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Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biologicals application form

Version 1.0, July 2011

Therapeutic Goods Administration

About the Therapeutic Goods Administration (TGA) The TGA is a division of the Australian Government Department of Health and Ageing, and is responsible for regulating biologicals, medicines and medical devices. TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance), when necessary. The work of the TGA is based on applying scientific and clinical expertise to decision-making, to ensure that the benefits to consumers outweigh any risks associated with the use of biologicals, medicines and medical devices. The TGA relies on the public, healthcare professionals and industry to report problems with biologicals, medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. To report a problem with a biological, medicine or medical device, please see the information on the TGA website.

Copyright© Commonwealth of Australia 2011This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General’s Department, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological applicationV1.0 October 2010V1.0 June 2011


Version history

Version Description of change Author Effective dateV1.0 Original BSS July 2011

Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41


ContentsIntroduction 6

Part I: Accessing the Biological Application form 71. Accessing the eBS portal___________________________________________________72. Navigating the eBS portal__________________________________________________92.1 Drafts____________________________________________________________________________________92.2 Lodged Submissions__________________________________________________________________103. Code Tables________________________________________________________________114. Ingredients_________________________________________________________________135. Adding new entries to the Code Tables or Ingredients List_________145.1 Code Table changes___________________________________________________________________145.2 Ingredients List changes_____________________________________________________________14

Part II: Completing the Biological Application form 151. Navigating the application form________________________________________152. Application_________________________________________________________________172.1 Applicant Name_______________________________________________________________________172.2 Sponsor Name_________________________________________________________________________172.3 Sponsor Address______________________________________________________________________172.4 Sponsor Preferred Billing Address__________________________________________________172.5 Sponsor Regulatory Correspondence Address_____________________________________182.6 Contact Name_________________________________________________________________________182.7 Contact Phone Number_______________________________________________________________182.8 Contact Fax Number__________________________________________________________________182.9 Contact Email_________________________________________________________________________182.10 This Application is to________________________________________________________________182.11 Application Fee______________________________________________________________________182.12 Exempt from Payment?_____________________________________________________________183. Registration________________________________________________________________193.1 Class of Biological_____________________________________________________________________193.2 Product Type__________________________________________________________________________193.3 Label Name____________________________________________________________________________203.4 Standards______________________________________________________________________________20



4. Manufacturers_____________________________________________________________204.1 Add Manufacturer____________________________________________________________________204.2 Remove Selected_____________________________________________________________________234.3 Apply for a New Manufacturer______________________________________________________235. Product_____________________________________________________________________245.1 Class of Application___________________________________________________________________245.2 Is this Biological Product_____________________________________________________________245.3 Add product___________________________________________________________________________256. Supporting information__________________________________________________326.1 Attach a Document____________________________________________________________________326.2 Remove Selected Documents________________________________________________________336.3 Refresh List of Files___________________________________________________________________337. Validation__________________________________________________________________338. Audit log____________________________________________________________________349. Submitting an Application_______________________________________________349.1 Close Button___________________________________________________________________________359.2 Client Name___________________________________________________________________________359.3 Applicant Billing Address____________________________________________________________359.4 Sponsor Name_________________________________________________________________________359.5 Class of Biological_____________________________________________________________________359.6 Eligible Applications__________________________________________________________________359.7 Submit Button_________________________________________________________________________36

References 37



IntroductionThis document is intended to provide guidance to the eBS Biological Application form. The requirement to complete this form is stated in sections 32DA and 32DD of the Therapeutic Goods Act 1989 (TG Act) where, for a biological to be included in the Australian Register of Therapeutic Goods (ARTG) an application is made in accordance with a form that has been approved by the Secretary. The contents of this form directly inform the ARTG, and only electronic submission of this document is permitted. This is consistent with the medicine and medical device application systems. Please note that the information provided in this document is current at the time of publication. Changes may be required to the application form and while the TGA will endeavour to update this document, it is possible that images or information may vary from the live form from time to time.If you have any queries or would like further information please contact the Biological Science Section of the TGA at [email protected] or on: 1800 678 799


mailto:[email protected]


Part I: Accessing the Biological Application formThe biological application form is accessed via the TGA’s secure online eBusiness System (eBS) portal, https://www.ebs.tga.gov.au.The eBS home page contains eBS access forms, including obtaining a new client ID for the TGA’s client database, accessing the eBS systems, account setup and administration, terms and conditions, and other guidance documents. A secure eBS login is required to access all application forms, including the biologicals application form.If the applicant does not already have a login for the secure eBS portal, and requires one, the eBS Access Request Form must be completed and forward it to the TGA by fax or post (contact details can be found at the bottom of the eBS home page)For any questions regarding the eBS system, the eBS service team can be contacted at [email protected], or 1800 010 624.1. Accessing the eBS portal To log into the secure eBS portal, click the “Secure Login” link found at the bottom of the left hand side menu on the eBS home page (see Figure 1a). Figure 1a Accessing eBS

