1. 1
Streptomirus (Streptovancin):
A miracle treatment for Necrotizing Fasciitis
By: Elsa Chen & Tosha Dave
RGA 6201
3/19/2015

2. 2
Table of Content
Executive Summary ------------------------------------------------------------------------------------------3
Necrotizing Fasciitis Background
Unmet Medical Need and Rationale for Innovation of Streptomirus
Summary of Streptovancin Development, Targeted Market
Introduction ----------------------------------------------------------------------------------------------------4
Company Overview ------------------------------------------------------------------------------------------5
Product Development Program -----------------------------------------------------------------------------6
Non-Clinical Studies -----------------------------------------------------------------------------------------6
Animal Pharmacology and Toxicology
Pharmacokinetics
Pharmacodynamics
GLP Statement ------------------------------------------------------------------------------------------------8
Chemistry, Manufacturing, and Controls ------------------------------------------------------------------9
Drug Substance
Drug Substance Manufacturing
Drug Product
Drug Product Manufacturing
Environmental Impact Analysis Report
Packaging Establishment
IND Waiver and Requirement for Orphan Drug Designation ----------------------------------------12
Clinical Trials ------------------------------------------------------------------------------------------------13
Phase I
Phase II
Phase III
Clinical Pharmacology -------------------------------------------------------------------------------------16
Pharmacodynamics
Pharmacokinetics
Label Information -------------------------------------------------------------------------------------------18
Label Design -------------------------------------------------------------------------------------------------19
Post Market Plan --------------------------------------------------------------------------------------------20

3. 3
Executive Summary
Necrotizing Fasciitis Background:
Necrotizing fasciitis (NF) is a severe bacterial infection of skin. It is also known as Flesh- eating
infection or Flesh- eating Bacteria syndrome. NF, the name itself, defines the disease condition;
Necrotizing indicates the necrosis-premature death of cells and Fasciitis is indicator for Fascial
planes-bands of connective tissue (Davis, 2014). The infection initiates in the subcutaneous
tissue and spreads through fascial planes causing ample soft tissue destruction. NF can affect in
any part of body- more commonly the arms, legs, and abdominal wall (Davis, 2014) Patients of
NF may experience fever, chills, skin ulceration or necrotic scars on the skin. Although it can
affect people of any age group, any gender and any ethnicity, people with compromised immune
system (i.e. patients of diabetic, cancer, renal impairment or other chronic conditions) are more
prone to develop this infection. (Necrotizing Fasciitis: A Rare disease, especially for healthy,
2013). According to Center for Disease Control, almost 650-800 cases of NF are reported every
year in the United States (Necrotizing Fasciitis: A Rare disease, especially for healthy, 2013).
The mortality for the infection ranges from 20% to as high as 80% (Edlich, 2014). The total
incidents of NF recorded in the United States are less than 200,000; it falls under the category of
rare diseases under 21 CFR 316 (Orphan Drug Act , 2013).
Unmet Medical Need and Rationale for Innovation of Streptomirus
Few years back, surgical removal of the infectious part of body combined with supplemental
high doses of antibiotics was the only available treatment regimen for NF. In 2014, three other
treatments named Dalvance®, Sivextro® and Orbactiv™ got FDA approval for similar skin
infections. All of these treatments help terminating the disease progression but they do not help
curing the damage already caused to the body. These treatments require a prolonged intravenous

4. 4
infusion (the longest one is 3 hours of infusion) and they take almost 48 to 72 hours to show any
therapeutic effects, after the administration of first dose. In that case patients will be suffering
from so much difficulties at least for two days even after receiving the treatment. In addition,
these treatments share similar profile of side effects including diarrhea, headache, nausea,
abscesses (limb and subcutaneous), vomiting, tachycardia, and infusion site reactions. In a
nutshell, it is necessary to develop a new, more effective and faster acting drug that is also able
to revert the tissue damage happened during the progression of the disease.
Summary of Streptovancin Development
Streptomirus (Streptovancin), a classical fermentation accidently found by two scientists of
Brigham and Women’s Hospital, was proven safer, faster and more effective treatment of NF in
non-clinical studies. Catalent Pharmaceutical Inc. legally took over all the rights over
Streptovancin and developed it further. In two adequate, well-controlled trials confirmed the
efficacy of Streptomirus and presented it a safer and more effective treatment compared to the
other three available treatments.
Targeted Market
NF is affecting people in many different countries of the world. As Streptomirus was a drug for a
rare disease, it falls under the category of the Orphan drug (Orphan drug act 1984). As all the
patients of NF should be benefited from a significantly advanced treatment, Catalent decided to
launch Streptomirus globally. Catalent prepared for both FDA and EMEA Orphan Drug
Designations simultaneously. The priority was set for US market approval.
Introduction
Necrotizing Fasciitis can be caused by many different bacteria including group A Streptococcus
(group A strep), Klebsiella, Clostridium, E. coli, Staphylococcus aureus, and Aeromonas

