Preclinical and Clinical Development Consideration in Herbals & Biologics in USA

It is overview of preclinical and clinical development consideration for herbals and biologics in USA.
In this details discussion of preclinical and clinical consideration in USA. This is belong to Subject Regulatory Aspects of Herbals and Biologics

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

2. 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

3. 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

4. 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

5. INTRODUCTION 5 Anjali Yadav

6. 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

7. 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

8. COMPARISON OF PRE-CLINICAL CONSIDERATION OF HERBALS & BIOLOGICS Pre- Clinical Development Consideration for Herbals Pre- Clinical Development Consideration for Biologics Regulatory Guidelines and Compliance Regulatory Guidelines and 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

9. COMPARISON OF CLINICAL CONSIDERATION OF HERBALS & BIOLOGICS Clinical Development Consideration for Herbals Clinical Development Consideration for Biologics Phase I, II, and III Trials Considerations Phase I, II, and III Trials 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

10. CHECKLIST FOR HERBALS Pre- Clinical Development Consideration Clinical Development Consideration Regulatory Guidelines and Compliance Phase I, II, and III Trials 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

11. PRECLINICAL DEVELOPMENT CONSIDERATIONS FOR HERBALS 11 Anjali Yadav

12. PRECLINICAL DEVELOPMENT CONSIDERATIONS FOR HERBALS 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. 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

13. PRECLINICAL DEVELOPMENT CONSIDERATIONS FOR HERBALS 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

14. PRECLINICAL DEVELOPMENT CONSIDERATIONS FOR HERBALS 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

15. CLINICAL DEVELOPMENT CONSIDERATIONS FOR HERBALS 15 Anjali Yadav

16. CLINICAL DEVELOPMENT CONSIDERATIONS FOR HERBALS 16 Anjali Yadav

17. CLINICAL DEVELOPMENT CONSIDERATIONS FOR HERBALS 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

18. CLINICAL DEVELOPMENT CONSIDERATIONS FOR HERBALS 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

19. CLINICAL DEVELOPMENT CONSIDERATIONS FOR HERBALS 19 Anjali Yadav

20. 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

21. CHECKLIST FOR BIOLOGICS Pre- Clinical Development Consideration Clinical Development Consideration Regulatory Guidelines and Compliance Phase I, II, and III Trials 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

22. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 22 Anjali Yadav

23. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

24. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

25. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

26. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

27. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

28. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

29. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

30. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

31. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

32. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

33. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

34. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

35. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

36. PRE - CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

37. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 37 Anjali Yadav

38. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

39. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

40. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

41. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

42. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

43. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

44. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

45. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

46. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

47. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

48. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

49. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

50. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

51. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

52. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

53. CLINICAL DEVELOPMENT CONSIDERATIONS FOR BIOLOGICS 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

54. REFERENCES Botanical Drug Development Guidance for Industry: https://www.fda.gov/files/drugs/published/Botanical-Drug-Development--Guidance-for-Industry.pdf S6 Addendum to Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals: https://www.fda.gov/media/78034/download 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/ https://southernresearch.org/expertise/biologics/ 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,requires%20answering%20multiple%20questions:%20What%20data%20are 54 Anjali Yadav

55. 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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678978/ 10. Clinical Implications of Herbal Supplements  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375827/ 55 Anjali Yadav

56. THANK YOU 56 Anjali Yadav