for
comparison originator
1.3.2 Labelling
1.3.3 Patient information leaflet (PIL)
1.3.3 ar Arabic leaflet
1.3.3 en English leaflet and Comparison For generics: comparison
with originator leaflet
1.3.4 Artwork (Mock-ups)
1.7 Certificates and Documents
1.7.1 Manufacturing Sites Documents Copy of JFDA API and
finished product
manufacturer approval
1.7.2 CPP or Free-Sales Legalized CPP/FSC
1.7.3 Certificate of analysis - Drug Substance &
Finished Product
1.7.4 Certificate of analysis - Excipients
1.7.5 Declaration of Ingredients from human origin List of human or animal
origin substances entering in
the composition of the
product and its source and
the related certificates
1.7.6 Pork-content declaration
1.8 Price
1.8.1 Price Certificate Legalized price certificate
1.8.2 Other documents related Copy of JFDA pricing
certificates
Additional Data

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 Copy of JFDA MA
certificate
Copy of all JFDA approval
on any variation submitted
Comparison table between
registered dossier & renewal
dossier
Registration status world
wide
Declaration letter from
manufacturer with no
changes (Manufacturing
process, MoA, formula,
packaging material,
specifications, ….) if
change it should be
submitted.
Updated technical
agreement in case of
contract manufacturing
Copy of COO approval for
plasma master file
Module 3 :
3.2.P.1 Description and Composition of the Drug Composition certificate
Product
3.2.P.5.1 Specification(s) Release and shelf life
specification mentioning the
last one approved (number,
date).
3.2.P.8.3 Stability Data Ongoing stability study for
at least one new production
badge
3.2.R 1- Updated plasma master file 3.2.R If applicable
Module 5
5.3.6 Reports of Postmarketing Experience Updated post marketing
safety reports/ PSUR (if
applicable)

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 J2: Second Renewal
Section Description Remarks
1.0 Cover letter CL from applicant
requesting re-registration in
addition to
Cover letter from MAH
requesting re-registration
1.2 Application Forms
1.7.2 CPP or Free-Sales Legalized CPP/FSC (not
required for local products)
1.8 Price
1.8.1 Price Certificate Legalized price certificate
(not required for local
products)
1.8.2 Other documents related Copy of latest JFDA pricing
letter
Additional Data
Copy of JFDA renewal
certificate

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 Appendix K: Baseline Requirements

Module 1: Regional Administrative Information

1- Cover letter
2- Application Form
3- Product Information
a. Summary of Product Characteristics (SPC) and comparison
b. Labelling
c. Patient information leaflet (PIL)
i. Arabic leaflet
ii. English leaflet and comparison
d. Artwork (Mock-ups)
4- Certificates and Documents
5- CPP or Free-sales

Module 3: Quality
1- Drug Substance
2- Drug Product
3- Appendices

Page 48 of 54
 Appendix L: BE/ Comparative dissolution checklists

L1: BE Check List

Agent Name …………… Date of submission:..............................

Administrative part Title Page
 Declaration from product manufacturer of the following:
* Name of test product/dosage form/conc ------------------------
* Name of reference product/dosage form/conc -----------------
* Bio-batch manufacturer……………………………………………
* Finished product manufacturer……………..
* MAH………………
* Source of the API of the bio-batch…………….
* Bio-batch size & type ( production /pilot)
* Bio-analysis date ( start-end)
* Declaration from MAN/MAH that no change in formula of test product since
study time.
* Study title/Date of study : -------------------------------------------------------------
* Study type (fed .fast ) ------------------------------------------------------------------------
* Name and address of sponsor…………………………..
* Name and address of CRO ( clinical site)
* Name and address of clinical laboratory( bio-analytical site)
 Name, address of the clinical investigator-----------------------------------------
 Copy of GMP certificate of the bio-batch manufacturer if it's not approved ------
If approved copy of health authorities approval of the site --------------------------
 Approval of following GCP from Health Authorities of country of clinical
investigator /or inspection reports of the study according to adopted BE
guidance
 Approval of following GLP from Health Authorities of country of clinical
laboratory/or inspection reports of the study according to adopted BE guidance
 Copy of protocol approval from health authorities if the CRO is in Jordan or
copy of protocol approval by IRB committee
 Composition of the bio-batch /copy of the recent CPP of test product
 Certificate of analysis of study batches (T&R)

