UDENYCA

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Splenic Rupture [see Warnings and Precautions ( 5.1 )] Acute Respiratory Distress Syndrome [see Warnings and Precautions ( 5.2 )] Serious Allergic Reactions [see Warnings and Precautions ( 5.3 )] Use in Patients with Sickle Cell Disorders [see Warnings and Precautions ( 5.4 )] Glomerulonephritis [see Warnings and Precautions ( 5.5 )] Leukocytosis [see Warnings and Precautions ( 5.6 )] Thrombocytopenia [see Warnings and Precautions ( 5.7 )] Capillary Leak Syndrome [see Warnings and Precautions ( 5.8 )] Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions ( 5.9 )] Myelodysplastic syndrome [see Warnings and Precautions ( 5.10 )] Acute myeloid leukemia [see Warnings and Precautions ( 5.10 )] Aortitis [see Warnings and Precautions ( 5.11 )] Most common adverse reactions (≥ 5% difference in incidence compared to placebo) are bone pain and pain in extremity. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Coherus BioSciences at 1-800-4UDENYCA (1-800-483-3692) or FDA at 1-800-FDA-1088 (1-800-332-1088) or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Pegfilgrastim clinical trials safety data are based upon 932 patients receiving pegfilgrastim in seven randomized clinical trials. The population was 21 to 88 years of age and 92% female. The ethnicity was 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian. Patients with breast (n = 823), lung and thoracic tumors (n = 53) and lymphoma (n = 56) received pegfilgrastim after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles. The following adverse reaction data in Table 2 are from a randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer receiving docetaxel 100 mg/m 2 every 21 days (Study 3). A total of 928 patients were randomized to receive either 6 mg pegfilgrastim (n = 467) or placebo (n = 461). The patients were 21 to 88 years of age and 99% female. The ethnicity was 66% Caucasian, 31% Hispanic, 2% Black, and <1% Asian, Native American or other. The most common adverse reactions occurring in ≥ 5% of patients and with a between-group difference of ≥ 5% higher in the pegfilgrastim arm in placebo controlled clinical trials are bone pain and pain in extremity. Table 2. Adverse Reactions with ≥ 5% Higher Incidence in pegfilgrastim Patients Compared to Placebo in Study 3 Body System Adverse Reaction Placebo (N = 461) pegfilgrastim 6 mg SC on Day 2 (N = 467) Musculoskeletal and connective tissue disorders Bone pain 26% 31% Pain in extremity 4% 9% Leukocytosis In clinical studies, leukocytosis (WBC counts > 100 x 10 9 /L was observed in less than 1% of 932 patients with non-myeloid malignancies receiving pegfilgrastim. No complications attributable to leukocytosis were reported in clinical studies. 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other pegfilgrastim products may be misleading. Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastim-treated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizing antibodies detected using a cell-based bioassay. 6.3 Postmarketing Experience The following adverse reactions have been identified during post approval use of pegfilgrastim products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Splenic rupture and splenomegaly (enlarged spleen) [see Warnings and Precautions ( 5.1 )] Acute respiratory distress syndrome (ARDS) [see Warnings and Precautions ( 5.2 )] Allergic reactions/hypersensitivity, including anaphylaxis, skin rash, urticaria, generalized erythema and flushing [see Warnings and Precautions ( 5.3 )] Sickle cell crisis [see Warnings and Precautions ( 5.4 )] Glomerulonephritis [see Warnings and Precautions ( 5.5 )] Leukocytosis [see Warnings and Precautions ( 5.6 )] Thrombocytopenia [see Warnings and Precautions ( 5.7 )] Capillary leak syndrome [see Warnings and Precautions ( 5.8 )] Injection site reactions Sweet’s syndrome ( acute febrile neutrophilic dermatosis ), cutaneous vasculitis Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer receiving chemotherapy and/or radiotherapy [see Warnings and Precautions ( 5.10 )] Aortitis [see Warnings and Precautions ( 5.11 )] Alveolar hemorrhage

4 CONTRAINDICATIONS UDENYCA is contraindicated in patients with a history of serious allergic reactions to pegfilgrastim products or filgrastim products. Reactions have included anaphylaxis [see Warnings and Precautions ( 5.3 )] . Patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors such as pegfilgrastim products or filgrastim products. ( 4 )

11 DESCRIPTION Pegfilgrastim-cbqv is a covalent conjugate of recombinant methionyl human G-CSF and monomethoxypolyethylene glycol. Recombinant methionyl human G-CSF is a water-soluble, 175 amino acid protein with a molecular weight of approximately 19 kilodaltons (kDa). Recombinant methionyl human G-CSF is obtained from the bacterial fermentation of a strain of E coli transformed with a genetically engineered plasmid containing the human G-CSF gene. During the pegfilgrastim-cbqv manufacturing process, fermentation is carried out in nutrient medium containing the antibiotic kanamycin. However, kanamycin is cleared in the manufacturing process and is not detectable in the final product. To produce pegfilgrastim-cbqv, a 20 kDa monomethoxypolyethylene glycol molecule is covalently bound to the N-terminal methionyl residue of recombinant methionyl human G-CSF. The average molecular weight of pegfilgrastim-cbqv is approximately 39 kDa. UDENYCA (pegfilgrastim-cbqv) injection is supplied as a 0.6 mL prefilled single-dose autoinjector or a 0.6 mL prefilled single-dose syringe for manual subcutaneous injection. The prefilled syringe does not bear graduation marks and is designed to deliver the entire contents of the syringe (6 mg/0.6 mL). The UDENYCA prefilled autoinjector delivers the entire contents (6mg in 0.6mL) in a single injection and is not adjustable. Each single-dose prefilled syringe or prefilled autoinjector contains 6 mg pegfilgrastim-cbqv (based on protein weight) in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), polysorbate 20 (0.02 mg), sodium (0.02 mg), and sorbitol (30 mg) in Water for Injection, USP.

