FREQUENTLY ASKED QUESTIONS ON COVID-19 VACCINES

The current landscape of COVID-19 vaccine initiatives in the country is still dynamic - as discussions are still ongoing with potential partners. Here are some of the frequently asked questions (FAQs) on COVID-19 vaccine initiatives, as addressed by the country's Vaccines Experts Panel. Contents of these FAQs will be updated regularly.

ON VACCINE DEVELOPMENT

1. Why is it that only rich countries like the USA, Germany, Japan, Russia, China and other European countries can make vaccines while a poor country like us cannot make one? Is the Philippines also working on a vaccine? If we are not working on a vaccine, why not?

Vaccine development and production require huge investments and resources. Whereas the Philippines may now be considered a Low Middle Income country, the government has priority programs, and leadership in S&T ranks the lowest in the aspirational conditions that our country should attain in the Ambisyon 2040 survey. R&D for vaccines needs a lot of initial scientific talent, planning, infrastructure, capacity building for state of the art laboratory facilities, and training of sufficient human resources on various expertise required for the different stages from vaccine discovery and development of candidate molecules (basic research to identify best potential vaccine candidates) to pre-clinical development and studies in animals, to clinical trials (Phases I to IV), production/ manufacturing and commercialization.  The regulatory requirements are enormous and would require the highest level of political commitment, government support, and public private partnership.   

We don’t have the capacity to make COVID19 vaccine at the moment. But there are plans to have infrastructure and state-of-the-art facilities for us to be able to make vaccines.



2. How much is the cost to make a vaccine, that is why we cannot make one?

According to a report in 2006 in the USA, vaccines could cost around $800 million dollars to develop. The cost of developing a vaccine, including basic research and clinical trials involving tens or hundreds of thousands of people, can be as little as $150 million if researchers are lucky and stumble quickly on something that works, according to Lewis, up to well past a billion dollars for more advanced technologies used.

Back in 2015, a private vaccine company proposed to build a vaccine manufacturing facility for some PhP1.2 billion, and recently, the RITM proposed PhP1.8 billion to set up its immunobiological facility outside Metro Manila. 

The good news is, vaccines produced by the more affluent advanced countries that cost US$200 per dose in the US might cost $3-4 a dose in 50-60 lowest income countries in the world.  This may possible with equity in vaccine distribution forged by international vaccine foundations.

3. How long is the efficacy of all vaccines being developed by different countries?

    •   Efficacy refers to the capacity of the vaccine to protect against the disease, ex, COVID 19 vaccine.
    •   Efficacy usually correlates with the production of neutralizing antibodies against the virus, or the detection of
        cytotoxic T cell responses. The magnitude and quality of the immune responses, whether B cell or T cell
        responses, will determine efficacy.

    •   Efficacy rate refers to the percentage of people vaccinated who are protected from the disease under natural
        conditions of exposure to the wild type virus.
    •   Data on efficacy of COVID19 vaccines will not be available until about 6 months from when the phase III trials
        started in other countries



IMPORTANCE OF CLINICAL TRIALS

1. What are the necessary processes needed to be completed before a vaccine could be administered to the public?

       a. What is preclinical testing? 
           
Pre-clinical testing includes all aspects of testing the vaccine, product
           characterization, proof of concept/immunogenicity studies and safety testing in animals conducted prior to
           clinical testing of the product in humans

       b. What are clinical trials? Clinical trials involve testing the vaccine candidates in humans. There are 4 phases:

           Phase I studies assess the safety of a vaccine. It usually includes a small number of healthy volunteers (10 to
           100), it investigates the side effects of the investigational vaccine.

           Phase II studies test the safety and immunogenicity of the vaccine on a bigger number of volunteers, usually
           100-1000. This phase may determine the optimum dose or the number of doses that will elicit optimum
           immune responses tot eh vaccine.

           Phase III studies involve randomized and blind testing in several thousand individuals. This large-scale testing
           provides the vaccine company and the FDA with a more thorough understanding of the effectiveness/ efficacy
           of the vaccine, the benefits and the range of possible adverse reactions. Once Phase III is successfully                             completed, FDA may grant approval for marketing the vaccine.


           Phase IV
 studies, often called Post Marketing Surveillance Trials, are conducted after a vaccine has been
           approved for consumer sale. It will monitor a vaccine’s long-term effectiveness and impact on a patient's
           quality of life and  detect rare adverse events that could only be

 


2. How are clinical trials done? What are the participants expected to do during the trials?

A clinical trial is a research study in which volunteers receive investigational treatments, in this case, vaccines, under the supervision of experienced physicians and other health professionals. The clinical trial is conducted to determine the safety and benefits of investigational vaccines.
Clinical trials recruit healthy individuals using inclusion and exclusion criteria.

