extended EudraVigilance Medicinal Product Report Message (XEVPRM) Step-by-Step Guide

Transcription

1 extended EudraVigilance Medicinal Product Report Message (XEVPRM) Step-by-Step Insert of a Development Medicinal Product (DMP) 30 Churchill Place Canary Wharf London E14 5EU United Kingdom Telephone +44 (0) Facsimile +44 (0) Send a question via our website An agency of the European Union European Medicines Agency, Reproduction is authorised provided the source is acknowledged.

2 Table of contents 1.1. DMP Example specification Create an XEVPRM Type EV Code Sender Local Code Sponsor Product Code Product Name Product Other Name Comment Pharmaceutical Product Drug Routes Drug Ingredients Drug ATC Drug Indications Product Attachments Validate and send an XEVPRM Retrieve the XEVPRM Acknowledgement (XEVPRM ACK) All examples used in this step-by-step guide are fictitious and intended for demonstration purposes only. EMA/308954/2012 Page 2/87

3 1.1. DMP Example specification For the purpose of this step-by-step exercise, the DMP should be inserted as per the below specifications: SPONSOR Labox High street Dublin DU12 5NN Ireland PHARMACEUTICAL FORM AND METHOD OF ADMINISTRATION Capsule for oral use QUALITATIVE AND QUANTITATIVE COMPOSITION The drug to which the sponsor refers to as MK005 is studied as a capsule for the treatment of low back pain and contains the following ingredients: 100 mg of Paracetamol (active ingredient) Up to 200 mg of "SubstanceB", which is a newly developed chemical substance (active ingredient) Orange flavour (excipient) EMA/308954/2012 Page 3/87

4 1.2. Create an XEVPRM 1) Log in to the requested EVWEB environment: EVWEB production: XCOMP (test) environment: EVWEB training environment: In the restricted area, click on "EVWEB": EMA/308954/2012 Page 4/87

5 You are now logged in EVWEB the organisation ID under which you are logged in is shown in the top right corner: 2) Go to "Create and Send Product Reports" section: 3) With your mouse, click on the area next to the "Message Number". It is a free-text field. The area will become highlighted in blue: 4) Press "Enter" on your keyboard or click on the "E" ("Text Edit") button. Both actions will activate the field and allow you to write the name you wish to assign to you XEVPRM: EMA/308954/2012 Page 5/87

6 5) Type in the message number you wish to assign to your XEVPRM, then press "Enter" on your keyboard: 6) Expand the tree-view area by clicking on the "+" sign (see screenshot above) and click on the "Products" section, or double click on "Products" in the active area: 7) Select "New Development Product " by ticking the relevant box in the active area: EMA/308954/2012 Page 6/87

7 The active area will display the fields relevant for a DMP entity: The "Operation type" field displays "Insert (1)" as a default. It is not possible to assign a different operation type. Mandatory fields that must be populated are highlighted with the text "Field is Mandatory" or "Field is Mandatory Optional". Please note that not all mandatory fields are highlighted this way (some fields are business rules dependent). Additional mandatory fields/fields that must contain specific value may be highlighted during the validation process (see section 1.3. Validate and send an XEVPRM). When information is entered in the individual mandatory fields, the text "Field is Mandatory"/"Field is Mandatory Optional" disappears. Some of the fields contain look-up tables with pre-defined values. These values will be displayed if you press "Enter" on your keyboard. Enter the relevant information in the individual fields as per guidance provided for each field in the extended EudraVigilance Medicinal Product Dictionary (XEVMPD) Data-Entry Tool (EVWEB) User Manual, section Insert of a development medicinal product (DMP). EMA/308954/2012 Page 7/87

8 Type The value in the "Type" field is automatically set to "Development" as per your selection EV Code The EV Code field is a field which will automatically display the assigned EV Code if maintenance related operation (i.e. NOT an insert) is performed. In your example, this field is blank because you are performing an insert of an entity Sender Local Code "Sender Local Code" is a non-mandatory field. It is a free text field. Should you wish to assign your own local code for your internal reference, use the same process as described in steps Sponsor The "Sponsor" field is a field that will allow you to search available values. Using your mouse, click on the area next to "Sponsor". The area will become highlighted in blue: Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button and the remote look-up search area becomes available: EMA/308954/2012 Page 8/87

9 As per your example, the sponsor of your DMP is "Labox". You should therefore query the Sponsor organisation name for "Labox". You can also use one of the wild cards (*): Enter the sponsor name in the search field and press "Enter" on your keyboard. If this sponsor organisation is available in the remote look-up list, the result will be displayed below the query area. In this case, the following message is displayed on your screen: EMA/308954/2012 Page 9/87

10 You can therefore presume that this sponsor organisation is not yet available in the XEVMPD. In order to reference this sponsor organisation in your DMP entity, you need to insert this sponsor organisation in the XEVMPD as new via the same XEVPRM through which you are submitting your DMP. Dismiss the displayed message by clicking on "OK". Using your mouse, click on the "Organisations" section in the tree-view area and select "New Sponsor" by ticking the relevant box in the active area: The active area will display the fields relevant for a sponsor organisation entity: EMA/308954/2012 Page 10/87