2 DOSAGE AND ADMINISTRATION Patients with cancer receiving myelosuppressive chemotherapy 6 mg administered subcutaneously once per chemotherapy cycle. ( 2.1 ) Do not administer between 14 days before and 24 hours after administration of cytotoxic chemotherapy. ( 2.1 ) Use weight based dosing for pediatric patients weighing less than 45 kg; refer to Table 1 . ( 2.3 ) Patients acutely exposed to myelosuppressive doses of radiation Two doses, 6 mg each, administered subcutaneously one week apart. Administer the first dose as soon as possible after suspected or confirmed exposure to myelosuppressive doses of radiation, and a second dose one week after. ( 2.2 ) Use weight based dosing for pediatric patients weighing less than 45 kg; refer to Table 1 . ( 2.3 ) 2.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy The recommended dosage of UDENYCA is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle. For dosing in pediatric patients weighing less than 45 kg, refer to Table 1 . Do not administer UDENYCA between 14 days before and 24 hours after administration of cytotoxic chemotherapy. 2.2 Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome The recommended dose of UDENYCA is two doses, 6 mg each, administered subcutaneously one week apart. For dosing in pediatric patients weighing less than 45 kg, refer to Table 1 . Administer the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Administer the second dose one week after the first dose. Obtain a baseline complete blood count (CBC). Do not delay administration of UDENYCA if a CBC is not readily available. Estimate a patient’s absorbed radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics. 2.3 Administration UDENYCA is administered subcutaneously via a single-dose prefilled autoinjector or a single-dose prefilled syringe for manual use. Prior to use‚ remove the carton from the refrigerator and allow UDENYCA to reach room temperature for a minimum of 30 minutes. Discard any UDENYCA left at room temperature for greater than 48 hours. Visually inspect parenteral drug products (prefilled syringe or prefilled autoinjector) for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer UDENYCA if discoloration or particulates are observed. The needle cap on the prefilled syringe and prefilled autoinjector is not made with natural rubber latex. Pediatric Patients Weighing Less than 45 kg The UDENYCA prefilled syringe is not designed to allow for direct administration of doses less than 0.6 mL (6 mg). The syringe does not bear graduation marks which are necessary to accurately measure doses of UDENYCA less than 0.6 mL (6 mg) for direct administration to patients. Thus, the direct administration to patients requiring dosing of less than 0.6 mL (6 mg) is not recommended due to the potential for dosing errors. Refer to Table 1 . Table 1. Dosing of UDENYCA for pediatric patients weighing less than 45 kg Body Weight UDENYCA Dose Volume to Administer Less than 10 kg For pediatric patients weighing less than 10 kg, administer 0.1 mg/kg (0.01 mL/kg) of UDENYCA See below See below 10 - 20 kg 1.5 mg 0.15 mL 21 - 30 kg 2.5 mg 0.25 mL 31 - 44 kg 4 mg 0.4 mL The UDENYCA prefilled autoinjector is not suitable for use in pediatric patients weighing less than 45 kg. The UDENYCA prefilled autoinjector delivers the entire contents (6 mg in 0.6 mL) in a single injection and is not adjustable. 2.4 Advice to Give to Patients or Caregivers Regarding Administration via the Prefilled Autoinjector Only adults can self-administer UDENYCA with the prefilled autoinjector. If subcutaneous injections can be given at home, refer the patient or caregiver to the dose delivery information provided in the Instructions for Use. Provide training to patients or caregivers to ensure they understand how to administer UDENYCA via the prefilled autoinjector. Ensure patients or caregivers understand how to identify that a full dose has been administered by listening for the second 'click' and checking that the 'Orange Indicator' completely blocks the viewing window. Instruct patients or caregivers using the prefilled autoinjector to notify their healthcare provider immediately in order to determine the need for a replacement dose of UDENYCA if they suspect that the full dose may not have been administered.

1 INDICATIONS AND USAGE UDENYCA is a leukocyte growth factor indicated to Decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. ( 1.1 ) Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome). ( 1.2 ) Limitations of Use UDENYCA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. 1.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy UDENYCA is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia [see Clinical Studies ( 14.1 )] . Limitations of Use UDENYCA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. 1.2 Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome UDENYCA is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation [see Dosage and Administration ( 2.2 ) and Clinical Studies ( 14.2 )] .

10 OVERDOSAGE Overdosage of pegfilgrastim products may result in leukocytosis and bone pain. Events of edema, dyspnea, and pleural effusion have been reported in a single patient who administered pegfilgrastim on 8 consecutive days in error. In the event of overdose, the patient should be monitored for adverse reactions [see Adverse Reactions ( 6 )] .

