The COVID-19 Situation and the Search for a Vaccine
The rapid and continued spread of COVID-191 has rendered imperative the development of a vaccine to combat the disease. Toward this end, various collaborative efforts, typically transcending national lines, have been launched.2 As of May 8, 2020, at least 95 vaccines related to COVID-19 are being explored.3 However, as with most vaccines, it would take some time before a COVID-19 vaccine is developed and approved because the regular process of vaccine development requires several years of research and clinical trials. For instance, it took 15 years to develop vaccines for the human papillomavirus and rotavirus,4 while nine years lapsed between the isolation of the measles virus in 1954 and the approval and licensing of a measles vaccine in 1963.5 The mumps vaccine, considered to be the fastest developed and approved vaccine, was approved and licensed in 1967, four years after the collection of viral samples.6
Lately, efforts have been undertaken to fast-track the development of a COVID-19 vaccine. A biopharmaceutical company has been reported to expect to begin clinical trials for a COVID-19 vaccine later this year and, if successful, the vaccine could be ready by late 2021.7 In the Philippines, President Rodrigo Duterte offered a reward of P50 Million to Filipino scientists who can develop a COVID-19 vaccine.8 The Philippine Department of Science and Technology recently took steps to correspond with four foreign partners for possible clinical trials of a coronavirus vaccine or drug.9
However, the accelerated pace of vaccine development gives rise to legitimate concerns regarding the safety and efficacy of a potential COVID-19 vaccine. The possibility looms that a promising vaccine could make it easier for a person to catch the virus or appear to worsen the symptoms of an infected person, as in the case of a few HIV drugs and vaccines for dengue fever, “because of the process called vaccine-induced enhancement, in which the body reacts unexpectedly and makes the disease more dangerous”.10 Experts warn that the potential COVID-19 vaccines being developed “might be more likely to fail because of the swift march through the research phase”.11
Legal Framework on Vaccine Testing in the Philippines
In order to address the relevant concerns, or at least minimize the adverse health effects arising from a hastily-developed vaccine, the Philippines has in place a legal framework for the testing and approval of vaccines.
Under Philippine law, all persons and entities must first secure a license to operate (“LTO”) from the Philippine Food and Drug Administration (“FDA”) before operating or engaging in the manufacture and testing of health products, including vaccines.12 Once an LTO is issued, the licensee sponsoring the clinical trial may initiate the process of clinical trial of the vaccine by applying for a Permit for Clinical Investigational Use (“PCIU”).13 Upon the FDA’s issuance of a PCIU, the licensee may proceed with the first three phases of clinical trial.14 However, before undertaking each phase of the trial, the licensee must likewise secure the FDA’s approval of its clinical trial protocol,15 through the FDA’s Policy Planning and Advocacy Division (“PPAD”).16 The FDA shall act on the clinical trial protocol based on the recommendation of the Ethical Review Board/Committee (“ERB/ERC”).17
Phase I Clinical Vaccine Trial is the initial testing of the test vaccine, which is administered to a small number of healthy adult volunteers and, occasionally, to actual patients suffering the target disease. The primary objectives of this phase include safety evaluation, tolerability, immune response, and dose findings. This phase also aims to establish the approximate levels of patient tolerance for single or multiple dosing of the test vaccine.18
Phase II Clinical Vaccine Trial is a randomized (chance allocation of treatments)19 , double-blinded (both investigator and participant are unaware of the nature of treatment)20 , and placebo-controlled (an inactive substance is given to a group for results comparison)21 clinical trial designed to evaluate the efficacy and safety of the test vaccine based on dose/response, tolerability, and acceptance of the test vaccine in a small number of subjects, usually affected individuals for whom the test vaccine is intended. This phase of clinical vaccine trial is made up of two parts, i.e., Phase II-a, consisting of a selected population that is artificially or deliberately infected with the pathogen, and Phase II-b, consisting of a selected population that is naturally infected.22
Phase III Clinical Vaccine Trial is a large-scale study of the effects of the test vaccine on the affected or target population. This phase necessarily requires a higher number of subjects, usually in the thousands.23 The primary objective is to evaluate the efficacy, safety, tolerability, and acceptance in a larger target population, at the same time, rare side effects or adverse events are monitored. During this phase, different clinical endpoints or measurable study outcomes to determine if the vaccine is beneficial24 are determined and established.25 Once Phase III is completed, the test vaccine may be considered as a “new vaccine” that may be the subject of a Certificate of Product Registration, provided that it has neither been registered nor licensed for general use by a national regulatory authority of any country.26
The performance of an Extended Phase III Clinical Vaccine Trial may be undertaken either after the completion of Phase III or as part of Phase IV Clinical Vaccine Trial. This extended phase involves a larger number of participants and are performed under normal conditions of use. “Assessment of the additional endpoints to determine immune response vs. protection, efficacy in different subgroups, effects on mortality, efficacy under controlled trials vs. effectiveness under routine use, required information to recommend vaccination on a routine basis, logistics for mass vaccination and evaluation for alternatives, effects on severity relapses, rare side effects or events, and establish[ment of] the duration of protection are regularly undertaken”.