11 The "Operation type" field displays "Insert (1)" as a default. It is not possible to assign a different operation type. Mandatory fields that must be populated are highlighted with the text "Field is Mandatory". Please note that not all mandatory fields are highlighted this way (some fields are business rules dependent). Additional mandatory fields/fields that must contain specific value may be highlighted during the validation process (see section 1.3. Validate and send an XEVPRM). When information is entered in the individual mandatory fields, the text "Field is Mandatory" disappears. Some of the fields contain look-up tables with pre-defined values. These values will be displayed if you press "Enter" on your keyboard EV Code The EV Code field is a field which will automatically display the assigned EV Code if maintenance related operation (i.e. NOT an insert) is performed. In your example, this field is blank because you are performing an insert of an entity Type The value in the "Type" field is automatically set to "Sponsor" as per your selection Sponsor Name It is mandatory to provide information in the Sponsor Name field. EMA/308954/2012 Page 11/87

12 This is a free-text field. Using your mouse, click on the area next to "Sponsor Name". The area will become highlighted in blue: Press "Enter" on your keyboard or use the "E" ("Text Edit") button. Both actions will activate the field and allow you to write your text: Type in the requested text and press "Enter" on your keyboard. The name of your sponsor will be displayed in the "Sponsor Name" field: EMA/308954/2012 Page 12/87

13 Sponsor Sender ID It is not mandatory to provide information in this field. This is a free text field. The organisation ID that corresponds to the same organisation as assigned in the EudraVigilance registration system may be provided. Should you wish to enter the organisation ID in this field, use the same process as described in section Sponsor Name Address, City, Region and Postcode It is mandatory to provide information in the "Address", "City" and "Postcode" fields. It is not mandatory to provide information in the "Region" field. These are all free-text fields. To enter the requested information in these fields, use the same process as described in section Sponsor Name: EMA/308954/2012 Page 13/87

14 Country Code It is mandatory to provide information in this field. The "Country Code" field is a field that will allow you to select one of the available pre-defined values. Using your mouse, click on the area next to "Country Code". The area will become highlighted in blue: Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button. The values available for this field will be displayed: EMA/308954/2012 Page 14/87

15 Using your mouse, select the requested value. It will become highlighted in black: Once you click on the selected value, it will be displayed in the "Country Code" field: EMA/308954/2012 Page 15/87

16 Tel Number, Extension, Country Code, Fax Number, Fax Extension, Fax Country Code and address It is not mandatory to provide information in these fields. These are free-text fields. Should you wish to enter the requested information in these fields, use the same process as described in section Sponsor Name Comment This is a free- text field, in which information can be entered using the same process as described in section Sponsor Name. As per the applicable business rules, the "Comment" field must contain the reason for nullification if operation type 'Nullification (4)' is used on the sponsor entity. No information should be entered in this field in this particular case since you are performing an 'Insert (1)' of an entity. EMA/308954/2012 Page 16/87

17 You have now populated the fields for a sponsor organisation entity "Labox": To reference the newly created sponsor organisation in your DMP entity, go back to your development medicinal product entry by clicking on "Insert (1) Development" at the top of the tree-view area: The active area will display the fields relevant for a DMP submission: EMA/308954/2012 Page 17/87

18 Using your mouse, click on the area next to "Sponsor". The area will become highlighted in blue: By clicking on the "L" (Local look-up") button, the field will become highlighted in grey and the available local look-up table becomes available, displaying the organisation name, which you inserted in the "Organisations" section of your XEVPRM: Using your mouse, select the sponsor name you wish to reference in the "Sponsor" field. The name will become highlighted in black: EMA/308954/2012 Page 18/87

19 Once you press "Enter" on your keyboard or click on the selected value with our mouse, the sponsor name will be displayed in the "Sponsor" field: Product Code This is a free-text field. Using your mouse, click on the area next to "Product Code". The area will become highlighted in blue: Press "Enter" on your keyboard or use the "E" ("Text Edit") button. Both actions will activate the field and allow you to write your text: EMA/308954/2012 Page 19/87

20 Type in the requested text and press "Enter" on your keyboard. The text will be displayed in the "Product Code" field: Product Name This is a free-text field. As per guidance provided in section Insert of a development medicinal product (DMP) of the extended EudraVigilance Medicinal Product Dictionary (XEVMPD) Data-Entry Tool (EVWEB) User Manual, in our example, the "Product Name" field can be left blank or contain a name created as a concatenation of the substance code or name and concentration. Should you wish to assign an XEVMPD name to your DMP, use the same process as described in steps 3 5 or Sponsor Name. EMA/308954/2012 Page 20/87

