New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 1
New Drugs of 2016: Part 2
May 12, 2017
Featured Speaker: Mary Lynn Moody, BSPharmDirector, Business DevelopmentDrug Information and Prior Authorization GroupUniversity of Illinois at Chicago
LUNCH AND LEARN
CE Activity Information & Accreditation
ProCE, Inc. (Pharmacist and Tech CE)
1.0 contact hour
2
Funding: This activity is self‐funded through PharMEDium.
It is the policy of ProCE, Inc. to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Ms. Moody has served as a speaker for Baxter Healthcare and Salveo Health Communications.
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 2
3
Submission of an online self‐assessment and evaluation is the only way to obtain CE credit for this webinar
Go to www.ProCE.com/PharMEDiumRx
Print your CE Statement online
Live CE Deadline: June 9, 2017
CPE Monitor– CE information automatically uploaded to NABP/CPE Monitor upon
completion of the self‐assessment and evaluation (user must complete the “claim credit” step)
Online Evaluation, Self-Assessmentand CE Credit
Attendance Code
Code will be provided at the end of today’s activityAttendance Code not needed for On‐Demand
Ask a Question
Submit your questions to your site manager.
Questions will be answered at the end of the presentation.
4
Your question. . . ?
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 3
Resources
Visit www.ProCE.com/PharMEDiumRx to access:
– Handouts
– Activity information
– Upcoming live webinar dates
– Links to receive CE credit
5
Mary Lynn Moody BSPharm
Clinical Associate Professor
Department of Pharmacy Practice
University of Illinois at Chicago
6
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 4
Learning Objectives - Pharmacists
Describe the new drugs approved by the Food and Drug Administration in 2016
Discuss the role of these agents in therapy
Summarize the adverse effects and potential drug interactions of these new agents
7
Learning Objectives - Technicians
Describe the new drugs approved by the Food and Drug Administration in 2016
Discuss any unique preparation and/or dispensing requirements for these agents
Summarize the adverse effects and potential drug interactions of these new agents that may require pharmacist intervention
8
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 5
9
Brivaracetam (Briviact®)3
Approved February 18, 2016
Indicated as adjunctive therapy in partial-onset seizures
Analog of levetiracetam (Keppra)
New epilepsy drugs are often only approved for this indication
10
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 6
Brivaracetam 3
Binds selectively to protein 2A (SV2A) in the brain
Modulates neurotransmitter release into the synapse
10- to 30-fold higher affinity for SV2A than levetiracetam
Higher brain permeability, more rapid onset of action than levetiracetam
11
Brivaracetam Dosing 3
Starting dosage is 50 mg twice daily (orally)
Can be decreased to 25 mg twice daily or increased to 100 mg twice daily
May be taken with or without food
Liver impairment: Starting dose is 25 mg twice daily and the maximum dose is 75 mg twice daily
12
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 7
Brivaracetam Pharmacokinetics 3
Tmax- One hour (fasting); delayed 3 hours with high fat meal
Metabolized by hydrolysis
95% excreted in the urine, 10% unchanged
Elimination half-life is 9 hours
13
Brivaracetam Efficacy 4
3 randomized, double-blind, placebo-controlled 12-week trials
Primary endpoint of mean reduction in seizure frequency
Study 1 and 2: Brivaracetam was not beneficial for the 20% of patients receiving concomitant levetiracetam
Study 3: Adjunctive brivaracetam significantly reduced seizure frequency among the patients who had previously tried and discontinued levetiracetam.
