An overview of Intellectual Property Barriers in Generic Vaccines & how to circumvent these. Issues of affordability in tough Patent regime has also been mentioned.
Bharat Biotech’s research stems from the need to innovate and the necessity to address public health requirements of the developing nations, while adhering to IPR. Our business model is to support the advancement of technologies through strong collaborative research, and simultaneously support the establishment of strong innovative technology platforms for intellectual property reputed driven enterprise R&D.
Bharat Biotech is an Indian biotechnology company that specializes in developing and manufacturing vaccines and biotherapeutics focused on public health in developing nations. It supplies vaccines to the Indian government and over 65 other countries. Bharat Biotech has large manufacturing facilities in Hyderabad, India that meet stringent international standards. The company is a leader in innovation and research and development, with a focus on diseases prevalent in developing market populations.
Market Exclusivity Under the Waxman-Hatch ActMichael Swit
March 19, 2007 presentation to the San Diego County Bar Association IP Section, with a focus on:
•Orphan Drug Exclusivity (Seven Years)
•Five-Year Exclusivity
•Three-Year Exclusivity
•Pediatric Exclusivity (Six Months)
•180-Day Exclusivity
June 14, 2018 presentation to the San Diego Regulatory Affairs Network (SDRAN) Regulatory Affairs Certification (RAC) Review Course on the basics of FDA regulation of generic drugs and biosimilars.
The document discusses the FDA 510(k) premarket notification process for medical devices. It explains that Class I, II, and III medical devices intended for commercial distribution in the US require FDA clearance obtained through a 510(k) or Premarket Approval (PMA). A 510(k) involves demonstrating that a new device is substantially equivalent to a predicate device already legally marketed in the US. The submission must provide device descriptions, intended use, performance testing results and labeling to establish safety and effectiveness.
This document provides an overview of biosimilars. It discusses that biosimilars are similar versions of biologic drugs that are set to lose patent protection. This presents both opportunities to make cheaper biologics to increase access, as well as regulatory challenges to demonstrate similarity. The global biosimilars market is growing, driven by both developed and emerging markets. India is emerging as a key player, with companies developing biosimilars for both domestic and export markets. However, hurdles remain around establishing clear regulatory pathways and demonstrating similarity to reference biologics.
This SlideShare gives an overview on how a drug is discovered, researched, developed, tested and reviewed for approval. It follows the current standard of approval set by the Food and Drug Administration (FDA), a federal agency of the United States Department of Health and Human Services. The process is generally divided into 4 Stages: Pre-Clinical, Clinical, New Drug Application (NDA) Review & Post-Marketing.
Sharing my learning in dealing with complexity and uncertainty and shed some light on:
(a) Understanding the ‘biosimilar paradox’
(b) Accelerating our “QbD” Journey – focusing on ‘from Generics to Biosimilars’
(c) In preparing this talk, collect my thoughts to help NIPTE consider ways for developing its program on Biosimilars to help the Nation improve assurance of quality with confidence and lower costs
(D) Invite the audience to get to know NIPTE and provide us ways to collaborate with industry
Bharat Biotech’s research stems from the need to innovate and the necessity to address public health requirements of the developing nations, while adhering to IPR. Our business model is to support the advancement of technologies through strong collaborative research, and simultaneously support the establishment of strong innovative technology platforms for intellectual property reputed driven enterprise R&D.
Bharat Biotech is an Indian biotechnology company that specializes in developing and manufacturing vaccines and biotherapeutics focused on public health in developing nations. It supplies vaccines to the Indian government and over 65 other countries. Bharat Biotech has large manufacturing facilities in Hyderabad, India that meet stringent international standards. The company is a leader in innovation and research and development, with a focus on diseases prevalent in developing market populations.
Market Exclusivity Under the Waxman-Hatch ActMichael Swit
March 19, 2007 presentation to the San Diego County Bar Association IP Section, with a focus on:
•Orphan Drug Exclusivity (Seven Years)
•Five-Year Exclusivity
•Three-Year Exclusivity
•Pediatric Exclusivity (Six Months)
•180-Day Exclusivity
June 14, 2018 presentation to the San Diego Regulatory Affairs Network (SDRAN) Regulatory Affairs Certification (RAC) Review Course on the basics of FDA regulation of generic drugs and biosimilars.
The document discusses the FDA 510(k) premarket notification process for medical devices. It explains that Class I, II, and III medical devices intended for commercial distribution in the US require FDA clearance obtained through a 510(k) or Premarket Approval (PMA). A 510(k) involves demonstrating that a new device is substantially equivalent to a predicate device already legally marketed in the US. The submission must provide device descriptions, intended use, performance testing results and labeling to establish safety and effectiveness.
This document provides an overview of biosimilars. It discusses that biosimilars are similar versions of biologic drugs that are set to lose patent protection. This presents both opportunities to make cheaper biologics to increase access, as well as regulatory challenges to demonstrate similarity. The global biosimilars market is growing, driven by both developed and emerging markets. India is emerging as a key player, with companies developing biosimilars for both domestic and export markets. However, hurdles remain around establishing clear regulatory pathways and demonstrating similarity to reference biologics.
This SlideShare gives an overview on how a drug is discovered, researched, developed, tested and reviewed for approval. It follows the current standard of approval set by the Food and Drug Administration (FDA), a federal agency of the United States Department of Health and Human Services. The process is generally divided into 4 Stages: Pre-Clinical, Clinical, New Drug Application (NDA) Review & Post-Marketing.
Sharing my learning in dealing with complexity and uncertainty and shed some light on:
(a) Understanding the ‘biosimilar paradox’
(b) Accelerating our “QbD” Journey – focusing on ‘from Generics to Biosimilars’
(c) In preparing this talk, collect my thoughts to help NIPTE consider ways for developing its program on Biosimilars to help the Nation improve assurance of quality with confidence and lower costs
(D) Invite the audience to get to know NIPTE and provide us ways to collaborate with industry
The document discusses the Abbreviated New Drug Application (ANDA) process for generic drugs in the United States. An ANDA is a request to the FDA to manufacture and market a generic drug, and is abbreviated since it does not require clinical trials like a New Drug Application. The key points covered include basic generic drug requirements, the objective of reducing drug costs, comparisons between innovator and generic drugs and between NDAs and ANDAs, the Hatch-Waxman Act of 1984 which established the ANDA pathway, patent certification requirements, and an overview of the ANDA review process.
This document discusses generics drugs and provides an overview of their history, types, current state, and future prospects. It notes that generics are copies of branded drugs that are cheaper due to not having research and development costs. The 1984 Hatch-Waxman Act created an abbreviated approval pathway for generics in the US. Today, generics make up a large and growing portion of the global drug market, projected to reach $380 billion by 2021. However, generics still face challenges such as patent litigation from brand manufacturers and price erosion as multiple generics enter the market.
Speaker: Anne Tomalin, BA, BSc, RAC (US, CAN & EU), President of CanReg Inc.
Topics Addressed
* Planning ahead to add credibility and value with your partners, investors and outside experts
* What is the landscape of various filings for a drug, a medical device or a diagnostic device?
* Developing a multi-disciplinary project team to manage your regulatory strategy:
o Different strategies for different products
o How to formulate a sound path to drug development decision-making
* What is needed for approval of a medical device
* The preclinical studies required for an IND filing
* The multiple components of the actual IND submission
* Management and communication between the teams assembling the IND
o When to outsource and bring in consultants
* Interacting with the regulatory authority
Download an audio file of this presentation at:
http://www.marsdd.com/bioent/jan15
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
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.
FDA Regulations and Medical Device Pathways to Market | Kevin Daly | Lunch & ...UCICove
The document discusses FDA regulations for medical devices. It defines a medical device and outlines the steps to determine regulatory requirements, including classifying a device and identifying premarket pathways like 510(k) or PMA. Class I devices have the least requirements while Class III devices require the most oversight like clinical trials. The document reviews elements of 510(k) submissions and other clearance options like de novo. It also discusses quality system requirements and regulations for mobile medical apps and clinical studies.
An Abbreviated New Drug Application (ANDA) contains data to allow the FDA to review and approve a generic drug. The ANDA establishes that the generic is bioequivalent to the reference drug through comparative dissolution or bioequivalence testing.
The FDA reviews the ANDA for bioequivalence, chemistry and manufacturing controls, microbiology, and labeling. If deficiencies are identified, the applicant is notified. If all aspects are acceptable, an approval or tentative approval is issued pending any patent issues. The generic can be marketed once all review steps are successfully completed.
David Glass Presentation at 2016 BIO World CongressDavid Glass
Presentation describing the status of the ongoing efforts to update and modernize the Federal Government's Coordinated Framework for Biotechnology Regulation.
The document discusses the regulation of medical devices in the United States. It begins by defining what constitutes a medical device according to the Code of Federal Regulations. It then outlines the key regulatory bodies that oversee medical devices, including the Center for Devices and Radiological Health and the Office of Combination Products. The document provides an overview of the classification system for medical devices and the different regulatory pathways for approval, including 510(k) premarket notification, investigational device exemptions, premarket approval, and humanitarian device exemption. It also summarizes the key requirements and processes for each approval pathway.
Is your product or medical device FDA-friendly? Learn about how to get a safe and effective product into the market, confronting risk management, complaints, and remediation services.
Presentation at 2016 Fuel Ethanol Workshop, describing U.S. regulatory pathways for approval of use of modified microorganisms in animal feed, and a proposal for making such pathways simpler and more efficient for modified strains of common microorganisms.
This document provides an overview of FDA regulation of medical devices in the United States. It defines key terms, describes the classification system for devices and corresponding levels of regulatory control. It outlines major premarket and postmarket requirements including establishment registration, 510(k) premarket notification, premarket approval, labeling, quality system regulation, medical device reporting and complaint handling. Major sections cover classification, premarket submissions, labeling and other compliance requirements enforced by the FDA to ensure device safety and effectiveness.
Pressure BioSciences is presenting their pressure cycling technology instruments and consumables. Their flagship product is the Barocycler 2320EXTREME instrument, which uses high pressure cycling to prepare biological samples for analysis. They have over 270 PCT systems installed worldwide and publications highlighting the advantages of PCT in biopharma sample preparation from discovery to clinical use. The company is poised for growth with their exclusive marketing agreement with SCIEX, expanded sales team, and focus on the multi-billion dollar biopharma market.
Pharmaceutical and Medical Device Developmentahelicher
This document summarizes the key steps in pharmaceutical and medical device development and regulatory approval processes. It discusses target identification, drug discovery methods, clinical trials, FDA approval pathways, post-marketing surveillance, and efforts to improve medical device safety. It also analyzes the comparative processes and a case study on Vioxx. The development timelines can take over 10 years and involve extensive testing and regulatory oversight by the FDA to ensure public safety.
Advanced Medical Isotope Corporation is developing RadioGel, a brachytherapy device, to treat cancers in humans and animals. The company plans to generate near-term revenue from veterinary clinics and international licensing, while pursuing FDA approval for human cancer indications. RadioGel consists of yttrium-90 phosphate particles delivered via a hydrogel vehicle that solidifies in the body. The company expects to begin sales to veterinary clinics in early 2018 and obtain international licensing revenue. Advanced Medical Isotope Corporation ultimately aims to gain FDA approval to treat cancers like skin cancer and liver cancer in humans using its RadioGel platform.
The document is a presentation about orphan drugs given by Dr. Atul Rajpara. It defines orphan drugs as those intended for the treatment of rare diseases or disorders. It discusses how rare diseases are defined in various countries and notes that over 7,000 rare diseases have been identified worldwide. The presentation outlines the Orphan Drug Act of 1983 in the US and its impact in incentivizing orphan drug development. It also discusses the orphan drug designation process and provides some examples of orphan drugs and their manufacturers. The presentation concludes by noting challenges to improving access to orphan drugs in India like affordability and a lack of incentives for drug developers.
David Glass Plenary Presentation at 4th Algal Biomass, Biofuels and Bioproduc...David Glass
The document discusses the history and current state of U.S. biotechnology regulation as it pertains to genetically modified algae. It notes that while the regulatory framework subjects genetically engineered organisms to additional scrutiny, approvals for commercial uses of GM algae are possible with proper planning and scientific evidence. It outlines the roles of the EPA, USDA and FDA in regulating GM organisms and provides details on relevant regulations. It also discusses scientific issues to address in risk assessments and the need for research to inform the regulatory process.
The Medicines Patent Pool aims to promote innovation and access to HIV medicines through public health-oriented licensing agreements. It has had some successes in negotiating voluntary licenses from patent holders that allow for generic production of HIV drugs in more developing countries. However, more work remains to be done to further expand access, including obtaining licenses for newer second and third line treatments, enabling the development of new fixed-dose combinations, and supporting more local manufacturing in developing regions. The Pool's goal is to establish a new norm of public health-focused licensing that benefits those in need of treatment globally.
Started to create milestones, we Electronica Hi Tech Machines Pvt. Ltd. marked our presence in the year 2007 and operates in the manufacturing/servicing of Turret Punch Presses, Horizontal Machining Centers, Laser Cutting Machine, Profile Bending Machines, Tube Bending Machine since 4 years. Our quality services/products have always won us many appreciations from our clients. Our spontaneous performance and confident approach in offering the excellent range of Turret Punch Presses, Horizontal Machining Centers, Laser Cutting Machine, Profile Bending Machines, Tube Bending Machine, Finance and Loan Services for Industries that has made us to deepen our roots in the market. We Electronica Hi Tech Machines Pvt. Ltd. breathe with the aim to satisfy our clients with our smart products/services. We are a unit of highly experienced professionals who all contribute best of their potentials to offer high efficiency.