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Technical part Table of contents
 Study resumes.
 Name, and signature of the investigator (s).
 Name, and signature of the clinical investigator (s).
 Product information (Pharmacology, Pharmacokinetic)
 Summary of Bioequivalence study.
 Summary of bioequivalence data.
 Figure of mean plasma concentration-time profile (Log, Normal).
 Figure of mean cumulative urinary excretion (if used). ( Log ,Normal
 Figure of mean urinary excretion rates (if used). ( Log ,Normal)
 In vitro testing.
1. Certificate of analysis of study batches (T&R) by the sponsor
2. Full composition of bio-batch of test product
3. Dissolution method and validation
4. Comparative dissolution profile
5. Content uniformity testing.
 Study designs.
1. Introduction.
2. Summary and type of the study.
3. Signature of IRB committee
4. Study Protocol.(no of subjects, exclusion and inclusion criteria)
5. Demographic characteristics of the subjects.
6. Informed consent form.
7. Details of clinical activity.
8. Deviations from protocol.
9. Adverse reactions report.
 Assay Methodology and Validation.
1. Assay method description (including description of the order analyzing real
samples and quality control samples.
2. Method Validation with chromatograms.
3. Data on linearity of standard samples.
4. Data on inter-day precision and accuracy of low, intermediate & high
concentration.
5. Data on intra-day precision and accuracy
6. Calibration / standard curves.
7. QC Chromatograms for low/ high ranges.
8. Chromatograms of standard and quality control samples. Complete serial
chromatograms for 5- 20% of subjects.
9. Data demonstrating stability of samples.
10.Short-term stability of the lowest concentration.
11.Long-term stability of the lowest concentration.
12.Limit of Quantification.

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 13.Freeze- thawing stability of lowest concentration
14.Discussion and Conclusion.
 Pharmacokinetic parameters.
 Table and figure of mean plasma concentration-time profile( Log ,Normal).
 Table and figure of individual subject plasma concentration time profiles.
 Figure of mean accumulative urinary excretion (if applicable).
 Figures of individual subject cumulative urinary Excretion (if applicable).
 Figure of mean-urinary excretion rates (if applicable).
 Figures of individual subject urinary excretion rates.
 Results of analyzed data arranged by, Drug/period,
 Drug/sequence for volunteers.
 Statistical Analysis
1. Statistical consideration.
2. Summary of statistical significance.
3. Summary of statistical parameters.
4. Analysis of variance (ANOVA).
5. Parametric and additional nonparametric optional 90% confidence Intervals
(lower limit, upper limit and point estimate)
6. Two one-sided t-test (lower limits, upper limits of the calculated test statistics
and the tabulated t-value).
 Appendices
1. Analytical raw data (copies of chromatograms should be provided as obtained
from the instrument showing retention time and integrated peak areas)
2. Medical record and clinical reports.
3. Print out of pharmacokinetic analysis (optional).
4. Print out of statically analysis (optional)

* Please fill with data where is possible

1. I declare that all the documents which refer to in this check list are attached & number
of files Submitted for this application…………………………………
2. For office health authorities (use :
I declare that I received the files Submitted for this
application…………………………………

- Name & Sign of responsible Pharmacist in registration

Department:………………………………….
- Application Number:………………………… Date:…………………
- Fees 400JD Date:…………………

- Name & Sign of responsible Pharmacist:……………………………

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 L2: Comparative In vitro dissolution checklist

Item Page No.

 Declaration from product manufacturer of the following:
*Name of test product/dosage form/conc ------------------------
* Name of reference product/dosage form/conc -----------------
* Bio-waiver batch manufacturer……………………………………………
* Finished product manufacturer……………..
* MAH………………
* Source of the API of the bio-waiver batch…………….
* Bio-waiver batch size & type ( production /pilot)
* Declaration from MAN/MAH that no change in formula of test product since study time
* Reason for Biowaiver request (BE for another strength, BCS Class I or III,.. others)

Composition of each product /R&T /copy of the recent

CPP of test product.
Proof of Linear Pharmacokinetics covering the dosage
range of interest/(in case of strength waivering )
Proof of dosage proportionality (in tabular format)
between the test & reference drug products. /(in case of
strength waivering )
Proof of BCS classification (BCS Class I or III)
regarding solubility & permeability with solubility study.
/(in case of BCS waivering )
Proof of similarity with the reference drug product
composition according to JFDA adopted BE\BW
guidelines/(in case of BCS waivering )
Certificate of analysis of bio-waiver batch &
Certificate of analysis of reference batch
No of media/
Type of media
No of dosage form tested..
Method of analysis /validation
Dissolution/ in-vitro test … condition /speed…..
Details of results / tabulated
F2 value /Similarity calculation
Graphs
3. I declare that all the documents which refer to in this check list are attached &
number of files Submitted for this application
- Name & Sign of responsible Pharmacist:…………………………… Date:
…………………

4. For official (use :

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I declare that I received the files Submitted for this application…………………………………
- Name & Sign of responsible Pharmacist in registration Department:
…………………………………
- Application Number:………………………… Date:
………………………
- Fees 100 JD

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 Appendix M: Abbreviations and Acronyms

API Active pharmaceutical ingredient

CEP/COS Certificate of Suitability
COO Country of Origin
CPP Certificate of Pharmaceutical Product
CTD Common Technical Document
DMF Drug Master File
EDQM European Directorate for Quality of Medicines Certification unit.
eJDWS electronic Jordan Drug Workflow System
EXF Ex-factory price
FPP Finished pharmaceutical product
GMP Good manufacturing practices
INN The International Non-proprietary Name
JFDA Jordan Food and Drug Authority
MAA Marketing Authorization Application
NCE New Chemical Entity
PIL Patient Information Leaflet
SPC Summary of Product Characteristics
TSE CEP Transmissible Spongiform Encephalopathy.
WSP Whole Sale Price

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