Should a company be permitted to patent a mutated human gene that can be targeted for therapy or an endogenous protein that they would like to produce as a therapeutic

November 14, 2022/in Uncategorized /by Linus

Should a company be permitted to patent a mutated human gene that can be targeted for therapy or an endogenous protein that they would like to produce as a therapeutic?

1. The landscape of clinical trials has changed drastically over the last decade. The protocols are becoming more complex, leading to increased workload, burden on patients, and longer treatment times. Additionally, there has been an increase in the number of Phase 3 projects terminated, resulting in increasing costs of drug development – which is an accumulation from preclinical studies, failures, salaries, and the profit that could have been earned if the drug was approved. 2. The launch of ClinicalTrials.gov in 2000 provided key insight into the evolution of clinical trials. With the requirement by ICMJE to report prospective registration of clinical trials as a precondition for publication, this ensured that not only “successful” trials are published. The details required on ClinicalTrials.gov have expanded overtime, such as reporting results and adverse events. As of 2016, over 200,000 trials are listed and conducted in 191 countries. 3. Phases of clinical drug development are categorized as I, II, III, and IV. Phase I studies typically involve healthy volunteers or patients and conducted to determine responses to drug in humans and animals. The goal is to assess safety, efficacy, tolerability, and PK/PD of the drug. In Phase II trials, the drug is being studied in patients with the target disease for the first time to assess dosing requirements and study efficacy. When the drug development process fails, it typically happens in Phase II. Phase III studies are done in a much larger scale to further establish safety and efficacy. Phase IV trials are also known as Post Marketing Surveillance Trial, which may be required by regulatory authorities or sponsors to monitor the safety of the new drug in large number of patients. 4. A good protocol is designed to answer research questions. A good research question is constructed with three key points in mind: feasibility, relevance, and justifiable costs. Regarding feasibility, one must consider whether there is sufficient patient population that can enroll in the study as well as whether the trial is manageable in scope. For relevance, one must determine if the trial will advance scientific knowledge, guide further research, or affect public policies. Lastly, is the study aligned with the therapeutic focus of the sponsor to justify the costs it will take the conduct the study? 5. There are three ethical principles in clinical research that must be taken into consideration. First, it is the principle of Respect for the Person. This principle has two moral requirements – acknowledging that individuals should be treated as autonomous beings capable of representing their own goals and interests and acknowledging that people who are not capable of self-determination must be protected. Second, beneficence notes that scientists must refrain from knowingly harming their research subjects. Lastly, justice refers to the principle that the benefits and burdens of research must be fairly distributed. Principles of Drug Discovery: Patent Law in the Pharmaceutical Industry Paul A. Calvo, Ph.D., J.D. Director Sterne, Kessler, Goldstein & Fox Washington, DC 1 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. What is a patent? • A property right specified in Article I of the U.S. Constitution • Purpose: to promote the progress of science and useful arts by securing for limited times to authors and inventors the exclusive right to their respective writings and discoveries. 2 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. What is a patent – con’t • Term of a patent is 20 years from earliest filing date. • The rights are exclusionary • Is a right to exclude others AND NOT a right to make and use invention • Not an automatic right to practice invention – may need to obtain license for dominant patent 3 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Types of patents • Utility patent – Issued for the invention of a new and useful process, machine, manufacture, or composition of matter, or a new and useful improvement thereof 4 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Types of patents • Plant patent – for asexually reproduced distinct and new variety of plant Brunnera macrophylla Brunnera macrophylla ‘Sea Heart’ US PP24684 5 Brunnera macrophylla ‘Looking Glass’ US PP17829 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Types of patents • Design patent – legal protection granted to the ornamental design of a functional item 6 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. What is the value of patents? • • • • • • • 7 Used to raise capital Protects profitability and market share Ensures return on R&D dollars Aids access to competitors innovations Offensive uses (the sword) Defensive uses (the shield) Protects right to use (i.e., freedom to operate) • Stifles infringement charges by 3rd parties • Encourages cross-licensing arrangements to settle disputes S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Parts of a patent Face page 8 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Parts of a patent Written description 9 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Parts of a patent Figures 10 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Parts of a patent Claims 11 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Who is an inventor? • “The threshold question in determining inventorship is who conceived the invention. Unless a person contributes to the conception of the invention, he is not an inventor.” • Is a legal determination • Must be a person, not a corporation • Inventorship is determined on a claim-by-claim basis • Inventor not required to perform the work directly • Conception and reduction to practice • But performing work does not guarantee inventorship • Incorrect inventorship can be corrected 12 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Authorship vs. inventorship • Merely being an author does not satisfy the requirements of inventorship. • In the scientific world, authors of journal articles may be involved in designing or performing the experiments or in writing the resulting manuscripts. • Authorship is sometimes granted for the recognition of hard work or even for financial support. This is NOT to be confused with inventorship. 13 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Non-inventors • A person who: • Contributes an obvious element to the invention • Merely suggests an idea • Simply follows instructions • Explains how or why an invention works • Adopts derived information from another • Actually did the experiment, but did not conceive of the invention is NOT an inventor 14 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Conception and Reduction to Practice • An invention is conceived when a definite and permanent idea of an operative invention is known. Conception is complete when one of ordinary skill in the art could make the invention without undue research or experimentation. • Two kinds of reduction to practice • Actual reduction to practice requires making a working model of the invention that demonstrates that the invention will work to fulfill its intended purpose. • Constructive reduction to practice is accomplished by the filing of a patent application that enables one of ordinary skill in the art to make and use the invention without undue research or experimentation. 15 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Laboratory Notebooks • The Lab Notebook is the initial Record of the Invention • It is used to: • establish the date of the invention • overcome prior art • priority in a contest to determine who invented first • determine actual inventorship 16 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Laboratory Notebooks • Laboratory Notebooks should: • Be evidence of conception of the invention • Demonstrate diligence in reducing the invention to practice • Establish basis for corroboration by a non-inventor • Record discussions with collaborators • Every entry should be signed and dated by the Inventor, and • Be countersigned by a non-inventor 17 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Laboratory Notebooks • Notebooks are preferably: • Bound and written in ink • On sequentially numbered pages • Few or no eraser marks • Have an index • Be a coherent record of the experiments and their results • If using electronic notebooks: • Use software that permanently records dates of entries and an unalterable electronic signature • Print hard copies for corroboration • Adopt a standard procedure followed by all lab members 18 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. How to avoid inventorship issues? • Keep good records • Know your inventors • Know where they live, where they invented and what they invented • Know your invention • If you determine an error in inventorship – fix it! 19 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Federal Funding • Under the Bayh Dole Act, the US government encourages patenting of inventions made using government funds • Funding source MUST be disclosed in the patent application and in a separate form to the US government • The US Government has rights in the invention – they rarely take up these rights, but they do have them 20 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Types of applications • Provisional Application • Secures a priority date for the subject matter which is disclosed therein, but no more than this • No claims are required • Is not examined by the Patent Office • Expires after one year from the filing date unless it is converted to a non-provisional application • Small filing fee • May be used as a priority document for foreign filed application 21 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Types of applications • Non-provisional Application • Filed for all types of inventions • May claim priority date of prior provisional application • Published 18 months after earliest priority date • Must include claims • Is examined by the Patent Office • Proceeds through the process of prosecution until issue or abandonment • Filing fee depends on the number and type of claims filed 22 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Types of applications • Divisional application • Required by USPTO when 2 or more inventions are present in 1 application • Priority dates retained • Continuation in Part (CIP) application • Filed for improvements on existing applications • New material given priority of CIP filing • Old material retains original priority date • At least one common inventor 23 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Types of applications • Patent Cooperation Treaty (PCT) Application • International application • Single application designates selected member countries • Same filing date for selected countries • World Intellectual Property Organization (WIPO) • There is no such thing as a worldwide patent 24 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Patent claims • Composition versus Method claims • 1. A pharmaceutical composition comprising a tyrosine kinase inhibitor having the formula… • 1. A method of killing and/or inhibiting the growth of the blood stream form of a kinetoplastid protozoan of the species Trypanosoma brucei in a subject, the method comprising administering to the subject an effective amount of a tyrosine kinase inhibitor; wherein the tyrosine kinase inhibitor is a 4-anilinoquinazoline selected from the group consisting of AG1478, erlotinib, and lapatinib. 25 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Patent claims, continued • Dependent claims • The pharmaceutical composition of claim 1, wherein the tyrosinse kinase inhibitor is present at a concentration of 1-10 mM. • The method of claim 1, wherein the 4-anilinoquinazoline is administered at a dose of 10 ug/kg. 26 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Composition of matter claims • You cannot patent a composition that is already known • But… • You can get a composition claim to: • A new formulation of the composition • Combination of the composition to a delivery device 27 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Method claims • New use for an old drug is PATENTABLE • In fact, patents to multiple new uses can be obtained by several third parties provided that the new uses are novel and nonobvious variants 28 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Patent application timeline Priority Application PCT or Nonprovisional Application National/ Regional Phases Europe US Japan India China Etc. Grant Publication Start 1 year 18 months Additional data can be added to application 29 30 months 3-5 years Enforceable rights S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Requirements for patentability • • • • • • Utility Novelty (cannot have been described elsewhere) Non-obvious Enable a person of skill in the art to make and use invention Adequately described (Adequate written description) Best mode for carrying out invention – US Patent offices examine all of these requirements in view of what is CLAIMED. 