The document discusses the Abbreviated New Drug Application (ANDA) process for generic drugs in the United States. An ANDA is a request to the FDA to manufacture and market a generic drug, and is abbreviated since it does not require clinical trials like a New Drug Application. The key points covered include basic generic drug requirements, the objective of reducing drug costs, comparisons between innovator and generic drugs and between NDAs and ANDAs, the Hatch-Waxman Act of 1984 which established the ANDA pathway, patent certification requirements, and an overview of the ANDA review process.
This document discusses generics drugs and provides an overview of their history, types, current state, and future prospects. It notes that generics are copies of branded drugs that are cheaper due to not having research and development costs. The 1984 Hatch-Waxman Act created an abbreviated approval pathway for generics in the US. Today, generics make up a large and growing portion of the global drug market, projected to reach $380 billion by 2021. However, generics still face challenges such as patent litigation from brand manufacturers and price erosion as multiple generics enter the market.
Speaker: Anne Tomalin, BA, BSc, RAC (US, CAN & EU), President of CanReg Inc.
Topics Addressed
* Planning ahead to add credibility and value with your partners, investors and outside experts
* What is the landscape of various filings for a drug, a medical device or a diagnostic device?
* Developing a multi-disciplinary project team to manage your regulatory strategy:
o Different strategies for different products
o How to formulate a sound path to drug development decision-making
* What is needed for approval of a medical device
* The preclinical studies required for an IND filing
* The multiple components of the actual IND submission
* Management and communication between the teams assembling the IND
o When to outsource and bring in consultants
* Interacting with the regulatory authority
Download an audio file of this presentation at:
http://www.marsdd.com/bioent/jan15
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
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.
FDA Regulations and Medical Device Pathways to Market | Kevin Daly | Lunch & ...UCICove
The document discusses FDA regulations for medical devices. It defines a medical device and outlines the steps to determine regulatory requirements, including classifying a device and identifying premarket pathways like 510(k) or PMA. Class I devices have the least requirements while Class III devices require the most oversight like clinical trials. The document reviews elements of 510(k) submissions and other clearance options like de novo. It also discusses quality system requirements and regulations for mobile medical apps and clinical studies.
An Abbreviated New Drug Application (ANDA) contains data to allow the FDA to review and approve a generic drug. The ANDA establishes that the generic is bioequivalent to the reference drug through comparative dissolution or bioequivalence testing.
The FDA reviews the ANDA for bioequivalence, chemistry and manufacturing controls, microbiology, and labeling. If deficiencies are identified, the applicant is notified. If all aspects are acceptable, an approval or tentative approval is issued pending any patent issues. The generic can be marketed once all review steps are successfully completed.
David Glass Presentation at 2016 BIO World CongressDavid Glass
Presentation describing the status of the ongoing efforts to update and modernize the Federal Government's Coordinated Framework for Biotechnology Regulation.
The document discusses the regulation of medical devices in the United States. It begins by defining what constitutes a medical device according to the Code of Federal Regulations. It then outlines the key regulatory bodies that oversee medical devices, including the Center for Devices and Radiological Health and the Office of Combination Products. The document provides an overview of the classification system for medical devices and the different regulatory pathways for approval, including 510(k) premarket notification, investigational device exemptions, premarket approval, and humanitarian device exemption. It also summarizes the key requirements and processes for each approval pathway.
Is your product or medical device FDA-friendly? Learn about how to get a safe and effective product into the market, confronting risk management, complaints, and remediation services.
Presentation at 2016 Fuel Ethanol Workshop, describing U.S. regulatory pathways for approval of use of modified microorganisms in animal feed, and a proposal for making such pathways simpler and more efficient for modified strains of common microorganisms.
This document provides an overview of FDA regulation of medical devices in the United States. It defines key terms, describes the classification system for devices and corresponding levels of regulatory control. It outlines major premarket and postmarket requirements including establishment registration, 510(k) premarket notification, premarket approval, labeling, quality system regulation, medical device reporting and complaint handling. Major sections cover classification, premarket submissions, labeling and other compliance requirements enforced by the FDA to ensure device safety and effectiveness.
Pressure BioSciences is presenting their pressure cycling technology instruments and consumables. Their flagship product is the Barocycler 2320EXTREME instrument, which uses high pressure cycling to prepare biological samples for analysis. They have over 270 PCT systems installed worldwide and publications highlighting the advantages of PCT in biopharma sample preparation from discovery to clinical use. The company is poised for growth with their exclusive marketing agreement with SCIEX, expanded sales team, and focus on the multi-billion dollar biopharma market.
Pharmaceutical and Medical Device Developmentahelicher
This document summarizes the key steps in pharmaceutical and medical device development and regulatory approval processes. It discusses target identification, drug discovery methods, clinical trials, FDA approval pathways, post-marketing surveillance, and efforts to improve medical device safety. It also analyzes the comparative processes and a case study on Vioxx. The development timelines can take over 10 years and involve extensive testing and regulatory oversight by the FDA to ensure public safety.
Advanced Medical Isotope Corporation is developing RadioGel, a brachytherapy device, to treat cancers in humans and animals. The company plans to generate near-term revenue from veterinary clinics and international licensing, while pursuing FDA approval for human cancer indications. RadioGel consists of yttrium-90 phosphate particles delivered via a hydrogel vehicle that solidifies in the body. The company expects to begin sales to veterinary clinics in early 2018 and obtain international licensing revenue. Advanced Medical Isotope Corporation ultimately aims to gain FDA approval to treat cancers like skin cancer and liver cancer in humans using its RadioGel platform.
The document is a presentation about orphan drugs given by Dr. Atul Rajpara. It defines orphan drugs as those intended for the treatment of rare diseases or disorders. It discusses how rare diseases are defined in various countries and notes that over 7,000 rare diseases have been identified worldwide. The presentation outlines the Orphan Drug Act of 1983 in the US and its impact in incentivizing orphan drug development. It also discusses the orphan drug designation process and provides some examples of orphan drugs and their manufacturers. The presentation concludes by noting challenges to improving access to orphan drugs in India like affordability and a lack of incentives for drug developers.
David Glass Plenary Presentation at 4th Algal Biomass, Biofuels and Bioproduc...David Glass
The document discusses the history and current state of U.S. biotechnology regulation as it pertains to genetically modified algae. It notes that while the regulatory framework subjects genetically engineered organisms to additional scrutiny, approvals for commercial uses of GM algae are possible with proper planning and scientific evidence. It outlines the roles of the EPA, USDA and FDA in regulating GM organisms and provides details on relevant regulations. It also discusses scientific issues to address in risk assessments and the need for research to inform the regulatory process.
The Medicines Patent Pool aims to promote innovation and access to HIV medicines through public health-oriented licensing agreements. It has had some successes in negotiating voluntary licenses from patent holders that allow for generic production of HIV drugs in more developing countries. However, more work remains to be done to further expand access, including obtaining licenses for newer second and third line treatments, enabling the development of new fixed-dose combinations, and supporting more local manufacturing in developing regions. The Pool's goal is to establish a new norm of public health-focused licensing that benefits those in need of treatment globally.
Started to create milestones, we Electronica Hi Tech Machines Pvt. Ltd. marked our presence in the year 2007 and operates in the manufacturing/servicing of Turret Punch Presses, Horizontal Machining Centers, Laser Cutting Machine, Profile Bending Machines, Tube Bending Machine since 4 years. Our quality services/products have always won us many appreciations from our clients. Our spontaneous performance and confident approach in offering the excellent range of Turret Punch Presses, Horizontal Machining Centers, Laser Cutting Machine, Profile Bending Machines, Tube Bending Machine, Finance and Loan Services for Industries that has made us to deepen our roots in the market. We Electronica Hi Tech Machines Pvt. Ltd. breathe with the aim to satisfy our clients with our smart products/services. We are a unit of highly experienced professionals who all contribute best of their potentials to offer high efficiency.
1) Measles and mumps vaccines have been in use for over 60 years since being developed in the 1950s and 1960s.
2) Secondary vaccine failures where vaccinated individuals get infected have been observed for measles due to waning antibody levels over time or virus evolution.
3) Recent mumps outbreaks in Europe have affected both vaccinated and unvaccinated individuals, with many cases caused by genotype G, raising questions about vaccine effectiveness.
Molecular characterisation, attenuation and inactivation of very virulent inf...Majed Mohammed
This study aimed to adapt and attenuate a very virulent infectious bursal disease virus (vvIBDV) isolate in tissue culture for vaccine development. The vvIBDV isolate was successfully propagated in embryonated chicken eggs and adapted to grow in Vero and DF-1 cell lines over multiple passages. Molecular characterization found the virus was attenuated after passage 10, 15, and 20. Pathogenicity and immunogenicity tests in chickens found the passage 15 and 20 viruses conferred full protection against challenge when used to vaccinate chickens. Inactivated vaccines using the passage 15 virus in oil emulsion adjuvants also fully protected chickens. The study demonstrates the potential of using the adapted and attenuated vvIBDV in tissue culture to develop effective live
2 Antenatal screening audit 2015 Kate IsraelPHEScreening
This document summarizes the results of an audit of Chelsea and Westminster Hospital's antenatal screening programmes in 2015. The audit assessed compliance with guidelines for explaining screening tests to women, documenting screening results, and managing positive screening results. It found high levels of compliance, ranging from 89-99% for various screening processes. A few areas for improvement were identified, such as ensuring screening results are communicated within 5 days. An action plan was developed to address recommendations, including sharing results, updating training, and improving documentation. Continuous auditing will monitor progress in adhering to screening standards.
This document summarizes an MMR vaccination audit conducted from April 2014 to March 2015 at Princess Royal University Hospital. The audit aimed to identify women who were rubella non-immune and the uptake of the MMR vaccination. The audit identified 225 women as rubella non-immune, with 154 vaccinated, 12 declining vaccination, and 25 miscarried or transferring care. There were difficulties with timely identification, accessing offsite records, and a lack of vaccination knowledge. An action plan was created to improve vaccination documentation, education, and guidelines.
This document is the thesis of Majed H. Mohammed submitted in fulfillment of the requirements for a Doctor of Philosophy degree. The thesis studied the molecular characterization, attenuation, and inactivation of very virulent infectious bursal disease virus (vvIBDV) isolates from Malaysia for the development of tissue culture-based vaccines. Three vvIBDV isolates were propagated in embryonated chicken eggs and cell lines. One isolate, UPM0081, was successfully adapted to Vero and DF-1 cell lines after serial passage. Molecular analysis showed the virus accumulated amino acid substitutions in the VP2 gene with passage in cell culture. Passages 15 and 20 of UPM0081 were non-pathogenic but immunogenic, confer
This document discusses issues in evaluating the impact of a new meningococcal B vaccine. It provides background on the challenges of developing a vaccine for meningococcal B due to its polysaccharide composition. The vaccine Bexsero contains 4 antigens including recombinant proteins and outer membrane vesicles. Clinical trials showed it was safe and immunogenic. Evaluating its strain coverage requires the Meningococcal Antigen Typing System since coverage depends on antigen expression levels and variants. Post-licensure studies will descriptively analyze meningococcal epidemiology by vaccination status and evaluate Bexsero's effectiveness prospectively using methods like the screening method.
The document discusses forming solutions for increasing efficiency in manufacturing operations. It provides an overview of why forming is useful, examples of how it can replace or improve upon other processes like punching, and basics of forming like considerations for setup and maximum form heights. Key advantages of forming include increased efficiency, expanded capabilities, and elimination of secondary operations.
Methods for characterization of animal genomes(snp,str,qtl,rflp,rapd)Dr Vijayata choudhary
The document discusses several methods for characterizing animal genomes, including Restriction Fragment Length Polymorphism (RFLP), Random Amplified Polymorphic DNA (RAPD), Single Nucleotide Polymorphisms (SNPs), Short Tandem Repeats (STRs), and Quantitative Trait Loci (QTL). It provides detailed descriptions of each method, including how they are detected and analyzed as well as their applications in areas like genetic mapping, diversity studies, and phylogenetic analysis.
Does Price Discrimination Have a Place in Pharmaceutical Pricing in Developin...Office of Health Economics
At iHEA 2013, OHE's Adrian Towse participated in a session on implementing differential pricing schemes. He discussed the role of price discrimination strategies, including the use of discounts, access programmes and risk sharing agreements in increasing the number of patients who can benefit from new medications in LMICs. Real life examples illustrated differential pricing schemes between and within countries and provided background for exploring feasibility—particularly about how options relying on confidentiality and negotiation compare with those based on collaborative international agreement about how price differentiation is developed and implemented.
The document summarizes a training workshop on improved poultry farming techniques. It discusses objectives of equipping participants with health, husbandry and business skills. It covers poultry management topics like housing requirements, sources of chicks, transportation and proper management of day old chicks. Key factors for success like human resources, technical environment and disease control are outlined.