In a clinical trial, a volunteer is usually assigned a specific study group. Volunteers in one study group may receive the COVID19 vaccine while other volunteers may receive a placebo or a comparator vaccine.

A placebo or a comparator vaccine product is used to assess the experimental treatment's effectiveness. The participant, physician, and research staff may not know which volunteer receives a placebo and which receives the active treatment. Not knowing which participants are receiving the active treatment allows the physician and research staff to objectively observe the volunteers during the study. Regardless of which treatment volunteers receive, however, the level of medical attention and care that each receives is the same. 

The vaccine recipients are monitored for side effects at various time points during the trial, and tested for their immune responses to the vaccine components. They are given diary cards and are expected to report to the vaccine trial monitors any side effects or development of COVID19 signs and symptoms during the observation or clinical trial period. 

3. What are the risks associated with participation in clinical trials? How are these risks minimized?

Possible risks for volunteers will be explained at the time of recruitment or enrolment as follows:

•   There may be unpleasant adverse effects following immunization such as pain or tenderness, redness, or swelling
     at the injection site, or there could be systemic effects such as fever, headaches, nausea, vomiting, weakness or
     fatigue,
     diarrhea, seizures, allergic reaction, anaphylaxis
.
•   The experimental vaccine may not be effective and the person will not be protected against COVID19 disease, or
     there is a chance that the individual will 
receive the comparator vaccine.
•   In case of adverse events that will require medications, the volunteers will be provided the appropriate medical
    attention and intervention  

The protocol includes provisions for treating and/or compensating subjects who are harmed as a consequence of participation in the research study.

4. How can people volunteer themselves in clinical trials?

For COVID19 vaccine clinical trials, there will be groups who will be prioritized to participate, such as healthcare workers, front-liners, and contacts of COVID19 cases. Participants from the community will be informed about the clinical trial through mass communications with the help of community leaders and health personnel. Orientation meetings and other forms of social media communications may be used, with posters, brochures, etc.

5. What are the measures in case adverse events occur after receiving the trial vaccine?

During the administration of the vaccine, the participants is observed for any immediate side effects for at least 30 minutes. Diary cards will be provided for volunteers to document possible side effects/ adverse events they may experience for a specified time as prescribed in the study protocol.

6. How long will an individual be safe from Coronavirus-19 COVID19 infections once he is Vaccinated?

There is still limited data on the efficacy of COVID19 vaccines. Globally, there are now more than 6 candidate vaccines undergoing Phase III trials which are primarily aimed at establishing efficacy and safety. Data from the Phase 3 clinical trials and continuous surveillance will allow us to estimate the range of vaccine effectivity more accurately.   

7. Is there monetary compensation for participants when joining the CT?

There is a little compensation given to vaccine participants in the form of transportation allowance. This is usually around P500 to P1,000 per study visit.

The institutional ethics boards allow such compensation, provided it is not too much as to make monetary considerations the motivation for participating in the trial.

 8What’s the criteria for choosing the service provider?

Service Provider during Clinical Trials would refer to hospital trial sites or communities with adequate facilities and human resource to engage in the CT

Hospital sites are chosen based on the following:

  1. Initial participating sites expected to come from high COVID19 transmission areas such as the NCR, Metro Cebu, or Metro Davao. 
  2. Doctors and health care team experienced in conducting clinical trials: they are required to submit updated CV’s of principal and co-investigators and the rest of the team, Current Good Clinical Practice (GCP) certificates, Updated Professional Regulations Commission (PRC) licenses
  3. Willingness to sign FDA Confidentiality Data Agreement and Conflict of Interest declaration
  4. Affiliation with accredited hospitals and laboratories with accredited facilities for COVID19 diagnostics
  5. PHREB level-3 accredited Research Ethics Committees (REC)
  6. Able to integrate clinical research space into their existing clinical practices, providing space for vaccine storage, archive space and equipment as well as workspace for clinical research associates and clinical research coordinators.
9. What is the result of the human trials? What is the sample size?

Results of Phase I and II human trials from other countries are now available and have been published in scientific journals online. Most of the reported vaccine candidates showed good or acceptable safety profiles, as well as good results in terms of immunity generated, for both antibody responses and T cell mediated immune responses.