21 Product Other Name This is a free-text field. To enter information in this field, use the same process as described in steps 3 5 or section Sponsor Name should be used. For our example, you will leave this field blank Comment This is a free- text field, in which information can be entered using the same process as described in steps 3 5 or section Sponsor Name. As per the applicable business rules, the "Comment" field must contain the reason for nullification if operation type 'Nullification (4)' is used on the sponsor entity. No information should be entered in this field in this particular case since you are performing an 'Insert (1)' of an entity. You now need to provide information about the pharmaceutical product Pharmaceutical Product This is a repeatable section. Each medicinal product entry in the XEVMPD must contain at least one pharmaceutical product. The technical concept of a "pharmaceutical product" refers to the qualitative and quantitative composition of a medicinal product in the pharmaceutical form approved for administration. The "Administrable pharmaceutical form" refers to the pharmaceutical form for administration to the patient, after any necessary transformation of the authorised pharmaceutical form has been carried out. A medicinal product may contain one or more "pharmaceutical product". Click on the "Pharmaceutical Products" section in the tree-view area, or on "Pharmaceutical Products" in the active area: EMA/308954/2012 Page 21/87

22 Select "New Pharmaceutical Product" by ticking the relevant box in the active area: The active area will display the fields applicable for the (administrable) pharmaceutical product. The text next to "Administrable Pharmaceutical Form" is highlighted in blue: EMA/308954/2012 Page 22/87

23 Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button and the remote look-up search area becomes available: Type in the requested value (you can also use some of the wild cards) and press "Enter". The list of available values will be displayed: EMA/308954/2012 Page 23/87

24 If the standard term of the requested administrable pharmaceutical form is available in the Lookup table/controlled Vocabulary (CV) list published on the Agency's website (see "extended Eudravigilance Product Dictionary (XEVMPD) pharmaceutical dose forms"), such standard term should be used in the pharmaceutical product entity. If the required pharmaceutical form is NOT available as a standard term but is available as a proposed term in the Lookup table/controlled Vocabulary (CV) list published on the Agency's website (see "extended Eudravigilance Product Dictionary (XEVMPD) pharmaceutical dose forms"), such proposed term should be used in the pharmaceutical product entity. If the pharmaceutical form is not available as a standard or proposed term in the Lookup table/controlled Vocabulary (CV) list published on the Agency's website (see "extended Eudravigilance Product Dictionary (XEVMPD) pharmaceutical dose forms"), and: o o where an application for a new pharmaceutical form was/will be submitted to the maintenance Organisation (i.e. EDQM) with the request of adding it to the standard term list; and the requested pharmaceutical form is not included in the list of proposed pharmaceutical forms re-mapped to standard pharmaceutical forms in the spread sheet Re-mapped_PDFs published in the Controlled Vocabulary (CV) list "extended Eudravigilance Product Dictionary (XEVMPD) pharmaceutical dose forms, available at the Agency's website; the pharmaceutical form can be provided as a new proposed term via the XEVPRM. See section 1.8. Initial submission of an Authorised/Administrable Pharmaceutical Form of the published Chapter 3.II: Extended EudraVigilance product report message (XEVPRM) user guidance for related guidance. If the Sponsor developed a new pharmaceutical form, which is confidential and it is used in a clinical trial, such term can be entered in the XEVMPD as a new development term. Development terms can only be used in Development Medicinal Products only. See section 1.8. EMA/308954/2012 Page 24/87

25 Initial submission of an Authorised/Administrable Pharmaceutical Form of the published Chapter 3.II: Extended EudraVigilance product report message (XEVPRM) user guidance for related guidance. Select the requested value, double-click or press "Enter" on your keyboard. The selected value will be displayed in the "Administrable Pharmaceutical Form" field: Drug Routes This is a repeatable section. Administration route section describes the route(s) of administration i.e. the path by which the medicinal product (described as technical concept of a "pharmaceutical product") is taken into or makes contact with the body. Click on the "Drug Routes" section within the pharmaceutical product in the tree-view area, or on "Drug Routes" in the active area: EMA/308954/2012 Page 25/87

26 Select "New Drug Route" by ticking the relevant box in the active area: The active area will display the field (highlighted in blue) in which the route of administration of the pharmaceutical product must be specified based on the available values: EMA/308954/2012 Page 26/87

27 Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button and the remote look-up search area becomes available: Type in the requested value (you can also use some of the wild cards) and press "Enter". The list of available values will be displayed: EMA/308954/2012 Page 27/87

28 If the standard term of the required route of administration is available in the Lookup table/controlled Vocabulary (CV) list published on the Agency's website (see "extended Eudravigilance Product Dictionary (XEVMPD) pharmaceutical dose forms"), such standard term should be used in the pharmaceutical product entity. If the required route of administration is NOT available as a standard term but is available as a proposed term in the Lookup table/controlled Vocabulary (CV) list published on the Agency's website (see "extended Eudravigilance Product Dictionary (XEVMPD) pharmaceutical dose forms"), such proposed term should be used in the pharmaceutical product entity. If the required route of administration is not available as a standard or proposed term in the Lookup table/controlled Vocabulary (CV) list published on the Agency's website (see "extended Eudravigilance Product Dictionary (XEVMPD) pharmaceutical dose forms"), and: o o where an application for a new route of administration was/will be submitted to the maintenance Organisation (i.e. EDQM) with the request of adding it to the standard term list; and the requested pharmaceutical form is not included in the list of proposed routes of administration re-mapped to standard routes of administration in the spread sheet Re-mapped_RoAs published in the Controlled Vocabulary (CV) list "extended Eudravigilance Product Dictionary (XEVMPD) routes of administration, available on the Agency's website; the route of administration can be provided as a new proposed term via the XEVPRM. See section 1.9. Initial Submission of a Route of Administration (RoA) of the published Chapter 3.II: Extended EudraVigilance product report message (XEVPRM) user guidance for related guidance. If the Sponsor developed a new route of administration, which is confidential and it is used in a clinical trial, such term can be entered in the XEVMPD as a new development term. Development terms can only be used in Development Medicinal Products only. See section 1.9. EMA/308954/2012 Page 28/87

