FDA label 16e28bfa-1146-21c9-7ab3-a3ec08cdf2b4

5 WARNINGS AND PRECAUTIONS IgA deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions. (5.1) This product is made from human plasma and may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease agent. (5.2) 5.1 Sensitivity Hypersensitivity reactions may occur. Should evidence of an acute hypersensitivity reaction be observed, the infusion should be stopped promptly and appropriate countermeasures and supportive therapy should be administered. (See Patient Counseling Information [17] ) PROLASTIN-C may contain trace amounts of IgA. Patients with known antibodies to IgA, which can be present in patients with selective or severe IgA deficiency, have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. PROLASTIN-C is contraindicated in patients with antibodies against IgA. 5.2 Viral Clearance Products made from human plasma may carry a risk of transmitting infectious agents, e.g., viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. In each of 2 randomized, double-blind studies in which the predecessor product, PROLASTIN ® (Alpha1-Proteinase Inhibitor [Human]), was compared to other Alpha 1 products, there was a single case of parvovirus B19 seroconversion in the PROLASTIN arms of each trial. In each case, it could not be determined whether parvovirus B19 had been acquired from PROLASTIN or from the community. However, during clinical studies with PROLASTIN-C, there were no reported treatment emergent cases of hepatitis B, hepatitis C, HIV or parvovirus B19 viral infections. Furthermore, the PROLASTIN-C process incorporates additional plasma safety and virus reduction measures that minimize the residual risk of virus transmission (See Description [11] ) . The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to a patient. (See Patient Counseling Information [17] ) . All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Talecris Biotherapeutics, Inc. [1-800-520-2807].

6 ADVERSE REACTIONS The most serious adverse reaction observed during clinical studies with PROLASTIN-C was an abdominal and extremity rash in one subject. The rash resolved subsequent to outpatient treatment with antihistamines and steroids. Two instances of a less severe, pruritic abdominal rash were observed upon rechallenge despite continued antihistamine and steroid treatment, which led to withdrawal of the subject from the trial. The most common drug-related adverse reactions observed at a rate of ≥ 1% in subjects receiving PROLASTIN-C were chills, malaise, headache, rash, hot flush and pruritus. The most common drug related adverse reactions during clinical trials in ≥ 1% of subjects were chills, malaise, headache, rash, hot flush, and pruritus. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Talecris Biotherapeutics, Inc. at 1-800-520-2807 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice. Two separate clinical studies were conducted with PROLASTIN-C: (1) A 20 week, open-label, single arm safety study in 38 subjects, and (2) A 16 week, randomized, double-blind, crossover pharmacokinetic comparability study vs. PROLASTIN in 24 subjects, followed by an 8 week open-label treatment with PROLASTIN-C. Thus, 62 subjects were exposed to PROLASTIN-C in clinical trials. Adverse reactions considered drug related by the investigators occurring in 1.6% of subjects (one subject each) treated with PROLASTIN-C were malaise, headache, rash, hot flush, and pruritus. Drug related chills occurred in 3.2% (2 subjects) of PROLASTIN-C subjects. Adverse events occurring irrespective of causality in ≥ 5% of subjects in the first 8 weeks of treatment are shown in Table 1 . Adverse events which occurred in the first 8 weeks of treatment are shown in the table in order to control for the differing treatment durations of the safety and PK studies (20 weeks vs. two 8 week periods). Table 1: Adverse Events Occurring in ≥ 5% of Subjects in the First 8 Weeks of Treatment Irrespective of Causality PROLASTIN ® -C No. of subjects: 62 PROLASTIN ® No. of subjects: 24 Adverse Event No. of subjects with AE (percentage of all subjects) No. of subjects with AE (percentage of all subjects) Source: studies 11815 and 11816 Nausea 4 (6.5%) 0 Urinary Tract Infection 4 (6.5%) 0 Headache 3 (4.8%) 2 (8.3%) Arthralgia 2 (3.2%) 2 (8.3%) Table 2 below displays the overall adverse rate (> 0.5%), irrespective of causality, as a percentage of infusions received. Table 2: Adverse Event Frequency as a % of all infusions (> 0.5%) Irrespective of Causality PROLASTIN ® -C No. of infusions: 1132 PROLASTIN ® No. of infusions: 192 Adverse Event No. of AE (percentage of all infusions) No. of AE (percentage of all infusions) Source: studies 11815 and 11816 Upper respiratory tract infection 9 (0.8%) 1 (0.5%) Urinary tract infection 8 (0.7%) 0 Nausea 7 (0.6%) 0 Headache 4 (0.4%) 3 (1.6%) Arthralgia 2 (0.2%) 2 (1.0%) Table 3 below displays the overall rates of adverse events (≥ 5%), in the first eight weeks of treatment, that began during or within 72 hours of the end of an infusion of PROLASTIN-C or PROLASTIN. Table 3: Adverse Events Occurring in ≥ 5% of Subjects during or within 72 hours of the end of an infusion, in the First 8 Weeks of Treatment Irrespective of Causality PROLASTIN ® -C No. of subjects: 62 PROLASTIN ® No. of subjects: 24 Adverse Event No. of subjects with AE (percentage of all subjects) No. of subjects with AE (percentage of all subjects) Source: studies 11815 and 11816 Urinary Tract Infection 4 (6.5%) 0 Headache 3 (4.8%) 2 (8.3%) Ten exacerbations of chronic obstructive pulmonary disease were reported by 8 subjects in the 24 week pharmacokinetic crossover study. During the 16 week double-blind crossover phase, 4 subjects (17%) had a total of 4 exacerbations during PROLASTIN-C treatment and 4 subjects (17%) had a total of 4 exacerbations during PROLASTIN treatment. Two additional exacerbations in 2 subjects (8%) occurred during the 8 week open label treatment period with PROLASTIN-C. The overall rate of pulmonary exacerbations during treatment with either product was 0.9 exacerbations per subject-year. 6.2 Postmarketing Experience Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure. The following adverse reactions have been identified and reported during the post marketing use of the predecessor product, PROLASTIN: Respiratory: dyspnea Cardiac: tachycardia Skin and Subcutaneous: rash General/Body as a Whole: chest pain, chills, influenza-like illness Immune: hypersensitivity Vascular: hypotension, hypertension (including transient increases of blood pressure)

