JORDAN Module 1 ectd Specification Version 1.0.1

Transcription

1 المو سسة العامة للغذاء والدواء Jordan Food & Drug Administration JORDAN Module 1 ectd Specification Version Drug Directorate Jordan Food & Drug Administration Vision: To excel regionally & globally as a pioneer in the field of food, medicine and related materials, so as to enhance public health and consumer s confidence. Mission: Ensuring food safety & quality, as well as effectiveness, quality & safety of the drug materials through the application of controlled systems based on the scientific and international standards. Please visit JFDA s website at for the latest Jordan Food & Drug Administration 1

2 DOCUMENT CONTROL Version Date Authors s Drug Directorate Minor issued corrected Drug Directorate Approved version 1 Jordan Food & Drug Administration 2

3 TABLE Of CONTENTS 1 Introduction Background Scope Technical Requirements Change Control Glossary JO Module 1: Regional Information General Considerations Document Granularity Correspondence Sequence Numbers Bookmarks and Hypertext Links Regional Formats Module Modules 2 to Handling of Empty or Missing ectd Sections Technical information Use of Electronic Signatures Security Issues Virus Protection Password Protection General Architecture of Module Checksum Envelope XML Catalogue Directory / Structure Naming Convention Business Protocol Change Control Instructions for Extension Submissions Reformatting Universally Unique Identifier Baseline ectd Submission Requirements Introduction Technical Baseline Application and Timeline Baseline Starting as Sequence Baseline Cases For Products Submitted as Soft Copies of CTD/CTD: Jordan Food & Drug Administration 3

4 2. For Products Submitted as ectd For Renewal or Variation: Components of an ectd Baseline Submission: Requirements for Baseline APPENDIX Appendix 1: Envelope Element Description Appendix 2: Directory/ Structure for JO Module Appendix 3: Example Screenshot Appendix 5: Modularized DTD for JO Module Jordan Food & Drug Administration 4

5 1 Introduction This document specifies Module 1 of the electronic Common Technical Document (ectd) for Jordan Food and Drug Administration (JFDA). This document should be read together with the ICH ectd Specification to prepare a valid ectd submission for JFDA. The latest version of the ICH ectd Specification can be found at: The ICH M4 Expert Working Group (EWG) has defined the Common Technical Document (CTD). The ICH M8 EWG has defined in their current document, the specification for the Electronic Common Technical Document (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, life cycle management and archiving of electronic submissions. The ectd specification lists the criteria that will make an electronic submission technically valid. The focus of the specification is to provide the ability to transfer the registration application electronically from industry to a regulatory authority. Industry to industry and agency to agency transfer is not addressed Background The specification for the ectd is based upon content defined within the CTD issued by the ICH M4 EWG. The CTD describes the organization of modules, sections and documents. The structure and level of details specified in the CTD have been used as the basis for defining the ectd structure and content but, where appropriate, additional details have been developed within the ectd specification. The philosophy of the ectd is to use open standards. Open standards, including proprietary standards which through their widespread use can be considered de facto standards, are deemed to be appropriate in general Scope The CTD as defined by the M4 EWG does not cover the full submission structure that is to be made in a region. It describes only modules 2 to 5, which are common across all regions. The regional Administrative Information and Prescribing Information is described in Module 1. The CTD does not describe Jordan Food & Drug Administration 5

6 the content of module 1 because it is regional specific, nor does it describe documents that can be submitted as amendments or variations to the initial application. The value of producing a specification for the creation of an electronic submission based only upon the modules described in the CTD would be limited. Therefore, the M2 EWG has produced a specification for the ectd that is applicable to all modules of initial registration applications and for other submissions of information throughout the life cycle of the product, such as variations and amendments Technical Requirements The specification is designed to support high-level functional requirements such as the following: Copying and pasting Viewing and printing of documents Annotation of documentation Facilitating the export of information to fileshares and databases Searching within and across applications Navigating throughout the ectd and its subsequent amendments/variations 1.4. Change Control The specification for the ectd is likely to change within time. Factors that could affect the content of the specification include, but are not limited to: Change in the content of the CTD, either through the amendment of information, at the same level of detail, or by provision of more detailed definition of content and structure Change to the regional requirements for applications that are outside the scope of the CTD Updating standards that are already in use within the ectd Identification of new standards that provide additional value for the creation and/or usage of the ectd Identification of new functional requirements Experience of use of the ectd by all parties 1.5. Glossary A brief glossary of terms (for the purpose of this document only) is indicated below: Jordan Food & Drug Administration 6

