Understanding NDCTR 2019: A Key Guide for Pharma Manufacturers and Marketers Launching Products in India

India’s New Drugs and Clinical Trials Rules, 2019, mark a significant regulatory shift offering pharmaceutical companies streamlined pathways for new drug approvals and ethically sound clinical trials. Our expertise ensures your products align with these modern standards from development to CDSCO approvals.

1. Introduction

India's pharmaceutical and clinical research landscape underwent a major transformation with the introduction of the New Drugs and Clinical Trials Rules (NDCTR), 2019. These rules superseded the outdated provisions of Part XA and Schedule Y of the Drugs and Cosmetics Rules, 1945, establishing a regulatory framework for drug approval and clinical trials that is clearer, faster, and ethically robust. The pharmaceutical industry, research institutions, and other key stakeholders must understand and integrate these changes to ensure regulatory compliance and maintain a competitive edge. At Walter Healthcare, we are committed to educating and equipping our clients, from pharma innovators to clinical research professionals, with the knowledge and strategies needed to comply with the NDCTR. This post provides a comprehensive overview of the new regulatory environment and offers guidance on navigating it effectively.

2. Overview of NDCTR 2019

The Ministry of Health and Family Welfare introduced the New Drugs and Clinical Trials Rules (NDCTR), 2019, through GSR 227(E) on March 19, 2019. These rules were enacted to modernize India's drug regulatory system, replacing significant sections of Schedule Y from the Drugs and Cosmetics Rules, 1945. The NDCTR, 2019, now regulates the approval process for:

• New Drugs: Regulates the approval of entirely new pharmaceutical products for the Indian market.

• Investigational New Drugs (INDs): Govern unapproved drugs studied for safety and efficacy in clinical trials.

• Subsequent New Drugs (SNDs): Covers regulatory evaluation for new forms, strengths, or combinations of already approved drugs.

• Fixed Dose Combinations (FDCs): Regulates the approval and marketing of drug products combining multiple active pharmaceutical ingredients.

• Clinical Trials (CTs): Establish a comprehensive framework for conducting human clinical trials to assess drug safety and efficacy.

• Bioavailability/Bioequivalence (BA/BE) studies: Crucial studies demonstrating the therapeutic equivalence of generic drugs to innovator counterparts.

• Ethics Committees (ECs): Mandates independent ethics committees to safeguard clinical trial participants' rights, safety, and well-being.

2.1 Objectives of NDCTR, 2019

The NDCTR aims to:

• Simplify the clinical trial and drug approval process.

• Introduce time-bound approvals (e.g., 30 days for CTs).

• Ensure ethical oversight, participant safety, and data transparency.

• Facilitate academic research without DCGI approval under certain conditions.

• Align Indian standards with global practices such as ICH-GCP and WHO norms.

2.2 Role of CDSCO and DCGI

India's National Regulatory Authority is the Central Drugs Standard Control Organization (CDSCO). The Drugs Controller General of India (DCGI) leads the CDSCO, which is responsible for:

• Granting approvals for new drugs and clinical trials.

• Registering and auditing Ethics Committees.

• Monitoring pharmacovigilance, including SAE and compensation protocols.

3. Understanding the Pre-2019 Scenario

Before the introduction of the New Drugs and Clinical Trials Rules (NDCTR) in 2019, clinical trials and new drug approvals in India were regulated by Part XA and Schedule Y of the Drugs and Cosmetics Rules, 1945. However, these foundational provisions were characterized by ambiguity, inconsistent timelines, and administrative delays, posing significant challenges for industry stakeholders in terms of: 

• Securing timely approvals.

• Meeting unclear documentation requirements.

• Navigating ethical approvals across multiple layers.

Such inefficiencies not only hampered innovation but also deterred global sponsors from conducting research in India. 

3.1 Drugs and Cosmetics Act, 1940 (India): India's main law for regulating the import, manufacture, distribution, and sale of drugs and cosmetics is The Drugs and Cosmetics Act of 1940. This act primarily aims to guarantee that drugs and cosmetics provided to the Indian public are safe, effective, and of high quality.

