The US FDA approved GSK's MMR vaccine (Priorix) on June 6, 2022. The approval was based on data from six clinical trials involving over 12,000 participants aged 12 months and older. Preclinical testing in animals found no safety issues. Clinical inspections of investigators and manufacturing inspections found no significant problems. The FDA waived pediatric studies in infants under 12 months since the vaccine provides no meaningful benefit in that age group. The FDA review committee agreed the vaccine's benefits outweighed the risks based on the totality of evidence.

1. Approval Process for
Measles Vaccine by
USFDA
Sharvil Modi
22MPH810

2. Table of Contents-
1. Introduction
2. MMR Vaccine (Case Study)
a. Regulatory History & Chemistry-
b. Preclinical Data-
c. Clinical Data-
d. BIMO Inspections & Labeling-
e. Pediatrics-
f. Other Relevant Regulatory Issues-
3. References
2.

3. Introduction-
• A biological product used to stimulate an immune response in body and provide protection
against specific disease
• FDA describes vaccines as products that contain small amount of antigen, or piece of
disease-causing organism, that is designed to trigger an immune response in body
• Used to prevent wide range of infectious diseases, including measles, mumps, rubella,
influenza, and human papillomavirus (HPV), etc…
• US FDA regulates the development, testing, and approval of vaccines in the United States to
ensure that they are safe, effective, and of high quality
3.

4. Measles-
• highly contagious viral infection that affects respiratory system which spreads through air
when an infected person talks, coughs, or sneezes, and can also be spread through contact
with contaminated surfaces
• dangerous for young children, pregnant women, and people with weakened immune
systems
• Complications of measles can include-
1. ear infections,
2. pneumonia,
3. encephalitis,
4. and even death in rare cases
• MMR (measles, mumps, and rubella) vaccine. Typically given in two doses, with the-
1. first dose given between 12-15 months of age and
2. second dose given between 4-6 years of age
4.

5. 5.

6. MMR Vaccine (measles, mumps, and
rubella)
• There is currently only one FDA-approved biosimilar vaccines available in the United States:
MMR (measles, mumps, rubella) vaccine (PRIORIX) and other one is approved biologic by same
company MMRV (measles, mumps, rubella, varicella) vaccine
• Involves several stages, including-
1. preclinical testing,
2. clinical trials, and
3. post-marketing surveillance
Both vaccines have undergone extensive testing and have been shown to be safe and effective
at preventing measles
6.

7. HISTORY & CHEMISTRY-
• On June 4, 2021, GSK submitted BLA for vaccine and on June 6, 2022 officially got approval with
proposed proper name of MMR vaccine
Final name is PRIORIX which administered subcutaneously
• Composition of PRIORIX-
7.

8. Sr.
No
Events/ Milestones Date
1. IND submission July 8, 1997
2. End of Phase 2 meeting December 19, 2011
3. Pre-BLA meetings October 16, 2020 - Clinical
October 26, 2020 - CMC &
facilities
4. BLA 125748/0 submission June 4, 2021
5. BLA filed August 3, 2021
6. Mid-Cycle communication December 2, 2021
7. Late-Cycle meeting March 3, 2022 Cancelled by
GSK
8. PeRC meeting April 26, 2022
9. Action Due Date June 4, 2022
10. Approval June 6, 2022
8.

9. • For Stability Purpose, EoSL should have acceptance criteria-
1. Potency measles virus by not less than 3.4 log CCID50 per dose*
2. Potency mumps virus by not less than 4.2 log CCID50 per dose*
3. Potency rubella virus by not less than 3.3 log CCID50 per dose*
• Team Biologics performed surveillance inspection at GSK Vaccines in , and Form
FDA Form 483 was not issued at the end of the inspection. The inspection was
classified as NAI
9.

10. Preclinical Data-
 First registered in Europe in November 1997. GLP toxicology study with measles, mumps,
rubella, and varicella (MMRV) vaccine called PRIORIX –TETRA
 In submitted GLP toxicity study, Rhesus monkeys received full human dose (0.5 ml/injection)
containing either saline (control) or PRIORIX -TETRA subcutaneously
 Observations-
 Body weight evolution and food consumption were unaffected by MMRV vaccine treatment
 No deaths or clinical signs attributed to MMRV vaccine were observed
 No treatment-related changes in rectal body temperature following inoculation with MMRV
vaccine
 Ophthalmoscopy, electrocardiography, and blood pressure measurements revealed no
treatment-related findings
10.

11. Clinical Data-
 Applicant has submitted data from 6 randomized clinical studies-
• One Phase 2 trial provided data to justify mumps virus potency in vaccine formulation used in
Phase 3 studies
• Five Phase 3 trials provide primary data for intended indication in individuals 12 months of age
and older
 These 6 trials enrolled participants ≥12 months of age at more than 400 sites in 11 countries,
including US
The total number of subjects for all studies that received PRIORIX was 12,151 of which 6,391 were
from US
11.

12. BIMO Inspections & Labeling-
 Issued for four domestic Clinical Investigators who participated in conduct of
protocol MMR-158
and three of the clinical investigators also participated in the conduct of protocol
MMR-160
 Inspections did not reveal substantive issues that impact data submitted in
this BLA
 PRIORIX proprietary name, was reviewed by CBER’s APLB on April 5, 2022 and
found to be acceptable, package and container labels were found acceptable
12.

13. Pediatrics-
 Under IND, the Applicant submitted an iPSP on July 6, 2016, and an agreed iPSP on January 6,
2017
Under IND, the Applicant submitted an iPSP on July 6, 2016, and an Agreed iPSP on January 6,
2017, which included request for waiver of pediatric studies in infants
<12 months of age
 Under BLA, the final Pediatric Study Plan was presented to PeRC on April 26, 2022.
Safety and effectiveness of PRIORIX have not been established in individuals younger than 12
months of age in the US
 Applicant’s request for partial waiver for those less than 12 months of age was accepted by
PeRC because candidate vaccine does not represent meaningful therapeutic benefit and is
not likely to be used in this age group
13.

14. Other Relevant Regulatory Issues-
 However, with BLA, the Applicant submitted clinical trial data from Phase 2 Study MMR-157
that utilized lyophilized vaccine antigen in vial + the diluent in an ungraduated PFS presentation
for use so, applicant submitted URRA to their IND which included information that ungraduated
PFS presentation has been used in PRIORIX marketed in other countries
(PRIORIX Australia, AUS)
 Due to the similar presentation characteristics between PRIORIX US and PRIORIX AUS and the
Applicant’s report of the medication errors associated with use of PRIORIX AUS, the clinical
reviewer assessed that risk of medication errors associated with WC administration is low
 No advisory committee meeting was held because FDA review of this submission did not
identify concerns or issues
 Based on these data, Review Committee agrees that the risk/benefit balance for PRIORIX is
favorable and supports approval for use as a first dose in individuals 12 through 15 months of
age and as a second dose in individuals 4 through 6 years of age
14.

15. References-
1. https://www.fda.gov/media/159545/download (Accessed on 06-04-2023)
2. https://www.fda.gov/media/158962/download (Accessed on 08-04-2023)
3. https://www.fda.gov/media/158941/download (Accessed on 11-04-2023)
4. https://www.fda.gov/vaccines-blood-biologics/priorix (Accessed on 05-04-2023)
5. https://www.reuters.com/business/healthcare-pharmaceuticals/gsks-measles-
prevention-vaccine-gets-us-approval-2022-06-06/ (Accessed on 05-04-2023)
15.

16. ThankYou!