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Pegfilgrastim products are colony-stimulating factors that act on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. 12.2 Pharmacodynamics Animal data and clinical data in humans suggest a correlation between pegfilgrastim products exposure and the duration of severe neutropenia as a predictor of efficacy. Selection of the dosing regimen of UDENYCA is based on reducing the duration of severe neutropenia. 12.3 Pharmacokinetics The pharmacokinetics of pegfilgrastim were studied in 379 patients with cancer. The pharmacokinetics of pegfilgrastim were nonlinear, and clearance decreased with increases in dose. Neutrophil receptor binding is an important component of the clearance of pegfilgrastim, and serum clearance is directly related to the number of neutrophils. In addition to numbers of neutrophils, body weight appeared to be a factor. Patients with higher body weights experienced higher systemic exposure to pegfilgrastim after receiving a dose normalized for body weight. A large variability in the pharmacokinetics of pegfilgrastim was observed. The half-life of pegfilgrastim ranged from 15 to 80 hours after subcutaneous injection. Specific Populations No gender-related differences were observed in the pharmacokinetics of pegfilgrastim, and no differences were observed in the pharmacokinetics of geriatric patients (≥ 65 years of age) compared with younger patients (< 65 years of age) [see Use in Specific Populations ( 8.5 )] . Renal Impairment In a study of 30 subjects with varying degrees of renal dysfunction, including end stage renal disease, renal dysfunction had no effect on the pharmacokinetics of pegfilgrastim. Pediatric Patients with Cancer Receiving Myelosuppressive Chemotherapy The pharmacokinetics and safety of pegfilgrastim were studied in 37 pediatric patients with sarcoma in Study 4 [see Clinical Studies 14.1 ] . The mean (± standard deviation [SD]) systemic exposure (AUC 0-inf ) of pegfilgrastim after subcutaneous administration at 100 mcg/kg was 47.9 (± 22.5) mcg·hr/mL in the youngest age group (0 to 5 years, n = 11), 22.0 (± 13.1) mcg·hr/mL in the 6 to 11 years age group (n = 10), and 29.3 (± 23.2) mcg·hr/mL in the 12 to 21 years age group (n = 13). The terminal elimination half-lives of the corresponding age groups were 30.1 (± 38.2) hours, 20.2 (± 11.3) hours, and 21.2 (± 16.0) hours, respectively. Patients Acutely Exposed to Myelosuppressive Doses of Radiation The pharmacokinetics of pegfilgrastim products is not available in patients acutely exposed to myelosuppressive doses of radiation. Based on limited pharmacokinetic data in irradiated non-human primates, the area under the concentration-time curve (AUC), reflecting the exposure to pegfilgrastim in non-human primates following a 300 mcg/kg dose of pegfilgrastim, appears to be greater than in humans receiving a 6 mg dose. Results from population modeling and simulation indicate that two 6 mg doses of pegfilgrastim administered one week apart in adults result in clinically relevant effects on duration of grade 3 and 4 neutropenia. In addition, weight based dosing in pediatric patients weighing less than 45 kg [see Dosage and Administration, Section 2.3 , Table 1 ] provides exposures comparable to those in adults receiving two 6 mg doses one week apart.

12.1 Mechanism of Action Pegfilgrastim products are colony-stimulating factors that act on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation.

12.2 Pharmacodynamics Animal data and clinical data in humans suggest a correlation between pegfilgrastim products exposure and the duration of severe neutropenia as a predictor of efficacy. Selection of the dosing regimen of UDENYCA is based on reducing the duration of severe neutropenia.

12.3 Pharmacokinetics The pharmacokinetics of pegfilgrastim were studied in 379 patients with cancer. The pharmacokinetics of pegfilgrastim were nonlinear, and clearance decreased with increases in dose. Neutrophil receptor binding is an important component of the clearance of pegfilgrastim, and serum clearance is directly related to the number of neutrophils. In addition to numbers of neutrophils, body weight appeared to be a factor. Patients with higher body weights experienced higher systemic exposure to pegfilgrastim after receiving a dose normalized for body weight. A large variability in the pharmacokinetics of pegfilgrastim was observed. The half-life of pegfilgrastim ranged from 15 to 80 hours after subcutaneous injection. Specific Populations No gender-related differences were observed in the pharmacokinetics of pegfilgrastim, and no differences were observed in the pharmacokinetics of geriatric patients (≥ 65 years of age) compared with younger patients (< 65 years of age) [see Use in Specific Populations ( 8.5 )] . Renal Impairment In a study of 30 subjects with varying degrees of renal dysfunction, including end stage renal disease, renal dysfunction had no effect on the pharmacokinetics of pegfilgrastim. Pediatric Patients with Cancer Receiving Myelosuppressive Chemotherapy The pharmacokinetics and safety of pegfilgrastim were studied in 37 pediatric patients with sarcoma in Study 4 [see Clinical Studies 14.1 ] . The mean (± standard deviation [SD]) systemic exposure (AUC 0-inf ) of pegfilgrastim after subcutaneous administration at 100 mcg/kg was 47.9 (± 22.5) mcg·hr/mL in the youngest age group (0 to 5 years, n = 11), 22.0 (± 13.1) mcg·hr/mL in the 6 to 11 years age group (n = 10), and 29.3 (± 23.2) mcg·hr/mL in the 12 to 21 years age group (n = 13). The terminal elimination half-lives of the corresponding age groups were 30.1 (± 38.2) hours, 20.2 (± 11.3) hours, and 21.2 (± 16.0) hours, respectively. Patients Acutely Exposed to Myelosuppressive Doses of Radiation The pharmacokinetics of pegfilgrastim products is not available in patients acutely exposed to myelosuppressive doses of radiation. Based on limited pharmacokinetic data in irradiated non-human primates, the area under the concentration-time curve (AUC), reflecting the exposure to pegfilgrastim in non-human primates following a 300 mcg/kg dose of pegfilgrastim, appears to be greater than in humans receiving a 6 mg dose. Results from population modeling and simulation indicate that two 6 mg doses of pegfilgrastim administered one week apart in adults result in clinically relevant effects on duration of grade 3 and 4 neutropenia. In addition, weight based dosing in pediatric patients weighing less than 45 kg [see Dosage and Administration, Section 2.3 , Table 1 ] provides exposures comparable to those in adults receiving two 6 mg doses one week apart.