7 Applicant Application ASMF/DMF CEP CTD DTD ectd EWG Extension ICH JFDA JPEG MAA MAH Soft Copies of CTD PDF PMF PNG Procedure PSUSA Reformat Regulatory Activity Renewal RMP RTF A local pharmaceutical company or the agent of the foreign pharmaceutical company that is submitting information in support of an application. A collection of documents compiled by a pharmaceutical company or its agent in compliance with guidelines in order to seek a marketing authorization or any amendments thereof. Active Substance Master / Drug Master Certificate of Suitability to the monographs of the European Pharmacopoeia Common Technical Document is an international harmonized format for submissions for approval of pharmaceuticals for human use. The CTD provides a standardization of the presentation of the content. Document Type Definition electronic Common Technical Document An ectd application may comprise a number of sequences. Expert Working Group; charged with developing a harmonised guideline that meets the objectives in the Concept Paper and Business Plan Registration of different strength of already registered prodcuts, different dosage forms,.., The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Jordan Food and Drug Administration Joint Photographic Experts Group Marketing Authorisation Application Marketing Authorisation Holder Non-electronic Documents in Common Technical Document Structure Portable Document Format Plasma Master Portable Network Graphics A registration procedure for the authorization of medicinal products Periodic Safety Update Report Single Assessment procedure Intended to support the reformatting of an existing submission application from any format to ectd A single sequence or collection of sequences covering the start to the end of a specific business process, e.g. an initial MA application or TCA, RA, N1, N2 variation. It is a concept used in some review tools to group together several business related sequences. A process of renewing the marketing authorization license every five years. Risk Management Plan Rich Text Format Jordan Food & Drug Administration 7

8 Sequence Submission Submission Type Submission Unit SVG TOC USR UUID Variation XML XSL Electronic documents supplied at one particular time by the applicant as a part of or the complete application. Sequences may be related to one another within one regulatory activity. The related sequence number should always be stated. In case of activities with only one sequence or in the start sequence of a new regulatory activity the same sequence number will be used. A single set of information and/or documents supplied by the applicant as a part of or the complete application. In the context of ectd, this is equivalent to sequence. The submission type describes the regulatory activity to which the content will be submitted e.g. BGD, BLA, BLS (listed in Appendix 4). The submission unit element of the envelope metadata set describes the content at a lower level (a sub-activity ) which is submitted in relation to a defined regulatory activity such as the applicant response to validation issues or list of questions or any other additional information. Scalable Vector Graphics Table Of Contents Urgent Safety Restriction Universally Unique Identifier A process of informing the authority of any minor or moderate or major changes in the drug product. extensible Markup Language extensible Stylesheet Language 2 JO Module 1: Regional Information The ICH Common Technical Document (CTD) specifies that Module 1 should contain region specific administrative and Jordan product information. The content and numbering of Module 1 for Jordan is specified in the latest version of the Guidance for Submission that can be found at It should be noted that for subsequent submissions in the lifecycle of a medicinal product, e.g. for a variation, not all of the above mentioned kind of documents need be included in Module 1. In addition, other items such as the rationale for variations and renewal documentation could also be included in Module 1. This document describes only the region-specific information that is common to all ectd submissions in Jordan General Considerations Jordan Food & Drug Administration 8

9 Typically, an ectd application will cover all dosage forms and strengths of a product with any one invented name. but at the moment JFDA will accept ectd applications for each dosage form and each strengths of a product Document Granularity Submissions are a collection of documents and each document should be provided as a separate file. The detailed structure of the ectd should be according to the ICH and JO M1 specifications Correspondence In addition to the ectd application, information may need to be exchanged to assist the processing or handling of the application. Not all that correspondence should be included in the ectd and might be provided in a separate way, e.g. via Sequence Numbers Sequence numbers are used to differentiate between different submissions of the same application over the life cycle of the product Bookmarks and Hypertext Links Navigation through an electronic submission is greatly enhanced by the intelligent use of bookmarks and hypertext links. ICH guidance states It is expected that any document that has a Table of Contents (TOC) will have bookmarks (see the ectd specification for details). Documents without TOCs should have bookmarks included where it aids in the navigation around the document content. For example, 4-page document summarizing findings could require bookmarks to aid navigation. However, a 300-page file containing a single data listing might not require bookmarks as there is no further internal structure. In general terms, bookmarks and hyperlinks should be used to aid navigation. The overuse of hyperlinks may confuse rather than help assessors and may cause problems later in life cycle management. Additional details on creating bookmarks and hypertext links in PDF documents can be found in the ICH ectd Specification, Appendix 7. Jordan Food & Drug Administration 9

10 2.2. Regional Formats Module 1 The file formats that can be included in Module 1 are given in Table 1. XML is also an acceptable format for the delivery of structured data in Module 1, specifically the application form and product information, as long as the XML is produced according to the standard defined in the electronic Application Forms. Although the use of the file formats defined in Table 1 is strongly recommended, the JFDA and applicants could agree on the use of other formats in Module 1, for example, the proprietary format MS Word is for Product Information documents in Module 1.3 These documents, if requested, should not be referenced in the ectd backbone, and should always be provided in addition to the PDF versions, but in a separate folder outside the ectd sequence folder (e.g. working-documents ). Table 1: Acceptable file formats for JO Module 1 Document Format Remark Administrative forms: Application form and its annexes Variation application form incl. background for the variation XML, PDF, RTF PDF, RTF Renewal form and its PDF, RTF annexes signature. Product Information: Labeling text Packaging mock-ups Reference to Specimens Readability Testing Information relating to Orphan Applications Other XML, PDF, RTF XML, PDF, RTF PDF PDF PDF PDF, RTF Documents should be generated from electronic source documents, any signature may be embedded as graphic file in the PDF text if desired, although this is not necessary as the hard paper copy contains the legally binding If a higher resolution is necessary for the mock-ups, use JPEG, GIF, PNG or SVG on a case-by-case basis. Labeling texts can be submitted in XML format according to the PIM Data Exchange Standard. In that context, images can be transmitted in JPEG, GIF, PNG, TIF, SVG, or MathML. PDF preferably generated from electronic source Jordan Food & Drug Administration 10