30 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Utility • Likely the easiest of the patentability requirements • The invention must be useful 31 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Patentable Subject Matter: 35 U.S.C § 101 • Patentable Subject Matter: • Compounds/compositions of matter • Processes or methods of use • Machines (combination of elements that function together) • Non-patentable Subject matter • Products of nature • Printed materials (books, journals, etc.) • Abstract formulas/algorithms • Use of nuclear material or atomic energy 32 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Novelty • The invention was not known, described, or offered for sale prior to filing the patent application. 33 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Novelty: 35 U.S.C. § 102 • Publications or patents anywhere in the world • Journal articles as of the date of publication • Oral presentations • Public use in the United States • Experimental use • Clinical trials are exempt • Prior sale or offer for sale in the United States • Prior invention in the United States • Reference MUST TEACH ALL aspects of claimed invention – arranged as claimed 34 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Grace Period – U.S. • Time period prior to filing in which applicant’s own work cannot be used against them as prior art • Provides a limited time period to file after an intentional or accidental disclosure of the invention • Balances applicant needs with desire for early filing • NO GRACE PERIOD IN MOST COUNTRIES – ABSOLUTE NOVELTY REQUIREMENT! 35 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Obviousness • Inventions must be non-obvious • Cannot be simple modifications of an old invention • Obviousness is determined using Person of Ordinary Skill in the Art (POSA) standard 36 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Obviousness: 35 U.S.C. § 103 • Obviousness can be predicated on multiple references and/or general knowledge in the field • Must be reason to combine references however • Reference(s) must teach or suggest all of the claimed limitations • A POSA must have a reasonable expectation of success • VERY SUBJECTIVE TEST 37 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Obviousness – But wait! • Objective indicia of non-obviousness • Commercial success • Long felt but unmet need • Failure of others • Skepticism by experts • Praise by others • Copying of the invention by competitors 38 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Written Description • Patent specification must adequately describe the claimed invention in a manner as to enable a POSA to make and use the invention • Goal of written description is to show possession of invention • When claims encompass a genus – must describe a representative number of species or a structure common to members of genus 39 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Enablement • Experimentation is acceptable – just not UNDUE experimenation • Breadth of the claims; • Nature of the invention; • State of the prior art; • Level of ordinary skill in the art; • Predictability of the art; • Amount of direction provided in the specification; • Any working examples; and • Quantity of experimentation needed relative to the disclosure. 40 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Duty of disclosure in US • File Information Disclosure Statement • Duty on applicants, attorneys and anyone substantively involved in the patent application process to disclose all “material” information that they are aware of to the Patent Office • No duty to search • Duty continues until issuance • Failure to comply may render patent unenforceable 41 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Examination process in US 36 months US Examination Routine formalities Power of Attorney Reporting Events Official Filing Receipt Publication Information Disclosure Statement RCE Office Action Reply Notice of Allowability Final Office Action Reply Advisory Action Patent Granted 42 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Patent Application Process (3-5 Years on Average?) 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 43 Conceive the invention Write the application File the application Meet the application formalities – e.g., declaration, formal drawings Examination process begins Restriction requirement issued – sometimes Substantive Office Action issued Reply filed (usually there will be multiple iterations of this and the above step before an allowance is obtained) Appeal filed Application Allowed Pay necessary fees – file continuations? Patent issues Pay Maintenance Fees S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Patent term • 20 years from initial United States filing date • 17 years from issue date, if longer (older patents) • One patent per drug product can be extended up to 5 years due to FDA delay – Patent Term Extension (PTE) • Extensions may be possible for Patent and Trademark Office delay – Patent Term Adjustment (PTA) 44 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. America Invents Act (AIA) • Brings US in line with ROW – first to file system • Inventor will still have a personal grace-period, which is not available to inventors outside the US. • However, disclosures of third-parties who independently arrive at the invention information will be used against the inventor. • No grace-period relative to third party disclosures. 45 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. AIA proceedings Proceeding 46 Threshold Prior Art Estoppel? Third party pre-issuance submissions N/A Patents/printed publications N/A Post-grant review (PGR) More likely than not at least 1 claim unpatentable Any ground Raised or could have raised Inter partes review (after PGR) Reasonable likelihood that petitioner would prevail on at least 1 claim Patents/printed publications Raised or could have raised Ex parte reexam (unchanged) Substantial new question of patentability Patents/printed publications None Supplemental examination Substantial new question of patentability Any information N/A Derivation proceedings Claimed invention derived from another N/A N/A S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. AIA – Prior User Rights Defense • What happens when you are using a process that someone else later comes along and patents? Are you guilty of patent infringement even though you used the process before they filed? • NO! • The act provides a broader “prior use” defense when a business is using a process or machine as part of a process, and has been doing so for more than one year prior to the effective filing date of a patent that would cover the process or machine. • The defense is personal to the user, and can only be transferred with the business to which the process or machine relates. 47 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Should you always file for a patent? What about trade secrets?? 48 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. What is a trade secret? • Broadly speaking, any confidential business information which provides an enterprise a competitive edge may be considered a trade secret. • Trade secrets encompass manufacturing or industrial secrets and commercial secrets. • Unauthorized use of such information is regarded as an unfair practice and a violation of the trade secret. 49 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Advantages of Trade Secrets • • • • 50 Trade secret can cover abstract ideas Trade secret can last indefinitely Trade secret protection is comparatively cheap Trade secrets can create aura of mystique S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Patent versus Trade Secret • • 51 Advantages • Market exclusivity • Revenue opportunities – license • Leverage in negotiations and litigation • Deter/disrupt competitors Disadvantages • Disclosure is required • Cost (relative to maintaining know-how as trade secret) • Difficult to determine what to file on • Difficult to spot infringement • • S K G F. C O M Advantages • Maintain private competitive edge • Ability to protect know-how, embryonic ideas • No prosecution costs Disadvantages • Hard to police unathorized disclosure • No protection against reverse engineering • Employee turnover • Desire for inventors to publish © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Balance of issues Increased risk of unauthorized disclosure Increased harm of unauthorized disclosure 52 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Process patents can block marketing of product made • Process Patent Act – 35 U.S.C § 271(g) • Whoever without authority imports into the United States or sells or uses within the United States a product which is made by a process patented in the United States shall be liable as an infringer, if the importation, sale, or use of the product occurs during the term of such process patent. ….. A product which is made by a patented process will, for purposes of this title, not be considered to be so made after-• (1) it is materially changed by subsequent processes; or • (2) it becomes a trivial and nonessential component of another product. A+B→C 53 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Patenting and Commercializing Inventions: Is It Worth It? • Yes, and it is likely part of your job • The public benefits from innovation • IP is the only protection during development that provides cover for financial risks. • Patent prosecution can always be (and often is) abandoned – but cannot be started when it is too late (e.g., disclosures) • It will not interfere with the free exchange of information and reagents • Patenting does not preclude publishing 54 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Research Commercialization Provides Many Benefits • Provides means getting innovative products to the market for public benefit • Commercial & public recognition of important technologies • Attracts new R&D resources & partnerships for the University • Obtains return on investment • Stimulates economic development 55 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Research Commercialization: An Interdisciplinary Field Intellectual Property Discovery 56 Commercialization S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Product Commercialization: From Lab Bench to Customer TECHNOLOGY TRANSFER Discovery Intellectual Technology Property Transfer BUSINESS DEVELOPMENT ATTORNEYS Financial Corporate R&D Sales & Capital Partnership Clinical trials Marketing Regulatory Manufacturing 57 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. The Researcher’s Basic Obligations for Successful Commercialization • Keep accurate lab notebooks • Remember all disclosures can count against you so safeguard your rights • Work with tech transfer office staff, law firm and commercial partners. • CDAs/MTAs (Confidential Disclosure Agreements / Material Transfer Agreements) – are essential for the transfer of information and reagents 58 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Research Commercialization at Universities • University evaluate inventions for patenting • University work closely with inventors • Work with law firms and management of patents • Identify and negotiate with a commercial partner for license or collaboration agreements • Managing relationship with commercial partners 59 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Useful links and resources • Manual of Patent Examiners and Practitioners – MPEP • https://mpep.uspto.gov/RDMS/MPEP/current • US Patent and Trademark Office – USPTO • https://www.uspto.gov/ • World Intellectual Property Organization – WIPO • http://www.wipo.int/portal/en/index.html • Patent Law Blogs • http://patentlyo.com/ • http://www.patentdocs.org/ 60 S K G F. C O M © 2017 Sterne, Kessler, Goldstein & Fox P.L.L.C. All Rights Reserved. Biosimilars: Development and Approval Rita Raddatz Drexel 06 Mar17 1 Career Path  BS in Pharmacy  Student Co-op at Merrell Dow Pharmaceuticals Pharmacology  Licensed Pharmacist and Research Associate at Merrell Dow Pharmaceuticals  PhD Neuroscience with Molecular Pharmacology (Wash U)  Post – Doc in Pharmacology Dept. (MUSC)  Synaptic Pharmaceuticals  Astra Zeneca  Cephalon  Teva Branded Pharmaceutical Products R&D Director, Protein and Cell Sciences Global Bioassays and Technology 2 Outline 1 Introduction to Biosimilars 2 Approval Pathway Requirements 3 Case Studies 4 Future of Biosimilars in US 3 What is a Biosimilar?  The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) part of the Affordable Care Act was signed into law on March 23, 2010.  BPCI Act creates an abbreviated licensure pathway, 351(k) of the Public Health Service Act (PHS Act), for biological products shown to be biosimilar to or interchangeable with an FDA-licensed reference product.  Product is “highly similar” to an FDA-licensed biological product (the reference product), and there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product. 4 Why Biosimilars?  