Advanced Therapy Medicinal Products (ATMPs) are an emerging class of medicines based on genes, cells, or tissues that offer revolutionary treatment options, especially for diseases that are currently untreatable or poorly managed with conventional pharmaceuticals.

What are ATMPs?

Advanced Therapy Medicinal Products (ATMPs) are innovative biopharmaceuticals that utilize genes, cells, or engineered tissues to treat, prevent, or potentially cure a wide range of serious diseases. These therapies are particularly promising for conditions such as genetic disorders, cancers, autoimmune diseases, and tissue/organ damage, where conventional pharmaceuticals often fall short.

Types of ATMPs:

1.     Gene Therapy Medicinal Products (GTMPs):

1. Deliver functional genes to replace faulty ones or to provide new functions.
2. Example: Zolgensma (for spinal muscular atrophy).

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2.     Somatic Cell Therapy Medicinal Products (sCTMPs):

1. Use cells manipulated outside the body and reintroduced to repair or modify tissue function.
2. Example: Provenge (for prostate cancer).

3.     Tissue-Engineered Products (TEPs):

1. Use engineered cells or scaffolds to repair, regenerate, or replace damaged tissues.
2. Example: Holoclar (for corneal repair using limbal stem cells).

4.     Combined ATMPs:

1. Include one above integrated with a medical device (e.g., scaffolds, matrices).
2. Example: A tissue-engineered cartilage product with a biodegradable implant.

Significance of ATMPs over Traditional Pharmaceuticals

Challenges with ATMPs and GMP (Good Manufacturing Practice)

Advanced Therapy Medicinal Products (ATMPs) development and production present unique challenges beyond conventional pharmaceutical manufacturing. Due to their biological nature and high degree of customization, maintaining compliance with Good Manufacturing Practice (GMP) standards is significantly more complex.

1.      Product Complexity

• Biological Instability: ATMPs involve living cells, viral vectors, or inherently fragile genetic constructs and are prone to degradation.
• Variability: Biological raw materials and processes introduce high variability, making achieving batch-to-batch consistency difficult.

2.     Manufacturing Challenges

• Personalization: Many ATMPs are autologous, requiring manufacturing steps tailored to each individual patient.
• Scale and Infrastructure: Production is often small-scale, and requires specialized cleanrooms, closed systems, and aseptic processing to maintain sterility and viability.

3.     Supply Chain Issues

• Limited Shelf Life: Most ATMPs have short shelf life, sometimes just hours or days, demanding real-time coordination.
• Cold Chain Logistics: Strict temperature controls are needed throughout the supply chain to preserve product integrity.
• Just-in-Time Delivery: Manufacturing, testing, and delivery must be highly synchronized with clinical administration windows.

4.     Quality Control (QC)

• Limited Material for Testing: ATMPs are often produced in small batches with minimal excess material for quality testing.
• Complex In-Process Testing: Real-time monitoring of biological activity, identity, purity, and potency is essential and technically demanding.

5.     GMP Compliance Challenges

• Rigid Frameworks vs. Flexible Needs: Traditional GMP standards may not accommodate the dynamic nature of ATMP development, especially for individualized therapies.
• Hospital-Based Manufacturing: Integrating GMP principles in hospital or academic settings (for autologous or early-phase therapies) poses logistical and regulatory hurdles.
• Evolving Standards: Regulatory expectations and GMP guidelines for ATMPs still evolve and may vary across regions.

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Regulatory Approach on ATMPs

1.      EMA (European Medicines Agency) – EU

• Regulation: ATMPs in the European Union are governed by Regulation (EC) No 1394/2007, specifically designed to ensure the safety and efficacy of gene therapy, somatic cell therapy, and tissue-engineered products.
• Specialized Committee: The Committee for Advanced Therapies (CAT) evaluates the scientific aspects of ATMPs, ensuring they meet stringent standards for approval.
• Centralized Marketing Authorization: Centralized approval through the EMA is required for marketing ATMPs across all EU member states.
• Hospital Exemption (Article 3): Allows certain non-routine, personalized treatments (e.g., autologous therapies) to be exempt from centralized approval, provided they are produced and used within a single hospital or medical institution.

2.     FDA (U.S. Food and Drug Administration) – USA

• Regulation Body: ATMPs in the U.S. fall under the Center for Biologics Evaluation and Research (CBER) at the FDA, which oversees biologics, including gene therapy and cell therapy products.
• Regulatory Framework:
  • IND (Investigational New Drug): Required for clinical trials involving ATMPs to assess safety and efficacy before approval.
  • BLA (Biologics License Application): Needed for the commercial approval of ATMPs.
  • Expedited Pathways:
    • RMAT (Regenerative Medicine Advanced Therapy): Provides priority review and more flexible clinical trial designs for promising regenerative therapies.
    • Breakthrough Therapy Designation: Expedited development and review processes for therapies addressing serious or life-threatening conditions.

3.     TGA (Therapeutic Goods Administration) – Australia

• Regulation: In Australia, ATMPs are regulated under the Biologicals Framework which governs gene therapies, cell therapies, and tissue-engineered products.
• Risk-Based Classification: ATMPs are classified into four risk classes (Class 1 to 4) based on their complexity, patient risk, and potential for harm.
• Focus on Patient Safety: Emphasis on autologous therapies, ensuring that the safety of personalized treatments (derived from patient’s own cells) is thoroughly assessed.

4.     MSS (Malaysia’s National Pharmaceutical Regulatory Agency) – Malaysia

• Regulation: ATMPs are regulated by the Cell and Gene Therapy Products (CGTPs) Guidelines issued by the National Pharmaceutical Regulatory Agency (NPRA).
• Guideline Focus: These guidelines ensure that cells and gene therapies are handled under strict quality control, emphasizing traceability from collection through processing and administration.
• Compliance with GMP: ATMPs must comply with GMP and additional regulations specific to cell handling, genetic modifications, and patient safety.

5.     WHO (World Health Organization) – Global

• Technical Guidance: The WHO provides guidance on regulating cell-based therapies and genetic medicines globally, to ensure safe and ethical practices in developing and using ATMPs.
• Global Harmonization: The WHO fosters international regulatory harmonization, facilitating easier global access to ATMPs while maintaining safety and efficacy standards.
• Focus on Low-Income Regions: WHO’s efforts also focus on making advanced therapies accessible and affordable in resource-constrained settings, while ensuring that safety and quality are not compromised.

6.     ANVISA (Agência Nacional de Vigilância Sanitária) – Brazil

• Regulation: In Brazil, ATMPs are categorized as Advanced Cell Therapy Products (ACTPs), subject to regulatory frameworks set by ANVISA, the Brazilian Health Regulatory Agency.
• Regulatory Pathway: ANVISA has developed a dedicated regulatory pathway for expedited review, ensuring that promising treatments can be brought to market more quickly in Brazil.
• Clinical Trial and Approval Process: The approval process includes assessing clinical trial data, safety profiles, and post-market surveillance to ensure the ongoing safety of ATMPs in the population.

Contact Us

For technical, scientific, and GMP consulting services related to your ATMP (Advanced Therapy Medicinal Products) products, please get in touch with GxP Cellators Consultants at .