14
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 8
Brivaracetam Warnings 3,5
Potential for suicidal behavior
Bronchospasm and angioedema may occur if hypersensitivity-Do not rechallenge
Do not stop brivaracetam abruptly, taper slowly
15
Brivaracetam Adverse Effects 3,5
Common adverse effects
Somnolence and sedation (16%)
Dizziness (12%)
Fatigue (9%)
Nausea and vomiting (5%)
Psychiatric adverse reactions (13%), mostly anxiety and depression
16
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 9
Brivaracetam Drug Interactions 3,5
Rifampin decreases plasma concentrations of brivaracetam by 45%, increase brivaracetam dose by 100%
Brivaracetam increases active metabolite of carbamazepine
Brivaracetam increases levels of phenytoin by 20%, monitor levels
17
Brivaracetam Place in Therapy
Modestly effective as add-on treatment in adults with refractory partial-onset seizures
Useful in those who failed to respond to levetiracetam
May also be effective in myoclonic and primarily generalized seizures
Generic levetiracetam costs much less
18
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 10
Pharmacist Clinical Points
Discuss the risk of suicide ideation
Review the risks associated with abrupt cessation of brivaracetam
Conduct a clinical review of other medications to ensure there are no drug interactions
Warn patient about the risk of CNS side effects
19
Technician Points
Establish an alert process for the pharmacist for missed refills to ensure patient compliance
Alert the pharmacist of any new prescription or non-prescription medications to screen for interactions
20
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 11
21
Atezolizumab 6,7
Approved May 18, 2016 Indicated for metastatic non-small cell
lung cancer (NSCLC) Accelerated approval In 2017 received approval for use in
metastatic urothelial cancer The mechanism of action is a
Programmed death-ligand (PD-L) blocking antibody
22
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 12
Atezolizumab MOA 6,7
Binds to Programmed Death-Ligand 1 (PD-L1)
Blocks the interaction with the PD-1 and B7-1 receptors on T-lymphocytes
Blocking these receptors allows for restoration of anti-tumor T-cell activity
23
Atezolizumab Dosing 6,7
Give 1200 mg over 60 minutes every 3 weeks
Dilute with 0.9% sodium chloride by withdrawing 20 mL of atezolizumab and placing in 250 mL bag- Do not shake
Withhold dose if Grade 2 or 3 adverse reactions occur. May resume treatment when reduced to Grade 0 or 1
24
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 13
Atezolizumab Efficacy 8
Two multicenter, international, randomized, open-label trials in patients with metastatic NSCLC who progressed during or following a platinum-containing regimen
Study 2 was a trial in 1225 patients with the primary analysis consisting of the first 850 randomized patients
Study 3 was a trial in 287 patients
25
Atezolizumab Efficacy 8
Study 2 Analysis of first 850 patients. 425 patients in atezolizumab arm, 425 patients in
docetaxel arm Lower incidence of death with atezolizumab 271
cases (64%) vs docetaxel with 298 cases (70%) Longer survival time with atezolizumab 13.8 months
vs docetaxel with 9.6 months Study 3
144 pts in atezolizumab arm, 143 in docetaxel arm Lower incidence of death with atezolizumab 90
cases (63%) vs docetaxel 110 cases (77%) Longer survival time with atezolizumab 12.6 months
vs docetaxel 9.7 months
26
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 14
Atezolizumab Warnings 6,7
Pneumonitis, Hepatitis, Colitis These conditions require use of
corticosteroids; no clear alternate etiology
Administer 1-2 mg/kg/day of prednisone for Grade 2 toxicities, hold atezolizumab dose
Discontinue atezolizumab if Grade 3/4
Endocrine abnormalities
Infection
Infusion-related reaction
27
Atezolizumab Adverse Effects 6,7
ADEs reported in 20% of patients Fatigue, decreased appetite, nausea,
pyrexia, UTI and constipation
Serious ADEs Grade 3 or 4 adverse reactions in >2% of
patients○ Intestinal or urinary obstruction, hematuria,
dyspnea, kidney damage, VTE, infection
28
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 15
Atezolizumab Place in Therapy 7
NSCLC: EGFR or ALK genomic tumor aberrations should have disease progression on FDA approved therapy first
Urothelial Cancer: Not eligible for cisplatin-containing chemotherapy, or have disease progression during/following platinum chemotherapy, or within 12 months of neoadjuvant or adjuvant chemotherapy
29
Pharmacist Clinical Points
Review potential Grade 3 or 4 toxicities with patient/physician prior to dose
Ensure USP Chapter <800> guidelines are enforced, since the agent is a hazardous drug
30
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 16
Technician Points
Do not prepare product until patient is in clinic and dose is confirmed
Use immediately following preparation
May store at room temperature for 24 hours
Incorporate USP Chapter <800> guidelines in production
31
32
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 17
Reslizumab (Cinqair®) 9
Approved March 23, 2016
2nd Interleukin-5 antagonist approved
Indicated as add-on therapy in severe asthma in adults with eosinophilic phenotype
Reduces the levels of blood eosinophils
Maintenance therapy
33
Reslizumab Pharmacokinetics 6,9
Peak serum concentrations reported at the end of the infusion
Vd is 5 L
Metabolism is via enzymatic proteolysis
Half-life -24 days
No studies in hepatic or renal patients
34
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 18
Reslizumab MOA 9,10
Blocks binding to IL-5 receptors on the surface of eosinophils
Reduces the production and survival of eosinophils and decreases airway inflammation
35
Reslizumab Dosing 9
3 mg/kg infused intravenously over 20-50 minutes once every 4 weeks. Do not give IV Push.
