By Devan Patel
The development of new chemistry-based products for pharmaceutical organizations requires the expertise of many experienced researchers. However, most early-stage companies are not equipped with the means necessary for successful scale-up and commercialization. And in an industry that is increasingly competitive, not having sufficient expertise and infrastructure can put you at a major disadvantage. Contracting a competent partner provides an opportunity to use internal resources more effectively, accelerate product development, and maintain operating budgets. Yet, this is possible only if the partner can provide the support you need to address scale-up and commercialization challenges and ultimately beat your competitors to market.
The Importance of End-to-End Capabilities
Drug development is a race against the clock, and the early stages of discovery generally do not consider the efficiency of scale-up later. Instead, your chemists are likely focused on finding an effective compound with the potential to make the cut with the 12 percent of drugs that actually end up approved by the FDA.1 Nevertheless, the chemical synthesis that worked at bench scale may not be viable at a larger scale. That is why a key factor in ensuring successful scale-up is your formulation, as exploratory work is a vital part of figuring out how to generate the most efficient route for your molecule. You must know the critical quality attributes (CQAs) associated with each step of your process and what factors impact those in order to achieve the quality expected and required by the FDA.
Applying a Quality by Design (QbD) approach allows a better understanding of the science as it relates to the chemistry of the active ingredient, how it handles itself, and whether equilibrium properties, such as solubility, are well understood. Per the ICH Q8 process validation guidelines,2 “the information and knowledge gained from pharmaceutical development studies and manufacturing experience provide scientific understanding to support the establishment of the design space, specifications, and manufacturing controls.” An overall comprehensive exploration of your chemical reaction is the key to developing an efficient and robust synthesis for your compound. If there are too many limitations to your design space, you may create challenges during manufacturing, causing setbacks that could threaten the future of your product. In addition, converting these processes to meet regulatory requirements for scaled-up commercial production can also be time-consuming and extremely costly.
If you do not have the expertise in-house to navigate these nuances of drug development, you will have to seek an outsourcing partner to fulfill those needs. The decision of which one you select should be made with long-term goals in mind, as a CRO or CMO will not have the capabilities necessary to advance your drug all the way through to commercialization. Selecting a partner that cannot accommodate your needs from end to end will result in overseeing multiple avenues of supply chain and logistics, creating additional costs and longer timelines. Furthermore, not all CRO to CMO transitions are compatible, so managing one organization to another can be extremely difficult in the life cycle of a program.
If you underestimate the amount of work required to transfer work from a CRO to a CMO, such as testing, you may end up facing unexpected costs and challenges during that transition. A CDMO with the service options essential for each stage of development, such as formulation development, analytical support, manufacturing capabilities, and knowledge about quality and compliance, can offer the resources you need in one integrated process. This eliminates complicated logistics as well as extra costs and unexpected delays.
Effectively Working With Your CDMO
As the pharmaceutical industry continues to grow, so does the CDMO market. Choosing the right one is a critical step in bringing new drugs to market, especially for small to emerging companies pursuing new and innovative therapies. The complexity already inherent in drug development can be magnified if a CDMO does not have all of the key functions and expertise in place to bring a product from the development lab to a commercial GMP space. When vetting potential partners, do your due diligence by conducting audits or site visits to get a better idea of how the organization functions. A key piece of information to find out is a CDMO’s regulatory history. It must be able to maintain compliance with regulators in order to sustain a long-term commitment to you. Also, find out the number of commercial programs it has, what type of capabilities it offers, and what forms of expertise it has. A large staff does not necessarily mean a wide range of knowledge, so pinpoint some areas and question their capabilities from a scientific perspective. As already stated, science and manufacturing go hand in hand in drug development, so it is important the CDMO you work with appreciates the systematic approach and engineering necessary to turn a formulation into a finished dosage form and has the expertise needed to execute it.
For example, at Pharmaceutics International, Inc. (Pii), we recognize how important process knowledge is when it comes to scaling up your formulation, so we want to make sure we have the information we need to make the most effective decisions and recommendations. This requires an open dialogue with customers about your formulation and how it was developed, so we can ensure it was created using ICH 8 or QbD guidelines. We will also complete a gap analysis to gain a deeper understanding of what you will need from us to successfully manufacture your product. This applies not only as it relates to our procedures but also to our equipment. It may be necessary to convert a formulation into something that fits the mold of our quality system or our standard operating procedures in order to provide a consistent result each time. The goal is to ensure that any essential modifications are made ahead of time, so the finished dosage form is not impacted by what we have to do to onboard, scale up, and manufacture a product.
Additionally, safeguarding our relationships with our customers and the success of their products means maintaining transparency and communication throughout the course of a project. By making you part of the process and keeping you updated as a project progresses, we can establish a connectedness that is crucial in a partnership, especially for the management of timelines, budget, and other critical pieces of the puzzle. Being responsive and even flexible is what made the difference for Pii and a customer who recently faced a potential costly setback due to an unexpected change in demand. Despite the forecast provided to Pii, the customer discovered shortly before launch that its sales demand had gone up considerably from what was originally projected, and it required additional quantities immediately. Accommodating this request required creative solutions and strategies within a two-week span of production leading up to a scheduled facility shutdown. Nevertheless, through revised scheduling and quick thinking, Pii was able to meet the client’s needs and the launch is continuing as planned with the materials necessary.
In the end, while speed is important in first-to-market goals, appropriate planning and experienced guidance can mean the difference between jeopardizing your product goals and delivering a quality drug to patients in need. Finding a partner with the right resources and experience that also values your business can help you overcome the inevitable challenges of drug development, giving you the advantage you need to get ahead in an exciting but challenging industry.
- PhRMA, 2018 Biopharmaceutical Research Industry Profile and Toolkit — https://www.phrma.org/industryprofile/2018/
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2009). ICH Harmonised Tripartite Guideline Pharmaceutical Development Q8 (R2). Retrieved from https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_Guideline.pdf