The screen will then prompt for an eBS user name and password to be entered. After successfully logging in, the menu on the left hand side of the screen will change to the eBS Portal menu as shown in Figure 1b. Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41

mailto:[email protected]

https://www.ebs.tga.gov.au/


Figure 1b Expanded eBS menu

The Biological Application form can be accessed as follows:1. Click on “Portal – [Applicant Name]” to expand the menu. Note that the actual Applicant Name will be populated with the name associated with the log in used.2. Click on “Create Applications & Submissions” to further expand the menu3. Click on “Biologicals” to further expand the menu4. Click on “Biological Application” to gain access into the TGA eBS Biological Application Form


1342


2. Navigating the eBS portal 2.1 DraftsDraft applications may be accessed in the secure eBS portal. To view the drafts screen, click “View Drafts” in the expanded Portal menu (first option) to the left of the screen (Figure 1c)Figure 1c Viewing draft applications

From this screen the user may: search and open any of the drafts by clicking on it in the list create a copy of a draft by clicking the down arrow to the left of the draft application in the list, and selecting delete a draft by clicking the down arrow to the left of the draft application in the list, and selecting open a print preview of the draft application by clicking the down arrow to the left of the draft application in the list, and selecting .

The list of drafts may be filtered using the “Approval Area” and “Sponsor” fields at the top of the page, or alternatively the list may be searched by Date, Client Reference or Identifier. In addition, the list of drafts may be sorted by clicking any of the column headings (the date the application was created, the client reference or the application ID).



2.2 Lodged SubmissionsInformation regarding applications that have been submitted may also be viewed in the secure eBS portal. To view the submissions screen, click “View Lodged Submissions” in the expanded Portal menu (second option) to the left of the screen (Figure 1d).Figure 1d Viewing lodged submission

From this screen the user may: search and view the Workflow Status of the application (Submitted, Under Review, Rejected or Complete) view summary information by clicking the information button to the left of the application:

open the Submission Document by clicking the down arrow to the left of the application in the list, and selecting open a print preview of the submitted application by clicking the down arrow to the left of the application in the list, and selecting open the invoice by clicking the down arrow to the left of the application in the list, and selecting .

Note: The application form cannot be opened after the application has been successfully submitted.



3. Code TablesWithin the biological application form, a number of the fields are predefined, where the user must select an option from, for example, a drop-down list or via a search. The options available in these lists are informed via the TGA’s Code Tables. The contents of these code tables are available through the eBS homepage and are accessible on the public (non-secure) eBs view, as shown in Figure 1e, and from the secure eBS portal, as shown in Figure 1f. The code tables can be accessed from the left hand side menu on the eBS page. First click “Public TGA Information” to expand this menu, then click the “Code Tables” link (see the figures below).Figure 1e Viewing code tables from the public (non-secure) eBs view

Figure 1f Viewing code tables from the secure eBS portal

The code table that informs a specific field in the application form may not have the same name as that field – see Table 1 below. Please note that some code tables may not be publicly available.Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41


The code table of interest can be opened by clicking on the corresponding link. When the code table is opened, the complete list is available including a description. Search for a specific item in the list by typing it in the search field at the top of the page:

For information on how to seek an update to the Code Tables, see section Adding new entries to the Code Tables or Ingredients List5. Adding new entries to the Code Tables or Ingredients List below.Table 1: Code table name by relevant field name for biologicals application form

Field name Code tableRegistration tabClass of Biological Biological classProduct type Product codesList of standards Biological standardsManufacturer tabManufacturer name Client database and Manufacturer database Manufacturer steps Manufacturing stepsProduct tabIntended use Biologicals intended useRoute of administration Routes of administrationDosage form Dosage formFormulation boxIngredient name IngredientsIngredient quantity units Units of proportionAnimal species Animal originAnimal tissue Animal partsAnimal preparation Animal preparationCountry of origin Country codesContainer boxContainer type Container codeContainer material Container material



Shelf life Shelf life timeStorage temperature Shelf life temperatureStorage conditions Shelf life conditionsSterilisationSterilisation method SterilitySupporting information tabDocument type Biological document type

4. Ingredients Like the code tables, the ingredients available within the form are predefined, and the user must select an option via a search. The options available in this list are a selection from the TGA’s ingredients database, the eBS Australian Register of Therapeutic Goods Ingredients. These ingredients list is accessible on the public (non-secure) eBS view, as shown in Section 2. To access the code tables, click the “Ingredients” link found in the left hand side menu on the eBS home page (see Figures 1e and 1f).Figure 1g Searching the Ingredients database

From here, the list may be searched for specific ingredients by clicking the search button (shown above), or the list may be filtered using the provided options.Note that not all the ingredients listed here are available for use within the biological application form. If an ingredient that is listed in the eBS Australian Register of Therapeutic Goods Ingredients is not available in the biologicals application form the applicant believes should be available, please contact the Biological Science Section. Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41