29 Initial Submission of a Route of Administration (RoA) of the published Chapter 3.II: Extended EudraVigilance product report message (XEVPRM) user guidance for related guidance. Select the requested value, double-click or press "Enter" on your keyboard. The selected value will be displayed in the "Route of Administration" field: You now need to provide information about the active ingredients of the pharmaceutical product Drug Ingredients This is a repeatable section. Each pharmaceutical product must contain information on the active ingredient(s), including the active ingredient substance name(s) and its/their concentration(s). It is not mandatory to provide information on excipients for development medicinal products. Click on "Drug Ingredients" within the "Pharmaceutical Products" section in the tree-view area: EMA/308954/2012 Page 29/87

30 Select "New Drug Ingredient" by ticking the relevant box in the active area: The active area will display the fields applicable for the composition of the (administrable) pharmaceutical product: EMA/308954/2012 Page 30/87

31 Substance Name The substance(s) indicated as the active ingredient(s) of the medicinal product according to the clinical trial documentation must be specified. By clicking on the "Remote Lookup", the search area, where you can query values available for this field (i.e. substance names) will be displayed: Type in the requested value (you can also use some of the wild cards) and press "Enter". The list of available values will be displayed: EMA/308954/2012 Page 31/87

32 If the requested approved substance is not available, please follow the process described in the published communication "Changes to some business rules of the extended EudraVigilance Medicinal Product Dictionary (XEVMPD): Submission of substance information". If the requested substance is a new development substance, see section Insert of a development substance. Select the requested value, double-click or press "Enter" on your keyboard. The selected value will be displayed in the "Substance name" field: EMA/308954/2012 Page 32/87

33 Role of Ingredient In the "Role of Ingredient" section, click on the applicable value: You have now specified that the substance with the name "Paracetamol" is an active ingredient in our administrable pharmaceutical product: Ingredient Strength Information Whenever possible, the substance strength should be expressed as a unit of measurement. Strength must be entered in the XEVMPD in accordance with the ISO IDMP standards based on a numerator and denominator. Strength can be therefore expressed in two ways: As a Unit of Measure: When the strength of a medicinal product described as a technical concept of a Pharmaceutical Product that has undergone a transformation (for example reconstitution) is to be specified, it is to be specified using the strength resulting from transformation undertaken exactly in accordance with the regulated product information. EXAMPLES of units of measure: 10 milligrams per 100 millilitres, 10 milligrams per 1 single day. EMA/308954/2012 Page 33/87

34 As a unit a Presentation: The unit of presentation is a qualitative term describing the discrete unit in which a pharmaceutical product is presented to describe strength or quantity in cases where a quantitative unit of measurement is not appropriate. EXAMPLES of units of presentation: 250 milligrams per 1 single tablet, 10 millilitres per one single spoon. Unit of presentation can be expressed as: Strength; e.g. spray/puff contains 100 mcg per actuation (unit of presentation = actuation); Quantity; e.g. bottle contains 100 ml per bottle (unit of presentation = bottle). Where an ingredient is present in the form of a salt or hydrate, the quantitative composition may be expressed in terms of the mass [or biological activity in International (or other) units where appropriate] of the active moiety (base, acid or anhydrous material). If the strength is declared as the amount of base then the base is the substance to be declared as the ingredient. If the strength is declared as the amount of the salt then the salt is the substance to be declared as the ingredient. In the rare examples where the strength of the salt and the base are both declared, then the salt is the substance to be declared as the ingredient. This is in line with IDMP where the both the substance (salt) and the reference substance (base/active moiety) will need to be defined. EXAMPLE of Reference substance/strength: "60 mg toremifene (as citrate)" or "toremifene citrate equivalent to 60 mg toremifene" the substance 'toremifene' will be specified as the active ingredient in the pharmaceutical product. Where the active ingredient is an ester or pro-drug, the quantitative composition may be stated in terms of the quantity of that ester or pro-drug. The strength of the substance is to be specified as a quantity of the substance present in a medicinal product described as the technical concept of a "pharmaceutical product". The following concentration type values (amount value types) are available for use as part of the XEVMPD look-up table/controlled Vocabulary (CV) lists published on the Agency's website (see Extended EudraVigilance product report message concentration types): Equal (1) Range (2) Up to (3) Not less than (4) Approximately (5) Average (6) EMA/308954/2012 Page 34/87

