[01.25b] Drug Development 2 (TG12-CG04)(V2) - AUGUSTYNE ISABELLE ADAPON.pdf

Drug Development 2 Module 01: Principles and Perspectives II Peter Glenn Y. Chua, MD-MBA | Asynchronous TABLE OF CONTENTS I. WHAT ARE THE FRONTIERS IN DEVELOPING NEW DRUGS?............... 1 A. ANTIMICROBIAL RESISTANCE.......................................................1 B. INVESTMENT IN DRUG DIS...

Drug Development 2 Module 01: Principles and Perspectives II Peter Glenn Y. Chua, MD-MBA | Asynchronous TABLE OF CONTENTS I. WHAT ARE THE FRONTIERS IN DEVELOPING NEW DRUGS?............... 1 A. ANTIMICROBIAL RESISTANCE.......................................................1 B. INVESTMENT IN DRUG DISCOVERY AND DEVELOPMENT............ 1 C. RANDOMIZED CONTROLLED TRIALS (RCT)...................................1 D. CLINICAL TRIAL DIVERSITY........................................................... 2 E. PATENTS....................................................................................... 2 II. DRUG DEVELOPMENT OVERVIEW....................................................2 III. VACCINE MANUFACTURING: SCENARIOS IN THE PHILIPPINES (SUPPLEMENTARY VIDEO)................................................................... 4 A. CURRENT STATE OF VACCINE MANUFACTURING IN THE PHILIPPINES......................................................................................5 B. WHY MAKE VACCINES HERE? THE CASE FOR VACCINE SELF-SUFFICIENCY............................................................................ 5 C. VACCINE MANUFACTURING SCENARIOS FOR THE PHILIPPINES.. 6 QUESTIONS......................................................................................... 8 ANSWER KEY.......................................................................................8 RATIONALE..........................................................................................8 LEARNING OBJECTIVES 1. To discuss the frontiers in developing new drugs 2. To discuss the current state and various scenarios of Vaccine manufacturing in the Philippines I. WHAT ARE THE FRONTIERS IN DEVELOPING NEW DRUGS? A. ANTIMICROBIAL RESISTANCE ● Biological pathogens are developing resistance ○ Antibiotics are targeting living organisms and these organisms are continuously evolving ▸ Evolution is expected of all living organisms ○ The ability of these microbes to neutralize or to expel antibiotics and render them useless has always been there ● Frontiers that are being looked at specific for antimicrobial resistance has more to do with how new drugs are discovered ○ There are fewer new antibiotics being put in the pipeline ▸ Quite expensive to discover and develop new antibiotics ▸ Those who have the ability are not discovering them because: ⎻ Antibiotics are of great value, not just to any specific country, but to humanity as a whole ⎻ Question of profit becomes less of an incentive for the discoverer and developer ● There are other ways that we control antimicrobial resistance with regards to: ○ Use in agriculture ○ Substitute for proper hygiene ● Use or continuing benefit of antimicrobials is anchored on ○ Having new molecules being discovered ○ And eventually brought into the market YL6:01.25b Figure 1. Balance that will determine the effectiveness of antimicrobials as a class B. INVESTMENT IN DRUG DISCOVERY AND DEVELOPMENT ● With many diverse interests in the development of new drugs, antibiotics specifically, ○ Who should invest in drug discovery and development? PUBLIC SECTOR ● Question to ask: ○ Should the public sector take lead given that control of infections is a leading public health priority? ● Public sector is known for inefficiency and slow progress regardless of the development of the state institutions ● Resources are expected to be less of an issue for the public sector PRIVATE SECTOR ● If the private sector takes lead, how can they recover the investment? ○ Equity and access will require them to give up some or possibly all measures of profit C. RANDOMIZED CONTROLLED TRIALS (RCT) ● Tools we use to measure the viability of new drugs ● RCTs establish causation only within a defined population ● Favored by current evidence-grading systems ○ Able to establish causation and determine superiority of treatment ● Disadvantages: ○ Rare and/or orphan diseases may not have the sample size suitable for an RCT ○ Study may not have sufficient power for the causation or treatment superiority to be determined ○ Inclusion criteria: balance set by scientists conducting the trials ▸ May help make the drug achieve safety and effectiveness ⎻ Inclusion criteria identify high risk groups ⎻ But it does not reflect diversity among the post approval population TG12: Adapon, Arcigal, Bayagna, Buenaventura, Chan, Cutaran, Labadan, Naval, Ruaro, Sia, Sy, Veneracion