5. Adding new entries to the Code Tables or Ingredients List5.1 Code Table changesIf an applicant is not able to find the desired information in a drop-down list within the application form, it is suggested to first check the Code Table list as outlined above in Section 3. Code Tables. If the information is not available, it may be necessary to request addition of a new ‘code’ in the relevant table. To seek addition of a new ‘option’ to a code table in the Biologicals Application Form, the applicant should contact the Biological Science Section of the TGA. Requests to amend a Code Table will be assessed and a response provided. The request should include the name of the field and the relevant Code Table to be updated (as specified in Table 1, above). If approved, the code table will be amended which will then update the drop-down lists within the biological application form, as well as the code tables in eBS.5.2 Ingredients List changesTo request the addition of a new ingredient to the eBS Ingredient database, the following options are available:1. For a new Australian Approved Name (AAN) or Australian Biological Name (ABN) a application from must be downloaded from the TGA website, completed and forwarded to the TGA.2. For a new Australian Biological Ingredient (ABI), please contact the TGA on the details provided for ‘AANs and Proprietary Ingredients’. At minimum the name of the ABI and a brief definition should be provided.



Part II: Completing the Biological Application formThis Part provides detailed information on how to access and complete all aspects of the Biological Application form.Prerequisites for completing the application form are that the sponsor or agent must:

be entered on the TGA client database have obtained an eBS ‘master’ username and password and set up individual accounts (see Part 1) have pending or approved GMP manufacturing licence or clearance for all manufacturers determine the Class of the their Biological, and this should be confirmed with TGA if necessary have an awareness of the rules governing what can be included in a single or multiple product entry, based on the definition of ‘separate and distinct’ in section 32AB of the TG Act and regulation 11A of the TG RegulationsFor detailed information about how to access the form, please see Part 1, Section 1 of this document.

1. Navigating the application formThe opening page of the application form is shown in Figure 2 and includes key information and headings to assist the sponsor in navigating through the eBS Application form. Table 2 provides a brief description of each field/ button.Figure 2 Top section of the Biological Application Form

Table 2 Buttons and fields and their respective functions

Row Button/Field Action1 Application ID An automatically populated field displaying the Application ID and version number1 Status An automatically populated field displaying the current status of the Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41

Row 2Tab banner

Row 1


application form. 1 Client Reference Any text can be added here to assist the Client with tracing their application. This information is not submitted to the TGA.2 Close This button closes the application form and returns to the main eBS portal. Note that any unsaved information will be lost upon closing.2 Save This button saves current progress – applicants are encouraged to save regularly2 Validate This button ensures all the mandatory fields are populated and prompts the applicant accordingly2 Print Preview Provides applicant with a Print Preview of their application with the current information. A printed copy of the eBS application is a required component of the dossier. Tab bannerEach tab reveals a section of the Biological Application form. The applicant is required to select each tab for completion. On completion of one tab the applicant should then precede to the next section of the form by selecting the next tab in the banner; the applicant is not automatically forwarded to the next tab on completion of the tab. The tabs can be completed in any sequence, but it is strongly recommended completing the Application and Registration tabs first, as fields in subsequent tabs are dependent on initial information entered. Table 3 provides a brief description of each tab within the banner and the section of this Appendix where additional information is located.Table 3 Information located in Tab banner

Tab Description SectionApplication This tab is the part of the form pertaining to administrative information about the applicant/ sponsor 2Registration This tab is the part of the form where regulatory-based product specific information of the biological is specified 3Manufactures This tab is the part of the form where all Manufacturers details are entered 4Product This tab is the part of the form where product-specific information is entered 5Supporting Information This tab is where documents can be uploaded and attached to support your application (option is only available for Class 1 Biologicals Only) 6Validation This tab provides list of validation messages, such as errors, detected after the most recent request to “validate” 7Audit Log This tab contains a log of key activities conducted on the application e.g. outcomes of validation at different time points 8



2. ApplicationThe information to be completed under the Application tab comprises administrative information about the applicant/sponsor.Please note that the asterisk ( ) symbol indicates a mandatory field. Mandatory fields must be populated in order for the application to be successfully validated and subsequently lodged. Figure 3 The Application tab

2.1 Applicant Name: An automatically populated field (cannot be changed by the user) informed by eBS login information displaying the Name of the Applicant. 2.2 Sponsor Name: Name of Sponsor selected from the drop down menu provided. The names that appear in the drop down menu are restricted by information lodged in the TGA Client database. If this name is incorrect or not displayed, please update the information in Client.2.3 Sponsor Address: Address of Sponsor selected from the drop down menu provided. The addresses that appear in the drop down menu are restricted by information lodged in Client. If this address is incorrect or not displayed, please update the information in Client.2.4 Sponsor Preferred Billing Address: Preferred Billing Address of Sponsor selected from the drop down menu provided. The addresses that appear in the drop down menu are restricted by Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41