20230315

10

3 DOSAGE FORMS AND STRENGTHS Injection: 6 mg/0.6 mL clear, colorless, preservative-free solution in a single-dose prefilled syringe for manual use only. 6 mg/0.6 mL clear, colorless, preservative-free solution in a single-dose prefilled autoinjector. Injection: 6 mg/0.6 mL in a single-dose prefilled syringe for manual use only. ( 3 ) 6 mg/0.6 mL in a single-dose prefilled autoinjector. ( 3 )

UDENYCA pegfilgrastim-cbqv PEGFILGRASTIM PEGFILGRASTIM ACETATE ION POLYSORBATE 20 SODIUM SORBITOL WATER UDENYCA pegfilgrastim-cbqv PEGFILGRASTIM PEGFILGRASTIM ACETATE ION POLYSORBATE 20 SODIUM SORBITOL WATER

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No carcinogenicity or mutagenesis studies have been performed with pegfilgrastim products. Pegfilgrastim did not affect reproductive performance or fertility in male or female rats at cumulative weekly doses approximately 6 to 9 times higher than the recommended human dose (based on body surface area).

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No carcinogenicity or mutagenesis studies have been performed with pegfilgrastim products. Pegfilgrastim did not affect reproductive performance or fertility in male or female rats at cumulative weekly doses approximately 6 to 9 times higher than the recommended human dose (based on body surface area).

BLA761039

UDENYCA

pegfilgrastim-cbqv

70114-120

HUMAN PRESCRIPTION DRUG

SUBCUTANEOUS

Carton Label - One 6 mg/0.6 mL Single-Dose Prefilled Syringe - UDENYCA PRINCIPAL DISPLAY PANEL Coherus BioSciences 6 mg/ 0.6 mL NDC 70114-101-01 UDENYCA ® pegfilgrastim-cbqv Injection Rx Only 6 mg in 0.6 mL Single-Dose Prefilled Syringe For Subcutaneous Use Sterile Solution - No Preservative Pegylated Recombinant Methionyl Human Granulocyte Colony-Stimulating Factor (PEG-r-metHuG-CSF) derived from E. coli One 6 mg/0.6 mL single-dose Prefilled Syringe image of carton label - principal panel

Indication and Usage, Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome ( 1.2 ) 11/2022 Dosage and Administration, Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome ( 2.2 ) 11/2022

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ) Advise patients of the following risks and potential risks with UDENYCA: Splenic rupture and splenomegaly Acute Respiratory Distress Syndrome Serious allergic reactions Sickle cell crisis Glomerulonephritis Increased risk of Myelodysplastic Syndrome and/or Acute Myeloid Leukemia in patients with breast and lung cancer who receive UDENYCA in conjunction with chemotherapy and/or radiation therapy Capillary Leak Syndrome Aortitis Advise patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome) that efficacy studies of pegfilgrastim products for this indication could not be conducted in humans for ethical and feasibility reasons and that, therefore, approval of this use was based on efficacy studies conducted in animals [see Clinical Studies ( 14.2 )] . Instruct patients who self-administer UDENYCA using the single-dose prefilled syringe of the: Importance of following the Instructions for Use (see Instructions for Use ). Dangers of reusing syringes. Importance of following local requirements for proper disposal of used syringes. Coherus BioSciences For patients who will use the UDENYCA prefilled autoinjector, tell them that they: Will hear two "clicks" during the UDENYCA injection. The first 'click' means the start of injection and second 'click' means the end of injection. To start injection, push the prefilled autoinjector body down. Continue holding down after hearing the first 'click'. In the viewing window, the orange indicator will advance to show the progress of the injection. When injection has finished, there will be a second 'click' and the 'Orange Indicator' will completely block the viewing window. Coherus BioSciences UDENYCA ® (pegfilgrastim-cbqv) Manufactured by: Coherus BioSciences, Inc., Redwood City, California 94065-1442 U.S. License No. 2023 © 2023 Coherus BioSciences Inc. All rights reserved. For more information, go to www.UDENYCA.com or call 1-800-4UDENYCA (1-800-483-3692) PMD-0004, Rev. 07