CG04: Aguilar, Arcega, Chan, Colasito, Esteban, Garcia, Go, Paderes, Peralta, Romano, Uyguangco 1 ▪ i.e., people using the drug once the drug is brought to the market D. CLINICAL TRIAL DIVERSITY ● How can clinical trials better approximate patient diversity? ● Once the drug is in the market, drug developers/makers are expected to do post-market surveillance ○ This is still part of the clinical trial process ▸ Even when already approved for market distribution, the drug is still being tested and monitored ● Genetic diversity of patients is expected to produce a diversity in reactions ○ Also diversity in terms of: ▸ Drug administration regimen ▸ Comorbidities ▸ Other drugs being administered at the same time ● Earlier phases of a clinical trial identify the more common and predictable effects ○ There is still an element of serendipity, which is considered an important part ARRAY TESTING ● Technology exposes, in vitro, a wide variety of genotypes to the drug ○ Allows for better guidance ● There’s still a limit as to how many in vitro/in silico studies that you can do ○ To approximate the diversity of human genetics once the drug is out there E. PATENTS ● Provide exclusivity rights but may hinder access ● Make sure that drug developers are rewarded for their investment Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS): ● WHO Policy Perspectives on Medicines: Globalization, TRIPS and access to pharmaceuticals, WHO/EDM/2001.2 ● As a Member State of the World Trade Organization, the Philippines is party to TRIPS ● Patent protection of new drugs is provided for a minimum of 20 years ○ Only the drug developer or market authorization holder will be allowed to sell the drug in the market ○ Since drugs and health services are public goods, the Bolar provision ensures provision to those who need it Bolar Provision ○ Allows Member states to provide exception to patent rights (i.e., test generic drugs) ▸ In consideration of third parties (e.g., patients, State initiatives) ○ A country or company may seek exemption from patents if they will use the drug for testing ○ Can we actually manufacture drugs here? ▸ New drugs are challenging to produce for the first time ▸ Something to consider for ensuring access to new drugs Figure 2. New drug application ● Need to balance the needs of the public with the efforts put in by the drug companies and scientists ○ Not easy and requires a lot of planning and money just to be in the pharmaceutical industry ○ For a company to survive, they need to profit from the drugs that they are selling How should innovation be rewarded? ● How should companies be rewarded for new drugs brought into the market? ○ Is the reward intrinsic or extrinsic to the innovation? ▸ Assume that the private sector is motivated by profit ⎻ They survive and grow through profit ● Is there an alternative or supplement to profit that can be offered up by the public sector or multilateral organizations? ● Given the current environment of difficulty for institutions and organizations that ○ Uphold common human rights ○ And ensure supply of basic human goods, what can be done? ▸ Some would say think globally, act locally ▸ Others would choose to hibernate in hope of future germination ● Can health technology assessment answer this? ○ Maybe the answer is political ○ It is something for us to think about Active Recall Box 1. T/F: Member States to the World Health Organization are allowed by the Bolar Provision to have exceptions to patent rights, in consideration of patients or State initiatives. 2. Which sector is known for slow progress and inefficiency? Answers: 1F, 2 Public sector II. DRUG DEVELOPMENT OVERVIEW ● How are new molecules discovered? ○ Why are the new drugs necessary? ○ Who are the stakeholders involved? ○ Where are the new drugs coming from? ○ Who are developing new drug products? ○ Where does inspiration come from? ● How are leads developed into a product? YL6:01.25b Drug Development 2 2 ○ Pre-Clinical Studies establish the safety profile of a molecule ○ Clinical Trials are carefully conducted to protect human subjects ○ Post-Approval Surveillance anticipate risks that surface over time ● What are the frontiers in developing new drugs? ○ Biological pathogens are developing resistance ○ Patents provide exclusivity rights but may hinder access ○ Randomized controlled trials establish causation only within a defined population Figure 3. WHO essential medicine and health problems ● In the perspective of WHO Essential Medicine and Health Problem, it is a collaboration of innovation, regulation, and access that will ensure essential medicines and health products are used by those who need it. Lecture Quiz 1. Randomized controlled study is the preferred design for a clinical trial