2.12.22.32.42.52.62.72.82.92.102.112.12


information lodged in Client. If this address is incorrect or not displayed, please update the information in Client.2.5 Sponsor Regulatory Correspondence Address: Regulatory Correspondence Address of Sponsor selected from the drop down menu provided. The addresses that appear in the drop down menu are restricted by information lodged in Client. If this address is incorrect or not displayed, please update the information in Client.2.6 Contact Name: Preferred Contact Name for the individual responsible for liaison regarding the application. This person must be on the TGA Client database as an authorised contact or agent for the sponsor. If this name is incorrect or not displayed, please update the information in Client.2.7 Contact Phone Number: Preferred Contact Phone Number (include area code and country code for overseas applicants). This information is not automatically uploaded from TGA Client database and must be added manually.2.8 Contact Fax Number: Preferred Contact Fax Number (include area code and country code for overseas applicants). This information is not automatically uploaded from TGA Client database and must be added manually.2.9 Contact Email: Preferred Electronic mailing address of applicant2.10 This Application is to: Applicant should select the most suitable of the three options provided. Please note if “Vary a current Biological (or Export Only) entry” is selected a new mandatory field appears which requires the applicant to populate the “ARTG Entry for Variation”Note: The option to vary an ARTG entry will not be applicable until after one or more biologicals have been included on the ARTG for the sponsor.2.11 Application Fee: An automatically populated field displaying the Application Fee payable by the applicant to process the application.Note: This “Application Fee” initially displays as “0” and only correctly populates with the correct fee after completion and successful validation of the application form.2.12 Exempt from Payment? Applicant is required to consult with the TGA prior to selecting “Yes”. In some circumstances an agreement has been reached between the TGA and Sponsors for which an exemption may apply. Please note that this exemption field is not for use without prior confirmation from Biological Science Section, or the application will be rejected. For information on funding arrangements for Australian publicly funded facilities and not-for-profit hospital supply units please see the TGA website. Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41


3. RegistrationThe information to be completed within the Registration tab is regulatory information about the Biological for which the application is being made.Figure 4 The Registration tab

3.1 Class of Biological: Select the appropriate class (Class 1-4) of biological selected from the drop down menu provided. Currently the option to choose Class 1 is inactivated.How to determine the class of biologicalThere are four classes of biologicals with the level of regulation based on risk, extent of manipulation applied to the biological, and whether the intended use is its usual biological function. For a more comprehensive list on the definitions of the four classes and the level of regulation to be applied to each class please see Section 1.2 of the ARGB.

3.2 Product Type: Type of product selected from the drop down menu provided. This list may be updated from time to time.


3.13.23.33.4


3.3 Label Name (also referred to as the ARTG Label Name): This field is automatically populated after successful validation.What will the ARTG Label Name include?Class 1 and Class 2: Label Name will be the Product Type + Sponsor NameClass 3 and Class 4: Label Name will be the Product Type + Product Name + Sponsor Name + Dosage Form + Container Type

3.4 Standards: The standards applicable to the biological product. At least one must be selected for successful validation. This list may be updated from time to time. All applicable standards must be selected and compliance must be demonstrated in the product dossier.4. ManufacturersThe Manufacturers tab requires information about each individual manufacturer of the biological(s) for which the application is being made. At minimum the applicant must have pending or approved GMP manufacturing licence or clearance for all manufacturers. If a TGA manufacturing licence or clearance have been granted the information on the certificate should be used to inform the information required under this tab. Further information on manufacturing licences is available on the TGA website.Figure 5 The Manufacturers tab

4.1 Add Manufacturer: Selecting this button will open the screen shown in Figure 6. Depending on if the manufacturer is Australian (Figure 6a) or and overseas manufacturer (Figure 6b) the required information will vary slightly. All information required should be identifiable on the current license for the manufacturer.


4.1 4.2 4.3


Figure 6a The ‘Add Manufacturer’ screen (Australian Manufacturer selected)

Figure 6b The ‘Add Manufacturer’ screen (Overseas Manufacturer selected)

4.1.1 Where: Location of the Manufacturer (Australian Manufacturer or Overseas Manufacturer)4.1.2 Context: The applicant needs to select the method to search for and locate a manufacturer.

Name: Search and locate by Name of Manufacturer. ID: search and locate by Client ID of Manufacturer. Licence: If Australian Manufacturer is selected, this option becomes available. This allows the applicant to search for the Manufacturer by GMP Licence Number. Clearance: If Overseas Manufacturer is selected, this option becomes available. This allows the applicant to search for the Manufacturer by GMP Overseas Clearance Number. Note: this must be a clearance number, not a certification number.

4.1.3 Enter part/all of a manufacturer’s name: Locate the manufacturer by the context selected in the previous field e.g. If Manufacturer ID is selected as the “Context” then enter the Manufacturer ID.


4.1.14.1.24.1.34.1.44.1.54.1.6


1. To search by Name, type all or part of the manufacturer name for which to search. To search by ID, Licence, or Clearance, the complete Client ID, license number or clearance number must be entered for the search to work correctly. 2. Activate the search by clicking the “Search” button to the right of the field: The field will then inform the user of the status of the search, with the option to click the “cancel” button to stop the search:

3. When the search is complete (this should not take more than a few seconds, depending on how specific the search is) the number of matches will appear in red text above and to the right of the field:4. The desired manufacturer can then be selected by using the drop down arrow to show the list of search results.5. To start a new search, the search can be reset by clicking the “new search” button to the right of the field, and then restart the search process as of step 1.

