Biosimilar development is not about conducting breakthrough research. Rather, it is about hitting the ground running and pressing the fast-forward button by using existing technologies to ensure first-in-class market access. Swift execution also incorporates the need to accept that some options must be left aside so as not to slow the overall process.
Product development is complex; it involves many different specialists and must address many wide-ranging issues, so a big danger lies in inappropriate decision-making. Too often, a good head start is lost because managers are unable to agree on an idea that should be skipped to stay focused and in fast forward mode. Dragging along too many alternatives and slowing down the development process very often results from one poor project manager being charged with full responsibility while others sit and watch the project branch-off down the wrong track.
At Finox Biotech, the project manager is neither 'in charge' nor left alone. In fact, a broad management team takes responsibility for achieving overall development goals. This is all the more important given that a single project manager cannot usually cope with the multiple strategic issues that occur in biosimilar development. The ever-evolving quality and regulatory landscapes need to be continuously integrated into product development strategy formulation and execution. The IP environment must also be followed closely with product development adapted accordingly. Attention must be paid to what is coming off patent but also, and perhaps more importantly, to what is going on patent, which is potentially one of the more damaging defensive strategies of originator companies against biosimilar competitors. Last but not least, the cost of goods sold (COGS) will be one major enabler of competitiveness and the project manager alone will have difficulties in presenting a satisfying result if he alone is managing COGS. Overall, there needs to be a spirit of execution that enables a high decision-making rhythm as well as a sense of maintaining focus on the essential attributes that the final product offering should present. One must not waste time and dissipate energy on a set of alternative opportunities.
Product development should be supported by constant confirmatory exchanges with regulatory authorities. Biosimilars are a nascent class of products, so authorities learn alongside companies developing products in this field. Accordingly, authorities’ expectations evolve during product development and an agreement sought some time ago may not reflect the expectations in the future.
Be it the FDA or the EMA, both agencies provide supportive instruments for ensuring development progresses according to the respective guideline indications. Indeed, both agencies share the company’s overall goals of bringing safe, efficient and affordable medicines to patients. However, sometimes the detailed understanding of what is required to achieve this overall goal may differ between the company and the agency. Finox Biotech’s experience is that it is worth challenging agency requests. Sometimes, one might want to take an alternative route than what the agency proposed to achieve a certain goal. Our experience shows that if a different approach is scientifically justified, the agencies are open to negotiation. Sometimes it is worth saying "no" in order to achieve a more attractive, commonly agreed upon "yes" thereafter.
A biosimilar, by definition, should not differ from the reference product in terms of safety and efficacy criteria. That said, there are still many opportunities for product differentiation beyond price. To avoid the danger of price-only competition and ever-eroding margins, the biosimilar under development needs to embody a different set of values.
In many cases, the originator product was developed some years ago with technologies of that time. Current technologies may allow improvements for a biosimilar. For example, with regards to formulation, using today’s state of the art excipients could lead to improved product stability or reduce undesired product aspects. When communicating with prescribing physicians, one may find that packaging sizes or dose volumes of the originator product no longer match clinical practice, so a biosimilar can differentiate itself by addressing these issues. Over the last two decades there have also been many improvements realized in the area of medical technologies, so there is potential for biosimilars to take advantage of state of the art delivery devices.
If a thorough differentiation approach is followed, the product can gain its own character. Add a brand to represent this specific character and it becomes a value-adding, branded pharma product rather than representing a ‘same but less expensive’ generic product. Not only will the prescribing physician better recognize your product, but investors are also likely to be happier in the end.
It is clear that reducing time-to-market is one of the most important criteria in biosimilar development, but under no circumstances should shortcuts be taken. One pillar of success is the credibility that can be built up through solid product development, especially for an unknown startup, such as Finox Biotech.
The first 'customer' of a product will be the regulatory authorities because they will judge product adequacy for approval. The previously recommended continuous involvement of such authorities in the development process—from the start when drawing the overall development plan to the end when preparing submission documents—will be the essential for maintaining credibility with agencies. The agreements made and the recommendations given during these interactions should be followed precisely. It is possible to further enhance credibility by going the extra mile or one step beyond agreed goals; typically adding only marginal costs and time to the development program the return is much enhanced product credibility. For example, one may choose slightly smaller acceptance margins than previously agreed, the power for the clinical trial may be higher than widely accepted 80%, or trials can be given to those with the highest academic rigor.
The second group of customers—the prescribing physicians—must also be convinced of the product’s credibility. Similarity to the reference product is a prerequisite for a biosimilar and essential for approval, so there is no marketing argument to be made on efficacy or safety. Therefore, one needs to go beyond similarities by adding value and differentiated product characteristics in line with a scientifically sound, comprehensible and credible product development story.
A common defensive strategy used by originator companies against biosimilars is unfounded suggestions as to the questionable source and background of such products. Company representatives love to poetically provide imagery of a backyard–underground lab where, under suspicious conditions, the biosimilar competitor is produced. The very same negative insinuation is then used for non-clinical and clinical development. In reality, biosimilars in highly regulated markets are produced using state of the art processes, whilst satisfying the current, highest quality standards and are justifiably at least as good as originator products. In some aspects, biosimilars may be even better than originator products for the very fact that they are developed and regulated with current knowledge. Therefore, it is the biosimilar industry’s task to deliver this message to the market, a task best done through products that satisfy the toughest standards and thus gain the highest credibility.
Being part of a nascent industry is exciting, but there is a necessity to continuously adapt to a changing environment and to help shape the industry for the good of its players. Finox Biotech has not yet proven its success, but the company aims to do so by applying the recommendations on which I have elaborated in this article.
Only by very careful target selection with deep consideration over strengths and weaknesses can one bring about an attractive business case. In a virtual set-up, such a business case can only be translated into product success by carefully choosing the right network of partners. Special attention needs to be paid to the creation of overall product understanding and commitment among selected external partners to satisfy the credo that 'the process is the product.' Reduced time-to-market and low COGS are essential for biosimilar competitiveness, so it is crucial to form a spirit of swift execution and a strong awareness of essential product attributes rather than wasting time on alternative options. Last but not least, to avoid competition on price alone, a biosimilar must exhibit value-adding characteristics to differentiate it from the reference product. If all of these ingredients are mixed together in the most demanding development environment, answering to the highest standards, a credible and attractive product will emerge.
Certainly, Finox Biotech aims to develop biosimilars that are more than just similar—a goal that will probably be the difference between failure and success in this new market.