Annual cost of Prolia: ~ $1,650 per year TNF blockers: $15, 000 – $25,000 per year*  Medical costs rising in many countries  Boom in biologics sales (ex: Humira highest selling drug at $16 billion world-wide in 2016+)  Blockbuster biologics set to go off patent  Cost reduction by biosimilars expected to be small in %, but still $$  Generics small molecule drugs common 5 *(Bonafede et al, Adv Ther 2012) +(AbbVie Jan 27, 2017 press release) How is biosimilar different from generic drug? mAb Aspirin Much higher R&D, legal and manufacturing costs Adapted from: Developing the Nation’s Biosimilars Program, NEJM 2011 6 Steven Kozlowski, M.D., Janet Woodcock, M.D., Karen Midthun, M.D., and Rachel Behrman Sherman, M.D., M.P.H. Current Status of Biosimilars in US  March, 2015 first approval of 351(k) biosimilar application, Sandoz Inc’s Zarxio, biosimilar to Amgen’s Neupogen (filgrastim, metG-CSF)  Celltrion and Pfizer’s Inflectra, biosimilar of Janssen Biotech’s Remicade (infliximab, anti-TNFα) approved April 2016  Approval of Sandoz’s Erelzi, biosimilar of Amgen’s Enbrel (etanercept, TNF blocker) Aug 2016  Amgen’s Amjevita approved as biosimilar of AbbVie’s Humira (adalimumab, anti-TNF α) Sept 2016  Biosimilar Sponsor must provide at least 180 day notice to reference product sponsor after approval before marketing, ongoing litigation  Several announced to be under review 7 Earlier Biosimilars in Europe– Why?  Starting in 2006, EC has authorized 23 biosimilars for sale  3 infliximabs (2013-2016) and one etanercept (2016), others less complex proteins  Some biologics that are off patent in US produced by others– but used full BLA pathway for approval  EMA guidelines available as early as 2005  In the absence of a well defined path, risk was on industry to bring 351(k) application to FDA 8 Presented at DIA Biosimilars meeting 2012 Niklas Ekman, Ph.D. Senior Researcher, Quality/CMC Assessor Finnish Medicine Agency (FIMEA) 9 FDA Biosimilars Guidances Drafts ~ 2012; Finalized 2014 – …….  Scientific Considerations in Demonstrating Biosimilarity to a Reference Product  Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product  Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009  Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants  Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product (Dec 2016)  Nonproprietary Naming of Biological Products (Jan 2017)  Interchangeability Draft Jan 2017, 60 days to comment, revisions likely 10 Outline 1 Introduction to Biosimilars 2 Approval Pathway Requirements 3 Case Studies 4 Future of Biosimilars in US 11 Basics of Demonstrating Biosimilarity  Different than demonstrating a new drug is safe and effective.  Totality-of-the-evidence approach consistent throughout  The more evidence generated through the characterization process, the less clinical data a sponsor will be required to obtain  Faster time to market  Significantly less cost  Ethical considerations of clinical trials 12 Comparative Studies Clinical Safety and Efficacy “residual uncertainty” Clinical Immunogenicity, PK/PD Animal studies, toxicity Extensive structural and functional characterization Adapted from: FDA’s Overview of the Regulatory Guidance for the Development and Approval of Biosimilar Products in the US Leah Christl, Ph.D. Associate Director for Therapeutic Biologics 13 Practical Considerations to Biosimilarity  Biologics are complex products of cell lines or biological systems  Biosimilar development must begin with identical protein sequence, where applicable.  Similar concept to generic drugs that have the same chemical structure as the reference product.  Expression system as close as reasonable to reference product (ex: CHO cell or bacteria)  Originator company owns the actual clonal cell line expressing their protein (reference product)  Manufacturing process, purification, formulation, product characterization and control key to achieving biosimilarity  Iterative processes 14 Biologics Characterization  Biologics are too complex to completely characterize by traditional analytical methods  “The process is the product”  Aspects that may alter product:  Host cell line (CHO, yeast, …..)  Growth medium composition  Culture conditions (pH, temperature, aeration)  Production type (batch, fed batch, perfusion)  Growth regimen (duration, fed type, perfusion rate)  Culture history (genetic stability)  Hold times  Purification  Formulations  Storage (buffer, container, stoppers, temperature) 15 EBG Biosimilars Satellite Symposium European Association of Hospital Pharmacists Congress 17 March 2016 16 Biosimilars Development in Practice Analytical Similarity Data  Extensive structural and functional characterization of reference product  Quality Target Product Profile (QTPP) should be defined early in product development.  Understand the relationship between quality attributes and the clinical safety / efficacy profile  QTPP should be based on analytical data from several batches of the reference medicinal product  Includes impurities and product stability  Characterize proposed biosimilar product quality profile  Determine how proposed biosimilar lots compare to originator lots  Identify and evaluate impact of any differences 17 Comparison to Reference Products  Reference Product :  the single biological product, licensed under section 351(a) of the PHS Act, against which a biological product is evaluated in an application submitted under section 351(k) of the PHS Act.  Many lots of originator drug must be tested over several years  Quality attributes of product on the marker may shift with manufacturing changes  Example- comparison of glycans on lots of Enbrel before (light blue) and after (dark blue) change M Schiestl et al., Nat Biotech 2011 18 Animal Studies  From FDA Guidances:  Animal toxicity data are useful when uncertainties remain about the safety of the proposed product prior to initiating clinical studies.  A comparison of PK/PD in an animal model may be useful.  Not all biologics interact with target in relevant toxicology species  Some biologics highly immunogenic in animals  Sponsors should consult with FDA prior to the pre-IND/IND stage to ensure that they do not conduct unnecessary animal studies.  Immunogenicity in pre-clinical species not predictive of humans 19 Clinical Studies The nature and scope of clinical studies will depend on the extent of residual uncertainty about the biosimilarity of the two products after conducting extensive structural and functional characterization and, where relevant, animal studies.  Type of Clinical Data  PK (pharmacokinetcs) and PD (pharmacodynamics) if relevant  At least 1 clinical study that includes a comparison of the immunogenicity of the proposed and reference product  Comparative clinical study if there are residual uncertainties about whether there are clinically meaningful differences .  Extrapolation to indications not tested in clinical trial(s)  For example, Amjevita was approved for 6 of the 10 indications approved for Humira  Inflectra approved for all indications of Remicade, only rheumatoid arthritis and ankylosing spondylitis tested in comparative trials. 20 Sandoz Development Stages Strategy Sandoz advisory committee briefing document – public release 21 Outline 1 Introduction to Biosimilars 2 Approval Pathway Requirements 3 Case Studies 4 Future of Biosimilars in US 22 Sandoz/Novarits Zarxio Biosimilar to Amgen Neupogen  Amgen seeing ~ $1.2 B (billion!) a year in sales  Sandoz filgrastim (Zarzio) biosimilar approval from EMA in 2009  Filgrastim (GCSF; 18.8 kDa protein)  High homology across mammalian species  Treatment for neutropenia in cancer patients mostly  Stimulates leukocyte proliferation  Produced in bacterial cells, not glycosylated 23 Analytical Comparison: Zarxio to Neupogen  3- 16 lots compared in orthogonal tests covering:  Sequence and disulfide bond formation  N-terminal Edman sequencing  LC/MS/MS  Tryptic peptide map by HPLC  Folding  Circular dichroism  NMR  Functional assays  Target Binding  Cell -based potency  Size Variants  Size Exclusion chromatography  Sub visible particles (microflow imaging) Sandoz advisory committee briefing document – public release 24 Analytical Comparison: Zarxio to Neupogen Highly Similar but not identical  Variants profile  Deamidation  Truncated and norleucine variants  Oxidation (below) Sandoz advisory committee briefing document – public release 25 Zarxio : Neupogen in Animal Studies  Zarxio compared with Neupogen in five, GLP compliant, animal studies (rats and rabbits)  Pharmacodynamics (neutrophil count)  Toxicity (observations including blood chemistry, histopath)  Toxicokinetics (drug levels at different time points)  Local tolerance (hypersensitivity reactions)  Different buffering systems  Immunogenicity differences were investigated Sandoz advisory committee briefing document – public release 26 Zarxio : Neupogen Clinical Studies  Studies previously conducted comparing with EU Neupogen as reference product  Two pivotal trials specifically performed to compare Zarxio with US-licensed Neupogen  PK/PD in 174 healthy volunteers  Comparative safety and efficacy in 388 breast cancer patients. 90% confidence intervals AUC 27 Outline 1 Introduction to Biosimilars 2 Approval Pathway Requirements 3 Case Studies 4 Future of Biosimilars in US 28 CT-P13 (infliximab) Biosimilar to Remicade  Celltrion’s infliximab was first biosimilar monoclonal antibody in the world (EC approval 2013)  Biosimilar licensed in 67 countries (Inflectra /Remsima)  Remicade ~ $4 billion a year in US sales (J&J)  Anti-TNFα monoclonal antibody  Human/ mouse antibody chimera  More complex protein (~ 144 kDa) produced in mammalian cells  Remicade approved for use in  Crohn’s disease (adult and pediatric)  Ulcerative Colitis (adult and pediatric)  Psoriasis  Psoriatic Arthritis  Ankylosing Spondylitis  Rheumatoid Arthritis 29 Analytical Comparison: CT-P13 to Remicade 3-way Comparison to Bridge US to EU Remicade (infliximab)  Highly similar in key Quality Attributes  Differences characterized and impact assessed  Intact IgG (95.1% vs 98.2%, 98.3%) – cell potency results  Glycation – not in TNF binding regions, no potency differences, immunogenicity assessed in clinical trails  G0 content – 24 different ex vivo studies for function and binding comparisons Celltrion advisory committee briefing document – public release 30 Analytical Comparison of CT-P13 to Remicade (infliximab) Celltrion advisory committee briefing document – public release 31 Analytical Comparison of CT-P13 to Remicade (infliximab) Celltrion advisory committee briefing document – public release 32 CT-P13:Remicade in Animals and Clinical Trials  Infliximab does not bind non-human TNFα  Performed rat TK and immunogenicity assessment  Remaining uncertainties addressed in clinical studies  Charge variants  High molecular weight forms  Initially EU biosimilar approval based on 2 trials in AS and RA patients  Post marketing safety and extension studies  Pharmacodynamics, pharmacokinetics and safety compared  Immunogenicity key clinical comparison (CT-P13, US, EU groups, resp)  15%, 12% and 33% positive (109 CD patients)  27%, 11%, 25% positive (211 healthy volunteers) Celltrion advisory committee briefing document – public release 33 Comparison of CT-P13 to Remicade (infliximab)  3-way clinical PK study to bridge EU and US Remicade Celltrion advisory committee briefing document – public release 34 Summary of CT-P13 Biosimilarity to Remicade Celltrion advisory committee briefing document – public release 35 Outline 1 Introduction to Biosimilars 2 Approval Pathway Requirements 3 Case Studies 4 Future of Biosimilars in US 36 Remaining Questions  Extend indications (ex: Remicade licensed for 8 indications)  The potential exists for a biosimilar product to be approved for one or more conditions of use for which the US-licensed reference product is licensed based on extrapolation of data intended to demonstrate biosimilarity in one condition of use. *  Sufficient scientific justification for extrapolating data is necessary. *  Pricing (Zarxio 15% less than Neupogen)  Jan 2017 FDA Guidance on Naming – xxxx added to end to identify manufacturer for originator and biosimilar products  Sandoz’s Zarxio (filgrastim-sndz) and Erelzi (etanercept-szzs), Amgen’s Amjevita (adalimumab-atto), Celltrion’s Inflectra (infliximab-dyyb) *FDA’s Overview of the Regulatory Guidance for the Development and Approval of Biosimilar Products in the US Leah Christl, Ph.D. 37 Associate Director for Therapeutic Biologics Remaining Question of Interchangeability  Could be substituted at the pharmacy level  FDA draft guidance just published Jan 2017  Clinical trials may require multiple switches between proposed biosimilar and marketed drug  Subject to sate laws on substitution (18 states so far)  Tennessee : a prescriber must allow substitution unless the prescriber determines “the medical necessity”  New Jersey : the pharmacist must inform the prescriber of any substitution  In the EU, member states regulate interchangeability (GaBI Online, Thimmaraju et al, 2015) 38 Future of Biosimilars in US  Advisory Committees at least for first applicants with each new biosimilar target.  Acceptance by doctors and patients  FDA Continuing Medical Education  Engagement of patient advocacy groups  Patent protection strategies by originators:  Constitutionality of Act  Manufacture processes  Formulations  Delivery systems  Uses  FDA inspections of manufacturers? 39 Which Biologics to Make as Biosimilars? 40 Which Biologics to Make as Biosimilars?  Market / patient needs  Patent timing  Complexity / manufacturability  Fit with company’s portfolio and sales force  Investment: 9-12 years start to market 41 Udpa and Million, Nat Rev Drug Discov 2016 Main Points  Highly Similar – Not Identical  Heavy reliance on analytical comparison data  No clinically meaningful differences  Totality of Evidence 42