Instructions for Use UDENYCA ® (yoo-den-i-kah) (pegfilgrastim-cbqv) Injection Single-Dose Prefilled Syringe Guide to Parts Before Use Important: The needle is covered by a needle cap before use After Use Important Read the Patient Information for important information you need to know about UDENYCA before using these Instructions for Use. Storing the UDENYCA prefilled syringe Store UDENYCA prefilled syringes in the refrigerator between 36°F to 46° F (2°C to 8°C). Keep the UDENYCA prefilled syringe in the original carton to protect from light. Do not freeze UDENYCA. If UDENYCA is accidentally frozen, allow the prefilled syringe to thaw in the refrigerator before injecting. Throw away (dispose of) any UDENYCA prefilled syringes that have been frozen more than 1 time. Throw away (dispose of) any UDENYCA prefilled syringes that have been left out at room temperature for more than 48 hours. Keep the UDENYCA prefilled syringe out of the reach of children. Using the prefilled syringe It is important that you do not try to give the injection unless you or your caregiver has received training from your healthcare provider. Make sure that the name UDENYCA appears on the carton and prefilled syringe label. Check the carton and prefilled syringe label to make sure the dose strength is 6 mg/0.6 mL. You should not inject a dose of UDENYCA to children weighing less than 45 kg from a UDENYCA prefilled syringe. A dose less than 0.6 mL (6 mg) cannot be accurately measured using the UDENYCA prefilled syringe. Do not use a prefilled syringe after the expiration date on the label. Do not shake the prefilled syringe Do not remove the needle cap from the prefilled syringe until you are ready to inject. Do not use the prefilled syringe if the carton is open or damaged. Do not use a prefilled syringe if it has been dropped on a hard surface. The prefilled syringe may be broken even if you cannot see the break. Use a new prefilled syringe. Do not attempt to activate the needle safety guard prior to injection Call your healthcare provider if you have any questions. Prepare the injection 1 - Remove carton from refrigerator and check expiration date 1A: Remove the carton from the refrigerator and check the expiration date printed on the carton. (See Figure 3 ) Do not use if the expiration date has passed. 1B: Open the carton and remove the sealed syringe tray. (See Figure 4 ) 2 - Allow UDENYCA to reach room temperature and gather supplies 2A: Place the sealed syringe tray on a flat, clean work surface and allow it to sit at room temperature for at least 30 minutes. (See Figure 5 ) Do not attempt to warm up the syringe in any other way, such as a microwave, hot water, or direct sunlight. 2B: Gather the following supplies: (See Figure 6 ) Alcohol wipe Cotton ball or gauze 1 adhesive bandage Sharps disposal container 3 - Wash your hands and remove syringe from tray 3A: Wash your hands well with soap and warm water. (See Figure 7 ) 3B: Open the tray by peeling away the cover. Remove the prefilled syringe from the tray by grasping the middle of the syringe body and carefully pulling it out of the tray. (See Figure 8 ) For Safety reasons: Do not grab the plunger or the plunger head. Do not grab the needle cap. 4 - Inspect the syringe and medicine Check the medicine through the Inspection Window. The medicine should be clear and colorless. It is normal to see 1 or more air bubbles in the syringe. Removal of the air is not needed. (See Figure 9 ) Do not use the prefilled syringe if: the medicine appears discolored or cloudy. the medicine contains lumps, flakes, or particles. it appears used or damaged. the needle cap is missing or not securely attached. the expiration date printed on the label has passed. In all cases, use a new prefilled syringe and call your healthcare provider. Select and clean injection site 5 - Select and clean the injection site 5A: Select the injection site. The recommended injection sites for a subcutaneous injection are the: (See Figure 10 ) Abdomen (except for a two-inch area surrounding the navel) Thighs Back of upper arms (only if someone else is giving you the injection) Upper outer area of the buttocks (only if someone else is giving you the injection) Do not inject into moles, scars, birthmarks, or areas where the skin is tender, bruised, red, or hard. If you want to use the same injection site, make sure it is not the same spot on the injection site you used for a previous injection. 5B: Clean the injection site with an alcohol wipe. (See Figure 11 ) Do not touch this area again before injection. Inject the dose 6 - Remove needle cap Remove the needle cap by pulling it straight off. (See Figure 12 ) Do not remove the needle cap from the prefilled syringe until you are ready to inject. Do not twist or bend the needle cap. Do not hold the prefilled syringe by the plunger rod Do not put the needle cap back onto the syringe. Dispose of (throw away) the needle cap in your household trash Do not use the prefilled syringe if it has been dropped with the needle cap removed. 7 – Position fingers Grasp the body of the syringe like a dart (just under the finger grips) with your thumb and index fingers. (See Figure 13 ) Do not touch the plunger or grasp the syringe above the finger grips. 8 – Pinch the skin and insert the needle 8A: Use your free hand to gently pinch the cleaned injection site to create a firm surface. (See Figure 14 ) 8B: Hold the pinch. Insert the needle into the skin at a 45 to 90-degree angle. (See Figure 15 ) Do not touch the plunger head while inserting the needle into the skin. Do not touch the cleaned area of the skin 8C: After fully inserting the needle, release the pinched skin and use your free hand to stabilize the bottom of the syringe. Then move your other hand into injection position with your thumb on the plunger head. (See Figure 16 ) 9 – Push plunger head down to deliver dose 9A: Using slow and constant pressure, push the plunger head down until it reaches the bottom. This will help to ensure that you receive the full dose. (See Figure 17 ) 9B: While the needle is still inserted, slowly move your thumb back, allowing the plunger to rise. This will release the needle safety guard to safely cover the needle. Then remove the syringe from the injection site. (See Figure 18 ) Important: When you remove the syringe, if it looks like the medicine is still in the syringe, this means you have not received a full dose. Call your healthcare provider right away. If you see drops of blood at the injection site, treat by pressing a cotton ball or gauze to the site as needed. Dispose 10 – Dispose of used prefilled syringes Put the used prefilled syringe into an FDA-cleared sharps disposal container right away after use. Do not throw away the syringe in the household trash. (See Figure 19 ) If you do not have a FDA-cleared sharps disposal container, you may use a household container that is: made of a heavy-duty plastic can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out upright and stable during use leak-resistant properly labeled to warn of hazardous waste inside the container When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal. Do not reuse the prefilled syringe. Do not recycle prefilled syringes or sharps disposal container or throw them into household trash. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Issued: 09/2019 Coherus BioSciences UDENYCA ® (pegfilgrastim-cbqv) Manufactured by: Coherus BioSciences, Inc., Redwood City, California 94065-1442 U.S. License No. 2023 © 2019 Coherus BioSciences Inc. All rights reserved. For more Information go to www.UDENYCA.com or call 1-800-4UDENYCA (1-800-483-3692) PMD-0005, Rev. 02 image of UDENYCA before use image of UDENYCA after use image of storage - instructions for use image of removal from storage - instructions for use image of opening UDENYCA - instructions for use image of time to reach room temp - instructions for use image of gathering supplies - instructions for use image of proper hand washing - instructions for use image of removal of UDENYCA from tray - instructions of use image of visual inspection - instructions for use image of injection site selection - instructions for use image of cleaning injection site - instructions for use image of removal of needle cap - instructions for use image of position of fingers - instructions for use image of pinching skin of injection site - instructions for use image of proper needle insertion - instructions for use image of injection finger positioning - instructions for use image of plunger push - instructions for use image of needle retraction - instructions for use image of disposal - instructions for use

