It explains about 510k Approval process for Biologics as well as Medical Devices in Us

1. Premarket Notification 510(k) for Biologics
Presented by :
T.SUSMITHA
621209527007
I/II M. Pharmacy(DRA)
A.U. College Of Pharmaceutical Sciences

2. Contents
Introduction
Who can submit 510(k)
When 510(k) is required
When 510(k) is not required
Contents & format
Types of Submission
Pre- Submission
Submission to FDA
Submission process
Decision making process
Ref:
2

3. 510(k)
 A 510(k) is a Premarket submission made to FDA to demonstrate that the biologics/device to be marketed is
as safe and effective, that is, substantially equivalent (SE), to a legally marketed biologics/devices.
 The medical devices regulated by CBER are intimately associated with the blood collection and processing
procedures as well as the cellular therapies regulated by CBER.
 Allows FDA to determine Substantial Equivalence.
 Before marketing a device, each submitter must receive an order, in the form of a letter, from FDA which
finds the Biological product/device to be substantially equivalent (SE) and states that the device can be
marketed in the U.S
 510(k) is not A Form
• Establishment Registration
• Device Listing
• Premarket Approval (PMA)
Ref: https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/premarket-notification-510k
3

4. Who can submit 510(k)
 According to The FD&C Act there is no specify who must submit 510(k) instead of this they specify which
actions, such as introducing a device to the U.S. market, require a 510(k) submission.
 Mainly there are four categories must submit a 510(k) to the FDA
1.Domestic manufacturers introducing a biologic/device to the U.S. market
2. Specification developers introducing a biologic/device to the U.S. market
3. Repackers or relabelers who make labeling changes or whose operations significantly affect the device
4. Foreign manufacturers/exporters or U.S. representatives of foreign manufacturers/exporters introducing a
device to the U.S. market.
Ref: https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/premarket-notification-510k
4

5. When a 510(k) is Required
 Unless exempt, introducing a device into commercial distribution (marketing) for the first time. anyone who
wants to sell a device in the U.S. is required to make a 510(k) submission at least 90 days prior to offering
the device for sale, even though it may have been under development or clinical investigation before that
date.
 A new 510(k) submission is required for changes or modifications to an existing device, where the
modifications could significantly affect the safety or effectiveness of the device or the device is to be
marketed for a new or different intended use.
Ref: https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/premarket-notification-510k
5

6. When 510(k) is not required
 You sell unfinished biologic/devices to another firm for further processing or sell components to
be used in the assembling of devices by other firms.
 Your biologic/device is not being marketed or commercially distributed. You do not need a 510(k)
to develop, evaluate, or test .
 You distribute another firm's domestically manufactured biologic/device. You may place a label on
the device, "Distributed by ABC Firm" or "Manufactured for ABC Firm," and sell it to end users
without submission of a 510(k).
Ref: https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/premarket-notification-510k
6

7. Contents involved in 510(k)
 It contains information regarding submitter's name, address, telephone number, a contact person, and the
date the summary was prepared.
 The name of the biological product/device, including the trade or proprietary name if applicable.
 An identification of the legally marketed device/biological product to which the submitter claims
equivalence.
 Describe the biological product/device about their Physical appearance, functions, specifications and
performance along with materials used for manufacturing.
 A statement of the intended use of the device
 A brief discussion of the clinical/nonclinical tests done& submitted
 The conclusions drawn from the nonclinical and clinical tests that demonstrate that the device is as safe, as
effective, and performs well.
Ref: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-807/subpart-E
7

8. Types of 510(K) submissions
There are 3 types of Submission: 1.Traditional 510(k) Required elements (21 CFR 807.87)
2. Abbreviated 510(k)
3.Special 510(k)
1.The Traditional 510(k) method can be used under any circumstance. The Abbreviated 510(k) and Special
510(k) methods can only be used if certain criteria are met.
2.Under certain conditions, sponsors may not need to submit test data in an Abbreviated 510(k).
3.Modification does NOT affect the intended use or fundamental scientific technology
No data is evaluated by FDA
Ref: https://www.fda.gov/files/about%20fda/published/Presentation---CDRH-Learn--The-510%28k%29-Program--November-4--2014.pdf
8

9. Pre-Sub for a 510(k)
 Guidance: Requests for Feedback on Medical Device
Submissions: The Pre-Submission Program and Meetings with FDA Staff
 Method to obtain FDA feedback prior to submission of your 510(k); typically for unique situations (e.g. need
for clinical data)
 Submit a formal written request to the FDA
 Request either a formal written response, meeting, or teleconference to address their concerns, questions, etc.
 Subject to eCopy requirements
Ref: https://www.fda.gov/files/about%20fda/published/Presentation---CDRH-Learn--The-510%28k%29-Program--November-4--2014.pdf
9

10. Submission to FDA
 Must submit 2 copies of 510(k) one of them submitted in an electronic format. FDA doesn’t return back
510(k) after review.
 An eCopy is defined as an exact duplicate of the paper submission, created and submitted on a CD, DVD, or
a flash drive. An eCopy is accompanied by a paper copy of the signed cover letter and the complete paper
submission
 Questions regarding eCopy requirements or responses to eCopy holds should be sent to CDRH-
eCopyinfo@fda.hhs.gov
 Where do you mail your 510(k)?
Food and Drug Administration
Center for Devices and Radiological Health
Document Control Center (DCC) - WO66-G609
10903 New Hampshire Avenue
Silver Spring, Maryland 20993-0002.
Ref: https://www.fda.gov/files/about%20fda/published/Presentation---CDRH-Learn--The-510%28k%29-Program--November-4--2014.pdf
10