International Business

November 14, 2022/in Uncategorized /by Linus

International Business

MIT Classification: Trusted 1. Apparel Industry 2. Computers, Office Equipment Industry RMIT Classification: Trusted 3. Household and Personal Products Industry 4. Internet Services and Retailing Industry RMIT Classification: Trusted 5. Pharmaceuticals Industry Global information economy Dr Joseph H. Kim School of Management RMIT University 1 1 Today’s lecture • Era of global information economy • Innovation and R&D • Implications for MNEs 2 2 Competing in the global information economy “We live in an information economy. The problem is that information’s usually impossible to get, at least in the right place, at the right time.” (Steve Jobs) 3 3 Global information economy • Industrial economy: productivity as source of competitinvess (e.g. division of labour, use of machinery, assembly lines etc) • GIE: “intangibles” such as information, innovation and creativity as both input and output • “The most important management in [GIE] is to manage intelligent workers.” (Peter Drucker) Industrial economy Information economy 4 4 Birth of Fordism: mass production in auto industry 5 5 Toyota Production System: “Automation with a human touch” (jidoka) 6 6 Software, Tesla’s competitiveness in auto industry? 7 7 “Smiling curve”: where value is created in GIE? 8 8 E-commerce in GIE • ICT impact on firms expanding into new markets • E-commerce: internet used as a transaction medium • Frequently refers to B2C, but also includes B2B and C2C • Overcoming the problems of distance and costs • Delivery of e-commerce services in foreign markets may be affected by IT infrastructure, logistics, cyber security and online payment services etc 9 9 Sharing economy in GIE • • • often referred to a “peer-to-peer” market an economic arrangement allowing people to collaboratively make use of underutilised assets (e.g. vehicles, bikes, houses, tools etc) through fee-based sharing using a digital platform intrinsically an international phenomenon 10 10 E-commerce & change in industry dynamics Porter’s Five Forces 11 11 Social media in GIE • Social media are interactive online communication technologies that facilitate the creation or sharing of information • Social media has become a critical part of MNE’s strategy – – • solicit opinions on new product development build relationships with both existing and potential customers create brand and product awareness customer support and education monitor and respond to consumer feedback Need locally responsive social media strategy 12 12 Innovation & R&D in GIE Where should MNEs locate their R&D activities? Innovation: Introduction and spread of new and improved products and processes in the economy R&D: Turning new knowledge and ideas into tangible products or processes 13 13 Samsung Electronics global R&D centres 14 14 Pfizer consolidating R&D sites 15 15 Measuring R&D intensity OECD (2022), Gross domestic spending on R&D indicator 16 16 Bloomberg Innovation Index 2021 17 17 Other indicators of innovation Patent activity: number of annual patent and grant filings High-tech density: volume of domestic, high-tech public companies and employees (e.g. aerospace, biotech, IT, renewable energy etc) Tertiary efficiency: total enrolment in higher education, the share of labour force with advanced education levels, and the share of STEM graduates and in the labour force etc 18 18 Innovation cluster • “a geographic concentration of business initiatives, suppliers and associated institutions in a particular field” (Michael Porter) • foster innovation and knowledge creation by bringing together educational and research institutions • knowledge spill-over driving innovation 19 19 Political Economy of Global Business Dr Joseph H. Kim School of Management RMIT University 1 1 Today’s lecture • • • Understanding political economy of global business Changes in business-government relationship Rise of populism 2 2 What is political economy? Why it matters in GB? • Political economy: interaction between political and economic systems • Understanding the impact of government decisions is businesses critical for MNEs • for assessing opportunities and risks; • formulating strategies 3 3 “Reshoring” to “Friend-shoring” Trump administration’s reshoring: Biden administration’s friend-shoring: “I’m going to get Apple to start making their computers and their iPhones on our land, not in China” “The idea [of friend-shoring] is for a group of countries with shared values to deploy policies encouraging companies to spread manufacturing within that group” (Donald Trump during his election campaign, 2016) (Washington Post, 2022) 4 4 Political economic decisions at global level “Global governance is governing, without sovereign authority, relationships that transcend national frontiers. Global governance is doing internationally what governments do at home“ (Frinkelstein, 1995, p. 369) “Global governance is … instance of governance in the absence of government” (Ruggie, 2014, p. 5) • Implies absence of central authority and the need for collaboration and cooperation among national governments • Backlash against political globalisation in recent years: as geopolitical landscape and political thinking change so do the role and impact of multilateral / regional institutions 5 5 Selected global and regional institutions and agreements Policy agenda Global Regional Trade WTO EU, NAFTA, ASEAN, Mercosur Monetary IMF EU (Eurozone), CFA franc Peace UN OSCE World Bank ADB, AfDB, EBRD, IDB Development finance Climate change Kyoto Agreement, Copenhagen Accord, Paris Accord Financial sector regulation Basel Committee 6 6 Australia’s free trade agreements (FTAs) 7 7 Role of national governments in GB • Political decisions by national governments based on sovereign rights • Key roles governments play include; o setting up, monitoring and managing an economic system – regulating and supporting business activities o encouraging FDI – tax incentives, improving infrastructure, removing administrative barriers o discouraging / limiting FDI – protecting local industries or key resources – maintaining political and economic independence – sanctions: e.g. sanction on Russia in the context of the Russia-Ukraine conflict o state capitalism: – government undertaking business activities (e.g. SOEs in oil industry) 8 8 State-owned oil companies 9 9 10 Changes in businessgovernment relationship 1930s – 1970s: Interventionism • Era of big government: Keynesianism and welfare state in the post WWII period 1980s – mid 2000s: Liberalism • “Small and efficient” government: rise of neoliberalism, NPM (new public management) and global integration 2008 – present: Back to interventionism • “Small and strong” government vs “big and strong” government?: GFC, COVID-19 and the rise of populism 10 10 11 What is populism? • An ideology which pits a virtuous and homogenous people against a set of elites and dangerous ‘others’ who are together depicted as depriving (or attempting to deprive) the sovereign people of their rights, values, prosperity, identity and voice. Albertazzi & McDonnell (2008) • “[Brexit]…a victory for real people, a victory for ordinary people, a victory for decent people. We have fought against the multinationals, we have fought against the big merchant banks, we have fought against big politics, we have fought against lies, corruption and deceit.” Nigel Farage, leader of Brexit Party 11 11 https://www.statista.com/chart/16180/europeans-livingunder-governments-with-at-least-one-populist-in-cabinet/ 12 12 13 Causes and consequences of populism • Causes? • Economic crisis and social inequality • Backlash against hyper-globalisation and pluralism • Consequences • Anti-trade & anti-immigrationContact details policies • Uncertainty for businesses 13 13 14 14 15 Implications for MNEs? • Current business environment presents novel challenge to the way businesses engage with politics • Market strategies are no longer enough: MNEs need non-market strategies to work with social and political imperatives – “Public policy is no longer a spectator sport for business.” (Murray Weidenbaum, 1980) – Corporate political activities: “corporate attempts to shape government policy in ways favourable to the firm” (Hillman et al., 2004) – E.g. lobbying, coalition formation, communication with governments and the wider public etc 15 15 Week 6 Stakeholders in IB and responsible management of MNES Dr Joseph H. Kim School of Management RMIT University 1 1 Today’s lecture • Stakeholder view of corporate social responsibility (CSR) • Key theoretical frameworks of CSR • Responsible and strategic management: “doing well by doing good” 2 2 CSR: Shareholder vs stakeholder approach • Corporate Social Responsibility (CSR) – refers to the idea that managers should consider the social consequences of economic actions when making business decisions Two opposing views on CSR Shareholder view of firm Q. Why does a business exist? Q. Who should the business serve? 