Preclinical and Clinical Development Consideration in Herbals & Biologics in USA

PRE-CLINICAL & CLINICAL
DEVELOPMENT
CONSIDERATION
PRESENTED BY:
Anjali Chandrashekhar Yadav
2nd M.Pharm Regulatory Affairs
1
Anjali Yadav

CONTENT
HERBALS BIOLOGICS
• Abbreviation
• Introduction
• Regulation of Herbals in
USA
• Regulation of Biologics in
USA
• Pre - Clinical Development
Consideration For Herbals
• Pre - Clinical Development
Consideration For Biologics
• Clinical Development
Consideration For Herbals
• Clinical Development
Consideration For Biologics
• References
2
Anjali Yadav

ABBREVIATION
3
• GLP - Good Laboratory Practices
• FDA - Food and Drug Administration
• ADME - Absorption, Distribution, Metabolism, and
Excretion
• CBER - Center for Biologics Evaluation and Research
• LOAEL - Lowest Observed Adverse Effect Levels
• NOAEL - No Observed Adverse Effect Levels
• RIA - Radioimmunoassays
• ELISA - Enzyme-linked immunosorbent assays
• NMR - Nuclear Magnetic Resonance
• HPLC - High-performance liquid chromatography
Anjali Yadav

ABBREVIATION
4
• MS - Mass spectrometry
• CE - Capillary electrophoresis
• ECs - Ethics Committees
• IRBs - Independent Regulatory Bodies
• DMCs - Data Monitoring Committees
• RMPs - Risk Management Plans
• PSURs - Periodic Safety Update Reports
• RWD - Real-world Data
• EHRs - Electronic Health Records
• PBRERs - Periodic Benefit-Risk Evaluation Reports
Anjali Yadav

INTRODUCTION
In the United States of America, herbals and biologics are two
different classes of medicinal products that go through rigorous
development and regulation.
Herbals are mainly found from plants that have been used traditionally
in medicine; on the other hand, biologics are complex compounds that
come from living things.
Before gaining regulatory approval, both must undergo comprehensive
preclinical and clinical testing to guarantee their quality, safety, and
efficacy.
An essential part of managing this process to protect public health.
5
Anjali Yadav

REGULATION
OF HERBALS
IN USA
• In the USA, herbal medicine would come under
botanicals.
• The FDA considers herbal supplements to be
foods, not medicines, so they are not subject to
the same testing, manufacturing, and labelling
standards and regulations as medicines.
• The United States Food and Drug Administration
(FDA) regulates herbal products under the
Dietary Supplement Health and Education
Act of 1994.
• Herbal products are generally regulated as
dietary supplements, meaning that standards are
lighter.
6
Anjali Yadav

PRE - CLINICAL DEVELOPMENT OF
HERBALS
• For herbal products, preclinical development is an important stage that comes before
clinical trials with the goal of assessing the product's quality, safety, and efficacy.
• This stage includes several comprehensive investigations and tests to collect extensive
data.
• Establishing preliminary efficacy, determining to safe dosages, and detecting possible
hazards are the main goals.
• To ensure that preclinical research is conducted in accordance with quality and safety
standards, regulatory organizations like the U.S. FDA set guidelines and regulations.
• Preclinical development can take many months to years, depending on complexity
of the product so timeframe varies accordingly.
7
Anjali Yadav

COMPARISON OF PRE-CLINICAL
CONSIDERATION OF HERBALS & BIOLOGICS
Pre- Clinical Development
Consideration for Herbals
Consideration for Biologics
• Regulatory Guidelines and
Compliance
Compliance
• Safety Pharmacology Studies • Pharmacology Studies
• Toxicology Studies • Toxicology Studies
• Dose Selection • Dose Selection
• Quality Control • Immunogenicity Assessments
• Efficacy Studies • Structural Characterization
• Impurity Profiles
8
Anjali Yadav

