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Congratulations! Clinical trials have proven successful and now on to the next major decision as you prepare for product launch: finding the right commercial manufacturer for your Active Pharmaceutical Ingredient (API).
Typically, API manufacturing is outsourced. A new report by business intelligence provider Visiongain forecasts that the worldwide contract manufacturing services industry will grow to $83.9 billion in revenues in 2020 with strong potential for further growth over the next decade.
It’s a large market, with many commercial API manufacturers to choose from.
That brings up the first five questions to address when deciding which Contract Manufacturing Organizations (CMO) is right for your specific needs:
- What will be the annual projected demand for the API?
- Which CMOs can manufacture the necessary quantities, whether large or small? Can they bridge the quantity gap if larger quantities are required down the road?
- Can producing commercial quantities of the API, whether grams or multiple kilograms, be accomplished profitably?
- Does the CMO follow the highest cGMP standards?
- Has the CMO passed FDA inspections with flying colors?
Ultimately the final API needs to work for its intended purpose, and the many factors that can impact cGMP manufacturing of APIs must be taken into consideration when choosing a CMO. Commercial manufacturing is one of the most technically challenging aspect of the entire drug development process – sometimes even more so than developing the API for clinical trials.
How to Choose a CMO for Commercial Scale API Manufacturing
When trying to determine whether a CMO can efficiently manufacture quality APIs at a reasonable cost of goods, consider CMOs that:
- Are capable of ensuring that robust processes can achieve critical quality attributes (CQAS).
Multiple intermediaries using different processes are often required in the manufacture of small-molecule APIs. To consistently achieve the desired CQAs, it is necessary to ensure that each of the processes is robust1. Ask potential CMOs about their relevant experience.
- Have process controls in place that can reduce the risk of out of spec impurities.
For APIs, the most common CQAs relate to impurities from the chemical processes they undergo. Controlling impurities is essential for safety. Quality guidelines for acceptable levels of impurities are provided by the International Council for Harmonization (ICH). Ask potential CMOs about their approach to process controls.
- Have process controls in place that can achieve product consistency.
Another critical consideration relates to such API physical properties as particle size of the drug substance. Control of the API’s properties is essential if one is to achieve consistent bioavailability. Moisture content may also need to be controlled to reduce or eliminate any accelerated degradation of the drug product. Ask what steps the CMO takes to ensure consistency, especially if the annual amount of the API to be manufactured is small.
- Has a good supply chain.
Availability of key raw materials is essential, and the preferred CMO should have a supply chain capable of ensuring long-term timely delivery of needed raw material quantities to avoid any raw materials supply limitations, whether raw materials are sourced domestically or imported. Make sure to ask about how the CMO works with qualifies it’s suppliers.
- Can handle and properly dispose of hazardous waste.
By-products and waste products are produced in small quantities in the lab. However, when reaching commercial scale, their disposal can become problematic. Choose a CMO that can handle and dispose of such waste properly. This is probably an area many overlook but it’s still an important part of the process that needs to be handled appropriately.
- Continuously focuses on process improvement.
Sponsors, patients and the environment benefit when a watchful CMO continuously monitors and tweaks the manufacturing process to streamline production processes and improves yield. The more efficient the process, the lower the API cost and the greater the reduction in waste. Ask for examples of how the CMO has implemented process improvements while keeping within regulatory approvals.
- Has dedicated, experienced project managers.
A strong project manager is essential through all project phases, including commercial API manufacturing. This is a person you can rely on for project coordination, open and frequent communication, and assurance of creating and meeting realistic production timelines. Ask about the people who will be assigned to your project, including their experience and time with the CMO. (A senior person who has been job hopping could be a red flag.)
- Is focused on speed to market.
At PCI Synthesis, we take pride in deploying innovative scale-up solutions that can reduce your cost of goods and optimize throughput to bring products to market as quickly as possible. Ask potential CMOs for examples of finding solutions that reduced costs and increased speed to market.
- Has won numerous awards.
We don’t like to toot our own horn, but we’re very proud of the fact that the hard work of our highly experienced scientists and project managers, day in and day out, has been recognized by industry leaders, earning PCI Synthesis numerous CMO awards. Ask prospective partners about industry validation and awards as part of the reference check.
- Has the equipment to seamlessly transition from lab to commercial manufacturing.
Our plant’s 22,000 gallon capacity enables our sponsors to seamlessly transition from pilot quantities through commercial manufacture, saving time and money.
- 65,000 sq. ft. facility
- 23 reaction vessels with 22,000 gallon total capacity
- Class 100,000 cGMP kilo suites
- Temperature capability of -50 to 225oC
- Hastelloy, Glass and Stainless reaction vessels
- Filtration/Drying capabilities
- Validated Purified Water
From pre-tox to commercial manufacture, PCI Synthesis has the equipment and the experience to be with you every step of the way. With our decades of expertise in developing and manufacturing APIs and NCEs, you can count on us for consistently proactive management of project budgets and timelines.
Getting to commercial API manufacturing is a great step. But the work continues, and the 10 factors we’ve identified are important when deciding on the clinical manufacturer with whom to partner. If you have questions, our experienced R&D team is ready to talk with you to help you accelerate your most pressing commercial API manufacturing project. You can call us at (978) 462-5555. Or sign up for our newsletter with other helpful topics.
- Challenger, Cynthia: QbD in API Manufacturing. Pharmaceutical Technology 38:9, Sept. 2, 2014
- Siew, Adeline. Optimizing API Manufacturing. Pharmaceutical Technology Supplement: September 1, 2016: s6-s10.
About the Author
Ed is the President and CEO of PCI Synthesis (PCI), he serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA).
Do you have questions? Talk to Ed.