Anaphylaxis has occurred as early as 2nd
dose. May occur during or within 20 minutes of completing the infusion.
Withdrawal symptoms could occur if inhaled or systemic corticosteroids are stopped abruptly when reslizumab therapy is started.
36
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 19
Reslizumab Efficacy 10
4 clinical trials included 981 patients
2 trials were 52 weeks duration
Significant reduction in the rate of asthma exacerbations Less systemic corticosteroid used
Fewer required hospitalization or an ED visit
Significantly improved lung function [increase in forced expiratory volume in 1 second (FEV1) determinations]
37
Reslizumab Warnings 9
Black box warning - Anaphylaxis Potentially life-threatening
Reported in 0.3% of patients
Can occur as early as second dose
Monitor patient during and after receiving dose
Discontinue if anaphylaxis occurs
38
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 20
Reslizumab Adverse Effects 9
Common adverse effects Musculoskeletal adverse reactions on the day of infusion
(2.2% vs 1.5%) Oropharyngeal pain (2.6% vs 2.2%) Creatine phosphokinase (CPK) elevations (14% vs 9%) Myalgia (1.0% vs 0.5%)
Serious adverse events Anaphylaxis (0.3% vs 0%) Malignancy (0.6% vs 0.3%)
Antibodies to reslizumab developed in about 5% of patients treated with the drug in clinical trials; they did not appear to affect the clinical efficacy of the drug.
39
Pharmacist Clinical Points
Ensure patient is monitored during and after infusion for anaphylaxis
Anaphylaxis can appear as dyspnea, wheezing, decreased oxygen saturation, vomiting, skin and mucosal reactions
40
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 21
Technician Tips
To minimize foaming, do not shake drug vials
Withdraw dose from vial and slowly add to 50 mL bag of 0.9% sodium chloride
Administer immediately after preparation Do not give as IV push or bolus. Flush line
with 0.9% sodium chloride to ensure complete dose given
Infusion must be complete by 16 hours after compounding
41
42
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 22
Ixekizumab 11
Approved March 22, 2016
Moderate to severe plaque psoriasis
Interleukin 17A antagonist
Available as auto-injector and prefilled syringe
43
Ixekizumab Pharmacokinetics 11
60-81% absorbed following SQ dose
Higher bioavailability when dosed in thigh
Vd=7.11 L
Metabolism is not characterized
Eliminated via catabolism like IgG
Elimination half-life is 13 days
44
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 23
Ixekizumab MOA 11,12
IL-17A is a cytokine involved in normal inflammatory and immune responses
Ixekizumab is an IgG4 monoclonal antibody that selectively binds with IL-17A
45
Ixekizumab Dosing 6,11
Administered as subcutaneous injection
Give 160 mg (two 80 mg injections) initially and then 80 mg every 2 weeks for a total of 7 doses
Then extend dosing interval to every 4 weeks thereafter
Give into upper arm, thigh or abdomen
46
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 24
Ixekizumab Efficacy 12
3 clinical trials compare ixekizumab to placebo
PASI 75 and sPGA scores were 12 week endpoints
82% of patients had a positive sPGA score
87-90% had 75% reduction in PASI score
47
Ixekizumab Warnings 11
Contraindicated if hypersensitivity to drug or components
Screen patients for tuberculosis
Treat all latent TB before starting ixekizumab. Do not give if active TB.
Increased risk for infection
Avoid live vaccines
Risk for inflammatory bowel disease
48
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 25
Ixekizumab Adverse Effects 11
Injection site reactions
Upper respiratory tract infections
Nausea
Tinea infection
Oral candidiasis
Conjunctivitis
49
Ixekizumab Drug Interactions 11
May normalize CYP450 enzymes
Monitor drugs with narrow therapeutic index Warfarin
Cyclosporine
50
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 26
Pharmacist Clinical Points
Verify patient does not have an infection, including tuberculosis
Reinforce need to avoid live vaccines (e.g. Shingles)
Do not inject into tender or inflamed skin
Discuss what to do if an infection develops
51
Technician Tips
Store in the refrigerator, protect from light
Do not shake ixekizumab syringe or auto-injector
Do not substitute the different dosage forms. Patients may not know how to use an auto-injector.