5. 5
hydrophila (Necrotizing Fasciitis: A Rare disease, especially for healthy, 2013). The most
common cause for NF is Group A Streptococcus bacteria (GAS). The GAS bacteria may enter
human body through an existing cut, lesion, insect bites or followed by a surgery (Necrotizing
Fasciitis (Flesh-Eating Bacteria), 2014). These entry points of bacteria shows signs such as
redness of skin and swelling; subsequent skin changes such as skin ulceration, thin-walled fluid-
filled blisters, black scars, gas formation in tissue and fluid accumulation and draining from the
infection site can occur with the infection progression. In addition, patients may also suffer from
fever and chills. The infection progresses very fast, therefore, early diagnosis and faster
treatment became very necessary. Streptomirus was proven to be safer, faster and more effective
treatment for NF from the analysis of clinical trials and now is approved by FDA for the
treatment of NF as of February 25, 2015.
Company overview
We, Catalent Pharmaceutical Inc. (located at 24 Peachtree Rd., Lexington, MA 02420) are in
high interest of developing treatments for rare diseases. Catalent has its own clinical trial sites,
manufacturing facility and packaging line- all in compliance with ICH guidelines (E6, GCPs)
and FDA regulations (21 CFR 50, 21 CFR 54, 21 CFR 56, 21 CFR 210, 21 CFR 211, 21 CFR
201). All the facilities are registered with FDA. The scientists from Brigham and Women’s
Hospital scheduled a meeting with us in August 2009 to discuss the study results from animal
studies of Streptovancin and request the further development of Streptovancin. After a detailed
review of the animal studies by scientist and microbiology experts, Catalent Pharmaceutical Inc.
agreed to take over the molecule Streptovancin for further development. Catalent took the
complete responsibility to bring Streptovancin to commercial market to benefit the patients of
NF. In order to perform all the necessary process without conflicts, Catalent legally bought all

6. 6
the rights over Streptovancin and collected all the animal- testing data from the laboratory of
Brigham and Women’s Hospital.
Product Development Program
As Streptomirus was a treatment for rare disease, Catalent wanted to go global for the launch of
Streptomirus. As Streptomirus was developed as an Orphan drug, no Investigational New Drug
Application (IND) was required but the Orphan Drug Designation (DO A DESIGNATION: FDA
Orphan Drug Workshop, 2011). Catalent started clinical trials soon after the Streptovancin take
over. After observing therapeutic effects results in Phase 2, Catalent required Orphan Drug
Designation. Under the plan of going global, Catalent filed the request for Orphan Drug
Designation with both the OOPD of FDA - under 21 U.S.C. 360bb, FDCA section 506 and 21
CFR Part 316 and EMEA -under (EC) No 141/2000 and (EC) No 847/2000 (COMMON EMEA
/ FDA APPLICATION FOR ORPHAN MEDICINAL PRODUCT DESIGNATION, 2011).
Catalent got both the approval in July, 2013. In EOP2 meeting, Catalent discussed whether
Streptomirus is eligible for priority review. Catalent submitted a request for priority review in
March 2014 and got positive response from FDA. The Priority review NDA application for
Streptomirus was submitted on September 29, 2014 and just received approval letter on February
25, 2015. Catalent is currently deciding the launch date for Streptomirus in USA. It is also
preparing for marketing authorization application from EU simultaneously. Achieving marketing
approvals from Japan, Australia, China and India will be Catalent’s next step.
Non-clinical Studies (Cubist Pharmaceuticals, Inc., 2014) (Durata Therapeutics Inc., 2014)
All the non-clinical studies were done in Chen’s Laboratory at Brigham and Women’s Hospital
with the help of NIH grants. Animals were used in accordance with the National Institutes of
Health's Guide to the Care and Use of Laboratory Animals, and the study was approved by the

