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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Vaccines

Consult Review Memo - MenHibrix

From:Rabia Ballica, PhD, CBER/OCBQ/DMPQ/BI, HFM-675 Consult Reviewer
Through:Carolyn Renshaw, Chief, CBER/OCBQ/DMPQ/BI, HFM-675
To:STN 125363/0
Applicant:GlaxoSmithKline Biologicals, License #1617
Product:Meningococcal Groups C and Y and Haemophilus b Tetanus Conjugate Vaccine (MenHibrix vaccine)
Subject:Consult Review Memo for extractables and leachables information provided in Biological License Application (BLA) for the container closure system of the lyophilized vaccine and the 0.9% sodium chloride diluent vial presentation.

Recommendation:

A PMC is recommended:

Please conduct a leachable study --------(b)(4)-------------------- conditions for the reconstituted MenHibrix vaccine vials (e.g., on the randomly selected vials) to identify leachables from the container closure systems of both the diluent and the lyophilized vaccine. This study will also evaluate potential toxicity and product quality impact of the identified leachables (e.g., by using a risk assessment approach). Please submit the results from this study in a PMC submission. Please provide the date of PMC submission.

SUMMARY

This BLA application provides information to support the use of MenHibrix in infants

and toddlers, from 6 weeks through 15 months of age. MenHibrix is a lyophilized vaccine supplied in a (b)(4) monodose glass container - stoppered with rubber closures. The vaccine is reconstituted prior to intramuscular injection, with 0.9% sodium Chloride diluent.

0.9% sodium chloride diluent vial presentation is manufactured by ------------(b)(4)--------------------. The diluent vial presentation will allow for a measured volume for administration. Note that the diluent is not in contact with the vaccine product until reconstitution, and therefore potential leachables from the container closure system of the diluent is not expected to have any impact on the vaccine quality attributes. Extractables/leachables (E/Ls) information and E/Ls toxicological evaluation for the diluent closure system -----------(b)(4)---------------------- is reviewed under STN 125347/(b)(4) (refer to the consult review memo uploaded in EDR). Therefore, for this memo, extractables/leachables information on the lyophilized vaccine vial presentation is reviewed.

The primary container closure system for the lyophilized vaccine consists of the following components (BLA 125363/0 – m3.2.P.7 Container Closure System – Hib-MenCY-TT GSK Biologics): 1. Container (b)(4)-- glass vial), 2. Closure--------------------------------(b)(4)---------------------------------, and 3. Seal (b)(4)---. Note that the same -b(4)---- glass vials, stoppers and caps proposed for use of with Hib-MenCY-TT vaccine are approved for use with GSK’s BLA Rotarix (STN 125265, approved April 03, 2008). Also, note that stability studies for the lyophilized vaccine product - stored in this glass vial (which has higher product contact surface area compared to that of the stopper) are conducted. It is also stated in this BLA submission that the (b)(4)- glass vials for lyophilized vaccine meet -----------(b)(4)--------------- for “Glass containers for pharmaceutical use”. All the tests and specifications for glass vials are provided in the BLA submission. Therefore, extractables information on the glass vial is not included in this review memo.

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

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

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

 

1 page redacted due to (b)(4)

 

information indicates that either a leachable study under actual storage conditions or a verification testing for potential leachables in the selected vials (e.g., randomly selected) of the lyophilized vaccine needs to be conducted under a PMC to verify that the container and closure system for the lyophilized vaccine is free of leachable contaminants (21CFR 600.11(h)).

Because the 0.9% NaCl diluent container closure system is covered under the approved PAS 125347 /(b)(4) and GSK committed to test leachables in the diluent under actual in use (storage) conditions, a PMC for the same diluent under this BLA is not recommended. This information will be submitted as a PMC submission by 3Q 2014. However, I recommend that an E/L PMC be requested for the reconstituted vaccine to cover all leachables from the container and closures of both the diluent and the lyophilized vaccine, instead of those only from the lyophilized vaccine container closure. In conclusion, results of a leachable study conducted for the randomly selected vials containing the reconstituted vaccine need to be submitted in a PMC submission. Identified leachables also need to be evaluated for potential toxicological risk and product quality impact and related evaluation report needs to be included in this PMC. Note that this leachable study should use the diluent and the lyophilized vaccine that are stored under the actual storage conditions.

REVIEW

Background

MenHibrix is a lyophilized vaccine supplied in a (b)(4) monodose glass container -stoppered with rubber closures. The vaccine is reconstituted prior to intramuscular injection, with 0.9% sodium Chloride diluent.

For the vaccine reconstitution, a 0.9% sodium chloride diluent vial presentation - manufactured by -------------(b)(4)-----------------------, will be used. This diluent presentation will allow for a measured volume for administration. Healthcare providers will be instructed to withdraw 0.6 ml of 0.9% sodium chloride from the accompanying vial, transfer the diluent into the lyophilized vaccine vial, shake the vial well, then after reconstitution, withdraw 0.5 ml of reconstituted vaccine and administer intramuscularly. Thus, an exact volume is available for reconstitution of the lyophilized vaccine, and an exact volume is available for administration intramuscularly.

Extractables/leachables information for the diluent container closure system was reviewed under STN 125347/(b)(4) (refer to the consult review memo uploaded in EDR). Therefore, for this memo, extractables/leachables information on container closure system of the lyophilized vaccine vial presentation is reviewed.

Formulation of the Hib-MenCY-TT vaccine takes place in ------(b)(4)-------------------- under aseptic conditions ---------------(b)(4)------------------------. A concentrated sucrose solution of –(b)(4)--- nominal concentration and a concentrated Tris-HCl buffer of (b)(4)

6 pages redacted due to (b)(4)