3.2 Drugs and Cosmetics Rules, 1945 (India): Underpinned by the Drugs and Cosmetics Act of 1940, the Drugs and Cosmetics Rules of 1945 established comprehensive procedures and guidelines for their enforcement. These Rules are fundamental to India's drug regulatory framework, encompassing all aspects from licensing and manufacturing to labeling, testing, import, sale, and clinical trials.

3.2.1 Part XA - Import and Manufacture of New Drugs for Clinical Trials or Marketing

Introduced in 1988, Part XA lays down the legal framework for:

• New Drug Import and Manufacturing: Regulations govern the import and production of new pharmaceutical products.

• Clinical Trial Permissions: Specific permissions are required to conduct clinical trials.

• Investigational New Drugs (INDs): The rules establish regulatory oversight for INDs and their subsequent approval processes.

Key Provisions of Part XA: 

• Defines what constitutes a new drug.

• Mandatory CDSCO Approval: Requires explicit permission from the Central Drugs Standard Control Organization (CDSCO) for both conducting clinical trials and marketing new drugs.

• Streamlined Application Process: Details the necessary application procedures, including the use of Form 44 for new drug approvals.

• Evidence-Based Approval: Emphasizes that all new drugs must demonstrate safety and efficacy, supported by robust clinical trial data, whether from India or abroad.

3.2.2 Schedule Y - Requirements and Guidelines for Clinical Trials and New Drug Approval

Schedule Y provides scientific and procedural guidelines for:

• Submitting clinical data for new drug applications.

• Conducting clinical trials (Phase I to IV).

• Ensuring compliance with Good Clinical Practices (GCP).

Key Elements of Schedule Y:

• Definitions: New drug, clinical trial phases, bioavailability, bioequivalence, etc.

• Ethics Approval: Mandates review by the Institutional Ethics Committee (IEC).

• Informed consent is essential for all human participants.

Trial Phases:

• Phase I: Safety in healthy volunteers.

• Phase II: Efficacy in a small patient group.

• Phase III: Larger, multicenter trials to confirm effectiveness.

• Phase IV: Post-marketing surveillance.

4. Key Pillars of New Rules

The NDCT Rules, 2019, are fundamentally built upon these core principles:

1. Patient Safety and Ethical Conduct: The foremost objective of these rules is to introduce stringent measures for informed consent, enhance the role and accountability of Ethics Committees, mandate clear compensation for trial-related injuries/deaths, and ensure post-trial access to beneficial drugs.

2. Streamlined and Predictable Regulatory Framework: The 2019 New Drugs and Clinical Trials Rules enhance the predictability and efficiency of clinical research in India. By establishing strict approval timelines and a "deemed approval" process, these regulations aim to streamline operations, reduce bureaucratic obstacles, and ultimately foster a more favorable environment for business.

3. Promotion of Clinical Research and Innovation in India: These rules aim to establish India as a reliable and appealing hub for clinical trials. By tackling past challenges related to unpredictability and ethical concerns, they foster both international and domestic pharmaceutical companies to undertake research within India, capitalizing on its diverse patient base and scientific expertise. The provision of "deemed approval" for indigenous drugs particularly champions local research and development.

4. Expedited Access to New Drugs for the Indian Population: To reduce the historical "lag time" and ensure essential, innovative medications reach Indian patients faster, the new rules allow for waiving local clinical trials for certain drugs already approved globally.

5. Enhanced Transparency and Accountability: Greater transparency is achieved through the mandatory registration of trials on the CTRI and detailed reporting requirements for adverse events. This also promotes greater accountability within the clinical trial ecosystem, as clear responsibilities are outlined for all stakeholders.

