How to Guide: 6 Tips to Successfully Outsource Process Development

Introduction
This how to guide will help you to avoid some of the common pitfalls of outsourcing process development (PD). It lays out a framework and defines six key areas of focus for anyone considering outsourcing any portion of process development, and is starting to evaluate potential partners.
By following the framework and checklist, you will be better prepared when approaching an outsourcing partner. You will be better informed, will know what to look for during evaluation, and ultimately this will lead to a higher probability of a successful project with your chosen partner.

1. Striking a Balance with Cost Containment
Cost plays a significant role in the development of any drug. Companies must find ways to control and lower overall spending, especially in today’s climate where drug prices have come under increased scrutiny. When it comes to PD, cost containment is achieved by limiting the number of development runs. But a word of caution – to guarantee efficient process scale-up, gathering sufficient knowledge to build a robust and cost-effective manufacturing processes is mandatory. When there is insufficient process knowledge, data or high quality biological material, troubleshooting at the development stage as well as large scale is extremely difficult and can be expensive. Therefore, fine-tuning process parameters at the PD stage should be focused on increasing product yield and defining process limits. Attention to detail and gathering of process information during this phase will almost certainly enable late stage manufacturing and lead to significant cost reduction. In other words, spending more on PD may result in higher margins when the drug product is manufactured.
An excellent place to start exploring the possibility of outsourcing your PD is by fully understanding your budget. The size of your budget will be dependent upon your current process knowledge and the requirements for overall drug quantities required to fully treat your patient population. Determining the end goal of your process and establishing the requirements for locking in an optimized and robust manufacturing process is mandatory because this data will provide you with a rough estimate of your overall costs. With high competition, everyone is constantly vying for funding. If you find yourself in that place, ask your preferred PD partner for help in putting together a compelling case to illustrate why proper PD funding is critical for your company’s long-term success.

Don’t get caught up in trying to move too fast or be tempted to cut corners in areas such as process development. It is essential to ensure that your therapeutic is built on a reliable process. This will save you time, reduce risk, and avoid challenges in the future.

2. Setting Realistic Timelines
If you are outsourcing PD, it is highly recommended that you allow sufficient time to reach your goals and dedicate the appropriate resources to the project. Poor planning can cause significant delays to the developmental timeline and may even result in failures. As such, we recommend that you balance realistic expectations with optimism when it comes to setting project timelines and risk mitigation plan.
Your chosen partner should be able to provide estimates for project duration after you have engaged in in-depth discussions about your product requirements and status of your developmental program. It is critical to prospectively build out a few possible scenarios for delivery of milestones and assure that these strategies are clearly communicated to your leadership. Best and worst-case scenarios should be considered and a plan created for each. Visual project management is an extremely useful tool that should be used.
Be aware of pitfalls that occur when teams don’t account for logistics. When you are vetting an outsourcing partner, spend time asking questions about how the team will handle logistics for your projects – specifically around processing, reporting, and communication. Ask about how they track inventory, and their re-order points both internally and with third parties.
Your partner should also be able to provide you with insight into regulatory requirements that are associated with shipping biologic materials.

Make sure the proposed project Gannt chart accounts for logistics and clearly maps out nonscientific action items. Significant project delays can occur when teams only consider scientific action items and neglect those that are nonscientific.

3. Variability in Process and Platform Development
It is critical to account for variability when developing a process for your therapeutic. Acknowledging and understanding the potential causes of variability allows teams to engage in productive discussions on how to prospectively plan for potential challenges that may be encountered throughout all stages of PD. This interaction will facilitate the process of addressing short-term risks, especially when trying to scaleup the process. It also avoids being caught offguard when entering clinical manufacturing.
Process variability studies tend to be deprioritized during PD. This can result in significant expenses at later stages in the drug development process, caused by the need to troubleshoot and establish these parameters.
So, what can you do? Start by asking if your outsourcing partner will perform qualification studies of your process. Don’t assume this activity will be performed, given it’s a significant and costly undertaking and many don’t offer it or have the capability. If some type of qualification is provided, make sure to understand if the partner will establish a range that is deemed acceptable for manufacturing. Regardless of whether your current PD partner offers qualification or not, you need a plan for testing relevant critical quality attributes of your product that will be used as release criteria during clinical manufacturing.
Robust and predictive assays should be in place before you initiate process development because without these tools, you will not be able to accurately assess the consequences of process changes as you scale to larger volumes.
Additionally, your acceptance range for product yield potency and purity should be well defined before entering clinical manufacturing. Not having established these conditions and ranges can cause release delays and impacts to your bottom line.