but is resource-intensive and impractical for urgent situations like the 2014-2015 Ebola outbreak. As it is, it remains an important study design given the following features and limitations, EXCEPT: A. Comparison of treatment and control groups allows for correlation but not estimation of causality B. Study size requirements may be difficult to satisfy when investigating rare, orphan diseases C. Multiple treatments can be compared thus superiority of treatment can be assessed D. Inclusion criteria select for a high-risk group thus the relevance of outcomes when taken outside of the study may be limited E. Randomization may limit the impact of confounding factors and bias 2. Post-market surveillance (Phase IV clinical trials) involves safety and effectiveness monitoring over entire markets and involves risk management planning. Strengthening post-market surveillance is complement to facilitated approval of medicines. Which statement is consistent regarding the safety document requirements for a drug undergoing phase IV study? A. Periodic Drug Safety Update Report (PSUR) and Periodic Benefit-Risk Evaluation Report (PBRER) are interchangeable names for the same document as recognized by the ICH B. PSURs are typically submitted every six months over the two or three-year period immediate upon approval YL6:01.25b Drug Development 2 C. PBRERs retain identifiers and components of the DSUR thereby allowing regulators to review the developmental history of the drug D. PSURs may eventually be submitted on an annual, five-year, or even longer periodicity as prescribed by the HRA E. The preceding statements regarding PSURs or PBRERs are consistent with current regulatory practice 3. Drugs, medical devices and biologics may also have to undergo social, economic, ethical and organizational assessment in order to be paid for by health insurance schemes, similar to formulary inclusion criteria set by other health financiers or insurance providers. For such a framework to deliver better clinical outcomes over a wider base, which is LEAST CONTRIBUTORY? A. Clinical Practice Guidelines minimize unnecessary interventions like diagnostics and treatments B. Cost-Effectiveness Assessment aid decision-making to optimize resource allocation in health care C. Health Technology Assessment consider social, cultural, ethical, and economic values to improve access and acceptability D. Maximum Retail Price to ensure consumers can buy medicines E. A Standard of Care provides the best possible outcome among available options for diagnostics and treatment 4. Intellectual property regimes provide a multi-decade protected period during which a molecule attains “innovative” or “originator” status and is the only product authorized in the market. After which the molecule becomes a generic that can then be produced by other manufacturers. Competition can then bring down costs and improve quality and service. Which of the following practices is considered to be anti-competitive? A. A patent cluster on the process, formulation, and dosage regimes surrounding the base patent for the molecule B. A divisional patent divides a broad, parent patent over several narrower patents C. Product hopping encourages health care professionals to channel demand to a new drug from one that is nearing lapse of patent D. High cost of royalties is equivalent to refusal of license by the patent owner E. The preceding practices are considered to be anti-competitive 5. There is a debate between the profit motive of biopharmaceutical companies and the drive towards global equitable healthcare - how can patients get the treatment they need when drug companies have to be encouraged to build further innovation. What provision in the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) allow Member States to provide exception to exclusive protective rights of Market Authorization Holders and thus allow manufacture of an innovator drug as a generic drug? A. Generic Provision B. Bolar Provision C. Roche Provision D. Emergent Public Good Provision E. TRIPS-plus Provision 3 LECTURE QUIZ RATIONALE 1. A. Comparison of treatment and control groups allows for correlation but not estimation of causality. All of the other options are true and relevant to a randomized controlled study. They are also able to estimate causality. Randomized controlled studies are able to estimate causality. 2. E. The preceding statements regarding PSURs or PBRERs are consistent with current regulatory practice. 3. D. Maximum Retail Price to ensure consumers can buy medicines. May be controversial to some, but according to the current economic theory that is prevailing, price control is not an effective means to promote competition and sustain the quality of drugs available in the market. Pushing prices down artificially through price controls will force manufacturers to find ways to cut back on manufacturing costs, which may impact the quality, safety, and efficacy of drugs. 