Streptomirus (Streptovancin) is a new treatment for necrotizing fasciitis (NF) developed by Catalent Pharmaceutical Inc. Non-clinical studies in mice and dogs showed Streptomirus was safer, faster-acting, and more effective than current NF treatments. Clinical trials confirmed Streptomirus' efficacy and safety profile. Catalent is seeking FDA approval to market Streptomirus globally as an orphan drug for NF, an unmet medical need with high mortality. If approved, Streptomirus would provide a more effective treatment option for NF patients.
The CLARITY Aneurysm Clip is intended for permanent occlusion of cerebral aneurysms. It is made of PEEK polymer, while the predicate Sugita Titanium Aneurysm Clip is made of Elgiloy alloy. Testing showed the CLARITY Clip performs comparable to the predicate in biocompatibility, corrosion resistance, and MRI safety. Though different materials, the CLARITY Clip's intended use, jaw-based occlusion mechanism, and substantial equivalence to the RoG Suture Anchor reference device support that it is as safe and effective as existing aneurysm clips.
Premier Device Consultants was contracted to develop a regulatory strategy for the Laser Therapeutics Company's new medical device called NEULASER, which uses lasers for eye surgery. Premier determined NEULASER is a Class II device that can be cleared through an abbreviated 510(k) by demonstrating substantial equivalence to similar predicate devices. Premier recommended establishing quality management systems, developing documentation for design controls and postmarket surveillance, and preparing all required documents and user fees for the 510(k) submission to obtain FDA clearance to market NEULASER in the United States by the second quarter of 2015.
Premarket Notification The 510(k) ProcessMichael Swit
June 5, 2012 presentation to the Food & Drug Law Institute Introduction to Medical Device Law Conference, Palo Alto, CA, focusing on:
I.The Legal Framework For 510(k) Determinations
II.510(k) Preparation – From Planning to Content
A. Predicates: researching predicates, combination predicates, and pre-amendment predicates
B. Strategy: choosing the right claim and introducing new features
C. Assessing data requirements/pre-IDE meetings
III. Device Modifications - Choosing The Right Regulatory Mechanism
IV.The FDA Review
V.What To Do When Your Substantial Equivalence Argument Is Rejected
V. Special Topics: User Fees, Combination Products
VI. Lessons Learned: Seeing The 510(k) From The Reviewer’s Perspective
VII. Recent Trends, 510(k) Reform
VIII. Case Study
As part of device description, required by 21 CFR 807.92(a)(4), medical device manufacturers will have to present how the device functions, the scientific concepts that form the basis for the device, and the significant physical and performance characteristics of the device, such as device design, materials used, physical, chemical and biological properties.
This document outlines the rules and regulations for medical devices in Pakistan, including classification, licensing, registration, labeling, and other requirements. Key points include:
- The Medical Device Board is responsible for regulating medical devices and conformity assessment bodies.
- Medical devices must be classified based on risk and undergo conformity assessment prior to registration and import/sale.
- Manufacturers and importers must obtain establishment licenses, which require meeting quality and premises standards and are valid for 5 years.
- Detailed procedures are defined for licensing, registration, labeling, post-market surveillance, exemptions, and other aspects of the medical device approval process.
Medical device as per india and usa special reference with 510(k)vikash vyas
1. medical device as per usa:
a) classification
b) 510(k)
c) 510(k) submission process
d) pre market approval(PMA)
2. medical device as per india
a) definition
b) organization of medical device reviewer
c) registration process
d) document required for the registration of medical device as per cdsco
The CLARITY Aneurysm Clip is intended for permanent occlusion of cerebral aneurysms. It is made of PEEK polymer, while the predicate Sugita Titanium Aneurysm Clip is made of Elgiloy alloy. Testing showed the CLARITY Clip performs comparable to the predicate in biocompatibility, corrosion resistance, and MRI safety. Though different materials, the CLARITY Clip's intended use, jaw-based occlusion mechanism, and substantial equivalence to the RoG Suture Anchor reference device support that it is as safe and effective as existing aneurysm clips.
Premier Device Consultants was contracted to develop a regulatory strategy for the Laser Therapeutics Company's new medical device called NEULASER, which uses lasers for eye surgery. Premier determined NEULASER is a Class II device that can be cleared through an abbreviated 510(k) by demonstrating substantial equivalence to similar predicate devices. Premier recommended establishing quality management systems, developing documentation for design controls and postmarket surveillance, and preparing all required documents and user fees for the 510(k) submission to obtain FDA clearance to market NEULASER in the United States by the second quarter of 2015.
