There have been breathtaking developments in life science and modern biotechnology in recent years. Scientists have developed novel ways to handle, manipulate and deliver biological materials, including genes, tissues and cells, into the body to combat a wide array of symptoms and diseases. The developments have been reflected by increased funding, with the European Commission’s Research Framework VI setting aside e17.5bn (£12.22bn) to fund research projects in biotechnology and genomics.
At present, most of the drug therapies are based on small molecules or products with defined molecular structures. Certain chronic conditions or serious genetically predisposed conditions are, however, inadequately addressed by existing drugs or surgical interventions. Novel biotechnology products, based on genes, cells and tissues, may offer an alternative therapeutic approach.
Changes to regulation
These scientific endeavours present new challenges to the existing regulatory framework and stimulate debate on the bioethics of using the new technology platforms.
For example, interests in the development of embryonic stem cell research and its relationship with cloning have sparked great controversies, some of which have precipitated in challenges before courts. In the UK, the ProLife Alliance has tested the validity of the UK Government’s long-held position that the primary legislation was sufficient in scope to encompass any proposed development of human cloning. However, the Government has acknowledged that the technique used in the creation of Dolly the sheep, based on cell nuclear replacement (CNR), was different from the procedure as set out in the Human Fertilisation and Embryology Act 1990. The case brought before the English Courts, which was subsequently settled in the House of Lords, was run by and largely on whether the process of CNR falls within the scope of the primary legislation.
In December 2001, the UK enacted the Human Reproductive Cloning Act 2001, which “prohibits the placing in a woman of a human embryo which has been created otherwise than by fertilisation”. However, experimental research on embryonic stem cells continues to be regulated by the UK Competent Authority. The European Group on Ethics in Science and New Technologies, which advises the Commission, stated in its 1998 report that there was an urgent need to regulate, based on appropriate ethical and scientific considerations, the conditions under which human tissues circulate within the European market. The recommendations made in this report were taken into account in the drafting of a proposed directive for regulating the procurement and storage of human tissues and cells for their clinical application.
Intellectual property issues
The intellectual property position critical to the development of stem cells also presents new challenges. In the US, any type of stem cell, regardless of whether the source is human or non-human, is patentable, provided the invention fulfils the requirements for patentability.
The European position is more restrictive. In the UK, for example, the Patent Office distinguishes stem cells that can be used as the source material for creating various cell or tissue types (pluripotent) and those that are capable of developing into an entire human body (totipotent). The latter are not patentable according to the Patent Office.
This fine distinction seems to be artificial from a scientific perspective and perhaps influenced by the bioethical considerations. The well-known ‘Edinburgh’ patent in its original form described a method of using genetic engineering to isolate stem cells, including embryonic stem cells, from more differentiated cells in a cell culture in order to obtain pure stem cell cultures. The patent has now been amended to exclude human or animal embryonic stem cells, but still covers other types of stem cell in order to render it compatible with the European Patent Convention. The Opposition Division of the European Patent Office explained that it was bound in its decisions by the European Patent Convention and the applicable international and European law.
Brave new world
Despite all these scientific and research developments, regulatory laws may not necessarily move at the same pace. And yet life sciences industries, including those developing pharmaceuticals and medical devices, are among the most highly regulated.
Navigating an ever-changing regulatory landscape is becoming an increasingly complex and essentially unavoidable task for industry in its research and development programmes. The European regulatory laws are particularly complex in that they have undergone amendments over the years and are still evolving to respond to the enlargement of the EU and changes resulting from new scientific developments.
At a policy level, the potential of life sciences and biotechnology as the next wave of the knowledge-based economy is fully recognised by the Commission in its recent communications. In order to realise the potential opportunities of life sciences and biotechnology, there is a need to develop sustainable and responsible policies to address a number of key issues, including the ways to improve the Community Regulatory Framework, which governs a diversity of products that utilise biotechnology processes.
It is acknowledged that there is already existing European Community legislation that oversees the authorisation of pharmaceutical products and the release and marketing of products consisting of, or derived from, genetically modified organisms. An improvement in the coherence, transparency and efficiency of the Community Regulatory Framework, emphasising the importance of the scientific component in risk evaluation, is crucial to patient safety. This strategy will engender greater consumer confidence in the development of novel technology products and increase the competitiveness of Europe in an increasingly global market.
Some of the recommendations have been reflected in the current review exercise of the pharmaceutical legislation, including reinforcing the scientific advice procedure and conditional approval process. At the same time, the EU is also in the process of developing regulatory strategies to encourage the research and development of medicines for rare diseases and for children. Changes have also been made to the pharmaceutical legislation in terms of the regulatory standards applied to the approval of ‘advanced therapy medicinal products’ in the EU, including gene transfer and cell-based therapeutic products. The new regulatory rules for this new class of products also recognise that conventional testing requirements may not always be appropriate due to their unique biological properties. Nevertheless, emphasis has been placed on long-term patient monitoring for avoiding late-stage complications.
In the same manner, the recently adopted directive governing the conduct of clinical trials has been important in harmonising the rules across the EU for protecting trial subjects from exposure to unjustified risk in clinical trials.
A key milestone
The conclusion of the Confidentiality Agreement between the US Food and Drug Administration (FDA) and the EU in September of this year marks an important regulatory milestone in fostering closer global cooperation between two of the most influential regulatory authorities. It is also reflective of the growing recognition of the European authorities in the regulatory arena.
The regulatory approach based on risk management has gained wider acceptance on both sides of the Atlantic in recent years. It is of particular significance for regulating new technology products in view of the recently reported serious adverse events associated with certain types of gene transfer products in the early phase of clinical development. All these adverse events have precipitated reviews by key regulatory agencies around the world in understanding the cause(s) in order to improve the regulatory approval process for novel technology products. Risk management to regulation is particularly pertinent to areas where the science is evolving and in instances where the scientific evidence may be uncertain, incomplete or inconclusive.
In August, the FDA unveiled a five-part strategic plan for improving the performance of the regulatory agency in its overall mission to serve public health needs. FDA commissioner Dr Mark McCellan considered that this strategic action plan was the agency’s coordinated effort to respond to some of the most challenging threats to, and opportunities for, public health that the FDA had ever faced. The initiative includes a science-based risk management approach to ensure consumer protection.
The Commission also indicated, in various communications, the necessity to adopt precautionary principles in regulating certain consumer products, including pharmaceuticals derived from novel technology platforms and medical devices.
In September this year, the European Court of Justice also highlighted the importance of a risk-based approach to achieving the European Community interest of public health protection, and considered risk assessment the bedrock for justifying certain regulatory measures to be taken, subject to legal safeguards based on proportionality. The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, a global regulatory initiative, has also formulated a set of guidelines in addressing risk management to ensure the continued safety of medicines.
Lincoln Tsang is of counsel at Arnold & Porter, London