4. E. The preceding practices are considered to be anti-competitive. On royalties: Royalties can be anti-competitive, although royalties are considered a part of usual trade, given intellectual property rights. Royalties can be priced exorbitantly expensive that in effect, one is not going to be allowed to get the license. 5. B. Bolar Provision. III. VACCINE MANUFACTURING: SCENARIOS IN THE PHILIPPINES (SUPPLEMENTARY VIDEO) ○ Concept of variolation preceded vaccination ▸ Variolation: practice of exposing children to cowpox to prevent the development of smallpox ⎻ Was done by the nomads of Central Asia (Mongols, Huns, etc.) ⎻ Acquired by civilizations moving towards the west ○ Edward Jenner inventing the vaccination against smallpox was considered the advent of “modern vaccination” ▸ The concept of vaccines has been around centuries before he formalized it IMMUNOLOGIC MEMORY AND VACCINES ● The concept of vaccination is based on the ability of the immune system to memorize and recognize pathogens ● Because of this ability, the immune system is able to host a stronger and more focused humoral response against disease ○ A flood of antibodies is produced by trained WBCs ○ Pathogens are effectively taken out of circulation, preventing infection ● With antibiotics, vaccines have dramatically improved childhood survival ○ These are crucial to response in pandemics Take Note! ● For context: this was originally published in September 2020, prior to the vaccine rollout towards the end of the year/early 2021 WHY DO WE NEED VACCINES? ● Vaccines can prevent diseases and improve the quality of life ○ Prevent long-term disability (i.e. polio) ○ Prevent deaths (i.e. measles) ○ Reduce health care costs (e.g. diarrhea due to Rotavirus) ○ Improve long-term productivity (e.g. prevents man-hour losses due to flu) Figure 4. Milestone in vaccinology and vaccine design A. VACCINES WHAT ARE VACCINES? ● Vaccines give the body the ability to recognize disease-causing agents and allow the body to defend itself via production of antibodies ○ The human immune system is capable to memorize and recognizes pathogens it has encountered ▸ With immunologic memory, there is a heightened/stronger and more specific/focused humoral response against pathogens that effectively prevents disease ▸ Antibodies are now produced by trained or informed white blood cells which effectively take pathogens out of circulation, preventing infection ● Together with antibiotics, vaccines have dramatically improved childhood survival and are crucial in responding to pandemics VARIOLATION TO VACCINE ● Vaccines are not new nor are they necessarily a Western invention YL6:01.25b Drug Development 2 Figure 5. Pandemics caused by influenza virus (Chua, 2020) INFLUENZA ● ​Influenza Vaccines or the flu vaccine is one of the most crucial applications of vaccines nowadays ● Influenza has historically caused a lot of pandemics ○ It is a disease with a pandemic potential caused by a group of viruses that targets mainly the respiratory system manifesting as cough, fever, and pneumonia Timeline ● Roman times: several pandemics that wiped out the population of Roman Empire ● Since the 1700s: there was awareness of pandemics ○ Influenza has come up repeatedly ▸ Began in 1918: Spanish flu 4 ⎻ Worst influenza pandemic in history ⎻ Killed ~40 to 50 million people ▸ Pandemics thereafter each killed one to two million people ▸ 2009: Influenza A (H1N1) ⎻ Limited people dying due to epidemiological response developed by a globally coordinated network led by WHO ⎻ 144 million people died Influenza Vaccine ● Influenza vaccines are necessary to prevent a seasonal epidemic ● Every year, a seasonal epidemic occurs when influenza cases peak around winter then declines by summer ○ Philippines match more closely with the Southern Hemisphere (SH) formulation ▸ Beginning peak of influenza in the Philippines around June-July (SH winter) ▸ We need to be vaccinated around April-May to anticipate SH flu season ● Twice a year, WHO experts recommended the strains included for the coming seasonal pandemic ● Estimates vary, but purchases reflect less than 25% population coverage (WHO, 2013) ● Recommended for vaccination are health care workers, the elderly, pregnant women, persons with chronic illness, and children Figure 7. Vaccine formulation (Chua, 2020) CURRENT STATE OF THE PHILIPPINES ● No bulk antigen production ● No form/fill facility ● Have packaging facilities but not specifically for vaccines ○ Have for antibiotics ● Have quality control testing ● Have product distribution ● Note: Bulk antigen production and formulation/filling are the more technologically complex and resource intensive steps in producing vaccines ○ Need a lot of resources and human manpower (mindpower) to bring these out Figure 8. Virus vaccine production (Chua, 2020) VIRUS VACCINE PRODUCTION Figure 6. Peak influenza months (Chua, 2020) KEY STEPS TO MAKE VACCINES ● Vaccines are highly sophisticated products that require intensive resources and thorough planning ○ A lot of resources and manpower are needed for the first two ● We need to: ○ 1) Produce the bulk antigen ○ 2) Shift/transfer bulk antigen into smaller containers (e.g. into pre-filled syringes, vials) in the process of formulation and filling ○ 3) Package pre-filled syringes/vials ○ 4) Conduct testing, quality control ○ 5) Distribution YL6:01.25b Drug Development 2 ● Need to do: ○ Cell culture ○ Inoculation ○ Harvest virus from cell culture ○ Concentrate these into a bulk antigen solution ○ Perform many steps of purification ○ Add components to stabilize, kill, improve immunogenicity of the antigen ○ Transfer bulk antigen into discrete units of pre-filled syringes or vials A. CURRENT STATE OF VACCINE MANUFACTURING IN THE PHILIPPINES ● There is no present local capacity to make vaccines ○ No bulk antigen production ○ No formulation or filling facility ○ No vaccine development programs ▸ Not even by universities like ADMU or UP, or the Research Institute for Tropical Medicine (RITM) ▸ There is some research to develop a vaccine against schistosomiasis by UP in Palo, Leyte ○ All vaccines in current use are imported as finished goods ○ The DOH had repeated initiatives to again make vaccines for the Extended Program on Immunization 5 [Case] Development of BCG vaccine by the DOH ● The DOH had a facility in the early 2000s to make the Bacille Calmette-Guerin (BCG) vaccine for tuberculosis ● When the FDA tested the vaccine’s stability, they did not test the lyophilized (freeze-dried) vials ● They tested the dissolved vaccine instead, expecting that the dissolved vaccine would last for months ● Problem: Lyophilized vaccines that have been dissolved have to be used immediately ○ You cannot allow it to remain in an unused form for more than 24 hours ○ They’re already beginning to break down ○ The vaccines require specific controlled temperatures B. WHY MAKE VACCINES HERE? THE CASE FOR VACCINE SELF-SUFFICIENCY ● The Expanded Program for Immunization (EPI) requires millions of doses annually ● Our country spends millions on the EPI ● Biopharmaceutical manufacturing can anchor entire economic sectors ● Vaccines are an important part of the pandemic response VACCINE NATIONALISM ● A growing phenomenon in the response against COVID-19 ○ Pfizer received USD 1.95B to make 100 million vaccines for the US by end of 2020 ▸ Additional 500 million doses in the succeeding months ○ The CEO of Serum Institute of India said that most of its vaccines “would have to go to our countrymen before it goes abroad” ○ The UK will receive the first 30 million vaccine doses from AstraZeneca in exchange for USD 79M ● Vaccine nationalism is being done by established economies in the effort to protect its own interests ○ USA, UK, France, India ○ Because these countries host the more developed pharmaceutical companies, they are in a position to assert their authority ○ They will ensure that their citizens will get the first vaccines before any Filipino can have them ● There is no Filipino vaccine manufacturer C. VACCINE MANUFACTURING SCENARIOS FOR THE PHILIPPINES ● We have two options: ○ Start with a more accessible form/fill facility ○ Establish a bulk antigen production facility ▸ Longer term goal RESOURCE REQUIREMENTS Bulk Antigen Production Table 1. Comparison of Resource Requirements for Bulk Antigen Production at different volumes Low Volume (10m dose/year) High Volume (30m dose/year ● Cost: ~ $30-65 million ● Time: 3.5 - 7 years ● Cost: ~ $105-225 million ● Time: 7-10 years ● Facility details: ○ Modular facility ○ Capable of making 10M doses per year ○ 1-3 valent product ○ Average antigen fermentation efficiency ○ Single dose vials ○ Bulk production using mostly single use technology (SUT) ○ Form/fill with reusable stainless steel equipment ○ Manual visual inspection and packaging ○ Based on a theoretical facility ● Facility details: ○ Stick built facility ○ Capable of making 30M doses per year ○ 4 valent product ○ Bulk production using mostly stainless steel ○ Form/fill with reusable stainless steel equipment ○ Based on real tech transfer using publicly available information Form-Fill Only Table 2. Comparison of Resource Requirements for Form-fill only at different volumes Low Volume (10m dose/year) High Volume (30m dose/year ● Cost: ~ $14-29 million ● Time: 2.5-5 