35 In the "Ingredient Strength Information" section, click on the applicable value: You are prompted to select whether the concentration (of the active ingredient) should be expressed as "Units of Measure" or "Units of Presentation". As per our DMP example specification, the capsule contains 100 mg of Paracetamol (active ingredient) - you will enter the concentration of the active ingredient as "Units of Presentation". Click on "Units of Presentation": EMA/308954/2012 Page 35/87

36 The numerator value is a free-text field. Type in the requested value: The numerator prefix is a look-up list containing pre-defined values. Click on the arrow and select the requested value: EMA/308954/2012 Page 36/87

37 The numerator prefix value is now displayed in the "Prefix" section: The numerator unit is a look-up list containing pre-defined values. Click on the arrow and select the requested value: EMA/308954/2012 Page 37/87

38 The numerator unit value is now displayed in the "Unit" section: The denominator value is a free-text field. Type in the requested value: The denominator prefix is a look-up list containing pre-defined values. Click on the arrow and select the requested value: EMA/308954/2012 Page 38/87

39 The denominator prefix value is now displayed in the "Prefix" section: The denominator unit is a look-up list containing pre-defined values. Click on the arrow and select the requested value: EMA/308954/2012 Page 39/87

40 The denominator unit value is now displayed in the "Unit" section and you have now entered that one capsule contains 100 mg of the active substance paracetamol: EMA/308954/2012 Page 40/87

41 Since our administrable pharmaceutical product contains not one but two active ingredients, you will also need to enter "SubstanceB" and its concentration (up to 200 mg) as another active ingredient. In the tree-view area, within the "Pharmaceutical Products" section, click on the text "Drug Ingredients": The active are displays the previously entered substance name, its role and concentration. Select "New Drug Ingredient" by ticking the relevant box: The active area will display the fields applicable for the composition of the (administrable) pharmaceutical product: EMA/308954/2012 Page 41/87

42 By clicking on the "Remote Lookup", the search area, where you can query values available for this field (i.e. substance names) will be displayed: Type in the requested value (you can also use some of the wild cards) and press "Enter". The list of available values will be displayed. In this particular case, a warning message is displayed, informing us that "SubstanceB" cannot be retrieved in the available substance list: EMA/308954/2012 Page 42/87

43 You can therefore presume that this substance name is not yet available in the XEVMPD. Dismiss the displayed message by clicking on "OK". In order to reference this substance name in your DMP entity, you need to insert this substance in the XEVMPD as new via the same XEVPRM through which you are submitting your DMP. Any substance under investigation in a clinical trial in the EEA, and which is not part of any authorised medicinal product (AMP) should be submitted as a new development substance Insert of a development substance Using your mouse, click on the "Substances" section in the tree-view area and select "New Development Substance" by ticking the relevant box in the active area: EMA/308954/2012 Page 43/87

44 The active area will display the fields relevant for a development substance entity: The "Operation type" field displays "Insert (1)" as a default. It is not possible to assign a different operation type. Mandatory fields that must be populated are highlighted with the text "Field is Mandatory". EMA/308954/2012 Page 44/87

45 Please note that not all mandatory fields are highlighted this way (some fields are business rules dependent). Additional mandatory fields/fields that must contain specific value may be highlighted during the validation process (see section 1.3. Validate and send an XEVPRM). When information is entered in the individual mandatory fields, the text "Field is Mandatory" disappears. Some of the fields contain look-up tables with pre-defined values. These values will be displayed if you press "Enter" on your keyboard. Enter the relevant information in the individual fields as per guidance provided for each field in the extended EudraVigilance Medicinal Product Dictionary (XEVMPD) Data-Entry Tool (EVWEB) User Manual, section Insert of a development substance Type The value in the "Type" field is automatically set to "Development" as per our selection EV Code The EV Code field is a field which will automatically display the assigned EV Code if maintenance related operation (i.e. NOT an insert) is performed. In our example, this field is blank because you are performing an insert of an entity Current Name or Code This is a free-text field. Using your mouse, click on the area next to "Current Name or Code". The area will become highlighted in blue: EMA/308954/2012 Page 45/87

46 Press "Enter" on your keyboard or use the "E" ("Text Edit") button. Both actions will activate the field and allow you to write your text: EMA/308954/2012 Page 46/87

47 Type in the requested text and press "Enter" on your keyboard. The text will be displayed in the "Current Name or Code" field: Is Name or Code The "Is Name or Code" field is a field that will allow you to select one of the available pre-defined values. Using your mouse, click on the area next to "Is Name or Code. The area will become highlighted in blue: EMA/308954/2012 Page 47/87

48 Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button. The values available for this field will be displayed: Using your mouse, select the requested value. It will become highlighted in black: EMA/308954/2012 Page 48/87

49 Once you click on the selected value, it will be displayed in the "Is Name or Code" field: Class The "Class" field is a field that will allow you to select one of the available pre-defined values. Using your mouse, click on the area next to "Class. The area will become highlighted in blue: EMA/308954/2012 Page 49/87