•   Phase I CT usually enroll 10-100 volunteers
•   Phase II CT enroll 100-1000 volunteers
•   Phase III CT are still ongoing and enroll tens of thousands of participants who will be monitored for efficacy, safety
    and immune responses.
For example, the global target for the WHO solidarity trials is 20,000 participants per
    COVID19 vaccine, and another 20,000 for the comparator vaccine. The Phase III trials must be conducted in high
    prevalence areas (hotspots) for more effective data monitoring

10. What are your acceptance criteria?

The vaccine technical evaluators use the WHO internationally accepted standards for vaccines for pandemic or outbreak response use or for long term use. The WHO Target Product Profiles are used as reference standards, as well as other WHO Technical standards and FDA requirements.

A matrix is prepared to give weights on compliance of the vaccine candidates with respect to the following vaccine characteristics: indication for use, contraindication, target population, safety/ reactogenicity, measures of efficacy, dose regimen, durability of protection, route of administration, product stability and storage, co-administration with other vaccines, presentation, WHO   Emergency Use Listing registration and pre-qualification, and accessibility. All pre-clinical and clinical data are rigorously evaluated


11. What is the assurance that the appraiser judgments are accurate and precise?

The vaccine technical evaluators are selected from a pool of experts in vaccine development, vaccine trials, vaccine safety, adaptive design, clinical trial statistics, epidemiology, clinical trial design, generation of randomized evidence, surveillance of vaccine preventable diseases, among others. The experts review technical data on vaccine parameters according to established standards and norms.  


STATUS OF PH partnerships for the implementation of CT

1. Do we have an FDA approved vaccine?

As of August 18, 2020 NO Covid19 vaccine has been approved by Phil FDA for use.  Only FDA approved / registered vaccines will be allowed to be commercialized in the Philippines. Regulatory requirements can be accessed on FDA websites.

2. How does the Philippines fare on the global setting in terms of the number of clinical trials being conducted?

•   No FDA approved CT is being conducted locally yet as of August 18, 2020
•   Talks and country agreements about the WHO Solidarity Trial for COVID19 vaccines are underway. Philippine
     Vaccine teams have been invited to discuss plans for operationalization of the clinical trials locally. It may be
     possible to start by October or November 2020. 
•    At least one vaccine company from China hopes to submit CT application to FDA by end of August 2020, which
     will make it possible, at the earliest, to commence the CT by October 2020.
•   Russia’s Gamaleya National Research Institute for Epidemiology and Microbiology has submitted a synopsis of
     of their Phase I/II trials in their country and this is now being reviewed. Philippine FDA requirements, specifically,
     DOH AO 2020-0010 and the required application forms and other guidelines have already been sent to the
     Russian government for their application for the parallel Phase III clinical trial in the Philippines.  
•   If Russia is able to submit the complete requirements by September 2020, the earliest they could start the trial will
     be October or November 2020. The trial will take at least 6 months to generate results, after which interim
     analyses  will be made. If all data show the vaccine to be safe, able to produce quality immune responses and 
     can protect against COVID19 disease, registration or licensure approval may be granted by FDA (under
     emergency use list as prescribed under WHO and US FDA guidelines for pandemic vaccines) by May or
     June 2021.


3. When will the Philippines have a vaccine for COVID-19?


FDA Approval: Assuming the WHO Solidarity Trial for COVID19 vaccines starts in October 2020, and it will take 3-6 months to complete it, plus 2-3 months to evaluate results and grant approval to license (under pandemic Emergency Use listing), we are looking at March to June 2021 for successful COVID19 Vaccine candidates to be approved for general use. Availability for special groups like elderly with pre-existing medical conditions and children will require separate clinical trials and approval may take longer.

Supply Availability: There is no local manufacturing capability for covid19 vaccines so all supplies must be imported. The Philippines is a member of the COVAX initiative that strives to ensure global equity in vaccine supply. However, it is not clear when and how much the Philippines stands to get from the initial stock build-up. 

4. If these vaccines are already administered to the population of other countries, is it automatic that Filipinos could receive these vaccines as well?

    •   Data from other countries need to be reviewed for scientific soundness and applicability to our population.
        As a rule of thumb, all new investigational products such as the COVID 19 vaccines produced by old or
        tested vaccine technologies and novel platforms, should undergo LOCAL Phase III Clinical Trials and proven
        safe and effective before the vaccines will be allowed for commercialization. 


