Health-related markets in Canada amount to approximately 10% of the GDP. In 2006, pharmaceuticals accounted for an estimated 17% of all health care spending in Canada.1 Generic pharmaceuticals have an important role in drug costs, thus, it is an important subject when discussing this issue.
While pharmaceutical drugs are composed of molecules that generally can be synthesized once the chemical formula is known, biological products are composed of larger and more complex structures that are not easily identified or characterized. In some cases a biologic may consist of a mixture of such large complex structures. Biologics are manufactured through the use of animals, plants or micro-organisms such as bacteria or viruses and then purified. Examples of biologics include blood and blood components and gene therapy products.
In Canada, biologics are drugs listed on Schedule D to the Food and Drugs Act and include products such as drugs, other than antibiotics, prepared by micro-organisms. In Canada, the Biologics and Genetic Therapies Directorate ("BGTD") of Health Canada regulates biologics under the Food and Drugs Regulations. Careful attention is paid to raw material controls, product purification, product testing and viral/bacterial inactivation to prevent risks caused by the growth of viruses or the initial presence of pathogens.
Manufacturers provide information to verify that the biologic meets quality, safety and efficacy requirements, and that the benefits outweigh the risks of the biologic for its use. BGTD tests intermediates and final products. Similar to pharmaceuticals, a notice of compliance ("NOC") and drug identification number ("DIN") are issued when the products are authorized for sale or distribution in Canada. BGTD regulates biologics under Divisions 1, 1A, 2, 4, 5 and 8 of Part C of the Food and Drugs Regulations.
The process involved in obtaining production or distribution of a drug by a generic is well established. However, the approval procedure for a generic biologic is more involved than the filing of an abbreviated new drug submission, as can be done for a generic drug. The term "subsequent entry biologic" is a term currently used by BGTD to describe a biologic product to be used by a generic. Manufacturers of subsequent entry biologics are required to file a new drug submission ("NDS") for review. An analysis of the comparability and details of the clinical data is then made. An NDS for a subsequent entry biologic requires detailed information such as a clinical package demonstrating the safety and efficacy of the subsequent entry biologic, including comparative studies between it and innovative products, and pharmacodynamic data to demonstrate comparable bioactivity based on clinically relevant parameters.
All animals from which drugs are prepared and preserved are to be under the direct supervision of competent medical or veterinary personnel, kept in quarantine for at least seven days before use, and healthy and free from infectious disease.
Not surprisingly, the labeling requirement for biologics includes detailed information, such as a statement that the drug shall be stored at a temperature of not less than 2°C and not more than 10°C, unless the Minister has received evidence demonstrating that such a statement is not required.
One challenge of subsequent entry biologics is, given the complexity of the biologics, that the production of copies is complicated. Particularly where the biologic is a mixture of compounds, the challenge of establishing the generic version to be equivalent to a previously approved product is very difficult. This is the basis for the current policy of requiring a more detailed NDS filing for generic biologics.
As analytical techniques and computational analysis continue to improve in sensitivity and power, the ability to reliably characterize increasingly complex structures is becoming available. This improved ability to characterize biologics should not only make it easier for generics to copy biologics as their patent protection expires, it should also make the task of government agencies in evaluating generic biologics less complex.