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 market. New technologies also have the potential to be game changing, both in terms of efficacy and novel technological platforms.
3 Biologic asset revaluation: The biologic drug model, both in pre‐commercialization and commercialization stages is now well understood and proven to be effective. Confidence in the growing role that biologics are playing in the pharmaceutical market is impacting on company acquisition trends.
4 Biosimilars bring value: We are entering a transformative period where the largest selling biologics will soon face biosimilar competition in all major international markets. Legal opinions and regulatory guidelines adopted during this initial phase of patent loss will have lasting impact beyond 2020.
5 Competition and market environment: While previously many new biologics were first‐in‐class to go to market, now many biologics are entering the market competing with other biologics with the same mechanisms of action, increasing the ferocity of market competition. As third‐party payers find they have increasing choice in many therapeutic areas, such as autoimmune diseases, competitive dynamics for biologics increasingly resemble those of mature small molecule drug areas and payers place pressure on prices and discounts.
These five market trends will transform the biologic space in the next five years. Market players with interest in biologics face both challenges and opportunities in this new era; what is clear is that the biologic market will be far more complex and evolve far more rapidly than is the case currently.9
2.4 Player Archetypes in a Maturing Market
These biologic maturation events will have differing impact depending on individual player's strategic position.
2.4.1 Established Biologic Players
The largest biologic players are not just large within the biologic drug space, but the scale of their biologic drug success has made them global pharmaceutical leaders. Examples are Roche, Sanofi, and Amgen. These players face pressure to remain key leaders in their therapeutic areas of focus:
Revenue erosion. The greatest challenge is the threat of biosimilars eroding revenues. Follow‐on biologics such as PEGylated filgrastim and modern insulins have been successful in capturing and protecting franchise revenue in the past. However, recent follow‐on launches such as those in the insulin space have not performed as well as expected or predicted, leaving many large biologics vulnerable to biosimilar erosion. The current payer environment is not as open to innovation on the franchise model. Follow‐on innovation remains important for improving patient outcomes, but to achieve wider adoption, they must also be designed with the payer's perspective. Roche's subcutaneous formulation of Herceptin® in European markets is an example of when follow‐on can succeed. The new formulation reduces treatment time from 30–90 minutes to 5 minutes, saving time for the patient and bed/staff resources for the clinic. It has taken 28% of human epidermal growth factor receptor 2 (HER2) franchise sales and their share is growing. HER2‐positive breast cancers tend to be more aggressive than other types