This document discusses measles, mumps, and rubella. Measles causes a rash and is spread through respiratory droplets. It can lead to complications like pneumonia or encephalitis. Mumps causes swelling of the salivary glands and is common in children ages 2-12. It spreads through respiratory droplets. Rubella, also called German measles, causes a rash and inflammation and is spread through the air or close contact. All three diseases can be prevented through routine immunization with the MMR vaccine.
The cholera outbreak in Haiti has resulted in over 664,000 cases and 8,000 deaths since 2010. Cholera spreads rapidly in areas with contaminated water and poor sanitation. Factors exacerbating the outbreak in Haiti include a lack of immunity, poverty, damage from natural disasters, and an increased virulence in the cholera strain. NGOs like Oxfam have implemented water, sanitation, and hygiene programs to control transmission, including chlorine dispensers, wells, latrines, and health education. However, ongoing issues like flooding and funding gaps increase the risk of further cholera spread.
This ppt provide information about the conventional methods of animal vaccine production..it is somewhat differ from my earlier ppt of vaccine production techniques..
To synthesize a live attenuated vaccine, the disease-causing organism is grown under special laboratory conditions ,Vaccine production and purification
The document discusses the MMR vaccine, which protects against measles, mumps, and rubella. It describes the diseases the vaccine protects against and how the vaccine was developed using weakened live viruses. The document notes common side effects of the vaccine are mild and temporary, like fever or rash, and that severe reactions are very rare. It addresses concerns about links between the MMR vaccine and autism.
This document provides information about deep drawing and sheet metal forming equipment. It discusses the history and definition of deep drawing, the mechanics and process of drawing, types of deep drawing stations like blanking, drawing, piercing and trimming. It also describes the metal flow during drawing, recommended tool materials, lubrication and cooling methods, common defects, advantages and disadvantages of deep drawing. Different applications of deep drawing in Pakistani industry are highlighted. Comparisons are made between deep drawing and superplastic forming. Finally, various metal forming tools and types of forming dies are explained.
This document discusses neglected tropical diseases (NTDs), which are a group of diseases that plague millions in tropical areas in developing countries. It describes the 17 NTDs profiled by the WHO, which are caused by a variety of pathogens including parasites, bacteria and viruses. NTDs disproportionately impact those living in poverty without access to clean water and sanitation. While some NTDs can be cured, many cause long-term disability and social stigma. The WHO's strategies to control NTDs include preventive chemotherapy, intensified case management, vector control, and improving water/sanitation.
This document discusses opportunistic infections (OIs) that occur in patients with AIDS. It defines AIDS according to CDC and NACO criteria involving OIs or low CD4 counts. Common OIs seen in India are described such as tuberculosis, candidiasis, cryptosporidiosis, herpes zoster, toxoplasmosis, and Pneumocystis pneumonia. Symptoms, diagnosis, and treatment of these OIs are outlined. The role of patient education in prevention and treatment adherence is also discussed.
The document summarizes a platform technology called the Hemopurifier that can address bioterrorism threats. The Hemopurifier is a medical device that removes infectious viruses and immunosuppressive proteins from the entire circulatory system before infection occurs. It has been demonstrated to be safe in human studies and can capture pathogens like Ebola, smallpox, and influenza. The Hemopurifier offers a broad-spectrum treatment approach against bioterrorism threats as an alternative or addition to single-target drug and vaccine strategies, which have limitations and high costs. The company believes the Hemopurifier is the most advanced countermeasure against viral threats that could be weaponized.
The document provides 6 questions and their solutions related to applications of biotechnology. It discusses topics like induced pluripotent stem cells, Biotechnology Innovation Organization, applications of gene therapy, orphan drugs, bioprospecting, and the Human Genome Project. The questions aim to test the reader's understanding of these concepts and recent developments in biotechnology.
Orphan Drugs – the Challenges and Benefits of Navigating FDA’s Regime Governi...Michael Swit
Webinar sponsored by The Weinberg Group on Orphan Drugs, covering these topics:
The Basics of the Orphan Drug Act
Benefits of Orphan Drug status
Exclusivity
Protocol assistance, tax credits, and research grants
When is an indication is “rare”?
Orphan Drug Designation Requests – ensuring yours
robust and persuasive
Approval criteria for orphan products – how they
compare to non-orphan products
Challenges in the Orphan Drug Process
This document discusses biosimilars, which are biologic drugs that are similar but not identical to already approved biologic drugs (reference biologics). It provides background on biologics and biosimilars, including that biosimilars take longer and cost less to develop than original biologics. Several regulatory issues for biosimilars are also discussed, such as naming, substitution, approval of indications, and reimbursement. The US recently approved its first biosimilar, but still lags behind Europe in approving and using biosimilars.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay
This document discusses the Orphan Drug Act and rare disease policies. It provides background on the US Orphan Drug Act of 1983, which aims to facilitate rare disease drug development by providing incentives. Key points include that the Act defines rare diseases as affecting fewer than 200,000 people, and has led to over 450 approved orphan drugs. However, the document notes that rare disease policies and the Orphan Drug Act are not the same. It advocates for India to enact its own rare disease policies and definitions to improve diagnosis, treatment and research. The Organization for Rare Diseases India is working towards this goal.
1- MarketingBefore putting the product into the market, the prod.docxmonicafrancis71118
1- Marketing
Before putting the product into the market, the product goes through several stages. One of the most important stages is to determine the price of the product. After that, it will be studied by asking questions to customers and anticipate their requirements in terms of shape, colour phrases recorded on it. It can be applied using servery or interview the customer. Finally, the product needs to be promoting before it is been released, so electronic, and visual and audio can be used as advertising. However, in this experiment, we will focus only on the total cost of the product and then work on finding who develops the product….[9] [10].
1.1 Estimating of the total price.
For the antibiotic spray, it can be estimate the total price depend on the type of the material which were be used. Thus, the material in the table estimates the total price.
Material
Discerption
Brand/ manufacture
Price Ink VAT.
[1] Cefuroxime(as Cefuroxime sodium) 1.5 gram.
CEFUROXIME is a cephalosporin antibiotic. It is used to treat certain kinds of bacterial infections. It will not work for colds, flu, or other viral infections
£4.70
[2] Sterile Water (1000ml)
Single Bottle of Sterile Water (1000ml)
Baxter
£3.54
[3] 73.5 mg of sodium
Sodium Bicarbonate 2kg - Pharmaceutical Grade (Bicarb/Bicarbonate of Soda)
£6.49
[1] Metronidazole
Metronidazole 500mg/100ml infusion 100ml bags (A A H Pharmaceuticals Ltd)
£63.86
[4] Phosphatebuffer (pKa=7.2)
PBS405.1 Virtual PHOSPHATE BUFFERED SALINE pH 7.4 10X Liquid Concentrate, 1L
£22.75
[5] Brilliant Blue FCF
1 kilogram
£6-8
[6] 100ml Stainless Steel
Empty stainless bottle spray
£7-9
Total price
£118
2- Companies and industry
There are many companies interested to work on or collaborate for developing the antibiotic. Following, there are some of the companies, Charities and universities, which they work hardly to improve public health and more specifically in the development of antibiotics. Thus, the product will be a focuses for them and new idea that can be started to develop and prove its effectiveness. Then, it can be put in the market, which many people can take advantage of the ease and licences of the product.
2.1. GSK Company [13]
At GSK, they are at the forefront of researching new ways to tackle some of the world’s biggest healthcare challenges. So as antibiotic resistance grows, they are investing in new ways to fight infection.
Their approach is to make the most of their own expertise and experience, while at the same time forming complementary partnerships and alliances with others who bring different kinds of expertise. Their vision for the world, where everyone has access to the vaccines they need, depends on a steady supply of great ideas and brilliant science. They have much to offer and through collaboration, they can achieve so much more.
For example, more than 90% of the vaccines in their pipeline are being developed in partnership with others. They have a long track rec.
The document proposes a new model called the Health Impact Fund (HIF) to stimulate research and development of life-saving pharmaceuticals. The HIF would reward drug developers based on the actual health impact of their products, as measured by quality-adjusted life years (QALYs). Developers could opt into the HIF and sell their drugs at low prices in exchange for reward payments over 10 years. The HIF aims to address current inefficiencies in drug development and access by incentivizing research for neglected diseases and making drugs affordable for more people. A pilot program is suggested to test the HIF model.
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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 a high-level overview of the vaccine development process from research and testing in animals through clinical trials in humans and regulatory approval. It discusses key stages including preclinical research in animal models to test safety and efficacy, phases of human clinical trials, requirements for good manufacturing practices and regulatory compliance, and the role of quality assurance. It also provides examples of DVC's experience developing vaccines for biodefense threats like anthrax, smallpox, and plague.
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In order to promote the uptake of biosimilars across the U.S., stakeholders must be informed about the basic science of these important medicines. Created out of the Biosimilars Forum's Biosimilars Roundtable (formerly the Biosimilars Forum Stakeholder Workshop group), this two page document incorporates feedback from nearly 40 stakeholder groups, from patient advocacy organizations to physician and payer groups, and presents the basic knowledge that all stakeholders need to know about the safety and efficacy of biosimilars, including answers to common myths about them.
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Dr. Ravi Dhar reviews "IP Barriers in Generic Vaccines in 2014"
1. IP Barriers
in
Developing
Generic Vaccines
&
How to Tackle these!
(F)
Ravi Dhar, Ph.D.
(rdhar_in@yahoo.com)
(rdhar.birac@nic.in)
5.3.2014
(Mobile: 987-162-0439)
Affiliation:
BIRAC-DBT, GoI, India
Past Affiliations:
University of Kashmir, India
University of Delhi, India
National Institute of Immunology, India
Johns Hopkins University, U.S.A.
LSU, U.S.A.
OTT, Boston University, U.S.A.
OTT, NIH, U.S.A.
4/6/2014 1RD_Vaccine Meet_2014
“Protecting the bottom line: Tackling IP barriers in
developing generic vaccines”.
Vaccine World Summit-2014, Hyderabad, India
2. 4/6/2014 RD_Vaccine Meet_2014
Acknowledgements
IMAPAC_2014, Singapore
NIH PubMed
Scientific Community across world
DBT, GoI
NII, India
Dr. M.K. Bhan, India
Dr. Gerald T. Keusch, BU, USA
Dr. Asley Stevens, BU, USA
DELCON Library @BIRAC
Various Websites
USPTO/EPO/IPO
Nature Biotechnology
& other Journals
GHI & OTT, Boston University, USA
OTT, NIH, USA
2
4. 4/6/2014 RD_Vaccine Meet_2014 4
Basic Information:
When a new product like drug or vaccine is developed, it is patented.
Generic drugs or vaccines can be legally produced as drugs when:
1) the patent has expired,
2) the generic company certifies the brand company's patents are either
invalid, unenforceable or will not be infringed,
3) for drugs which have never held patents, or
4) in countries where a patent(s) is/are not in force.
The expiration of a patent removes the monopoly of the patent holder on drug sales licensing.
Patent lifetime differs from country to country, and typically there is no way to renew a patent after it expires.
A new version of the drug/vaccine with significant changes to the
compound or structure could be patented, but this requires new clinical
trials.
In addition, a patent on a changed compound/ or component of vaccine
does not prevent sales of the generic versions of the original drug unless
regulators take the original drug off the market
5. 4/6/2014 RD_Vaccine Meet_2014 5
Issue on Generics
Patented Medical interventions
vs.
Requirement of wide range of affordable Medical interventions:
Drugs/vaccines/devices/ diagnostics
Do we need to produce Generic Products
or
Modify Intellectual Property Laws
&
Modify International Treaties
6. 4/6/2014 RD_Vaccine Meet_2014 6
The first task in developing a utilitarian
theory of intellectual property is
translating the ideal of the "greatest
good of the greatest number” (social
welfare in mind), yet allowing the
creator to maximize wealth.
(Source: Richard Posner, Economic Analysis of Law (3rd ed., Boston: Little, Brown,
1986), pp. 11-15)
7. 4/6/2014 RD_Vaccine Meet_2014 7
Importance of Generics (U.S. example):
In USA 80% of U.S. prescriptions filled with a generic medicine
Food and Drug Administration (FDA): This agency must approve
every generic medicine before it can be sold in the United States
Proving Bio-equivalance
80-85% cost savings by consuming generic medicines
$1 Trillion! According to IMS Health, generic medications saved
the American health care system $1 trillion between 2002 and
2011
GBR® — Generic Brand Reference Guide
This easy-to-use guide—available as a smart phone app or by mail—offers health
care professionals cross-referenced lists of brand name and generic medicines.
8. 4/6/2014 RD_Vaccine Meet_2014 8
“To gain FDA approval, generic medicines must be proven to be
“bioequivalent” to their brand name counterparts. That means
generic and brand name medicines are the same in the following
ways:
Active ingredient
Maximum amount of medicine in the blood at any given time
Total amount of medicine in the blood from the time it’s taken until
the body eliminates it
Strength and dosage
Route of administration—tablet, injection, etc.
Expected safety and efficacy
FDA evaluation of manufacturing facilities
Just because products have the same active ingredient does not
mean they are bioequivalent. Once generic bioequivalence is proven,
the FDA considers a generic medicine interchangeable with the
brand name medicine.”