COMPARISON OF CLINICAL CONSIDERATION
OF HERBALS & BIOLOGICS
Clinical Development Consideration
for Herbals
for Biologics
• Phase I, II, and III Trials
Considerations
• Informed Consent and Ethical • Informed Consent and Ethical
• Safety Monitoring • Safety Monitoring
• Efficacy Assessment • Efficacy Assessment
• Pharmacovigilance • Pharmacovigilance
• Post-marketing Surveillance • Post-marketing Surveillance
• Regulatory Reporting Requirements • Patient Population Considerations
• Immunogenicity Monitoring 9
Anjali Yadav

CHECKLIST FOR HERBALS
Consideration
Compliance
• Considerations
• Safety Pharmacology Studies • Informed Consent and Ethical
• Toxicology Studies • Safety Monitoring
• Dose Selection • Efficacy Assessment
• Quality Control • Pharmacovigilance
• Efficacy Studies • Post-marketing Surveillance
• Regulatory Reporting Requirements
10
Anjali Yadav

PRECLINICAL DEVELOPMENT
CONSIDERATIONS FOR HERBALS
Regulatory Guidelines and Compliance
Safety Pharmacology Studies
Toxicology Studies
Dose Selection
Quality Control
Efficacy Studies
11
Anjali Yadav

1. Regulatory Guideline and Compliance: Developing herbal products
successfully depends on adherence to regulatory rules. The requirements
for preclinical testing, such as research design, data integrity, and
adherence to Good Laboratory Practices (GLP), are outlined in
recommendations that have been established by U.S FDA.
2. Safety Pharmacology Studies: Determine how a herbal product might
affect the body's critical physiological systems, including the
respiratory, central neurological, and cardiovascular systems. These
investigations help in determining appropriate initial dosages for
clinical trials as well as any safety issues.
12
Anjali Yadav

3. Toxicology Studies: These studies assess the herbal product's
possible impact on different organ systems and physiological
processes. Studies on acute, subacute, and chronic toxicity are
carried out to determine the dosage ranges at which side effects
occur.
4. Dose Selection: Choosing the right doses for human studies is
essential to ensuring safety and efficacy. In animal models,
pharmacokinetic investigations evaluate the herbal product's
absorption, distribution, metabolism, and excretion (ADME). Studies
examining the correlation between dosage and therapeutic results
are known as dose-response studies.
13
Anjali Yadav

5. Quality Control: The consistency, safety, and purity of the herbal
product are ensured by quality control measures. Analytical
techniques such as HPLC or GC-MS are used to identify and
quantify the active components in order to regulate the active
ingredients. Potential harmful substances including pesticides and
heavy metals are found through contamination analysis.
6. Efficacy Studies: To evaluate the pharmacological actions of a
herbal product, efficacy studies test it on particular cell lines or
animal models. While in vivo studies involve animal models to
evaluate efficacy in a more complex biological system, in vitro
studies evaluate the product's activity upon isolated cells or tissues.
14
Anjali Yadav

CLINICAL DEVELOPMENT
Phase I, II, and III Trials
Informed Consent and Ethical Considerations
Safety Monitoring
Efficacy Assessment
Pharmacovigilance
Post-marketing Surveillance
Regulatory Reporting Requirements
15
Anjali Yadav

Phases I, II,
and III Trials
Phase I: The main concerns at this first stage are safety and
pharmacokinetics. To find the highest dose that can be
tolerated and evaluate any adverse effects, a small group of
healthy volunteers is used for the herbal product's testing.
Phase II: During this stage, a larger number of people with the
disease the herbal medicine is meant to cure are used to test the
product. Preliminary efficacy evaluation, dose-response
relationship investigation, and common side effect
identification are the main priorities.
Phase III: In this stage, the safety and effectiveness of the
product are verified in larger populations. In order to present
strong evidence of its benefits and risks, randomized and
controlled trials are used.
16
Anjali Yadav

• Ethical Considerations and Informed Consent: Obtaining informed
consent ensures that study participants are fully aware of the benefits
and risks. Safeguarding the rights, privacy, and welfare of participants
is a crucial ethical consideration. Ethical review boards supervise trial
procedures to ensure compliance to ethical guidelines.
• Safety Monitoring: Continuous monitoring of adverse events,
laboratory abnormalities, and serious adverse events is
crucial. Throughout the trial, safety data is collected and reviewed in
order to identify any possible risks.
17
Anjali Yadav

