The age-old debate of whether to outsource production to a contract manufacturing organization (CMO) remains for mature, emerging and virtual biopharmaceutical companies.
The core of the issue is brand protection. While outsourcing can minimize capital and labor costs, the challenge lies in the process of evaluating and selecting the right CMO as your manufacturing partner. How can you minimize potential consequences, including damage to your brand and loss of market share and revenue? How can you minimize the risks to product quality? Can you ensure that equipment, processes and procedures used in manufacturing will maintain the intended strength, integrity, safety, purity and quality of the drug or product? And how can you do it all within budget?
While the answers to these questions will be specific to each company and its products and processes, below are some key drivers to help you make the right decision if you do turn to a CMO. Keep in mind, these drivers need to be in line with your business goals and ultimately take your product to market in a safe, compliant and cost-effective manner.
Contract manufacturing organization considerations
A CMO that already has a number of clients may have a small window in which to produce your drug. Consider some of the following questions:
- Does the batch size and length of filling time required to produce your drug on their machines increase your risk?
- Does the speed of their machines match your batch size in volume, timing and capacity?
- Will your batch size and number of lots be a small fish in a large pond or possibly overwhelm their production schedule?
- If there’s an upset in manufacturing, will your manufacturing date get postponed? If you are manufacturing for a specific time period or seasonal distribution, and you miss the date, you could lose your market share. Technical competence, available machinery and resources must be accounted for.
- Is the equipment built to reduce rejects?
- Does the equipment have the dose accuracy or volume control to meet your user requirements?
- Can the bulk of the batch be preserved if a machine failure occurs?
- Can the CMO staff provide feedback of developmental work or troubleshooting work they have successfully executed?
Technology/equipment capacity and capability
Each product will have its own unique set of critical quality attributes and process parameters that will need to be considered to determine whether the CMO has the correct fit of technology and expertise:
- Does your product have special handling or temperature requirements?
- Is the product susceptible to foaming or clumping?
- Is the product shear sensitive?
- Is the product uniform or homogenous, or does it require some type of mixing or blending?
- What is the sensitivity to bio-decontamination or cleaning chemicals?
- Is the product highly viscous or sensitive to temperature, light or oxygen?
- Is the product a controlled substance?
- Is the CMO set up to handle this type of end product?
- If the product has to be recirculated, does the CMO have the right in-line process equipment? What does that cost? Is it included in the proposal cost? How automated will it be?
- What controls are in place to prevent excursions?
- How much experience does the CMO have with this technology or these types of products?
Operator exposure limit understanding and containment strategy
Because CMOs may run two days of product for one client and then two days for another, cross-contamination prevention will be key. If there are any highly hazardous compounds that are produced in the facility, how is it controlled and contained? What are the cleaning procedures between products? While each facility should have its own thought-out containment strategy, companies may still want to have a dedicated set of equipment format and product contact parts exclusively used for their runs. Drug products created for specific high-risk populations may have additional containment requirements as well. Ensure the CMO can accommodate them.
Equipment reliability and lifecycle
Manufacturing equipment is advancing very rapidly—especially in the area of microelectronic sensors, vision systems and analytical instrumentation—so fast, in fact, that equipment more than five years old is likely to be obsolete to achieve all your requirements. Equipment even older than that may not have the sensors or instrumentation to detect many of your critical defects in line. This translates into lost product and lost revenue. When touring the facility, ask how old the existing equipment is and ask to see it run. Inquire about the equipment manufacturer and any problems with it. Maybe the equipment has been in the storage room for four years, but when examined, it is actually 20 years old. If so, how will the CMO replace a spare part if needed? Are the controllers on the machine even available for purchase, or is the CMO shopping online bidding sites to find replacement parts?
Take a closer look at a potential contract manufacturing organization
Check out the history of observations by regulatory agencies
Manufacturing facilities are built to protect the operator, the product and the patients, so quality systems and facility and equipment design are critical. When considering a CMO, do your homework. Research its history with regulatory agencies, its documentation practices and its process and testing procedures, including responsiveness to problems and corrective and preventative actions previously documented. Are their operators well trained? Do they understand the Current Good Manufacturing Practices and the nature of why your procedures are written the way they are? Search the Food and Drug Administration’s website for a CMO’s previous inspection observation summaries. Some questions to ask include when was the last inspection, what were the findings, what were the responses to remediate the observations? Were the responses accepted, and were the corrective actions completed and verified?
Conduct personal interviews
You can’t just rely on industry reputation and past experience; you must conduct personal interviews with the CMO’s executives, management and current staff on site before you sign a contract. You will need to interview previous and existing customers and rely on vendor feedback. When touring the facility, ask about the existing equipment and its history:
- How old is the equipment?
- What products were produced on the equipment?
- What is their reject rate for a given batch size?
- Will any new equipment need to be purchased for your runs? Will that be included in the quoted price?
- What is the delivery lead time of that equipment?
- When will it be qualified?
- During their last process simulation, what were their findings? Did they have any issues?
- Have they had any recalls? Why? What is the root cause, and was it corrected?
Overall, the evaluation of a potential contract manufacturing organization should be driven by the specific parameters of your unique process and business goals. Partnering with a third-party process specialist like CRB with the necessary industry knowledge and experience will be critical to identifying potential risk and cultivating a relationship with the right CMO.