Premarket Notification The 510(k) ProcessMichael Swit
June 5, 2012 presentation to the Food & Drug Law Institute Introduction to Medical Device Law Conference, Palo Alto, CA, focusing on:
I.The Legal Framework For 510(k) Determinations
II.510(k) Preparation – From Planning to Content
A. Predicates: researching predicates, combination predicates, and pre-amendment predicates
B. Strategy: choosing the right claim and introducing new features
C. Assessing data requirements/pre-IDE meetings
III. Device Modifications - Choosing The Right Regulatory Mechanism
IV.The FDA Review
V.What To Do When Your Substantial Equivalence Argument Is Rejected
V. Special Topics: User Fees, Combination Products
VI. Lessons Learned: Seeing The 510(k) From The Reviewer’s Perspective
VII. Recent Trends, 510(k) Reform
VIII. Case Study
As part of device description, required by 21 CFR 807.92(a)(4), medical device manufacturers will have to present how the device functions, the scientific concepts that form the basis for the device, and the significant physical and performance characteristics of the device, such as device design, materials used, physical, chemical and biological properties.
This document outlines the rules and regulations for medical devices in Pakistan, including classification, licensing, registration, labeling, and other requirements. Key points include:
- The Medical Device Board is responsible for regulating medical devices and conformity assessment bodies.
- Medical devices must be classified based on risk and undergo conformity assessment prior to registration and import/sale.
- Manufacturers and importers must obtain establishment licenses, which require meeting quality and premises standards and are valid for 5 years.
- Detailed procedures are defined for licensing, registration, labeling, post-market surveillance, exemptions, and other aspects of the medical device approval process.
Medical device as per india and usa special reference with 510(k)vikash vyas
1. medical device as per usa:
a) classification
b) 510(k)
c) 510(k) submission process
d) pre market approval(PMA)
2. medical device as per india
a) definition
b) organization of medical device reviewer
c) registration process
d) document required for the registration of medical device as per cdsco
The document outlines the procedures for registering medical devices in Pakistan according to the Medical Devices Rules of 2015. It discusses what constitutes a medical device and the application process for initial registration and renewal of registration. It lists the conditions of registration including maintaining records of clinical investigations and reporting adverse events. It also describes the procedures for cancelling or suspending a registration if the conditions are not met.
Stivax neurostimulator and fda powerpointMaxiMedRx
STIVAX INNOVATIVE THERAPY: It goes without saying that tried and tested methods are the best therapy in medicine, with innovative, clinically-tested approaches providing a valuable complement for patient therapies. This is the basis for STIVAX therapy. The STIVAX NEUROSTIMULATION THERAPY is a conservative treatment for Chronic Pain and PAD patients extends walking distances to a multiple of original values and supports wound healing. The STIVAX STIMULATOR is a integral component of STIVAX therapy. The mechanism of action is based on the stimulation of the vagus nerve.
The document outlines the steps for preparing a premarket notification submission or 510(k) for a medical device. The first step is to identify the product code, regulation number and review panel by searching the FDA classification database. The second step is identifying a predicate device that is already legally marketed and determining substantial equivalence by comparing the intended use, materials, and other characteristics. The third step is preparing the submission file which should refer to any special control guidance documents and take the format of an abbreviated or traditional 510(k) depending on guidance availability.
A failure of the device to meet its performance specifications or otherwise perform as intended. Performance specifications include all claims made in the labeling for the device. A malfunction should be considered reportable if any one of the following is true:
1. The chance of a death or serious injury
2.The malfunction affect the device in a catastrophic manner that may lead to a death or serious injury
3. The device fail to perform its essential function
4. The malfunction would be likely to cause or contribute to death or serious injury, regardless of how the device is used.
This proposal outlines the commercialization pathway for an investigational in vitro diagnostic (IVD) device for nonalcoholic fatty liver disease (NAFLD). They were unable to identify a substantially equivalent predicate device, so they plan to submit a formal pre-submission to the FDA to obtain guidance on the appropriate regulatory pathway. The proposed studies funded by this proposal would support information needed for the pre-submission, including analytical validation and performance characteristics of the test. Depending on FDA feedback, the pathway may involve de novo classification, reclassification, or premarket approval.
The VISX CV SI-1 CustomVue Slit Illuminator is a diagnostic device intended to facilitate inspection of the anterior eye segment. It consists of a slit illuminator and charger unit. Non-clinical testing showed compliance with electrical safety standards and no new safety concerns. The FDA determined it to be substantially equivalent to legally marketed predicate devices.