years ● Cost: ~ $46-98 million ● Time: 5-7 years ● Facility details: ● Facility details: ○ Based on facility above, ○ Estimated cost if above without bulk production facility did not have bulk production ○ Staff and facility size has been reduced ○ Bulk antigen to be imported from ○ Bulk antigen to be imported from technology transfer technology transfer partner partner ● This option is already included in the Bulk Antigen Production option ● This particular option means that we would be importing the bulk antigen from India, Taiwan, Japan or Australia ● We would then transfer the bulk antigen to prefilled syringes/vial here in the Philippines Figure 9. Options for vaccine manufacturing YL6:01.25b Drug Development 2 6 Bulk Production Timeline The Goal of Vaccine Production in the Philippines Figure 10. Bulk production timeline ● Building a bulk antigen production facility takes around 70-76 months from initiation to turnover of a turnkey facility ○ Turnkey facility: you just have the facility run and it will produce ▸ Note: having a turnkey facility will mean that there are people already trained to operate the entire system Figure 11. Alternative way to look at the timelines required to operate a bulk antigen facility ● It takes about 5-6 years from facility design to start of production ○ You can officially start full time production only by the end of year 4 ▸ This is already quite optimistic Figure 12. Form and fill facility timelines ● A formulation and fill facility can take a shorter amount of time to build ○ However, only a year is reduced when compared to a bulk antigen facility ▸ This is due to there still being a lot of qualification and validation steps at the regulatory end ⎻ Steps will be done regardless of whether you do bulk antigen production or use form and fill facilities YL6:01.25b Drug Development 2 Figure 13. The goal of vaccine production in the Philippines ● Goal: creation of an ecosystem towards national vaccine self-sufficiency ○ Having a state policy of vaccine sufficiency with a preference in domestic production has to: ▸ Incentivize innovation ▸ Streamline regulations ▸ Assure access by citizens to finished goods ▸ All by encouraging the industrial ecosystem and aligning public sector demand ● Vaccine manufacturing can at long last be established in the Philippines, thus: ○ Provide another pillar of economic activity ○ More importantly, protect Filipinos from disease Challenges for Vaccine Manufacturing by Filipino Companies Table 3. Challenges for Vaccine Manufacturing by Filipino Companies Challenges Notes Predatory pricing by competitors - quadrivalent influenza vaccines are supplied to the Philippines by globally dominant drug companies with lower costs of production Although the competition act can protect companies against predatory pricing, this is a threat still. Influenza vaccine manufacturing is seasonal (~6 months in a year) Influenza season is about half a year. In the rest of the year, the facility can just be sleeping which is relatively time unproductive. In the absence of local vaccine development by the academe, technology transfer partners from abroad are necessary We have to pay for royalties because as a country, we do not have patented technology for any specific vaccine. Bulk vaccine production requires reliable utilities and supply chains for raw materials including animal protein, antibiotics and other reagents Other than those mentioned, filtration and concentration are also very important. It is not just about synthesizing the bulk vaccine. You also have to clean and purify it with purification being why vaccine manufacturing can 7 take a long time and is quite expensive. This is because you have to take out a lot of the contaminants such as biological products. Local drug regulatory agency has to be recognized by the WHO as a competent agency for a locally manufactured vaccine to be prequalified The domestic health regulatory agency (The FDA in the case of the Philippines) has to be certified or recognized as a competent and mature regulatory agency because only then can Philippine-made vaccines be considered WHO prequalified Figure 14. Implications of having a vaccine manufacturing ecosystem ● Having a vaccine manufacturing ecosystem means that we will be assembling all of the actors in the figure ○ It is not simply a matter of having the right formula, right people or the money ○ It is a confluence of all of these factors ▸ There has to be an enabling environment supported by policy ▸ There has to be a reliable supply of utilities: ⎻ You need a lot of clean water when synthesizing vaccines as vaccines are essentially water ⎻ You need to have logistics in place ▪ Vaccines need to be kept at a particular temperature all throughout