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Bingham and Woman’s Hospital Animal Care Committee. Testing was performed on Swiss
Webster mice (in total 200: 3 sets of 50s and 1 set of 50 as control) and Beagles dogs (in total 24:
3 sets of 6 and 1 set of 6 as control).
Microbiology Testing
Mechanism of Action
The antibacterial activities of Streptovancin are caused by binding with the bacterial plasma
ribosome, inhibit protein synthesis process, eliminate the growth factor for GAS and decrease the
toxin production. Streptovancin alter the selective process of the bacterial cell membrane,
preventing toxins from leaving the cell to cause tissue damage. Streptovancin is bacteriostatic
against group A streptococci.
Mechanism of Resistance
The development of bacterial resistant to Streptovancin has not been observed, either in vitro or
in animal infection experiment.
Interaction with other Antimicrobials
Streptovancin showed synergistic interactions with nafcillin when tested in vitro. Streptovancin
did not show synergistic interactions with the following antibacterial agents: linezolid, rifampin
daptomycin, aztreonam, vancomycin, ketoconazole, and levofloxacin. The clinical significance
of these findings is currently unknown.
Acute and Sub chronic toxicity
Increased level of lever enzyme (ALT, AST) was shown in toxicology studies in mice and dogs
when Streptovancin was administered daily for 20-29 days. Splenic B cells level was
significantly decreased in a two-month immunotoxicology study in mice when Streptovancin
was administered at 45mg/kg/day for 15 consecutive days. Hepatocyte necrosis was observed in

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dogs when Streptovancin was administered at 60mg/kg/day for 25 consecutive days. The
relationship between these findings in the animal toxicology studies after 16 and 25 consecutive
dosing days to the indicated clinical dose are unclear. Animal toxicology testing are in
compliances with ICH S4, and 21 CFR part 58.
Genotoxicity
Streptovancin was tested negative in all in vitro tests in mouse bone marrow micronucleus
assays. All Genotoxicity testing were conducted with compliance of ICH S2.
Reproductive toxicology
In a fertility study, Streptovancin had no adverse effects on the fertility at a dose of 24mg/kg/day
in mice. Reduction of fertility in male and female mice were observed at a dose of 48mg/kg/day,
signs of parental toxicity were also observed at this dose. All testing were conducted in
compliances with ICH S5, and 21 CFR part 58.
Drug Interaction
No potential drug interactions were identified. Nonclinical studies demonstrated that
Streptovancin is not a substrate, inhibitor, or inducer for hepatic CYP450 enzymes.
Streptovancin pharmacokinetics was not affected by co-administration with known CYP450
substrates, inducers, or inhibitors, or by individual medications.
Carcinogenicity
Long-term carcinogenesis studies have not been conducted with Streptovancin, in accordance
with ICH S1B.
GLP Statement
Catalent Pharmaceuticals Inc., 24 Peachtree Rd., Lexington, MA 02420, has been inspected by
the FDA and has been found to be in compliance to OECD Principles of Good Laboratory

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Practice (GLP) valid from January 1, 2010 to December 31, 2015. The FDA recognizes and
confirms that the test facility is able to conduct studies in compliance with the OECD principles
of GLP.
Chemistry, Manufacturing, and Controls (Cubist Pharmaceuticals, Inc., 2014) (Durata
Therapeutics Inc., 2014)
The CMC section is to summarize our product and manufacturing method, to demonstrate that
Streptovancin is a safe and effective new drug to treat necrotizing fasciitis caused by GAS. This
section is development in accordance with current GMP guidance by the FDA, also complied
with ICH guideline Q6B, Q7, Q8, Q9, and Q10. Stability testing is done during the
manufacturing process according to 21 CFR 312.23, ICH guideline Q1A (R2), Q5C, and Q1E.
Final product release criteria testing are performed on each lot of product manufactured in
accordance with 21 CFR 211.165.
Drug Substance
The chemical name and Structure of Streptovancin are shown below:
Structure

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Chemical name
4,34-dichloro-26-demethyl-42deoxy-72-O-glucopyranuronosy-6-[(methylundecanoy)propyl]-43-
N-carbamoy-3 oxxoxazolidin-8-methyl-tetrachlorophosphate-5-Benzodiaciglucan-37
hydrochloride
Chemical Formula and Molecular Weight
C162H206O26N17Cl11P, 3220 g/mol
Physical Description
Streptovancin is a crystal white powder; it has a sweet and fruity odor, odor threshold is
6,42PPM. The taste threshold in water is 70 mg/l. It has a density of 16.4g/cm3
, boiling point at
32o
C, and a melting point at 152o
C.
Drug Substance Manufacturing
Catalent Pharmaceuticals, Inc. is the manufacturer of Streptovancin. Catalent Pharmaceuticals is
functioning in compliance with current GMP guidance published by the FDA, and ICH Q7.
Streptovancin is a product from fermentation of the N. vaccinii species of the Streptococcus
bacteria. N. vaccinii is a plant pathogen; they were collected from blueberry plants in the wild,
screened, identified, and sterile by the scientist, then cultivated in the manufacturing facility.
Once the bacteria are collected, a fermentation process is done by mixing the bacteria with
alcohol and 78% concentration of CO2, then store in a fermentation box with a constant
temperature of 140o
F (60o
C) for 5 days. After the fermentation period, we have a sterilization
process, and then we have our product, Streptovancin. The harvesting stage takes approximately
10 days, including the collection of the bacteria and the fermentation process.
Drug Product

