Regulation of Vaccines: Strengthening the Science Base

Journal of Public Health Policy,  2004  by Milstien, Julie B

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In contrast to the safety precautions used in field trials, where all safety tests were repeated in three different laboratories, no similar controls nor confirmation of consistency of production or inactivation were required for commercial manufacture. The only legal requirements for licensing of the six polio vaccine manufacturers were written protocols for vaccine production and safety testing. The protocols filed by the manufacturers did not contain enough detail to evaluate vaccine safety.

Current GMP procedures would have prevented the Cutter incident, through requirements for test validation, complete protocols for safety evaluation, manufacturer inspection, and required reporting of lots not meeting specifications. Regulation based on testing alone would not suffice.

2. Regulatory approach. At its 42nd meeting, the WHO Expert Committee on Biological Standardization approved Guidelines for national authorities on quality assurance for biological products (17), codifying for the first time at the global level the expectations of the regulatory process. This was followed by Regulation and licensing of biological products in countries with newly developing regulatory authorities in its 45th Report (18), which prioritized activities for countries just beginning to develop regulatory authorities. The WHO document defined five essential regulatory functions in addition to laboratory testing: licensing and registration; surveillance for field impact (including adverse events and lack of efficacy); lot release; enforcement of GMP compliance; and clinical trials authorization and data evaluation. A subsequent report, based on country inputs, spelled out performance indicators for each of these functions (19). A similar range of functions has been outlined in recent guidelines on combination vaccines issued by the FDA (20), as well as in other documents found in reference 2. Figure 1 illustrates how the regulatory functions follow the product development and use process.

THE CURRENT REGULATORY SITUATION

Changes in the regulatory process

Thanks to vaccines against many killer diseases of childhood, the incidence of these diseases has greatly decreased. As risk from disease has declined, the public has increasingly expected "zero risk" from the protective measures as well, at least in the industrialized world. This has led to a litigious atmosphere, escalating regulatory decisions, and a tendency for the more developed regulatory agencies to be extremely conservative in their approaches, exemplified by rigid application of guidelines, a tendency to higher expectations from manufacturers, larger clinical trials, and greater margins of safety.

Regulators also put more emphasis on raising GMP compliance levels, even if the required changes may not be strictly necessary for a pure, safe and efficacious product. This usually increases the cost of compliance for manufacturers. Accordingly, several manufacturers have left the industry rather than make the necessary investments for full compliance.