In pursuit of leaner business models, many of pharma’s leaders and innovators are turning to effective strategic outsourcing strategies to assure the reliable development and manufacture of active pharmaceutical ingredients (APIs), the most critical component of their drugs and therapeutic products.

What makes a custom API supplier relationship strategic?
Biopharma companies are changing how they go to market and the growth of contract services providers in the past eight years is proof of it. Although most of biopharma is outsourcing to a certain degree, demand is still growing for competent and strategic long-term partners to manufacture their drugs and assure reliable drug substance supply. Times are changing however, and biopharma’s developers are turning to their contractors for long-term, intelligent collaboration and much higher levels of support, including achieving more efficient synthesis routes and scale pathways to help drive costs out and overcome any development and manufacturing challenges.

Most drug product and drug substance developers understand commercialization routes for popular drugs and therapeutic compounds are relatively well known but plagued with many barriers and significant financial risk. Even more risk is associated with developing the new high-potency, hard-to-make APIs the market is demanding. Deeper relationships with strong custom API developers who are equipped with the science and experience will help mitigate inherent risk and cost and provide better pathways to success.

Certainly, navigating drugs through all the complexities of development and manufacture will remain challenging because each compound or drug product has its own unique known, and unknown qualities, relative to a whole host of economic and market drivers. In particular, hard-to-make APIs require an experienced partner and track record of getting to the most efficient synthesis routes. 

Making custom API supplier relationships more strategic
Recent industry polling* reveals that suppliers who can deliver attributes like quality, reliability, productivity and regulatory vision, are what sustain relationships with contract development providers. But what do drug developers think make the relationship strategic? A 2017 study* revealed regulatory experience, geographic convenience, global presence and maintaining highest quality standards were at the top of the list.

As pharmaceutical companies continue reducing their manufacturing footprints or avoiding them entirely with virtual companies, it’s becoming an even more strategic imperative for outsourcing managers to understand what can make a contract manufacturing services provider the kind of strategic, high-value, long-term partner they need to successfully manufacture their products so that they can deliver their drug to markets and patients.

Does experience make a supplier more strategic?
In many ways, yes, but it has to be the right experience and of course, there must be a record of success to go along with it.

Experienced CDMOs know how to start off on the right foot, beginning with a planned, structured dialogue that sets expectations and early on reveals opportunities for process optimization and process timeline economies.

This dialogue and subsequent conversations should include scaling tactics, the outcome of instituting efficient synthesis or cleaner chemistry methods, mitigating process variability and stability issues and framing raw material economies.

Expertise and strategic partnerships
Business strategy drives partnering strategies and suppliers with particular expertise can offer drug developers the leverage they need. Long-term sourcing strategies suggest that the more expertise a contract services supplier has with its customers’ target compounds the better most outcomes will be.

Better support comes from expert partners with great science. Approximately 60%* of drugs in the current R&D pipeline are small molecule and contract services and substance suppliers with small molecule expertise–especially for hard-to-make and high-potency APIs—will remain in high demand.

Processes need to be robust and repeatable as both drug strategies and regulators demand it. During tech transfer into a production environment, a synthesis proven in the lab may demonstrate process stability problems or issues on scale-up. Careful evaluation and analysis may reveal the synthesis route can be subject to variation or volatility at scale, present unsustainable expensive intermediate steps and other technical and financial issues at commercial scale.

That’s why understanding your contract API developer’s process for evaluating this early on is essential. The first step is to look at proof of chemistry and evaluate it for quality and yield but also for waste generation, reactivity of reagents for safety and other key aspects.

The next step is to examine proof of process which involves evaluating material handling and answering questions including: Does the API or intermediate crystallize into a well-formed crystal that will filter quickly in the plant? Are transfers of reaction mixtures easy to handle? Basically, it’s taking a practical approach to reviewing and optimizing all the physical attributes of the process and making sure it’s going to be a good fit in your contract API partner’s site.  

Improving yield is a critical element of effective development support, since poor yield leaves money on the table. To boost yield for example, opportunities might lie with fine-tuning crystallization conditions to reduce API losses or use analytical process monitoring to achieve an ideal reaction endpoint at large scale.

Look for a CDMO with a roster of analytical chemists, organic chemists and engineers who are adept at developing and trouble-shooting analytical methods and processes and have the expertise to scale up your API process.

Quality = reliability
Product quality and reliability of business-critical supplies are tightly linked; the more expertise and experience your contract and supply partners have manufacturing high-quality, compliant products, the more likely it will be able to assure continued reliable delivery of APIs and critical intermediates to sustain product strategies and respond to market swings.

Mitigating supply chain risk is a primary concern but has to be achieved economically; partners that provide unwavering product quality and deliver on time and in full are by definition strategic. A kilo of API that cannot be used due to quality issues or because it is late is a costly mistake.

Improving yield and delivering better quality as a continuing element of an outsourcing relationship is another sign of strength and the potential for longer-term value. If initial dialogue doesn’t include ways to fine-tune processes so that they will work as intended in the equipment, the risks of later-stage issues can grow. If there’s opportunity for yield gains, the API manufacturer should recommend and implement them early to limit future changes down the road which would cost time and money.

Similarly, reliability is also contingent on the demonstrated performance and health of the organization, financially and operationally. Strategic suppliers and contract partners with solid financials and compliance performance will always offer a more stable, long-term platform to source drug substance and APIs without the anxiety of supply interruptions.

Lastly, quality and reliability are also servant to the time, money and resources a contract partner invests in its people, science operations and facilities. Partners that have an eye towards continuous improvement will remain the kind of partner a strategic relationship can be built upon.

The importance of demonstrating responsiveness
Because most product plans are unique, acquiring API suppliers that can help get a drug from lab to market can be a challenge. Those with experience and vision will likely be able to bring to the relationship an intelligent approach to partnering and the insight needed to innovate solutions at the speed of business. All of this can aid in creating an environment that is responsive, agile and more capable of performing over the long run.

Whatever your product’s market agenda might be, drug owner and drug maker often have to build a common base of knowledge and do it together. Better drugs begin with a better, smarter collaboration and the sooner both parties can put their collective heads together, the better. A strategic partner will always be seeking ways to innovate and improve your compound or product’s value and do it with the dedication of a partner, not just a supplier. 

*https://www.pharmasalmanac.com/articles/the-cdmo-and-the-international-supply-chain