Introduction: Since 2006, biosimilars have been available in several countries worldwide, thus allowing for potential savings in pharmaceutical expenditure. However, there have been numerous debates about the interchangeability of biosimilars and reference products based on concerns of immunogenicity by switching between biological products, which may cause lack of effect and toxicity.
Areas covered: The authors provide the reader with an overview of the different positions of regulatory authorities on the interchangeability and automatic substitution of biosimilars and reference products. Presently, the FDA allows automatic substitution without prescriber intervention if the biosimilar is interchangeable with reference products, while the European Medicines Agency delegate to each single EU member state.
Expert opinion: Different approaches in defining interchangeability and automatic substitution call for harmonization to increase confidence of healthcare professionals and patients about the clinical impact of switching. Networks of electronic healthcare records and administrative databases, potentially linkable to clinical charts and registries may rapidly assess frequency and benefit-risk profile of different switching patterns in routine care at different levels, thus integrating and strengthening pre-marketing evidence. 相似文献
Whole tumor cell lysates can serve as excellent multivalent vaccines for priming tumor-specific CD8+ and CD4+ T cells. Whole cell vaccines can be prepared with hypochlorous acid oxidation, UVB-irradiation and repeat cycles of freeze and thaw. One major obstacle to successful immunotherapy is breaking self-tolerance to tumor antigens. Clinically approved adjuvants, including Montanide? ISA-51 and 720, and keyhole-limpet proteins can be used to enhance tumor cell immunogenicity by stimulating both humoral and cellular anti-tumor responses. Other potential adjuvants, such as Toll-like receptor agonists (e.g., CpG, MPLA and PolyI:C), and cytokines (e.g., granulocyte-macrophage colony stimulating factor), have also been investigated. 相似文献
Human bocavirus (HBoV), a recently identified pathogen with a worldwide distribution is closely related to paediatric acute respiratory infection and gastroenteritis. The present study was performed to evaluate the immunogenicity of HBoV1 and HBoV2 virus‐like particles (VLPs) as vaccine candidates in mice. Both HBoV1 and HBoV2 VLPs were expressed in the bacmid virus–SF9 cell system. Mice were inoculated three times at 3‐week intervals with HBoV VLPs at one dose intramuscular (i.m.) or intradermal (i.d.) with or without the addition of the alum adjuvant. ELISA was used to detected antibody, and ELISPOT was used to test cellular immune responses. HBoV‐specific IgG antibodies were induced and alum adjuvant improved the antibody titres and avidity, while the inoculation pathway had no influence. T helper type 1/ type 2 immune responses were balanced induced by HBoV1 VLPs but not HBoV2 VLPs. Serum IgG antibody cross‐reactivity rates of the two subtypes were similar, but cross‐reactions of HBoV1 immunization groups were higher. The single i.m. group had more interferon‐γ‐secreting splenocytes. These data indicate that HBoV VP2 VLPs have good immunogenicity with induction of strong humoral and cellular immune responses, and they may be potential candidate vaccines for HBoV infection. 相似文献
The advent of biopharmaceuticals (BPs) has led to significant improvements in the treatment of many chronic inflammatory diseases, and the number of BPs on the market and of diseases treated reflects their success. However, repetitive parenteral administration and intrinsic immunogenic properties of the drug can elicit an immune response, leading to production of anti-drug antibodies (ADA). This is a major limitation of the use of BPs and has to be taken into consideration in clinical practice and during drug development. With increasing knowledge about the immunogenicity of BPs and regular ADA testing in patients, we ensure optimized long-term treatment for the individual and thus optimal use of health care resources. This field has already been extensively investigated in the treatment of multiple sclerosis with IFN-β, but there is a clear need for consensus from academia, health care providers and the BP industry in managing ADA across all BPs and diseases. 相似文献
Although biologic agents are effective in the treatment of rheumatoid arthritis, the high price of drugs and restricted health care budgets have restricted easy access to biologics. Eventually, the use of biologic disease-modifying antirheumatic drugs might be inversely associated with disease activity in countries with low gross domestic product. The EMA approved an infliximab biosimilar for the first time in September 2013. The first approval of a biosimilar monoclonal antibody by a major regulatory authority provided a global standard for subsequent biosimilars and for biopharmaceutical companies developing biosimilars. Biosimilars with a highly similar quality and efficacy profile at an acceptable lower cost would significantly increase affordability of biologic disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis. Here, we will review the current status of first biosimilar antibody agent and the potential discussion points raised against biosimilars. In addition, the importance of awareness on biosimilars for stakeholders is discussed. 相似文献