Note: If the Manufacturer cannot be located, consider the following options: try an alternative search (e.g. client ID rather than Name) check the search details used are correct against the manufacturer details in eBS. Note that for an overseas manufacturer there may be multiple TGA Clearances, with each specific to a designated Sponsor check the format of the Client ID, licence or clearance numbers if an application for a new manufacturer has recently been lodged with the TGA, please allow a few days for the details to be entered in to the TGA Client database. At this time it will become a visible manufacturer if the manufacturer is still not available, they are likely not in the system with a current TGA licence or clearance. An application for a new manufacturer can be lodged through eBS.

4.1.4 Manufacturer Site: Manufacturer site selected from the drop down menu provided, which is informed by TGA Client, and is dependent on which manufacturer has been selected in the previous field.4.1.5 Manufacturer pending approval: This must be selected in the instance that a Manufacturer is pending licence/clearance approval from the TGA. Note that approval must be granted before the biological can be added to the ARTG.4.1.6 Steps performed by this Manufacturer: Select the appropriate Manufacturing steps performed at the selected Manufacturing Site. The desired steps can either be selected by clicking the arrow and scrolling through the steps to find those wanted, OR by typing text in the field, whereby any steps containing the text will be displayed in a list below the field, and can be selected. Once the desired step is selected, click the “add” button to the right of the field to add it to the table below. Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41


More than one step can be added, and unwanted steps may be removed by selecting the box to the left of the unwanted step/s, and clicking the “remove” button to the right of the field.

Only include the manufacturing steps performed at the selected manufacturing site relevant to the product in the current application form.Note: The selected steps are strictly validated against the manufacturing steps approved by Office of Manufacturing Quality and as stated verbatim on the GMP clearance or licence.When all the fields have been correctly populated click the button at the bottom left of the window to add the information and close the “search for a manufacturer” window.If it any time you wish to return back to the initial screen click .Note: Any information that may be populated in the “search for a manufacturer” window will be lost if the applicant chooses to close the window. To make further amendments to the added manufacturers, double-click the required manufacturer from the list in under “Manufacturers” tab and make the appropriate changes.This will update the Manufacturer’s list to include the information provided by the applicant. If additional Manufacturing Sites need to be added then repeat from 4.1 4.2 Remove Selected: Select the Manufacturing Site(s) that you wish to remove and click on the “Remove Selected” button.4.3 Apply for a New Manufacturer: Clicking this will allow a new manufacturer to be entered (Class 1 only).



5. ProductThe information to be completed under the Product tab is information about the formulation, container and other vital information about the Biological for which the application is being made.A red asterisk ( ) indicates a mandatory field. Mandatory fields must be populated in order for the application to be successfully validated and subsequently lodged. In order for this tab to be successfully completed, the 'Class of Biological' must be selected from within the 'Registration' tab.Figure 7 Product screen

5.1 Class of Application: The class of the application will appear based on the class of Biological selected under the Registration tab5.2 Is this Biological Product: The current application is for a Single Product or Multiple Products. The applicant will not be able to make a selection if the Class of Biological was not previously selected. Only applications for Class 1 or Class 2 Biologicals can include multiple products.

Separate and DistinctThe rules governing what can be included in a multiple product entry is based on the definition of ‘separate and distinct’ in section 32AB of the TG Act and Part 3 Section 11A of the TG Regulations. If Class 1 or Class 2 Biologicals are NOT ‘separate and distinct’ then they are permitted to be submitted as a multiple product application. See Section 1.2.5 of the ARGB for details about the requirements for separate and distinct biologicals and separate ARTG entries.


5.15.2

5.3 5.4


5.3 Add product: Select this button to open the product details screen, as shown in Figures 8a and 8b. Figure 8a The product details screen (for class 1 and 2 biologicals)

For Class 3 & 4 biologicals the initial ‘Intended Use’ field is replaced with ‘Proposed Therapeutic Indications’, as shown in Figure 8b.Figure 8b Alternative field for Classes 3 and 4: “Proposed Therapeutic Indications”