50 Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button. The values available for this field will be displayed: EMA/308954/2012 Page 50/87

51 Using your mouse, select the requested value. It will become highlighted in black: Once you click on the selected value, it will be displayed in the "Class" field: EMA/308954/2012 Page 51/87

52 Sponsor The "Sponsor" field is a field that will allow you to search available values. Using your mouse, click on the area next to "Sponsor. The area will become highlighted in blue: EMA/308954/2012 Page 52/87

53 You already know that the sponsor organisation "Labox" was not inserted in the XEVMPD (and therefore no EVCode was assigned) and is therefore not available in the remote look-up list. You should therefore search the local look-up list by clicking on the "L" (Local look-up") button. The field will become highlighted in grey and the available local look-up table becomes available, displaying the organisation name, which you inserted in the "Organisations" section of your XEVPRM: Using your mouse, select the sponsor name you wish to reference in the "Sponsor" field. The name will become highlighted in black: Once you press "Enter" on your keyboard or click on the selected value with our mouse, the sponsor name will be displayed in the "Sponsor" field: EMA/308954/2012 Page 53/87

54 CAS Number, Molecular Formula and Chemical/Biological Description These are free-text field. The requested information in these fields can be specified using the same process as described in steps 3 5 or section Sponsor Name. In our example, you will leave these fields blank Comment This is a free- text field, in which information can be entered using the same process as described in steps 3 5 or section Sponsor Name. As per the applicable business rules, the "Comment" field must contain the reason for nullification if operation type 'Nullification (4)' is used on the sponsor entity. No information should be entered in this field in this particular case since you are performing an 'Insert (1)' of an entity Previous Name/Codes (of the development substance) This is a repeatable section. Since no previous substance name/code is stated in the DMP example specification, this section should not contain any information. EMA/308954/2012 Page 54/87

55 Should you wish to add the relevant information, click on "Previous Name/Codes" section in the treeview area, or on "Previous Name/Codes" in the active area: Select "New" by ticking the relevant box in the active area: EMA/308954/2012 Page 55/87

56 The active area will display the fields applicable for the previous name or code. The text next to "Substance Name or Code" is highlighted in blue: It is a free-text field. Should you wish to add the information, the same process as described in section Current Name or Code should be followed. To specify whether the entered information is a name or a code, click on the area next to "Is Name or Code". It is a field that will allow you to select one of the available pre-defined values. The same process as described in section Is Name or Code should be followed International Code This is a repeatable section. Since no international code is stated in the DMP example specification, this section should not contain any information. Should you wish to add the information, the same processes as described in section Previous Name/Codes (of the development substance) should be followed Substance Parent Code This is a repeatable section. Since no substance parent code code is stated in the DMP example specification, this section should not contain any information. Should you wish to add the information, the same processes as described in section Previous Name/Codes (of the development substance) should be followed Substance Attachment For development substances, attachments may be absent. Should you wish to add a substance attachment, follow the processes described in section Insert of Printed Substance Information (PSI) of the extended EudraVigilance Medicinal Product Dictionary (XEVMPD) Data-Entry Tool (EVWEB) User Manual. You have now populated the fields for a development substance "SubstanceB". To reference the newly created substance in the pharmaceutical product of your DMP entity, go back to the "Drug Ingredient" section in the tree-view area and select "Drug Ingredient": EMA/308954/2012 Page 56/87

57 The active area will display the fields applicable for the composition of the (administrable) pharmaceutical product: Click on the "L" (Local look-up") button to display the available local look-up containing the substance name, which you inserted in the "Substances" section of your XEVPRM: EMA/308954/2012 Page 57/87

58 Using your mouse, select the substance name you wish to reference in the "Substance Name" field. The name will become highlighted in black: Once you press "Enter" on your keyboard or click on the selected value with our mouse, the substance name will be displayed in the "Substance Name" field: EMA/308954/2012 Page 58/87

59 To specify the role of the ingredient and the ingredient strength information, follow the same processes as described in sections Role of Ingredient and Ingredient Strength Information. Once completed, the information should be displayed as follows: The tree-view area now displays two substance names and their role under "Drug Ingredients": EMA/308954/2012 Page 59/87

60 If you click on the text "Drug Ingredients" in the tree-view area, the details of the two ingredients will be displayed in the active area: To insert your third substance (i.e. orange flavour) as an excipient, click on "Drug Ingredients" within the "Pharmaceutical Products" section in the tree-view area and select "New Drug Ingredient" by ticking the relevant box in the active area: EMA/308954/2012 Page 60/87

61 The active area will display the fields applicable for the composition of the (administrable) pharmaceutical product: Click on the "Remote Lookup" and the search area, where you can query values available for this field (i.e. substance names) will be displayed: EMA/308954/2012 Page 61/87

62 Type in the requested value (you can also use some of the wild cards) and press "Enter". The list of available values will be displayed: EMA/308954/2012 Page 62/87