11 Document Type Definitions and Stylesheets Modules 2 to 5 DTD, XSL These are XML specific file formats and must only be the specified versions of the specific files required for the submission of electronic Application Forms No additional file formats are defined for Modules 2 to 5 other than those mentioned in the ICH ectd Specification Document. The JFDA and pharmaceutical companies could agree on a case-by-case basis to use formats other than the common formats (e.g. RTF). However, the use of formats other than those specified by the ICH ectd Specification Document is discouraged, as this might lead to validation errors of the ectd sequence Handling of Empty or Missing ectd Sections For new applications (including generic applications), detailed statements justifying the absence of data or specific ectd sections should be provided in the relevant Quality Overall Summary and/or Non-Clinical/Clinical Overviews (Module 2.3, 2.4, 2.5). Note that placeholder documents highlighting 'no relevant content' should not be placed in the ectd structure, as these would create a document lifecycle for non- existent documents, and unnecessary complication and maintenance of the ectd. Note: for a generic application, there is no need to provide a justification for content that is typically absent Technical Information 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 Security Issues The physical security of the submission during transportation is the responsibility of the applicant. Once received by national competent authority, Jordan Food & Drug Administration 11

12 security and submission integrity is the sole responsibility of the national competent authority Virus Protection The applicant is responsible for checking the submission for viruses. Checking should be performed with an up-to-date virus checker and be confirmed in the cover letter Password Protection Submission or file level security is not permitted. If one-time security settings or password protection of electronic submissions are used, this could constitute grounds for the rejection of the submission General Architecture of Module 1 The JO Module 1 architecture is similar to that of modules 2 to 5 of the ectd, comprising a directory structure and a backbone with leaves. The backbone must be a valid XML document according to the Jordan Regional Document Type Definition (DTD). The backbone instance (the jo-regional.xml file) contains meta-data for the leaves, including pointers to the files in the directory structure. In addition, the JO Regional DTD defines meta-data at the submission level in the form of an envelope. A full description of the JO Regional DTD can be found in Appendix 5 of this specification Checksum See checksum.pdf for complete hash values Envelope The envelope provides meta-data at the submission level. A description of each "envelope" element is provided in Appendix 1 of this specification XML Catalogue The XML catalogue provides meta-data at the leaf level including pointers to the location of files in a directory structure (There may at times be what is seen to be a 'redundant' directory structure, but this is necessary in order to be able to use the same file/directory structure for all procedures.) Jordan Food & Drug Administration 12

13 Directory / Structure The JO Module 1 Specification provides the directory and file structure (see Appendix 2) Naming Convention The ectd file naming conventions described in the ICH M2 ectd Specification and this document are highly recommended. If an applicant wishes to submit multiple files in one section, where only one highly recommended name is available, this can be achieved using a suffix to the filename or by using the variable filename component. names have fixed and variable components. Components are separated by a hyphen. No hyphens or spaces should be used within each component. Fixed components are mandatory. The variable component is optional and should be used as appropriate to further define these files. The variable component, if used, should be a meaningful concatenation of words without separation and should be kept as brief and descriptive as possible. extensions in line with this specification should be applied as applicable. The first component in a file name must be the document type code. There is no country code necessary as part of the file name. The second component, if necessary, should be the variable component. There are no recommendations for variable components in this specification. The format of the file is indicated by the file extension. names must always be in lowercase, in line with the ICH ectd specification. Examples are: Cover.pdf Form.pdf 2.6. Business Protocol The detailed business process between industry and the JFDA will form part of the Guidance for Submission. For some period of time the exchange of regulatory information will take place through exchange of physical media such as CD/DVD-Rs: Jordan Food & Drug Administration 13

14 The actual submission of the physical media on which the application is contained should be accompanied by at least a signed paper copy of the cover letter (the content of this cover letter is defined in the ICH ectd Specification Document Appendix 5, as is the packaging of the media units). The JFDA will acknowledge the proper receipt and result of the validation process (technical [e.g. virus check, XML check, etc.] and content based) to the local Pharmaceutica One (l) Company or the Agent that submitted the ectd Change Control The JO Module 1 specification is likely to change within time. Factors that could affect the content of the specification include, but are not limited to: Change in the content of the Module 1 for the CTD, either through the amendment of information, at the same level of detail, or by provision of more detailed definition of content and structure Change to the regional requirements for applications that are outside the scope of the CTD Update of standards that are already in use within the ectd Identification of new standards that provide additional value for the creation and/or usage of the ectd Identification of new functional requirements Experience of use of the ectd by all parties, in particular Module Instructions for Extension Submissions A separate ectd application should be submitted for each dosage form, route of administration or different strengths,. Use single ectds for each strength or form of a product and include full data concerning the extension applied for within the submitted ectd and therefore Jordan Food & Drug Administration 14