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The finished dosage form of Streptovancin is a sterile white powder, Edetate disodium (EDTA)
and sodium hydroxide is added with Streptovancin in the package to pH adjustment.
Drug Product Manufacturing
After collecting the Streptovancin, Edetate disodium (EDTA) and sodium hydroxide is added to
the mixture, then sterilized with Ethylene oxide before individual packaging. For every 40 mg of
Streptovancin, 1.5 mg of EDTA and 0.4 mg of sodium hydroxide is added for pH adjustment.
Every vial of Streptomirus contains a total of 41.9 mg of Streptovancin mixture.
Environmental Impact Analysis Report
In accordance with Guidance for Industry: Environmental Assessment of Human Drugs and
Biologics Applications, Catalent Pharmaceuticals Inc. has filed an NDA pursuant to section
505(b) of the Federal Food, Drug, and Cosmetic Act for Streptomirus (Streptovancin), 40 mg,
packaged in single-use vials. An EA has been submitted in pursuant to 21 CFR part 25.
Streptomirus is treatment drug for necrotizing fasciitis; it is intended to be used in hospitals and
clinics by healthcare professionals, disposal methods for Streptomirus are determined by the end
users’ policy for drug product.
Packaging Establishment
Packaging – Content, Quality, and Net Weight
Each box of Streptomirus contains 12 vials of Streptovancin; each vial includes 41.9 mg of
Streptovancin mixture (equivalent to 40 mg of Streptovancin). The net weight of the one
Streptomirus box is 760g.
Shelf Life
The shelf life for Streptomirus is two years in original package.
Container Closure System

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Streptovancin are stored and sealed in single dose glass fliptop vials after production to prevent
contamination. The fliptop vials have three layer of protection: rubber seal with the glass
container, an aluminum foil layer on top, then the plastic fliptop lid. To open the vial, first
remove the plastic lid, it will peel off the center of the aluminum foil, thus exposing the rubber
seal for needle puncture.
Storage Condition
Unreconstituted Streptomirus (Streptovancin) should be stored at 25o
C (77o
F); excursions
permitted to 15 to 30o
C (59 to 86o
F). Package should avoid prolong exposure to direct sunlight.
Streptomirus should not be stored in areas that are higher than 60% in humidity.
IND Waiver and Requirement for Orphan Drug Designation
Catalent was not required to submit an IND application as Streptovancin was to be developed as
Orphan drug and all the clinical trials were conducted within borders of Massachusetts. Even
though IND submission was not required, it did not change other standard protocols and
regulations for clinical research and NDA submission. Catalent was required to request for
Orphan Drug Designation under 21 CFR 316 before the marketing approval. According to 21
CFR 316.20 and 21 CFR 316.21, Orphan Drug Designation request includes some clinical safety
and efficacy data; Catalent waited to get some data from Phase 2 trials.
Under the plan of going global, Catalent filed the request for Orphan Drug Designation with both
the OOPD of FDA - under 21 U.S.C. 360bb, FDCA section 506 and 21 CFR Part 316 and
EMEA -under (EC) No 141/2000 and (EC) No 847/2000 (COMMON EMEA / FDA
APPLICATION FOR ORPHAN MEDICINAL PRODUCT DESIGNATION, 2011). Catalent
got both the approval in July, 2013.

