# C. Responses to a submission and query

The scope of two-way communication is communication of non-documentation
related information about an application. The communication is between
the applicant and regulatory authority; not individuals in either
organization. Although the message is from organization to organization,
the letter in the communication can be addressed to an individual.

The Regulated Product Submission's project team is aware there are
existing business policies and procedures. Our intent is for this
message to be able to be used within existing operations. For example,
if a regulatory authority has a process with extensive review of a
communication and only sends formal requests, that process does not have
to change. However, if an organization revisits their processes, each
organization can choose to change their business process to take
advantage of features in the RPS Standard.

# C1. Associate a regulatory action on a submission

The regulatory authority is in the process of deciding if the Calming
Myst product, a medication for heart burn, is safe and effective for
general use. After careful deliberations, the regulatory authority
decides to approve this submission. The regulatory authority generates
an approval letter. That letter is transmitted in a message to the
applicant. The status of the submission is now approved.

Note: Status of a submission could be pending, on hold, approved, not
approvable, etc. -- We need to complete this list

# C2. Associate a regulatory action on multiple submissions

Wonder drug is a drug product that relieves severe pain and nausea. Five
milligrams of this dug product should be released in the blood stream
every six hours. Perfect Injection is a device that can perform such a
task. This product has two independent submissions, one for pain and one
for nausea. Both submissions are in progress with a regulatory
authority.

Perfect Injection causes Wonder Drug to be absorbed in the blood stream
at faster rate than expected. Due to the faster absorption rate, the
regulatory authority believes this combination product is not safe. The
regulatory authority drafts a letter that puts an on hold order on all
of the clinical trials using wonder drug with the perfect injection
device. That letter is transmitted in a message to the applicant. The
statuses of both submissions are on hold.

Note: Status of a submission could be pending, on hold, approved, not
approvable, etc. -- We need to complete this list

# C3. Ask questions to a particular file

In the Calming Myst submission, a protocol document was provided for a
particular study. The regulatory authority asks why are there so many
planned visits in the beginning of the study. The regulatory authority
creates a document asking this particular question. That question is
rolled in a message, tied to that specific protocol file, and sent to
the applicant.

# C4. Ask questions to a particular logical document

There are several submitted studies in a Calming Myst submission. The
regulatory authority asks why were several more observations taken from
patients in a particularly study then originally planned. The regulatory
authority creates a document asking this particular question. That
question is rolled in a message, tied to that specific study, and sent
to the applicant.

# C5. Responding to a question for a regulatory authority

In the Calming Myst submission, the regulatory authority asked why there
were so many planned visits in the beginning of the study. The applicant
felt the answer to this question was already explained in the existing
documentation. The applicant would create a message, point the
regulatory authority to the documentation that answers their question,
tag the response to the original question, and then send that message to
the regulatory authority.

Note: The regulatory authority can respond to an applicant; thus,
creating a communication thread on a specific topic.

# C6. Ask questions to a particular application/submission/submission unit

Several submission units have been transmitted from the applicant to the
regulatory authority. The regulatory authority is close to approving
this submission. However, the regulatory authority needs clarification
about safety information relating to subjects over the age of fifty. The
regulatory authority creates a document asking for more information.
That question is rolled in a message, tied to the particular submission,
and sent to the applicant.

# C7. Acknowledgment of receipt of message

A submission unit for super device was sent to the regulatory authority.
In this submission unit, there were 20 files transmitted and 30 files
referenced. One of the transmitted files has an integrity check value
(checksum) that did not match the computed checksum. Therefore, that
file was either tampered with, corrupt, or the correct checksum was not
inputted correctly in the submission unit message.

In addition, one of the referenced files was coded as a drug product
nomenclature. Drug product nomenclature is not a valid coded value for
this device submission. The regulatory authority transmits an
acknowledgment message stating they received the submission unit. The
acknowledgment message also states that one file had an incorrect
checksum value and the context of one file has an incorrect coded values
based on the specified submission type.

Note: Some form of acknowledgment should occur for all messages. The
acknowledgment can come in many forms, a conformation e-mail, a return
message, a log file created noting the action taken on the transmitted
message, etc.

# C8. Changing an amendment to a new supplement/variation

An amendment to the Claming Myst submission was delivered to a
regulatory authority. However, since this amendment describes a new use
for this product, the regulatory authority decides that this submission
unit is not an amendment to an existing submission but a new
variation/supplement in this application. The regulatory authority
transmits an acknowledgment message stating they received the submission
unit. The acknowledgment message also reclassifies this submission unit
as a new supplement in the application.

Note: It is also possible for the regulatory authority to reclassify a
supplement/variation to an original submission in a new application.

# C9. Separate a supplement to more than one submission

Manufacturing equipment is being replaced that effect four submissions,
an original and three supplements. Since this manufacturing change has
no negative effect on the submission the applicant sent only one
manufacturing supplement. The regulatory authority asked to break this
supplement into four distinct supplements. Since the equipment change
effect two products in the same manner and the other two products
differently, the applicant creates three submission units. One
submission unit applies to two supplements and the other submission unit
applies to only one supplement.

However, since the files are already submitted to the regulatory
authority, only the new messages will have to be delivered. Each message
would only point to the ID value of the already submitted files.

Note: Only the applicant can choose what files belong to which
submission.

# C10. Communication about documentation submitted outside of the Standard

An issue that have not been properly identified and dealt with from a
messaging standpoint in RPS is delivered to the regulatory authority.
The regulatory authority has a question about this documentation. The
regulatory authority describes the date and type of documentation that
was delivered outside of the RPS message, and attaches that query to the
submission.

Note: This issue is how to deal with \"error\" conditions when the
design does not completely cover the situation at hand.

# C11. Question on non-application specific items

A one page marketing material is sent to the regulatory authority for
approval for dissemination. The material implies effectiveness beyond
what has been previously agreed to in labeling negotiations. The
regulatory authority questions particular phrases of the marketing
material.

The type of communication is out of scope. Any communication that is not
directly tied to submission is out of scope.

# C12. Answer a question by navigating through a common view

Several submission units have been transmitted from the applicant to the
regulatory authority. The regulatory authority is close to approving
this submission. However, the regulatory authority needs clarification
about safety information relating to subjects over the age of fifty. The
regulatory authority creates a document asking for more information.
That question is rolled in a message, tied to the particular submission,
and sent to the applicant. In response the applicant contacts the
reviewer to point out where the clarification exists in the submission.
The reviewer and applicant while discussing the submission open up the
same view of the submission and the applicant guides the reviewer to the
location in the submission that may answer the reviewers question.