White Paper

Guidelines To Bring Your Biologic To Market: Are You Prepared?

proactive-planning

Realizing the vision and avoiding common pitfalls: key considerations and questions to ask

You are determined to find an effective therapy for a particular disease. You’ve learned a lot, determined a possible mechanism of action, and selected the most promising biologic molecule from several good candidates. Perhaps you have already completed some pre-clinical work, and determined efficacy in animal models. You’ve even got investors who agree that this is worthy of a go-to-market run.

So, what now? Are you up to the task of bringing a biologic drug to market? Do you have the talent and resources you need? You know what the steps are, but how can you develop a strategy and plan for moving forward?

Here we explore, from a biopharma process development and drug manufacturing perspective, some of the questions to consider in order to map out a successful pathway and avoid pitfalls along the way.

As elementary as it may seem, start as you would with any strategic plan: define your goal. This will point you towards a lot of the elements that you must consider.

I want to bring to market a [therapy] for [indication].

Define a goal that is both achievable and meaningful. Keeping the elements and end goal in mind as you make decisions along the way can help you avoid pitfalls and make decisions that will move you forward on the most efficient path.

First, consider the indication, which will determine the prospective patient population. A thorough understanding of the patient population, size, age, geography will be critical to clinical study design, and will also determine potential target market size, quantity requirements and geography. Keeping this vision of what success will look like in mind will help you make strategic decisions along the way.

Looking at your target molecule, how well do you understand the molecule and the mechanism of action (MoA)? What is the best cell line to produce your molecule with the required critical quality attributes supporting the MoA? Will you be able to scale up the cell line you have been using for research? Will it yield sufficient cell density to be practical for production of quantities for clinical trial quantities, or even larger? Will bioprocessing changes affect the efficacy of the molecule? Will a change in cell culture medium lead to different behavior?

If you are developing a cell therapy, the issues will be somewhat different, but understanding the biology of your therapy is still key. How will you target your genetic modification? What vector will be most appropriate? How will you conduct clinical trials, and how will you manufacture and deliver the therapy to patients?

Where and how will you market your therapy? It may seem early to plan for this, but it should be part of your strategic plan. This is closely intertwined with your selection of indication and therapy. Are other treatments available for this indication? What is the competition? Understand, too, what you need for financial success. What is your drug development timeline? Will you have funding to carry you the distance? What is the likely reimbursement path?

Finally, “bring to market” implies manufacturing at commercial scale and gaining regulatory approval, not only at specified milestones along the way, but also approval of the final drug and manufacturing process in the countries where it will be sold. This should inform choices you make throughout development and clinical trials. You can ultimately save time and money for redevelopment if you use from the outset materials, equipment and methods that can be utilized at commercial scale and validated for production for human use.

Take advantage of bioprocess technology advances for speed and efficiency: don’t reinvent the wheel

Recently we have seen a developing trend that more small companies are reaching pre-clinical and Phase I trials. The cumulative effects of technological advances have contributed to this, reducing drug development time, manufacturing costs, and the costs to get to and through clinical trials.

  • Highly-productive cell lines enable the production of clinical and commercial quantities of biologics in smaller facilities, which are suitable for single-use bioprocessing.
  • Single-use technology (SUT) can be set up in the “ballroom” model, where the system is closed, greatly reducing clean-room requirements.
  • Perfusion, or continuous processing, can further increase productivity.

Together, these advances can result in significant savings in both capital and operational expenditures, as well as greater speed to market.

With new methods and materials, the time for developing production cell lines has been brought down from a year to months.

  • Powerful new protein analysis tools and sequencing tools are leading to better understanding of molecules, and the ability to target specific genes.
  • Viral vector platforms are being developed to shorten the development time for cell therapies.

A savvy CDMO can help you access these technologies to shorten drug development time and advance your molecule or cell therapy to market efficiently. Attracting and recruiting this type of scientific lab expertise in-house can be challenging and expensive.

Whether you choose to outsource drug development or keep all development work in-house, one must-have is expertise in process controls and in implementing GMP processes that can be validated.

Clinical trials: the big enchilada

Clinical trials for mAbs can take up to ten years—even longer for vaccines—and will consume most of your time, energy and funds. While you will certainly want to include someone with clinical trial expertise on your leadership team, you should also consider utilizing the services of a contract research organization (CRO) specialized in clinical trial services directly relevant to your indication. This can not only bring down costs and save time, but also give you access to resources and expertise with broad and deep experience. 

