| In April 2009 the Department of Health and Human | | | | only contained insufficient evidence that this |
| Services issued a warning letter to Baxter | | | | formulation was superior to any competing product, |
| International, Inc., manufacturers of the surgical | | | | but, also, were dependent upon the previously |
| hemostatic drug TISSEEL®, to cease misbranding | | | | mentioned references which quoted different |
| of this product as superior to other <a | | | | percents associated with the 1998 formulation, not |
| rel="nofollow" | | | | the 2006 approved formulation. |
| onclick="javascript:_gaq.push(['_trackPageview', ' | | | | All three of Baxter’s product documents |
| outgoing/article_exit_link']);" href= agents</a> | | | | described TISSEEL’s superiority to |
| used to stop bleeding during surgical procedures. | | | | competitor’s agents with the following |
| Additionally, Baxter has been warned to cease | | | | statements, which remain unsubstantiated by the |
| advertising a false level of efficacy that says | | | | references Baxter cites as evidence: |
| TISSEEL® is more effective than studies and | | | | “This concentration human fibrinogen in TISSEEL |
| clinical experience indicate. | | | | [Fibrin Sealant] – over 20 times the concentration |
| This warning addressed to information being provided | | | | in human plasma – provides tensile strength up to |
| about the newest formulation of TISSEEL, which | | | | 4 times higher than that of a high-salt, fibrin sealant |
| received FDA approval in 2006 replacing an earlier | | | | with a non-physiologic clot structure.” |
| formulation approved in 1998. The newer formulation | | | | "TISSEEL is the only sealant and hemostat in the U.S. |
| is not inferior to any other formulation approved to | | | | containing aprotinin as anantifibrinolytic to preclude |
| achieve hemostasis under the same conditions, and it | | | | premature clot lysis.... |
| is not the formulation or product that is under | | | | • ... extending the life of the clot when the natural |
| scrutiny. Rather, the promotional and informational | | | | process of fibrinolysis orhyperfibrinolytic surgical |
| materials disseminated by Baxter are misleading | | | | situations (e.g., surgeries involving cardiopulmonary |
| physicians about its quality and efficacy in <a | | | | bypass or trauma) might otherwise threaten it." |
| rel="nofollow" | | | | "In pre-clinical studies, the addition of aprotinin to |
| onclick="javascript:_gaq.push(['_trackPageview', ' | | | | TISSEEL was demonstratedto improve clot |
| outgoing/article_exit_link']);" href= of FDA | | | | persistence” |
| regulations</a>. | | | | "In vitro and in vivo studies have shown that |
| The warning mentioned three specific documents | | | | aprotinin-free sealant degradessignificantly faster than |
| that were reviewed: | | | | that containing aprotinin” |
| ? Baxter’s TISSEEL National Accounts | | | | "No competing fibrin sealant offers surgeons, this |
| Presentation | | | | combination” |
| ? TISSEEL General Surgery Brochure | | | | The warning further stated that Baxter’s |
| ? TISSEEL Cardiac Sell Sheet | | | | Presentation and Brochure included claims suggesting |
| The review found that Baxter overstated the | | | | that the FDA approval of TISEEL was for a broader |
| efficacy of TISSEEL by making the statement, | | | | indication that it had actually intended. These |
| “97.5% effective in achieving hemostasis in fully | | | | documents contained the taglines |
| heparinized patients undergoing cardiopulmonary | | | | • "Seals Tissues, Stops Bleeding" (tagline) |
| bypass,” | | | | • "Only TISSEEL does both" (tagline) |
| This statement misrepresented the actual references | | | | • "TISSEEL is the only fibrin sealant that can both |
| cited by Baxter, which actually demonstrated 88.2% | | | | seal tissue and stop bleeding" |
| efficacy in the intent-to-treat analysis and 87.8% in | | | | The letter from Mary A. Malarkey, Director of the |
| the per protocol analysis, neither of which come close | | | | Office of Compliance and Biologics Quality says that |
| to the 97.5% efficacy rate Baxter claims for this | | | | these taglines imply that TISSEEL was approved by |
| formulation. | | | | the FDA as a general hemostatic agent and sealant, |
| Furthermore, the patient groups involved in the | | | | which is misleading and untruthful. She demanded that |
| studies that were used as a reference for this | | | | Baxter submit a plan to “disseminate truthful, |
| statistic actually received the previous formulation | | | | non-misleading, and complete corrective messages |
| approved in 1998, whose efficacy rate was only | | | | about these issues to the audiences that received |
| 92.6%, still lower than the claimed rate of 97.5%. | | | | the violative promotional material.” |
| Baxter’s TISSEEL National Accounts Presentation | | | | Although there is no problem with TISSEEL as a |
| stated: | | | | hemostatic agent, and no recall is involved with this |
| “In a randomized trial, TISSEEL has been found | | | | product, the fact that physicians may be encouraged |
| to be superior to conventional agents during redos* | | | | to choose it over another product based on false |
| and resternotomies” … “*(93.1% versus | | | | claims of its efficacy could have serious ramifications |
| 12.6% success), (83.3% versus 10% success)” | | | | where another product choice might be a better one. |
| Again, the references cited to support this fact not | | | | |