52
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 27
53
Glargine/Lixisenatide (Soliqua™) 13
Approved November 21, 2016
Glargine long acting human insulin
Lixisenatide Glucagon-Like Peptide-1 Receptor agonist (GLP-1)
Approved to treat type 2 diabetes mellitus Inadequately controlled on basal insulin or
lixisenatide
Not studied in combination with prandial insulin
54
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 28
Glargine/Lixisenatide Dosage 6,13
Dosage Form: 3 mL injection pen
Strength: 100 Units glargine per ml and 33 mcg lixisenatide per ml
Administration: Once daily, within 1 hour prior to 1st meal
Administer subcutaneously (SQ) in the
abdomen, arm or thigh Prior Basal Insulin Dose
Initial Soliqua Dose Titration
< 30 Units 15 Units/5 mcg 2-4 Units/week
30-60 Units 30 Units/10 mcg 2-4 Units/week55
Glargine/Lixisenatide Pharmacokinetics 13
Metabolism/elimination:
Glargine 2 active human insulin in SQ
Lixisenatide Renal and proteolytic degradation
Half-life: ~3 hours
Dose adjustments:
eGFR 15-29 ml/min clinical experience is limited
eGFR <15 ml/min do not use
56
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 29
Glargine/Lixisenatide Efficacy 14
Two phase-3 clinical trials: randomized, active-controlled, and open-label
N = 834 Duration = 30 weeks
Primary endpoint: Change (∆) in HbA1c from baseline to week 30
Results: Mean change in HbA1c from baseline to Week 30.
Study Treatment Arms
BaselineHbA1c(%)
∆ HbA1c (%)
P-value
Study 1 FRC*GlargineLixisenatide
8.088.088.13
-1.63-1.34-0.85
<0.0001<0.0001
Study 2 FRC*Glargine
8.078.08
-1.13-0.62 <0.0001
*FRC = Fixed Ratio Combination 57
Glargine/Lixisenatide Safety 13
Adverse Reactions (≥5%) Nausea 10%
Hypoglycemia 8%
Nasopharyngitis 7%
Diarrhea 7%
URTIs 5.5%
Headache 5.4%
58
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 30
Glargine/Lixisenatide Warnings 13
Hypoglycemia
Pancreatitis: discontinue if suspected
Acute kidney injury: not recommended in ESKD
Immunogenicity: antibodies may develop to glargine/lixisenatide
Hypokalemia: monitor potassium levels
59
Pharmacist Clinical Points
Explain importance of adherence to this combination
Review dosing schedule; reinforce dose is within one hour prior to 1st meal
Discuss need to monitor HbA1C
Discuss proper storage and use of product
60
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 31
Technician Tips
Alert pharmacist if refills are late or missed
Alert pharmacist of any OTC drugs that are being purchased in case of interactions
Ensure patient has necessary supplies
61
Conclusions
Much fewer number of drugs approved in 2016
Majority of those approved were orphan, fast track agents
Not much impact on compounding business
Critical to understand these new agents
62
New Drugs of 2016: Part 2PharMEDium Lunch and Learn Series
ProCE, Inc.www.ProCE.com 32
References1. United States Food and Drug Administration. Novel Drug Approvals 2016.
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm483775.htm. Accessed January 8, 2017.
2. United States Food and Drug Administration. Novel Drugs Summary 2016. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm534863.htm. Accessed March 3, 2017.