3 3 Stakeholder view of firm Shareholder view of CSR “There is one and only one social responsibility of business- to use its resources and engage in activities designed to increase its profits so long as its stays within the rule of the game” (Milton Friedman) • If firms attempt to attain social goals, such as providing employment and social welfare, managers will lose their focus on profit maximisation, and therefore not appropriate 4 4 Stakeholder view of CSR • Social responsibility of firms goes beyond economic and legal responsibilities to adapt to changing societal conditions and pursue long-term goals that are good for society – A stakeholder is “any group or individual who can affect or is affected by the achievement of the organisation’s objectives” 5 5 Growing recognition about the importance of CSR “Most large companies, and even some smaller ones, now feature CSR (or sustainability) reports, managers, departments, or at least CSR (or sustainability) –project and the subject is increasingly promoted as a core area of management, next to marketing, accounting, or finance” Crane, Matten & Spence (2008) 6 6 7 7 MNEs changing the world? Fortune Magazine: “Change the World” Company List 8 8 Carroll’s pyramid of CSR Desired Expected Required 9 9 Triple bottom line and CSR 10 10 Case: Sustainability at Unilever • Considered as a leading advocate of business sustainability • Implemented through the Unilever Sustainable Living Plan (USLP) 11 11 Case: Sustainability at Unilever https://www.unilever.com/sustainable-living/ 12 12 Sustainability and strategy • Traditional view: “Arm-wrestling match”: Trade-off between social / environmental benefits and industry’s private costs • Realisation that sustainability is the right thing to do, and can also drive revenue, savings, and give a competitive edge • CSR can be more than just a cost, constraint or charitable deed – • “Properly designed environmental standards can improve resource productivity” (Porter and van der Linde, 1995) Can MNEs’ involvement in CSR generate opportunity, innovation and competitive advantage – while solving social problems? 13 13 Circular economy • Alternative to a make, use, dispose model with as much re-use and recycling as possible • Extending the life of products and materials to prevent the overgeneration of waste • The longer materials and resources are in use, the more value is extracted from them https://www.ellenmacarthurfoundation.org/circular-economy/concept 14 14 Paths to develop sustainable products high ACCENTUATE ANY OF THE THREE ACQUIRE ARCHITECT EXISTING “GREENABLE” ATTRIBUTES low low DEVELOPMENT CAPABILITIES OF “GREEN” PRODUCTS high Source: Unruh and Ettenson, 2010 15 15 Paths to develop sustainable products • Path #1. Accentuate • Playing up existing green attributes in the company’s portfolio • Credibility of its sustainability efforts is crucial – Important not to overreach in its sustainability claims which may attract activist and consumer backlash, and undermine the company’s legitimate sustainability claims • E.g. Brita – growing criticism towards water bottlers for clogging landfills – company research: replacing bottled water with Brita system could potentially keep millions of bottles a year out of landfills – adopted an integrated cross-media communication strategy to tout Brita’s green attributes, educate consumers about bottle waste and encourage a switch to greener alternatives – water pitcher sales jumped by 23% within a year (compared to 2% for the category) 16 16 Paths to develop sustainable products • Path #2. Acquire • Buying other company’s green brand when there is no obvious candidates for accentuation • E.g. High profile green acquisitions – The Body Shop by L’Oréal – Ben & Jerry’s by Unilever – Tom’s of Maine by Colgate-Palmolive 17 17 Paths to develop sustainable products • Path #3. Architect • Building new offerings from scratch • Can be slower and more costly than the other options, but may allow the company to build valuable competencies • E.g. Toyota – Development of a hybrid car, Prius – Dominates fast-growing market for fuel-efficient cars – Successfully transferred the expertise and know-how to luxury cars market (Lexus) 18 18 Week 7: Understanding MNEs Dr Joseph H. Kim School of Management RMIT University 1 1 Today’s lecture • MNE and FDI: Eclectic paradigm of FDI • Competitive advantage and MNE • Sources of competitive advantage ◦ Industry-based approach ◦ Resource-based approach 2 2 Multinational enterprise (MNE) A firm that engages in foreign direct investment and operates in multiple countries 3 3 The FDI vocabulary • FDI vs FPI ◦ Foreign Direct Investment (FDI): investment in business activities outside a firm’s home country, giving it controlling ownership over those activities ◦ Foreign Portfolio Investment (FPI): investment in a portfolio of foreign securities such as stocks and bonds • FDI vs exporting & licensing ◦ Exporting: sales of products produced in one country to residents in another ◦ Licensing: occurs when a firm (the licensor) licenses the right to produce its product, use its production processes, or use its brand name or trademark to another firm (the licensee) 4 4 Challenges in operating in foreign markets Liability of foreignness 5 5 Why do firms become MNEs by engaging in FDI? Ownership advantages Dunning’s eclectic (OLI) paradigm Location advantages Internalisation advantages 6 6 6 Ownership advantages (Why of FDI) • Embraces market power theory (Hymer, 1960) ◦ When entering foreign markets, firms have innate disadvantages against competing local firms ◦ If they are to engage in FDI, the firms must possess firmspecific assets (FSA) which create advantages over local firms e.g. technology, patents, managerial/marketing know-how, brand name, access to information, product differentiation and skilled personnel etc ◦ Ownership of FSA makes FDI a viable option 7 7 7 Location advantages (Where of FDI) • Different location advantages may be exploited by firms according to different motives ◦ Market-related location advantages − − − − Larger & fast growing market Interaction with customers Transportation: perishable? breakable? heavy? Protectionism ◦ Resource-related location advantages − − Natural resources Low labour costs ◦ Knowledge-related location advantages ◦ Network-related location advantages 8 8 8 Internalisation theory (How of FDI) • Based on the market imperfection and transaction cost theories: Market failure induces FDI (Buckley, Casson, Hennart in the 1960s and 1970s) ◦ Examples of market impediments − Transportation costs − Trade barriers − Transaction costs • FDI “internalises” (replaces) external market relationships within one firm (the focal MNE) owning and controlling activities • Focuses on modes of transaction (entry): Why does FDI occur instead of exporting or licensing? 9 9 9 Internalisation theory: market vs firm Export Turnkey Licensing Franchising Joint venture Wholly-owned subsidiary Less commitment/ investment More commitment/ investment Less control More control Reliance on market Internal to firm 10 10 Strategic alliance 10 Competitive advantage in IB • Competitive advantage is obtained “when an organisation develops or acquires a set of attributes (or executes actions) that allow it to outperform its competitors” (Wang, 2014) • A firms is said to have a competitive advantage “when it is implementing a value creating strategy not simultaneously being implemented by any current or potential competitors” (Barney, 1991) 11 11 11 Sources of competitiveness: industry vs firm Industry-based view Resource-based view 12 12 12 Industry-based view • What is industry? – A group of firms producing products that are similar to each other • Theories of industry competition – Industrial organisation (IO) economics model Industry structure determines firm’s conduct (strategy) and performance (SCP model) Structure Conduct Performance 13 13 Porter’s Five Forces Framework • “Translated” and extended from the SCP model in 1980 by Michael Porter • Firm’s competitiveness depends on the degree of ‘five forces’ within the industry • The framework is evidence that; – not all industries are equal in terms of their potential profitability – industry-specific conditions play an important role in determining firm performance 14 14 Porter’s Five Forces Framework 15 15 Resource-based View • Firm specific resources and capabilities drive firm strategy and performance – Firm: a heterogeneous bundle of resources and capabilities 16 16 How can a firm create sustained competitive advantage? 17 17 How valuable / rare is the resource? • Valuable: do the resources and capabilities add value? ◦ Only value-adding resources can possibly lead to competitive advantage • Rare: are the resources and capabilities rare? ◦ The basic condition of competitive advantage: scarcity – Resources that are valuable but not rare lead to competitive parity, not advantage. – “If everyone has it, you can’t make money from it” 18 18 How imitable is the resource? • Resources that can be easily copied or imitated provide little scope for competitive advantage • Competitive advantage from complex, tacit and hard-to-describe knowledge – Tacit knowledge: difficult to articulate, write down or codify as an algorithm, formula, or set of rules • Valuable, rare, but imitable resources/capabilities = temporary advantage • Only valuable, rare and hard-to-imitate resources/capabilities = sustained competitive advantage 19 19 Are the firms organised to exploit resources and capabilities? • Question of Organisation – How is a firm organised to develop and leverage the full potential of its resources and capabilities