• Efficacy Assessment: The efficacy of the herbal medicine is determined using
established outcome measures, such as symptoms, biomarkers, or quality of life
evaluations. The efficacy of the product is evaluated by analysing efficacy data
using statistical methods.
• Pharmacovigilance: Monitoring adverse event reporting systems, patient
databases, and observational studies is part of post-marketing surveillance for
long-term safety and efficacy. Pharmacovigilance ensures that safety is
continuously monitored after approval.
• Regulatory Reporting Requirements: Adherence to regulatory reporting
requirements for adverse events, serious adverse events, and annual safety
reports is essential. Compliance with regulatory reporting ensures transparency
and accountability.
18
Anjali Yadav

Post-Marketing Surveillance: Product quality and patient
safety are ensured by continuous monitoring for long-term
safety and efficacy after approval. Long-term efficacy,
unexpected interactions, and uncommon adverse reactions are
all monitored in such a manner.
19
Anjali Yadav

REGULATION OF BIOLOGICS IN USA
• Biologics are isolated from a variety of natural sources - human, animal, or
microorganism - and may be produced by biotechnology methods and other
cutting-edge technologies.
• Wide range of products are included such as vaccines, blood and blood
components, allergenics, somatic cells, gene therapy, tissues, and recombinant
therapeutic proteins.
• The Center for Biologics Evaluation and Research (CBER) is the FDA
department that regulates biological products for human use.
• The first biologic approved for human use by the FDA was Humulin in 1982.
20
Anjali Yadav

CHECKLIST FOR BIOLOGICS
Consideration
Compliance
• Pharmacology Studies • Informed Consent and Ethical
• Toxicology Studies • Safety Monitoring
• Dose Selection • Efficacy Assessment
• Immunogenicity Assessments • Pharmacovigilance
• Structural Characterization • Post-marketing Surveillance
• Impurity Profiles • Patient Population Considerations
21
Anjali Yadav

PRE - CLINICAL DEVELOPMENT
CONSIDERATIONS FOR BIOLOGICS
Regulatory Guidelines and Compliance
Pharmacology Studies
Toxicology Studies
Dose Selection
Immunogenicity Assessments
Structural Characterization
Impurity Profiles
22
Anjali Yadav

1. Regulatory Guidelines and Compliance:
• Preclinical testing, Biologics, Regulatory body, FDA guidelines
• Efficacy, Safety, Quality, Compliance to these guidelines
• Regulatory standards, Clinical trials, Appropriate data collection techniques
• Study design, Documentation, Ensure that the biologic meets regulatory
standards.
23
Anjali Yadav

1. Regulatory Guidelines and Compliance:
• Specific guidelines for preclinical testing of biologics are provided
by regulatory body (FDA).
• The guidelines ensure efficacy, safety, and quality considering the
unique characteristics of biologics.
• Compliance to these guidelines is important in order to ensure that
the biologic meets regulatory standards and can proceed to clinical
trials.
• For regulatory compliance, appropriate data collection techniques,
study design, and documentation are essential.
24
Anjali Yadav

2. Pharmacology Studies:
• Pharmacology studies, Potential adverse effects, Vital physiological functions.
• Specialized assays, Biomarkers, Specific safety concerns.
• Major organ systems, Primary goal, Pharmacokinetic properties Absorption,
Distribution, Metabolism, Excretion (ADME)
• Pharmacodynamics, Dosage methods, Relationship, Clinical trials.
25
Anjali Yadav

2. Pharmacology Studies:
• Studies on pharmacology evaluate the biologic's potential adverse effects on vital
physiological functions.
• Specialized assays and biomarkers may be used to assess specific safety concerns
related to the biologic.
• Identifying any potential adverse effects on major organ systems and physiological
functions is the primary goal.
• Pharmacology studies help identify potential risks and guide dose selection for clinical
trials.
• The pharmacokinetic properties of the biologic, such as absorption, distribution,
metabolism, and excretion (ADME), may also be evaluated by pharmacology studies.
• Relationships between pharmacokinetics and pharmacodynamics are being studied to
improve dosage methods.
26
Anjali Yadav