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Clinical Trials
All the clinical trials were performed at Catalent’s clinical sites, it was Catalent’s primary
responsibility to protect the rights, safety and welfare of the subjects participating in clinical trial
under 21 CFR 312.50. Catalent submitted the clinical study protocol, Informed Consent Forms
and Investigator’s Brochure to the IRB (following all the regulations under 21 CFR 56) for
review. Catalent did not start the subject enrollment until the study protocol got IRB approval
(21 CFR 312.50). Informed Consent Forms were explained in detail to the participants of the
clinical trials; participants were given sufficient time to discuss with family member before
signing the ICFs. Signed ICFs were collected before any clinical study and submitted to
following the 21 CFR 50 Subpart B. Catalent also examined whether all the investigators
involved in clinical study were adequately qualified and certified (21 CFR 312.50). All the
investigators had to sign Form FDA 1572 for the financial disclosures before the end of clinical
trials, the Forms were submitted to FDA (21 CFR 54.4). All clinical trial information and the
SAEs were recorded in accordance with 21 CFR 312.60. Everything was performed in
compliance with ICH guideline M3 (R2) and E6.
Phase I
Phase 1 clinical trials were performed under ICH guidelines M3 (R2) and E6, 21 CFR 50, 21
CFR 54, 21 CFR 56.
Total of 56 [45 Adults (Age 21 to 45) and 11 geriatric patients (age 65 and over)] Healthy
volunteers were tested for acute and repeated dose toxicity for 10 consecutive days with a
maximum daily dose of 300mg. The reasons behind choosing geriatric patients were: (1) they
represent a larger part of US population and most of them have compromised immune system,
ultimately they are more susceptible for NF. (2) Most of the geriatric patients are already on

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other medication for chronic diseases such as diabetes, hypertension, and rheumatoid arthritis; by
enrolling them in clinical studies, drug-drug interactions could be studied passively, if any.
Results: The No Observed Adverse Effect Level (NOAEL) observed at 240mg per day. Minor
metabolites of Streptovancin found in Urine of all volunteers. Nausea, vomiting and minor
dizziness were observed in 90% of patients but no other significant adverse reactions were
recorded. Streptovancin showed sufficient results to prove the safety of the drug in healthy
Volunteers.
Patient enrollment details for Phase II and Phase III trials are shown in Table 1.
Table 1. Patient enrollment details for Phase II and Phase III trials
Phase of clinical trial Phase II Phase III
Study Design Randomized Adequate, well-controlled
Total Enrollment 220 1614
Eligibility criteria Inclusion criteria:
Diagnosis of Necrotizing
Fasciitis
Age ranged from 21 to 75
Exclusion criteria:
Pregnancy
Severe systemic disease
Inclusion criteria:
Diagnosis of Necrotizing
Fasciitis
Age ranged from 21 to 75
Exclusion criteria:
Pregnancy
Severe systemic disease
Gender Both (125 men, 95 women) Both (887 men, 727 women)
Age 21 to 75 21 to 75
Ethnicity: Caucasian
African American
Asian
Hispanic/ Latino
198
7
15
0
1253
87
239
35
Phase II
Phase II Clinical trials were performed in compliance with ICH Guideline E4, E6 and E8.
In two randomized trials, 110 patients were tested for single-dose (IV injection) toxicity studies
and 110 patients were tested for multi-dose regimen (IV injection) with total dose ranging from

15. 15
200mg to no greater than 300mg per day at different time intervals. The efficacy endpoint was to
study no increase in the skin lesion in the patients of Necrotizing Fasciitis.
Results: The patients who were administered with multi-dose regimen of Streptovancin showed
better results; no increase in skin lesion was observed after 25-29 hours. The patients with single-
dose administration showed a little increase in skin lesion after 15 hours of administration.
Higher percentage of adverse events of nausea, dizziness, diarrhea and vomiting were observed
as side effects of Streptovancin. Blurred vision was observed in some patients.
Phase III
This clinical trial was performed under ICH Guidelines E4, E6, E8, E9, and E10. Dose selection
was done in compliance with ICH guideline S1C (R2).
Two adequate, well-controlled trials were performed; 941 patients were treated with
Streptovancin and 673 patients were treated with comparison treatment of Sivextro, Dalvance
and Orbactiv. The primary endpoint of the study was to see no increase in the skin lesion after
the first day and the secondary endpoint was to observe 30% decrease in skin lesions.
Results: Best dosing regimen analyzed was IV injection of 40mg of Streptovancin, every 4 hours
for a day followed by 40mg of Streptovancin IV injection twice a day for 3 days. No increase in
skin lesion after first day and 35%-40% decrease in skin lesions after 48-55 hours depending on
the severity were observed.
During the entire clinical study, 2 patients withdrawal from adverse events (extreme vomiting
and diarrhea) from Streptovancin were recorded and 7 patients dropped from the side effects of
comparative treatments. Follow-up with those patients was performed according to ICH E6.