Quality Management in Healthcare

November 11, 2022/0 Comments/in /by

Dr. Wendy Walsh Gives ideas on esattamente battle Sexual Harassment on the job

November 9, 2022/in Uncategorized /by bella mso

La Rapida tipo: Sessuale molestia in realtà un argomento caldo affecting dipendenti in-service tasks, the technology market, the policy mondo, e vari alcuni altri lavoro percorsi. A lot of coraggiose femmine hanno ultimamente si sono fatte avanti verso affrontare lavoro sessista condizioni che preda di pietà e silenzio. Relationship expert e psicologa Dr. Wendy Walsh {è diventata|trasformata in una sostenitrice delle molestie intime nel 2017 ogni volta si è trasferita community con accuse di cattiva condotta intima da parte dell’allora Fox News varietà Bill O’Reilly. informando la loro storia, ha legittimato le affermazioni di vario altro malati e incoraggiato molti altri a basta prendere a stand quando oggettivato, molestato o vittima di bullismo a causa del efficace. La dott.ssa Wendy ha dato tutti noi alcuni consigli su navigare incontri online, interazioni e molestie nel presente ambiente di lavoro rendere veramente il luogo di lavoro più equo e meno pericoloso per tutti.

Mostra

una scuola amico di mio finito per essere di solito un overachiever. Ha finito la donna compiti volte in anticipo, gestito ricerca eventi prima di esami e si è laureato con un diploma di laurea / magistrale grado in contabilità entro solo quattro anni. Era stato non sorprendente quando si impadroniva di una postura a un alto azienda una volta lei era stato 22.

era una sorpresa quando rimanendo l’impresa dopo inferiore a un anno. ho chiesto la signora solo cosa era accaduto, e lei rivelato che non poteva sedere l ‘posto di lavoro sessista più. Lei datori di lavoro e colleghi capitava di essere generalmente maschi, quindi lei spesso ottenuto indesiderato interesse. Lei era stata fresca lontana da school e decisamente caldo, ma era anche un lavoratore impiegato solo chi si è rifiutato sopportare qualsiasi individuo contattando la signora neonato o carina di lavoro.

La donna conoscenza in realtà purtroppo comune per le donne sul posto di lavoro. Per un Cosmopolitan.com recensione, uno su tre donne molti anni da 18 a 34 hanno sperimentato una sorta di intima in ufficio. Cosa è effettivamente anche peggio, il 71 % di quelli intervistati menzionato loro non denunciare la molestia. Il mio buon amico mi ha informato che ha gettato la spugna su reporting eventi quando ha visto nessun indicazione di conseguenze o modifiche. Lei non desidera acquisire la reputazione di lamentatore o create surf insieme a lei datori di lavoro.

Vittime di molestie intime tipicamente feel sotto pressione per aiutare a mantenere tranquillo per assortiti spiegazioni, ma così facendo semplicemente si rafforza lo condition quo. Talking out is an important initial step to altering a work tradition built on silenzio e sessismo.

A livello nazionale consigliato unione specialista La dottoressa Wendy Walsh rivelato come efficace individuo testimonianza sono per il fight sessuali predatori sul posto di lavoro. Nel 2017, ha parlato candidamente e apertamente di un’attività cena che aveva con l’allora Fox Notizie numero Bill O’Reilly molti anni prima. Lui menzionato lui voleva esplorare la donna futuro come collaboratore di loro programma, ma loro termini trasformato aspro ogni volta ha negato un invito ad venire con lui al suo accommodation.

“credo cattivo che molti di questi vecchi ragazzi stanno utilizzando accoppiamento trucchi che sono stati accettabili in anni ’50 di conseguenza sono forse non appropriato oggi “, il dottor Wendy ha detto in a New York istanze meeting.

Dr. Wendy è venuto verso aumento comprensione riguardo pervadente carattere di sessuale molestia e ha oggi {diventato|divenuto|un nome di alto profilo leader la discussione di suggerimenti migliorare luogo di lavoro e protect dipendenti. Lei nel registro commenti si è unito vari altro accuse e innescato il convenzionale televisione varietà lasciando Fox Notizie.

Oggigiorno, la partnership consigliere ha effettivamente spostato il donna focus da generale appassionato argomenti a enfatizzare proprio come il flirt risulta essere molestia e come la connessione può provocare intimo comportamento scorretto. Questa donna è attualmente numero della radio programma televisivo su KFI AM 640 l. a. che sono ascoltati dovunque dal iHeartRadio application.

Abbiamo richiesto lei idee su ufficio interazioni per aiutare tutto nostro visitatori stare lontano da inadatto scenari, gestire problematico dilemmi e giorno moralmente lavoro.

“Un sacco di romantico soci soddisfare sul lavoro , “Il dottor Wendy ha notato. “Siamo tutti umano, e noi costantemente comunichiamo con l’un l’altro al tuo posto di lavoro, così è solo normal. Everything you need to do dopo che è effettivamente trova un modo ancora al lavoro e prevenire una causa sessuale. “

La tua abilità in un ambiente di lavoro ostile

Quando contro un aggressivo ambiente di lavoro, numerosi staff non so i posti migliori per cerca result in the concern go away. Qualche preoccupazione retribuzione per elaborazione un rapporto o dubbio unici problemi probabilmente sarà dato serio Attenzione. Basato su Elefante dentro Valley, uno studio collaborativo che ha esposto il sessismo durante il technology market, 39 percent di donne menzionato che avevano stato molestato al particolare attività fallito fare nulla perché loro pensavano potrebbe danneggiare le loro professions.

Non è molto facile segnalare molestie sessuali lavoro, ma questo è l’unico metodo per certamente permetti di essere prevent una volta per tutte. Creating the state are accountable to HR dovrebbe essere il very first strategia per tutti avere inadatto sessualmente addebitato osservazioni, comportamenti o progressi. Per troppo tempo, sessuale molestia è andata non segnalata e spazzata in tappeto, leader un sacco di vittime sentire proprio come se sono sopportare da solo. A volte può portare a brillante donne, come mio personale scuola amico, spargimento dall’esterno forza lavoro, caduta campagne e disimpegnarsi da incoraggiare professioni.

If you feel that the hour division or any other methods in posizione al tuo posto di lavoro non efficacemente riparare o gestire tuo preoccupazione, puoi sempre consultare un lavoro avvocato. La dottoressa Wendy notato che ci sono molte fonti da supportare soggetti di molestie in emotivo e appropriato problemi.

