What does the regulatory landscape for ATMPs look like?

EU Common Terminology

USA Common Terminology

Regenerative medicine therapy is defined as

i) a cell therapy, therapeutic tissue-engineering product, human cell and tissue product, or any combination product using such therapies or products, explicitly excluding HCT/Ps;

ii) that is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition;

iii) and if the preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition. 

EU Subclassification for ATMPs

USA Subclassification for ATMPs

• Somatic Cell Therapies

Inclusions:

• • Cancer vaccines
  • Cellular immunotherapies
  • Other types of autologous and allogeneic cells therapies
  • Xenogeneic living cells
  • Stem cells and derived products
  • Genetically modified cells

Exclusions:

• • Products exclusively containing non-viable cells or tissue that do not produce pharmacological, immunological, or metabolic action

• Gene Therapies

Inclusions:

• • Plasmids DNA
  • Viral vectors
  • Genetically engineered microorganisms
  • Human gene editing technology
  • Patient-derived cellular gene therapy products

Exclusions:

• • Non-biological products (e.g., chemically synthesized nucleic acids)
  • Vaccines against infectious diseases

• Tissue Engineered Therapies

Inclusions:

• • Products containing animal cells or tissues
  • Products may also contain additional substances, such as cellular products, bio-molecules, biomaterials, chemical substances, scaffolds, or matrices
  • Products for cartilage or cardiac defects, among others
  • Stem cells and derived products

Exclusions

• • Products exclusively containing non-viable cells or tissue with no pharmacological, immunological, or metabolic action

• Combined ATMPs (cATMPs)

• Cell Therapies

Inclusions:

• • Cancer vaccine
  • Cellular immunotherapies
  • Other types of autologous and allogeneic cells
  • Xenogeneic living cells
  • Stem cells and derived products
  • Genetically modified cells

Exclusions:

• • HCT/Ps under PHSA Section 361
    
    

• Gene Therapies

Inclusions:

• • Plasmid DNA
  • Viral vectors
  • Genetically engineered microorganisms
  • Human gene-editing technology
  • Patient-derived cellular gene therapy products

Exclusions:

• • Non-biological products (e.g., chemically synthesized nucleic acids)

• • Products destined for the treatment or prophylaxis of infectious diseases

EU Authorities

USA Authorities

• The competent national authority of each member state is responsible for clinical trials
• The Committee for Medicinal Products for Human Use (CHMP) is responsible for producing positive opinion
• Comittee for Advanced Therapies (CAT) is responsible for the draft opinion

• Center for Biologics Evaluation and Research (CBER)
• Office of Tissues and Advanced Therapies (OTAT)

EU Important Legislation

USA Important Legislation

• Directive 2001/83/EC for medicinal products in human use
• Directive 2009/120/EC for advanced therapy medicinal products
• Regulation 726/2004/EC community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European medical agency
• Regulation 1394/2007/EC and Regulation (EC) No 726/2004

• Section 351 of PHSA and FDCA
• Title 21 CFR 600-680 Regulation on biologics
• 21 CFR 1271 to prevent the spread of infectious diseases
• RMAT Designation: Section 3033 of the 21^st Century Cures Act (21 USC 356 [g](8)

EU Special Provisions

USA Special Provisions

• Priority Medicine Designation Scheme
  
  
• Designed for medicines that target an unmet medical need.
• Accelerated assessment, conditional approval, and scientific advice.
• Initiate early dialogue between the European Medicines Agency and the therapy developer.
• Grant accelerated treatment.
• Application review time reduced from 210 days to 150 days.
  
  
• Conditional Marketing Authorization
  
  
• Designed for medicinal products with promising yet incomplete efficacy data are granted conditional market authorization, provided they will be further evaluated while on the market.
  
  
• Authorization Under Exceptional Circumstances
  
  
• Applicable to therapies for rare diseases with difficult-to-measure clinical endpoints.
• Granted on the condition that the applicant agrees to continuously monitor safety data and report any product incidents to the competent authority.
• The license is valid for five years with annual reassessment.
• Generally, products licensed under this program have an ‘Orphan Drug’ designation.
  
  
• Orphan Designation
• Compassionate Use
• Hospital Exemption

• Fast Track Designation (FTD)
  
  
• This program was developed to expedite the development and review process of medicines intended for severe or life-threatening conditions where clinical or nonclinical data indicate these medicines address an unmet medical need.
• Potentially eligible for Accelerated Approval and Priority Review.
• Developers are permitted to market their products while continuing to conduct confirmatory studies to obtain full marketing approval.
• A priority review reduces the therapy approval process from ten months to just six months.
  
  
• Breakthrough Therapy Designation (BTD)
  
  
• Expedited development and review process for ATMPs designed to treat severe life-threatening conditions with at least one clinically significant endpoint over currently available medicines.
• Eligible for priority review and accelerated approval.
  
  
• The Cures Act has established an expedited product development program called the ‘Regenerative Medicine Advanced Therapy (RMAT) Program.’
  
  
• The RMAT designation offers an option for expedited evaluation of the product.
• If the biological component provides the primary mode of action, a combination product can also be eligible for RMAT designation.