Regulation and harmonisation of genomic data

21 CFR 312.23, 21 CFR 314.50, and 21 CFR 314.81 codify the regulations and guidelines regarding genomic data and applications to the USFDA. This matrix of genomic data submissions requirements and voluntary guides are confusing and difficult to navigate.

Some of the guidelines provide standards for investigational new drug applications; others for new (or unapproved) drug applications (NDAs) and biological licence applications (BLAs), and still others are directed to previously approved NDAs and BLAs. These standards vary for known valid biomarkers, for probably valid biomarkers, and for exploratory or research pharmacogenomics data.

The good news is that the navigated pathways established for a USFDA submission need not be re-explored for a European Medicine Agency (EMEA): USFDA, the European Commission and the EMEA have agreed to joint standards, review and acceptance of voluntary reporting data. In the area of genomic regulation, international harmonisation is a reality.

Targeted treatments with fewer adverse events and treating the right patient with the correct drug are the promises of genomics research. The clinical application of genomics for biologics, pharmaceuticals and devices is still in its infancy. Some of the best-known applications include screening for response to certain pharmaceuticals and biologics used to treat cancer.

The USFDA is constantly performing a balancing act, trying to assure the safety of pharmaceutical (and other) products while simultaneously maximising public access to those products. Complicating that balance is the recent emergence of end-user cost as a primary factor in access: with rising health-care costs taking an increasing share of family budgets, any unnecessary expense added to a pharmaceutical product makes that drug less accessible to a growing curve of users. This equation has two relevant aspects: first, while genomic data can potentially increase the safety of a product, it does represent a significant cost-increasing access deterrent. But second, and perhaps more important, the Voluntary Genomic Data Submission Program (VGDS) represents a major cost-savings trend.

VGDS is arguably the most important example of cooperation between the European Commission/EMEA and the USFDA. The Guidance for Industry: Pharmacogenomic Data Submissions (FDA) and Guideline on Pharmacogenetics Briefing Meetings (EMEA) (both dated 2006) both represent common principles for the voluntary submission of genomic data. In practical terms, it is possible and practical for a pharmaceutical company to prepare parallel documents simultaneously, differing only in minor format aspects. The VGDS program is the Holy Grail of cost containment: a major step toward common regulatory submissions. A drug company can request a joint VGDS meeting, working with FDA and EMEA simultaneously in a single setting.

Consider the alternative. With all too many regulation submissions - new drug applications, pre-market approval device applications, biologics licence agreements, et cetera - standards and procedures differ so significantly that an applicant is forced to make two separate petitions to the FDA and the EMEA. Because of the time required to assemble such a submission, the desirability of feedback from one agency before approaching the second, and the scheduling issues surrounding product launch, most organisations opt to submit sequentially. The result is long delays and added preparatory expenses that are ultimately passed on to the consumer and negatively impact on financial access to products. If NDA requirements, review procedures and standards were joint, and if decisions for approval were made by a joint committee, a single submission could substantially reduce review time and related expenses. After years of negotiation by the Organisation for Economic Co-operation and Development (OECD), an example and test case of how that cooperation might function has finally evolved.

The VGDS model divides data into three submission categories: ‘known biomarker’, ‘probable biomarker’ and ‘exploratory or research data’. Within each category, separate guidelines apply to investigational new drugs (INDs), new NDAs/BLAs and existing NDAs/BLAs. The three-by-three matrix creates nine separate procedures.

Generally, then, the FDA and EMEA are asking for data if the biomarker is known in support of INDs, NDAs and BLAs; and that annual reports on NDAs/BLAs include summaries of known biomarker genomic data and suspected or probable biomarker genomic data. Meeting to discuss these requirements, and the definition and hence implementation of these requirements, are joint FDA/EMEA activities. While a drug company may be submitting separate reports to FDA and EMEA (if separate NDAs have been filed) those reports can be identical and will be evaluated according to common guidelines.

Genomics used for risk stratification, therapy response and susceptibility is one of the most promising areas of medical research. The fact that the FDA and EMEA have decided to harmonise in this area first is laudable. The impact of harmonisation is decreased cost of development, and increased access to breakthrough diagnostics and targeted treatments, which produce fewer adverse events. Harmonisation for biologics and pharmaceuticals is welcomed.