Regulated Product Submission Release 2 (RPS R2) Business Scenario Development

This page consolidates the information drafted and discussed during the business scenario development sessions at the July 24, 2008, Requirements Kick-off meeting in Silver Spring, Maryland. The business

scenarios have three categories, corresponsing to the three scoping statements:

• #Two-way Communication
• #Referencing
• #Information about the Submission

Two-way Communication

1. Submission Activities

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Request for Submission Number (with the idea that this may be done in an automated pre-submission manner).
Additional Information	Review Guidance Documents from each Authority (Note: May be difficult for EU)
Issues and Questions	Should Post-Market Commitment be included in Regulatory Actions? What is the definitions of correspondence and message? What differentiates a submission unit from correspondence? Will any correspondence get part of the application? It is usually considered part of the application documentation. Can this business scenario also capture the administrative activities (i.e., technical issues, validations, etc.)?

2. Meeting Requests and Responses

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Request Meeting (e.g., End of Phase I Meeting, Phase II Meeting, Meeting during review, Pre-Submission Meeting, Meeting request may come from either regulated industry or regulatory authority Meeting request response (from requested party) Related pre-meeting materials should be sent from one party to another Resulting meeting minutes, materials, action items should be sent
Additional Information	-
Issues and Questions	Are there specific metadata requirements? Will the activities (request meeting etc.) fall into the scope of correspondence or would it be valuable to categorize minutes as a submission unit because it might be relevant for future regulator decisions or it may define some aspects of the upcoming study agreed upon?

3. Follow-up/Post-market

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Regulatory Authority asks Regulated Industry about technical issues based on field experience Currently this occurs via e-mail, fax or phone correspondence
Additional Information	-
Issues and Questions	Does this only occur on a postmarket basis due to some field activity? Is this based on a field inspection (compliance) that may result in questions to the regulated industry based on information that was not required to be submitted to the regulatory authority?

4. Pre-submission Activities

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Communications between regulators to plan details of review Communications between sponsor and regulators May take the form of one of the following: - Face-to-face meetings - E-mail - Phone - FDA Meeting Minutes Meetings for a contractor to discuss facility requirements (sponsor requested meeting) Giving overall advice on planned submission or development activities Giving “scientific advice” (relates to one or multiple applications) Communications may not ever connect to a submission
Additional Information	-
Issues and Questions	The group indicated that "presubmission" requires definition.

5. Informal Interactions

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Questions not associated with a submission Questions associated with a submission
Additional Information	Refer to FDA/CDRH Guidance for Interactive Review
Issues and Questions	How are these conversations recorded today? Are all communications captured in a letter or e-mail? Do they all become part of the official record? To formalize the documentation of phone calls may be very time consuming and therefore realistically not performed. E-mail communication in a highly structured form will require e.g. a portal providing all the relevant meta data. Again, it will not be feasible to key in all meta data again and again manually even if you use the reply function. May be a request or an option should be foreseen. If this becomes automated - How does the “system” weed out the “out of office” type of e-mails? This scenario needs examples of questions that may be considered “informal”

6. Waiver Requests

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Sponsor sends Waiver Request related to a submission Sponsor sends Waiver Request not related to a submission
Additional Information	-
Issues and Questions	This scenario needs examples of waivers

7. Notification of Decision

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Regulator(s) notify sponsor(s) and/or other Agencies of decision regarding the submission (and/or reviewable unit) Example of a multilayered – combination product (includes indication, formulation, clinical trial, manufacturing change, raw materials) Conditions/Status Options -Yes with No Conditions -Yes with Conditions that are open ended (fixed duration) -Yes with Conditions that are open ended (lifecycle commitment) -Yes with Conditions that are closed -No with Justification -No (conditional) -Reimbursement
Additional Information	-
Issues and Questions	Are there any other status options?

8. Recalls

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Health Authority contacts sponsor of required recall
Additional Information	Example: FDA/CFSAN > Court > FDA > Sponsor Example: Health Authority > Multiple Sponsors for a mass recall for products for excipients
Issues and Questions	-

9. Withdraw from Market after Approval

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	The Regulatory Authority contacts sponsor and/or other regulatory authorities requesting withdraw from market for application/product(s) The Sponsor contacts the regulatory authority of withdraw from market for application/product(s)
Additional Information	More common for the sponsor to withdraw application If a Master File has been reference once, the application cannot be withdrawn.
Issues and Questions	-