Phase IV Clinical Vaccine Trial is a mandatory study of a newly registered vaccine for a period of five years from registration. The primary objective is to determine the public health impact of the vaccine, including the epidemiological impact on infectious and non-infectious diseases and the impact of the vaccine in terms of acceptance. This phase has the following objectives, among others: “to determine and establish the efficacy of different vaccination schedules (doses and intervals), long-term antibody kinetics vs. protection, evaluation under different conditions, prediction/modeling in transmission/protection[,] social acceptability if repeated vaccination is required, and surveillance strategies”.29
Liability for Violations During Testing
In case violations are committed during any phase of the test vaccine’s clinical trial, the FDA may impose the appropriate sanctions on the persons or entities responsible for such violations. The violations, which are the subject of an incident report prepared by the FDA’s Legal Division, may include incorrect performance of processes and procedures, such as in the injection of the vaccine, and other acts that lead to unforeseen, unexpected, rare, unusual, and life-threatening adverse reactions or events.30 Major violations are those which are significant, serious, and/or numerous in nature, and the scope, severity, or pattern of which support a finding that: (1) the subjects under the care of the investigator and the trial team would be or have been exposed to an unreasonable and significant risk of illness or injury; (2) the subjects’ rights would be or have been seriously compromised; (3) the integrity or reliability of the data is or has been compromised; (4) the investigator and/or other members of the trial team failed to disclose a conflict of interest; and (5) the test subject’s informed consent was not obtained.31
For major violations committed by a sponsor, i.e., “an individual, company, institution, organization, or entity which takes the responsibility for the initiation, management, and/or financing of a clinical trial”,32 the FDA may terminate the clinical trial and invalidate any data for drug registration purposes.33 Since the sponsor of a clinical vaccine trial is normally the pharmaceutical company that developed the vaccine, this means that the pharmaceutical company would not be able to secure from the FDA a Certificate of Registration for the vaccine.
In case of major violations by the researcher or investigator, i.e., the person responsible for the conduct of the clinical trial or under whose immediate direction the test vaccine is administered or dispensed to or used on a test subject,34 the FDA may impose the penalty of suspension from conducting researches and clinical trials for a period that could range in months or years depending on the type and degree of violation.35 Typically, the researcher or investigator is a pharmacist or a physician, in which case their respective licenses/certificates of registration may also be suspended or revoked by the Professional Regulation Commission.36
Notwithstanding the foregoing, and except in case of failure to obtain the test subject’s informed consent, a pharmacist and/or physician who served as principal investigator or otherwise took part in the clinical vaccine trial as a researcher may invoke as a defense the doctrine of assumption of risk. This doctrine states that “one who voluntarily exposes himself to an obvious, known and appreciated danger assumes the risk of injury that may result therefrom.”37 Thus, whether the pharmacist and/or physician exercised proper caution or not is immaterial in determining liability. Further, considering that prior to the conduct of clinical trials the test subjects are mostly required to execute consent/waiver forms, the pharmacist and/or physician may likewise cite such waivers as a defense in an action for negligence or malpractice, provided that the pharmacist and/or physician establishes these elements of a valid waiver: “(a) existence of a right; (b) the knowledge of the existence thereof; and, (c) an intention to relinquish such right”.38 Nonetheless, the favorable appreciation of these defenses rests in the discretion of the court depending on the evidence presented by the pharmacist and/or physician.
Patient’s Informed Consent
Participation in a clinical vaccine trial is on a purely voluntary basis. For this reason, Art. V (G) (1) (c) (5) of FDA Administrative Circular No. 2012-007 provides that the failure to obtain a test subject’s informed consent is a major violation in a clinical trial. Consequently, it is imperative to secure the test subjects’ informed consent before proceeding with the clinical trial of a potential COVID-19 vaccine.