5.3.15.3.25.3.45.3.35.3.5

5.3.6

5.3.75.3.85.3.95.3.105.3.115.3.12


5.3.1 Product Name: A list of preferred product names and the principles applied to the naming of Biologicals is provided on the TGA website. Where an appropriate name is not listed please contact the TGA to confirm the appropriateness of the designated product name.5.3.2 Intended Use/Proposed Therapeutic Indications: For Class 2 products the indicated use can be chosen from a pull-down menu. If a suitable intended clinical use is not included in the drop down menu the TGA should be contacted and additional intended clinical use 'phrases' can be added, if appropriate (see Adding new entries to the code tables). Additional guidance on the definition of intended use for a Class 2 biological can be found in Section 5, Appendix 1 of the ARGB.For Class 3 and Class 4 free text entry for proposed therapeutic indications is available. 5.3.3 Route of Administration: Select the route/s of administration from the drop down menu provided and then click . Multiple routes may be added. If a suitable route of administration is not included in the drop down menu the TGA should be contacted and additional terms can be added, if appropriate (see Adding new entries to the code tables).5.3.4 Values selected: Route/s of administration will be listed here, as selected in 5.3.3.5.3.5 Dosage form: Select the dosage form from the drop down menu. If a suitable dosage form is not included in the drop down menu the TGA should be contacted and additional terms can be added, if appropriate (see Adding new entries to the code tables).5.3.6 Add formulation: Clicking “Add Formulation” will cause the screen seen in Figure 9 to appear. Every ingredient present in the finished product must be listed in this box. For example, if the biological component is released in a storage solution, details of the biological component and each constituent of that storage medium would need to be entered here, unless the medium is registered as a ‘proprietary ingredient’.Figure 9 The formulation details screen

5.3.6.1. Formulation Type: Type of Ingredient. The ‘Active’ ingredient is the component(s) with a direct therapeutic role, for example the tissue or cell population. The ‘Excipient’ ingredient(s) is a component of a finished dosage form other than an active ingredient. For combination products, such as a regenerative medicine product combined with a matrix, both components should be listed as separate formulations.Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41

5.3.6.15.3.6.25.3.6.35.3.6.45.3.6.55.3.6.65.3.6.7


5.3.6.2. Ingredient Role: By default the ingredient role is ‘Standard’, but some excipient ingredients may be ‘Proprietary’. The term ‘Proprietary Ingredient’ means a confidential formulation usually containing two or more ingredients and about which information is not in the public domain. If your ingredient does not fit the above definition, the applicant is advised to select “Standard”. In order for a biological that contains proprietary ingredients to be included on the ARTG the formulation details must be supplied to the Therapeutic Goods Administration (TGA). The Notification of a new proprietary ingredient form is the mechanism that allows Proprietary Ingredient formulations to be entered onto the ARTG and is available on the TGA website.Note: Since there are currently no active ingredients which are subsequently proprietary ingredients, the applicant will only be able to select “Standard” as the Ingredient Role after selecting “Active” as the Formulation Type.5.3.6.3. Ingredient Name: The ingredient name to add to the formulation. See Part 1, Section 3 for details on the Ingredients database that informs this field of the application form. The options available to populate this field are: 1. Enter the desired search text. This may be all or part of the ingredient name of interest.2. Activate the search by clicking the “Search” button to the right of the field. The field will then inform the user of the status of the search, with the option to click the “cancel” button to stop the search:

3. When the search is complete (this should not take more than a few moments, depending on how specific the search is) the number of matches will appear in red text above and to the right of the field:4. The desired ingredient can then be selected by either using the drop down arrow to show the list of search results, or the user can type text in the field to populate it with an entry available in the list containing the text typed.5. To start a new search, the search can be reset by clicking the “new search” button, to the right of the field, and begin a new search as from step 1.

If a suitable ingredient is not included in the menu the TGA should be contacted and additional terms can be added, if appropriate (see Adding new entries to the ingredients list).5.3.6.4. Select Quantity Options: Select if the ingredient quantity is a nominal value or a range of values.If “Ingredient Quantity Range” is selected, the following fields appear (to replace the “Ingredient Quantity field” which is the present at default):5.3.6.5. Ingredient Quantity (or Ingredient Quantity From/Ingredient Quantity To): Enter number(s) corresponding to the ingredient quantity and select the corresponding units from the drop down menu provided. If ingredient quantity is “greater than” or similar, please enter this under “additional ingredient information”. Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41


5.3.6.6. Additional Ingredient Information: The applicant may include any additional information they regard as necessary and that may facilitate the application review process. For example, it should be noted if an ingredient is sourced from more than one supplier and the purity varies significantly.5.3.6.7. Is this ingredient of animal or human origin?: Selecting ‘Yes’ will cause the table shown in Figure 10 to appear below. Figure 10 Animal or Human Origin

If the ingredient currently being entered is of animal or human origin, select yes. By clicking the button, the screen shown in figure 11 will appear, and the details can be filled out appropriately:Figure 11 Animal or Human Origin screen

5.3.6.7.1 Species: Select species from drop down menu.5.3.6.7.2 Tissue: Select source tissue from drop down menu.5.3.6.7.3 Preparation: Select preparation from drop down menu.5.3.6.7.4 Country: Select country/countries of origin from drop down menu and click to include selected country. Multiple countries can be listed.5.3.6.7.5 Values selected: Selected country/countries of origin appear here. When all the fields have been correctly populated press Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41

5.3.6.7.15.3.6.7.25.3.6.7.35.3.6.7.45.3.6.7.5


5.3.7 Has material of human or animal origin been used that is not present in final product? Examples of such material may include porcine trypsin used to remove adherent cells from cell culture plates, bovine serum albumen used in buffers or foetal calf serum used in cell culture media, or feeder cell layers used to support growth of stem cells. Selecting ‘Yes’ will cause the table shown in Figure 12 to appear.Figure 12 Has material of human or animal origin been used that is not present in final product?