Neuro-Stim System Neurostim FDA K140530 Electro Acupuncture Devicemcalipo
Neuro-Stim Electro Acupuncture device and Electro Acupuncture Stimulator. The Electro Auricular Device or PENS (Percutaneous Electrical Nerve Stimulation). Neurostimulation pain therapy medical devices deliver a therapeutic electrical signal into auricular nerves to help release endorphins and provide pain relief.
https://www.laserspineinstitute.com/spinal_orthopedic_procedures/neurostim/
This document summarizes a presentation on future compliance requirements related to medical devices. It discusses changes coming in how medical devices are named (GMDN), tracked (UDI), and have data captured (AIDC/GS1 coding). The Global Medical Device Nomenclature (GMDN) will standardize device names. Unique Device Identification (UDI) will assign each device a unique identifier tracked in a public database. Automatic identification like GS1 coding will help interface equipment and data. Hospitals should prepare by understanding these changes to integrate new identification standards.
The De Novo 510(k) Process - Is There Hope at FDA for Lower Risk Innovative D...Michael Swit
This document summarizes a presentation given by Michael Swit on the FDA's de novo classification process for novel medical devices. It discusses the origins of the de novo pathway, how devices become eligible for de novo review, and the two approaches outlined in a recent draft guidance (pre-de novo submission and traditional petition). It provides details on the format and timing for a pre-de novo submission and de novo petition, as well as how FDA reviews and responds to each. Statistics on de novo petitions approved from 1998-2011 are also presented, broken down by therapeutic area and year. Finally, special controls commonly required as part of the de novo process are summarized.
The document outlines the Medical Devices Rules 2015 introduced by the Drug Regulatory Authority of Pakistan. Some key points:
- The rules were introduced to regulate over 1 million medical devices in Pakistan and protect public health by ensuring safety and effectiveness.
- A Medical Devices Board (MDB) is established as the regulatory authority responsible for registration of devices and conformity assessment bodies, issuing licenses, and enforcing implementation of the rules.
- The rules cover various aspects of medical devices including classification, registration, import/export, labeling, usage and advertising. Formats and a fee chart for various regulatory activities are also provided.
This document provides guidance on obtaining an import license for medical devices intended for demonstration or training purposes only in Saudi Arabia. It defines key terms and sets out the requirements, required documents, and application process. Importers must submit an electronic application form, invoice copy, bill of lading/air waybill copy, and signed attestation to the Saudi Food and Drug Authority (SFDA). If approved, SFDA will issue an import license. Importers must ensure devices are only used for stated purposes and later exported or destroyed.
Nowadays, health is given much priority in all aspects. The present
generation is very much conscious about having periodic checkups
and maintaining a good health. This awareness has given an upper
hand to the medical equipment business. The healthcare industry is
booming like no other field and because of this, Medical Device
Regulation India has also become equally complicated. Unlike
previous years, nowadays most medical devices are required to be
registered and need approval for business
Clinical Affairs Excellence: Benchmarking Clinical Trial Strategies To Ensure...Best Practices
This document summarizes the findings of a benchmarking study conducted by Best Practices, LLC on clinical trial strategies for medical device companies. Key findings include:
- The average medical device company in the study had $3.8 billion in annual revenue and spent $39 million (1.1% of revenue) on clinical affairs.
- Most device companies conducted the majority (72%) of clinical trials in-house, with 22% outsourced and 4% offshore. Pharma companies outsourced more activities.
- Regulators had extensive questions about outside the US trial data for 46% of device companies and 38% felt data led to extensive regulatory conversations.
- Device companies did not out
In this presentation we want to outline the principles of medical device regulations and the 510(k) Premarket notification process for an efficient product approval with the FDA.
Understanding FDA Requirements Medical Devicesmarchell
The medical device market is experiencing explosive growth. Currently valued at $90 billion, market growth will continue to accelerate as demographics and market drivers increase their pressure for new and innovative product offerings.
Moreover, a substantial investment of time and resources is required to properly evaluate a new product idea and estimate its potential for success. So when a company executive declines a seemingly good product idea, what is probably being declined is the expense of properly evaluating the idea, and after having paid these expenses, the prospect of embarking on an expensive commercialization effort that has a 90 percent chance of failing.
FDA Regulations and Medical Device Pathways to MarketMethodSense, Inc.
Bringing your medical device to market requires in-depth attention to its safety, reliability and compliance. In addition to designing a quality medical device, it’s critical that you anticipate and address the requirements that allow you to introduce it to the market successfully.
Life Science consulting firm, MethodSense, discusses important FDA regulations as they relate to bringing a medical device to market, including 21 CFR Part 821, 510(k) approval and 21 CFR Part 11.
