Errata – FDA Briefing Document

 

RIASTAPTM [Fibrinogen concentrate (Human)]

CSL Behring GmBH, Germany

 

Blood Products Advisory Committee Meeting

January 9, 2009

 

Formatting changes, including revised pagination, were made to the briefing document.  The substantive revisions to the document are listed below.

 

  1. Page 4, 1st paragraph, line 5: deleted sentences, “The labeled amount of RIASTAPTM is 1 g of fibrinogen.  When reconstituted, each vial contains 900 to 1300 mg fibrinogen, 400 to 700 mg human albumin, 375 to 660 mg L-arginine hydrochloride, 200 to 350 mg sodium chloride and 50 to 100 mg sodium citrate.  Sodium hydroxide and hydrochloric acid may have been used to adjust the pH.”
  2. Page 4, 2nd paragraph line 13: changed 105 to 104
  3. Page 4, 3rd paragraph, line 2:  changed Appendix 4 to Appendix 5
  4. Page 5, line 4: changed 1985 to 1986
  5. Page 5, under Potency: revised section to read, “The actual fibrinogen potency in mg/vial for each lot is printed on the vial label.  Generally, each vial will contain 900-1,300 mg fibrinogen and 400-700mg human albumin. The lyophilized fibrinogen in a single-use vial for reconstitution with 50 mL Sterile Water for Injection.”
  6. Page 6, 3rd paragraph, 2nd sentence: revised sentence to read, “Studies B13023_2001, B13023_3001 (under a U.S. IND) and CE1221_1 to support the indication.”
  7. Page 7, Table row 1 and throughout the document (page 8, 3rd paragraph, line 11; page 12, 3rd paragraph, line 10; page 14,1st paragraph, line 4; page 18, 3rd paragraph, line 10; page 19, section 5.2 title; page 20, section 5.3.1 title):  “Phase 4” replaced with “postmarketing”
  8. Page 7, Table row 3, treatment column: added, “or other fibrinogen concentrates”
  9. Page 8, 2nd paragraph, line 5:  273 changed to 2.73 
  10. Page 12, 4th paragraph, line 1: changed “7 European countries” to “12 countries"
  11. Page 19, #2, line 5: changed, “first” to “every” infusion
  12. Page 21, section 5.3.2:  amended title to read, “STUDY 7MN-101FM PHASE 1 PK STUDY (CONDUCTED IN EUROPE)
  13. Page 24, section 5.5, first sentence:  changed “45” to “48” adverse event reports
  14. Page 24, section 5.5, third sentence: added “and FDA’s” assessment
  15. Page 24, chart revised to read as follows:

 

      Overview of ADRs reported 1986-2008:

Adverse drug reaction

Number of cases

 Sponsor Causality

FDA Causality Assessment

Allergic/anaphylactoid reactions

20a

16 possibly related

3 insufficient information

1 unlikely

 All possibly related

Thromboembolic events

9

1 acquired, 8  congenital deficiency

8 possibly related

1  insufficient data

All possibly related

Suspected viral transmission

14

(12 acquired and 2 in congenital deficiency)

13 unrelated, 1 insufficient data

 

Agrees with the sponsor

Lack of effect

3

2 insufficient data, 1 unrelated

Insufficient information to assess

Leucocytosis

1

unrelated

unrelated

Lung infiltration

1

unrelated

unrelated

a FDA considers a case of bone pains and chills, identified as unexpected by the sponsor, to be an allergic reaction and related.

 

  1. Page 35, Appendix 5, Deleted chart titled “Cumulative (Log10) Virus Inactivation/Reduction in RIASTAP Manufacturing Step” and replaced it with the  following chart:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  1. Page 40, chart titled, “Post marketing thromboembolic events in Europe (1986-2008)” amended to read as follows:

 

 

Post marketing thromboembolic events in Europe (1986-2008)

 

Age (yrs)

Indication for Treatment

Major Symptoms/Underlying Conditions (Comment)

Dosing of Fibrinogen concentrate

Time between Last Fibrinogen Dose and Event

Eventa

Co-suspect Products

15 days

AD, pulmonary bleeding after cardiac surgery

Congenital heart defect

2 g total dose

7 days

Thrombosis of SC arteries and truncus brachio-cephalicus

 

Activated FVII, activated PCC

44

CD afib

(possible antibody interference with heparin)

Prophylactic dosing for 21 yrs (4 g/wk)

NA

Recurrent occlusion of anterior tibial artery

Recurred despite heparin, lepirudin therapy

41

CD afib

-

Dosed for 2 yrs
(2 g every 7-14 days)

3 days

Central retinal vein thrombosis

-

39

CD afib,
hx or ICH

Hand paresis

Prophylactic dosing for 15 yrs (6 g every 2 wks)

10 days

Small thrombosis of aortic arch/mild CVA

-

18

CD afib

Implanted infusaport

Prophylactic dosing for many yrs; dose increased for
surgical procedure

15 days post-op

SC/jugular thrombosis

-

23

CD afib

-

1 g total dose

NA

Multiple arterial thromboses

4.5 g of another fibrinogen concentrate

32

CD afib

-

On-demand tx for massive hemorrhage after iatrogenic arterial injury (8-g single doses)

NA

Massive proximal DVT/ success-fully treated

-

69

CD hypfib

Hematoma and hemorrhage/ AML

Not reported

48 hrs

Micro- vascular thrombosis

Aprotinin (i.v. and infusion)

 

32

CD afib

-

On-demand tx for large SDH (2 g every other day for 3 wk)

3 wks

Pulmonary embolus/ recovered

-