FDA Approvals: CYLTEZO

FDA BRIEF: Week of August 21, 2017

FDA approved

Image result for CYLTEZO logo

CYLTEZO (adalimumab-adbm)

Boehringer Ingelheim Pharmaceuticals, Inc.


  • Rheumatoid Arthritis (RA): reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.
  • Juvenile Idiopathic Arthritis (JIA): reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older.
  • Psoriatic Arthritis (PsA): reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis.
  • Ankylosing Spondylitis (AS): reducing signs and symptoms in adult patients with active ankylosing spondylitis.
  • Adult Crohn’s Disease (CD): reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
  • Ulcerative Colitis (UC): inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine or 6-mercaptopurine (6-MP).
  • Plaque Psoriasis (Ps): the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate.


  • Second Biosimilar to Humira
  • Highly similar to reference product (Humira) with no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products
  • Several deferred pediatric asessments

Information on Biosimilars


Image Credit: Boehringer Ingelheim



FDA News and Views: Early Feasibility Studies, Pediatric Opioid Medications for Cough, Medication Use during Pregnancy

FDA Brief: Week of August 21, 2017


Early Feasibility Studies and Investigation Device Exemption

Early Feasibility Studies (EFS) Program provides opportunities to gain early clinical experience with innovative technology

  • enrolls small number of subjects
  • is used to evaluate the device design concept with respect to initial clinical safety and device functionality
  • may guide device modifications

CDRH’s  efforts to streamline the clinical trial initiative


Have a Baby or Young Child With a Cold? Most Don't Need Medicines

 FDA is carefully evaluating prescription opioid medications approved to treat cough in children

Vital to understand potential complications in children using opioid-containing medications, even according to labeled instruction

  • Added contraindication to drug labels alerting that codeine should not be used for any reason, including treatment of cough, in children younger than 12 years

Pediatric Advisory Committee scheduled on Sep 11th will focus on

  • use of prescription opioid products containing hydrocodone or codeine for the treatment of cough in pediatric patients
  • current treatment practices
  • benefit-risk considerations
  • help inform Agency’s decision-making processes related to these medications

Additional efforts:

  • tips for consumers on how to safely treat a child’s cold
  • funding research to develop comprehensive, consumer-centered approaches on best practices for the safe use of pediatric cough and cold medications


Pregnancy Research

Working to Improve Information on Medication Use during Pregnancy

Very few prescription medications specifically approved for use during pregnancy

  • About half of the 6.3 million preganant women/year take at least one medication

Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC)

  • Established by the 21st Century Cures Act
  • Research aimed at optimizing therapies for pregnant women and nursing mothers
  • Led by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Labeling requirements for the pregnancy and lactation subsections

  • Implemented in 2015
  • Provided framework for clearly communicating benefits/risks
  • Removed the decades-old pregnancy category letter system

Pregnancy research initiatives

  • Led by Office of Women’s Health
  • Using predictive modeling to anticipate response to drug
  • Understand safety, efficacy and effects of products e.g.  vaccine safety, MRI effects, drug toxicity

Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP)

  • Research collaboration between FDA, academia and health insurers
  • Learn  about medication effects by linking healthcare records for moms and babies
  • Epidemiologic study to evaluate effect of prescription opioids

Real-World Research and Safety Monitoring

  • Pregnancy Registry
  • Pregnancy outreach activities


Image credit: FDA


FDARA & User Fees


FDARA and FDA User Fee Programs

President signed into law the Food and Drug Administration Reauthorization Act (FDARA)

  • Revises and extends FDA’s user-fee programs for prescription drugs (PDUFA), medical devices (MDUFA), generic drugs (GDUFA) and biosimilar (BsUFA) products
  • Provides FDA resources for increasing regulatory efficiency and expedite availability of innovative, safe and effective medical products
  • Read how FDARA is making a difference

Drug User Fees


Medical Device User Fees






FDA BRIEF: Week of  August 14, 2017

FDA approved

Lynparza logo

LYNPARZA (olaparib) tablets


INDICATION FOR USE: Maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy

ADDRESSING UNMET NEED: Addition of new indication and new formulation (tablet)