Another strategy is to inform your partner on the number of molecules in your portfolio and ask if they can test (not validate) if their process can be adapted to those molecules. Ultimately, it is sensible to ask yourself how many rounds of testing would give you confidence at production scale before transfer to manufacturing. You need to strike a balance between demonstrating robustness and qualification which will encompass many runs.

4. Choosing the Right Partner
Companies specializing in process development offer a wide range of services, and not all providers are equal. Some specialize in earlystage PD, others possess deep expertise in scale-up, whilst others offer the full gambit of development services including early-stage development through pre-clinical, clinical and GMP manufacturing.
When evaluating potential partners, the first order of business should be to gauge where you fall in the PD journey. This analysis will reveal what type of service you require. For example, if you have not screened and established the best media and cell line, then you will likely need partners who have expertise in early-stage PD. While evaluating partners, have them list their expertise. Take that list and compare it against your current process needs. Deep dive into their claimed competencies to understand whether these are based on inhouse knowledge or are they leveraging outside vendors, such as cell line development. If you are outsourcing early-stage process development, find out if the partner has capabilities to industrialize or scale-up the process.

Depending upon your internal expertise and needs, it might be necessary to engage a partner that can provide regulatory guidance and one that possesses the capabilities to manufacture your drug product under GMP processes. These capabilities are associated with cost, so as previously mentioned, it is important to evaluate your needs and balance them with your overall budget. In many cases, it is sensible to initiate your early PD with a skilled organization that has extensive expertise in early stage PD and industrialization of processes. This can save on cost and can be especially attractive if the chosen partner has strong working relationships with contract manufacturing organizations (CMO) that can work with the provider to seamlessly transfer the optimized industrialized process into their facilities.

5. Communication
Good communication is vital for efficient PD success. It is essential for both the client and partner to establish clear and open lines of communication, where relevant PD information is consistently shared.
First, ensure that your team is willing and capable of being fully transparent with the chosen partner and that the partner has the same mindset. This is critical because without full transparency your partner can be left blindsided and incapable of delivering results or quickly addressing problems which arise during PD. Second, ensure that communication is at the top of the list during your evaluation of a partner.

There are several questions to consider when evaluating your PD partner’s communication skills. These include:

• Their proposed method and cadence of communication with you and your team
– Do you have direct access to their subject matter experts?
– Do they schedule regular technical meetings to discuss results and define next steps?
– Are they willing and able to engage in unplanned meetings to address challenges that may unexpectedly arise during process runs?
– These and other similar considerations should be discussed with the potential partner during exploratory meetings. A preferred partner will align with your expectations and requirements

• Their mode of communications
– Start by assessing how they interact with customers
– It is important to assess whether they can offer secure portal(s) for transfer of sensitive documents and protection of communications

• Whether or not the partner is outside your native country
– If they are located in another country it is recommended that you request examples of how their team has worked with international customers and what were the results as well as experience and know-how on importation of biological materials

• Whether or not the team communicates challenges in a proactive manner and has a history of working collaboratively to take appropriate actions to ensure projects will not fail
– Learn and look at examples of how their team handles challenging communication and deals with ambiguity

6. Planning Technical Transfer
It is well documented, that the transfer of processes from one site to another can cause significant bottlenecks in PD. Tech transfer also represents one of the highest risk areas which can delay execution of PD projects. This includes both the first tech transfer from the client to the partner, as well as the final tech transfer of the locked process from the partner back to the customer.
A successful tech transfer requires the commitment of time and resources from both you and your partner in many areas. Attention to detail when planning the tech transfer is key.
A successful tech transfer includes plans around the following:

• Sufficient and accurate technical information describing your process
• Planning logistics around material transportation and ordering supplies and any necessary equipment
• Clear understanding of regulatory requirements for exchange of materials between sites
• Sufficient resource allocation

The time and effort expended mapping out all logistics required for your process are well worth the investment. As an example, you should obtain a clear understanding of shipping schedules of equipment required to run your process, along with any required consumables. These should be prospectively identified. Ordering and receipt of the appropriate materials should occur well before a transfer is scheduled.

Take a closer look at historic delivery timelines from the vendor and incorporate those into your overall plan. Discuss who will be sent to train you or CMO staff, and how much time will be allocated for the training.

Summary
When it comes to scientific research and experimentation, including outsourcing process development, there is no silver bullet for success. Each project will have its highs and lows.
Pall’s PD experience working with many customers has helped us develop a multistage process. Recommendations contained within this guide will increase the probability of achieving desired results for your drug product, as well as forming a lasting collaborative partnership.

Final Check List

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