Why to conduct clinical trials in Ukraine? Ukrainian CRODariaAbulova
- Why to conduct clinical trials in Ukraine?
- Who we are - JERELO CRO
- Area of expertise of JERELO
- Cardio surgery case of JERELO CRO
- Stages of MD lifecycle and our facilities for clinical researches on its every stage
- Regulatory services and services of the Authorized Representative in Ukraine
All these issues are described in our presentation.
JERELO is your reliable CRO in Ukraine.
This letter from the FDA informs Zynex Medical that its NexWave electrical stimulator device has been found to be substantially equivalent to legally marketed predicate devices, and can be marketed in the United States. The device is classified as a Class II device intended for symptomatic relief of chronic pain and muscle re-education/stimulation. While the FDA issued a substantial equivalence determination, Zynex Medical must still comply with all applicable regulations regarding device labeling, manufacturing, reporting and other requirements.
This 510(k) submission is for the WedgeXTM Bone Wedge, a titanium bone wedge intended for internal bone fixation in the ankle and foot. The device is substantially equivalent to the predicate BIOFOAM® Bone Wedge. Testing showed the WedgeXTM Bone Wedge passed biocompatibility testing according to ISO 10993 and performance bench testing including static, fatigue, and flexural testing. The device will be provided sterile for prescription use and is intended as an alternative to bone grafts for procedures such as opening wedge osteotomies and arthrodesis of the foot and ankle.
This document provides information on the GYNECARE TVT SECUR System, including:
- A 510(k) summary outlining the device description, intended use, and substantial equivalence determination.
- Correspondence between the FDA and manufacturer regarding clearance of the device.
- Original submission documents and reviewer information providing details on the device, intended use, and clinical data to support a determination of substantial equivalence.
- A supplement adding additional data to the original submission.
The document contains the manufacturer's request for 510(k) clearance and the FDA's response determining the GYNECARE TVT SECUR System to be substantially equivalent to legally marketed predicate devices.
The document outlines the procedures for registering medical devices in Pakistan according to the Medical Devices Rules of 2015. It discusses what constitutes a medical device and the application process for initial registration and renewal of registration. It lists the conditions of registration including maintaining records of clinical investigations and reporting adverse events. It also describes the procedures for cancelling or suspending a registration if the conditions are not met.
Stivax neurostimulator and fda powerpointMaxiMedRx
STIVAX INNOVATIVE THERAPY: It goes without saying that tried and tested methods are the best therapy in medicine, with innovative, clinically-tested approaches providing a valuable complement for patient therapies. This is the basis for STIVAX therapy. The STIVAX NEUROSTIMULATION THERAPY is a conservative treatment for Chronic Pain and PAD patients extends walking distances to a multiple of original values and supports wound healing. The STIVAX STIMULATOR is a integral component of STIVAX therapy. The mechanism of action is based on the stimulation of the vagus nerve.
The document outlines the steps for preparing a premarket notification submission or 510(k) for a medical device. The first step is to identify the product code, regulation number and review panel by searching the FDA classification database. The second step is identifying a predicate device that is already legally marketed and determining substantial equivalence by comparing the intended use, materials, and other characteristics. The third step is preparing the submission file which should refer to any special control guidance documents and take the format of an abbreviated or traditional 510(k) depending on guidance availability.
A failure of the device to meet its performance specifications or otherwise perform as intended. Performance specifications include all claims made in the labeling for the device. A malfunction should be considered reportable if any one of the following is true:
1. The chance of a death or serious injury
2.The malfunction affect the device in a catastrophic manner that may lead to a death or serious injury
3. The device fail to perform its essential function
4. The malfunction would be likely to cause or contribute to death or serious injury, regardless of how the device is used.
This proposal outlines the commercialization pathway for an investigational in vitro diagnostic (IVD) device for nonalcoholic fatty liver disease (NAFLD). They were unable to identify a substantially equivalent predicate device, so they plan to submit a formal pre-submission to the FDA to obtain guidance on the appropriate regulatory pathway. The proposed studies funded by this proposal would support information needed for the pre-submission, including analytical validation and performance characteristics of the test. Depending on FDA feedback, the pathway may involve de novo classification, reclassification, or premarket approval.
The VISX CV SI-1 CustomVue Slit Illuminator is a diagnostic device intended to facilitate inspection of the anterior eye segment. It consists of a slit illuminator and charger unit. Non-clinical testing showed compliance with electrical safety standards and no new safety concerns. The FDA determined it to be substantially equivalent to legally marketed predicate devices.
