Scientific progress in regenerative medicine is advancing at an exceptional rate and holds the promise of previously unimaginable clinical therapies. However, these advancements are struggling to make the transition from lab to clinic, where the pathway is still being developed within the major markets of the US, Europe and Japan.
Regulation is commonly cited as one of the main barriers to the translation of regenerative medicine products. Aspects of the regulators" requirements, such as the assessment of safety, efficacy and characterisation of materials, cells and tissues, can all be addressed to some extent through the development of standards.
Standards are often perceived by companies as a burden , adding unnecessary costs and time delays and even stifling innovation. Typically they are not recognised by the academic community, but actually they can be extremely useful for harmonising definitions, helping to provide a path to commercialisation and can add gravitas to lab-based measurements.
These attributes are particularly important for emerging technologies, such as the development of nanomaterials and controlled nano-textured surfaces for use within regenerative medicine. These technologies can be used, for example, to track and guide the differentiation of stem cells, to tailor surfaces or to provide the building blocks for self-assembling 3D porous matrices that mimic native tissue architectures, all of which are subject to an as yet unknown level of risk, particularly in the longer term.
Regulators have the unenviable task of balancing these risks against potential benefits to patient health and quality of life. In recent years regulatory authorities have been accused of becoming increasingly conservative, with a move from efficacious drugs with relative safety, to safe drugs with relative efficacy.
Gene therapy, cell-based therapy, tissue-engineering and nanomedicine are leading-edge technologies that could pose substantial risks to humans, animals and the environment. They must therefore be subjected to rigorous pre-clinical and clinical testing to establish their safety and efficacy. Unfortunately, a lack of clarity in previous years over the requirements of regulators has greatly hindered innovators wishing to commercialise their products.
The European position was clarified in 2007 when the EC published regulation No 1394/2007 on advanced therapy medicinal products. Legally gene therapies, cell therapies and tissue engineered products are classified as medicines under Directive 2001/83/EC. In the US, the terminology used is different, however, the basic idea behind classification of medical products is similar and is based on the principle mode of action: medicines. act primarily through pharmacological, immunological or metabolic means, while devices. act primarily through physical means.
define products early
Classification has huge implications for the degree of safety and efficacy that must be demonstrated, and hence on the time and cost of development, which can be an order of magnitude greater for medicines than for medical devices - typically five years and an average of £25m as a device, and eight years and around £400m as a medicine. This highlights the importance of a carefully considered regulatory approach early on in new product development.
Standards organisations (BSI, ISO, ASTM International and CLSI) are working closely with regulators (EMEA, FDA and MHRA) to develop industry guidelines to assist with conformity assessment, and ease the process of commercialisation.
BSI and ASTM International have published a number of complementary terminology documents, some of which can be downloaded free of charge. These cover all aspects of this multidisciplinary topic, including the bio-nano interface, and provide a common lexicon, not only for researchers working within the field who may not be aware of the definitions of terms outside their area of expertise, but also for regulators and legal experts.
The current portfolio of international standards consists mainly of "standard guides". These documents are intended to provide an overview of a particular measurement issue, such as characterisation of tissue scaffolds and methods for assessing cell viability, indicating the pros and cons of the range of available techniques. As such, the documents provide an excellent introduction to what are often complex issues that haven't yet been resolved. Such guides are intended to be understood by experts, e.g. cell biologists, engineers and material scientists who may be working outside their field or who may require a broader understanding of the subject as a whole.
Over the next decade the current standards portfolio will expand significantly as knowledge of regenerative medicine grows and will move towards more "prescriptive" documents as and when the need arises. These will contain descriptions of test protocols with which commercially available products may need to comply, helping to establish the commercial markets and clinical uptake of regenerative medicine products. Standards today are starting to address some issues faced by the regenerative medicine community concerning safety (e.g. test methods for assessing in vivo toxicology of nanoparticles), consistency (measurement of nanoparticle sizes) and product efficacy (e.g. cartilage repair, cell viability).
Selected standards
- PAS 83 Guidance on standards, standardised methods and regulation for cell-based therapeutics, from basic research to clinical application
- PAS 84 Regenerative medicine. Glossary
- ASTM F2451 - 05 Standard Guide for in vivo Assessment of Implantable Devices Intended to Repair or Regenerate Articular Cartilage
- ASTM F2450 - 09 Standard Guide for Assessing Microstructure of Polymeric Scaffolds for Use in Tissue Engineered Medical Products
- ASTM F2739 - 08 Standard Guide for Quantitating Cell Viability Within Biomaterial Scaffolds
Useful links
- ASTM International
British Standards Institution
Clinical and Laboratories Standards Institute
ISO - International Organisation for Standardisation
MHRA - Medicines and Healthcare products Regulatory Agency (UK)
