Digital CMC Regulatory Lifecycle (DCRL) Framework

Providing a structured, science-based approach to the development, assessment, and regulatory use of digital predictive tools in pharmaceutical Chemistry, Manufacturing and Controls (CMC).

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DCRL Framework Overview

The Digital CMC Regulatory Lifecycle (DCRL) Framework is a practical, science-based approach developed by the Digital CMC CERSI to support the responsible use of digital predictive tools, including AI and machine learning, in pharmaceutical Chemistry, Manufacturing and Controls (CMC). Its purpose is to help innovators, manufacturers and regulators build shared confidence that digital tools are reliable, transparent, proportionate to risk, and suitable for their intended regulatory or manufacturing use.

What it supports

The DCRL framework provides guidance across:

  • Context of use definition

  • Risk-proportionate credibility assessment

  • Validation and uncertainty evaluation

  • Lifecycle management

  • Regulatory documentation readiness

  • Inspection and submission preparedness

It promotes predictable, proportionate adoption of digital and AI-enabled tools in regulated environments.

Key principles

The framework is underpinned by core regulatory and scientific principles:

  • Risk-based implementation

  • Human accountability and oversight

  • Transparency and explainability

  • Robust data governance

  • Lifecycle management and control

  • Regulatory readiness and traceability

These principles align with international guidance including ICH, EMA, FDA, MHRA, and relevant standards and best practice.

The framework supports the CERSI’s wider aim: to accelerate safe, sustainable and efficient medicines development while protecting product quality, patient safety and regulatory trust. It provides a common language and workflow for industry, academia and global regulators, reducing uncertainty around evidence expectations, model credibility, documentation and lifecycle oversight.

Informing Digital Predictive Tool Development in CMC

The DCRL framework has three connected layers:

  • The DCRL framework is supported by four enablers that facilitate practical adoption and shared understanding across stakeholders. These include 4 regulatory use cases to demonstrate real-world application, Virtual Expert for Regulatory Assistance (VERA), a collaborative Digital CMC Sandbox  for static credibility assessment with an interactive element and evidence generation, and targeted, modular and interactive training platforms (e.g. SkillsFactory) to build capability.

    Together, these enablers provide the consistent language, approach, templates, knowledge for regulators, industry and academia to translate principles into consistent, regulator-ready practice.

  • The pathway guides digital tools through 4 levels of maturity readiness from early concept through development, validation, regulatory use and lifecycle management: concept and risk analysis; development and verification; validation and credibility assessment; and regulatory use and lifecycle management.

    Ten detailed workflow stages help users define the question of interest, context of use, model type, model risk, data requirements, credibility evidence, regulatory documentation and post-deployment control.

  • The bottom layer anchors the framework in five core principles adapted for Digital CMC which are applicable to knowledge driven, data-driven (incl. AI, and empirical) and hybrid models :

    • Safety, security and robustness

    • Transparency and explainability

    • Fairness and avoidance of bias

    • Accountability and governance

    • Contestability, human oversight and redress.

    Not all the principles are applicable to all model types, but by collating them and adapting them for a CMC context, they provide a valuable aide-memoir resource to ensure users consider all aspects to ensure their credibility assessments are regulatory-aligned.  These principles are aligned to collated global regulatory guidance, standards and scientific literature, including ICH guidance, FDA, EMA and MHRA expectations, ASME standards, and peer-reviewed best practice (Figure 3)

Digital CMC Regulatory Lifecycle (DCRL) Framework

Regulatory, Standards and Scientific Best Practice Basis for DCRL Framework

Interactive DCRL Framework

An interactive DCRL Framework has been developed  to help the user consider the relevant principles that apply to their computational models at various stages of the workflow and provides key regulatory and standards links.

Together, these layers make the DCRL framework a regulator-ready bridge between digital innovation and pharmaceutical quality assurance. It enables digital tools to be developed and assessed consistently, supports global harmonisation, and helps ensure that digital transformation in CMC delivers faster access to medicines without compromising quality, safety or public trust.

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