  • Initial approval of capsule formulation in 2014 for the treatment of BRCA-mutated advanced ovarian cancer
  • New tablet formulation also approved for this indicaiton and new indication
  • Tablets and capsules are not interchangeable; capsules will be phased out of market and will be available only through Lynparza Specialty Pharmacy Network
  • Postmarketing commitments:  progression-free survival (PFS) and molecular characteristics,  overall response rate (ORR) and duration of response (DOR) from ongoing clinical studies 

MECHANISM OF ACTION: Inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes that are involved in DNA transcription and DNA repair


  • Two randomized, placebo-controlled, double-blind, multicenter studies, n=295, 265, patients with recurrent ovarian cancers who were in response to platinum-based therapy
  • Major efficacy outcome: Investigator-assessed PFS evaluated according to RECIST, version 1.1.
  • Study 1 (recurrent germline BRCA-mutated cancer): Estimated median PFS was 19.1 vs. 5.5 months (olaparib vs. placebo),  p<0.0001)
  • Study 2 (regardless of BRCA status):  Median PFS was 8.4 months vs. 4.8 months, p<0.0001


  • Most common adverse reactions: Anemia, nausea, fatigue (including asthenia), vomiting, nasopharyngitis, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and stomatitis
  • Most common laboratory abnormalities: Decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, decrease in leukocytes, decrease in absolute neutrophil count, increase in serum creatinine, and decrease in platelets


Image for trademark with serial number 86916876

BESPONSA (inotuzumab ozogamicin) for injection


INDICATION:  Treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)


  • 5,970 in United States will be diagnosed with ALL in 2017; ~1,440 will die from disease
  • Low life expectancy for B-cell ALL patients with nonresponsive / relapsed cancer
  • New, targeted treatment option

REG PATHWAY: BLA, Orphan drug designation, Priority Review, Breakthrough Therapy

  • Postmarketing requirements: Characterize toxicity after hematopoietic stem cell transplantation (HSCT) in adult and pediatric patients, randomized trial in patients with relapsed or refractory acute lymphoblastic leukemia, Bioburden and endotoxin test method qualification

MECHANISM OF ACTION:  CD22-directed antibody-drug conjugate (ADC), is a cytotoxic agent covalently attached to antibody via linker. Anticancer activity due to binding of the ADC to CD22-expressing tumor cells


  • Randomized (1:1), open-label, international, multicenter study in patients with relapsed or refractory ALL, n= 326, BESPONSA vs.  Investigator’s choice of chemotherapy
  • Efficacy: Complete Response (CR), duration of remission (DoR) and Overall Survival



  • Boxed warning: Severe liver damage (hepatotoxicity), including blockage of veins in the liver
  • Other serious side effects: Myelosuppression, infusion-related reactions, QT interval prolongation, reproductive toxicity
  • Common side effects:  Thrombocytopenia, neutropenia, leukopenia, infection, anemia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, liver damage, abdominal pain, hyperbilirubinemia


Image credit: AstraZeneca, Pfizer

FDA News and Views: Prescription Drug Advertising, Tools for Zika

FDA BRIEF: Week of August 14, 2017

Be Smart About Prescription Drug Advertising: A Guide for Consumers

Content of Risk Information in the Major Statement in Prescription Drug Direct-to-Consumer Broadcast Advertisements

Prescription Drug Advertising regulations require direct-to-consumer (DTC) advertisements with product claims include information on  major side effects and contraindications

  • Called the major statement
  • Also provide adequate provision for dissemination of approved package labeling
  • FDA issued Guidance

FDA interested in ensuring advertisements provide clear and useful information

  • Concern that major statement not fulfilling purpose
  • Too long, minimization of important risk information, therapeutic noncompliance caused by fear of side effects

Office of Prescription Drug Promotion (OPDP), CDER,  investigating effectiveness of a limited risks plus disclosure strategy

  • Limiting  major statement to those that are severe (life-threatening), serious, or actionable
  • Disclosure that  other product risks not included in the advertisement
  • Present fair balance of risk information and avoid misleading presentation on  risk-benefit profile
  • Requesting comments on Federal Register notice

Federal Register notice

FDA In Brief

ZikaNew FDA tools for development and proper evaluation of tests for detecting Zika virus infection

FDA has made available a panel of human plasma samples for regulatory evaluation of serological tests to detect recent Zika virus infection