3. Briviact [package insert]. Smyrna GA: UCB Inc. March 2016.4. Mumoli L, Palleria C, Gasparini S et al. Brivaracetam: review of its pharmacology and potential use as
adjunctive therapy in patients with partial onset seizures. Drug Des Devel Ther 2015; 9(10):5719-5725. 5. Brivaracetam (Briviact) for Epilepsy. Med Lett Drugs Ther. 2016;58(1499):95-96.6. Facts and Comparisons. [database online] Indianapolis, IN: Clinical Drug Information. LLC;
http://online.factsandcomparisons.com. Accessed January 15, 2017.7. Tecentriq [package insert]. South San Francisco CA: Genentech Inc. April 2017.8. Atezolizumab (Tecentriq) for Bladder Cancer and NSCLC. Med Lett Drugs Ther. 2017;59(1515):e40-41.9. Cinqair [package insert]. Frazer PA: Teva Respiratory. May 2016.10. Deeks ED, Bruselle G. Reslizumab in eosinophilic asthma: a review. Drugs. 2017;77(7):777-784.11. Taltz [package insert]. Indianapolis IN: Eli Lilly and Company. January 2017.12. Ixekizumab (Taltz) - A Second IL-17A Inhibitor for Psoriasis. Med Lett Drugs Ther. 2016;58(1494):59-60.13. Soliqua [package insert]. Bridgewater NJ: Sanofi-Aventis LLC. May 2016.14. Davies MJ, Leiter LA, Guerci B et al. Impact of baseline HbA1c, diabetes duration and BMI on clinical
outcomes in the LixiLan-O trial testing iGlarLixi (insulin glargine/lixisenatide titratable fixed-ratio combination) versus insulin glargine and lixisenatide monocomponents. Diabetes Obes Metab. 2017 Apr 22. doi: 10.1111/dom.12980. [Epub ahead of print].
63
64
New Drugs of 2016 Table 1- New drugs of 2016, listed in order of approval date1
Generic Name Brand Name Approval Date Indication Elbasvir (ELB as vir) and Grazoprevir (graz OH pre vir)
Zepatier (ZEP-ah-teer)
1-28-2016 Chronic hepatitis C (HCV) genotypes 1 and 4 infection
Brivaracetam (BRIV a RA se tam)
Briviact 2-18-2016 Partial onset seizures
Obiltoxaximab (oh-bil-tox-AX-i-mab)
Anthim 3-18-2016 Inhalational anthrax
Ixekizumab (IX ee KIZ ue mab)
Taltz 3-22-2016 Moderate to severe plaque psoriasis
Reslizumab (res LIZ ue mab)
Cinqair 3-23-2016 Severe asthma
Defibrotide sodium (de FYE broe tide)
Defitelio 3-30-2016 Hepatic veno-occlusive disease following stem cell transplant
Venetoclax (ven ET oh klax)
Venclexta 4-11-2016 Chronic lymphocytic leukemia in patients with a specific chromosomal abnormality
Pimavanserin (PIM a VAN ser in)
Nuplazid 4-29-2016 Treatment of hallucinations and delusions from psychosis in Parkinson’s disease
Atezolizumab (A te zoe LIZ ue mab)
Tecentriq 5-18-2016 Urothelial type bladder cancer
Daclizumab (dah KLIH zyoo mab)
Zinbryta 5-27-2016 Multiple sclerosis
Obeticholic acid (oh BET i KOE lik AS id)
Ocaliva 5-27-2016 Rare chronic liver disease
Fluciclovine F 18 Axumin 5-27-2016 Diagnostic imaging agent for recurrent prostate cancer detection
Gallium Ga 68 dotatate (GAL-ee-um Ga 68 DOE-ta-tate)
NETSPOT 6-1-2016 Diagnostic imaging agent for rare neuroendocrine tumors
Sofosbuvir (soe FOS bue vir) and Velpatasvir (vel PAT as vir)
Epclusa 6-28-2016 Treatment of all 6 major forms of hepatitis C virus
Lifitegrast (LIF e TEG rast)
Xiidra 7-11-2016 Treat signs and symptoms of dry eye
Lixisenatide (LIX i SEN a tide)
Adlyxin 7-27-2016 Diabetes type 2
Eteplirsen (e TEP lir sen)
Exondys 51 9-19-2016 Duchenne muscular dystrophy
Olaratumab (OH lar AT ue mab)
Lartruvo 10-19-2016 Soft tissue sarcoma
Bezlotoxumab (BEZ loe TOX ue mab)
Zinplava 10-21-2016 Reduce the recurrence of Clostridium difficile infection in adults
Crisaborole (KRIS a BOR ole)
Eucrisa 12-14-2016 Atopic dermatitis in patients two years of age or older
Rucaparib (roo KAP a rib)
Rubraca 12-19-2016 Ovarian cancer
Nusinersen (NUE si NER sen)
Spinraza 12-23-2016 Spinal muscular atrophy
References: 1. United States Food and Drug Administration. Novel Drug Approvals 2016.
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm483775.htm. Accessed January 8, 2017.
Top Related