From Idea to Impact: The Ultimate Guide to New Product Development

Introduction

The new product development process should ensure that the drug possesses quality, safety efficacy, and compliance with the regulatory requirements. The life cycle of a drug (Pharmakon) or biologic is initiated to address a disease or an ailment for which there is an unmet clinical need or to improve existing therapies. The process involved in developing a new drug from the initial idea to the marketing of a finished product is a complex and stringent process that takes 12–15 years, approx., and costs around $1 billion.

Pharmaceutical products (Drugs, Biologics) involve 05 stages from target identification to finished product.

• Drug Discovery & Development
• Non-Clinical Development
• Clinical & CMC Development
• Regulatory Review & Market Approval
• Post Marketing Surveillance

Stage 1: Discovery & Development

A knowledge of the physiology of a system and the patho-physiology of a particular disease is a fundamental step in the discovery process. Biological pathways implicated in disease states are identified through basic research, which also involves formulating a hypothesis to find a target (gene, RNA, or protein) and designing a product with therapeutic benefits. Target selection and validation are the most crucial step in the development of a new medication.

Once the therapeutic target is identified, the biological mechanism is investigated to validate its efficacy, safety, and meet clinical, commercial needs; above all target should be “DRUGGABLE”. The ‘HIT’ compounds are screened for biological activity using combinatorial chemistry and HTS (high throughput Screening).

The combinatorial chemistry-generated library is screened for biological activity, in an in-vitro system, in which a known biochemical process, which is thought to mimic a human disease or disorder, is agonized or antagonized.

High throughput and other compound screens are developed and run to identify molecules that interact with the drug target, chemistry programmes are run to improve the potency, selectivity and physio-chemical properties of the molecule, the development of biological assays to be used for the identification of molecules with activity at the drug target and data continue to be developed to support the hypothesis that intervention at the drug target will have efficacy in the disease state.

There are two types of assays, cell-based assays and biochemical assays.

Cell-based assays (CBA), targets membrane receptors, ion channels and nuclear receptors to produce a functional effect leading to compound activity.

Bio-chemical assays (BCA), targets to both receptor and enzyme targets, measuring the affinity of the test compound for the target protein.

The factors to be considered in Assay development are:

• Pharmacological relevance
• Reproducibility Costs
• Assay quality
• Effects of compounds in Assay

The assays should be designed to provide important information with regard to absorption, distribution, metabolism and excretion (ADME) properties as well as physico-chemical and pharmacokinetic (PK) measurements.

The number of doses required to reach steady state depends on the lead’s pharmacokinetic profile in the same animal model. These pharmacology evaluations assist in the selection of dose levels and route and frequency of administration for preliminary and definitive toxicology, safety and tolerance human trials.

Compounds are screened for Drug-like properties such as Lipinski Rule, clogP, Caco2 permeability, and hERG affinity which maintained their potency and selectivity at the principal target to generate ‘LEAD’ series for further development. Lead compound`s metabolism in the pharmacological and proposed toxicological animal species is evaluated to assists in selecting the species that are similar to humans for definitive toxicology studies.

The compounds are optimized for favourable properties, improving on deficiencies in the lead structure. Once the lead is optimized, candidate referred to be suitable and recommended for pre-clinical development to assess the safety and toxicity profile to address feasibility to administer in to humans.

Stage 2: Non-Clinical Development

Pre-Clinical Assessment: 

Before a drug is tested in humans, it must undergo preclinical research, which involves laboratory and animal studies. The purpose of the pre-clinical phase is to gather preliminary data on the drug’s safety, biological activity, and mechanism of action.

This involves laboratory and animal studies to assess the basic safety and biological activity of the drug. This phase is essential to determine whether the drug has the potential to be effective and safe for human use. These studies help determine whether the drug is safe enough to be tested in humans.

Key Objectives:

• Toxicology Testing: Evaluate the potential toxic effects of the drug. This is usually done in animal models to identify possible acute and chronic toxicities.