  • FDA worked with manufacturers to encourage development of diagnostic tests
  • Ensure they were available using Emergency Use Authorization (EUA)

Two primary blood diagnostic tests

  • Nucleic acid tests: Identify infection by confirming  virus’ RNA
  • Serological tests: Identify antibodies produced by body’s immune system upon Zika detection
  • Development of tests challenging because Zika antibodies produced by the body difficult to differentiate from other related virus antibodies (dengue, West Nile)

FDA’s sample panel

  • Plasma samples from individuals infected with Zika, West Nile, or dengue
  • Diagnostic developers use to check if test can distinguish Zika vs. others
  • Also use to compare test vs. other Zika tests approved via EUA
  • Available to developers who have interacted with the FDA through the pre-EUA process and have devices in final stages of validation


Image credit: FDA












FDA News and Views: Software PreCert Pilot, Medical Device Tool Development, GUDID Data Quality, China joins ICH

FDA BRIEF: Week of August 7, 2017

Software Precertification Pilot program

Part of Digital Health Innovation Acton Plan,  conforming to software
provisions of the 21st Century Cures legislation

  • Voluntary program for medical device software manufacturers
  • Need to demonstrate Culture of Quality and Organizational Excellence (CQOE)

Pre-Cert status allows

  • Ability to get software to market faster
  • Iterate based on real world experience
  • Have regulatory predictability

FDA Goals

  • Modern and efficient regulatory framework
  • Easy to obtain and maintain FDA Pre-Cert
  • High quality, safe and effective software throughout product life
  • Enable companies to demonstrate CQOE and measure Key Performance Indicators
  • Enable scalability, variation and evolution of software development
  • Learn and adapt based on program effectiveness


Collage; 1st picture is cross section of a human head; 2nd is a body with skeleton showing; 3rd is hand holding a blood pressure meterMedical Device Tool Development (MDDT)

MDDT program for qualification of tools for medical device sponsors in the development and evaluation of medical devices

  • Promotes innovation in medical device development
  • Bridge gap between research of devices and the delivery of devices to patients

‘Qualification’ based on FDA evaluation of  evidence that

  • tool produces scientifically-plausible measurements
  • works as intended within the specified context of use

Context of Use

  • tool or product area
  • specific output or measure
  • role in device development
  • applicable phases of device development


  • Clinical outcome assessment
  • Biomarker test
  • Nonclinical assessment model


Final Guidance

Optimizing GUDID Data Quality

The Global Unique Device Identification Database (GUDID)

  • FDA database to serve as a reference device catalog device with an identifier
  • Labeler of each medical device labeled with a unique device identifier (UDI) must submit information concerning that device to the GUDID
  • UDI integration from manufacturing through supply chain to patients,electronic health records (EHRs) and registries

FDA’s Focus on GUDID Data

  • Acceptable quality to realize public health benefits
  • Accuracy and completeness of data
  • Engage with stakeholders to optimize data quality and utility


Group photo from trip to China


China Joins ICH in Pursuit of Global Harmonization of Drug Development Standards

By: Theresa M. Mullin, Ph.D., Director of FDA’s Office of Strategic Programs, CDER

Drug development is a global endeavor

  • Requires consistent standards adopted and adhered to global drug makers and regulatory authorities

FDA meeting with China Food and Drug Administration (CFDA)

  • CFDA joins the existing International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)
  • Currently includes eight regulatory authorities and six industry associations from across the globe

Steps taken by CFDA

  • Implemented reforms to align China’s regulations with global standards
  • Reformed drug review system, dedicated additional resources, implemented ICH Guidelines
  • Will visit FDA to continue conversation on regulatory modernization


Image credit: FDA



FDA BRIEF: Week of July 31, 2017




Safe Obstetrics Systems, Ltd

INDICATION FOR USE: To elevate the fetal head and facilitate delivery of the fetus in
women requiring a Caesarean Section at full dilation or those requiring a Caesarean
Section after a failed instrumental vaginal delivery. Fetal Pillow is indicated for use at a
gestational age ≥37 weeks.

