Interchangeability of biosimilars: A study of expert views and visions regarding the science and substitution.

Healthcare systems have reached a critical point regarding the question of whether biosimilar substitution should become common practice. To move the discussion forward, the study objective was to investigate the views of experts from medicines agencies and the pharmaceutical industry on the science underpinning interchangeability of biosimilars. We conducted an empirical qualitative study using semi-structured interviews informed by a cross-disciplinary approach encompassing regulatory science, law, and pharmaceutical policy. In total 25 individuals with experience within biologics participated during September 2018-August 2019. Eight participants were EU national medicines authority regulators, and 17 had pharmaceutical industry background: five from two originator-only companies, four from two companies with both biosimilar and originator products, and eight from seven biosimilar-only companies. Two analysts independently conducted inductive content analysis, resulting in data-driven themes capturing the meaning of the data. The participants reported that interchangeability was more than a scientific question of likeness between biosimilar and reference products: it also pertained to regulatory practices and trust. Participants were overall confident in the science behind exchanging biosimilar products for the reference products via switching, i.e., with physician involvement. However, their opinions differed regarding the scientific risk associated with biosimilar substitution, i.e., without physician involvement. Almost all participants saw no need for additional scientific data to support substitution. Moreover, the participants did not believe that switching studies, as required in the US, were appropriate for obtaining scientific certainty due to their small size. It is unclear why biosimilar switching is viewed as scientifically safer than substitution; therefore, we expect greater policy debate on biosimilar substitution in the near future. We urge European and UK policymakers and regulators to clarify their visions for biosimilar substitution; the positions of these two frontrunners are likely to influence other jurisdictions on the future of biosimilar use.

Biosimilar competition in the United States: statutory incentives, payers, and pharmacy benefit managers.

Widespread adoption of generic medications, made possible by the Hatch-Waxman Act of 1984, has contained the cost of small-molecule drugs in the United States. Biologics, however, have yet to face competition from follow-on products and represent the fastest-growing sector of the US pharmaceutical market. We compare the legislative framework governing small-molecule generics to that which regulates follow-on biologics, and we examine management tools that are likely to be most successful in promoting biosimilars' adoption. The Biologics Price Competition and Innovation Act established an abbreviated pathway for follow-on biologics, but weak statutory incentives create barriers to entry. Many authors have raised concerns that competition under the biologics act may be weaker than that posed by small-molecule generics under Hatch-Waxman, in part because of legislative choices such as the absence of market exclusivity for the first biosimilar approved and a requirement that follow-on manufacturers disclose their manufacturing processes to the manufacturer of the reference product. Provider skepticism and limited competition from biosimilars will challenge payers and pharmacy benefit managers to reduce prices and maximize uptake of follow-on biologics. Successful payers and pharmacy benefit managers will employ various strategies, including tiered formularies and innovative fee schedules, that can control spending by promoting uptake of biosimilars across both the pharmacy and medical benefits.

Allergen source materials: state-of-the-art.

A variety of positive outcomes can be realized from validation and risk management activities (see Table 4). They are dependent on the participation of multiple functional groups including the quality unit, regulatory and legal affairs, engineering and production operations, research and development, and sales and marketing. Quality risk management is receiving increased attention in the area of public health, pharmacovigilance, and pharmaceutical manufacturing. Recent examples of its regulatory use in our industry include the assessment of the potential risks of transmissible spongiform encephalopathies (TSE) agents through contaminated products], the risks of precipitates in allergenic extracts, and the revision of the potency limits for standardized dust mite and grass allergen vaccines. Its application to allergen source material process validation activities allowed for a practical strategy, especially in a complex manufacturing environment involving hundreds of products with multiple intended uses. In addition, the use of tools such as FMEA was useful in evaluating proposed changes made to manufacturing procedures and product specifications, new regulatory actions, and customer feedback or complaints. The success of such a quality assurance programs will ultimately be reflected in the elimination or reduction of product failures, improvement in the detection and prediction of potential product failures, and increased confidence in product quality.

[Regulation of natural medicines in Israel and abroad].

Hand-in-hand with the public's growing interest in health care, there has been an increasing demand for natural health products considered both safe and medically effective. But many such products have not been shown to meet efficacy and safety criteria and therefore can not be registered as pharmaceuticals. On the other hand, it is quite clear that some products do have pharmacological activity and are being used for therapeutic or preventive effects. In Israel, the marketing rules for food or dietary supplements prevent their manufacturers from claiming medicinal/healing properties that the product might have, and allow only limited health statements. But great demand for these products has created massive publication attributing medicinal indications for products whose quality, efficacy and safety have neither been examined nor proven according to accepted medical criteria. We review the regulation and supervision of natural health products in Israel and other developed countries and find a broad range of opinions about natural health products. They range from acceptance as conventional drugs reimbursable by health insurance, as in Switzerland and Germany, to their status as dietary supplements requiring no significant authorization or supervision, as in the USA. Analysis of the current situation in Israel and the western world would indicate that some natural health products do possess pharmacological activity and therefore manufacturers should be allowed to make limited claims for specified therapeutic properties. A stricter set of registration regulations are needed for proof of safety, efficacy and quality of these products, but more lenient than those for registering a pharmaceutical product.

European regulatory issues.

Current EU regulations do not cover all aspects of the manufacture and control of blood products. Recent legislation coming into force on 1 January 1995 has established the European Medicines Evaluation Agency and introduced revised systems for approving pharmaceutical products, including blood products. There remains a need for comprehensive harmonized legislation covering plasma collection and screening, virus validation studies, and batch release.