Anti-tumor necrosis factor biosimilars and intended copies in rheumatology: Perspective from the Asia Pacific region.

Although anti-tumor necrosis factor (TNF) agents have greatly improved the management of rheumatic diseases, their cost limits access to many patients throughout the world. As a result, patients and clinicians have turned to biosimilars to provide similar efficacy at a lower cost. Many of the regulatory guidelines in the Asia Pacific region are largely based on those of the European Medicines Agency and the World Health Organization; however, there are variations between countries. Additionally, in some countries, intended copies are available that were approved prior to the development of guidelines and have not fulfilled the requirements of a biosimilar. We review the various regulatory requirements for biosimilars in the Asia Pacific region, the anti-TNF biosimilars and intended copies approved in the region, and whether clinical data are available for these agents. We discuss concerns about the need for additional regulations and education, and we provide recommendations for a multidisciplinary pharmacovigilance approach that closely monitors the safety of biosimilar use.

Biosimilars in Oncology in the United States: A Review.

IMPORTANCE: Biosimilars are biological medicines that contain a highly similar version of the active substance of an already approved biologic reference product. The availability of biosimilars might provide an opportunity to lower health care expenditures as a result of the inherent price competition with their reference product. Understanding how biosimilar cancer drugs are regulated, approved, and paid for, as well as their impact in a value-based care environment, is essential for physicians and other stakeholders in oncology. OBSERVATIONS: Important structural and regulatory differences exist between biosimilar and generic medications. Minor differences in clinically inactive components with no clinically meaningful differences between biosimilars and their reference biologic are allowed. A biosimilar uses the same mechanism of action as the reference biologic, and its condition of use is the same as the approved indication, although extrapolation is permitted across indications under regulatory guidance. A biosimilar has to have a similar route of administration, dosage, and strength as the reference biologic. As patent expiration of multiple cancer biologics will occur in the next few years, more biosimilars might enter the market. Whether the approval and use of biosmilars as replacements for these heavily prescribed reference biologics will ultimately lead to cost savings is unknown and requires longer follow-up. Two biosimilars with an oncology supportive care indication are currently approved in the United States; both are myeloid growth factors. CONCLUSIONS AND RELEVANCE: The financial impact of generic drug competition can be dramatic, but significant differences in regulatory and development processes between generics and biosimilars limit such comparisons and likely present significant challenges for biosimilar approval and adoption in the US market. However, a value-based care environment and their cost-savings potential make biosimilars an attractive option for the therapeutic arsenal. Oncologists' understanding of biosimilars is critical to moving forward.

Hot Topics in Primary Care: Demystifying the Differences: Follow-on Biologics, Biosimilars, and Generics.

Sponsors of follow-on biologics can submit their applications for approval by the US Food and Drug Administration (FDA) under 2 distinct pathways. The submission pathway is determined by the pathway previously used by the reference biologic product, which is the biologic product upon which the follow-on product relies for evidence of safety and efficacy.

Biosimilar Naming Conventions: Pharmacist Perceptions and Impact on Confidence in Dispensing Biologics.

BACKGROUND: The approval of the first biosimilar in the United States has placed increased pressure on the FDA to provide guidance on the naming convention that will be assigned to current and future biosimilars. The release of the FDA draft guidance on nonproprietary naming of biosimilars in August 2015 established a naming convention for all biologic products, including biosimilars. However, the draft guidance is nonbinding while the FDA continues to receive input from stakeholders, and it does not address the naming convention that will be used for products designated as interchangeable biologics. OBJECTIVES: To (a) determine pharmacist perceptions of biosimilar naming conventions and their impact on confidence to dispense biosimilars and (b) measure the burden that is created by laws and regulations requiring pharmacists to complete postdispense notifications. METHODS: A cross-sectional survey of 781 members of the Academy of Managed Care Pharmacy and the Hematology/Oncology Pharmacy Association was conducted using an online survey software program. RESULTS: Participants reported preferring a biosimilar naming convention that uses a nonproprietary base with a designated suffix (48.1%), compared with the use of a nonproprietary base alone (26.3%), nonproprietary base plus a prefix (14.2%), or a unique brand name (11.4%). However, when participants were asked to report their confidence levels when dispensing a biosimilar in place of the reference biologic, more participants reported high levels of confidence when the products shared the same nonproprietary name (62.9%). A majority of participants (64.9%) reported perceptions of increased burden when required to provide a postdispense notification to prescribers when dispensing biosimilars. CONCLUSIONS: According to the survey used in this study, pharmacists prefer the use of a naming convention for biosimilars that includes a nonproprietary proper name with a designated suffix; however, levels of confidence in substituting a biosimilar for the reference biologic are highest when products share the same nonproprietary name. In addition, the results of this study suggest that the naming convention and postdispense notification requirements may affect the willingness of some pharmacists to dispense interchangeable biologics. This effect will be minimized if interchangeable biologics share the same nonproprietary name as the reference biologics. DISCLOSURES: Funding for this study was provided by the Academy of Managed Care Pharmacy. The author reports no conflicts of interest. Tomaszewski was responsible for all aspects of project and manuscript development.