5. Impact and implications of Pharmaceutical Stakeholders

Under the New Drugs and Clinical Trials Rules (NDCTR), 2019

The implementation of the rule has brought both responsibilities and opportunities for stakeholders in the Indian pharmaceutical and clinical research sectors. These Rules usher in a new regulatory era, emphasizing a structured, time-bound, and ethically sound approach that will directly impact company operations, strategies, and compliance efforts. At Walter Healthcare, we work closely with our clients to interpret the impact of the NDCTR, guiding them in aligning their operational models, documentation, and development timelines to the revised regulatory expectations.

1. For Drug Manufacturers (Own Manufacturing / Loan Licensees)

Implications:

• Manufacture of New Drugs Requires CDSCO Permission: Even if the manufacturing license is issued by the State Licensing Authority (SLA), the formulation of a new drug cannot be initiated without a CDSCO license under NDCTR.

• Batch Release Only After Approval: No commercial manufacturing can begin until the formulation is approved under the applicable Form CT-21 or CT-23, depending on the category.

• Accountability in Post-Marketing Safety: Manufacturers are expected to support the marketing holder in preparing and submitting PSURs (Periodic Safety Update Reports).

Opportunities:

• Defined timelines bring predictability in batch planning and scale-up post-approval.

• Export-oriented units benefit from global alignment and faster drug recognition in regulatory markets.

2. For Marketing Authorization Holders (MAHs)

Implications:

• Central Approval is Key: The MAH, not the manufacturer, holds primary responsibility for CDSCO product approval.

• GMP Compliance Not Enough: Manufacturer's GMP compliance doesn't substitute central approval for New Drugs, Subsequent New Drugs, or Fixed Dose Combinations under NDCTR.

• Legal Liability: Marketers face legal consequences for non-compliance, including compensation, recalls, or prosecution.

Opportunities:

• Faster approval routes (90 days for SNDs) allow marketers to introduce innovations and line extensions quickly.

• Approvals granted under NDCTR (Form CT-21) serve as solid regulatory proof during investor audits, exports, or M&A activities.

3. For Third-Party Players (CROs, Consultants, Contract Manufacturers)

Implications:

• Documentation & Dossier Development: Consultants and CROs supporting applications must now work with standardized NDCTR formats (CT-04, CT-21, CT-23, etc.), ensuring robust and audit-ready submissions.

• Accountability in Clinical Trials: If managing trial operations, CROs must comply with Good Clinical Practices (GCP) and submit periodic updates to the CDSCO.

• Contract Manufacturers: Cannot manufacture new drugs, SNDs, or FDCs without CDSCO approval being secured by the marketing firm or client.

Opportunities:

• Greater demand for regulatory consultants, CDMOs, and CROs to navigate NDCTR filings, especially for companies unfamiliar with CDSCO submissions.

• Potential to position as regulatory knowledge partners through audits, training, or compliance support.

Walter Healthcare’s Advisory Role

• Identify whether your product falls under the new drug, SND, or FDC categories.

• Guide the preparation of dossiers, stability data, PSURs, and submission forms.

• Train teams on compliance, labelling, and regulatory communication with CDSCO.

• Support regulatory due diligence for product portfolios marketed under third-party models.

 6. Insight Table: Key Elements of NDCTR, 2019 for Stakeholders

7. Conclusion

India's pharmaceutical sector has been transformed by the New Drugs and Clinical Trials Rules (NDCTR), 2019, which modernized the regulatory framework for drug approvals and clinical trials. Emphasizing transparency, efficiency, and patient safety, the NDCTR is crucial for manufacturers, marketers, and stakeholders aiming for responsible growth. Navigating these dynamic rules demands specialized expert guidance. At Walter Healthcare, we help clients understand and implement the NDCTR. Our advisory services cover regulatory classification, dossier preparation, team training, and managing communications with the CDSCO, ensuring compliance, competitiveness, and audit readiness. Non-compliance can lead to severe legal, reputational, and financial consequences. Strategically embracing the NDCTR can expedite product launches, boost pharmaceutical investor confidence, and foster international acceptance. Let Walter Healthcare guide you through the NDCTR, turning regulatory challenges into opportunities for innovation and leadership.