3. Toxicology Studies
• Toxicology studies, Physiological processes, Organ systems, Safety profile, Research
• Structural changes, Functional changes
• Histopathological examinations, Clinical pathology evaluations, Functional
assessments
• Comprehensive safety evaluations, Genotoxicity, Carcinogenicity, Toxicity to
reproduction and development
• Safe starting doses, Dose escalation methods, Clinical trials
• Lowest Observed Adverse Effect Levels (LOAEL), No Observed Adverse Effect
Levels (NOAEL), Safety margin calculation.
27
Anjali Yadav

3. Toxicology Studies
• Extensive toxicological studies assess possible impact on different physiological
processes and organ systems. comprehension the safety profile of the biologic requires
a comprehension of these research.
• The delivery of the biologic may cause structural or functional changes that are
identified by histopathological examinations, clinical pathology evaluations, and
functional assessments.
• To ensure comprehensive safety evaluations, these investigations additionally evaluate
genotoxicity, carcinogenicity, and toxicity to reproduction and development.
• To determine safe starting doses and dose escalation methods for clinical trials,
toxicology study results are considered. Lowest Observed Adverse Effect Levels
(LOAEL) or No Observed Adverse Effect Levels (NOAEL) are the bases on which the
safety margin is calculated. 28
Anjali Yadav

4. Dose Selection:
• Dose-response studies, Dosage and therapeutic outcomes relationship, Clinical trials
• Ideal dosage range, Therapeutic efficacy, Potential adverse effects
• Dose selection process, Pharmacokinetic characteristics, Pharmacodynamic
characteristics
• Population pharmacokinetics analyses, Dosage modifications, Specific patient
populations
• Active comparator, Placebo-controlled comparator, Multiple dose levels.
29
Anjali Yadav

4. Dose Selection:
• Studies evaluating the relationship between dosage and therapeutic outcomes are
known as dose-response studies. The ideal dosage range for further evaluation in
clinical trials is established primarily by these studies.
• Optimal dose selection is crucial to ensure therapeutic efficacy while minimizing
potential adverse effects. An effective dose selection process requires an
understanding of the biologic's pharmacokinetic and pharmacodynamic
characteristics.
• Analyses of population pharmacokinetics can be used to assess how differently
patients are exposed to drugs. This helps in understanding dosage modifications for
specific patient populations.
• These studies may contain active or placebo-controlled comparator, and they often
include multiple dose levels. 30
Anjali Yadav

5. Immunogenicity Assessments
• Immunogenicity evaluations, Capacity to induce immune system, Large, complex
molecules, Immune response potential,
• Validated assays, Screening for antibodies, Neutralizing antibodies, Safety,
Effectiveness, Regulatory guidelines, Validated methodologies,
• Cell-based assays, Radioimmunoassays (RIA), Enzyme-linked immunosorbent
assays (ELISA).
31
Anjali Yadav

5. Immunogenicity Assessments
• Evaluations of immunogenicity determine whether a biologic has the capacity to
induce a patient's immune system. Large, complex molecules like biologics have
the potential to trigger an immune response.
• Using validated assays, these evaluations involve screening for antibodies against
the biologic. Particularly of significance are neutralizing antibodies that could
affect the safety or effectiveness of the biologic.
• Assessments of immunogenicity are conducted out in accordance with regulatory
guidelines and validated methodologies. These techniques could use cell-based
assays, radioimmunoassays (RIA), or enzyme-linked immunosorbent assays
(ELISA).
32
Anjali Yadav

6. Structural Characterization
• Structural characterization process, Molecular structure, Primary, Secondary,
Tertiary, Quaternary levels, Composition, Conformation
• Mass spectrometry, Nuclear magnetic resonance (NMR), X-ray crystallography,
Chromatography, Uniformity, Quality, Effectiveness
• Product, Structural alterations, Safety, Comparability studies, Analyses.
33
Anjali Yadav

6. Structural Characterization
• The molecular structure of the biologic is thoroughly analyzed as part of the
structural characterization process. This comprises structural investigations at the
primary, secondary, tertiary, and quaternary levels to understand the composition
and conformation of the biologic.
• For structural characterization, methods like mass spectrometry, nuclear magnetic
resonance (NMR), X-ray crystallography, and chromatography are employed. To
ensure the uniformity, quality, and effectiveness of the product, it is essential to
understand the structure of the biologic.
• To demonstrate that structural alterations have no effect on the biologic's safety or
effectiveness, comparability studies are often carried out, Through a wide range of
analyses.
34
Anjali Yadav

