Risk and Regulation of Novel Therapeutic Products: A Case Study of Biologics and Emerging Genetic Technologies (CIHR MOP 74473). 

The Health Products and Food Branch, the regulatory arm of Health Canada is responsible for the protection and management of risks for the entire range of drugs and therapeutic devices.  The determination of regulatory policy, the reach of regulatory activity, and the scientific and ethical competencies of regulators are central to the debate about the nature of a just society and the relative importance of public health issues.  But, for many Canadians, regulatory processes are obscure, unclear, unfathomable.  This project allowed the TRRU team to describe a set of regulatory actors and their tasks, map the regulatory territory of scientific evidence and policy decisions, and illustrate how a regulatory system adapts in response to external factors, rapidly emerging scientific and policy changes, and contingency.  Graham's primary field site was the Biologics & Genetic Therapies Directorate of the Health Products and Food Branch, where she sought to dispel the prevalent image of "the black box" of regulation.

This study followed the step-by step process of product submission and regulatory review as teams of research scientists, biologists, medical officers, and technicians, equipped with state-of-the-art technologies and instrumentation, tweak basic science in response to regulatory needs. Scientists, clinical evaluators and policy advisors review submissions, sample consistency, conduct extensive chemistry and manufacture confirmatory tests, reanalyze data and check back with the sponsors for missing data or for any queries they might have about the submitted evidence. Decision-making frameworks have been established by the various parties, but decisions to submit, re-submit or finally withdraw the application are almost completely in the hands of the sponsor.  Inevitably the actors on both sides must balance legislated deadlines with partial data, and weigh individual and public health safety against public and industry desires.  The oft-heard expressions that "biologicals are illogical" and "biologics are different" underlie the special status these categories of therapies and diagnostics hold. Biologics are heterogeneous products involving inherently process-related events unlike the purity/impurity profile of a chemical drug product. Unlike synthetic pharmaceuticals, complex biologics require stringent containment conditions to prevent adventitious agents and impurities during cell culture based production. Antibody response to a protein presents immunogenicity issues. Protein products from molecular pharming present emerging issues, as do combination products which represent hybrid chemistry/biologic/medical device crossovers challenging existing classifications. Unlike a pill that can be stored on a shelf for five years, many biologicals last only days, perhaps only hours in the case of radiopharmaceuticals.

The principle objectives of this five-year project (2004-2009) were:

• to follow a sample of emerging scientific technologies (biologics, radiopharmaceuticals and new genetic therapies) through the stages of regulatory approval in order to describe, analyze and portray the structure and practices of regulatory scientists, clinicians, policy analysts and industry sponsors;

• to explore the dynamics of scientific, social and moral encounter among these actors; and

• to document and examine the relations between science and policy within the regulatory framework at BGTD and to locate policies and local decisions within an expanded international context of economic and technological innovation and harmonization.
  

Principal investigator:

• Janice E. Graham

Postdoctoral researchers:

• Mavis Jones is conducting ethnographic research within the Office of Consumer and Public Involvement in the Canadian Health Products and Food Branch. Her work focuses on the implementation of the Branch's Review of Regulated Products: Policy on Public Input. Mavis' work is funded by a CIHR Postdoctoral Fellowship (Institute of Genetics - Ethics, Law and Society).

• Rob Nuttall is examining the approval and post-market surveillance of biological therapies in Canada. While the pharmaceutical industry touts these products as being the future of health care, Rob's research questions their innovation and examines their safety, revealing fault lines between Health Canada's regulatory intent and industry practice.

• Emma Varley joined the TRRU team in September 2008 to commence a Killam postdoctoral fellowship under the Risks & Regs project. 

• Marylène Dugas is conducting ethnographic research in Burkino Faso. She addresses the relationship between global health, disease and society. Her research explores the bioethical issues of transfer of knowledge necessary to obtain the informed consent in clinical research on the African community. Her projects are located at the junction of critical anthropology and health sciences, combining basic research and empirical research, and testing models that incorporate approaches of medical anthropology in the field of global health.

• Christina Holmes' postdoctoral research focused on plant molecular pharming, or the
  cultivation of plants for biomolecules of use to industry, medicine or science, rather
  than for traditional uses of food, feed or fibre; a growing area of biotechnological
  research employing techniques of genetic engineering. Molecular pharming represents a new frontier for regulatory regimes, who must incorporate a variety of complex issues, while at the same time ensuring the safety, efficacy, and quality of the products produced
  through novel methods. Her ongoing research (as an Assistant Professor in the Sociology
  and Social Anthropology Dept. at Dalhousie) focuses on the tension between the
  development of molecular pharming research and regulatory requirements.

• Farah Huzair investigates the evolving Subsequent Entry Biologics (SEB) regulatory pipeline and the impacts of new regulation on the innovation, development and production of SEB vaccines. The study has a qualitative methodology and will involve a comparison of two vaccine cases in Canada. The overall aim of the project is to be able to discuss the implications of the evolving regulation for the Canadian SEB vaccine industry.

• Amrita Mishra's work involves an ethnographic examination of the new questions and issues for the field of cervical cancer prevention with the availability of vaccination against high risk HPV. Contending views on vaccination seem to take on a keener significance in the case of Nova Scotia, a Canadian province with one of Canada's well established and organized cervical cancer screening programs (the other is British Columbia). The QEII Health Sciences Centre is one of the actors that has been involved in clinical trials of GlaxoSmithKline's Cervarix. Amrita will examine the work of the infectious disease specialists both at the laboratory end and at the clinical application end. She plans to interview people who enter clinical trials and vaccination drives or admit their children to it. Her methodology would also involve an ethnographic engagement with the laboratories at Dalhousie Med/Dalhousie University involved in or interested in virally induced oncogenesis, cancer biomarkers, and vaccination.