<table ID="t1" border="1" rules="all" width="90%"> <caption>Table 1: Adverse Events Occurring in &#x2265; 5% of Subjects in the First 8 Weeks of Treatment Irrespective of Causality</caption> <colgroup> <col width="40%"/> <col width="30%"/> <col width="30%"/> </colgroup> <thead> <tr> <th> </th> <th align="center">PROLASTIN^&#xAE; -C No. of subjects: 62</th> <th align="center">PROLASTIN^&#xAE; No. of subjects: 24</th> </tr> <tr> <th align="left">Adverse Event</th> <th align="center">No. of subjects with AE (percentage of all subjects)</th> <th align="center">No. of subjects with AE (percentage of all subjects)</th> </tr> </thead> <tfoot> <tr> <td colspan="3">Source: studies 11815 and 11816</td> </tr> </tfoot> <tbody> <tr> <td>Nausea</td> <td align="center">4 (6.5%)</td> <td align="center">0</td> </tr> <tr> <td>Urinary Tract Infection</td> <td align="center">4 (6.5%)</td> <td align="center">0</td> </tr> <tr> <td>Headache</td> <td align="center">3 (4.8%)</td> <td align="center">2 (8.3%)</td> </tr> <tr> <td>Arthralgia</td> <td align="center">2 (3.2%)</td> <td align="center">2 (8.3%)</td> </tr> </tbody> </table>

<table ID="t2" border="1" rules="all" width="90%"> <caption>Table 2: Adverse Event Frequency as a % of all infusions (&gt; 0.5%) Irrespective of Causality</caption> <colgroup> <col width="40%"/> <col width="30%"/> <col width="30%"/> </colgroup> <thead> <tr> <th> </th> <th align="center">PROLASTIN^&#xAE; -C No. of infusions: 1132 </th> <th align="center">PROLASTIN^&#xAE; No. of infusions: 192</th> </tr> <tr> <th align="left">Adverse Event </th> <th align="center">No. of AE (percentage of all infusions) </th> <th align="center">No. of AE (percentage of all infusions) </th> </tr> </thead> <tfoot> <tr> <td colspan="3">Source: studies 11815 and 11816</td> </tr> </tfoot> <tbody> <tr> <td>Upper respiratory tract infection</td> <td align="center">9 (0.8%)</td> <td align="center">1 (0.5%)</td> </tr> <tr> <td>Urinary tract infection</td> <td align="center">8 (0.7%)</td> <td align="center">0</td> </tr> <tr> <td>Nausea</td> <td align="center">7 (0.6%)</td> <td align="center">0</td> </tr> <tr> <td>Headache</td> <td align="center">4 (0.4%)</td> <td align="center">3 (1.6%)</td> </tr> <tr> <td>Arthralgia</td> <td align="center">2 (0.2%)</td> <td align="center">2 (1.0%)</td> </tr> </tbody> </table>

<table ID="t3" border="1" rules="all" width="90%"> <caption>Table 3: Adverse Events Occurring in &#x2265; 5% of Subjects during or within 72 hours of the end of an infusion, in the First 8 Weeks of Treatment Irrespective of Causality </caption> <colgroup> <col width="40%"/> <col width="30%"/> <col width="30%"/> </colgroup> <thead> <tr> <th> </th> <th align="center">PROLASTIN^&#xAE; -C No. of subjects: 62</th> <th align="center">PROLASTIN^&#xAE; No. of subjects: 24</th> </tr> <tr> <th align="left">Adverse Event</th> <th align="center">No. of subjects with AE (percentage of all subjects)</th> <th align="center">No. of subjects with AE (percentage of all subjects)</th> </tr> </thead> <tfoot> <tr> <td colspan="3">Source: studies 11815 and 11816</td> </tr> </tfoot> <tbody> <tr> <td>Urinary Tract Infection</td> <td align="center">4 (6.5%)</td> <td align="center">0</td> </tr> <tr> <td>Headache</td> <td align="center">3 (4.8%)</td> <td align="center">2 (8.3%)</td> </tr> </tbody> </table>