7. Impurity Profiles
• Impurity profiles, Biologic safety, Efficacy, Quality
• Stability, Immunogenicity, Critical quality attributes
• High-performance liquid chromatography (HPLC), Mass spectrometry (MS),
Capillary electrophoresis (CE)
• Impurity detection, Quantification, Analytical techniques
• Impurity control strategies, Development, Manufacturing process.
35
Anjali Yadav

7. Impurity Profiles
• Impurity profiles assess the presence of impurities in the biologic. Identification and
quantification of impurities are crucial for ensuring product safety, efficacy, and
quality.
• Some impurities may impact the biologic's stability, immunogenicity, or other critical
quality attributes.
• Analytical techniques such as high-performance liquid chromatography
(HPLC), mass spectrometry (MS), and capillary electrophoresis (CE) are used to
detect and quantify impurities. These techniques provide sensitive and specific
analyses of impurity profiles.
• Impurity control strategies are implemented throughout the biologic's development
and manufacturing process.
36
Anjali Yadav

Phase I, II, and III Trials
Informed Consent and Ethical Considerations
Safety Monitoring
Efficacy Assessment
Pharmacovigilance
Post-marketing Surveillance
Patient Population Considerations
Immunogenicity Monitoring
37
Anjali Yadav

1. Phases I, II & III Trials:
• Biologics clinical development, Three main phases, Objectives, Endpoints,
• Phase I studies, Healthy volunteers, Patients, Safety, Tolerance, Pharmacokinetics,
Pharmacodynamics, Potential benefits Risks
• Phase II trials, Larger studies, Safety, Effectiveness, Specific patient population,
Optimum dosage, Regimen
• Phase III trials, Pivotal, Large-scale studies, Effectiveness, Adverse events,
Comparison, Existing available therapies.
38
Anjali Yadav

1. Phases I, II & III Trials:
• Biologics clinical development is divided into three main phases, each with distinct
objectives and endpoints.
• In phase I studies, a small number of healthy volunteers or patients are used to assess
the biologic's safety, tolerance, pharmacokinetics, and pharmacodynamics. The
purpose of these trials is to offer initial insights on the potential benefits as well as
risks of the biologic.
• Phase II trials are larger studies intended for determining the safety and effectiveness
of the biologic in specific patient population. These studies help in determining the
optimum dosage and regimen for further evaluation in Phase III trials.
• Phase III trials are pivotal, large-scale studies that verify the biologic's effectiveness,
monitor adverse events, and assess it compared existing available therapies.
39
Anjali Yadav

2. Informed Consent and Ethical Considerations
• Informed consent, Clinical research, Trial's objective, Procedures, Risks, Benefits,
Ethical need,
• Ethics committees (ECs), Independent regulatory bodies (IRBs), Ethical reviews,
Rights, Welfare, Safety, Participants, Vulnerable populations, Minors, Pregnant
women, Mental disorders,
• Transparency, Participant trust, Healthcare providers, General public, Trial
findings, Adverse events, Conflicts of interest.
40
Anjali Yadav

2. Informed Consent and Ethical Considerations
• Ensuring that participants completely understand the trial's objective, procedures,
risks, and benefits before to enrolment is a fundamental ethical need in clinical
research. This is known as informed consent.
• Ethics committees (ECs) or independent regulatory bodies (IRBs) conduct
rigorous ethical reviews of clinical trials to ensure that the rights, welfare, and
safety of participants are protected. To ensure their protection, special
considerations are given to vulnerable populations, including minors, pregnant
women, and those with mental disorders.
• Throughout the study, transparency is crucial to preserving participant trust and
maintaining ethical standards with healthcare providers and the general public. To
maintain transparency, trial findings, adverse events, and possible conflicts of
interest are promptly and appropriately revealed. 41
Anjali Yadav