(Source: http://www.mylan.com/products/why-generics)
9. 4/6/2014 RD_Vaccine Meet_2014 9
Tackling Patent Reforms (US Academia view point-2013)
Discourage weak claims of patent infringement brought at least in part for nuisance value
Limit the scope of discovery in patent cases prior to the issuance of a claim construction
order
To contain/address un-necessary litigations. To facilitate the early adjudication of patent
infringement suits, we recommend that patentees be required to plead their infringement
allegations with greater specificity.
To increase transparency and confidence in the market for patent licensing:
(a) Government should ask patentees … to disclose and keep up-to-date the
identity of parties with an ownership stake or other direct financial interest in their patent
rights.
(b) Government should consider additional legislation designed to deter
fraudulent, misleading, or otherwise abusive patent licensing demands made outside of
court.
(Source: http://www.patentlyo.com/patent/2013/11/ip-law-professors-rise-up-against-patent-assertion-entities.html)
11. An Interesting Article:
GLOBAL HEALTH: A NORMATIVE ANALYSIS OF
INTELLECTUAL PROPERTY RIGHTS AND
GLOBAL DISTRIBUTIVE JUSTICE
by
Matthew Wayne DeCamp
Department of Philosophy
Duke University
Date: 25 April 2007
(http://dukespace.lib.duke.edu/dspace/bitstream/handle/10161/193/D_DeCamp_Matthew_Wayne_a_052007.pdf?sequence=1)
4/6/2014 11RD_Vaccine Meet_2014
12. VACCINE TECHNOLOGY TRANSFER: SUMMARY CHART
ERAS TECHNOLOGY ECONOMICS POLITICS REGULATION LEGAL AND
INTELLECTUAL
PROPERTY
TECHNOLOGY
TRANSFER
HEROIC Low Low cost Colonial policy
plus altruism
Nearly absent Absent Institut Pasteur
MID-CENTURY Moving Increasing cost National health
programs
Strengthening
from a low base
Absent WHO, national
institutes,
meetings,
education?
ERADICATION
PROGRAMS
Moving Pressure by
buyers
Altruism, global
budget issues
Strengthening,
WHO
prequalification
Nearly absent WHO, expert
groups, donor
funding
CURRENT High High cost/low
margin,
economies of
scale
Self-sufficiency,
biotechnology,
donor politics,
privatization
-Very high
domestic and
parallel
-WHO
prequalification
Strengthening but
mainly on
intermediates and
processes
WHO DCVMN,
biotechnology
programs,
corporate
strategic alliances,
donors
education
FUTURE? High Globalization? Access?
Financial
sustainability?
ICH? Research tool
issues?
Bio-terrorism
concerns?
Global
integration?
12
Source: J.Barton@Stanford, U.S.A.
4/6/2014 RD_Vaccine Meet_2014
13. 4/6/2014 RD_Vaccine Meet_2014 13
On Generics:
(1) A generic drug has lower development costs because
it can rely on the research data from the originator
product, As far as the generics are concerned, all they
have to show is bio-equivalency to the innovators
product and piggy-ride on the rest of the innovators
data. For challenging molecules, where bioavailability is
an issue, the generics have a tough time achieving bio-
equivalency, due to several factors, and are a cause for
concern.
(2) The patent life of a new molecule in the United state is 17 years from first discovery. It takes quite a few years
in preclinical, pharmacology, pharmacokinetics,/drug metabolism, toxicology and formulation development,
phase 1, 2 and 3 with longest time required in phase 3 depending on the diseases the drug is being targeted for.
By this time, in most instances, the time left for return, on about a billion dollars invested to discover and develop
a new molecule, is about 10 years or less.
15. 4/6/2014 RD_Vaccine Meet_2014 15
We need to answer the
following critical questions!
Q) Whether the current medical innovation
system works, and for whom.
Answer: It works & has delivered, however,
generics are important & affordable for
economically weak sections of society
Q) How best could governments balance
private commercial interests and public
health in their IP laws?
Answer: Difficult question for any developing or
under-developed country due to financial
constraints. However, to balance these, both are
equally important
Barrier=Obstruction/ Issue=Important Topic for debate
17. 4/6/2014 RD_Vaccine Meet_2014 17
Are there Generic Vaccines?
There is no (?) such thing as a
generic vaccine.
Even vaccines based as closely as possible on
licensed products must prove safety and
efficacy in clinical trials, although for many
well-established classes of vaccines, these trials
can be smaller than the trials used to license
the original vaccine.
Vaccines are also biologics, but are generally
even more complex than biologic drugs.
Source: Expert Rev. Vaccines 8(10): 1439-49.
18. 4/6/2014 RD_Vaccine Meet_2014 22
Why Generic Vaccines?
Generic vaccines are cheaper
A high percentage of vaccination would
drastically decrease the spread of disease
Benefits the Governments by
complementing preventive health
measures
Employers have to deal with healthy and
productive workforce
Families would benefit by gaining workable
man-days
Benefits individuals because of good health
quality & loss of man days
21. 4/6/2014 RD_Vaccine Meet_2014 21
Recent Policy of Indian
Government
The health ministry has revealed that Rs 16,000
crore have been earmarked for distribution of
free generic medicines under 12th five year plan
through various schemes.
"There is an outlay of Rs 16,000 crore for this initiative in the
12th Plan. The initiative is based on the Tamil Nadu model
where free medicines procured in bulk by the Tamil Nadu
Medical Services Corporation (TNMSC), in generic name, directly
from the manufacturers is supplied through an IT enabled
supply chain management system to the public” (Indian Health
minister-26.8.2013)
(http://www.biospectrumindia.com/biospecindia/news/194111/govt-free-generic-
medicines-priority#16387c;%20font-size:14px;%20display:block;%20text-
decoration:none;%20“)
24. 4/6/2014 RD_Vaccine Meet_2014 24
Vaccine Development
The development cycle is quite different from that of
traditional pharmaceuticals:
Exploratory stage: to understand the disease, its
epidemiological data and the right proteins (antigens)
to use in preventing or treating the disease;
Pre-clinical stage: to assess antigen safety and
select the best candidate vaccine;
Clinical development: from 10 (Phase I) to 1,000
people (Phase III) are involved in clinical trials and the
first batches are produced (clinical batches and
industrial batches for compliance);
Regulatory approval: all the data collected through
the preceding stages are submitted to the relevant
health authorities for approval;
Manufacturing process: takes up to 22 months to
produce a single batch of vaccine;
Quality control: approximately 70% of production
time is dedicated to quality control.
25. 4/6/2014 RD_Vaccine Meet_2014 25
CAUTION
Once a vaccine is ready, it needs to be
preceded by Implementation research (which is
an important step toward achieving high
vaccine coverage and the uptake of desirable
new vaccines) is a highly complex and requires
participation of stakeholders from diverse
backgrounds to ensure effective planning,
execution, interpretation, and adoption of
research outcomes.
Unlike other scientific disciplines,
implementation research is highly contextual
and depends on social, cultural, geographic,
and economic factors to make the findings
useful for local, national, and regional
applications.
26. 4/6/2014 RD_Vaccine Meet_2014 26
Problem Actions required
Inadequate preclinical data and lack of detailed
information on protective correlates of immunity
contribute to product failure in clinical trials
Development of more relevant animal models;
more human samples to be collected and analysed;
increased use of experimental human challenge
infections
Lack of information on the infectious exposures of
intended vaccine recipients
More human samples to be collected and analysed
Vaccines are to be used in populations with less-
responsive immune systems
Gain a greater understanding of the mechanisms of
action of currently used adjuvants; development of
vaccine delivery systems specifically for use in
immunocompromised populations
Antigenic variation requires constant updating of
vaccine formulations
Seek conserved antigens; monitor genetic variation
of infectious organisms in the community
High costs of vaccine development result in
premature abandonment of potentially useful
products
More investment in vaccine research
Inadequate access to vaccines in poorer countries,
especially those for use against tropical diseases
More tiered pricing strategies; facilitate the
development of vaccines in developing countries
The current challenges for vaccine development
J Med Microbiol July 2012 vol. 61 no. Pt 7 889-894
28. 4/6/2014 RD_Vaccine Meet_2014 28
The Contradiction in IP protection
“An R&D system exclusively based on IP does not
generate sufficient economic incentives for
pharmaceutical companies to develop medicines
needed predominantly in poor countries.
In fact, many pharmaceutical companies have
downsized or shut down their infectious-disease R&D
divisions, the recent one being Astra Zeneca closure in
india.
IP often by itself, acts as a barrier to innovation :
‘Patent thickets’severely limit the ability of researchers
to develop new treatments and technologies.
Increasingly, the existing approach to R&D is failing rich
countries too, with few pharmaceutical companies
successfully replenishing their drug pipelines”
29. 4/6/2014 RD_Vaccine Meet_2014 29
Possible Solution (Israeli experience)
Takeda (10th largest pharma company in the world),
advances a very strong late-stage pipeline to develop a
successful vaccine business that has the potential to be
commercially attractive while at the same time creating
low-cost health solutions (i.e. vaccines) for some of the
poorest countries in the world (i.e. emerging markets).
In order to do so, the company is building its strong vaccine
franchise network to achieve this goal.
30. 4/6/2014 RD_Vaccine Meet_2014 30
Recommendation of Sixty-fifth (65th) WHA, 194 Member States endorsed the
GVAP's goals and the following six strategic objectives (May 2012):
(1) All countries commit to immunization as a priority for all stakeholders in a country,
and establish good governance for effective, high-quality immunization services.
(2) Individuals and communities should demand immunization as both their right and
responsibility.
(3) Equitable access to immunization should be a core component of the Right to Health.
(4) Strong immunization systems should become integral parts of well-functioning health
systems so that it works in a coordinated manner to achieve national-level goals.
(5) Immunization programs should have sustainable and appropriate level of funding,
management, and oversight to ensure the sustainability of immunization programs.
(6) A continuous improvement and innovation in research and development is necessary
in all aspects of immunization, from communication to genomics at country, regional,
and global research levels to maximize the benefits of immunization
(Source :Alonso, P.L., deQudros C.A., Robert M. & Lal A.A. (2013) Editorial in Vaccine 31(2), April 2013)
31. 4/6/2014 RD_Vaccine Meet_2014 31
Generic vaccines are highly regulated!
Being biological products, Governments are
concerned about regulating all aspects of
vaccine development namely:-
Product safety
Clinical trials
Pricing
Reimbursement
Patent protection
R&D incentives
Mode of administration
Issues of thermo-stability managed by generic
manufacturers
Concept of differential pricing
34. 4/6/2014 RD_Vaccine Meet_2014 34
IP Barriers for Vaccine Development
Technical
Legal
Regulatory
Ethical
Societal
35. 4/6/2014 RD_Vaccine Meet_2014 35
IP Barriers
Technical
The term “Technology Barrier” refers to the use of laws, directives, regulations and standards to regulate trade
between countries. Utilizing certification, inspection and such process to impose new requirements on import
goods based on technology, health concern, packaging and labelling. On the surface, it is to raise the quality
standard of the merchandize, but the ultimate is to limit import. In this tariff verses non-tariff
era, the standards set for technology barriers are said to protect the welfare of the consumer and thus
favoured by all countries. Since it improves the quality and protects consumer rights, it is therefore, accepted
and implemented in different countries
Legal
Regulation
According to “article 20?(general exception) and “article 21?(safety exception) of GATT, nations have the right
to protect the safety of its people and its plants. When safety is threatened, they can take exceptions from
GATT in setting technical standards. This is outside the rules that regulate import quota base on the national
per capita income rule. However, as mentioned, technical standards are usually wrongfully used in
international trade for self-protection. It has become means to limit import. It has become barriers to free
trade. The Ecuador resolution results in the TBT treaty, , hereon referred as SPS Treaty. Besides the treaty,
there are also other conditions that constituted WTO’s restriction on utilizing technology barrier on
international trade.
Ethical
Societal: depends on economic status, poverty, affordability etc??
36. IP issues
Virus genes, gene sequences, treatments, and vaccines:
These include proprietary claims on viruses originating in developing countries and
that were shared with the international community for public health purposes
(H5N1 Vaccines)
Synthetic consensus Antigens:
The patent includes claims that cover the synthetic consensus H1 antigen and DNA
constructs and vaccines that include this antigen, including universal influenza
vaccine INO-3510. This patent also covers methods of treating a patient using the
SynCon® universal influenza vaccine
(http://www.news-medical.net/news/20120326/USPTO-issues-patent-to-Inovios-SynCon-H1N1-
influenza-vaccine.aspx)
Vaccine Stabilization Technology:
The novel technology could eliminate the need for cold-chain production,
transportation and storage for Alum adjuvanted vaccines. ThermoVax is
exclusively licensed to Soligenix by the University of Colorado. The main patent
claims describe methods to prepare an immunologically-active adjuvant-bound,
freeze-dried, thermostable vaccine composition in which the vaccine uses Alum
adjuvants. The main patent also includes claims for the adjuvant-bound
composition itself.