14 CLINICAL STUDIES 14.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy Pegfilgrastim was evaluated in three randomized, double-blind, controlled studies. Studies 1 and 2 were active- controlled studies that employed doxorubicin 60 mg/m 2 and docetaxel 75 mg/m 2 administered every 21 days for up to 4 cycles for the treatment of metastatic breast cancer. Study 1 investigated the utility of a fixed dose of pegfilgrastim. Study 2 employed a weight-adjusted dose. In the absence of growth factor support, similar chemotherapy regimens have been reported to result in a 100% incidence of severe neutropenia (ANC < 0.5 x 10 9 /L) with a mean duration of 5 to 7 days and a 30% to 40% incidence of febrile neutropenia. Based on the correlation between the duration of severe neutropenia and the incidence of febrile neutropenia found in studies with filgrastim, duration of severe neutropenia was chosen as the primary endpoint in both studies, and the efficacy of pegfilgrastim was demonstrated by establishing comparability to filgrastim-treated patients in the mean days of severe neutropenia. In Study 1, 157 patients were randomized to receive a single subcutaneous injection of pegfilgrastim (6 mg) on day 2 of each chemotherapy cycle or daily subcutaneous filgrastim (5 mcg/kg/day) beginning on day 2 of each chemotherapy cycle. In Study 2, 310 patients were randomized to receive a single subcutaneous injection of pegfilgrastim (100 mcg/kg) on day 2 or daily subcutaneous filgrastim (5 mcg/kg/day) beginning on day 2 of each chemotherapy cycle. Both studies met the major efficacy outcome measure of demonstrating that the mean days of severe neutropenia of pegfilgrastim-treated patients did not exceed that of filgrastim-treated patients by more than 1 day in cycle 1 of chemotherapy. The mean days of cycle 1 severe neutropenia in Study 1 were 1.8 days in the pegfilgrastim arm compared to 1.6 days in the filgrastim arm [difference in means 0.2 (95% CI -0.2, 0.6)] and in Study 2 were 1.7 days in the pegfilgrastim arm compared to 1.6 days in the filgrastim arm [difference in means 0.1 (95% CI -0.2, 0.4)]. A secondary endpoint in both studies was days of severe neutropenia in cycles 2 through 4 with results similar to those for cycle 1. Study 3 was a randomized, double-blind, placebo-controlled study that employed docetaxel 100 mg/m 2 administered every 21 days for up to 4 cycles for the treatment of metastatic or non-metastatic breast cancer. In this study, 928 patients were randomized to receive a single subcutaneous injection of pegfilgrastim (6 mg) or placebo on day 2 of each chemotherapy cycle. Study 3 met the major trial outcome measure of demonstrating that the incidence of febrile neutropenia (defined as temperature ≥ 38.2°C and ANC ≤ 0.5 x109/L) was lower for pegfilgrastim-treated patients as compared to placebo-treated patients (1% versus 17%, respectively, p < 0.001). The incidence of hospitalizations (1% versus 14%) and IV anti-infective use (2% versus 10%) for the treatment of febrile neutropenia was also lower in the pegfilgrastim-treated patients compared to the placebo-treated patients. Study 4 was a multicenter, randomized, open-label study to evaluate the efficacy, safety, and pharmacokinetics [see Clinical Pharmacology ( 12.3 )] of pegfilgrastim in pediatric and young adult patients with sarcoma. Patients with sarcoma receiving chemotherapy age 0 to 21 years were eligible. Patients were randomized to receive subcutaneous pegfilgrastim as a single dose of 100 mcg/kg (n= 37) or subcutaneous filgrastim at a dose 5 mcg/kg/day (n=6) following myelosuppressive chemotherapy. Recovery of neutrophil counts was similar in the pegfilgrastim and filgrastim groups. The most common adverse reaction reported was bone pain. 14.2 Patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome Efficacy studies of pegfilgrastim products could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. Approval of this indication was based on efficacy studies conducted in animals and data supporting pegfilgrastim's effect on severe neutropenia in patients with cancer receiving myelosuppressive chemotherapy [see Dosage and Administration ( 2.1 )] . The recommended dose of UDENYCA is two doses, 6 mg each, administered one week apart for humans exposed to myelosuppressive doses of radiation. For pediatric patients weighing less than 45 kg, dosing of UDENYCA is weight based and is provided in Table 1 [see Dosage and Administration ( 2.3 )] . This dosing regimen is based on population modeling and simulation analyses. The exposure associated with this dosing regimen is expected to provide sufficient pharmacodynamic activity to treat humans exposed to myelosuppressive doses of radiation [see Clinical Pharmacology ( 12.3 )] . The safety of pegfilgrastim at a dose of 6 mg has been assessed on the basis of clinical experience in patients with cancer receiving myelosuppressive chemotherapy. The efficacy of pegfilgrastim for the acute radiation syndrome setting was studied in a randomized, placebo- controlled non-human primate model of radiation injury. Rhesus macaques were randomized to either a control (n = 23) or treated (n = 23) cohort. On study day 0, animals (n = 6 to 8 per irradiation day) were exposed to total body irradiation (TBI) of 7.50 ± 0.15 Gy delivered at 0.8 ± 0.03 Gy/min, representing a dose that would be lethal in 50% of animals by 60 days of follow-up (LD50/60). Animals were administered subcutaneous injections of a blinded treatment (control article [5% dextrose in water] or pegfilgrastim [300-319 mcg/kg/day]) on study day 1 and on study day 8. The primary endpoint was survival. Animals received medical management consisting of intravenous fluids, antibiotics, blood transfusions, and other support as required. Pegfilgrastim significantly (at 0.0014 level of significance) increased 60-day survival in irradiated non-human primates: 91% survival (21/23) in the pegfilgrastim group compared to 48% survival (11/23) in the control group.

