Record of E-mail Communication 1 - July 14, 2009

 
RECORD OF E-MAIL COMMUNICATION

Submission Type: Original Application   Submission ID:  125347/0    Office: OVRR  

Product:

Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)

Applicant:                                                                        

GlaxoSmithKline Biologicals          

Telecon Date/Time:  14-JUL-2009 08:00 AM                Initiated by FDA?  Yes

Telephone Number:    

Communication Category:

Labeling via FAX/e-mail

Author:  JASON HUMBERT

Telecon Summary:

Comments to the revised label provided by GSK on July 10.

FDA Participants:   Jason Humbert

Non-FDA Participants:    Elisa Harkins, GSK

Telecon Body: The following PI comments were shared with GSK via e-mail:

1.  Page 2, Line 13:  Please revise as follows: 

. . . dose of HIBERIX is compared to a booster dose of a US-licensed Haemophilus b Conjugate Vaccine in children. . .

2. Page 3, Section 5.3 and Page 6, DRUG INTERACTIONS

In our June 26, 2009 comments on the HIBERIX package insert, we requested that in DRUG INTERACTIONS, you include a subsection, “Interference with Laboratory Tests”, to convey that HIBERIX might interfere with the diagnostic value of urine antigen detection tests in suspected disease to H. influenzae type b. We acknowledge your response that such a subsection would be redundant with Section 5.3. However, based on labeling regulations 21CFR201.57(c)(6) and 21CFR201.57(c)(8), it is our view that this information should be included in both WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS. To minimize redundancy, the information in WARNINGS AND PRECAUTIONS could be abbreviated with reference to more detailed information in DRUG INTERACTIONS. For example, please consider the following:

5.3 Interference With Laboratory Tests

Urine antigen detection may not have a diagnostic value in suspected disease due to

H. influenzae type b within 1 to 2 weeks after receipt of HIBERIX [see Drug Interactions (7.X)].

7.X Interference With Laboratory Tests

Haemophilus b capsular polysaccharide derived from Haemophilus b Conjugate Vaccines has been detected in the urine of some vaccinees.1Urine antigen detection may not have a diagnostic value in suspected disease due to H. influenzae type b within 1 to 2 weeks after receipt of a H. influenzae type b-containing vaccine, including HIBERIX [see Warnings and Precautions (5.3)].

3. Page 3, Line 58: The subheading “Vaccine Coverage” is not very specific to the information being conveyed. We recommend that you use a more specific subheading such as “Tetanus Immunization”.

4. Page 3, WARNINGS AND PRECAUTIONS Altered Immunocompetence:

We note that you have removed the subsection Altered Immunocompetence because the information that was conveyed is considered general medical knowledge. However, because children with certain immunosuppressive conditions may be at increased risk for invasive disease due to H. influenzae type b, we recommend that you include a subsection on altered immunocompetence in WARNINGS AND PRECUATIONS as follows:

5.X  Altered Immunocompetence

Safety and effectiveness of HIBERIX in immunosuppressed children have not been evaluated. If HIBERIX is administered to immunosuppressed children, including children receiving immunosuppressive therapy, the expected immune response may not be obtained.

5. Page 4, Lines 69-70: As agreed upon in the July 9, 2009 teleconference between CBER and GSK, please change “234” to “235” and please change “27” to “26”.

6. Page 4, Lines 73-75: Please revise the sentence that provides information on age of subjects as follows:    

Across studies, the mean age of subjects at the time of booster vaccination with HIBERIX ranged from 16 to 19 months; 172 (17.1%) subjects were 11 to 14 months of age, 642 (63.7%) were 15 to 18 months of age, and 194 (19.2%) were 19 to 25 months of age at the time of vaccination.

7. Page 4, Line 78: Please change “. . . of the following US-licensed” . . . to “of one of the following US-licensed”.

8. Page 4, Line 84: Please delete “also”.

9. Page 4, Line 85: Please revise as follows:

DTaP-HBV (GlaxoSmithKline, not licensed in US) concomitantly with HIBERIX.

10. Page 4, Lines 86-92: Please revise as follows:

Solicited Adverse Events: In an open-label, multicenter study conducted in Germany, 371 children received a booster dose of HIBERIX administered concomitantly with DTaP-HBV-IPV. The mean age at the time of vaccination was 16 months. Subjects in this study had previously received a primary series with either HIBERIX (N = 92), Haemophilus b Conjugate Vaccine manufactured by Sanofi Pasteur SA (N = 96), or Haemophilus b Conjugate Vaccine manufactured by Wyeth Pharmaceuticals Inc. (no longer licensed in the U.S.) (N = 183). All subjects previously received 3. . .

  [Numbers of subjects per priming group for those included in Table 1 of the package insert (N=371) were obtained from Tables 1 and 2 in the Modified Study Report Addendum 1 for Clinical Trial 217744028.] 

11. Page 5, Lines 109-110: Please change each occurrence of “temperature” to “fever”.  

12. Page 5, Line 114: In our June 26, 2009 comments, we requested that you include information on serious adverse events that occurred in the 31-day period following HIBERIX across all booster immunization studies. We acknowledge your response that you believe that the two serious adverse events that occurred in this period are not relevant for inclusion in the package insert. While there does not appear to be a plausible causal connection between vaccination and the event of accidental drug ingestion, we note that in the absence of a relevant control group, it is difficult to conclude lack of causal relationship between the observed serious adverse events (particularly, pneumonia 9 days post-vaccination) and vaccination. Therefore, we continue to request that you provide information on the serious adverse events that occurred in the 31-day period following booster immunization with HIBERIX. Suggested wording is provided below:

Two of 1,008 subjects reported a serious adverse event that occurred in the 31-day period following booster immunization with HIBERIX. One subject developed bilateral pneumonia 9 days post-vaccination and one subject experienced asthenia following accidental drug ingestion 18 days post-vaccination.      

13. Page 5, Line 118: Please consider revising “which have plausible causal connection” to “which have a plausible causal connection” .

14. Page 6 DRUG INTERACTIONS Please see CBER’s comment #3 above.

15. Page 6, Lines 131-133: For added clarification, please revise as follows:

In clinical studies, a booster dose of HIBERIX was administered concomitantly with one of the following vaccines: DTaP, DTaP-IPV, DTaP-HBV-IPV, or DTaP-HBV (GlaxoSmithKline, not licensed in the US). The formulations of DTaP, DTaP-IPV, and DTaP-HBV-IPV were non-US formulations (containing 2.5 mg 2-phenoxyethanol per dose as preservative) of the following US-licensed vaccines: INFANRIX, KINRIX, and PEDIARIX, respectively. In these studies, DTaP-IPV and DTaP-HBV-IPV. . .

16. Page 6, Line 150: Please insert “can” before “affect”.

17. Page 7, Line 183: Please delete “>”.

18. Page 7, Line 186: Please change “protection through a 1-year period.” to “protection through at least a 1-year period.”  

19. Page 7, Lines 194-196: Please revise as follows:

In six clinical studies, the immune response to HIBERIX administered as a booster dose was evaluated in a total of 415 children 11 to 23 months of age. At the time of vaccination, 30 children were 11 to 14 months of age, 316 children were 15 to 18 months of age, and 69 children were 19 to 23 months of age. Among subjects, X% to X% were male. Among subjects for whom information on race/ethnicity was available, nearly all subjects were white. None of the studies included a comparator group that received a booster dose with a US-licensed Haemophilus b Conjugate Vaccine. Characteristics of 3 of these studies are presented in Table 2.