15 clear information should be given to the assessor on what is new compared to earlier submitted data for the product to avoid unnecessary assessment Reformatting To support the reformatting of an existing submission application from any format (e.g. paper) to ectd, a baseline ectd submission containing no content change should be prepared. This baseline submission will not be subject to review and the submission unit type reformat should be used in the envelope. This submission unit type will always be used together with the submission type none Universally Unique Identifier The JO ectd envelope contains several pieces of information about the ectd application where the sequence belongs to, such as the reference number and the trade name. There have been instances when an ectd sequence has been loaded into the wrong application by the receiving agency. For this reason, all ectd sequences built in accordance with this specification must contain a Universally Unique Identifier (UUID), linking the sequence to the ectd application to which it belongs. The applicant should generate a UUID based on ISO/IEC 11578:1996 and ITU- T Rec X.667 ISO/IEC :2005. It is a hexadecimal number in the form of xxxxxxxx-xxxx-xxxx-xxxx-xxxxxxxxxxxx, showing 32 digits and 4 hyphens. The x will be replaced by a number or a letter. Creating with uppercases or lowercases is not restricted. It is recommended to use the version 4 of UUID types. A Version 4 UUID is a universally unique identifier that is generated using random numbers. Such UUID is represented for example as: f0d11e14-f b5d7-1a8b72a The format is characters. This structure guarantees uniqueness across applicants and application. The UUID will be generated for the first time when creating the first sequence Jordan Food & Drug Administration 15

16 following this version of the specification and will be provided in the ectd envelope. All subsequent sequences for that same application will contain the same UUID. In this way, sequences can be allocated automatically to the correct ectd application by the receiving agency. If an application is transferred to a new MAH, the UUID will be transferred as well and will remain the same. Any independent application with its own life cycle should have its own UUID. Jordan Food & Drug Administration 16

17 3 Baseline ectd Submission Requirements 3.1 Introduction To convert a dossier from CTD or Soft copies of CTD format to ectd, a baseline needs to be submitted, as this will greatly facilitate the review process. A baseline submission is the resubmission of currently valid documents to start the ectd lifecycle. 3.2 Technical Baseline Application and Timeline A baseline submission is a compiled submission of the current status of the dossier, i.e. resubmission of currently valid documents that have already been provided to JFDA but in another format. Submission of a baseline shall be before starting a new regulatory activity or after the end of a regulatory activity. i.e. the company will follow the same original submission for products under assessment until the end of the regulatory activity. It 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. 3.3 Baseline Starting as Sequence 0000 For product files that are submitted as CTD or Soft copies of CTD, the baseline submission 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. Jordan Food & Drug Administration 17

18 3.4 Baseline Cases 1. For Products Submitted as Soft Copies of CTD/CTD: If the product was submitted as Soft copies of CTD/CTD and has no regulatory activity or complete regulatory activity, a baseline shall be submitted as sequence The first regulatory activity after baseline (for example a variation request) shall be submitted as sequence For the next submissions, the sequence number will advance, 0002, 0003, etc. See table below: Sequence No. Submission no. 5* Submission Description Response to Question 0000 Baseline submission Submission Type Soft copies of CTD/CTD Submission Unit Related Sequence - - none reformat Variation var-tca inital Response to Questions * Paper submission do not have a sequence number Table 1: Example for starting an ectd with a baseline sequence var-tca response For Products Submitted as ectd For Renewal or Variation: For products submitted as ectd submission and approved by JFDA with no ongoing regulatory activity, the baseline sequence may continue from the last one. Table 2 demonstrates more on this case. Sequence No. Submission Description Submission Type Submission Unit Related Sequence 0000 Renewal renewal initial Response to Questions 0002 Response to Questions renewal response 0000 renewal response Variation var inital Response to var responses 0003 Questions 0005 Baseline Submission none reformat 0005 Table 2: Example for starting a baseline with a regulatory activity Jordan Food & Drug Administration 18

19 3.5 Components of an ectd Baseline Submission: It is composed of the currently valid documents in an ectd format (Refer to 3.7 for more details). The cover letter should include declaration that indicates there is no new information, only the format dossier has changed. Notes: JFDA encourage applicants to move to a full ectd (m1 to m5). The applicant has the right to upgrade to ectd in which it requires the submission of a baseline. However, once ectd is submitted going back to other format will not be accepted. An ectd baseline application should be submitted for each strength, dosage form, route of administration,. 3.6 Requirements for Baseline Section Requirements Module 1 Regional Administrative Information 1.0 Cover letter 1.2 Application Form Product Information Summary of Product Characteristics (SPC) and comparison Labeling Patient information leaflet (PIL) Arabic leaflet English leaflet and comparison Artwork (Mock-ups) 1.7 Certificates and Documents CPP or Free-sales additional data Module 3 Quality 3.2.S Drug Substance 3.2.P Drug Product 3.2.A Appendices 1 The application form submitted shall be the last valid application form created by using cejdws. Jordan Food & Drug Administration 19

20 3.7 References Regulatory Framework for Drug Approvals Guidance for Submission EMA Reference Documents: Harmonised Technical Guidance for ectd Submissions in the EU. Jordan Food & Drug Administration 20