Patient safety is central. Stringent regulatory requirements designed to protect patients’ rights and safety are in place, but may vary from country to country. Early understanding of the regulatory requirements, and engagement with regulators, will serve you well. For cell and gene therapies, transplantation regulations as well as drug regulations come into play. But, there is also openness on the part of regulators to engage earlier with developers of these new therapies; they are still learning the complexities, risks and requirements of these new treatment modalities.

Clinical trial patient population size may vary from as small as 10 to 100 for a rare disease or cell therapy, to many thousands for a vaccine. While patient safety is initially determined in Phase I, follow-up for all phases, even post-market, is also essential for patient safety.

Clinical production: in-house or with a CDMO—which will you choose?

You will most likely not be looking to outsource everything at this stage because it’s too early, and the prospect of the overall revenue sharing model through commercial manufacturing with a CMO at this stage may not be as enticing. That said, as a small start-up with limited capital, you might need to scale up your production for clinical trials, or even perhaps pre-clinical trials. Outsourcing to a CDMO might be a faster and easier route through this phase. This allows you more time to delay the decisions and hence the investment risks until you know more about the future of your company.

CDMO selection is complex; working with a consultant to help you develop your selection criteria and conduct an audit is worth the investment. Does the CDMO’s business model align with your goals? For instance, if you plan to outsource commercial manufacturing, working with a provider who offers that capability can avoid unnecessary tech transfer as you move from clinical to commercial quantities. Bear in mind, though, that there may still be considerable redevelopment costs if their commercial facilities are not consistent with their development and clinical manufacturing facilities and methods. If you envision investing in manufacturing capacity if and when your molecule or therapy is approved, how will your CDMO support your goals?

Bringing your drug to market: at last!

Congratulations—your therapy has received regulatory approval! Now, how will you go to market? Of course, you should be planning for this well before approval is in place. Your strategy will include both manufacturing, as we’ve already discussed, and marketing.

It has been typical in the bioprocess industry that larger players have entered the market with blockbuster molecules, but the dynamics have been changing, with an increasing number of emerging start-ups getting to market. The cost of manufacturing facilities is coming down, thanks to new technologies and design approaches that require less capital expenditure and lower the costs of market entry. For example, Amgen estimates that its new biomanufacturing facility in Rhode Island, announced in April of 2018, will be built at half the cost and in half the time that it would have taken for a more traditional plant. The decreases in time and costs to create new bioprocessing capacity reduce the barriers to entry for any company that wants to bring manufacturing of a new drug in-house.

China is a leader in this trend, utilizing newer technologies to rapidly build out its relatively new biopharma industry. With its aging population, China is the world’s fastest growing biologics market,  with predicted 16% compound annual growth (CAGR) from 2010 through 2021, and estimated manufacturing capacity growth of 10% just in 2017.

  • China-based companies such as Hangzhou Just Biotherapeutics (HJB) and WuXi Biologics are bringing large single-use biomanufacturing facilities on-line.
  • Global companies such as Pfizer and Lonza are also investing in bioprocessing capacity in China.

If you are bringing your manufacturing in-house, newer technologies enable rapid deployment, with a one-to-two year timeline as opposed to three-to-five years (in an existing building). If you have been working with a CDMO selected with this end-point in mind, they will be able to provide manufacturing services in parallel as you build your production capacity. During this time, they will also be working with you to train your production staff and implement a smooth technology transfer, overall saving you time to market, and with the benefit of tapping into expertise which will ensure you have a greater likelihood of success.

For companies choosing to outsource their commercial drug manufacturing, one potential go-to-market strategy is to enter global markets through commercialization agreements with established partners. Working with an experienced pharma company can be a win-win, expanding the established company’s offering, while giving the off-shore company access to local manufacturing, regulatory knowledge, marketing capabilities and sales channels.  For example, Celltrion, Inc. of South Korea has commercialization agreements with a number of pharmaceutical companies, including Hospira Healthcare, Teva Pharmaceutical Industries and Mundipharma International, to expand their market for biosimilars to Europe and the U.S.

There are many pitfalls in the road to developing and bringing a new therapy to market. Understanding some of these areas and being prepared to make the right decisions at the right time will help you avoid delays and in the end be more successful. Take advantage of available technologies and services that you can license or buy. Services are available for every step of the journey from lab to market; carefully weigh the costs of these services against the time and costs of going it alone, and your ultimate goals. Most importantly, develop a vision of your end-point, and let that vision inform the questions you ask and the decisions you make along the way.

About Fast Trak Services 
GE Healthcare has Fast Trak service centers in the USA, Sweden, India, South Korea and China and satellite Fast Trak Centers in Turkey, Japan and Singapore. The centers are specifically designed to help biopharmaceutical manufacturers increase their process productivity, reduce cost and enable them to bring their product to market faster. Contact us for more information.