        The extra scrutiny is especially needed for the COVID19 vaccines due to the limited information we have
        on COVID 19 infectiousness before and after the appearance and alleviation of symptoms 

5. Bakit ang ibang pharma sa US, Canada, etc hindi naman kukuha ng volunteers for clinical trials dito sa atin? Ang Russia at China lang?

May plano rin ang iba pang vaccine companies from USA , Canada, Australia, Hongkong, India na mag sasagawa ng clinical trial Phase III sa Pilipinas. Nakikipag-usap na ang ilan sa kanila for collaboration

6. Ready na ba yang vaccine ng Russia and China for human beings? Hindi pa naman ready ang vaccine ng Russia to be used for humans. I really do not know kung totoo yan.

HINDI pa maaring gamitin for mass immunization ang mga bakuna na Galing sa Russia at China . Kinakailangan nilang sumailalim sa clinical Trilal Phase III sa atin, kung saan susuruin ang safety, immunogenicity at efficacy nila.

7. Hindi kaya maulit ang isang controversy gaya ng sa Dengvaxia sa clinical trials nitong mga bakuna sa COVID-19?

Maraming regulatory requirements ang kailangan masunod ng mga vaccine companies mula sa FDA, sa WHO at sa mga Ethics Boards ng mga hospitals or institutions sa bansa kung saan gagawin ang clinical trials. Masusing pag aaralan ang lahat na posibleng maging epekto ng bakuna sa tao.  May sinusunod na pamantayan at parameters para makita at maanalyse ang mga ito. 


OTHER TECHNICAL QUESTIONS RELATED TO VACCINE:

1. Are there side effects once the vaccine is administered to the patient/person?

Generally, there may be local or systemic side effects experienced after vaccination.  Local side effects include pain, redness, itchiness or swelling at the injection site, which may last a few hours.  Systemic side effects may be in the form of fever, feeling of weakness or fatigue, headache, dizziness, diarrhea, nausea, and these side effects are determined if causally -related to the vaccine. The benefits of taking the vaccine outweighs the risks associated with the side effects.  

2. How many times will these vaccines be administered to individual human beings?

   •   Vaccines may be given as one dose or multiple doses for the primary series. In the case of COVID19
        vaccines, available data show that two doses administered 2, 3 or 4 weeks apart, elicit optimum immune
        responses in terms of neutralizing antibody responses. However, the duration of the immune response/
        immunity generated against COVID19 vaccines still needs to be determined, by monitoring vaccine
        recipients over several months or even years.


   •    Current study protocols for COVID19 vaccines would require following up vaccine recipients who
        seroconverted for persistence of their antibody response. It may also be possible to determine persistence
        of cellular immune responses, testing for T cell memory responses after several months.

3. How come there are vaccines that have a long-term effect on human body immunology while others have short effect?

   •   Different vaccine types elicit different immune responses. Some types produce high magnitude antibody
        responses that persist in the body for a long time. Vaccines that elicit memory T cell responses are the
        ones that will provide long term protection.

   •   Current vaccine development efforts consider designing vaccine candidates such that they are able to
        elicit both B cell and T cell responses.  Vaccine candidates may be structurally designed to possess certain
        conformations or configurations that make them better recognized by appropriate B cells and T cells.

4. Is it really not advisable to have vaccine especially among ages 50 and up?

On the contrary, for COVID19, the elderly group is at higher risk for more serious COVID 19 infection. For this reason, the elderly will be prioritized, as well as the younger ones who have comorbidities or existing medical conditions that put them at higher risk for the complications of COVID19.


5. Is there a process first before the vaccine is given? Like a swab?

All potential recipients of the vaccines under the clinical trial will first be screened for certain inclusion and exclusion criteria. These criteria include physical examination, general state of health, ability to follow instructions. Laboratory tests are performed such as baseline RT-PCR for SARS-CoV-2 viral RNA, IgM and IgG tests, clinical chemistry examinations to detect abnormalities or disease conditions that may not be detected on physical examination alone. 


6. Russia said they have finished their vaccine and will be conducting their widespread human trials soon. Indonesia is also saying their vaccine is almost finished. Do you think the vaccine is pre-determined by race?

The vaccines developed and produced by different countries use different vaccine technology formats which are not pre-determined by race, but are products of careful studies and considerations. If  the question refers to the use of local- country-specific microbial isolates as being pre-determined by race, that is not the case.