Neuro-Stim System Neurostim FDA K140530 Electro Acupuncture Devicemcalipo
Neuro-Stim Electro Acupuncture device and Electro Acupuncture Stimulator. The Electro Auricular Device or PENS (Percutaneous Electrical Nerve Stimulation). Neurostimulation pain therapy medical devices deliver a therapeutic electrical signal into auricular nerves to help release endorphins and provide pain relief.
https://www.laserspineinstitute.com/spinal_orthopedic_procedures/neurostim/
This document summarizes a presentation on future compliance requirements related to medical devices. It discusses changes coming in how medical devices are named (GMDN), tracked (UDI), and have data captured (AIDC/GS1 coding). The Global Medical Device Nomenclature (GMDN) will standardize device names. Unique Device Identification (UDI) will assign each device a unique identifier tracked in a public database. Automatic identification like GS1 coding will help interface equipment and data. Hospitals should prepare by understanding these changes to integrate new identification standards.
The De Novo 510(k) Process - Is There Hope at FDA for Lower Risk Innovative D...Michael Swit
This document summarizes a presentation given by Michael Swit on the FDA's de novo classification process for novel medical devices. It discusses the origins of the de novo pathway, how devices become eligible for de novo review, and the two approaches outlined in a recent draft guidance (pre-de novo submission and traditional petition). It provides details on the format and timing for a pre-de novo submission and de novo petition, as well as how FDA reviews and responds to each. Statistics on de novo petitions approved from 1998-2011 are also presented, broken down by therapeutic area and year. Finally, special controls commonly required as part of the de novo process are summarized.
The document outlines the Medical Devices Rules 2015 introduced by the Drug Regulatory Authority of Pakistan. Some key points:
- The rules were introduced to regulate over 1 million medical devices in Pakistan and protect public health by ensuring safety and effectiveness.
- A Medical Devices Board (MDB) is established as the regulatory authority responsible for registration of devices and conformity assessment bodies, issuing licenses, and enforcing implementation of the rules.
- The rules cover various aspects of medical devices including classification, registration, import/export, labeling, usage and advertising. Formats and a fee chart for various regulatory activities are also provided.
This document provides guidance on obtaining an import license for medical devices intended for demonstration or training purposes only in Saudi Arabia. It defines key terms and sets out the requirements, required documents, and application process. Importers must submit an electronic application form, invoice copy, bill of lading/air waybill copy, and signed attestation to the Saudi Food and Drug Authority (SFDA). If approved, SFDA will issue an import license. Importers must ensure devices are only used for stated purposes and later exported or destroyed.
Nowadays, health is given much priority in all aspects. The present
generation is very much conscious about having periodic checkups
and maintaining a good health. This awareness has given an upper
hand to the medical equipment business. The healthcare industry is
booming like no other field and because of this, Medical Device
Regulation India has also become equally complicated. Unlike
previous years, nowadays most medical devices are required to be
registered and need approval for business
Clinical Affairs Excellence: Benchmarking Clinical Trial Strategies To Ensure...Best Practices
This document summarizes the findings of a benchmarking study conducted by Best Practices, LLC on clinical trial strategies for medical device companies. Key findings include:
- The average medical device company in the study had $3.8 billion in annual revenue and spent $39 million (1.1% of revenue) on clinical affairs.
- Most device companies conducted the majority (72%) of clinical trials in-house, with 22% outsourced and 4% offshore. Pharma companies outsourced more activities.
- Regulators had extensive questions about outside the US trial data for 46% of device companies and 38% felt data led to extensive regulatory conversations.
- Device companies did not out
In this presentation we want to outline the principles of medical device regulations and the 510(k) Premarket notification process for an efficient product approval with the FDA.
Understanding FDA Requirements Medical Devicesmarchell
The medical device market is experiencing explosive growth. Currently valued at $90 billion, market growth will continue to accelerate as demographics and market drivers increase their pressure for new and innovative product offerings.
Moreover, a substantial investment of time and resources is required to properly evaluate a new product idea and estimate its potential for success. So when a company executive declines a seemingly good product idea, what is probably being declined is the expense of properly evaluating the idea, and after having paid these expenses, the prospect of embarking on an expensive commercialization effort that has a 90 percent chance of failing.
FDA Regulations and Medical Device Pathways to MarketMethodSense, Inc.
Bringing your medical device to market requires in-depth attention to its safety, reliability and compliance. In addition to designing a quality medical device, it’s critical that you anticipate and address the requirements that allow you to introduce it to the market successfully.
Life Science consulting firm, MethodSense, discusses important FDA regulations as they relate to bringing a medical device to market, including 21 CFR Part 821, 510(k) approval and 21 CFR Part 11.
