Date: July 16, 2009
To: Helen Gemignani
Consumer Safety Officer
From: Lisa Stockbridge, Ph.D.
Consumer Safety Officer
Through: Ele Ibarra-Pratt, RN, MPH
Subject:BLA 125259_47/0 Cervarix (Human Papillomavirus Vaccine) [Recombinant]
Comments on Revised Draft Product Labeling - Updated 13Jul09
This review concerns revised draft labeling for Cervarix (Human Papillomavirus Vaccine) [Recombinant] . APLB’s initial comments on the draft prescribing information (PI) were provided in a review memorandum dated October 31, 2007. On March 30, 2009, GlaxoSmithKline proposed a revised PI in their resubmission to the BLA (STN 125259_47), which was based on the Complete Response letter issued by OVRR on December 14, 2007. The first round of comments on the revised PI was sent to the sponsor on July 13, 2009. The draft under consideration is attached below.
APLB has revised the July 13, 2009 draft PI and has the following comments and concerns:
- Use command language whenever possible.
- Assure that the Warnings and Precautions subsection of the Highlights corresponds to the Warnings and Precautions section of the Full Prescribing Information.
- Consider placing the latex allergy information for prefilled syringes in Contraindications rather than in Warnings and Precautions. Moving this information to Contraindications will assure that it is readily accessible to the healthcare provider when determining what components of the vaccine could cause an allergic reaction.
- Abbreviated terms must be spelled out at first use.
- The Use in Specific Populations subsection of the Highlights does not need to include information relating to Pregnancy Category B. If it is desired that this information remain, then it should not be combined with information about other specific populations. The cross-reference to the existence of pregnancy registry should be the first bullet in this subsection and should cross-reference to the Pregnancy subsection 8.1 of the full prescribing information. Thus, the first bullet of the Use in Specific Populations subsection of the Highlights should read:
- Pregnancy registry available (8.1)
- If there are no differences, no need for special monitoring, or no dosing adjustments required for a specific population, there is no need to include that population in the Use in Specific Populations subsection of the Highlights. Thus, there is no need to mention nursing women, pediatric patients under the age of 10 years, or women 26 or older. This subsection is not for reiteration of the limitations of the indication.
Table of Contents (TOC)
- Assure that the TOC headings and subheadings correspond to those in the full prescribing information.
- TOC subsection headings must be indented and not bolded.
Full Prescribing Information
- The overall common adverse reactions should be included directly under the section heading 6 ADVERSE REACTIONS.
- In section 6 ADVERSE REACTIONS, avoid exhaustive lists of less common adverse reactions and adverse reaction rates equal to or less than placebo. The Clinical Trials Experience subsection is very long. For clarity, consider revising it to a more succinct presentation.
- Use the term “adverse reaction” when an event is believed to be associated with the vaccine. The term “adverse event” is used when it is not known whether there is an association (i.e., “all cause”).
- When describing clinical studies, refrain from the use of the terms “primary endpoint” and “secondary endpoint.” Instead, just describe the statistically significant or clinically meaningful outcomes that were used to support effectiveness.
The above comments are provided from a comprehension and an advertising and promotional labeling perspective to assist you in revising the proposed labeling materials. If you have any questions, please contact Lisa Stockbridge at 301-827-6226.