Regulation and Standards

Several countries have enacted legislation to ensure the quality, safety and efficacy of cell and gene therapies:

U.S. Code of Federal Regulation Title 21 Part 211

EU, Directive 2001/83/EC (as amended by Regulation (EC) No 1394/2007)

Japan, Pharmaceuticals and Medical Devices Act (PMD Act) (2014)

Under these statutes, manufacturers are required to operate under GMP quality systems, ensuring that active pharmaceutical ingredients (APIs) ‘meet the requirements for quality and purity that they purport or are represented to possess’.7

As part of GMP compliance, cell and gene therapy manufacturers are expected to control the quality of all ancillary materials used in their production processes according to a risk-based specification, an approach that reflects the importance of ancillary materials in supporting API quality.

At the international level, several standard development organizations (SDOs) such as the International Organization for Standardization (ISO) have begun to develop standards covering ancillary materials. Ultimately, ancillary materials standards represent a shared language, reducing the burden of risk-based materials qualification, simplifying and de-risking product selection, and supporting regulatory compliance by all parties. Below is a selected list of existing standards:

  • General
    • USP <89> Enzymes used as ancillary materials in pharmaceutical manufacturing
    • USP <92> Growth factors & cytokines used in cell therapy manufacturing scaffold human placental connective tissue matrix allograft
    • USP <1043> Ancillary materials for cell, gene and tissue-engineered products
  • Standards for human-derived materials
    • ASTM F2027-16 Standard guide for characterization and testing of raw or starting materials for tissue-engineered medicinal products
    • USP <92> Growth factors & cytokines used in cell therapy manufacturing scaffold human placental connective tissue matrix allograft
    • ICCBBA ST-002 ISBT 128 Global standard: Standard terminology for medicinal products of human origin
  • Standards for animal-derived materials
    • USP <1024> Bovine Serum
    • USP <90> Fetal bovine serum quality attributes & functionality tests
  • Standards for recombinant proteins
    • USP <130> Protein A
    • USP <89.1> Collagenase I
    • USP <89.2> Collagenase II
    • USP Trypsin recombinant porcine
  • Gene vector standards
    • ATCC-VR1616 rAAV (Recombinant adeno-associated virus) serotype 2 reference material
    • ATCC-VR1816 rAAV (Recombinant adeno-associated virus) serotype 8 reference material
    • ATCC RSM VR-1516 Adenovirus Type 5 reference material
    • ATCC MBA-331 TR-UF-11 vector plasmid
    • ATCC VR-539D Molecular standards for herpes simplex virus (HSV-1)

Akron has long engaged in the process of standards development, recognizing the importance of mitigating risk through the development of common nomenclature and standard definitions. Learn more about our ongoing efforts to foster greater standardization.

Read the recent guidance document published by the Center for Biologics Evaluation and Research (CBER) explaining the importance of standards in the development and regulatory control of novel therapies.