Evaluating AE Reporting of Two Off-Patent Biologics to Inform Future Biosimilar Naming and Reporting Practices.

Historical studies of voluntary, spontaneous drug reports show poor attribution of adverse events to generic versions of commonly prescribed medications. As biosimilars enter the market place, it may be similarly difficult to accurately attribute adverse events to their respective reference products. At this time, lack of global consensus with regard to biosimilar naming conventions may result in drug reporting confusion, misattribution of adverse events and insufficient active monitoring of safety signals. Now, with the first biosimilar approval in the USA and many biosimilars expected to be launched globally in the near future, US Food and Drug Administration (FDA) guidance on biosimilar naming conventions will be essential. To inform the FDA and the global drug development community, the Tufts Center for the Study of Drug Development (Tufts CSDD) examined primary suspect reports sent to the FDA's Adverse Event Reporting System (FAERS) from US reporters for two biologics that have lost patent exclusivity--somatropin and human insulin--and extracted 4703 insulin reports and 6487 somatropin reports from FAERS. The results show that reporting practices are inconsistent between the two biologics that were evaluated and that manufacturer identifiability and traceability are lacking. Ways to improve biosimilar naming conventions and improve reporting practices are suggested.

The similarity question for biologicals and non-biological complex drugs.

For small - low molecular weight - molecule medicines a robust regulatory system has evolved over the years. This system guarantees high and constant quality of our (generic) medicines. Pharmaceutical equivalence and bioequivalence assessment are the pillars under that system. But there are complex medicines where the question of equivalence is more challenging to answer. For biologicals the paradigm of similarity rather than equality (the emergence of 'biosimilars') was developed in the past decade. This has been a program where an evolutionary, science based approach has been chosen by the frontrunner regulatory body, the EMA, with a 'learn and confirm' character. In addition, there is another group of complex drugs, the non-biological complex drugs, NBCDs, where the generic paradigm can be challenged as well. The NBCDs are defined as: 1. consisting of a complex multitude of closely related structures; 2. the entire multitude is the active pharmaceutical ingredient; 3. the properties cannot be fully characterized by physicochemical analysis and 4. the consistent, tightly controlled manufacturing process is fundamental to reproduce the product. NBCDs encompass product families such as the glatiramoids, liposomes, iron-carbohydrate colloids and many candidates of the group of the upcoming nanoparticulate systems. Following the main principles of regulatory pathways for biologicals (with appropriate product-by-product adjustments), instead of that for small molecules, would be the more logical strategy for these NBCDs. The status and outstanding regulatory issues for biosimilars and NBCD-similars/follow on versions were discussed at a conference in Budapest, Hungary (October 2014) and this commentary touches upon the issues brought up in the presentations, deliberations and conclusions.

Obstacles to the universal application of INNs.

Anomalies in the international non-proprietary name (INN) nomenclature show that the international harmonisation of nonproprietary drug names has not been achieved. When pharmaceutical companies request a new INN, they try to obtain an INN that serves their interests, and then use it for promotional or anticompetitive purposes. Drug regulatory agencies are not fulfilling their duty to protect existing INNs, particularly with regard to biosimilars (copies of biotechnology-derived drugs), giving rise in particular to anomalous names. The independence of the World Health Organization INN programme must be safeguarded to ensure that the universal terminology it is responsible for developing is applied worldwide.

[Biologics - nomenclature and classification]. / Nomenklatur und Einteilung von Biologicals.

Biological medicines are a heterogeneous group of drugs that are produced by living organisms using genetic or biological technology. Unlike chemically derived small molecules biologics are structurally complex making characterization and manufacturing difficult. Moreover, biological medicines show a great variety concerning their clinical use. To appropriately consider these particularities, there are other standards and guidelines for approval of similar derivatives of biologics, the so-called biosimilars or follow-on biologics. In contrast to a generic medicinal product containing a chemically identical active ingredient, a biosimilar is only expected to be similar to the innovator drug. Nowadays, monoclonal antibodies, fragments of antibodies, and fusion proteins manufactured by recombinant procedures play an important role. They have been used in many specialties for diagnostic and therapeutic purposes and are subject to continuous further development and improvement. Their nomenclature is based on a classification by the WHO which allows drawing conclusions for class of substance, origin, and pharmacological target.