Reconciling the requirements of the US Food and Drug Administration and the European Medicines Agency (EMEA) can be a headache
for large, well-established biotech organizations and a matter of survival for early-stage companies on a short financial
leash. It's a delicate balance: companies do not want to maintain expensive and burdensome dual systems for meeting the requirements
of both agencies, nor do they want to under-invest to the point that their investigational new drugs are rejected by either
The FDA's July 2008 release of "Guidance for Industry: cGMP for Phase 1 Investigational New Drugs" (cGMP1)—whose EMEA counterpart
is "Good Automated Manufacturing Practices, version 5" (GAMP 5)—points up the dilemma anew. In the absence of an explicit
harmonization document, the best approach to the problem is to understand the philosophical differences between the two agencies,
examine the differences in the documents in light of those philosophical differences, and consider the most promising avenue
for reconciling them: Quality by Design (QbD).
Sandy Weinberg, PhD
PHILOSOPHY: SAFETY VERSUS ACCESS
To some extent, all regulatory agencies are involved in a dynamic tension between competing and often incompatible goals.
The EMEA and the FDA are charged by their respective governments to both ensure public access to drugs and ensure the safety
of those drug products. If the agency focuses on maximizing the public's access to potentially beneficial drugs, it adheres
to a policy of promotion, helping to ease the approval and the testing process. If, on the other hand, safety is the agency's
primary focus, it tends to restrict access by maximizing pre-release analysis and testing.
For historical, legal, and political reasons, the FDA has traditionally emphasized safety (resulting in a relatively small,
but presumably safe, pharmacopeia), whereas the EMEA has tended to maximize access, allowing patients and their physicians
greater flexibility in making their own determinations of safety. As a result, the EMEA is generally seen by the industry
as cooperative, helping to get drugs to market, whereas the FDA is often viewed as obstructionist, reducing access in the
name of safety.
Not surprisingly then, the EMEA focuses on the final drug product as tested in Phase 1 (and other phases), while the FDA spends
considerable energy and regulatory capital examining the active pharmaceutical ingredient (API) and raw materials that precede
the final product. In effect, the EMEA tests for purity, and the FDA audits and back-traces for the same assurances. In other
words, the EMEA emphasizes the end product, and the FDA emphasizes the process.