Cell & Gene Therapy

Greenleaf helps sponsors understand and respond to FDA requirements for cellular products regulated as human tissues and for cellular products subject to additional regulation as biological products and/or medical devices.

In addition, our team monitors and analyzes the regulatory environment for emerging trends in cell and gene therapy regulation ⎯ including orphan drug designation and exclusivity, long-term follow-up requirements, companion diagnostics, the development and use of real-world evidence, and other agency policies and actions that could potentially impact current development programs ⎯ as well as changes to the competitive landscape for cell and gene therapies.

When issues arise related to comparability of early-phase and later-phase data, our experts help sponsors address the FDA’s questions and make the strongest arguments in support of their submission.

For sponsors developing cell and gene therapies to treat rare and ultra-rare diseases, Greenleaf provides guidance on ways to maximize trial design using appropriate clinical endpoints and natural history study data in support of efficient product development.

Greenleaf experts assist sponsors developing requests to the FDA for product development designations and approaches, including:

• Orphan drug designation
• Fast track designation
• Regenerative medicine advanced therapy designation
• Breakthrough therapy designation
• Rare pediatric disease designation and other submissions related to priority review vouchers

The team also advises sponsors on accelerated approval and confirmatory studies when needed.

Greenleaf has effectively engaged with the FDA on behalf of clients to discuss, identify, and resolve potential technical and regulatory challenges related to emerging manufacturing technologies prior to regulatory submissions. Our team works with the Center for Biologics Evaluation and Research (CBER) Advanced Technologies Team (CATT) to support client development and implementation of cell and gene therapy manufacturing technology.

Manufacturers of cell and gene therapies are responsible for complying with multiple current GXP regulations, including: good manufacturing practice regulations (GMPs) and/or quality system regulations (QSRs); good laboratory practice regulations (GLPs); good clinical practice regulations (GCPs); and good tissue practice regulations (GTPs).

Greenleaf and our network of experts conduct compliance assessments and gap analyses at both the facility and corporate levels for manufacturing and quality practices and systems, including GMP, GCP, GTP, and QSR assessment, as well as:

• Identification of critical quality attributes (CQA)
• Chemistry manufacturing and controls (CMC) readiness
• Manufacturing platform (e.g., manufacturing steps, implementing new technologies, and automated systems)
• Quality- and compliance-related processes and procedures
• Corporate training programs and corporate-wide quality systems
• Audit programs
• Risk management
• Quality/compliance/clinical organizations

In these same areas, Greenleaf evaluates compliance assessments and delivers strategic and technical guidance and recommendations that will help the client implement system-wide quality enhancements.

Greenleaf and our network offer the following mock FDA inspection services to help clients prepare for routine GXP inspections and align the client’s organization with regulators’ expectations:

• Preparing and conducting mock inspections
• Conducting gap analyses
• Facilitating communications with CBER’s Advanced Technologies Team
• Identifying and prioritizing deficiencies
• Providing corrective action support
• Providing guidance during inspections
• Assisting with revision and preparation of all relevant documents
• Training and preparation in advance of an FDA inspection, covering such topics as: FDA inspection authority; inspection expectations; inspection terminology and guidelines; and inspection process, roles, and responsibilities

Greenleaf experts help clients prepare for and respond to identified GXP compliance problems with knowledgeable, objective analysis and evaluation of:

• FDA Form 483s and company responses
• Warning letters and company responses
• Untitled letters and company responses
• Internal and external audit reports
• Establishment inspection reports
• FDA regulatory correspondence and company responses
• FDA communications relating to inspectional observations
• Investigation and root cause analysis of deficiencies
• Corrective and preventive action plans
• Preparation for FDA meetings
• Comprehensive corporate-wide and facility implementation plans