Dentro discussione, la dottoressa Wendy inoltre ha sottolineato che intima molestia può accadere a chiunque, per nessuna colpa di proprio. L ‘colpevole dovrebbe dare la colpa a, forse no la bersaglio. “non importa se sei single o sposato”, il dottor Wendy menzionato . “farà nessuna differenza enorme to the people just who apply intimate harassment serially.”

How exactly to Date a Coworker in the correct manner â With Respect & Courtesy

Navigating work interactions could be a difficult business. At what point does flirtation come to be inappropriate? Just what in case you carry out about a-work crush? Would it be ethical to date an underling? Dr. Wendy provided her thoughts with our team on these complex dilemmas.

To start with, she remarked that employee-employer interactions are naturally imbalanced because someone is dependent upon additional with regards to salary. A date invite, consequently, throws undue strain on the employee. “you shouldn’t make a sexual suggestion to an underling,” she mentioned. “you need to think about, âDo they obviously have permission?’ And, in this scenario, they don’t really.”

Dr. Wendy warned women and men to be cautious concerning comments they make to coworkers. You might intend your own comment as flattery, however you could possibly be making some one feel uncomfortable. Be familiar with your environments, and ensure that it stays professional whenever emailing coworkers.

If you should be interested in some one you function with, the first thing must be to flip open your organization’s handbook and look in the internet dating plan. In most cases, inter-office connections tend to be perfectly okay. You may need to signal some paperwork, though. Some work environments have started instituting a so-called love contract to help keep staff from suing should a workplace love be fallible.

After you make the leap and get some body away, Dr. Wendy entreated singles to take no for a remedy. If for example the coworker doesn’t want to visit away along with you, you need to drop the issue and never keep asking and inquiring until you finish reported to HR for harassment. Rejection is hard for a few people to stomach, however it happens alot inside dating world and is merely a portion of the online game. You will not change the no to a yes when you are within face all the time. You will just alienate them further.

Should you decide handle the situation with poise and maturity, that is really a better way to curry favor and perhaps reveal the person that you are really worth a second look. On the whole, you should be a pal rather than a jerk.

“You’ve got any right to ask somebody out, however you do not have the to harass them about it,” Dr. Wendy said. “all sorts of things we should instead be much more sincere and clear-cut. We-all should be grown-ups about any of it and honor the other person.”

Not simply a ladies problem: guys Can be Victims, Too

It’s important to note that sexual harassment will come in numerous forms and influences many different people. The perpetrators aren’t all mustachioed CEOs, additionally the sufferers aren’t all 20-something secretaries. Occasionally, women are the people creating inappropriate ideas their male coworkers.

“guys can be intimately harassed, also,” Dr. Wendy reminded us. “It isn’t really flirty whether or not it’s undesired. Men and women have to be responsive to that.”

“You’ve got any to ask someone away, however you don’t have the right to harass all of them.” â Dr. Wendy Walsh, union specialist and psychologist

Intimate harassment in the office is a pervading issue that influences both men and women. However, females however compensate the majority of incidents, but progressively more the male is coming toward submit research about intimate misconduct. In accordance with the Equal job Opportunity Commission (EEOC), 83percent of sexual harassment claims happened to be submitted by feamales in 2015, down from 92% of situations in 1990.

Some men are not subjects by themselves but nonetheless feel disappointed and troubled of the subculture of sexist habits tainting the office. Dr. Wendy informed us that many males blogged to thank her on her behalf advocacy regarding the concern. “I found myself happily surprised by the good comments from men,” she mentioned. “we heard from several thousand males, the great men available, who were pleased becoming getting rid of the outdated method and making the office less dangerous with regards to their spouses, siblings, and daughters.”

Dr. Wendy Encourages staff members to dicuss Up & request Justice

So numerous workers, like my good friend, simply proceed to another business without talk up-and shine lighting on a common issue. Dr. Wendy made a striking choice in developing her story during the early 2017. Today, the woman instance and management have encouraged other people become available and truthful in order to counteract misogynistic business culture that encourages intimate harassment.

Dr. Wendy spoke passionately about the need for following through against intimate predators: “men and women must be brave, talk upwards, follow through, and report harassment with regards to happens.”

Any person, irrespective of what their age is, sex, or profession, can be a prey of intimate harassment, so it is vital that you rally collectively on issue. Many blunt Americans have actually refused to take the present work weather and begun pushing to really make it a lot more clear, fair, and secure. Dr. Wendy became a number one vocals in this debate and mentioned she already sees modification taking place.

“since this national discussion has brought location, the truth is a lot more investigations and much more sufferers coming onward and being given serious attention,” she said. “in order that’s the new trend that I hope to continue.”

proprio sito

Evolution of Laws

November 8, 2022/0 Comments/in /by

Evolution of Laws

MMA was signed by President Bush in 2003. The MMA brought about sweeping changes that increased enrollment and improved access to Medicare Plans. Similarly, the PPACA was signed into law by President Obama in 2010. The law is expected to significantly increase access to Medicaid for the uninsured, low-income families, and individuals. Medicaid managed care has been implemented by most states, mainly because of rising costs, plan quality, access to providers, and the decrease in state revenues and federal matching funding. Medicare has explored managed care for the same reasons: to reduce costs, improve quality and improve access to providers. Using the South University Online Library or the Internet, research the following two topics and write a paper evaluating the impact of these policies on Medicare and Medicaid managed care.

You need to research on the following two topics:

Medicare and managed care
Medicaid and managed care

Based on your research, answer the following questions:

Write a summary for each topic tying together the information learned about that topic.
Analyze the challenges Medicaid faces in terms of improving access to care, quality of care, and reducing the cost of care.
Analyze the challenges Medicare faces in terms of improving access to care, quality of care, and reducing the cost of care.
Draw conclusions about the future of managed care in each programâ€”will it grow or decline? What will be the challenges for success?
Select at least four reputable articles per topic that address the challenges facing Medicare and Medicaid managed care.

As in all assignments, cite your sources in your work and provide references for the citations in APA format.

This is a 3-5 page paper completed in APA format that includes an introduction and conclusion.

Please refer to the rubric for this assignment for full understanding of the requirements.

Submit your document to the Submissions Area by the due date assigned.

Current Trends

November 6, 2022/0 Comments/in /by

Current Trends and Issues in Managed Care

Using the South University Online library or the Internet, research on a series of topics that will help you understand the current issues regarding managed care. You can use keywords, such as (but not limited to) managed care, current trends and issues in managed care, pharmacy benefit management, or utilization management. Like many other aspects of health care, managed care is continually changing and evolving to meet current consumer and market demands. This week, you are required to write an essay on the following topics:

Pharmacy benefit management
Utilization management

Use the following guidelines for developing your essay:

Select at least two articles for each topic from the SUO library, and write a review for each source of information.
Present a summary for each topic tying together the information learned about that topic.
Describe and evaluate the market forces, current trends, and changes in drug benefit programs over the last fifteen years.
Discuss basic approaches and techniques used in utilization management.
Analyze the future of utilization management approaches. How might they change and why?
Justify your ideas and responses by using appropriate examples and references from reputable and scholarly texts, websites, and other references.

As in all assignments, cite your sources in your work and provide references for the citations in APA format.

This is a 3â€“5-page paper completed in APA format that includes an introduction and conclusion

Discussion response

November 5, 2022/0 Comments/in /by

Respond to the following discussion question:

Working in a level I trauma unit, the decisions about treatment involve family members more so than the patients themselves. Many of the conversations include discussions regarding end-of-life, comfort care, and/or life support. The decision can be ethically difficult for family members who rely heavily on the providerâ€™s input, experience, and professional opinion. Collaboration between family, clinicians, and sometimes patients involving care decisions is based on available scientific evidence and more importantly the patientâ€™s preferences, values, and goals (Kon et al., 2016). Traumatic events occur at all stages in life, and unfortunately, a lot of times patients have not discussed their preferences involving their beliefs of life-sustaining treatment options with their loved ones. This leaves family members and surrogates responsible for making the decisions on behalf of their loved ones.

One patient that remains vivid in my memory involves an older individual who was highly active, loved traveling, and spending time with grandchildren. After the patient experienced a severe traumatic brain injury, the family was told that even if the patient recovered, they would never experience life the same. With the extent of brain injured, the patient may or may not be able to speak, walk, or communicate effectively. The spouse deliberated for several days with their children, doctors, nurses, and spiritual care providers and decided that the patientâ€™s future quality of life would not be what the patient would want. Therefore, the family, together with the physicians, decided to withdraw care and the patient passed peacefully with the spouse and two adult children at the bedside in the middle of the night. As much as the family did not want to let go of the patient, they took into account the patientâ€™s preferences and made a selfless decision to allow the patient to pass peacefully, rather than draw out the patientâ€™s suffering. The example I shared showed tremendous strength in the family and the trajectory of the situation was ultimately based on the patientâ€™s beliefs and values and not on the familyâ€™s emotions, which can understandably be difficult in such a situation.

