Analysis of biosimilars and biologics forms to be one of the most important aspects towards the biologics and biosimilar development process. Biosimilars analytical methods for process development and validation as well as use of production technologies such as disposables and supply chain logistics can help companies establish facility flexibility.
This biosimilars global event also includes Bio analytical methods, Formulation, Bioassay for comparability and potency testing, GMP protein analysis, LC/MS analysis for discovery, preclinical, and clinical programs.
Increasing knowledge of human diseases, especially after the decoding of the human genome, has accelerated the discovery of disease-related chemicals and/or proteins. These targets form the basis for the design of pharmaceutical compounds to alter biological activities and clinical outcomes. Development of biologics is considerably more expensive and time-consuming than that of small molecules. The latter contain only carbon, oxygen and nitrogen, which are easier to synthesize with low batch-to-batch variability
Despite the high cost of development, due to their targeted nature with high efficacy, biologics are now taking on an increasingly important role in the treatment of common and/or serious diseases such as diabetes, cancer, chronic kidney disease, rheumatoid arthritis, psoriasis, blood disorders, vaccines and inflammatory bowel diseases.
In Europe and North America, regulatory agencies such as the European Medicines Association and FDA have developed clear regulatory guidelines for the evaluation and approval processes of biosimilars regarding their physical, chemical and clinical traits. To be called a biosimilar, these compounds need to demonstrate structural and functional similarities with comparable pharmacokinetic and pharmacodynamics properties to the originator compounds using sensitive indicators, for example, levels of cytokines, blood glucose or white cell counts.
Once these criteria are fulfilled, these biosimilars are often given similar indications as the originator drugs in order to reduce the development cost and hence the market price. Once approved, the inherent nature of these complex molecules calls for continuing surveillance to detect allergic reactions or rare events due to immunogenicity or other untoward reactions, which may not be detectable during the development stage. Besides, the batch-to-batch variations may also lead to efficacy and safety issues in the post marketing phase.
A biosimilar/ follow-on biologic / subsequent entry biologic is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. Biosimilars are officially approved versions of original "innovator" products and can be manufactured when the original product's patent expires. Reference to the innovator product is an integral component of the approval.
A bio better is a recombinant protein drug from the same class as an existing biopharmaceutical but is not identical; it is superior to the original. It isn’t exclusively a new drug, neither a generic version of a drug. Biosimilars and bio betters are both variants of a biologic; with the former being close copies of the originator, while the latter ones have been improved in terms of efficacy, safety, and tolerability or dosing regimen.
Some evidence points to the fact that the first biosimilars were not as good as their branded counterparts. Whereas in case of Bio betters gain in effectiveness may come with a larger price tag, as the drug would be touted as an improvement on the current standard of treatment, and not a direct competitor in the market. This does nothing to help the cost-conscious consumer looking for cheaper alternatives. Now the question arise Biosimilars or Bio better? Accessibility & similarity or efficacy & improvement what will you choose?
Over the past two decades, the United States and Europe experienced a dramatic and unsustainable rise in cancer health care costs. Eight of the top ten most expensive drugs are cancer drugs, notably the novel biologic agents arising out of the recent revolution in our understanding of the genetic and molecular basis of malignancy. As the protective patents on new biologic therapies reach expiration, the race to develop biosimilars has begun, hopefully increasing competition and reducing costs. Although authorities have developed regulations for the development and approval of biosimilars, it remains uncertain how rapid and broad their entry will be. The reasons for such uncertainty are multiple but fundamentally relate to the biologic nature of these agents: these drugs, unlike generic pharmaceuticals, are large, complex molecules derived from biologic processes that are similar but not identical to the original agent and, thus, subject to immunogenicity and drift over time. The demonstration of comparable efficacy and safety to the originator is a challenge for both regulators and companies, necessitating careful pharmacovigilance following approval.
FDA’s guidance on comparability protocols discusses the need and considerations for assessing any product or process change that may impact safety or efficacy of a drug product or drug substance. Areas to consider may include:
• Changes to the manufacturing process
• Changes to the analytical procedure or analytical method
• Changes in manufacturing equipment
• Changes in location or manufacturing facilities
• Changes to container closure systems
• Changes in materials, concentrations, and/or formulation
• Changes in process analytical technology (PAT) or process controls
• Any change that may influence safety or efficacy of the product.
Generally, a comparability protocol includes an analytical method(s), a study design, a representative data set, and associated acceptance criteria. The defined protocol is used to demonstrate comparability. There are typically two types of data analysis techniques that are used: statistical significance and practical significance or equivalence. In the case of statistical significance, the differences are always considered to be zero. In the case of practical significance, they are not considered to be zero; however, they are considered to be so small that they are considered to be practically zero. Often, testing using statistical significance (zero change) may result in the detection of real differences that are not practically meaningful and do not identify practically meaningful differences in the product.
Bioequivalence focuses on the equivalence of release of the active pharmaceutical ingredient from the pharmaceutical product and its subsequent absorption into the systemic circulation. This session has utmost importance in context to the fact that only a suitably bioequivalent drug candidate that conforms the results in all respects to the original licensed product can be called as biosimilar drug.