4/6/2014 36RD_Vaccine Meet_2014
37. 4/6/2014 RD_Vaccine Meet_2014 37
IP Barriers
Technical
The term “Technology Barrier” refers to the use of
laws, directives, regulations and standards to
regulate trade between countries. Utilizing
certification, inspection and such process to
impose new requirements on import goods based
on technology, health concern, packaging and
labelling. On the surface, it is to raise the quality
standard of the merchandize, but the ultimate is
to limit import. In this tariff verses non-tariff era,
the standards set for technology barriers are said
to protect the welfare of the consumer and thus
favoured by all countries. Since it improves the
quality and protects consumer rights, it is
therefore, accepted and implemented in different
countries
38. 4/6/2014 RD_Vaccine Meet_2014 38
IP Barriers
Legal
Infringements of various
scales – has become a
subsidiary business for some
39. 4/6/2014 RD_Vaccine Meet_2014 39
IP Barriers
Regulation
According to “article 20?(general exception) and
“article 21?(safety exception) of GATT, nations
have the right to protect the safety of its people
and its plants.
When safety is threatened, they can take exceptions from GATT in
setting technical standards. This is outside the rules that regulate
import quota base on the national per capita income rule.
However, as mentioned, technical standards are usually wrongfully
used in international trade for self-protection. It has become
means to limit import. It has become barriers to free trade. The
Ecuador resolution results in the TBT treaty, , hereon referred as
SPS Treaty. Besides the treaty, there are also other conditions that
constituted WTO’s restriction on utilizing technology barrier on
international trade.
40. 4/6/2014 RD_Vaccine Meet_2014 40
IP Barriers
Ethical
READ this: http://www.allergysa.org/journals/2009/november/vaccination-and-ethical-issues.pdf
????
“Compulsory vaccination was originally introduced for smallpox, and
mandatory immunisation is still in force in some countries. Vaccination is
no longer compulsory in South Africa, but carries significant benefits both
for individuals and for the community. An ethical dilemma is posed by the
fact that the vaccine is administered to a healthy child, with the intention
of protecting both the individual child and the community, but the risk
has to be borne by the child alone. The anti-vaccination lobby claims that
there is an association between measles-mumps-rubella (MMR) vaccine
and autism, but there are no data to support this. Parents generally have
the best interests of the child at heart, and parental autonomy to refuse
vaccination should be respected unless the child is considered to be at
significant risk from that refusal. Equity of access to vaccinations is
ensured by the public health system in South Africa. The introduction of
pneumococcal conjugate vaccine and rotavirus vaccine into the
immunisation programme is in the interests of the public, but carries
significant cost implications.”
41. 4/6/2014 RD_Vaccine Meet_2014 41
IP Barriers
Societal: depends on unmet
medical needs, economic status,
poverty, affordability etc??
42. 4/6/2014 RD_Vaccine Meet_2014 42
Inspite of all the issues, people need
generic vaccines even in developed countries.
This has become more important due to
increase in poverty levels world wide
47. 4/6/2014 RD_Vaccine Meet_2014 47
Platform Processes
DNA Sequences
Cell Lines
Antigen
Bio-processing/
Production
Expression of
Cells used
Vehicle
Immunostim
Formulations
&
Excipients
Animal
Models
Issues related to New
Clinical Trials
Delivery
Device
Yield
improvement
Know-how &
Trade Secrets
Fishing out new IP
Mechatronics used for vaccine
production
Reference
Reagents
Protocols
Adjuvant
VACCINES
(Source: http://www.wto.org/english/tratop_e/trips_e/techsymp_feb11_e/friede_18.2.11_e.pdf ) (modified)
48. 4/6/2014 RD_Vaccine Meet_2014 48
Do True Generic Drugs Exist?
True 'generic' vaccines do not exist
Complex biological drugs: equivalence can not
be demonstrated by simple tests.
Full clinical safety and efficacy (or surrogate)
testing of 'copy' required.
Even in absence of patent barriers numerous
barriers to vaccine production
– Expertise, know how, previous clinical data
– Cost (investment, production)
– Clinical studies (possibly very large if comparing
efficacy to existing vaccine)
http://www.who.int/phi/news/Presentation15.pdf
49. 4/6/2014 RD_Vaccine Meet_2014 49
Trade secrets/know-how
Many critical aspects of the operations of bio-
processing facilities are valuable knowledge.
In some jurisdictions, this knowledge can be protected
under trade secret law.
It is customary for any pharmaceutical production plant
to keep its standard operating procedures as trade
secrets, given the considerable time and resources
involved in fine tuning operations.
SOPs & Business Plans are also restricted
By extension, employees of such plants will need to be
informed of procedures for keeping information
confidential and should have related clauses in their
employment contracts.
Misappropriation: Merck vs SKB 1999
50. 4/6/2014 RD_Vaccine Meet_2014 50
Vaccines under development in India in academic institutions
Human vaccines
under
development
Institutions
involved
Status
Cholera vaccine
Dengue vaccine
Hepatitis A HIV
vaccine Japanese
encephalitis
vaccine
Leishmania
vaccine Malaria
vaccine Rotavirus
vaccine
Tuberculosis
vaccine Typhoid
vaccine
IMTECH,
Chandigarh; NICED,
Kolkata ICGEB, N.
Delhi NIV, Pune
THSTI, Gurgaon;
IAVI NII, N. Delhi NIV
and University of
Pune, Pune IOP and
IMM, N. Delhi ICGEB,
N. Delhi AIIMS, New
Delhi; CDC and NIH,
USA THSTI and
UDSC, N. Delhi
AIIMS, N. Delhi
Live oral cholera vaccine candidate vaccine strain VA1.4 Phase II studies
completed, Phase III will begin soon. Efforts on developing safe,
efficacious and inexpensive tetravalent dengue vaccine candidate are
underway. An agreement for transfer has been signed with BBIL for further
development. Efforts are underway to design of candidate vaccines to
elicit neutralizing antibodies against HIV. (1) Vero cell-derived inactivated
JEV vaccine developed was transferred to Panacea Biotech. (2) JE
chimeric peptide based vaccine has been transferred BBIL, Hyderabad.
Use of live-attenuated Leishmania donovani parasites as vaccine
candidates against visceral leishmaniasis is being tested at laboratory
scale. PvDBPII for P. vivax and JAIVAC-1 vaccine for P. falciparum has
been transferred to BBIL, Hyderabad. Phase I clinical trials completed.
Phase III clinical trial of rotavirus vaccine 116E underway at three sites:
SAS, N. Delhi; CMC, Vellore; KEM Hospital Pune. Recombinant BCG 85c
(rBCG85c), one of several candidates that showed promising results in
animals, is being developed as a TB vaccine. A Vi-conjugate typhoid
vaccine technology has been transferred to USV Ltd. Mumbai.
AIIMS, All India Institute of Medical Sciences; BBIL, Bharat Biotech International Ltd.; CDC, US Centers for Disease Control and Protection; HIV, Human immunodeficiency virus; IAVI, International AIDS Vaccine
Initiative; ICGEB, International Center for Genetic Engineering and Biotechnology; IMM, Institute of Molecular Medicine; IMTECH, Institute of Microbial Technology; IOP, Institute of Pathology; JEV, Japanese
encephalitis virus; NICED, National Institute of Cholera and Infectious Diseases NII, National Institute of Immunology; NIH, US National Institutes of Health; NIV, National Institute of Virology; THSTI, Translational
Health Science Technology Institute; UDSC, University of Delhi, South Campus. a Compiled from Annual reports of Department of Biotechnology and Indian Council of Medical Research.
Source: Sen Gupta, Sanjukta, et al. (2013) Vaccine development and deployment: Opportunities and challenges in India. Vaccine 31(2), B43-B53
51. 4/6/2014 RD_Vaccine Meet_2014 51
Bolar Provision/Research
Exemption
Implemented from 2003 in India
Useful for Indian generic manufacturers
Technical consultations should be carried out to examine the
possibility of any alteration in vaccine formulation (e.g. vaccines
with or without preservative, with or without adjuvant, liquid or
lyophilized etc.) that could enable the use of a vaccine in the
existing schedule. Such a consultative process should include
scientists, program managers, cold chain managers and
representatives of the manufacturers.
The combinations vaccines have shown to improve coverage,
and reduce non-program costs, especially in countries with
similar issues. These factors should be considered before
making a decision on the use of combination vaccines
Source: National Vaccine Policy, India, 2011
52. 4/6/2014 RD_Vaccine Meet_2014 52
Drug Applications and Current Good
Manufacturing Practice (cGMP)
Regulations (US-FDA)
FDA ensures the quality of drug products by carefully monitoring drug manufacturers' compliance with its Current Good
Manufacturing Practice (CGMP) regulations. The CGMP regulations for drugs contain minimum requirements for the methods,
facilities, and controls used in manufacturing, processing, and packing of a drug product. The regulations make sure that a
product is safe for use, and that it has the ingredients and strength it claims to have.
The approval process for new drug and generic drug marketing
applications includes a review of the manufacturer's
compliance with the cGMP.
53. 4/6/2014 RD_Vaccine Meet_2014 53
Need for Effective databases
Lack of patent claim information in publicly available
Indian patent databases hampers pace of R&D.
Bharat Biotech’s R&D was delayed due to uncertainty
about the status of patent protection for HPV antigens in
India.
Moreover, many countries in Africa, Latin America and
Southeast Asia – potential markets for HPV vaccines –
lack online patent databases, making it very difficult to
determine which LMCs have pending or granted patents.
More importantly, LMC companies generally lack the
substantial financial and human resources necessary to
perform freedom to operate (FTO) analyses using
proprietary databases available in developed countries.
IPO database needs to be more robust??
Source: Serum Institute of India & Bharat Biotech
54. 4/6/2014 RD_Vaccine Meet_2014 54
Padmanabhan S. et al. (2010) Intellectual Property, Technology Transfer and
Developing Country Manufacture of Low-cost HPV vaccines - A Case Study of
India.
Nat Biotechnol. 2010 July; 28(7): 671–678. doi: 10.1038/nbt0710-671 , PMCID:
PMC3138722, NIHMSID: NIHMS270118
MoHFW -
http://mohfw.nic.in/WriteReadData/l892s/1084811197NATIONAL%20VACCI
NE%20POLICY%20BOOK.pdf
55. 4/6/2014 RD_Vaccine Meet_2014 55
Circumventing Patent Laws for affordable
Vaccines
Credits: S. Padmanabhan, Nature Biotechnology, 2010
56. 4/6/2014 RD_Vaccine Meet_2014 56
http://mohfw.nic.in/WriteReadData/l892s/1084811197NATIONAL%20VACCINE%20POLICY%20BOOK.pdf
MoHFW, GoI
Improving the institutional capacity for intellectual property (IP) management and technology
transfer will help investigators involved in the research to understand the patent claims and will
enable them to make sound judgments, during the product development. There are a few steps
needed in
this arena:
• Strengthening Indian patent office, reducing the time to examine and grant a patent, and
creation of more comprehensive IP databases in India
• Encouraging technology transfer from multinational companies to develop products and
gaining access to technologies and know-how
• Indian patent law may have provisions to permit compulsory licensing in special situations like
the H1N1 pandemic or in situations, where a technology/intermediate is needed for vaccine
development.
• The country should develop/use expertise to study the flexibilities enshrined in the Trade
Related Aspects of Intellectual Property rights (TRIPS) agreement to reduce the negative impact
of the patents. The arrangements like ‘Bolar provision’ which permits the manufacturers of
generic pharmaceuticals to begin product development, while the patent is still in force. This
could be particularly helpful in reducing the lead-time to obtain regulatory clearances during
vaccine development.
• Collective management of IPR and open access agreements should be resorted to improve
innovation and access. Innovations in ways to deal with IPR of new vaccines need to emerge
through innovative funding of R&D.
• It is suggested that a body is created to acquire and hold IPR for technologies beneficial for use
in public health. This body could then license the technology to emerging manufacturers on
acceptable terms for development of vaccines and related products.
57. 4/6/2014 RD_Vaccine Meet_2014 57
Local R&D Effort:
Success Stories: Rotavirus Vaccine
(2013)
•India’s new rotavirus vaccine, promises to
drastically reduce diarrhoeal deaths
•Rotavac can be safely administered along
with oral polio drops
•When licensed, Rotavac will be available at
a dollar-per-dose and compares well with
existing vaccines
58. IP Coverage on Vaccine
Patents
Vaccine
Methods of prophylaxis and treatment
Modified de-activated organism
DNA, amino acid sequence of antigens,
modifications, fusion proteins
Expression systems
Adjuvants
Formulations, dosage, carriers, excipients,
diluents etc.
Delivery device and dosing regimen
Research tools and platform technologies
Processes – conjugation technology,
expression systems, manufacturing
and purification processes
4/6/2014 58RD_Vaccine Meet_2014
59. What are the Implications?
What is being patented?
Where are they patented?
What obstacles does patent protection
present for the development and
production of vaccines?
How can one legally manufacture and
import/ export vaccines?
What is the timeline for IPR protection
on the technologies?
What obstacles does patent protection
present for rapid dissemination of
vaccines in time of public health
need/crisis?