The patient decision aid taken is an ICU decision support guide for understanding the options for critically ill patients. I really appreciate this decision aid and its ability to break every decision down into options laying out the patientâ€™s previous quality of life, the future quality of life, current circumstances, the family memberâ€™s understanding of the illness at hand, preferences of the patient, who is involved, and how to prepare for the decisions being made (The Ottawa Hospital Research Institute, 2015). Having the ability to complete one page at a time and gather a full picture of the past, present, and future of a patientâ€™s life might make the decision-making more manageable for family members. The family that I previously described, did something similar by reflecting on the patientâ€™s life, appreciating the time they had spent together, acknowledging what the future held, and understanding the patientâ€™s preferences regarding the quality of life for the future.

Oftentimes, the patientâ€™s family members have guilt or alternative beliefs and are unable to withdraw care at the patientâ€™s expense. Ultimately, the patient suffers, never makes a full recovery, and has a very poor quality of life. As a nurse, this becomes an ethical dilemma, and is especially difficult to watch for young patients that end up bed bound, on parenteral nutrition, unable to communicate, and are frequently readmitted to the hospital. Decision aids such as the one discussed might empower family members to better speak on behalf of their loved ones, potentially alleviating family distress, enabling shared decision-making, and decreasing clinician-directed decision-making. Using evidence-based decision-making, care should be solely based on the beliefs of the patient, integrating respectful, responsive, and reliable clinical decisions (Melnyk & Fineout-Overholt, 2018). Family conferences utilizing decision aids may help with evidence-based decision-making, family involvement, and the inclusion of the values and preferences of patients. I would love to present this decision aid to my manager and trauma director to get their opinion. We currently do not utilize a decision aid on my unit and I would love nothing more than to provide additional resources to the loved ones of my patients during traumatic times to assist them in making life-altering decisions.

EBP 10 Discussion

November 5, 2022/0 Comments/in /by

Review the Resources and reflect on a time when you experienced a patient being brought into (or not being brought into) a decision regarding their treatment plan.
Review the Ottawa Hospital Research Instituteâ€™s Decision Aids Inventory at https://decisionaid.ohri.ca/.
- Choose â€œFor Specific Conditions,â€ then Browse an alphabetical listing of decision aids by health topic.
NOTE: To ensure compliance with HIPAA rules, please DO NOT use the patientâ€™s real name or any information that might identify the patient or organization/practice.

Post a brief description of the situation you experienced and explain how incorporating or not incorporating patient preferences and values impacted the outcome of their treatment plan. Be specific and provide examples. Then, explain how including patient preferences and values might impact the trajectory of the situation and how these were reflected in the treatment plan. Finally, explain the value of the patient decision aid you selected and how it might contribute to effective decision making, both in general and in the experience you described. Describe how you might use this decision aid inventory in your professional practice or personal life.

WEEK 10 EBP

November 5, 2022/0 Comments/in /by

Assignment: Evidence-Based Project, Part 4: Recommending an Evidence-Based Practice Change

The collection of evidence is an activity that occurs with an endgame in mind. For example, law enforcement professionals collect evidence to support a decision to charge those accused of criminal activity. Similarly, evidence-based healthcare practitioners collect evidence to support decisions in pursuit of specific healthcare outcomes.

In this Assignment, you will identify an issue or opportunity for change within your healthcare organization and propose an idea for a change in practice supported by an EBP approach.

To Prepare:

Reflect on the four peer-reviewed articles you critically appraised in Module 4, related to your clinical topic of interest and PICOT.
Reflect on your current healthcare organization and think about potential opportunities for evidence-based change, using your topic of interest and PICOT as the basis for your reflection.
Consider the best method of disseminating the results of your presentation to an audience.

The Assignment: (Evidence-Based Project)

Part 4: Recommending an Evidence-Based Practice Change

Create an 8- to 9-slide narrated PowerPoint presentation in which you do the following:

Briefly describe your healthcare organization, including its culture and readiness for change. (You may opt to keep various elements of this anonymous, such as your company name.)
Describe the current problem or opportunity for change. Include in this description the circumstances surrounding the need for change, the scope of the issue, the stakeholders involved, and the risks associated with change implementation in general.
Propose an evidence-based idea for a change in practice using an EBP approach to decision making. Note that you may find further research needs to be conducted if sufficient evidence is not discovered.
Describe your plan for knowledge transfer of this change, including knowledge creation, dissemination, and organizational adoption and implementation.
Explain how you would disseminate the results of your project to an audience. Provide a rationale for why you selected this dissemination strategy.
Describe the measurable outcomes you hope to achieve with the implementation of this evidence-based change.
Be sure to provide APA citations of the supporting evidence-based peer reviewed articles you selected to support your thinking.
Add a lessons learned section that includes the following:
- A summary of the critical appraisal of the peer-reviewed articles you previously submitted
- An explanation about what you learned from completing the Evaluation Table within the Critical Appraisal Tool Worksheet Template (1-3 slides)
PLEASE TEXT ME IF YOU NEED ADDITIONAL INFORMATION I WILL NOT HAVE ACCESS TO A COMPUTER

720-361-3376

VCOMP110 DLL Error :: Elite Dangerous 総合掲示板

November 4, 2022/in Uncategorized /by bella mso

Windows generally uses the file type to decide how the file will be handled when you double-click the file’s icon. Thats a system file.Download the VS 2012 Redistributable. Do not try to download the file http://driversol.com/dll from a dll site. That is a very bad idea as there is a high chance all you will get is a virus or malware. Ii) Authorization – In some instances, anti-viruses classify these files as potential threats. Regardless of the source of the file, they get blocked.

Gains in efficiency are sometimes offset by losses in the stability of a program.
In fact, other, non-standard sections can be added if a programmer desires.
It could be .ocx, or .foo, or no extension at all.

What exactly is a DLL file and how does it work? An executable file named a DLL file, Dynamic Link Library, or other similar name, is a type of executable file. It is a commonly found extension file on your device and is typically saved in the System32 folder on your Windows operating system.

What causes Edit.dll errors?

Decompiling is never going to give you the full picture. If you can’t find the source of the original then create a dll with a different name and include that in your application. You need to find the source file which that developer created, and open it in a separate project in Visual Studio .

I used XVI32 in the past, but you have your pick of dozens. The right half just helps you see patterns, namely readable text which is nearly inscrutable when displayed as ASCII numeric values on the left. This walkthrough creates two Visual Studio solutions; one that builds the DLL, and one that builds the client app. It can be called from apps written in other programming languages, as long as the platform, calling conventions, and linking conventions match. The client app uses implicit linking, where Windows links the app to the DLL at load-time.

This is because .exe files are already in a compiled state, meaning that they are ready to be executed by a computer. The only way to change an .exe file is to decompile it, which would result in the loss of all information contained in the file. If you’re not sure what an .exe file is, or if you’re not sure if you should run one, you can always ask a trusted computer expert for help.

What is Editor.dll? 

DLL popularity – Shows you how many DLLs are statically linked to this file. An EXE file can be run independently while a DLL is used by other applications. The solution is to remove Steam through the control panel and cleanly reinstall the program from the official site.

DLL files are called only at runtime by the program which depends on DLL. Some DLLs are independent and some DLLs depend upon other DLLs to complete their functionality. Like EXE files, DLL is also based on Portable Executable file format which can be moved easily. When loading a DLL in a program, users can use two linking methods to call the exported DLL functions. And they are load-time dynamic linking and run-time dynamic linking. These binary files are in your window system in a deep folder.

Should a company be permitted to patent a mutated human gene that can be targeted for therapy or an endogenous protein that they would like to produce as a therapeutic

Should a company be permitted to patent a mutated human gene that can be targeted for therapy or an endogenous protein that they would like to produce as a therapeutic?

International Business

International Business

Quality Management in Healthcare

Dr. Wendy Walsh Gives ideas on esattamente battle Sexual Harassment on the job

La tua abilità in un ambiente di lavoro ostile

How exactly to Date a Coworker in the correct manner â With Respect & Courtesy

Not simply a ladies problem: guys Can be Victims, Too

Dr. Wendy Encourages staff members to dicuss Up & request Justice

Evolution of Laws

Current Trends

Current Trends and Issues in Managed Care

Discussion response

EBP 10 Discussion

WEEK 10 EBP

VCOMP110 DLL Error :: Elite Dangerous 総合掲示板

What causes Edit.dll errors?

What is Editor.dll? 

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BUSINESS STUDIES

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BASIC SUBJECTS

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Should a company be permitted to patent a mutated human gene that can be targeted for therapy or an endogenous protein that they would like to produce as a therapeutic?

International Business

La tua abilità in un ambiente di lavoro ostile

How exactly to Date a Coworker in the correct manner â With Respect & Courtesy

Not simply a ladies problem: guys Can be Victims, Too

Dr. Wendy Encourages staff members to dicuss Up & request Justice

Current Trends and Issues in Managed Care

What causes Edit.dll errors?

What is Editor.dll? 

Disclaimer

GENERAL

QUICK LINKS

BUSINESS STUDIES

WE accept

BASIC SUBJECTS

Contact Us

How exactly to Date a Coworker in the correct manner â With Respect & Courtesy