3. Safety Monitoring
• Safety monitoring, Continuous procedure, Adverse events, Safety concerns
• Reporting procedures, Safety data, Regular reviews, Discrepancies, Potential risks
• Risk management plans, Risk mitigation strategies, Safety monitoring plans,
Independent safety monitoring committees, Data Monitoring Committees
(DMCs), Trial continuation, Modification, Termination, Suggestions.
42
Anjali Yadav

3. Safety Monitoring
• Throughout the process of clinical development, safety monitoring is a continuous
procedure that aims to identify and managing potential adverse events and safety
concerns.
• Entire procedures for reporting adverse events have been established in place to
monitor and evaluate safety data during the study. Reviews of safety data are
carried out on a regular basis in order to identify any discrepancies or
potential that might need more research.
• Risk management plans, including risk mitigation strategies and safety monitoring
plans, are developed to proactively manage and minimize potential risks. To
monitor safety data and provide suggestions for trial continuation, modification, or
termination, independent safety monitoring committees, also known as Data
Monitoring Committees (DMCs), are sometimes established. 43
Anjali Yadav

4. Efficacy Assessment
• Clinical trials, Efficacy assessment, Therapeutic benefits, Placebo, Standard
treatments
• Endpoints, Biomarkers, Clinical results, Surrogate endpoints, Statistical
techniques, Sensitivity analyses, Confidence intervals, Hypothesis testing
• Blinding, Randomization, Bias reduction, Reliability, Dose-response relationships,
Ideal dose range, Regimen, Maximum therapeutic benefit, Tolerable dose.
44
Anjali Yadav

4. Efficacy Assessment
• In clinical trials, efficacy assessment involves evaluating the biologic's therapeutic
benefits and comparing them with a placebo or standard treatments.
• Appropriate endpoints, including biomarkers, clinical results, or surrogate
endpoints, are selected to accurately evaluate effectiveness. Rigorous statistical
techniques, including as sensitivity analyses, confidence intervals, and hypothesis
testing, are used to assess efficacy in a reliable and robust manner.
• Methods such as blinding and randomization are used to reduce bias and ensure
the reliability of efficacy assessments. To determine the ideal dose range and
regimen which provides maximum therapeutic benefit with tolerable dose, dose-
response relationships are assessed.
45
Anjali Yadav

5. Pharmacovigilance
• Pharmacovigilance efforts, Potential risks, Biologic lifecycle, Detect, Assess,
Control, Thorough risk assessments
• Risk management plans (RMPs), Transparency, Adherence, Regulatory bodies,
Safety data reporting, Real-world settings
• Post-marketing safety monitoring initiatives
• Periodic safety update reports (PSURs), Observational studies, Patient databases.
46
Anjali Yadav

5. Pharmacovigilance
• The primary objectives of pharmacovigilance efforts are to detect, assess, and
control any potential risks related to the biologic throughout its lifecycle.
• To determine the possible impact and seriousness of risks that have been
identified, thorough risk assessments are carried out.
• The purpose of risk management plans (RMPs) is to proactively manage and
reduce risks that have been recognized. Transparency and adherence to
pharmacovigilance regulations are ensured by the timely and accurate reporting of
safety data to regulatory bodies.
• The safety of biologics is monitored in real-world settings through post-marketing
safety monitoring initiatives, such as periodic safety update reports (PSURs),
observational studies, and patient databases.
47
Anjali Yadav

6. Post Marketing Surveillance
• Post-marketing surveillance, Efficacy, Safety, Real-world situations,
• Clinical trial data, Real-world data (RWD), Patient registries, Observational
studies, Electronic health records (EHRs), Insights, Long-term use, Broader
patient populations, Regulatory bodies, Periodic safety update reports (PSURs),
Periodic benefit-risk evaluation reports (PBRERs), Updates, Safety profile,
• Potential risks, Ongoing monitoring.
48
Anjali Yadav

6. Post Marketing Surveillance
• Once the biologic has been approved and marketed, post-marketing surveillance
involves monitoring its efficacy and safety in real-world situations.
• Clinical trial data is backed up by real-world data (RWD) from patient registries,
observational studies, and electronic health records (EHRs), providing insights
into long-term use and broader patient populations. The regulatory bodies receive
periodic safety update reports (PSURs) or periodic benefit-risk evaluation reports
(PBRERs), which are reports that offer updates on the safety profile of biologics
based on post-marketing data.
• It is possible to identify potential risks by ongoing monitoring of real-world data
that may not have been seen during clinical studies.
49
Anjali Yadav