63 If the requested approved substance is not available, please follow the process described in the published communication "Changes to some business rules of the extended EudraVigilance Medicinal Product Dictionary (XEVMPD): Submission of substance information". If the requested substance is a new development substance, see section Insert of a development substance. Select the requested value, double-click or press "Enter" on your keyboard. The selected value will be displayed in the "Substance name" field: To indicate that "Orange flavour" is an excipient, click on "Excipient" in the "Role of Ingredient" section: It is not mandatory to enter the concentration of excipients. The tree-view area now displays three substance names and their role under "Drug Ingredients": EMA/308954/2012 Page 63/87

64 If you click on the text "Drug Ingredients" in the tree-view area, the details of the three ingredients will be displayed in the active area: Drug ATC This is a repeatable section. It is not mandatory to provide ATC Code information in a DMP entity. Should you wish to do so, the same process as described in section Drug Routes should be followed. EMA/308954/2012 Page 64/87

65 If the standard term of the requested ATC Code is available in the Lookup table, such standard term should be used in the pharmaceutical product entity. If the required ATC Code is NOT available as a standard term but it is available as a proposed term in the Lookup table, such proposed term should be used in the pharmaceutical product entity. If the Sponsor created a new ATC Code, which is confidential, such term can be entered in the XEVMPD as a new development term. Development terms can be used in Development Medicinal Products only. See section 1.7. Initial submission of an ATC Code of the published Chapter 3.II: Extended EudraVigilance product report message (XEVPRM) user guidance for related guidance Drug Indications This is a repeatable section. It is not mandatory to provide Drug Indications information in a DMP entity. Should you wish to do so, the below described process should be followed. The information in the "Drug Indications" section should be entered as per business rules and guidance provided in Chapter 3.II: Extended EudraVigilance product report message (XEVPRM) user guidance; section AMP - Product Indications (AP.INDs). Click on the "Drug Indications" text in the tree-view area: Select "New Drug Indication" by ticking the relevant box in the active area: EMA/308954/2012 Page 65/87

66 The active area will display the fields applicable for MedDRA coding: MedDRA Version The area next to the "MedDRA Version" is highlighted in blue: Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button. The values available for this field will be displayed: EMA/308954/2012 Page 66/87

67 Using your mouse, select the requested value. It will become highlighted in black: Once you click on the selected value, it will be displayed in the "MedDRA Version" field: MedDRA Level Click on the area next to the "MedDRA Level". The area will become highlighted in blue: Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button. The values available for this field will be displayed: EMA/308954/2012 Page 67/87

68 Using your mouse, select the requested value. It will become highlighted in black: Once you click on the selected value, it will be displayed in the "MedDRA Level" field: MedDRA Term Click on the area next to the "MedDRA Term". The area will become highlighted in blue: Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button and the remote look-up search area becomes available: EMA/308954/2012 Page 68/87

69 Select your query mode and type in the requested value (you can also use some of the wild cards) and press "Enter". The list of available values will be displayed: Select the requested value, double-click or press "Enter" on your keyboard. The selected value will be displayed in the "MedDRA Term" field: EMA/308954/2012 Page 69/87

70 To enter additional drug indications, click on "Drug Indications" in the tree-view area and select "New Drug Indication". The same process as described in section Drug Indications should be followed Product Attachments This is a repeatable section. It is not mandatory to provide Product Attachments in a DMP entity. Should you wish to do so, the below described process should be followed to attach the Investigator's Brochure or other clinical trial documentation: Click on the "Product attachments" text in the tree-view area: Select "New Product Attachment" by ticking the relevant box in the active area: EMA/308954/2012 Page 70/87

71 The area next to "Product Attachment" is highlighted in blue: Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button and the remote look-up search area becomes available: As per your example, the code of the medicinal product is "MK005". You should therefore search for a document name that contains part of this code. You can also use one of the available wild cards. Type in the requested text and press "Enter" on your keyboard. If document containing such text was previously submitted to the XEVMPD (and an EV Code was assigned), a result of your search would be displayed in the search area. In this case, the following message is displayed on your screen: EMA/308954/2012 Page 71/87

72 You can therefore presume that a document for such medicinal product was not previously inserted in the XEVMPD and can therefore be inserted as new. In the tree-view are, click on the "Attachments" section: Select "New PPI Attachment" by ticking the relevant box in the active area: The active area will display the fields applicable for a PPI attachment. EMA/308954/2012 Page 72/87

73 Enter the relevant information in the individual fields as per the below guidance: File type The "File Type" field is a field that will allow you to select one of the available pre-defined values. "PDF (1)" will be automatically assigned and highlighted in blue: Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button. The other values available for this field will be displayed: Using your mouse, select the requested value. It will become highlighted in black: EMA/308954/2012 Page 73/87

74 Once you click on the selected value, it will be displayed in the "File Type" field: Name This is a free-text field. Using your mouse, click on the area next to "Name". The area will become highlighted in blue: Press "Enter" on your keyboard or use the "E" ("Text Edit") button. Both actions will activate the field and allow you to write your text: Type in the requested text and press "Enter" on your keyboard. The name of your attachment will be displayed in the "Name" field: Type The type of your attachment is automatically assigned as per your earlier indication: EMA/308954/2012 Page 74/87

