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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Vaccines

Relative Potency of Cervarix

MEMORANDUM

Date: August 7, 2009
From: Gennady Rezapkin, Ph.D., HFM-470
Thru: Konstantin Chumakov, Ph.D., HFM-470
To: file
Subject: -(b)(4)- in-vitro Relative Potency of Cervarix®

This is a report of ------------------------(b)(4)--------------------------- for the determination of in-vitro relative potency (antigenicity) for Human Papillomavirus types 16 and 18 Virus Like Particles in GSK Cervarix® HPV Recombinant Vaccine. The testing was done as a part of product licensure process. The following materials were tested:

Internal controls, standards, and -(b)(4)- of HPV16 antigen:

Standard (ST) against which antigen concentration is measured: lot ------(b)(4)-----
Internal control (IC) for test validation: lot -----(b)(4)-----
------------------(b)(4)----------------------
-----------------------------------------------
-----------------------------------------------

 Internal controls, standards, and -(b)(4)- of HPV18 antigen:

Standard (ST) against which antigen concentration is measured: lot ------(b)(4)-----
Internal control (IC) for test validation: lot -----(b)(4)-----
------------------(b)(4)----------------------

Final containers:

Final container (FC) lot ------(b)(4)-----
Final container (FC) lot ------(b)(4)-----

General description of the method

Each -(b)(4)- experiment included an appropriate internal control (depending on the serotype of antigen tested). In some experiments ----(b)(4)---- materials were tested against ----(b)(4)---- antigen to determine specificity of the reaction. -----------------------(b)(4)--------------------- of the ------(b)(4)----- product were also tested to determine the ---------(b)(4)--------- of the vaccine. One additional control (to determine the background level) was performed by testing placebo adjuvant without added antigens.

The results are expressed as an average of antigen concentration from several experiments. It is calculated as a ----------------------------------------(b)(4)------------------------------------------------ --------------------------------------------------------------------------------------------------------------.

Materials and Methods

-----------------------------------------------------(b)(4)----------------------------------------------------- ---------------------------------------------------------------------------------------------------------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------ ---------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------- ---------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------ ----------------------------------------------------------------------------------------------------------------- --------------------

-(b)(4)---------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------ ----------------------------------------------------

-(b)(4)----------------------------------------------------------------------------- -------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

One (1) page determined to be non-releasable: (b)(4)

the GSK result. The acceptable results must be in the range specified for --------(b)(4)-------- of -(b)(4)- for HPV 16, and --(b)(4)-- for HPV 18 --b(4)--.

Results

Tables 1 and 2 show the results obtained by -(b)(4)- testing for HPV16 and HPV18 antigens for the above samples. They demonstrated that:

  • The test is specific: -(b)(4)- potency test for HPV16 does not detect HPV18 antigen, and vice versa.
  • 100% of the antigen is absorbed by the adjuvant, since ----(b)(4)--- contained no antigen.
  • Adjuvant does not contribute to increased background, and therefore the use of unabsorbed standard and internal control is justified.
  • Final containers contained vaccine with potency very close to nominal values.
  • Potency of submitted HPV 16 ---------------------(b)(4)-------------------- materials were substantially lower than expected.

Conclusion

The results demonstrated that t he ------(b)(4)------ test is adequate, and possesses the necessary sensitivity and specificity. Final containers submitted in support of Cervarix licensure meet potency specifications for both HPV16 and HPV18 antigens. However, potency of HPV 16 -(b)(4)- materials was significantly below what was expected based on the data submitted by the sponsor. Since potency in Final Containers produced from these -(b)(4)- was adequate, this could have been a result of mislabeling or inadequate storage conditions for these -(b)(4)-. To resolve this discrepancy the raw -(b)(4)- data were send to GSK and GSK was requested to submit new -(b)(4)- materials of HPV16 along with a more detailed description and results of potency tests performed by the sponsor.

Results for the second set of samples

The second set of -(b)(4)- samples included:
-(b)(4)---------------------------------------
-----------------------------------------------
-----------------------------------------------
-----------------------------------------------
-----------------------------------------------

--------(b)(4)--------- from first and second sets were tested in the same test and on the same -(b)(4)- panel. Tables 3 shows the results obtained by -(b)(4)- testing for HPV16 L1 VLP antigens for the second set of -(b)(4)- samples. All results were in acceptable range. The differences in potency between first and second sets were confirmed.

It should be noted that two sets of samples arrived in different containers. The first -(b)(4)- material was delivered in -(b)(4)-, and the second one was aliquoted in -(b)(4)-. This may mean that the processing of these samples was different and this may be explain significant differences in -(b)(4)- potency results for the two sets.

Final conclusion

  • The GSK -(b)(4)- potency test is acceptable and adequate to measure the potency of the HPV16 (18) L1 VLP antigens in Cervarix vaccine, ------(b)(4)------ Final containers.
  • The test is specific: -(b)(4)- potency test for HPV16 does not detect HPV18 antigen, and vice versa.
  • 100% of the antigen is absorbed by the adjuvant, since ----(b)(4)---- contained no antigen.
  • Adjuvant does not contribute to increased background, and therefore the use of unabsorbed internal control is justified.
  • Final containers ---(b)(4)--- vaccines contained vaccine with potency in the specified range.

Three (3) pages determined to be non-releasable: (b)(4)