REG PATHWAY: De Novo request

  • Regulation Number: 21 CFR 884.4350
  • Regulation Name: Fetal head elevator
  • Regulatory Classification: Class II
  • Product Code: PWB

GENERIC DEVICE TYPE: Fetal head elevator

  • prescription device consisting of a mechanism that elevates the fetal head to facilitate delivery during a Caesarean section


  • Adverse tissue reaction: Biocompatibility evaluation
  • Infection: Sterilization validation, Shelf life testing, Labeling
  • Fetal injury due to device failure: Non-clinical performance testing, Shelf life testing, Labeling
  • Maternal injury due to device failure: Non-clinical performance testing, Shelf life testing, Labeling
  • Use error: Labeling


  • Biocompatibility, Performance data, Non-clinical performance data, Labeling



Quantitation of Organophosphate Metabolites in Urine by LC/MS/MS

Centers for Disease Control and Prevention (CDC)

INTENDED USE/INDICATION FOR USE: Quantitation of specific organophosphate metabolites by LC/MS/MS. The device system includes organophosphate metabolite calibrators to calibrate the system and organophosphate metabolite controls for quality control monitoring of the system. This device is intended for use in a single laboratory to detect and measure the concentration of specific
organophosphate metabolites in human urine from individuals who have signs and
symptoms consistent with cholinesterase poisoning. The data obtained by this
device will be used following an exposure or suspected exposure event to confirm
exposure, identify the causative agent, and distinguish exposed from the
unexposed patients.

REG PATHWAY: De Novo request

  • Regulation Number: 21 CFR 862.3652
  • Regulation Name: Organophosphate Test System\
  • Regulatory Classification: Class II (special controls)
  • Product Code: PDY

GENERIC DEVICE TYPE:  Organophosphate test system

  • intended to measure organophosphate metabolites quantitatively in human urine from individuals who have signs and symptoms consistent with cholinesterase poisoning. The data obtained by this device is intended to aid in the confirmation and investigation of organophosphate exposure


  • Internal standards for calibrators and quality control materials
  • Solid phase extraction cartridge initially used to extract metabolites
  • Separation and analysis on a tandem mass spectrometer and HPLC system


  • Analytical Performance: Precision/Reproducibility, Linearity/assay reportable range, Traceability, Stability, Expected values, Detection limit, Analytical specificity


  • False Positive, False Negative, Public Health Risk from Incorrect Test Results: Limited distribution, analytical testing


  • Limited distribution to laboratories with experienced personnel
  • Analytical testing for performance characteristics


FDA approved

STELLAREX 0.035” OTW Drug-Coated Angioplasty Balloon

Spectranetics Corporation

INDICATION FOR USE: For percutaneous transluminal angioplasty (PTA), after appropriate vessel preparation, of de novo or restenotic lesions up to 180 mm in length in native superficial femoral or popliteal arteries with reference vessel diameters of 4-6 mm


  • Classification: III
  • Device Procode: ONU


  • Sterile, single-use, over-the-wire (OTW) device/drug combination product
  • Base PTA Catheter: Percutaneous transluminal angioplasty balloon catheter uses mechanical force of balloon expansion across a lesion to establish patency
  • Drug Coating: Paclitaxel incorporated in an excipient, to serve as an adjunct to the mechanical action of balloon angioplasty and assist in maintaining long term vessel patency post-procedure


  • Prospective, randomized, multi-center, singleblind study, Stellarex 035 DCB vs. standard balloon angioplasty (PTA)
  • Primary effectiveness endpoint: Primary patency at 12 months
  • 76.3% in the DCB group vs. 57.6% in the PTA group (p=0.003)
  • Secondary effectiveness endpoints, including target lesion revascularization (TLR) showed favorable results


  • Primary Safety Composite: 12-month freedom 92.1% (DCB) vs. 83.2% (PTA), p=0.0246
  • No significant safety signal on rare or long-term adverse device or drug effects.