Why to conduct clinical trials in Ukraine? Ukrainian CRODariaAbulova
- Why to conduct clinical trials in Ukraine?
- Who we are - JERELO CRO
- Area of expertise of JERELO
- Cardio surgery case of JERELO CRO
- Stages of MD lifecycle and our facilities for clinical researches on its every stage
- Regulatory services and services of the Authorized Representative in Ukraine
All these issues are described in our presentation.
JERELO is your reliable CRO in Ukraine.
This letter from the FDA informs Zynex Medical that its NexWave electrical stimulator device has been found to be substantially equivalent to legally marketed predicate devices, and can be marketed in the United States. The device is classified as a Class II device intended for symptomatic relief of chronic pain and muscle re-education/stimulation. While the FDA issued a substantial equivalence determination, Zynex Medical must still comply with all applicable regulations regarding device labeling, manufacturing, reporting and other requirements.
This 510(k) submission is for the WedgeXTM Bone Wedge, a titanium bone wedge intended for internal bone fixation in the ankle and foot. The device is substantially equivalent to the predicate BIOFOAM® Bone Wedge. Testing showed the WedgeXTM Bone Wedge passed biocompatibility testing according to ISO 10993 and performance bench testing including static, fatigue, and flexural testing. The device will be provided sterile for prescription use and is intended as an alternative to bone grafts for procedures such as opening wedge osteotomies and arthrodesis of the foot and ankle.
This document provides information on the GYNECARE TVT SECUR System, including:
- A 510(k) summary outlining the device description, intended use, and substantial equivalence determination.
- Correspondence between the FDA and manufacturer regarding clearance of the device.
- Original submission documents and reviewer information providing details on the device, intended use, and clinical data to support a determination of substantial equivalence.
- A supplement adding additional data to the original submission.
The document contains the manufacturer's request for 510(k) clearance and the FDA's response determining the GYNECARE TVT SECUR System to be substantially equivalent to legally marketed predicate devices.
This document provides an overview of the FDA 510(k) submission process for medical devices. It begins with background on FDA authority over medical devices and device classification. It then covers key aspects of preparing a 510(k) submission, including what a 510(k) is, where and when to start the process, how FDA reviews submissions, and tips for formatting a 510(k). The document reviews the typical 510(k) review cycle and outcomes, including potential requests for additional information and decisions of substantial equivalence or non-equivalence. It aims to help medical device companies navigate the 510(k) process and timelines.
Webinar or Online Training on A comprehensive overview of 510(k) submissionComplianz World
Complianz World is a US based company, and a leading GRC training provider has announced to conduct
Webinar or Online Training on
A comprehensive overview of 510(k) submission
This 510(k) submission from Medstrong Inc. provides information on their Viceroy Aneurysm Clip and Marquis Aneurysm Clip Applier. The devices are intended for occlusion of cerebral aneurysms, temporarily or permanently. Supporting data includes descriptions of the devices, their indications for use, comparison to the predicate Yasargil Aneurysm Clips and Appliers, and summaries of bench, animal, and clinical testing performed. The submission contains documentation of biocompatibility testing, sterilization validation, and other required information to demonstrate substantial equivalence to the predicate device.
This PDF will discuss the key information that is required for a medical device 510k submission. The information presented in this PDF pertains to just one of the many best practices in a medical device 510K preparation and submission.
Regulatory strategy for medical device start-upsRina Nir
The document discusses regulatory considerations for medical device startups. It notes that the regulatory environment will significantly impact business plans by influencing budgets, timelines, staffing needs and more. Startups must thoroughly assess their regulatory situation and strategy to navigate the complex approval processes in both the US and EU. Later slides provide more details on specific regulatory pathways, standards, and trends to consider for medical device development.
Marketing Strategy for a medical device companysaurabhmalani
This is a marketing strategy for a leading medical device company for a new product launch. This presentation won the Babson Marketing Case Competition - 2012 with prize money of $5000. 16 schools across the globe were competing in this competition.
Early phase drug development and the fda roadmap final version 2axE. Dennis Bashaw
This is the slide deck used in my webinar that was presented on 2/1/2018 on the FDA Predictive Toxicology Roadmap. It was presented at a webinar hosted by BioIVT in my private capacity and is not an official statement of FDA policy
BP804 ET: PHARMACEUTICAL REGULATORY SCIENCE (Theory)2. unit ii, chapter-1 reg...Audumbar Mali
The document provides information on the regulatory approval process for drugs. It discusses the various stages of approval including investigational new drug applications (IND), new drug applications (NDA), and abbreviated new drug applications (ANDA).
