Guidance-for-Applicants For eCTD Submission
Guidance-for-Applicants For eCTD Submission
Guidance-for-Applicants For eCTD 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
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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.
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).
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
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.
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.
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.
5.3 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.
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.
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6. Document Requirements
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
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:
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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:
Notes:
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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 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”.
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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
1.3.5 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
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
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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.
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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.
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).
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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.
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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.
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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.).
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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.3.2 Impurities
Specify impurity profile.
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Standard name and its manufacturer (provide COA of API reference standard).
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.2.1 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).
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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.2.4 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).
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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.3.4 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).
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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.4.5 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
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
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.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.
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.
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 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.
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5.3.2 Reports of Studies Pertinent to Pharmacokinetics using Human Biomaterials
For Generic: Not Applicable
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).
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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.
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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:
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
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Appendix J: Renewal Requirements
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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 3: Quality
1- Drug Substance
2- Drug Product
3- Appendices
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Appendix L: BE/ Comparative dissolution checklists
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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)
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L2: Comparative In vitro dissolution checklist
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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
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