7. Will the Indonesian vaccine be more applicable to us Asians rather than the Russian or any Western vaccine?

   •   The Indonesian vaccine as far as we know, uses the whole virus specifically from the COVID19 virus
        strain spread in Indonesia. The vaccine is being developed by the Indonesian state-owned enterprise
        Bio Farma in partnership with Sinovac Biotech of China. Vaccine development is expected to be completed
        by mid2021 according to Indonesian President Joko Widodo.

   •   The Russian vaccine is based on adenovirus-vectors (AD5 and Ad26) carrying the genes for spike proteins
        of SARS-CoV-2.

   •   Most of the COVID19 vaccine candidates in advanced stages of development either use the whole inactivated
        virus or parts of the virus , in particular, the spike proteins (forming the crown or corona of the SARS-CoV2)
        that have been determined to elicit protective immune responses. The spike proteins are expected to be the
        same if the manufacturers used the same sequence of the genes that encode for such proteins from one
        source only, i.e, the Wuhan strain whose genetic sequence was published online in January 2020.

8. Will the vaccine eradicate the virus, like smallpox, or will it just make it more tolerable for us when we contract the virus, like flu?

   •   Eradication is defined by US CDC as a permanent reduction to zero of the worldwide incidence or
        prevalence of infection caused by a specific agent as a result of deliberate efforts; intervention measures
        are no longer needed. Example: smallpox.

   •   The current COVID19 pandemic and what little we know about its natural course of infection does not allow
        any consideration for eradication or even elimination.

   •   At best, COVID19 could be controlled, which means it is possible to reduce disease incidence, prevalence,
        morbidity or mortality to a locally acceptable level as a result of deliberate efforts; However, continued
        intervention measures are required to maintain the reduction.

   •   There are many requirements for an infectious agent to be “eradicated” or considered for eradication, among
        which are the following:

               1.  An effective intervention is available to interrupt transmission of the agent. Until a vaccine for
                    COVID19 that is highly efficacious and provides long lasting immunity is developed, eradication
                    is far-fetched.

               2.  Practical diagnostic tools with sufficient sensitivity and specificity are available to detect levels
                    of infection that can lead to transmission; and

               3.   People are the only reservoir.  Hundreds of diseases can be transmitted between insects,
                    animals and humans. In the case of coronaviruses such as SARS-Cov-1, MERS, or SARS-Cov-2,
                    transmission occurs between and among animals such as bats, camel, and humans, making
                    it difficult to control.


9. Free ba vaccine or if not, how much and sino una mabibigyan ng vaccine?

Under clinical trials, vaccines are free. Once approved / registered or licensed by FDA, the government will procure the approved vaccines for priority groups like health care workers, front liners and senior citizens who pass the social criteria…those who could not afford the vaccines. But for all others who can afford, they need to pay. We do not know yet how much, maybe P500-P5,000per dose?

10. May programa ba ang gobyerno para mabakunahan ang mga homeless persons?

Pag-aaralan mabuti ng gobyerno natin kung sinong mga grupo ang dapat ma prioritize na bibigyan ng libreng bakuna…ang pinaka vulnerable na population groups ang uunahin.

11. Takot po akong magpabakuna dahil sa mga nababasa ko sa social media. Paano po madidispel ang mga rumors about sa bakuna in general?

Ang ganitong mga forum or pag-explain sa publiko ay importante para mainitindihan ng mga tao ang benefits ng bakuna at posibleng mga side effects nito. Kailangan ipaliwanag na ang bakuna ay maka protect sa sakit kagaya ng measles, polio, flu, or sa COVID19. Ang bakuna ay version ng mikrobyo na pinahina or mga parts lang ng mikrobyo na mag eelicit ng panlaban sa tutoong virus or bacteria or mikrobyo.

Example, dahil sa bakuna contra polio,  marami nang tao ang nagka proteksiyon sa buong mundo, at maari na itong ma eradicate sa mga susunod na taon. Maraming bata at matanda ay naka iwas sa paralysis na dulot ng polio virus.

Di hamak na mas malaki ang benepisyo kaysa sa panganib ang pagpapabakuna. Marami sa mga agam-agam ng mga tao ay galing sa mga lumang ingredients na hindi na ginagamit at mga kasulatan na mahina sa siyensiya. Isang kasulatan nung 1998 ay bumanggit sa posibleng relasyon ng autism at MMR vaccine. Mahina ang siyensiya na binasihan ng kasulatang ito at tinanggal ang publication na ito sa mga scientific journals.