8.2 Lactation Risk Summary There are no data on the presence of pegfilgrastim products in human milk, the effects on the breastfed child, or the effects on milk production. Other filgrastim products are secreted poorly into breast milk, and filgrastim products are not orally absorbed by neonates. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for UDENYCA and any potential adverse effects on the breastfed child from UDENYCA or from the underlying maternal condition.

8.5 Geriatric Use Of the 932 patients with cancer who received pegfilgrastim in clinical studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and over. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.

8.1 Pregnancy Risk Summary Although available data with UDENYCA or pegfilgrastim product use in pregnant women are insufficient to establish whether there is a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, there are available data from published studies in pregnant women exposed to filgrastim products. These studies have not established an association of filgrastim product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, no evidence of reproductive/developmental toxicity occurred in the offspring of pregnant rats that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area). In pregnant rabbits, increased embryolethality and spontaneous abortions occurred at 4 times the maximum recommended human dose simultaneously with signs of maternal toxicity ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Pregnant rabbits were dosed with pegfilgrastim subcutaneously every other day during the period of organogenesis. At cumulative doses ranging from the approximate human dose to approximately 4 times the recommended human dose (based on body surface area), treated rabbits exhibited decreased maternal food consumption, maternal weight loss, as well as reduced fetal body weights and delayed ossification of the fetal skull; however, no structural anomalies were observed in the offspring from either study. Increased incidences of post-implantation losses and spontaneous abortions (more than half the pregnancies) were observed at cumulative doses approximately 4 times the recommended human dose, which were not seen when pregnant rabbits were exposed to the recommended human dose. Three studies were conducted in pregnant rats dosed with pegfilgrastim at cumulative doses up to approximately 10 times the recommended human dose at the following stages of gestation: during the period of organogenesis, from mating through the first half of pregnancy, and from the first trimester through delivery and lactation. No evidence of fetal loss or structural malformations was observed in any study. Cumulative doses equivalent to approximately 3 and 10 times the recommended human dose resulted in transient evidence of wavy ribs in fetuses of treated mothers (detected at the end of gestation but no longer present in pups evaluated at the end of lactation).

