With two workshops on the issue now completed, the FDA should be in a position to move the process along and press on with its promised background document on follow-on protein products, a position paper and guidance on immunogenicity and other issues.
"There is no reason to delay consumer access to affordable biopharmaceuticals when sound science supports their approval under a shortened and less costly abbreviated approval pathway," said the Generic Pharmaceuticals Association (GPhA) in an open letter to the agency.
Generic biopharmaceuticals - referred to by the FDA as 'follow-on' protein products, are expected to yield tremendous cost savings for healthcare systems around the world. However, there have been difficulties in developing standard testing procedures to prove that copies of biologic drugs that are off patent are bioequivalent - as safe and effective - as their branded counterparts.
The GPhA's letter also gives its position on topics - including biological characterisation, pharmacokinetics and pharmacodynamics, immunogenicity, animal pharmacology-toxicology, and clinical safety and efficacy - considered to be at the heart of the matter.
These scientific topics emerged at an FDA-organised workshop on follow-on protein products in February, at which the agency reiterated its overarching principle in this area, namely that structure equals function. In other words, if companies can demonstrate that their 'biogeneric' is identical in structure to the brand, they can win approval without having to carry out exhaustive and expensive safety and efficacy studies.
The baseline of this approach starts with characterisation, according to GPhA CEO Kathleen Jaeger. Current analytical capabilities already allow for the characterisation of most protein products, as well as the glycan groups that can have a dramatic impact on their activity, and are already being used by biotech companies to validate changes in production processes or drug delivery formats for their biopharmaceuticals.
"These analytical approaches, combined with FDA's expertise and judgment, allow both the applicant and FDA to make a risk assessment and to determine if additional testing is necessary, according to Jaeger. This includes immunogenicity, an important factor determining a therapeutic protein's biological activity, safety and efficacy.
However, the GPhA is concerned that some speakers at the FDA workshop suggested levels of immunogenicity testing that go beyond what is required for the initial approval of a biologic drug.
After a comprehensive analytical comparison, suggests the GPhA, other testing may be necessary on a case-by-case basis, and depending on factors such as the marketing history of the brand name product, its safety profile, dose and indications. The comparative performance of a biogeneric could be confirmed using a suite of testing approaches, such as PK/PD, animal pharmacology-toxicology testing and immunogenicity, as well as targetted clinical safety and efficacy testing in some cases.
This view ties in with comments by Charles Cooney, who chairs the Advisory Committee for Pharmaceutical Science at the FDA, who recently noted: "It is the incorporation of prior knowledge, innovation of new technology and new methods, and publicly available data that defines the operative space we work in."
Marketed biopharmaceutical products account for approximately $30 billion (€23bn) in US sales and 12 per cent of total pharmaceutical sales. By 2010, sales are expected to exceed $60 billion, according to the GPhA, which points out that the average cost to a major US employer for a one-day supply of biopharmaceutical drugs is $45, while traditional drugs cost an average of $1.66 per day. Generic medicines can cost up to 80 per cent less than their brand counterparts.
The industry group also believes that the FDA should also allow appropriate marketing applications for biogenerics while this process is ongoing, pointing out that it has already permitted albumins and allergenics, among other products, to come to market with abbreviated data packages.