The regulator's perspective: How should new therapies and follow-on products for MS be clinically evaluated in the future?

BACKGROUND: Although there is still no cure for multiple sclerosis (MS), the introduction of several innovative drugs with modes of action different from that of the existing drug arsenal and the progress in monitoring disease progression by imaging and using biomarkers are currently causing a knowledge surge. This provides opportunities for improving patient disease management. New therapies are also under development and pose challenges to the regulatory bodies regarding the optimal design of clinical trials with more patient-focused clinical endpoints. Moreover, with the upcoming patent expiry of some of the key first-line MS treatments in Europe, regulatory bodies will also face the challenge of recommending marketing authorisation for generic and abridged versions based on appropriate requirements for demonstrating equality/similarity to the innovator's product. OBJECTIVE: The goal of this article is to improve the understanding of the relevant guidance documents of the European Medicines Agency (EMA) on clinical investigation of medicinal products and to highlight the issues that the agency will need to clarify regarding follow-on products of first-line MS treatments. CONCLUSION: Today, it is clear that close collaboration between patients, healthcare professionals, regulatory bodies and industry is crucial for developing new safe and effective drugs, which satisfy the needs of MS patients.

Scientific considerations for complex drugs in light of established and emerging regulatory guidance.

On March 9, 2012, the New York Academy of Sciences brought together experts representing a variety of perspectives--including academic, industrial, regulatory, as well as those from physicians and consumers--to discuss considerations for the non-biological complex drug (NBCD) regulatory approval pathway, given the emerging regulatory guidelines for biosimilars (follow-on biological complex drugs). Some of the organizers of the conference expressed their belief that NBCDs share a number of characteristic features with biologicals: the structure cannot be fully defined by the available (physicochemical) analytical tests, and quality assurance is based on in-depth knowledge, consistency, and control of the production process. However, their view on NBCDs was not universally accepted among the experts who participated in the conference. Plenary sessions addressed the most recent regulatory developments, experimental design, interchangeability, and immunogenicity issues for follow-on versions of complex drugs from the perspective of key audiences, including industry, regulatory agencies, physicians, and consumers. This report summarizes these various perspectives on NBCDs and the scientific and regulatory considerations associated with complex drug categories.

Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process.

Exercise involving lengthening muscle actions, such as downhill running, results in delayed onset muscle soreness (DOMS), which may be attributable to reactive oxygen species (ROS). Although exercise causes oxidative stress, any link between ROS and DOMS remains speculative. There is emerging evidence to suggest that ROS play an important physiological role, assisting in the recovery process and protecting the cell from future damage; however, this has not been fully established. Despite this uncertainty as to the precise role of ROS, attempts to prevent post-exercise ROS production through antioxidant intervention are still common. The study investigated the effects of ascorbic acid supplementation on ROS production and DOMS following downhill running. Subjects were assigned to two groups. The ascorbic acid group (group AA) received 1 g ascorbic acid 2 h pre-, and for 14 d post-downhill running, whilst the placebo group (Pl group) received a placebo. Blood samples were drawn pre-supplement, pre- and post-exercise, and then 1, 2, 3, 4, 7 and 14 d post-exercise for analysis of ascorbate, malonaldehyde and total glutathione. DOMS was assessed using a visual analogue scale and pressure algometry. Muscle function was assessed using isokinetic dynamometry. Plasma ascorbate was elevated throughout in group AA compared with the Pl group. Downhill running resulted in DOMS in both groups. Muscle function was impaired post-exercise in both groups, although a delayed recovery was noted in group AA. Malonaldehyde increased 4 d post-exercise in the Pl group only. Ascorbic acid supplementation attenuates ROS production following downhill running, without affecting DOMS. Furthermore, ascorbic acid supplementation may inhibit the recovery of muscle function.