The stages include pre-clinical testing, clinical trials through multiple phases, and regulatory review and approval. An IND must be approved by the FDA before clinical trials in humans can begin. If clinical trials are successful, manufacturers can file an NDA to request approval to market the drug. For generic drugs, an ANDA can be filed to demonstrate bioequivalence to an existing approved drug, without needing to re-conduct clinical trials. The approval process is complex and lengthy, usually taking 10-
Different Stages of Medical Device Development and Drug Development: PepgraDi...PEPGRA Healthcare
The difference between medical device product development and pharmaceuticals that are supposed to be launched are based on industry composition where above 80% small and medium-sized companies require medical devices and large multinational organizations seek new medicines. Pepgra gives you the different stages of Medical Device Development and Drug Development, some are:
1. Lead discovery optimization
2. Pre-clinical Research
3.. Clinical Research
4. Post- Market safety monitoring
Continue Reading: https://bit.ly/3ryCQC4
Youtube: https://www.youtube.com/watch?v=cYz_BOArGhA
If you need any further information, then please contact via
Email us: sales.cro@pepgra.com
Whatsapp: +91 9884350006
This document summarizes key aspects of non-clinical drug development. It discusses how non-clinical studies are performed in silico, in vitro, and in vivo to assess safety, efficacy, pharmacokinetics, and manufacturing viability before human clinical trials. It also describes the Investigational New Drug application process which is required to begin clinical trials in humans, and provides an overview of the New Drug Application submitted for marketing approval. The document concludes by outlining the contents of an Investigational Medicinal Products Dossier which forms the basis for approval of multinational clinical trials in the European Union.
The document provides an overview of the Investigational New Drug Application (IND) and New Drug Application (NDA) processes required by the FDA to develop and approve new drugs. It describes how developing a new drug takes 15 years and over $900 million on average. The IND allows testing of new drugs in humans and provides safety data, while the NDA provides all clinical trial data for the FDA to determine if the drug is safe and effective for approval. Both the IND and NDA are lengthy applications that require extensive non-clinical and clinical data to gain FDA approval to market a new prescription drug.
An Investigational New Drug (IND) application allows a sponsor to legally test an unapproved or investigational drug in clinical trials. The sponsor must provide preclinical data on pharmacology, toxicology and manufacturing to show the drug is reasonably safe for initial human testing. After submitting an IND, clinical trials can begin if FDA does not disapprove the application within 30 days. The IND application process and clinical trials are regulated to ensure data quality and subject safety.
The document discusses regulatory requirements and procedures for approval of new vaccines in India. It provides definitions of key terms like drugs, new drugs and vaccines. It describes the information and data required to be submitted for approval, including safety and efficacy data from clinical trials. It also discusses post-marketing surveillance requirements and procedures for investigating and reporting adverse events following immunization.
Kartheek Dokka -Drug Trial that went wrong!Kartheek Dokka
The clinical trial of the drug TGN1412 conducted by TeGenero and Parexel went disastrously wrong. The drug was intended to treat cancers and arthritis but caused a severe cytokine release syndrome in all six participants who received the active drug dose. The drug was administered much more quickly than approved and proper procedures for dealing with potential side effects were not followed. As a result, the participants experienced catastrophic multi-system failure and long-term damage. The trial failed to properly test the drug in animals first and did not consider the risks of administering the drug to healthy volunteers in such a manner.
This document discusses Investigational New Drug Applications (INDs), which are required for clinical studies involving investigational drugs. There are three main types of INDs: investigator INDs submitted by physicians, emergency use INDs for emergency situations, and treatment INDs for drugs showing promise for serious conditions. The FDA reviews INDs to ensure proposed clinical trials will not expose subjects to unnecessary risks, investigators are qualified, and informed consent and institutional review board oversight are in place. IND applications must provide preclinical and manufacturing data as well as detailed protocols for proposed clinical studies. The FDA's objectives in reviewing INDs are to ensure safety, rights of subjects, and adequate scientific evaluation of a drug's effectiveness.
Clinical research : Drug regulatory affairs and Pharmacovigilance.ProfDnyaneshwariJosh
Schedule Y, FDA, Appendices, Post marketing surveillance,Clinical trial,WHO,ICH-GCP, FDA-CFR, Safety,Adverse Drug reaction, Adverse Event(AE), Serious Adverse Event(SAE),Reporting, IND , 3500A form
FDA classify Medical Devices and how to report device problems A Systematic R...Pubrica
The typical time it takes to get a device to market is 3 to 7 years, compared to 12 years for pharmaceuticals. However, there are concerns that the Food and Drug Administration's Systematic Review Writing methods may not be adequate to satisfy the required guarantees of safety and efficacy.
