china speed meets the quality headwind(part I)

In my previous blogs, I described the rapid progress of the biotech industry in China, from non-existing to beginning to get noticed in the world stage, the trends in the past decade by "waves", the widely used concept of "surpassing at the curve" and, the overall, the successes and failures from these endeavors. My main focus in this blog series has been to uncover some of the key issues that have prevented the Chinese national strategic focus to be successful, measured by gaining respect globally, and yielding higher ROIs.

In this post, I would like to present the case that one of the major challenges that the Chinese biotech industry has had to contend with is the conflict between SPEED vs. QUALITY.

How Is Biologics Drug Manufacturing and Quality Different from other Manufacturings?

• China is known as the world's factory for many decades now. The successes there are attributed to strong government support, cheaper and abundant local labor and natural resources, lower technological barrier for entry, an open market for foreign investment, and an incredible speed for implementation in massive scales, known as the "China Speed". Pharmaceutical, especially biopharmaceutical industry, however, are highly regulated industries; the standards for product quality must be strictly regulated for protection of public health. The bio-therapeutic products not only represent the latest in scientific and technological innovations for biomedical applications, they are also aimed at meeting currently unmet medical needs in the world, which are serious and often life-threatening diseases. As such, the rigor in regulations directly reflects the critical needs of ensuring safety and efficacy consistently for these products, as it has direct and serious impact on human lives. This applies to all stages of product life cycle, especially starting from human clinical trials.

• Additionally, the rapidly evolving nature of the biological therapeutics also makes it difficult to use simple, cookie-cutter rules for regulations as it is a field with complex product platforms varying greatly from one to another. For example, an antibody drug conjugate (ADC), a virus based cell and gene therapy, and a mRNA based vaccine vary significantly in key raw materials used, manufacturing processes and controls applied, product stabilities etc. With the exception of monoclonal antibodies, available public information on CMC of each of these platforms is limited. However, global regulations are rapidly changing and maturing as the regulators and industry gain more experiences. For the drug developers, deep understanding of not only how to design the product manufacturing process based on desired target product profiles, but also how to design a control strategy including all process and product quality controls, standards, and acceptable variations, and carrying them out in an effective quality assurance systems. This becomes extremely challenging throughout the drug development processes, which could last 5-15 years, in order to ensure the biologics product manufactured would consistently meet the designed quality attributes, and in compliance with drug regulatory standards for the intended markets.
  

Why Does Chinese Biotech Industry Face a Most Serious Drug Quality Problem?

• The complexity and criticality of product quality as described above require that each biologics developer in China has an experienced quality management team, and a drug regulatory agency that is capable of upholding quality and compliance standards for regulating these complex products. As China has had a much longer and more mature R&D history for the pharmaceutical industry, recent R&D programs have been yielding massive numbers of (albeit highly redundant) pre-clinical pipelines. Hence, the race to product development towards market authorization for these pre-clinical assets require huge number of leaders and trained professionals in GMP manufacturing and Quality management field, which are simply not available in China.

• When I returned to China after over 15 years of working as a Sr. leader in GMP quality in the US for leading global biopharma, I was viewed as a rarity amongst the "sea turtles". (‘海龟“, the term referring to Chinese high tech professionals returning from Western education and work experiences). I was therefore in a unique position to bring modern pharmaceutical quality management concepts and biologics -tailored quality systems to the biotech industry in China over the next decade. My experience of serving as the quality head for top Chinese biotech companies, as well as the founder for a comprehensive biologics quality management service firm in China for the 8 yrs to follow, allowed me to have a comprehensive view of the huge gaps in demands and availability of quality expertise and leadership in the local industry.

• Over 90% of the Chinese biotech entrepreneurs came from R&D backgrounds from the west. Except for a very few, venture capitals investing heavily into the biotech industry also did not have any experience in biotech industry. More often than not, company's founding leadership do not understand the huge risks their knowledge and system gaps pose to the realization of their R&D pipelines, and viewed investment in quality as a waste of money. As a result, quality systems in the majority of the biotech firms, even to this date, are ill-developed, and unfit for the type of products they manufacture. This has been a wide-spread problem and accounts for why majority of the Chinese biotech startup companies lack qualified leadership in GMP manufacturing and quality at appropriate stages of their product development journeys.

• Along with progression of the pipelines from early stage to late stage clinical development, in the past 5 years, many biotech companies in China began to realize the gaps they have in their existing quality systems and quality management capabilities. Unfortunately, such realization usually comes from significant failures in drug quality and manufacturing, which results in regulatory agency rejections/delays for IND or BLA applications, especially those to US FDA and EMA. I have seen many such examples first hand, including from some of my clients' that we have served over the years. Even in those situations, Chinese clients still would emphasize speed and price over the necessary investment needed to fix or mitigate the significant quality issues overall. This "latent" presentation of the CMC issues, especially quality issues are almost never visible right away and tend to result in more complications and serious consequences down the road. We have seen quite a few number of cancelled licensing deals between Chinese biotech and MNCs in the past few years many of which were due to CMC issues. Needless to say, such results damage the reputation of the Chinese biotech industry in the world, and lowers the overall ROI, and continued interest from the MNCs to work with Chinese companies beyond R&D.

• Chinese drug regulatory agency has undergone tremendous improvements in the past decade. I have seen impressive improvements in the expertise and experiences of the Chinese regulators over the past decade and continues to improve rapidly. The most solid demonstration of the improvements are on the regulatory guideline fronts with China NMPA publishing guidelines that quickly follow the US FDA, and ICH guidelines, with similar requirements, in Chinese language. However, due to the high turn-over of leadership at the agencies, and the overall short history of handling biologics drug regulation, there is still tremendous gaps in the abilities to actually execute the day to day regulatory duties for the industry.

• Based on the above, it could be concluded that the over-heated Chinese biotech industry, in the backdrop of the massive number of startups engaged in biologics product development activities in China, invariably creates a severe shortage of competent quality leadership and professionals. As "Fast Follow-on" concept focuses heavily on SPEED, QUALITY often becomes an after-thought, when risks have long accumulated and become harder to fix.
  

China Speed Meets the Quality Headwind (Part II) Preview :

This blog is the Part I of 2 in which I present one of the most critical challenges China faces for improving their biotech ROI. In Part II, I will share my thoughts on some of the possible solutions indicating the feasibilities of making those improvements.