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Although available data with UDENYCA or pegfilgrastim product use in pregnant women are insufficient to establish whether there is a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, there are available data from published studies in pregnant women exposed to filgrastim products. These studies have not established an association of filgrastim product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, no evidence of reproductive/developmental toxicity occurred in the offspring of pregnant rats that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area). In pregnant rabbits, increased embryolethality and spontaneous abortions occurred at 4 times the maximum recommended human dose simultaneously with signs of maternal toxicity ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Pregnant rabbits were dosed with pegfilgrastim subcutaneously every other day during the period of organogenesis. At cumulative doses ranging from the approximate human dose to approximately 4 times the recommended human dose (based on body surface area), treated rabbits exhibited decreased maternal food consumption, maternal weight loss, as well as reduced fetal body weights and delayed ossification of the fetal skull; however, no structural anomalies were observed in the offspring from either study. Increased incidences of post-implantation losses and spontaneous abortions (more than half the pregnancies) were observed at cumulative doses approximately 4 times the recommended human dose, which were not seen when pregnant rabbits were exposed to the recommended human dose. Three studies were conducted in pregnant rats dosed with pegfilgrastim at cumulative doses up to approximately 10 times the recommended human dose at the following stages of gestation: during the period of organogenesis, from mating through the first half of pregnancy, and from the first trimester through delivery and lactation. No evidence of fetal loss or structural malformations was observed in any study. Cumulative doses equivalent to approximately 3 and 10 times the recommended human dose resulted in transient evidence of wavy ribs in fetuses of treated mothers (detected at the end of gestation but no longer present in pups evaluated at the end of lactation). 8.2 Lactation Risk Summary There are no data on the presence of pegfilgrastim products in human milk, the effects on the breastfed child, or the effects on milk production. Other filgrastim products are secreted poorly into breast milk, and filgrastim products are not orally absorbed by neonates. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for UDENYCA and any potential adverse effects on the breastfed child from UDENYCA or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of pegfilgrastim have been established in pediatric patients. No overall differences in safety were identified between adult and pediatric patients with pegfilgrastim based on postmarketing surveillance and review of the scientific literature. Use of pegfilgrastim in pediatric patients for chemotherapy-induced neutropenia is based on adequate and well controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients with sarcoma [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14 )] . The use of pegfilgrastim to increase survival in pediatric patients acutely exposed to myelosuppressive doses of radiation is based on efficacy studies conducted in animals and clinical data supporting the use of pegfilgrastim in patients with cancer receiving myelosuppressive chemotherapy. Efficacy studies of pegfilgrastim products could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. Results from population modeling and simulation indicate that two doses of pegfilgrastim (Table 1), administered one week apart provide pediatric patients with exposures comparable to that in adults receiving two 6 mg doses one week apart [see Dosage and Administration ( 2.3 ), Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.2 )] . 8.5 Geriatric Use Of the 932 patients with cancer who received pegfilgrastim in clinical studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and over. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.

16 HOW SUPPLIED/STORAGE AND HANDLING UDENYCA single-dose prefilled syringe for manual use UDENYCA (pegfilgrastim-cbqv) injection is a clear, colorless, preservative-free solution supplied in a prefilled single-dose syringe containing 6 mg pegfilgrastim-cbqv, supplied with a 29-gauge, 1⁄2-inch needle with an UltraSafe Passive ™ Needle Guard. The needle cap of the prefilled syringe is not made with natural rubber latex. UDENYCA is provided in a dispensing pack containing one sterile 6 mg/0.6 mL prefilled syringe (NDC 70114-101-01). UDENYCA prefilled syringe does not bear graduation marks and is intended only to deliver the entire contents of the syringe (6 mg/0.6 mL) for direct administration. Use of the prefilled syringe is not recommended for direct administration for pediatric patients weighing less than 45 kg who require doses that are less than the full contents of the syringe. Store refrigerated between 2° to 8°C (36° to 46°F) in the carton to protect from light. Do not shake. Discard UDENYCA stored at room temperature for more than 48 hours. Avoid freezing; if frozen, thaw in the refrigerator before administration. Discard UDENYCA if frozen more than once. UDENYCA single-dose prefilled autoinjector UDENYCA (pegfilgrastim-cbqv) injection is a clear, colorless, preservative-free solution supplied in a prefilled single-dose autoinjector containing 6 mg pegfilgrastim-cbqv. The needle cap of the prefilled autoinjector is not made with natural rubber latex. UDENYCA is provided in a dispensing pack containing one 6 mg/0.6 mL prefilled autoinjector (NDC 70114-120-01). The UDENYCA prefilled autoinjector is not suitable for use in pediatric patients weighing less than 45 kg. The UDENYCA prefilled autoinjector delivers the entire contents (6 mg in 0.6 mL) in a single injection and is not adjustable. Store refrigerated between 2° to 8°C (36° to 46°F) in the carton to protect from light. Do not shake. Discard UDENYCA stored at room temperature for more than 48 hours. Avoid freezing; if frozen, thaw in the refrigerator before administration. Discard UDENYCA if frozen more than once.