TaqPath™ Zika Virus Kit (ZIKV)

Thermo Fisher Scientific


Real-time RT-PCR test intended for the qualitative detection of RNA from the Zika virus in serum and urine (collected alongside a patient-matched serum specimen) from individuals meeting CDC Zika virus clinical criteria (e.g., clinical signs and symptoms associated with Zika virus infection) and/or CDC Zika virus epidemiological criteria (e.g., history of residence in or travel to a geographic region with active Zika transmission at the time of travel, or other epidemiologic criteria for which Zika virus testing may be indicated), by laboratories in the US  certified under CLIA

REG PATHWAY: Emergency Use Authorization

DEVICE DESCRIPTION: Lyophilized real-time reverse transcription polymerase chain reaction (rRT-PCR) assay for the qualitative detection of RNA from Zika virus in human
serum, urine (collected alongside a patient-matched serum specimen), and other authorized specimen types


Image Credit: Safe Obstetrics Systems, CDC, Spectranetics




FDA BRIEF: Week of July 31, 2017

FDA approved

IDHIFA (enasidenib)

Celgene Corp

Abbott RealTime IDH2

Abbott Molecular Inc.

INDICATION: Treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.

Approved for use with a companion diagnostic, the RealTime IDH2 Assay, to detect specific mutations in the IDH2 gene in patients with AML.


  • Orphan Drug Designation, Priority Review
  • Postmaketing requirements: Characterization of long-term safety in AML, Cllinical PK studies for CYP interaction, hepatic impairment
  • Companion Diagnostic: Somatic Gene Mutation Detection System

MECHANISM OF ACTION:  Inhibitor of the isocitrate dehydrogenase 2 (IDH2) enzyme, decreasing 2-hydroxyglutarate (2-HG) levels, reduced blast counts and increased percentages of mature myeloid cells


  • Open-label, single-arm, multicenter, two-cohort clinical trial, n= 199,  patients with relapsed or refractory AML and IDH2 mutation (confirmed by RealTime IDH2 Diagnostic)
  • Endpoint: Rate of complete response (CR)/complete response with
    partial hematologic recovery (CRh), duration of response (DOR), rate of conversion from transfusion dependence to transfusion independence


  • Boxed Warning: Differentiation syndrome-can be fatal if not treated
  • Common side effects: Nausea, vomiting, diarrhea, increased levels of bilirubin (substance found in bile) and decreased appetite. Women who are pregnant or breastfeeding should not take Idhifa because it may cause harm to a developing fetus or a newborn baby



VYXEOS (liposome-encapsulated combination of daunorubicin and cytarabine)

 Jazz Pharmaceuticals, Inc.

INDICATION: Treatment of adults with newly-diagnosed therapy-related acute
myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC)

ADDRESSING UNMET NEED:  First FDA-approved treatment specifically for patients with t-AML or AML-MRC.

REG PATHWAY: NDA,  505(b)(2) pathway

  • Orphan designation, Priority review
  • Postmarketing requirements: Characterize nature, incidence, severity of infusion-related reactions,  determine appropriate in patients with renal impairment

MECHANISM OF ACTION:  Daunorubicin has antimitotic and cytotoxic activity and  Cytarabine is a cell cycle phase-specific antineoplastic agent


  • Randomized, multicenter, open-label, active-controlled study, n=309,  VYXEOS to a standard combination of cytarabine and daunorubicin (7+3), patients  with newly diagnosed t-AML or AML-MRC
  • Endpoint:  Overall survival from the date of randomization to death
    from any cause
  • 9.6 months vs. 5.9 months, p=0.005


  • Most common adverse reactions:  Hemorrhage events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders and vomiting


IMBRUVICA (ibrutinib) capsules

 Pharmacyclics LLC

EXPANDED INDICATION:  Treatment of adult patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy


  • cGVHD is life-threatening;  occurs in 30-70% patients who receive HSCT
  • This is the first FDA-approved therapy for the treatment of cGVHD


  • Priority Review,  Breakthrough Therapy, Orphan Drug Designation
  • Previously approved for certain indications in treating chronic lymphocytic leukemia, Waldenström’s macroglobulinemia and marginal zone lymphoma, as well as under accelerated approval status for mantle cell lymphoma


  • Open-label, multi-center, single-arm trial, n=42, patients with cGVHD after failure of first line corticosteroid therapy and requiring additional therapy
  • Endpoint: Best Overall Response Rate (ORR) and Sustained Response Rate based on Investigator Assessment
  • ORR: 28 (67%), Sustained Response Rate 20 (48%)


  • Serious side effects: Severe hemorrhage, infections, cytopenia, atrial fibrillation, hypertension, second primary malignancies, tumor lysis syndrome. May harm developing fetus or newborn
  • Common side effects: Fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, stomatitis, nausea, hemorrhage, anemia and pneumonia


MAVYRET (glecaprevir and pibrentasvir) tablet

AbbVie Inc.


  • Treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A)
  • Treatment of adult patients with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor (PI), but not both


  • 2.7 to 3.9 million people in US have chronic HCV
  • First eight week treatment duration; provides a shorter treatment duration for many patients
  • Treatment option for certain patients with genotype 1 infection, the most common HCV genotype in US


  • Required pediatric assessment
  • Postmarketing commitments: Reports form ongoing studies, study in  HCV
    genotype 1,  phenotypic effect of the NS3/4A or NS5A substitutions

MECHANISM OF ACTION:   Fixed-dose combination of glecaprevir and pibrentasvir, which are direct-acting antiviral agents against  HCV


  • Several clinical trials, n=2,300 adults with genotype 1, 2, 3, 4, 5 or 6 HCV infection without cirrhosis or with mild cirrhosis, 12 or 16 weeks
  • Serum HCV RNA values were measured during the clinical trials using the Roche COBAS AmpliPrep/COBAS Taqman HCV test
  •  92-100% with no virus detected in blood 12 weeks after finishing treatment, suggesting that patients’ infection had been cured


  • Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected adult patients
  • Not recommended in patients with moderate cirrhosis and contraindicated in patients with severe cirrhosis. It is also contraindicated in patients taking the drugs atazanavir and rifampin.
  • Most common adverse reactions: Headache, fatigue and nausea


Image Credit: Celgene, Jazz, Janssen, AbbVie












FDA News and Views: FDARA, FDA Import Decisions

FDA BRIEF: Week of July 31, 2017

FDA Reauthorization Act (FDARA)

Congress passed the FDA Reauthorization Act (FDARA) of 2017

  • Reauthorizes user fee programs necessary for pre-market evaluation of prescription drugs (PDUFA), medical devices (MDUFA), generic drugs (GDUFA), and biosimilar (BsUFA) products
  • Ensures continuity for medical product review programs


ACE bar graph

New System Speeds FDA Import Decisions

by: Douglas Stearn, Program Director, Office of Enforcement and Import Operations, Office of Regulatory Affairs

Automated Commercial Environment (ACE), piloted in 2015  

  • for determining whether FDA-regulated products can enter the US
  • uses to determine the admissibility of imports
  • tools include inspections of manufacturing plants abroad, physical inspection of goods, import alerts
  • better automation of admissibility process with lower-risk products

Improvements under ACE

  • automated messages that an import “may proceed” into U.S. without manual review
  • less need to request additional information from the importers
  • improved processing times-  average within 1 minute and 36 seconds
  • improvements for products that require manual processing



FDA Guidances: Antibacterial Therapies, Child-Resistant Packaging

FDA BRIEF: Week of July 31, 2017

fda guidances

Antibacterial Therapies for Patients With an Unmet Medical Need for the Treatment of Serious Bacterial Diseases


  • streamlined development programs for antibacterial drugs to treat serious bacterial diseases
  • unmet medical need – serious bacterial disease for which effective antibacterial drugs are limited or lacking
  •  may also be candidates for LPAD, per section 3042 of the 21st Century Cures Act


  • types of antibacterial drugs appropriate for streamlined development program
  • drug that treats a single species of bacteria be a candidate
  • important nonclinical considerations
  • clinical trial design considerations
  • noninferiority clinical trials
  • nested noninferiority/superiority clinical trials
  • statistical approaches or randomization strategies
  • importance of PK/PD (exposure-response) data
  • size of the premarketing safety database


Child-Resistant Packaging Statements in Drug Product Labeling


  • assist applicants, manufacturers, packagers, and distributors on
    child-resistant packaging (CRP)
  • what information should be included to support CRP statements in labeling
  • for NDAs, ANDAs, BLAs, and supplement
  • also labeling for nonprescription and Over-the-Counter drug products


  • Prescribing Information: child-resistant cap, child-resistant sachets
  • Patient Information: child-resistant package, sealed child-resistant foil pouch
  • Carton Labeling and Container Labels: Keep out of reach of children