16. 16
Clinical Pharmacology (Cubist Pharmaceuticals, Inc., 2014) (Durata Therapeutics Inc., 2014)
Pharmacokinetics
Streptovancin pharmacokinetic parameters have been characterized in healthy subjects and
patients. All testing were conducted in compliance with ICH S7A. Pharmacokinetic parameters
following administration of Streptovancin following intravenous administration of 40mg every 4
hours for the first 24 hours are shown in Table 2.
Table 2. Mean (Standard Deviation) Streptovancin Pharmacokinetic Parameters Following
Multiple Intravenous Administration of 40mg Every 4 hours For the First 24 Hours
Pharmacokinetic Parameters of
Streptovancinv
Intravenous Injection
Steady State
Cmax (mcg/mL) 3.5 (0.8)
Tmax (hr)✚
2.5 (1.0-8.5)
AUC (mc hr/mL)¤
30.2 (7.4)
CL or CL/F (L/hr) 7.3 (3.5)
v
Cmax, maximum concentration; Tmax, time to reach Cmax; AUC, area under the concentration-
time curve; CL, systemic clearance; CL/F, apparent oral clearance
✚
Median (range)
¤
AUC is AUC0-∞ (AUC from time 0 to infinity) for first day doses administration and AUC0-24
(AUC from time 0 to 24 hours) for multiple-dose administration
Absorption
Peak concentration reached at the end of the first intravenous injection of Streptovancin.
Concentration-time profile suggested one does of 40mg every 4 hours for the first 24 hours,
followed by 40mg twice a day for 3 days. Streptovancin is formulated for intravenous injection;
the bioavailability for this administration is 100%.
Distribution
Streptovancin is reversibly bound to human plasma proteins, approximately 93-97%. The mean
steady state volume of distribution of Streptovancin in healthy adults following six doses 40mg
injection ranged from 75 to 87 L (approximately twice total body water). The mean

17. 17
concentrations of Streptovancin achieved in skin blister fluid remain above 25mg/L up to 4 days
post dose.
Metabolism
A minor metabolite of Streptovancin (benzozolin) was observed in the urine of healthy subjects.
There was no degradation of Streptovancin observed in human liver microsomes; Streptovancin
is not a substrate, inhibitor, or inducer for hepatic CYP450 enzymes. No other significant
circulating metabolites were found in humans.
Excretion
Following administration of 40mg of Streptovancin every 4 hours for the first 24 hours in
healthy subjects, 60% of the doses were eliminated via the liver, 25% of the doses were excreted
in urine. Most of the elimination process occurs within 104 hours after injection.
Pharmacodynamics
The antibacterial activity of Streptovancin appears to best correlate with the ratio of area under
the concentration-time curve to minimal inhibitory concentration (AUC/MIC) for Group A
Streptococcus based on animal models of infection. An exposure-response analysis of a single
study in patients with complicated skin and skin structure infections supports the 40mg per dose,
12 continuous doses regimen. All testing were conducted with compliance of ICH S7A and ICH
M3.
Cardiac
Electrophysiology
In
a
randomized,
positive-­‐
and
placebo-­‐controlled
crossover
thorough
QT/QTc
study,
56
enrolled
healthy
subjects
received
a
therapeutic
dose
of
Streptovancin
240mg,
supratherapeutic
dose
of
Streptovancin
300mg,
and
placebo.
No
significant
effects
of

18. 18
Streptovancin
on
heart
rate
or
electrocardiogram
morphology
were
shown.
Streptovancin
does
not
have
any
clinical
relevant
adverse
effect
on
cardiac
repolarization.
Label information (Cubist Pharmaceuticals, Inc., 2014) (Durata Therapeutics Inc., 2014)

19. 19
Label Design
Principal Display Panel
NDC 01869-040-01
Streptomirus
(Streptovancin) for injection
40 mg per vial
For Intravenous Injection Only
Sterile Single Dose Vial
12 Vials

20. 20
Post Market Plans
No pediatric study was performed because Streptomirus, being an Orphan Drug, is exempt from
the pediatric study according to the regulation of PREA.
All the data collection extent will be decided with the help of FDA Draft Guidance: Guidance for
Industry: Determining the Extent of Safety Data Collection Needed in Late Stage Premarket and
Postapproval Clinical Investigations, published in February 2010.
Adverse events will be reported to MedWatch by physicians and the general public under 21
CFR 314.80 and 21 CFR 314.81.
We are about to submit marketing approval application for EU; we are also planning to get
marketing approval from Japan, China, India, and Australia.

21. 21
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A
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