The foregoing summarizes the needle’s eye through which a proposed vaccine must pass before acceptance into general use. Notably, a vaccine undergoing clinical trial still has a long way to go to prove itself in terms of efficacy and safety. Hence, before a vaccine is able to hurdle this intense scrutiny, informed consent is essential for the protection of an individual’s rights.
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This article is intended for informational purposes only and should not be considered as legal nor medical advice.
[1]As of 5:00 p.m. (Philippine Standard Time) on May 8, 2020, there were 3,916,338 confirmed cases of COVID-19 infection worldwide, with 1,343,054 total recoveries and 270,711 total deaths (data sourced from https://www.coronatracker.com/analytics/, last accessed on May 8, 2020).
[2]https://indianexpress.com/article/explained/covid-vaccine-search-progress-university-of-oxford-6397382/, last accessed on May 8, 2020.
[3]https://www.nytimes.com/interactive/2020/04/30/opinion/coronavirus-covid-vaccine.html, last accessed on May 8, 2020.
[4]Ibid.
[5]https://www.cdc.gov/measles/about/history.html, last accessed on May 8, 2020.[6]https://www.nationalgeographic.com/science/2020/04/why-coronavirus-vaccine-could-take-way-longer-than-a-year/, last accessed on May 8, 2020.
[7]Supra note 3.
[8]https://www.rappler.com/nation/258884-duterte-raises-reward-coronavirus-vaccine-discovery, last accessed on May 8, 2020.
[9]Ibid.
[10]Supra note 3.
[11]https://www.nytimes.com/interactive/2020/04/30/opinion/coronavirus-covid-vaccine.html, last accessed on May 8, 2020.
[12] Republic Act No. 3720, as amended, Secs. 10 (ff), 10 (ii), and 11 (j), in relation to Art. V (A) of Department of Health Administrative (“DOH”) Order No. 2014-0034 and Art. IV (B) of the Guidelines on the Unified Licensing Requirements and Procedures of the Food and Drug Administration.
[13] DOH Administrative Order No. 47-a, series of 2001, Sec. II (1) (1.2).
[14] Id., Sec. I (1) (1.3).
[15] Id., Sec. III (1) (1.1) and (1.2) and FDA Administrative Circular No. 2012-007, Art. IV (A) and (B).
[16] FDA Administrative Circular No. 2012-007, Art. V (A).
[17] Id., Art. IV (A).
[18] DOH Administrative Order No. 47-a, series of 2001, Sec. I (1.16).
[19] Source: https://www.medicinenet.com/script/main/art.asp?articlekey=39532, last accessed on 14 May 2020.
[20] Source: https://www.medicinenet.com/script/main/art.asp?articlekey=38696, last accessed on 14 May 2020.
[21] Source: https://www.medicinenet.com/script/main/art.asp?articlekey=38699, last accessed on 14 May 2020.
[22] DOH Administrative Order No. 47-a, series of 2001, Sec. I (1.17).
[23] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/, last accessed on 08 May 2020.
[24] Source: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/endpoint, last accessed on 14 May 2020.
[25] DOH Administrative Order No. 47-a, series of 2001, Sec. I (1) (1.18).
[26] Id., Secs. I (1) (1.6) and (1.19).
[27] Id., Secs. I (1) (1.18) and (1.19).
[28] Id., Sec. I (1) (1.18).
[29] Id., Sec. I (1) (1.19).
[30] Id., Sec. I (1) (1.22).
[31] FDA Administrative Circular No. 2012-007, Art. V (G) (1) (c).
[32] DOH Administrative Order No. 2014-0034, Art. VI (A) (A.5).
[33] FDA Administrative Circular No. 2012-007, Art. V (G) (2).
[34] FDA Circular No. 2015-003, Art. II (3)
[35] FDA Administrative Circular No. 2012-007, Art. V (G) (2).
[36] Republic Act No. 10918, Sec. 44 (a), (c), and (o), in the case of pharmacists and Republic Act No. 2383, as amended, Sec. 24, in the case of physicians.
[37] Abrogar vs. Cosmos Bottling Company, G.R. No. 164749, March 15, 2017.
[38] Heirs of Cipriano Reyes vs. Calumpang, G.R. No. 138463, October 30, 2006.