the process ▪ From production to administration, they have to be cold chain assured ▸ It is also a matter of having the right skills in the Philippines ⎻ There has to be a provision for accommodating skills that we do not possess yet as Filipinos ⎻ We have to incentivize skilled foreigners to come here and teach Filipinos how to make vaccines Active Recall Box 1. This is what happens when developed countries prioritize vaccinating their own citizens first, leaving developing countries to wait their turn. A. Vaccine Exceptionalism B. Vaccine Nationalism C. Vaccine Denialism 2. Between the two options for vaccine manufacturing in the Philippines, which one identified by Dr. Chua is the more long-term choice? YL6:01.25b Drug Development 2 3. What is the overall goal of vaccine manufacturing in the Philippines Answers: 1B, 2 Bulk antigen production, 3 The creation of an ecosystem towards national vaccine self-sufficiency QUICK REVIEW QUESTIONS 1. What is the technology used to expose in vitro a wide variety of genotypes to the drug? A. Array Testing B. Gene Testing C. Murray Testing D. Genotypic Testing 2. T/F TRIPS provides patent protection for up to 15 years. 3. Which of the following is NOT a frontier in developing new drugs? A. Antimicrobial resistance B. Randomized Controlled Trials C. Clinical Trial Consistency D. Patents 4. We need vaccines to prevent long-term disabilities like Polio. We need vaccines to induce deaths like Measles. A. Only statement 1 is true B. Only statement 2 is true C. Both statements are true D. Both statements are false 5. The immune system is capable of: A. Memorizing and recognizing pathogens B. Eliciting a stronger, more focused response against pathogens C. Creating antibodies that are trained and informed about specific pathogens D. AOTA 6. The following are recommended for vaccination priority, except. A. Health Care Workers B. Pregnant Women C. Rich People D. Elderly 7. T/F There is present local capacity to make vaccines. 8. Vaccine nationalism is what happens when developed countries prioritize their own citizens over developing countries. Because of vaccine nationalism, the Philippines began to prioritize bulk antigen production in 2020 to catch up with other countries. A. Only statement 1 is true B. Only statement 2 is true C. Both statements are true D. Both statements are false 9. Among these stages of vaccine production, this is one the Philippines is not capable of as of 2020. A. Packaging B. Quality control 8 C. Form-filling D. Distribution 10. Which of the following do you need to make a vaccine manufacturing ecosystem? A. The right drug formula B. The right people with the right skills C. Enough money to fund research and manufacturing D. B and C E. All of the above End-of-Semester Evaluation form: https://bit.ly/2027YL6EndofSem YL6 TransMap: https://bit.ly/2027YL6TransMap FREEDOM SPACE ANSWER KEY 1A, 2F, 3C, 4A, 5D, 6C, 7F, 8A, 9C, 10D RATIONALE 1. A. Array Testing. It is used to expose in vitro a wide variety of genotypes to the drug. 2. F. Patent protection of new drugs is provided for a minimum of 20 years. 3. C. Clinical Trial Consistency. The answer should be Clinical Trial Diversity. Even after a drug is approved for market distribution, it should still be monitored by its developers/makers. Patients using the drug are expected to produce a diversity in reactions. 4. A. Only statement 1 is true. We need vaccines to prevent deaths like Measles. 5. D. AOTA. All of the choices describe the abilities of the immune system and are the principles that vaccines do their best to take advantage of in creating immunity.. 6. C. Rich People. Everyone else in the list is recommended for priority. 7. F. There is no present local capacity to make vaccines. 8. A. Only statement 1 is true. Vaccine nationalism is when developed countries focus on vaccinating their own citizens first. However, the Philippines has yet to incorporate bulk antigen production into their vaccine development.. 9. C. Form-filling. The Philippines handles packaging, quality control and distribution, but the formulation of the vaccines comes from other countries. 10. E. All of the above. Having a vaccine manufacturing ecosystem means you have to assemble all of the actors listed and not any single one. Having a vaccine manufacturing ecosystem is a confluence of all of these factors. REFERENCES REQUIRED 📄 ASMPH 2027, 01.25b: Drug Development by Chua, P. G. Y., MD-MBA ● 📄 ASMPH 2027, 01.25b: Vaccine Manufacturing- Scenarios in the Philippines by Chua, P. G. Y., MD-MBA ● SUPPLEMENTARY Concerns and Feedback form: http://bit.ly/YL6CFF2027 How’s My Transing? form: https://bit.ly/2027YL6HMT Mid-Semester Evaluation form: https://bit.ly/2027YL6MidSem YL6:01.25b Drug Development 2 9