7. Patient Population Considerations
• Clinical trials, Patient populations, Inclusion criteria, Exclusion criteria,
• Trial sample, Representative, Demographics, Dosage, Safety monitoring,
Informed consent, Children, Elderly, Pregnant women, Patients with renal or
hepatic impairment,
• Preferences, Requirements, Perspectives, Patient recruitment, Retention, Trial
success.
50
Anjali Yadav

7. Patient Population Considerations
• To ensure that the findings of clinical trials may be applied to larger patient
populations, the wide range of the patient population must be considered.
• To reduce potential biases and ensure the trial sample is representative of the
intended patient population, inclusion and exclusion criteria are carefully chosen.
Certain demographics need to be taken into consideration when it comes to
dosage, safety monitoring, and informed consent. Examples of these populations
include children, the elderly, pregnant women, and patients with renal or hepatic
impairment.
• Understanding and taking into consideration the preferences, requirements, and
perspectives of patients can improve patient recruitment, retention, and trial
success in overall.
51
Anjali Yadav

8. Immunogenicity Monitoring
• Monitoring immunogenicity, Biologic's ability, Immunologic responses, Antibody
production,
• Validated techniques, Enzyme-linked immunosorbent assays (ELISA),
Radioimmunoassays (RIA), Cell-based assays, Immunogenicity profile, Safety,
Effectiveness, Pharmacokinetics, Pharmacodynamics,
• Continuous monitoring, Adaptation, Emerging data, Comprehensive evaluations,
Informed decision-making.
52
Anjali Yadav

8. Immunogenicity Monitoring
• Monitoring immunogenicity evaluates the biologic's ability to induce
immunologic responses, such as the production of antibodies directed against the
biologic.
• Immunogenicity evaluations are conducted using validated techniques, such as
enzyme-linked immunosorbent assays (ELISA), radioimmunoassays (RIA), or
cell-based assays. Understanding the biologic's immunogenicity profile is essential
for evaluating its effects on safety, effectiveness, pharmacokinetics, and
pharmacodynamics.
• Continuous monitoring and adaptation of immunogenicity assessments based on
emerging data ensure comprehensive evaluations and informed decision-making.
53
Anjali Yadav

REFERENCES
1. Botanical Drug Development Guidance for Industry:
https://www.fda.gov/files/drugs/published/Botanical-Drug-Development--Guidance-for-
Industry.pdf
2. S6 Addendum to Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals:
https://www.fda.gov/media/78034/download
3. Preclinical Development: The Safety Hurdle Prior to Human Trials:
https://www.americanpharmaceuticalreview.com/Featured-Articles/187349-Preclinical-
Development-The-Safety-Hurdle-Prior-to-Human-Trials/
4. https://southernresearch.org/expertise/biologics/
5. Building an Early Development Strategy for Complex Biologics:
https://www.certara.com/blog/building-an-early-development-strategy-for-complex-
biologics/#:~:text=A%20few%20of%20the%20primary%20preclinical%20development,require
s%20answering%20multiple%20questions:%20What%20data%20are
54
Anjali Yadav

REFERENCES
6. Biologics Guidance
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-
biologics/biologics-guidances
7. Immunogenicity Assessment for Therapeutic Proteins
https://www.fda.gov/media/85017/download
8. Clinical pharmacology considerations in biologics development
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011353/
9. Challenges and guidelines for clinical trial of herbal drugs
10. Clinical Implications of Herbal Supplements
55
Anjali Yadav

Preclinical and Clinical Development Consideration in Herbals & Biologics in USA

Recomendados

Recomendados

Mais conteúdo relacionado

Semelhante a Preclinical and Clinical Development Consideration in Herbals & Biologics in USA

Semelhante a Preclinical and Clinical Development Consideration in Herbals & Biologics in USA (20)

Último

Último (20)

Preclinical and Clinical Development Consideration in Herbals & Biologics in USA