10. Public Health Risk Notification

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	The Regulatory Authority may contact other Regulatory Authority regarding regulatory actions for public health risk
Additional Information	Within a BoH BoH to BoH (is this out of scope?) BoH to notify Sponsor
Issues and Questions	DEFINE ACRONYM: Does BoH mean Board of Health

11. Labeling Negotiations: Request for Additional Information

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Once the sponsor submits labeling the Regulatory Authority may request/suggest changes Negotiations may be conducted by e-mail or phone
Additional Information	-
Issues and Questions	What is captured by the Regulatory Authority about the negotiations? Are questions asked? -Is there a change to the documentation that results from the questions asked? -Is there a mechanism to ask follow up questions and/or clarification to the Regulatory Authority’s questions/suggestions/change requests?

12. Interagency Negotiations

Actors	Regulatory Authorities
Description	One Agency (Agency Division) asks another Agency a question or shares comments; the receiving Agency can send answers Informal assessment process (at some agencies); when it impacts the decision it is formal) Formal communication is traced as condition/commitments. Optional question or answer can refer to documentation, application or submission.
Additional Information	-
Issues and Questions	Can the two agencies exchange questions once the negotiation is initiated?

13. Questions about where to find content (“I can’t find it”)

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Information was included in the submission unit, but the reviewer is not able to find the information Sponsor responds (e.g., identification of the location with previously submitted documents, I have it and will send it, don’t have it and will create it)
Additional Information	This communication is accepted by e-mail, phone, fax, or formal letter.
Issues and Questions	Is this an informal interaction? Once the information was not located within previously submitted documentation, is that when it becomes formal?

14. Questions from Sponsor to Agency and Resulting Response

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	The sponsor contacts the Regulatory Authority regarding questions on an application. For example, mid-study the sponsor needs advice from the Regulatory Authority on the study. - Feedback on study (data sets from safety signaling) - Whether to continue with the study - To ask if additional (3rd year) data is needed The questions can be to clarify content, placement, technical, standards The Regulatory Authority will provide a response
Additional Information	This communication is accepted by e-mail, phone, or formal letter
Issues and Questions

15. Questions from Regulatory Authority and Sponsor Response

Actors	Regulated Industry (e.g., Sponsor, Applicant, “Submitting Entity”) Regulatory Authorities
Description	Agency creates questions to send the sponsor Sponsor receives a number (multiple) of questions Questions may or may not have timelines (due dates) Sponsor may respond to one or many or all of the questions at once or at different times Agency needs to track when all of th questions have been answered Some negotiations may happen (i.e., when there are questions about questions that require clarification) Clarifications can be received by email or phone Agency may approve the response to question 1 but need additional information after receiving the response to question 2 The status will remain open for all responses that the Agency finds inadequate Multiple responses may come in for one question over time. For example, the response may require input from the applicant (some amendments or clarifications), from an active substance master file holder (amendments on the closed parts) and a Member State (composition of the referenced product). The applicant may need to send the response to multiple Member States.
Additional Information	-
Issues and Questions	-

Referencing

16. Reference Document within Submission Unit

Actors
Description
Additional Information
Issues and Questions

17. Referencing document between submissions

Actors
Description
Additional Information
Issues and Questions

18. Referencing outside submission unit, but within application

Actors
Description
Additional Information
Issues and Questions

19. Reference Information in another Application

Actors
Description
Additional Information
Issues and Questions

20. Referencing Information owned by an External Party

Actors
Description
Additional Information
Issues and Questions

21. Updating Information that links to other information

Actors
Description
Additional Information
Issues and Questions

22. Update a Referenced Document in a Previous Submission

Actors
Description
Additional Information
Issues and Questions

23. Indirect Referencing

Actors
Description
Additional Information
Issues and Questions

24. Reference Paper Information from Electronic Source

Actors
Description
Additional Information
Issues and Questions

25. Reference External Electronic Source/Non-Retrievable

Actors
Description
Additional Information
Issues and Questions

26. Reference Electronic Source/Retrievable

Actors
Description
Additional Information
Issues and Questions

27. Referencing Approval Information

Actors
Description
Additional Information
Issues and Questions

28. Provide Access/Permission to a Submission

Actors
Description
Additional Information
Issues and Questions

29. Permit Use of Master File/Master Access

Actors
Description
Additional Information
Issues and Questions

30. Comparison Information

Actors
Description
Additional Information
Issues and Questions

Information about the Submission

31. Information about the Submission

Actors
Description
Additional Information
Issues and Questions

32. Identify Administrative Actions

Actors
Description
Additional Information
Issues and Questions