75 Language The "Language" field is a field that will allow you to select one of the available pre-defined values. Using your mouse, click on the area next to "Language. The area will become highlighted in blue: Press "Enter" on your keyboard, double-click on the field, or click on the "R" (Remote look-up) button. The values available for this field will be displayed: Using your mouse, select the requested value. It will become highlighted in black: Once you click on the selected value, it will be displayed in the "Language" field: EMA/308954/2012 Page 75/87

76 Version number This is a free-text field. Using your mouse, click on the area next to "Version Number". The area will become highlighted in blue: Press "Enter" on your keyboard or use the "E" ("Text Edit") button. Both actions will activate the field and allow you to write your text: Type in the requested text and press "Enter" on your keyboard. The version number will be displayed in the "Version Number" field: Version Date The "Version Date" field is a graphical interface that recalls a calendar, which allows you to select the requested date. EMA/308954/2012 Page 76/87

77 Using your mouse, click on the area next to "Version Date". The area will become highlighted in blue: Press "Enter" on your keyboard or double-click with your mouse. A calendar will be displayed. Using the relevant arrows, select the requested date: Once you click on the requested date, the date will be displayed in the field: You have entered information for all fields required for the submission of a PPI attachment. To reference the newly created PPI attachment in your DMP entity, go back to your development medicinal product entity by clicking on the "Product Attachment" in the "Product Attachments" section in the tree-view area (highlighted in red): EMA/308954/2012 Page 77/87

78 The active area will display the fields relevant for an attachment submission Product Attachment The area next to "Product Attachment" is highlighted in blue: EMA/308954/2012 Page 78/87

79 Click on the "L" (Local look-up") button - the area will become highlighted in grey and the local look-up table becomes available, displaying the attachment, which you inserted in the "Attachments" section of your XEVPRM: Using your mouse, select the attachment name you wish to reference in the "Product Attachment" field. The name will become highlighted in black: Once you press "Enter" on your keyboard or click on the selected value with your mouse, the attachment name will be displayed in the "Product Attachment" field: Validity declaration Since we are performing an insert of a DMP and no previous attachment was referenced to this DMP entity, it is not necessary to enter the "Validity declaration" information in this particular case. EMA/308954/2012 Page 79/87

80 You have now completed all fields requested for a DMP submission as per the DMP example specification. EMA/308954/2012 Page 80/87

81 1.3. Validate and send an XEVPRM 1) Validate your XEVPRM by clicking with your mouse on the "Validate" button. New window will be displayed on your screen, showing the result of your validation. If your XEVPRM contains any technical errors (i.e. mandatory information is missing), an error message will be displayed on your screen, describing the number of errors and specifying the location of the first error: Once you click on "OK" in the error message the application will direct you to the first error. The field(s) where information is missing will contain the text "Field is Mandatory", e.g.: You should enter the required information /correct the submitted information and validate the XEVPRM again. If your XEVPRM has been created correctly, the new window will display the text "Validate OK", which mans that no errors were reported: EMA/308954/2012 Page 81/87

82 You can dismiss the message by clicking on "OK". 2) Save the XEVPRM for your reference by clicking on the relevant button: 3) Send the XEVPRM by clicking on the "Send" button. The below message will be displayed on your screen if you included a submission of a PPI attachment for your development product: Retrieve your PPI attachment from the location on your computer and upload the file: EMA/308954/2012 Page 82/87

83 Once you click on "Upload File", the following message will be displayed in a new window: Dismiss the message by clicking on "OK". The below message will confirm that your XEVPRM has been sent: If you want to view/save your file, click on "OK". The below message will be displayed, enabling you to save your XEVPRM file on your computer: EMA/308954/2012 Page 83/87

84 1.4. Retrieve the XEVPRM Acknowledgement (XEVPRM ACK) 1) Go to the "Web Trader" section 2) Click on "Inbox" (or "Archived Inbox" under "Archive", depending on when you decide to retrieve your XEVPRM ACK). The application will appear "frozen" for a second or two: After a few seconds, the active area will display XEVPRM ACKs sent to your organisation's ID (the first message will be automatically highlighted in blue): To view the ACK name in full, expand the section by placing your cursor on the separator line between "Name" and "Num/Count", click and drag towards the right until the full name is visible: EMA/308954/2012 Page 84/87

85 3) Based on the XEVPRM number, which you assigned to your message find the XEVPRM ACK. Click on the relevant row with your mouse (the message will be highlighted in blue): Press "Enter" on your keyboard or double-click with your mouse and the XML of the XEVPRM ACK will be displayed on your screen, showing the operation result and the assigned EVCode(s): EMA/308954/2012 Page 85/87

86 4) You can save the XML file of the XEVPRM ACK on your computer by going to "File" and selecting "Save As": EMA/308954/2012 Page 86/87

87 You have now successfully retrieved the XEVPRM Acknowledgement. EMA/308954/2012 Page 87/87