21 APPENDIX Appendix 1: Envelope Element Description The jo-envelope element is the root element that defines meta-data of the submission. This element may contain only one envelope entry. Element Attribute Description/Instructions Example Constraint Occurrence jo-envelope Root element that provides meta-data for the Mandatory Unique submission envelope country Country code jo Mandatory Unique application identifier applicant agency mah atc submission code Parent element for the reference number of the product as taken from ejdws As identifier a UUID as specified by ISO/IEC 11578:1996 and ITU- T Rec X.667 ISO/IEC :2005 is used. The same UUID will be used for all sequences of an ectd application The name of the company submitting the ectd (a local pharmaceutical company or the agent of the foreign pharmaceutical company that is submitting the ectd application) Parent element for the identification of the receiving agency (see appendix 4) BGD e7caf ba97ae28203d8 195b JO- Pharma/JO- DS JO-JFDA Mandatory Repeatable Mandatory Unique Mandatory Unique Mandatory Unique Marketing Authorisation Pharmacompany Holder Mandatory Unique ATC code(s) of active substance(s) Optional Repeatable Provides administrative information associated with the submission Mandatory Unique type See appendix 4 new-nce Mandatory Unique Jordan Food & Drug Administration 21

22 Element Attribute Description/Instructions Example Constraint Occurrence Describes actions within the regulatory activity like initial submission, update, submission-unit responses to questions, any Mandatory Unique additional information or consolidation submissions respectively when closing a regulatory activity type See appendix 4 reformat Mandatory Unique procedure See appendix 4 national Mandatory Unique invented-name The name of the medicinal Dawa product Mandatory Repeatable International Non-proprietary Name, used to identify pharmaceutical substances or inn active pharmaceutical ingredients. Each INN is a unique name that is globally recognized and is public property. A nonproprietary name is also known as a generic name. Allopurinol Optional Repeatable This is the sequence number of the submission this should start at 0000 sequence for the initial submission, and then increase incrementally with each subsequent submission related to the same product e.g. 0000, 0001, 0002, 0003, etc Mandatory Unique This is the sequence number of a previous submission to which this submission relates relatedsequence e.g. the responses to questions to a particular variation. In the case of submission unit types initial and reformat related sequence is identical to the sequence number 0000 Mandatory Repeatable submissiondescription This element is used to briefly describe the submission Mandatory Unique Jordan Food & Drug Administration 22

23 Element Attribute Description/Instructions Example Constraint Occurrence This is the reference number of the product allocated by the BGD Mandatory The number number regulatory authority. If is created Repeatable the number is not yet allocated at the time point of submission, to be advised should be added instead and replaced by the number in follow-up submissions when registered. 247/GD/ 2017 (as the registration number) only after review & approval of the MA in this case use «to be advised» Examples of the Use of the Related Sequence: The related sequence number describes the relationship of additional information to the original submission or subsequent submissions. The related-sequence element is used to identify sequences belonging to the same regulatory activity. An illustration of how the related sequence number is used to describe the relationship of additional information to the original and subsequent submissions is provided in table 1. It is generally expected that there is usually just one related sequence, but there are occasions where more than one related sequence should be provided: For instance a single response (sequence 0010) is produced that relates to 2 submissions: sequence 0008 and sequence Jordan Food & Drug Administration 23

24 Example of how the Related Sequence should be used: Sequence Submission Submission Related Submission description Type sequence unit type 0000 Original MAA maa 0000 initial This is the beginning of a new regulatory activity and so the application submission unit type is initial 0001 Responses to question 0002 Responses to further questions on the original application maa 0000 response maa 0000 response 0003 maa 0000 additional TCA variation for addition of new indication 0005 RA variation for a change in manufacturing site info var-tca 0004 initial var-ra 0005 initial This is a continuation of the regulatory activity maa initiated in 0000 and so the related sequence points to the beginning of that activity. The submission unit type describes the actual contribution response being submitted within maa regulatory activity This is a continuation of the regulatory activity maa initiated in 0000 and so the related sequence points to the beginning of that activity. The submission unit type describes the actual contribution response being submitted within maa regulatory activity This is a continuation of the regulatory activity initiated in 0000 and so the related sequence points to the beginning of that activity. The submission unit describes the actual contribution additional-info being submitted within maa regulatory activity This is the beginning of a new regulatory activity vartca and so the submission unit is initial. The related sequence will be identical with the sequence number This is the beginning of another new regulatory activity var-ra and so the submission unit is initial. Again, the related sequence will be identical with the sequence number Jordan Food & Drug Administration 24

25 0006 Responses to questions on tca variation for addition of new indication var-tca 0004 response This is a continuation of the regulatory activity initiated in 0004 and so the related sequence points to the beginning of that activity. The submission unit type response indicates that this is a response to questions. Example of the use of the submission unit type reformat The submission unit type reformat should be used for each baseline submission. Related sequence should be equal to the sequence number. Sequence Submission Description Submission Type Related Sequence Submission Unit Type 0000 Baseline of Module 3 none 0000 reformat 0001 Variation for a new indication var-tca 0001 initial Jordan Food & Drug Administration 25

