Since enactment of the BPCIA in 2009, as of 29 May 2019, 19 biosimilars, for nine reference products, have been licensed in the United States. However, many of these licensed biosimilars are not yet available to patients, primarily due to ongoing litigation, although various other factors may impact the uptake of biosimilars.4
2.2.2 European Medicines Agency
The EMA is the European Union (EU) body responsible for coordinating the existing scientific resources put at its disposal by Member States for the evaluation, supervision, and pharmacovigilance of medicinal products. The mission of the EMA is to foster scientific excellence in the evaluation and supervision of medicines, for the benefit of public and animal health. The agency provides the Member States and the institutions of the EU the best‐possible scientific advice on any question relating to the evaluation of the quality, safety, and efficacy of medicinal products for human or veterinary use referred to it in accordance with the provisions of EU legislation relating to medicinal products.5
2.2.3 Pharmaceuticals and Medical Devices Agency (Japan)
Until recently, reviews and related operations for pharmaceutical medications were handled by two organizations. The Pharmaceuticals and Medical Devices Evaluation Center (PMDEC) was the main product review body comprising of 8–10 specialists while the Organisation for Pharmaceutical Safety and Research (OPSR or KIKO or DO) was an independent consultation body. The PMDEC and KIKO worked closely together and both made use of “experts,” which would often comprise the same people. The Ministry of Health, Labour and Welfare (MHLW) supervised PMDEC and KIKO and granted approval. As part of the reforms that have been ongoing recently, the PMDEC and KIKO, along with the Japanese Association for the Advancement of Medical Equipment (JAAME), were merged in April 2004 to form the Pharmaceuticals and Medical Devices Agency (PMDA). The PMDA now handles the whole process from clinical study stage, providing “face to face” advice, through the approval phase and is also responsible for post marketing safety measures. The PMDA comprises 25 work sites, 6 groupings (or sections), and the Kansai and Hokuriku branches. The PMDA is currently attempting to accomplish objectives under the Third Medium Range Plan (2014–2018). The role of the PMDA is to provide consultations concerning the clinical trials of new drugs and medical devices, and to conduct approval reviews and surveys of the reliability of application data.6
2.2.4 Therapeutic Goods Administration (Australia)
The Therapeutic Goods Administration (TGA) is Australia's drug regulatory agency for therapeutic goods. It carries out appraisal and checking to guarantee therapeutic goods accessible in Australia are of an appropriate standard with the aim of guaranteeing that Australians have timely access to safe and efficacious therapeutic advances and innovative treatments.
The regulatory framework for biologicals medicines is based on the authorization premise of guidelines on human tissue and cell‐derived products and live animal cells, tissues, or organs that are provided and available in Australia or exported from Australia.
The biologicals enactment was initiated on 31 May 2011, after a suggestion from Ward, State, and Domain wellbeing experts to improve the guidelines on human tissues and cell‐based treatments. All items within the purview of the system need to consent to the necessary rules that cover the enactment.
The regulatory framework applies various levels of guidelines to the particular items and the risks associated with their utilization. The regulatory framework and the subsequent guidelines and processes for approval of biologic medicines including biosimilars is intended to be adaptable and agile to suit developing emerging therapeutic innovations.7
2.2.5 Centre of Drug Evaluation, CDE (China)
China's hard‐to‐navigate drug approval system, slow processing, and unfavorable intellectual property protection environment have been major concerns for foreign Biopharma companies, but highly ranked central government officials have pledged to tackle these issues to encourage more advanced foreign drugs into the Chinese market and the Chinese health system. However, while China offers many opportunities, it still poses numerous challenges for biologic drug developers seeking to optimize biologics development and reduce product registration timelines. Global pharmaceutical companies are conducting more clinical trials in China as part of their international multicenter drug development programs.
Success in China depends on the regulatory know‐how in navigating the country's evolving drug regulatory landscape. Drug developers need to balance the great advantages of China's large (often chemo‐naive) patient population base and efficient study participant enrollment with obstacles posed by registration pathways for new and existing small molecule and biologic drugs.
The China Food and Drug Administration (CFDA), formerly the State Food and Drug Administration, considers drugs that are approved and marketed in other countries as new drugs in China. The CFDA designates previously approved therapies as category III “import drugs” and requires clinical data from trials conducted in China to support an application for an import drug license (IDL). This is currently the requirement for all drugs already marketed in another country.
However, for drugs that have not been approved in another international jurisdiction as yet, drug developers might choose to conduct a full clinical development program in China and submit a new drug application to gain market approval that may be achieved a several years earlier when compared with the category III pathway (China‐manufactured generic drug that is only approved outside China).
In China, multinational companies operate in a climate of rapid change and increasing harmonization with research standards and processes of mature drug markets. They also encounter some dramatic differences compared with the regulatory processes of the U.S. Food and Drug Administration (FDA), the EMA, and other major drug regulatory authorities. The CFDA has developed its own standards for good clinical practices (GCP), good laboratory practices (GLP), and good manufacturing practices (GMP). CFDA technical evaluation and administrative review takes from 7 to 12 months, compared to 30 days for the FDA's IND review and 60 days for an EMA CTA review.8
2.3 Maturation of the Biologic Market
Small molecule drugs have had a 110‐year history of scientific advancement and regulatory and industry evolution. In contrast, the modern biologic industry is relatively nascent. The earliest marketed example of a biologic medicine was only 35 years ago with the approval of the first recombinant therapeutic protein, human insulin. Biologics have enormous potential; yet much of this potential is still largely untapped, in terms of therapeutic spread, medical efficacy, and population access. This potential will gradually be fully realized as biologic technologies are translated into routine treatments, occasionally transformational lifesaving treatments. Within the next 5–10 years, the biologics drug market will undergo a transformational period of rapid evolution and maturation compared with the current biologic drug discovery paradigm and business/financial model:
1 Biologics entering nontraditional biologic disease areas: Biologics are entering therapeutic areas where they have not been present historically, such as asthma, dyslipidaemia, and allergy. They will expand treatment options for patients with these disease indications, many of which are underserved currently. Collectively these are important areas for future biologic drug growth but will also present challenges for market creation and maturation.
2 Disruptive drugs and technologies: The number of novel biologic molecules approved by the EMA and FDA has surged in the past three years. In 2016, 50% of FDA new chemical entity approvals were for biologics. This period of high biologic innovation output will bring biologic drugs that will compete with and expand the current innovator biologic and biosimilars