To add details of the material of human or animal origin that been used that is not present in final product, click the button to the left of the table, which will bring up the window shown in Figure 13. Figure 13 The product starting material screen

5.3.7.1. Ingredient Name: Name of ingredient selected from the drop down menu provided. See Part 1, Section 3 for details on the Ingredients database that informs this field of the application form. If a suitable ingredient is not included in the menu the TGA should be contacted and additional terms can be added, if appropriate (see Adding new entries to the ingredients list).5.3.7.2. Additional Ingredient Information: The applicant may include any additional information they regard as necessary and that may facilitate the application review process. For example, name and/or description of feeder cells.5.3.7.3. Add animal origin: The window will appear as shown in Figure 5.3.6.7 to add animal/human origin details. For further information please see points 5.3.6.7.1 to 5.3.6.7.5. When all the fields have been correctly populated press .Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41

5.3.7.15.3.7.25.3.7.3


5.3.8. Product Container Details and Shelf Life: Clicking “Add Product Container” will cause the following screen to appear:Figure 14 The product container screen

5.3.8.1 Container Type: Type of container containing the biological selected from the drop down menu provided. If a suitable container is not included in the drop down menu the TGA should be contacted and additional terms can be added, if appropriate (see Adding new entries to the code tables).5.3.8.2 Container Material: The material from which the container is made selected from the drop down menu provided. In the case of a container that is made of more than one type of material, then the material that is primarily in contact with the product should be selected. If a suitable container material is not included in the drop down menu the TGA should be contacted and additional terms can be added, if appropriate (see Adding new entries to the code tables).5.3.8.3 Shelf Life Time: The length of time for which the biological product remains usable, fit for consumption, or saleable selected from the drop down menu provided. If a suitable shelf life time is not included in the drop down menu the TGA should be contacted and additional terms can be added, if appropriate (see Adding new entries to the code tables).5.3.8.4 Shelf Life Temperature: The temperature at which the biological product remains usable, fit for consumption, or saleable selected from the drop down menu provided. If a suitable shelf life temperature is not included in the drop down menu the TGA should be contacted and additional terms can be added, if appropriate (see Adding new entries to the code tables).5.3.8.5 Shelf Life Conditions: Specific storage conditions imposed on the biological product by the applicant. This field is mandatory for Classes 2, 3 and 4. Select condition from drop down menu and click to include selection. Multiple conditions can be listed. When all the fields have been correctly populated press .Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41

5.3.8.15.3.8.25.3.8.35.3.8.45.3.8.5


5.3.9 Additional shelf life information: The applicant may include any additional information regarded as necessary. For example, ‘once at room temperature, do not re-freeze and use within 24 hours. 5.3.10 Has this product been subject to bioburden reduction?: The applicant is required to indicate if bioburden reduction processes are applied to the Biological. Selecting “Yes” will enable a drop down menu, from which the bioburden reduction method should be selected. If a suitable method is not included in the drop down menu the TGA should be contacted and additional terms can be added, if appropriate (see Adding new entries to the code tables).5.3.11 Has this product been terminally sterilized?: The applicant is required to indicate if terminal sterilization processes are applied to the Biological. Selecting “Yes” will enable a drop down menu, from which the terminal sterilization method should be selected. If a suitable method is not included in the drop down menu the TGA should be contacted and additional terms can be added, if appropriate (see Adding new entries to the code tables).5.3.12 Has this product been aseptically processed?: Indicate if aseptic processing has occurred during the manufacturing process, subsequent to the initial collection of the biological starting material.



6. Supporting informationThis section is for Class 1 products only.Figure 15 Supporting information screen

6.1 Attach a Document: Clicking this will cause the following screen to appear:Figure 16 Attach a document screen

6.1.1Classification: Specify the security classification of the attached document. For example, commercial-in-confidence6.1.2 Title: Specify the title of the attached document6.1.3Description: A brief description of the contents of the attached document6.1.4 Attachment: To insert an attachment click Browse and select the relevant document from the ‘choose a file to upload’ dialog.After the document has been selected press The following text should appear at the top of the window: “File uploaded/saved successfully”The applicant will be given an opportunity to upload additional documents. Once all the documents have been uploaded press to return to the previous menu. Australian Regulatory Guidelines for BiologicalsAppendix 10 – Guide to Biological application V1.0 July 2011 of 41

6.1 6.2 6.3

6.1.16.1.26.1.36.1.4

Biologicals Framework LtdBiologicals Framework LtdPO Box 1, CanberraPO Box 1, CanberraPO Box 1, Canberra


6.2 Remove Selected Documents: Select the Document(s) that you wish to remove and click on “Remove Selected Documents”6.3 Refresh List of Files: Provides an up-to-date list of attached documents. Applicants are encouraged to utilize this option to ensure all the relevant documentation has been successfully uploaded.7. Validation When all the details in the form have been completed the applicant must validate the information by pressing in the row above the tab banner (see Section 1). This will automatically take the applicant to the Validation section of the form.The Validation section contains a list of error messages. These are hyperlinked to the section of the Application Form where the error(s) has occurred.The applicant will be unable to successfully lodge an application until all the issues listed are addressed and rectified.Figure 17 and 18 provide an example of a Validation resulting in an error and process taken to address and rectify the error:Figure 17 Validation error screen

Double-click on the validation error message to be taken to the relevant sectionFigure 18 Missing data resulting in validation error

Following the amending of the error click on When all errors have been resolved validation will complete.