26 Appendix 2: Directory/ Structure for JO Module 1 The directory / file structure is defined in this appendix as a table containing the following information: Sequential number Number Title Element /Directory Each item in the table has a unique sequentially assigned reference number. These reference numbers can change with each version of this appendix. CTD section number CTD title Element name in the JO Backbone /Directory name from m1-jo should be relative path from jo-m1 e.g. 12-form/form.pdf This is consistent with ICH standards. The file extension corresponds to the file type; i.e., the pdf extension is only illustrative. s The names of the actual files and directories used should be presented in lower case in accordance with the ectd specification. The codes VAR and EXT represent a variable component of the file name and a representation of a file extension, respectively. The use of upper case for those codes is for illustrative purposes only to show differentiation between the variable part and the fixed part of the name. Please note that LL represents the language code. 1 Number Title JO Module 1 Element m1-jo Directory m1/jo Top level directory for the JO Module 1 as per ICH ectd Specification 2 Number Title JO Module 1 DTD version 1.0 Element m1/jo/jo-regional.xml The JO Regional XML instance including the envelope information. Note that the operation attribute for the joregional.xml should always be set to new 3 Number 1.0 Title Cover letter Element m1-0-cover Directory m1\jo\10-cover General place holder for cover letter information m1\jo\10-cover\. Jordan Food & Drug Administration 26

27 4 Number Title Element Directory Cover letter m1-0-cover m1\jo\10-cover cover-var.ext General placeholder for the cover letter. 5 Number 1.2 Title Application form Element m1-2-application-form Directory m1\jo\12-form form-var.ext General place holder for application form information. 6 Number 1.3 Title Product Information Element m1-3-product-information Directory m1\jo\13-pi General placeholder for Product Information 7 Number Title Summary of Product Characteristics (SPC) and Comparison Element m1-3-1-spc Directory m1\jo\13-pi\131-spc spc-var.ext spccomp-var.ext General placeholder for SPC and comparison. English SPC the directory is m1\jo\13-pi\131-spc\en 8 Number Title Labeling Element m1-3-2-label Directory m1\jo\13-pi\132-labeling label-var.ext General placeholder for labeling The directory is m1\jo\13-pi\132-labeling\ll 9 Number Title Patient information leaflet Element m1-3-3-pil Directory m1\jo\13-pi\133-leaflet General placeholder for Patient information leaflet 10 Number Title Arabic Patient information leaflet Element m1-3-3-pil Directory m1\jo\13-pi\133-leaflet\ar pil-var.ext Document in Arabic Jordan Food & Drug Administration 27

28 11 Number Title English Patient information leaflet and comparison Element m1-3-3-pil Directory m1\jo\13-pi\133-leaflet\en pil-var-ext pilcomp-var.ext Document in English and comparison 12 Number Title Artwork (mock-ups) Element m1-3-4-mockup Directory m1\jo\13-pi\134-artwork artwork-var.ext Artwork or Mock-ups 13 Number Title Samples Element m1-3-5-samples Directory m1\jo\13-pi\135-samples samples-var.ext Samples 14 Number 1.4 Title Information on the Experts Element m1-4-expert Directory m1\jo\14-expert 15 Number Title Quality Element m1-4-1-quality Directory m1\jo\14-expert\141-quality quality-var.ext 16 Number Title Non clinical Element m1-4-2-non-clinical Directory m1\jo\14-expert\142-nonclinical nonclinical-var.ext 17 Number Title Clinical Element m1-4-3-clinical Directory m1\jo\14-expert\143-clinical clinical-var.ext Jordan Food & Drug Administration 28

29 18 Number 1.5 Title Environmental Risk Assessment Element m1-5-environrisk Directory m1\jo\15-environrisk 19 Number Title Non-GMO Element m1-5-1-non-gmo Directory m1\jo\15-environrisk\151-nongmo nongmo-var.ext A document can be added to this section, if no document is added in section Number Title GMO Element m1-5-2-gmo Directory m1\jo\15-environrisk\152-gmo gmo-var.ext A document can be added to this section, if no document is added in section Number 1.6 Title Pharmacovigilance Element m1-6-pharmacovigilance Directory m1\jo\16-pharmacovigilance 22 Number Title Pharmacovigilance System Element m1-6-pharmacovigilance-system Directory m1\jo\16-pharmacovigilance\161-phvig-system phvigsystem-var.ext 23 Number Title Risk Management Plan Element m1-6-2-risk-management-system Directory m1\jo\16-pharmacovigilance\162-riskmgt-system riskmgtsystem-var.ext 24 Number 1.7 Title Certificates and Documents Element m1-7-certificates Directory m1\jo\17-certificates Jordan Food & Drug Administration 29

30 25 Number Title Manufacturing Sites Documents(MSD) Element m1-7-1-msd Directory m1\jo\17-manufacturingsites\171-msd msd-var.ext 26 Number Title CPP or Free-sales Element m1-7-2-cpp Directory m1\jo\17-certificates\172-cpp cpp-var.ext 27 Number Title Certificate of analysis Drug Substance / Finished Product Element m1-7-3-analysis-substance Directory m1\jo\17-certificates\173-analysis-substance drugsubstance-var.ext 28 Number Title Certificate of analysis Excipients Element m1-7-4-analysis-excipients Directory m1\jo\17-certificates\174-analysis-excipients excipients-var.ext 29 Number Title Declaration of Ingredients from human origin Element m human-origin Directory m1\jo\17-certificates\175- human-origin humanorigin-var.ext 30 Number Title Pork-content declaration Element m1-7-6-pork-content porkcontent-var.ext Directory m1\jo\17-certificates\176-pork-content 31 Number Title Certificate of suitability for TSE Element m1-7-7-certificate-tse Directory m1\jo\17-certificates\177-certificate-tse tse-var.ext Jordan Food & Drug Administration 30