Claim overlap periods
Claim 1
Claim 7
Claim 10
Claim 11
4/6/2014 59RD_Vaccine Meet_2014
60. 4/6/2014 RD_Vaccine Meet_2014 60
IP Issues Related to Antigens
•First-generation cervical cancer
vaccines "do not seriously inhibit" the
efforts of developing country vaccine
manufacturers (DCVMs) to develop
these vaccines
•The current vaccines do not protect
against several cancer-causing strains
of HPV that present in low-income
countries, and suggest that DCVMs
could make products that include
antigens missing in the patented
versions
61. 4/6/2014 RD_Vaccine Meet_2014 61
Issues related to DNA sequences
Poorly designed analysis (H5N1 case):
“There are many techniques for filing invention
disclosures that render the searchability of DNA or
protein sequences very difficult” & “ finding DNA or
protein sequences disclosed in or claimed
In patents is extraordinarily difficult”.
Claims on less variable “conserved” parts of
genome
Follow one system of classification while doing
FTOs or searches
Non-disclosure of sequences in less known but
potent organisms
(Source: TWN-2011)
62. (http://www.ipaustralia.gov.au/get-the-right-ip/patents/about-patents/what-can-be-patented/patents-for-biological-inventions/)
Patents for Expression Vectors & biological inventions
A standard patent can be obtained for isloated bacteria, cell lines, hybridomas,
related biological materials and their use, and genetically manipulated organisms.
Examples of patentable inventions include:
isolated bacteria and other prokaryotes, fungi (including yeast), algae, protozoa,
plasmids, viruses, prions
cell lines, cell organelles, hybridomas
genetic vectors and expression systems
apparatus or processes for enzymology or microbiology
compositions of micro-organisms or enzymes
propagating, preserving or maintaining micro-organisms
mutagenesis or genetic engineering
fermentation or enzyme using processes to synthesise a desired compound or
composition
measuring or testing processes involving enzymes or micro-organisms
processes using enzymes or micro-organisms to liberate, separate, purify or
clean
the use of micro-organisms to produce food or beverages.
4/6/2014 62RD_Vaccine Meet_2014
63. 4/6/2014 RD_Vaccine Meet_2014 63
Genetic inventions and their patent claims (A)
For genetic inventions, many different types of patent can be found. They
vary as to the kinds of claims used and how the set of claims is structured.
There are at least three common categories of patent in this field.
DNA coding for industrially useful expression products. The cloning of a
DNA coding sequence can enable the commercial production of an
important therapeutic protein, such as a blood protein or a vaccine. Such
an achievement can represent a clear advance in pharmaceutical
technology and deserve legal protection, provided the innovation meets
standard criteria of patentability. Similarly, the cloning of DNA coding
sequences which leads to advances in plant biotechnology, thereby
improving agricultural Products like plant derived vaccines, practices and
productivity, is patentable.
A typical claims structure in such a therapeutic product patent will cover
the following:
1. DNA of specific function and/or nucleotide sequence.
2. A recombinant vector (plasmid) containing DNA of (1).
3. A genetically modified organism containing DNA of (1).
4. A method of production of polypeptide expressed by DNA of (1).
5. The expressed polypeptide per se (only if novel, i.e. differing in some
respect from the naturally occurring protein).
64. Patents for genetic modification or manipulation
A standard patent can also be obtained for inventions involving:
genotypically or phenotypically modified living organisms, for example, genetically
modified bacteria, plants and non-human organisms (patenting of plant varieties is
described in Plant Breeder's Rights)
isolated DNA, RNA, chromosomes and genes (including human DNA and genes)
isolated products of such DNA, RNA and genes including polypeptides and proteins.
Examples of patentable inventions include:
synthetic genes or DNA sequences
mutant forms and fragments of gene sequences
an isolated DNA coding sequence for a gene
an isolated protein expressed by a gene
vectors (such as plasmids or bacteriophage vectors or viruses) containing a transgene
methods of transformation using a gene
host cells carrying a transgene
higher plants or animals carrying a transgene
organisms for expression of a protein from a transgene
general recombinant DNA methods such as PCR and expression systems
4/6/2014 64RD_Vaccine Meet_2014
65. Patents for DNA or gene sequences
Human beings and the biological processes for their generation are not
patentable.
Although standard patents can be obtained for biological material such as
micro-organisms, nucleic acids, peptides and organelles, this material is only
patentable if it has been isolated from its natural environment, or has been
synthetically or produced by recombinant mode, e.g., DNA or genes in the
human body are not patentable. A DNA or gene sequence that has been
isolated may be patentable.
Patent specifications must also describe a specific use for a biological
material. For example, if the invention relates to a gene, the specification
must disclose a specific use for the gene, such as its use in the diagnosis or
treatment of a specific disease, or its use in a specific enzymatic reaction or
industrial process.
4/6/2014 65RD_Vaccine Meet_2014
66. 4/6/2014 RD_Vaccine Meet_2014 66
Examples of genetic inventions and their patent claims (B)
It should be noted that these different forms of claims may not all be present in a single patent; official
patent regulations in certain countries may require them to be divided into two or more separate patent
applications. The US patents on breast cancer genes (BRCA1 and BRCA2) and their use in diagnostic
testing are illustrative examples of this practice.
Genes which control biological pathways. Research continues to identify receptors and genes involved
in biological pathways. When such a gene is located, it may be possible to correlate a malfunction in
the pathway with a mutation or loss of this gene.
The cDNA and the encoded polypeptide would be considered targets for diagnosis and drug discovery or
vaccine development.
One type of invention in this category would be the use of the target to discover substances which
achieve some useful effect by binding to the target. This would also include substances which, by
blocking the target, prevent entry of pathogens such as viruses into the cell. Typical claims are:
1. The receptor peptide or polypeptide (protein) of a defined sequence.
2. DNA coding for the receptor (1).
3. A transformed cell expressing the receptor (1).
4. An assay system comprising the transformed cell (3).
5. A method of identifying an agonist or antagonist of the receptor.
6. Agonists or antagonists of receptor (1) identified by method (5), (a claim of this type is allowed with
great difficulty).
67. 4/6/2014 67RD_Vaccine Meet_2014
Why China is a genetic powerhouse with a
problem - The Globe and ...
www.theglobeandmail.com
Dec 15, 2012 - But not just human DNA. Once
known as the Beijing Genomics Institute, BGI is on
a mission to sequence the genomes of a vast array
of living…….
In the South China city of Shenzhen, a thriving
manufacturing hub known for cheap goods and
high-tech electronics, the genetic secrets of life
roll off machines by the minute. Here at the
global headquarters of BGI-Shenzhen, housed in a
former shoe factory, the genomic revolution runs
on an industrial scale. Powered by an army of
young lab technicians and banks of high-end,
U.S.-made sequencers that hum 24/7, the DNA of
human kind is decoded with conveyor-belt speed
and brute force
68. 4/6/2014 RD_Vaccine Meet_2014 68
Recent Pat Drug Deliv Formul. 2008;2(1):68-82
Potential of nanocarriers in genetic immunization.
Khatri K, Goyal AK, Vyas SP.
Source
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour
Vishwavidyalaya, Sagar, MP 470003, India.
Abstract
DNA vaccination (or genetic immunization) strategies provide important
opportunities for improving immunization, since both humoral and cell-
mediated responses are induced. The use of genetic vaccines for inducing
immunity to infectious agents can eliminate or significantly alleviate the
pathology associated with a broad range of infections. A requirement for
efficient DNA vaccination is the development of gene delivery systems
capable of overcoming barriers to gene transfection. Compared to viral
systems, nonviral systems are considered to be safe, cheap, multiple delivery
is possible and able to deliver larger pieces of DNA. Also, these nanocarriers
avoid DNA degradation and facilitate targeted delivery to antigen presenting
cells. This review describes the potential of non-viral nanocarrier construct(s)
in genetic immunization. Issued patents in the field were retrieved from the
US patent database. Various carrier systems used to deliver plasmid DNA
were reviewed in detail.
PMID:19075899 [PubMed - indexed for MEDLINE]
69. 4/6/2014 RD_Vaccine Meet_2014 69
Case History:
IP Issues in Influenza Vaccines
Further IP Considerations: Reverse Genetics
Patents and WHO GISN H5N1 Vaccine Seed
Strains
Antisera Research: Emerging Intellectual
Property Claims
Conflicting Priorities: Public Research and
Private Patents, Two ????
72. 4/6/2014 RD_Vaccine Meet_2014 72
1 7,223,411 Herpesvirus replication defective mutants
2 7,186,559 Apparatus and method for electroporation of biological
samples
3 7,141,425 Apparatus and method for electroporation of biological
samples
4 7,141,408 Plasmid maintenance system for antigen delivery
5 7,138,112 Plasmid maintenance system for antigen delivery
6 7,125,720 Plasmid maintenance system for antigen delivery
7 7,115,269 Attenuated Salmonella strain used as a vehicle for oral
immunization
8 7,078,218 Alphavirus particles and methods for preparation
9 7,045,335 Alphavirus replicon vector systems
10 7,029,916 Apparatus and method for flow electroporation of biological
samples
11 7,026,155 Method of reducing bacterial proliferation
12 6,995,008 Coordinate in vivo gene expression
Delivery Systems
73. 4/6/2014 RD_Vaccine Meet_2014 73
Bio-manufacturing of Vaccines
PAT. NO Title
1 8,440,791 Thimerosal removal device
2 8,388,955 Fc variants
3 8,367,805 Fc variants with altered binding to FcRn
4 8,338,574 FC variants with altered binding to FCRN
5 8,324,351 Fc variants with altered binding to FcRn
6 8,318,907 Fc variants with altered binding to FcRn
7 8,101,720 Immunoglobulin insertions, deletions and substitutions
8 8,093,357 Optimized Fc variants and methods for their generation
9 8,034,335 High-titer retroviral packaging cells
10 8,030,071 Restoration of cholesterol independence and its use as a selectable
marker in NS0 cell culture
11 7,964,403 Preparation of vaccine master cell lines using recombinant plant
suspension cultures
12 7,901,921 Viral purification methods
13 7,879,338 Vectors and methods for immunization against norovirus using
transgenic plants
14 7,553,666 Preparation of vaccine master cell lines using recombinant plant
suspension cultures
15 6,395,538 Method and system for providing real-time, in situ biomanufacturing
process monitoring and control in response to IR spectroscopy
16 6,266,569 Method and system of computing similar to a turing machine
74. 4/6/2014 RD_Vaccine Meet_2014 74
1 8,168,421 Microbial vaccine and vaccine vector
2 7,704,491 Recombinant human metapneumovirus and its use
3 7,169,396 Reference clones and sequences for non-subtype B
isolates of human immunodeficiency virus type 1
4 6,897,301 Reference clones and sequences for non-subtype B
isolates of human immunodeficiency virus type 1
5 6,492,110 Reference clones and sequences for non-subtype B
isolates of human immunodeficiency virus type 1
6 6,310,045 Compositions and methods for cancer
immunotherapy
7 5,662,896 Compositions and methods for cancer
immunotherapy
Reference Reagents
75. 4/6/2014 RD_Vaccine Meet_2014 75
1 8,507,658 Ex vivo animal or challenge model as method to measure
protective immunity directed against parasites and vaccines
shown to be protective in the method
2 8,507,445 Compositions and methods of use of targeting peptides for
diagnosis and therapy of human cancer
3 8,507,206 Monoclonal antibodies that target pathological assemblies
of amyloid .beta. (Abeta)
4 8,506,969 Efficient cell culture system for hepatitis C virus genotype 7a
5 8,501,194 Vaccine for viruses that cause persistent or latent infections
6 8,498,879 Automated systems and methods for obtaining, storing,
processing and utilizing immunologic information of
individuals and populations for various uses
7 8,497,351 Nucleic acid and corresponding protein entitled 162P1E6
useful in treatment and detection of cancer
8 8,497,292 Translational dysfunction based therapeutics
9 8,491,909 Methods and compositions for dosing of allergens
10 8,486,421 Antigen-norovirus P-domain monomers and dimers, antigen-
norovirus P-particle molecules, and methods for their
making and use
11 8,486,413 Immunological compositions as cancer therapeutics
Animal models for Vaccines
76. 4/6/2014 RD_Vaccine Meet_2014 76
Carriers for Vaccines
United States Patent # 8,506,968; Inventor: Akeefe, et al.; Eli Lilly and Company (Indianapolis,
IN);
Filed December 28, 2009, Date of Grant: August 13, 2013
SARS vaccine compositions and methods of making and using them
Abstract
Described is a composition and method for reducing the occurrence and severity of
infectious diseases, especially infectious diseases such as SARS, in which lipid-
containing infectious viral organisms are found in biological fluids, such as blood.
The present invention employs solvents useful for extracting lipids from the lipid-
containing infectious viral organism thereby creating immunogenic modified, partially
delipidated viral particles with reduced infectivity.
The present invention provides delipidated viral vaccine compositions, such as
therapeutic vaccine compositions, comprising these modified, partially delipidated viral
particles with reduced infectivity, optionally combined with a pharmaceutically acceptable
carrier or an immunostimulant.
The vaccine composition is administered to a patient to provide protection against the
lipid-containing infectious viral organism or, in case of a therapeutic vaccine, to treat or
alleviate infection against the lipid-containing infections viral organism.
The vaccine compositions of the present invention include combination vaccines of
modified viral particles obtained from one or more strains of a virus and/or one or more
types of virus.