11. Regulatory Submissions in Electronic Format to CBER
 Sponsors and applicants are encouraged to send applications and other regulatory submissions
electronically via the FDA Electronic Submissions Gateway (ESG) to CBER.
 When submitting via ESG, place all documents in a WebTrader folder and upload by folder to ESG.
 Submission of Lot Release Samples and Lot Release Protocols
• Official lot release samples should be sent to the CBER’s Sample Custodian address.
• Electronic lot release protocols can be submitted through the FDA Gateway at any time.
• Lot release protocols submitted in paper or CD-ROM electronic format should be sent to the CBER Sample Custodian
address.
 Sample Custodian Address at White Oak Campus
 FDA,CBER
Sample Custodian
10903 New Hampshire Avenue
WO75-G707
Silver Spring, MD 20993-0002
Ref: https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/regulatory-submissions-electronic-and-paper-format-cber-
regulated-products
11

12. Submission process
Ref: https://www.fda.gov/medical-devices/premarket-notification-510k/510k-submission-process
12

13. Refuse to Accept (RTA) Policy
Is the 510(k) submission administratively complete for substantive
review?
• Early Review – 15 calendar days from receipt
• Necessary elements and content of a complete 510(k) submission
• FDA clock begins on the date of receipt when the 510(k) is “accepted for review”
Substantive Interaction
FDA Notification that:
1. The 510(k) will not be placed on hold and outstanding deficiencies will be resolved via
Interactive Review, or
2. The 510(k) is being placed on hold via an Additional Information request which identifies
the outstanding deficiencies that need to be addressed before substantive review can continue.
Ref: https://www.fda.gov/media/82395/download
13

14. Interactive Review
Informal interaction between FDA and submitters during the review of 510(k) submissions
 Benefits: Prevent unnecessary delays; Reduce the overall time to decision; Ensure that FDA’s concerns are
clearly communicated;
 Minimize the number of review cycles; and Ensure timely responses
from submitters
 Interactive review requests do not stop the FDA clock
Ref: https://www.fda.gov/media/82395/download
14

15. Additional Information (AI) Requests
Why is additional information requested?
– Testing data required to demonstrate equivalence
– Reviewer has questions regarding labeling, wording, etc.
How is additional information requested?
– AI requests are sent via email
– AI responses are subject to eCopy requirements
How does this affect the submission review times?
– Clock stops when submission is officially placed on hold
– 180 days for a complete response to be received to DCC
Ref: https://www.fda.gov/media/82395/download
15

16. Ref: https://www.fda.gov/media/82395/download
16

17. Ref: https://www.fda.gov/files/about%20fda/published/Presentation---CDRH-Learn--The-510%28k%29-Program--November-4--2014.pdf
17

18. Why might you receive a NSE Decision?
1.There is no predicate device
2. Your device has a NEW intended use
3. Your device has different technological characteristics compared to the predicate device and raises
different questions regarding safety and effectiveness
4. You did not demonstrate that your device is at least as safe and effective as the predicate
What Happens After a Device is Cleared?
The following are posted on the FDA’s public 510(k) database:
– SE Letter
– Indications for Use Form
– 510(k) Summary (if provided instead of 510(k) Statement)
Ref: https://www.fda.gov/files/about%20fda/published/Presentation---CDRH-Learn--The-510%28k%29-Program--November-4--2014.pdf
18

19.  Until the submitter receives an order declaring a device SE, the submitter may not
proceed to market the device.
 Once the device is determined to be SE, it can then be marketed in the U.S. The SE
determination is usually made within 90 days and is made based on the information
submitted by the submitter.
 FDA does not typically perform 510(k) pre-clearance facility inspections.
 The submitter may market the device immediately after 510(k) clearance is granted.
 The manufacturer should be prepared for an FDA quality system (21 CFR 820)
inspection at any time after 510(k) clearance.
Ref: https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/premarket-notification-510k
19

20. Examples :
Number/Date Brand Name Indication
1/11-25-2019 Oxybryta Voxelotor To treat sickle cell
disease
2/7-25-2019 Accufer Ferric maltol To treat iron
deficiency anemia in
adults
3/11-08-2019 Reblozyl Luspatercept-
aamt
For the treatment of
anemia in adult
patients with beta
thalassemia who
require regular red
blood cell transfusion
Ref: https://www.thepharmaletter.com/article/us-fda-approved-48-new-drugs-and-biologics-in-2019
20

21. References
 https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-
submission/premarket-notification-510k
 https://www.fda.gov/files/about%20fda/published/Presentation---CDRH-Learn--The-
510%28k%29-Program--November-4--2014.pdf
 https://www.fda.gov/media/82395/download
 https://www.fda.gov/medical-devices/premarket-notification-510k/510k-submission-process
 https://www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-807/subpart-E
 https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/regulatory-
submissions-electronic-and-paper-format-cber-regulated-products
 https://www.thepharmaletter.com/article/us-fda-approved-48-new-drugs-and-biologics-in-2019
A.U. College Of Pharmaceutical Sciences
21