PrintingNote: A copy of the eBS application must be printed off and included with the product dossier. This can be done by selecting ‘Print Preview’. To ensure that all information is included in this, it should be printed following validation but before submission. This document can also be saved as an HTML file for records.8. Audit logThis section contains a comprehensive log of key activities conducted on the application. This includes all occasions that the application was saved and/or validated and the outcome of each activity along with the respective time and date that each activity was conducted.This allows the applicant to monitor all the activity conducted on the application. 9. Submitting an ApplicationWhen all components of the application form have been completed and validated the applicant need to submit the form to the TGA. The following instructions outline the location in eBS where the application is submitted, and describes the process.

1. Click on “Portal – Applicant Name” to expand the menu. Note that the actual Applicant Name is not visible in this instance.2. Click on “Create Applications & Submissions” to further expand the menu3. Click on “Biologicals” to further expand the menu4. Click on “Submission” to gain access into the “Biological Submissions” screen, which is shown in Figure 19 below.


Applicant Name


Figure 19 Biologicals submission screen

9.1 Close Button: At any time, the applicant can return to the eBS portal by clicking the close button at the top left hand of the screen. Any field selections made will be lost, and no applications submitted.9.2 Client Name: An automatically populated field displaying the Name of the Applicant, which is linked to the eBS login being used.9.3 Applicant Billing Address: Billing Address of Applicant selected from the drop down menu provided. If this address is incorrect or not displayed, please update the information in Client.9.4 Sponsor Name: Name of Sponsor selected from the drop down menu provided.9.5 Class of Biological: Select the class of the application you wish to submit from the drop down menu provided. This filters all valid applications to show only those from the chosen class to be displayed below.9.6 Eligible Applications: This table is populated depending on the options chosen in the previous fields. Namely, only validated applications for the chosen sponsor for the selected class will be available in this table for selection. An application can be chosen for submission by checking the box to the left of the Application ID.Applications selected for submission must:

Be of the same Class of Biological; Have the same Sponsor Billing Address; Have the same Principal Manufacturer undertaking the Release for Supply step; Class 1 or Class 2 selections must conform to the same Product Standards; Class 3 or Class 4 selections must have the same Active Ingredient.


9.29.39.49.5

9.6

9.19.7


Note: If the application did not validate (Status displayed as “Not Valid”) then it will not be available for submission until all errors are corrected and the application has been validated.9.7 Submit Button: At the time when the applicant is satisfied with the application/s selected for submission, the applications can be submitted by clicking the button at the top left hand of the screen. This will cause the screen to change, as per Figure 19:Figure 20 Declaration screen

The declaration shown below this text will change depending on the class of biological/s included in the submitted application.The applicant must read the declaration and if the terms are accepted, the submission can be progressed by clicking the accept button.If the applicant does not agree to the terms, the Decline button can be clicked which returns the applicant to the previous screen.Clicking the close button has the same effect as previously, returning the applicant to the eBS portal screen.If the applicant has read and agreed to the terms of the declaration by clicking ‘submit’, the following screen will appear:Figure 21 Acknowledgement of successful submission

At this screen the applicant can print the invoice, and also the submission document for inclusion in the product dossier. This is a required component of the dossier. If this is not printed at the above screen, it can be accessed through the eBS portal (see Part 1 section 2.2).



ReferencesResource URLTGA website http://www.tga.gov.auInformation on determining the class of biological http://www.tga.gov.au/pdf/biologicals-argb-p1.pdfInformation on exemption from fee payment http://www.tga.gov.au/industry/biologicals-framework-qa-p3.htmRequesting a new AAN or ABN http://www.tga.gov.au/industry/medicines-approved-terminology.htmRequesting a new ABI (contact details provided for ‘AANs and Proprietary Ingredients’) http://www.tga.gov.au/industry/artg.htmManufacturing information http://www.tga.gov.au/industry/manuf.htmInformation on proprietary ingredients http://www.tga.gov.au/industry/medicines-forms-propietary-ingredient.htm. eBusiness information http://www.tga.gov.au/about/ebs-about.htmTGA Biological Science Section http://www.tga.gov.au/industry/btb.htm



Therapeutic Goods AdministrationPO Box 100 Woden ACT 2606 AustraliaEmail: [email protected] Phone: 1800 020 653 Fax: 02 6232 8605www.tga.gov.au