• Pharmacokinetics (PK): Study how the drug is absorbed, distributed, metabolized, and excreted by the body (often referred to as ADME – Absorption, Distribution, Metabolism, Excretion).

• Pharmacodynamics (PD): Investigate how the drug interacts with its target (e.g., receptors, enzymes) and its potential effects on the body.

• Dose Selection: Establish a starting dose for human trials, often based on animal studies, and assess how the drug behaves at different dose levels.

During early preclinical development, the primary goal is to determine the candidate is reasonably safe for initial use in human and if it exhibits pharmacological activity that justifies commercial development.

A very detailed compilation of non-clinical data of investigational drug candidate supporting the dosage, frequency, method of administration and safety monitoring procedures should be submitted in the form of Investigational Brochure (IB) to support the clinical management of the study subjects.

Any investigator or a sponsor must get approval from regulatory authorities to investigate a new drug in humans. An application (IND or CTA) should describe the general investigation plan and the protocols ensuring human studies.

Researcher or a healthcare professional must enlighten volunteer participating in a trail about consequences to make a choice to accept or reject such test or treatment which familiarly considered as Informed Consent (IC).

Every trail plan, protocols and IC must be reviewed and approved in accordance G to GCP by IRB/IEC. They have authority to approve, recommend modifications in, or disapprove trails those are non-compliant with regulations.

Stage 3: Clinical and CMC Development

Clinical Development:

Phase I

Phase 1 trials are the first time a drug is tested in humans. This phase primarily focuses on safety and the pharmacokinetics of the drug in the human body. Phase 1 studies typically involve a small number of healthy volunteers (20-100 individuals), though in some cases (especially for life-threatening conditions), patients may be enrolled.

Key Objectives:

• Safety Assessment: Determine the most common side effects and whether the drug has any harmful effects on healthy individuals.

• Dose Escalation: Researchers begin by administering the drug at very low doses and progressively increase the dose to determine the highest dose that can be safely administered without causing severe side effects (Maximum Tolerated Dose, or MTD).

• Pharmacokinetics and Metabolism: Study how the drug is absorbed, metabolized, and cleared from the body. This includes identifying the optimal formulation and understanding drug interactions with other substances.

• Side Effects and Adverse Reactions: Monitor for any adverse effects, from mild (e.g., headache, nausea) to severe (e.g., organ toxicity, life-threatening events).

Phase I trials are usually not designed to test the drug’s effectiveness but rather its safety and biological response in humans.

Phase II

Phase 2 trials mark the first time a drug is tested in patients who have the condition the drug is meant to treat. This phase involves a larger sample size (100-300 participants) and focuses on evaluating the drug’s efficacy (whether it works for the intended purpose) while continuing to monitor for side effects.

Key Objectives:

• Efficacy Assessment: The primary goal of Phase 2 is to determine whether the drug shows enough benefit to warrant further testing in larger populations. Researchers look for evidence that the drug can effectively treat the disease or condition.

• Optimal Dosage: Fine-tuning the dosage to maximize therapeutic effects while minimizing side effects. Different dosages may be tested to find the most effective and safest dose.

• Safety Continuation: While efficacy is the focus, Phase 2 continues to assess the safety of the drug, including any new or emerging side effects not identified in Phase 1.

• Biomarker Identification: Researchers may identify specific biomarkers (biological indicators) that can be used to monitor drug effects or patient response in later phases.

In Phase 2, the trial may involve placebo groups or comparison with existing treatments (if any), providing more robust data about the drug’s effectiveness.

Phase III

Phase 3 trials are large-scale studies designed to confirm the drug’s effectiveness and to further assess its safety in a diverse patient population. This phase often involves hundreds or thousands of patients (300-3,000) and is the final step before seeking regulatory approval.

Key Objectives:

• Efficacy Confirmation: Confirm that the drug works as expected in a larger and more diverse population. Phase 3 trials often compare the experimental drug to a placebo or standard treatment to demonstrate its superior effectiveness.