31 32 Number Title The diluents and coloring agents in the product formula Element m1-7-8-diluent-coloring-agents Directory m1\jo\17-certificates\178-diluent-coloring-agents diluent-var.ext 33 Number Title Data Protection Element m data-protection Directory m1\jo\17-certificates\179-data-protection dataprotection-var.ext 34 Number Title Letter of access or acknowledgements to DMF Element m letter-access-dmf Directory m1\jo\17-certificates\1710-letter-access-dmf accessdmf-var.ext 35 Number 1.8 Title Pricing Element m1-8-pricing Directory m1\jo\18-pricing 36 Number Title Price certificates Element m1-8-1-price-certificates Directory m1\jo\18-pricing\181-price-certificates price-var.ext 37 Number Title Other documents related Element m1-8-2-other-document Directory m1\jo\18-pricing\182-other-doc others-var.ext 38 Number 1.9 Title Responses to questions Element m1-9-responses Directory m1\jo\19-responses\ responses-var.ext Jordan Food & Drug Administration 31

32 39 Number m1-additional-data Title Additional data Element m1-additional-data Directory m1\jo\additional-data\ additionaldata-var.ext Any additional data requested should be put on this place such as documents that don t really fit in any other sections (transfer agreement, declaration of conformity of translation, etc.) The bioequivalence reports should be submitted in this place. Jordan Food & Drug Administration 32

33 Appendix 3: Example Screenshot This appendix is included only to demonstrate how the directory structure may appear for the Jordan Envelope and Module 1 for Jordan. Jordan Envelope Jordan Food & Drug Administration 33

34 Jordan Module 1 Jordan Food & Drug Administration 34

35 Appendix 4: List of codes JO Agencies Country Code Agency Description Jordan JO-JFDA Jordan Food and Drug Adminstration Procedure Type JO national Jordan Procedure National procedure Description Submission Unit Type additional-info closing correction initial reformat response Description Other additional Information (could include, for example, missing files) and should only be used, if response is not suitable Submission unit that provides the final documents in the JFDA procedure following the decision of the JFDA committee Correction to the published annexes in the JFDA procedure (usually shortly after approval) Initial submission to start any regulatory activity Intended to support the reformatting of an existing submission application from any format to ectd, i.e. a baseline ectd submission containing no content change and which will not be subject to review. This type will always be used together with the submission type none Submission unit type that contains the response to any kind of question and outstanding information requested by the agency. This includes answers to questions during a procedure. Language ar en Language Arabic (when required) English Description Submission Type asmf Description Active Substance Master Jordan Food & Drug Administration 35

36 cep extension ord orv orn bgd bgv bgn mnd nvd nnd rrp rnr hrd bld blv blb bla bls vam vtr none pmf psur psusa pbrer renewal rmp transfer-ma usr var-tca var-ra var-n1 var-n2 withdrawal Submission that applies to an application on a Certificate of suitability CEP application (EDQM only). Extension Submission* MAA - Originator Drug MAA Originator Vitamine Drug Originator Narcotics Generic Drug Generic Vitamin Drug Generic Narcotics New Drug New Vitamin Drug New Narcotics Radiopharmceutical Ready-for-use Radiactive Product Radiopharmaceutical Non-Radioacitve Components (kits) Herbal Drug Biological Drug Biological Vaccine Biological Blood Product Biolocigal Allergen Biolocial Bio-similar Value added medicine Veterinary drug* In the exceptional case of reformatting the application no regulatory activity is allowed. Therefore, none must be stated. The submission unit will identify the sub-activity related to the product. Plasma Master Periodic Safety Update Report PSUR single assessment procedure Periodic Benefit Risk Evaluation Report Renewal of Marketing Authorization Risk Management Plan Transfer of Marketing Authorization Urgent Safety Restriction Technical committee approval Registration Department approval Notification without pricing Notification with pricing Withdrawal *consult JFDA Jordan Food & Drug Administration 36

37 Destination Country code JO Destination Hashemite Kingdom of Jordan Jordan Food & Drug Administration 37

38 Appendix 5: Modularized DTD for JO Module 1 JO Regional DTD <!-- ******************************************************** PUBLIC "-//JFDA/DTD ectd JFDA Backbone 1.0//EN" In the ectd Organisation: "util/dtd/jo-regional.dtd" Created: 17th July 2018 ******************************************************** Meaning or value of the suffixes:? : element must appear 0 or 1 time * : element must appear 0 or more time + : element must appear 1 or more times <none>: element must appear once and only once ******************************************************** --> <!-- General declarations, external modules references... --> <!ENTITY % countries "(jo)"> <!ENTITY % languages "(en ar)"> <!ENTITY % leaf-node "(( leaf node-extension )*)"> <!ENTITY % envelope-module SYSTEM "jo-envelope.mod" > %envelope-module; <!ENTITY % leaf-module SYSTEM "jo-leaf.mod" > %leaf-module; <!-- Root element... --> <!ELEMENT jo:jo-backbone ( jo-envelope, m1-jo )> <!ATTLIST jo:jo-backbone xmlns:jo CDATA #FIXED " xmlns:xlink CDATA #FIXED " xml:lang CDATA #IMPLIED dtd-version CDATA #FIXED "1.0" > <! > <!ELEMENT m1-jo ( m1-0-cover, m1-2-form?, m1-3-pi?, m1-4-expert?, m1-5-environrisk?, m1-6-pharmacovigilance?, m1-7-certificates?, m1-8-pricing?, m1-9-responses?, m1-additional-data? Jordan Food & Drug Administration 38