77. Issues related to Expression
systems
Axel Patent Story !!!! Columbia University
4/6/2014 77RD_Vaccine Meet_2014
79. IP issues in cells used for Expression Cells
Several of these cell lines have been used for many years and hence are not
covered by patents and can be obtained from public sources. However, in
order to get regulatory approval for vaccines produced in a cell line requires
that Master and Working cell banks are established and characterized, a very
lengthy and costly process. Manufacturers who have undertaken such
processes are unlikely to share their characterized cell line. Hence even in
absence of IP on the cell line, there is a significant barrier to the use of these
cells.
A possible exception to this is the Vero cell line which can be purchased with
full characterization.
There is IP on specific variants of these strains (e.g. MDCK-B-702 described in
US 6825036, a MDCK line with higher susceptibility to infection described in
WO 2005/113758), and on the new cell lines including the PerC6 cell lines
(e.g. US7192759) and avian embryonic lines (WO 2006/108846).
4/6/2014 79RD_Vaccine Meet_2014
80. (WO 2006/108846).
Cell over expressing a nucleic acid encoding
WO 2003/048348 sialyltransferase for production of virus Crucell
WO 2005/113758
A MDCK cell with higher susceptibility to viral infection than parenteral line
ID biomedical
US 6825036
process for preparing MDCK cell in serum-free suspension -specifically MDCK-
B-702 line.
Kumamoto-ken,
JP
US 7192759
human embryonic retinoblast cell encoding E1 gene of adenovirus to produce
influenza
Crucell
WO 2006/108846
avian embryonic stem cell. Replicating virus in suspension
Vivalis
EP 1108787
method for producing flu virus or antigen in cell encoding adenovirus E1 gene.
Crucell
In addition, as discussed below, there is IP on using cell lines for producing
influenza vaccines and also processes involving these cell lines, including the
http://www.who.int/vaccine_research/diseases/influenza/Mapping_Intellectual_Property_Pandemic_Influenza_Vaccines.pdf
4/6/2014 80RD_Vaccine Meet_2014
81. IP on cell culture inactivated vaccine production process
US 7132271 method for enhancing production using cell with targeted deletion in PKR or 2-5A gene U. California
US 6673591 use of cells with targeted deletion in PKR gene to enhance virus production in cells U. California
US 6686190
use of cells with targeted deletion in at least one ISG gene to enhance production in
cells U. California
WO 1997/008292 process to enhance virus production in cells by inhibiting PKR 2-5a synthetase U. California
US 6344354 Vaccine comprising flu virus produced on cells (isolate not been passaged on eggs) St Judes
US 6656720 MDCK cell adapted to suspension growth for influenza virus production Novartis
US 6455298 use of MDCK 33016 for replication of influenza virus in serum-free medium.
EP 870508 process to reduce DNA content in cell derived vaccine by use of DNAse and detergent Duphar
US 4500513 influenza vaccine production in liquid cell culture Miles Lab
US 5698433 Producing flu vaccine in Avian embryo cells: Infection prior to growth on monolayer. Baxter (Immuno )
US 5753489 producing virus in serum free monkey kidney cells Baxter (Immuno AG
US 6146873 producing virus in serum free monkey kidney cells Baxter (Immuno AG
US 5756341 producing in serum free monkey kidney cells, with modified cleavage site in HA Baxter (Immuno AG
US 5840565 Use of PKR antisense polynucleotide to enhance production of influenza virus in cells U. California
WO 2005/024039 Replacing NS gene of APR/8 with NS from A/England to produce high titer virus in cells St Judes
WO 2005/028658 two vectors, at least one containing a pol II promotor linked to a ribozyme sequence Wisconsin alumni
WO 2006/027698 tests to ensure that no pathogens other than influenza virus are growing in cell culture Chiron Behring
WO 2006/067211 use of bacteriophage polymerase promoter to produce influenza antigen in cells Solvay
WO 2007/002008 expression vector containing canine RNA polymerase regulatory sequence; MDCK MedImmune
WO 2007/045674 method for producing flu virus or antigen in cell encoding adenovirus E1 gene. Crucell
US 7037707 method of making a reassortant growing to high titer by using an alternative NS gene St Judes
4/6/2014 81RD_Vaccine Meet_2014
82. 4/6/2014 RD_Vaccine Meet_2014 82
IP Issues on Vehicles
Injection
Nanoparticles
The living epidermis and dermis are rich in antigen presenting cells (APCs). Their activation
can elicit a strong humoral and cellular immune response as well as mucosal immunity.
Therefore, the skin is a very attractive site for vaccination, and an intradermal application of
antigen may be much more effective than a subcutaneous or intramuscular injection.
However, the stratum corneum (SC) is a most effective barrier against the invasion of
topically applied vaccines. Products which have reached the stage of clinical testing, avoid
this problem by injecting the nano-vaccine intradermally or by employing a barrier
disrupting method and applying the vaccine to a relatively large skin area. Needle-free
vaccination is desirable from a number of aspects: ease of application, improved patient
acceptance and less risk of infection among them. Nanocarriers can be designed in a way
that they can overcome the SC. Also incorporation into nanocarriers protects instable
antigen from degradation, improves uptake and processing by APCs, and facilitates
endosomal escape and nuclear delivery of DNA vaccines. In addition, sustained release
systems may build a depot in the tissue gradually releasing antigen which may avoid
booster doses. Therefore, nanoformulations of vaccines for transcutaneous immunization
are currently a very dynamic field of research. Among the huge variety of nanocarrier
systems that are investigated hopes lie on ultra-flexible liposomes, superfine rigid
nanoparticles and nanocarriers, which are taken up by hair follicles. The potential and
pitfalls associated with these three classes of carriers will be discussed.
83. 4/6/2014 RD_Vaccine Meet_2014 83
IP Issues in Vaccination using gold nano-
particles
26 June 2013 | Source: Nanotechnology
Scientists in the US have developed a novel vaccination method that uses
tiny gold particles to mimic a virus and carry specific proteins to the body’s
specialist immune cells.
The technique differs from the traditional approach of using dead or
inactive viruses as a vaccine and was demonstrated in the lab using a
specific protein that sits on the surface of the respiratory syncytial virus
(RSV).
The results have been published today, 26 June 2013, in IOP Publishing’s
journal Nanotechnology by a team of researchers from Vanderbilt
University.
RSV is the leading viral cause of lower respiration tract infections, causing
several hundred thousand deaths and an estimated 65 million infections a
year, mainly in children and the elderly.
The detrimental effects of RSV come, in part, from a specific protein, called
the F protein, which coats the surface of the virus. The protein enables the
virus to enter into the cytoplasm of cells and also causes cells to stick
together, making the virus harder to eliminate.
84. 4/6/2014 RD_Vaccine Meet_2014 84
IP issues in Bio-manufacturing/NO
COLD CHAIN VACCINES
The nanopatch is designed to place a tiny amount of
vaccine just under the skin without the need for a needle
jab. Because it delivers the active ingredient right to where
it is needed, tests have shown it can generate the same
immune response with only a fraction of the dose needed
in a conventional vaccine.
Among other potential advantages of the nanopatch are
that it is pain free, low cost — it could be made for under
$1 a dose compared with more than $50 for many current
vaccines — and easily transportable. Kendall (biotech
company given grant by Merck) even ponders whether it
might be mailed to remote places for people to administer
it themselves
86. 4/6/2014 RD_Vaccine Meet_2014 86
Merck & Co. to Evaluate Transdermal Vaccine
Delivery System
Merck & Co. and vaccine delivery specialist Vaxxas started a research
collaboration focused on evaluating the use of the latter’s transdermal
Nanopatch™ vaccine delivery system with a Merck vaccine candidate. Under
terms of the deal Australian firm Vaxxas will receive an up-front fee, research
funding, and option fees if Merck exercises its option to the platform for the
development and commercialization of vaccine candidates for up to two
additional fields. Vaxxas will also be eligible for development and regulatory
milestone payments.
Vaxxas’ Nanopatch™ vaccine delivery technology consists of a 1 cm2 silicone
array that carries about 20,000 vaccine-coated microprojections that painlessly
perforate the outer layers of the skin when applied with the associated
applicator device, and deliver the vaccine directly to key immune cells
immediately below the skin surface. The firm believes the system can
significantly enhance the therapeutic potential of both existing and new
vaccine candidates by amplifying efficacy, reducing the required dose, and
obviating the need for adjuvants, as well as preventing needlestick injuries and
cross-contamination. Preclinical in vivo studies showed that use of Nanopatch
allowed a 100-fold reduction in the required dose of Fluvax® influenza vaccine.
The applicator device used with the Nanopatch array has in addition been
designed to achieve uniform penetration and delivery across the range of
natural variations in skin structure associated with age, gender, and health, and
overcome the inconsistencies associated with other transdermal vaccine
delivery approaches, Vaxxas claims.
Founded in August 2011 with a Aus$15 million venture capital investment
(about $15.3 million at today’s exchange rate), Vaxxas’ platform was originally
developed by researchers at UQ’s Australian Institute for Bioengineering and
Nanotechnology.
http://www.genengnews.com/gen-news-
highlights/merck-co-to-evaluate-transdermal-
vaccine-delivery-system/81247449/
87. Issues related to Immuno-stimulatory sequences
Background: Recent studies have demonstrated that bacterially derived
immunostimulatory sequences (ISSs) of DNA can activate the mammalian innate
immune system and promote the development of TH1 cells. Promotion of TH1
immunity by means of immunotherapy in allergic patients has led to the alleviation of
symptoms that result from allergen-specific TH2 responses.
Objective: Our purpose was to investigate whether the TH1- enhancing properties of
ISSs could be used to alter the TH2-dominated immune response of allergic PBMCs in
vitro.
Methods: Ragweed protein-linked ISS (PLI) was generated from a specific, highly active
22-base ISS and Amb a 1, the immunodominant allergen in ragweed pollen, to
combine the TH1-enhancing properties of ISSs with allergen selectivity, and its activity
was investigated in PBMC cultures from subjects with ragweed allergy.
Results: PLI was markedly successful at reversing the dominant allergen-induced TH2
profile while greatly enhancing IFN-γ production. Delivering ISSs in a linked form
proved to be much more effective at modulating the resulting cytokine profile than
delivering free ISSs in a mixture with unlinked Amb a 1. PLI also demonstrated
cytokine-modulating properties, even when used to stimulate cells that had already
been primed for 6 days with Amb a 1. The antigen specificity of the action of PLI was
confirmed by the observations that PLI enhances Amb a 1–specific T-cell proliferation.
Conclusion: These data indicate that delivery of ISSs within an antigen-specific context
exhibits potent cytokine-modulating activity and, combined with its reduced
allergenicity, makes this molecule a strong candidate for use in improved
immunotherapy applications. (J Allergy Clin Immunol 2001;108:191-7.)
4/6/2014 87RD_Vaccine Meet_2014
88. 4/6/2014 RD_Vaccine Meet_2014 88
Plant Derived vaccines
A new category of technology which may confound existing
IP regimes is plant derived vaccines (“PDVs”). The make-up
of this innovation is just as its name suggests – a
vaccination product derived from plants.
Although there is no trick to understanding the nature of
PDVs, deciding which IP regime may be utilized to protect
this invention can prove to be troublesome.
Due to the fact that the technology ties together several
elements which have previously stood alone as distinct
technological categories, PDVs fit simultaneously within
several existing categories, each of which offers unique
aspects of protection.
In basic terms, a PDV is a plant variety, a drug, a
biotechnological innovation and a developing nation-
focused product all-in-one.
It is therefore difficult to categorize PDVs for the purpose of
IP protection.
89. What will happen, if vaccines will
be derived from proprietary
variety??
The decision of the Supreme Court of
the United States on Merck v. Integra
Life Sciences in 2005, analysts
contend that, with the broadened
definition by the Supreme Court of
the Hatch-Waxman Act as it relates to
data exclusivity, research in
preparation of FDA approval is
exempt from the requirement for
research licenses
4/6/2014 89RD_Vaccine Meet_2014
90. 4/6/2014 RD_Vaccine Meet_2014 90
Will Vaccines Derived from Plants be Classified
under Drugs or Foods?
Ans:
Both – so IP issues become more complex
91. 4/6/2014 RD_Vaccine Meet_2014 91
Biotechnology products can benefit from
both trade secret and patent protection.
Each of these forms of IP are haunted by considerations beyond the
bounds of pure science, which arise in conjunction with the clinical trials
and commercialization stages in particular. These include ethical, social
and cultural concerns. In the words of E. Richard Gold and Wendy A.
Adams, “the health benefits to individual recipients of the products of
biotechnological innovation are self evident, although far from
uncontroversial.”
Others have voiced concerns as to whether extending strong IP rights to
biotechnological innovation is ethical, or even legally defensible. Specific
issues raised by PDVs include liabilities related to the growth of transgenic
plants and the production of drugs from these materials.
BIO has acknowledged that steps must be taken to minimize the risks
associated with the production of plant based genetically modified health
technologies, including control of exposure to transgenic plants and their
expression products. BIO’s caution is the type of issue that will likely be
addressed through regulation or policy initiatives to restrict the growth of
plants to confined facilities and to ensure that processing, milling and
extraction of transgenic plant materials is undertaken separate from
commercial food and feed channels. These represent physical protections
which may be achieved.
Recent case law has examined the legal protections available, through a
review of the validity and scope of claims which form the basis of patent
rights held in biotechnology inventions.