• Safety Monitoring: Assess both short-term and long-term safety in a broader group of patients, helping to identify rare or previously unknown side effects.

• Statistical Significance: Ensure that the results are statistically significant, meaning that the observed effects are unlikely to have occurred by chance. This is crucial for convincing regulatory agencies that the drug is safe and effective.

• Quality of Life and Secondary Endpoints: Many Phase 3 trials also assess the drug’s impact on quality of life (QoL), as well as secondary outcomes like symptom reduction or improvement in related health factors (e.g., mobility, psychological well-being).

This phase provides the most comprehensive data on the drug’s effectiveness and safety. If the Phase 3 trials are successful, the data is submitted to regulatory bodies like the FDA or EMA for drug approval.

Chemistry, Manufacturing, and Controls (CMC) Development (GMP):

Chemistry, Manufacturing, and Controls (CMC) is a crucial part of drug development that ensures the quality, safety, and consistency of a pharmaceutical product. It covers three main areas:

1. Chemistry: Focuses on the drug’s chemical composition and synthesis, ensuring purity, stability, and efficacy.

2. Manufacturing: Involves scaling up production processes, ensuring efficiency and compliance with Good Manufacturing Practices (GMP).

3. Controls: Includes quality control and testing to guarantee the drug meets safety standards and regulatory requirements.

CMC development is essential for regulatory approval and helps ensure the drug is consistently produced and safe for patients. Detailed CMC data is required by regulatory agencies like the FDA and EMA for market approval.

Stage 4: Regulatory Review & Market Approval

Health Authorities review and regulate products and supervises the associated clinical trials, marketing approval, and risk management processes with the main objectives to promote public health, assess the safety and efficacy of therapeutic products, and collaborate with experts to enhance product development.

The Authority perspective will be initiated when a sponsor starts a clinical trial to test a new chemical in Humans.

Once a Sponsor files an application for clinical trial, can precede further after a stipulated time to hear a response from authority in-case any conditions of hold or termination will be met.

As soon a drug has proved satisfactory after Phase III trials, the trial results along with the comprehensive description of animal studies, methods and manufacturing procedures, formulation details, and shelf life information makes up the “regulatory submission” that is submitted for review to the appropriate regulatory authorities to review, and give the approval to market the drug.

The agency will determine the adequacy of the submission for completeness as per requirements and accepts the application which otherwise can be rejected.

The Application contents will be sent to appropriate sub divisions within the authority for review that determine that the drug meets statutory standards for safety, efficacy. If they found any discrepancies, thy can be communicated to sponsor through various channels for modifications and if satisfied with all requirements, the authority will approve the drugs to be released in to interstate commerce.

Stage 5: Post Marketing Surveillance

Phase IV

Phase IV trial is also known as post-marketing surveillance Trial. Phase IV trials involve the safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives permission to be sold. Phase IV studies are required by regulatory authorities or will be undertaken by the sponsoring company for competitive or other reasons. The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials.

The minimum time period mandatory for Post Marketing Surveillance (Phase IV trials) is 2 years.

A comprehensive, concise, and critical analysis of new or emerging information on the risks of the medicinal product, and on its benefit in approved indications, to enable an appraisal of the product’s overall benefit-risk profile should be submitted in the form of a PBRER.

The main focus of each PBRER is the evaluation of relevant new safety information from the available data sources, placed within the context of any pertinent efficacy/effectiveness information.

Conclusion

The drug development process, from discovery to market approval, is a complex and collaborative effort ensuring treatments are safe, effective, and of high quality. Each stage, from initial research to clinical trials and regulatory review, plays a vital role in addressing medical needs. Advances in technology and personalized medicine are accelerating the process, enabling faster and more targeted therapies. Ultimately, this lifecycle highlights the dedication of all stakeholders in delivering innovative treatments to improve global health.