39 )> <! > <!ELEMENT m1-0-cover %leaf-node;> <! > <!ELEMENT m1-2-form %leaf-node;> <! > <!ELEMENT m1-3-pi ( m1-3-1-spc?, m1-3-2-label?, m1-3-3-pil?, m1-3-4-mockup?, m1-3-5-samples? )> <!ELEMENT m1-3-1-spc ( pi-doc+ )> <!ELEMENT m1-3-2-label ( pi-doc+ )> <!ELEMENT m1-3-3-pil ( pi-doc+ )> <!ELEMENT m1-3-4-mockup <!ELEMENT m1-3-5-samples %leaf-node;> %leaf-node;> <!ELEMENT pi-doc ( %leaf-node; )> <!ATTLIST pi-doc xml:lang %languages; #REQUIRED type (spc spccomp label pil pilcomp) #REQUIRED > <! > <!ELEMENT m1-4-expert ( m1-4-1-quality?, m1-4-2-non-clinical?, m1-4-3-clinical? )> <!ELEMENT m1-4-1-quality %leaf-node;> <!ELEMENT m1-4-2-non-clinical %leaf-node;> <!ELEMENT m1-4-3-clinical %leaf-node;> <! > <!ELEMENT m1-5-environrisk ( (m1-5-1-non-gmo m1-5-2-gmo)? )> <!ELEMENT m1-5-1-non-gmo %leaf-node;> <!ELEMENT m1-5-2-gmo %leaf-node;> <! > <!ELEMENT m1-6-pharmacovigilance ( m1-6-1-pharmacovigilance-system?, m1-6-2-risk-management-system? )> Jordan Food & Drug Administration 39

40 <!ELEMENT m1-6-1-pharmacovigilance-system %leaf-node;> <!ELEMENT m1-6-2-risk-management-system %leaf-node;> <! > <!ELEMENT m1-7-certificates ( m1-7-1-msd?, m1-7-2-cpp?, m1-7-3-analysis-substance?, m1-7-4-analysis-excipients?, m1-7-5-human-origin?, m1-7-6-pork-content?, m1-7-7-certificate-tse?, m1-7-8-diluent-coloring-agents?, m1-7-9-data-protection?, m letter-access-dmf? )> <!ELEMENT m1-7-1-msd %leaf-node;> <!ELEMENT m1-7-2-cpp %leaf-node;> <!ELEMENT m1-7-3-analysis-substance %leaf-node;> <!ELEMENT m1-7-4-analysis-excipients %leaf-node;> <!ELEMENT m1-7-5-human-origin %leaf-node;> <!ELEMENT m1-7-6-pork-content %leaf-node;> <!ELEMENT m1-7-7-certificate-tse %leaf-node;> <!ELEMENT m1-7-8-diluent-coloring-agents %leaf-node;> <!ELEMENT m1-7-9-data-protection %leaf-node;> <!ELEMENT m letter-access-dmf %leaf-node;> <! > <!ELEMENT m1-8-pricing ( m1-8-1-price-certificates?, m1-8-2-other-document? )> <!ELEMENT m1-8-1-price-certificates %leaf-node;> <!ELEMENT m1-8-2-other-document %leaf-node;> <! > <!ELEMENT m1-9-responses %leaf-node;> <! > <!ELEMENT m1-additional-data %leaf-node;> <! > JO Envelope <!-- In the ectd Organisation: "util/dtd/jo-envelope.mod" Version November > <! > <!ELEMENT jo-envelope ( envelope )> <!ELEMENT envelope ( Jordan Food & Drug Administration 40

41 )> application+, identifier, applicant, mah, agency, atc*, submission, submission-unit, procedure, invented-name+, inn*, sequence, related-sequence+, submission-description, number+ <! > <!ELEMENT application ( #PCDATA )> <!ELEMENT identifier ( #PCDATA )> <!ELEMENT applicant ( #PCDATA )> <!ELEMENT mah ( #PCDATA )> <!ELEMENT agency EMPTY> <!ELEMENT atc ( #PCDATA )> <!ELEMENT submission EMPTY> <!ELEMENT submission-unit EMPTY> <!ELEMENT procedure EMPTY> <!ELEMENT invented-name ( #PCDATA )> <!ELEMENT inn ( #PCDATA )> <!ELEMENT sequence ( #PCDATA )> <!ELEMENT related-sequence ( #PCDATA )> <!ELEMENT submission-description ( #PCDATA )> <!ELEMENT number ( #PCDATA )> <! > <!ATTLIST agency code ( JO-JFDA ) #REQUIRED> <! > <!ATTLIST procedure type ( jo national ) #REQUIRED> <! > <!ATTLIST submission type ( asmf cep extension ord orv orn bgd bgv bgn mnd nvd Jordan Food & Drug Administration 41