92. Issues of IP on Antigens
VACCINE COMPONENT ROYALTY ON SALES OF VACCINE
Antigen A, Proprietary to Company A 2%
Antigen B, Discovered with proprietary
tool of Company B
2%
Antigen C, Nonproprietary 0%
Proprietary assembly technique of
Company C
2%
Proprietary adjuvant 2%
4/6/2014 92RD_Vaccine Meet_2014
93. IP Issues: Vaccine composition
Component Purpose Example
Adjuvants enhance the immune response to a vaccine aluminium salts
Preservatives prevent bacterial or fungal contamination of
vaccine
thiomersal
Additives stabilise vaccines from adverse conditions
such as freeze-drying or heat, thereby
maintaining a vaccine’s potency
gelatine
Residuals from
manufacturing
process
Inactivating agents
Antibiotics - prevent bacterial contamination
during manufacturing process
Egg proteins- some vaccine viruses are
grown in chick embryo cells
Yeast proteins
formaldehyde
neomycin,
streptomycin,
polymyxin B
influenza, yellow
fever
HepB vaccine
4/6/2014 93
RD_Vaccine Meet_2014
94. cDNA clones
Methods of treatment
Human monoclonal antibodies
Compounds
genetic variants
Agonist and antagonist peptides
Method for production and purification
Highly active glycoproteins-process conditions and an efficient method for their production
Nucleic-acid programmable protein arrays
Detection of adventitious agents
Compositions and methods for extracting and using vaccines
composition containing synthetic adjuvant
Antibodies as vaccines
Vaccine formulations
Combinations of clades as in pneumococcal treatment
Compositions of PD-1 antagonists and methods of use
Inhibitors of angiopoietin-like 4 protein, combinations, and their use
Chemically programmable immunity use in gene modulation in vaccine development
Compositions and methods of enhancing immune responses
Humanized antibody compositions and methods
Influenza inhibiting compositions and methods
Compositions and methods modulating MG29 for the treatment of diabetes
Methods of generating libraries and uses thereof
Process for improved protein expression by strain engineering
Process for large scale production of plasmid DNA by fermentation
Method for producing storage stable viruses and immunogenic compositions thereof
Prostate carcinogenesis predictor
Antigen surrogates in autoimmune disease
Anti-avian influenza virus agent, and product containing anti-avian influenza virus agent
Compositions and methods for frozen particle compositions
Immunoconjugates, methods and uses
Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use
Genetic adjuvants for immunotherapy
Composition for prevention of influenza viral infection comprising tannic acid, air filter comprising the same and air cleaning device comprising the filter4/6/2014 94RD_Vaccine Meet_2014
95. 4/6/2014 RD_Vaccine Meet_2014 95
Bode C. et al. (2011) CpG DNA as a vaccine adjuvant. Expert Rev Vaccines. 2011 April; 10(4): 499–511
96. R&D Efforts in Adjuvants
• The project of extracting a new vaccine adjuvant from 'Ashwagandha' (Withania
somnifera), a medicinal plant used in Ayurveda as an immunity enhancer, was
sponsored by the Department of Science and Technology and was jointly executed
by the researchers from Pune based Serum Institute of India (SII) and University of
Pune's Inter-disciplinary School of Health Sciences (ISHS).
• The researchers already received a patent on this in India in 2007, but the US
patent was granted on August 6, 2013.
• The adjuvant extracted from Ashwagandha is believed to improve vaccine efficacy.
Further, the adjuvant showed properties where it could be useful in new vaccine
development such as the pentavalent vaccine targeting meningitis, or those
against dengue, pneumococcal diseases, polio, diphtheria, tetanus and hepatitis
and also holds promise against HIV, tuberculosis and malaria.
• The researchers have clarified that unlike earlier instances where companies tried
to patent turmeric, for example, the patent here was in an area not claimed by
Ayurveda.
4/6/2014 96RD_Vaccine Meet_2014
98. IP issues in Delivery Devices
4/6/2014 98RD_Vaccine Meet_2014
99. 4/6/2014 RD_Vaccine Meet_2014 99
Strategy : Contribution by PATH
Advancing novel vaccine formulations and processing methods.
Evaluating the technical and commercial feasibility of improving vaccine
thermo-stability.
Reducing needle stick injuries by developing immunization devices that shield or
eliminate needles.
Creating inherently simple and easy-to-use devices and user aids that improve
safety and ease immunization logistics.
Addressing issues of cost by developing and testing effective devices that enable
delivery of a reduced dosage of vaccine and help to decrease vaccine wastage.
Improving vaccine presentations and packaging to meet user needs and minimize
environmental impact.
Developing and facilitating access to new equipment that stores, monitors, and
transports vaccines at appropriate temperatures.
Analyzing the cost-effectiveness of various immunization strategies and
interventions to facilitate decision-making.
101. 4/6/2014 RD_Vaccine Meet_2014 101
Indian Vaccine Strength
http://www.slideshare.net/fababioasia/vaccines-
indias-strength-8501392
102. 4/6/2014 RD_Vaccine Meet_2014 102
Work Around to break Barriers to Existing
Vaccines for development of Generic
Vaccines w.r.t. basic vaccines
Use of pertactin/69K in acellular pertussis
vaccine
– GSK / Medeva
– Work-around: don’t include it (FHA/PT)
Combination vaccines containing low doses of
T,P, etc
– Use higher doses etc.
Stick to 'old' formulation or develop work-
arounds
– Requires R&D capacity
(Source: WHO)
Repositioning in Drugs**
103. 4/6/2014 RD_Vaccine Meet_2014 103
Original Drug Repositioned
Development Product Development Approved Repositioned Product
Subject to
Generic/Modified
Competition
Original API Patent (20 years)
New Use Indication Patent (20 years)
5 yr NCE
Exclusivity
14 years extended Patent Life
30 month stay
Approval of
Repositioning
Product
(Source: Drug Discovery Today: Therapeutic Strategies Vol.8(3-4), 135, (2011)
Subject to ANDA/505(b)2
Patent Challenge
Upto
5yr Ext
Shelved API
Never Previously Approved
NCE
New Indication
Illustration of exclusivities for repositioned product based
on shelved API
CanthisStrategybetriedforVaccines&Biologics?
105. 4/6/2014 RD_Vaccine Meet_2014 105
Solutions
Benchmarks on benefit sharing in the Nagoya protocol (not verbatim)
1. Monetary benefits may include, but not be limited to: Access fees/fee per sample
collected or otherwise acquired; Up-front, milestone, royalty payments; Licence fees in
case of commercialization; Special fees to be paid to trust funds supporting conservation
and sustainable use of biodiversity; Salaries and preferential terms where mutually agreed;
Research funding; Joint ventures and joint ownership of relevant intellectual property
rights.
2. Non-monetary benefits may include, but not be limited to: Sharing research and
development results and contribution to local economy; food and livelihoods; Social
recognition; Joint ownership of relevant intellectual property rights.
106. 4/6/2014 RD_Vaccine Meet_2014 106
Disruptive Innovations to tackle IP
barriers in generic vaccines
Generic drug formulators tend toward what is
tried and true, patents are built on a foundation
of the unexpected, and planning for the
unplanned requires special talents.
Our scientists should exhibit success as
inventors as a result of combination of extensive
experience, out-of-the-box creativity, attention
to the details of experimental outcomes, and
perseverance.
India should look at every problem in the drug
development pathway as a potential
opportunity to invent and protect.
108. 4/6/2014
RD_Vaccine Meet_2014 108
Indian Capacity to deliver
Complex Vaccines
Starting with a few public-sector
manufacturers in the late 1960s India has
emerged as the major supplier of basic
Expanded Programme on Immunization
vaccines to the United Nations Children's
Fund (UNICEF) because of substantial
private-sector investment in the area.
The Indian vaccine industry is now able to
produce new and more complex vaccines
such as the Meningitis, Haemophilus
influenzae type b, and Pneumococcal
conjugate vaccines, Rotavirus vaccine and
Influenza A (H1N1) vaccines.
110. 4/6/2014 RD_Vaccine Meet_2014 110
We need to balance IP issues with
Purchasing Power of the sick & needy??
India needs to further strengthen its IP
protection mechanism and speed up
examination process. However, when it comes
to development of new interventions for Type
II and III diseases, it is suggested that these be
registered with the appropriate government
body, and not much emphasis be placed on
complete IP protection before an intervention
is produced. This process would ensure that it
acknowledges the inventors or funding
agencies for their inventions yet reaches the
needy quickly.
It also needs to be borne in mind that for
public interest, choices of IP management
should be accordingly exercised, and should
not be in conflict with public good.
111. 4/6/2014 RD_Vaccine Meet_2014 111
Policy Issues
The American Association of Universities, for
example, has sought to create further barriers
to access by encouraging 12 years of data
exclusivity for follow-on biologics as part of
legislation under consideration in Congress.
This is in contrast to the five years of data
exclusivity in place for small molecule drugs,
and despite the facts that the mean
development time for biologics is only 7.4
months longer, and the break-even lifetimes
are virtually identical.
This stance, which would bolster companies’
bottom lines, threatens to unduly delay the
onset of cheaper follow-on biologics after
patent expiration.
http://www.med4all.org/fileadmin/med/pdf/2_Crager_
Formatted_June3_HPV-Impfung.pdf
112. 4/6/2014 RD_Vaccine Meet_2014 112
TRIPS Compliance
INDIA: At the start of the Uruguay Round
negotiations in 1986, over fifty countries did
not recognize product patents on
pharmaceuticals. The adoption of TRIPS
caused a seismic shift in the global IPR
regime, raising barriers to generic entry by
blocking producers from finding alternative,
lower-cost means of producing the same
drug.
Patent protection of the end product could
trump inventions over the process of
manufacturing generic versions of the drug.
Nowhere has this been of greater concern
than in India, which came into TRIPS
compliance in 2005. For low- and middle
income countries, Indian generic
manufacturers supply more than eighty
percent of antiretroviral drugs and nearly
ninety percent of the pediatric market for
such drugs.
However, since several key second- and third-
line antiretroviral drugs (ARVs) have recently
come under patent protection in India, it is
not likely that Indian generic competition will
be able to reduce the global prices for ARVs at
the rates seen for the first-line drugs.
THAILAND: The use of the TRIPS flexibilities,
such as compulsory licenses, can lead to
significant cost savings and increases in
coverage. Thailand’s compulsory license on
efavirenz was expected to halve the drug price
and provide an additional 20,000 patients with
the drug under the same budget. Generic
imports of the second-line ARV, Kaletra
(lopinavir/ritonavir), under compulsory license
were also expected to cut the price by over
eighty percent, allowing an additional 8,000
patients to access the drug. A comparison of
the market prices for the branded originator
drugs at the time of the compulsory licenses
with the prices of the imported generic
equivalents demonstrate a sixty-six percent
reduction in price for efavirenz and seventy
percent for lopinavir/ritonavir. It is expected
that the prices of the cancer drugs will be
between three percent and twenty-five percent
of the prices for the patented drugs
113. 4/6/2014 RD_Vaccine Meet_2014 113
Reduction of Complexity by Sharing
Information
Even in presence of patents, the emergence of markets for
technology is not straightforward because there are still
major obstacles to such markets (Teece, 1986).
To respond to a need for lower transaction costs on
technology markets, new actors have recently emerged –
such as Innocentive, Yet2.com, and Ocean Tomo - often
assisted by new information and communication
technologies. The role of those patent brokers is to
organize and facilitate exchanges between technology
sellers and buyers.
To do so, they provide technical assistance, audit, and
perform diagnostic tests to assess the value of a given
technology. Most importantly, they facilitate the circulation
of information (Yanagisawa and Guellec, 2009; Dushnitsky
and Klueter, 2011).
http://timreview.ca/article/502#sthash.LNJdhZ1s.dpuf
116. 4/6/2014 RD_Vaccine Meet_2014 116
https://www-935.ibm.com/services/uk/igs/pdf/g510-6342-00-5barriers-etr.pdf (modified)
Breaking Innovation to access Barriers
Techno-scientific Barriers:
Human Resource Barriers
Organizational barriers:
Inadequate funding,
Risk avoidance,
“Siloing,”
Time commitments
Incorrect measures
Bad Business Practices
117. 4/6/2014 RD_Vaccine Meet_2014 117
Summary of R&D challenges
• The current, market-based R&D system has failed
to develop vaccines for diseases such as TB and
malaria that affect large numbers of people as well
as vaccines for smaller markets such as dengue
or Meningitis A. In addition to new vaccines, there
is also a need for improved, cheaper, and more
suitable versions of existing vaccines.
• Although there has been progress and a number of
promising initiatives, these efforts still depend too
much on the established multinational firms, who
fund and conduct most late-stage vaccine R&D.
There is a great opportunity to exploit and expand
developing country capacity to develop needed
vaccines.
• Much vaccine technology is initially developed in
government and academic institutions, but these
inventions are typically licensed to big pharma for
rich-world applications.
• New mechanisms are needed to support technology
transfer and fund vaccine development.
118. 4/6/2014 RD_Vaccine Meet_2014 118
“With all this background, contribution of
Industry, Academia, NGOs, Governments,
and health care professionals should not
be underestimated
We need to be tolerant and do the balancing
act between various stake-holders for global
health issues” RD-2014