Of all attempts towards developing a follow on biologics or a biosimilar drug the main detection point stands at the bioequivalence assessment. Once the bioequivalence has been obtained it can be 70% ascertained the drug qualifies to be a suitable biologics or biosimilars.
Patents for several biologic blockbusters will expire in the next few years. The arrival of biosimilars, the biologic equivalent of chemical generics, will have an impact on the current biopharmaceuticals market. Five core capabilities have been identified as paramount for those companies aiming to enter the biosimilars market: research and development, manufacturing, supporting activities, marketing, and lobbying. Understanding the importance of each of these capabilities will be key to maximizing the value generated from the biologics patent cliff.
This biosimilars conference will look at the facets of current challenges in biosimilar development. This biosimilar conference will focus on multiple aspects of biosimilar product development to successfully deliver safe, potential and efficacious biologic products to the market.
The EU has pioneered the development of a regulatory system for biosimilar products. The guidelines outline an approach for comparing the proposed biosimilar to the reference biologic, covering quality, manufacturing process, safety and efficacy. To date the EMA has approved nineteen biosimilars for use in the EU including the recent landmark approval of monoclonal antibodies.
The EU and WHO guidelines have served as a basis for several countries to develop national biosimilar pathways. Australia, Malaysia, Singapore, Turkey and Japan have developed guidelines based on the EU model, whereas many of the Latin American countries have followed the WHO guidelines for their local regulatory legislation.
The US biosimilar pathway was signed into law in March 2010 as part of the Affordable Care Act. The US Food and Drug Administration (FDA) issued three draft guidance documents in February 2012 on biosimilar product development to assist industry in developing such products in the US. As these regulations will undergo further review and revision by the FDA, the US remains behind the EU, Latin America and Asia in terms of biosimilar drug development and commercialization.
Biologic trials require a customized approach based on the therapeutic indication and study specific goals. The CRO must work with the sponsor to develop an effective plan and execution strategy for these study types that includes subject recruitment, regulatory, clinical safety monitoring, specialized pharmacy expertise, and bio analytical support while ensuring subject safety throughout the entire trial. This is best accomplished with a detailed risk assessment to ensure all the bases are covered. The risk assessment isn’t just done once and then forgotten, but is a living document that is updated as new information about the molecule is gathered.
The Biologics Price Competition and Innovation Act (BPCIA) opened the door for companies to seek FDA approval to manufacture and sell biosimilar or interchangeable versions of brand name biological products. Due to the size and complexity of biological products, as compared to small molecule drugs, a biosimilar must be “highly similar” to the reference product with “no clinically meaningful differences” between the two. The BPCIA also provides reference product sponsors with 12 years of market exclusivity, but unlike the Hatch-Waxman Act, it does not require reference product sponsors to list patents in an Orange Book equivalent and does not include an automatic 30-month stay of FDA approval upon the timely filing of a lawsuit. The BPCIA, however, does provide pre-litigation procedures for the parties to follow, including identification of relevant patents and each party’s basis for infringement and invalidity.
Good Manufacturing practices aims at both production and Quality Control. Fact about Current Good Manufacturing Practices (cGMP) is aimed primarily at managing and minimizing the risks inherent in pharmaceutical manufacture to ensure the quality, safety and efficacy of products. Over the previous decade, a developing offer of the business' R&D yield has comprised of incremental enhancements to existing generic medications instead of new sub-atomic substances. Execution measures that consider just altogether new medications, for example, the quantity of NME endorsements every year miss that move and underestimate the business' R&D Field
Over the past ten years, regulatory authorities worldwide have been focusing on developing guidelines for biosimilars. However, until a global development strategy is adopted, regulatory, therapeutic and legal challenges remain. While the prospect of cost savings and efficiency make the biosimilar market attractive, companies and their outsourcing partners planning to enter this market must be aware of current regulations and issues in the global marketplace and be prepared to respond quickly to changes.
As global regulations and guidelines progress, questions such as the following are broadly being debated in the pharmaceutical industry:
- Should interchangeability and automatic substitution be allowed?
- Should biosimilars have the same international non-proprietary name as the reference product?
- How much longer will patent litigation hinder the U.S. market?
In countries without biosimilar guidelines, interaction with regulators can be challenging. It is advisable to approach agencies proactively for scientific advice to avoid potential questions and delays in clinical trial approval. In most cases, reviewers need to be guided through the FDA, EMA and PMDA (Japan) guidelines. This is important in order to receive agency validation of the development program, discuss issues, identify gaps in the submission package, review the protein characterization steps conducted, agree on the source of the reference product and familiarize the assessors with the biosimilar product before submitting clinical trial applications.
“Novel Drug delivery System (NDDS)” refers to the formulations, systems and technologies for transporting a pharmaceutical compound in the body as it is needed to safely achieve its desired therapeutic effects. Drug delivery systems (DDS), are based on approaches that are interdisciplinary and that combine pharmaceutics, bio conjugate chemistry, and molecular biology.
- Nano technology
- Controlling pharmacokinetics and dynamic properties
- Drug Delivery Carriers, Micelles, etc..,,
- Types of dosage forms
- Route of administration