Learn More : https://pubrica.com/services/research-services/systematic-review/
Reference: https://bit.ly/3xNHUsC
Why Pubrica:
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Introduction to Regulatory Affairs - Pauwels Consulting AcademyPauwels Consulting
On Tuesday, June 14, our colleagues Fiorenzo Savoretti, Senior Regulatory and Quality Consultant at Pfizer and Nick Deschacht, Senior RA Consultant at GSK, gave an interesting “Introduction to Regulatory Affairs”.
Fiorenzo and Nick talked about RA and their projects, each from their unique angle. They delivered their presentations for ## attendees at our Brussels office at the Lambroekstraat 5a in Diegem.
This document summarizes regulatory issues related to reporting and investigating adverse events following immunization (AEFI) in India. It provides definitions of key terms like drugs, adverse drug reactions, and serious adverse reactions. It describes the roles and responsibilities of different organizations in the regulatory framework, including the Central Drugs Standard Control Organization (CDSCO), National Regulatory Authority (NRA), and Central Drug Laboratory (CDL). It discusses some past AEFI cases reported to the Drug Controller General of India (DCGI) and the modus operandi adopted in investigations. Limitations and suggestions to strengthen the AEFI monitoring and response system are also highlighted.
Pharmaceutical product development and its associated quality system 01Abdirizak Mohammed
Drug development is a long, expensive, and risky process taking 10-15 years. It involves extensive testing of drug candidates in vitro and in animal models to establish safety and efficacy before clinical trials in humans. Clinical trials have three phases - phase I tests safety in healthy volunteers, phase II assesses efficacy and dosing in patients, and phase III confirms safety and efficacy in large patient populations. Only about 1 in 10 drugs that enter clinical trials will be approved due to the high failure rate of drug candidates. Getting a new drug approved is a significant challenge that involves demonstrating safety and efficacy to global regulatory standards.
A regulatory strategy is critical to the commercialization of biomedical technologies. In particular, technologies such as new drugs and medical devices have more regulatory needs, and the strategy should be considered simultaneous to a commercialization pathway.
This document provides guidelines for conducting clinical trials and importing or manufacturing new drugs for sale according to Schedule Y of the Drugs and Cosmetics Act of 1940 in India. It outlines the application process and required data to be submitted, including chemical/pharmaceutical information, pre-clinical toxicology and pharmacology studies in animals, protocols for human clinical trials through various phases, and post-marketing surveillance requirements. Ethics committee approval and informed consent of participants are necessary. Manufacturers must establish the drug's quality, safety, and efficacy primarily through clinical trials conducted in India.
FDA classify Medical Devices and how to report device problems A Systematic R...Pubrica
The typical time it takes to get a device to market is 3 to 7 years, compared to 12 years for pharmaceuticals. However, there are concerns that the Food and Drug Administration's Systematic Review Writing methods may not be adequate to satisfy the required guarantees of safety and efficacy.
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Reference: https://bit.ly/3xNHUsC
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Relationship Between Pharmacovigilance And Patient Safety[1]siddharthchachad
This document discusses challenges in pharmacovigilance and patient safety, including issues with accurate safety profiling, differences in safety reporting guidelines between countries, and limitations of only focusing on patient safety. It provides examples of drugs like thalidomide, vioxx, and celebrex that highlighted safety issues. Regulatory environments and safety reporting practices differ between countries like India, EU, and US. Standardization of terms and processes is important for effective pharmacovigilance.
This document discusses pharmacovigilance and the need for monitoring drug safety post approval. It describes how historical drug safety issues like the Elixir Sulfanilamide and Thalidomide tragedies revealed limitations in pre-approval testing and established the need for ongoing pharmacovigilance. The aims, application and reporting processes of pharmacovigilance are outlined along with terminology and examples of regulatory actions taken based on adverse event reporting.
Serious adverse event narratives are used in pharmacovigilance to document individual case safety reports and clinical study reports. They provide a comprehensive medical history summary of a patient's relevant clinical information, adverse event, and outcome. The narrative should be presented in logical chronological order. A sample SAE narrative is then provided that documents a case of acute renal insufficiency in a patient with cancer, including medical history, clinical course, treatment, and outcome assessment. Key considerations for writing effective SAE narratives are also outlined.
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
7. 7
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
8. 8
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
9. 9
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
10. 10
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
11. 11
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
12. 12
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.
13. 13
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
14. 14
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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