There has been a lot of discussion recently concerning process validation and technology transfer, including utilizing virtual technology transfers to quickly move products through the development flow or to expand manufacturing capabilities. The purpose of this blog is to provide insights into aligning technology transfer expectations with process validation requirements in a virtual world. We will provide you with an understanding of the methodology for tech transfer and show you the benefits of aligning analytical transfer and validation for efficient and successful results. We will also discuss how you can support operational expectations with requirements, and the importance of having a tech transfer validation program.
Per ICH Q10, “The goal of technology transfer activities is to transfer product and process knowledge between development and manufacturing, and within or between manufacturing sites to achieve product realization. This knowledge forms the basis for the manufacturing process, control strategy, process validation, and ongoing continual improvement.”
As a previous coach once told me: “Practice does not make perfect, only perfect practice makes perfect.” Performing a “perfect technology transfer” requires establishing a well thought out methodology utilizing process validation expectations.
ProPharma Group advocates for a stage gated technology transfer process aligned to feed directly into process validation without redundant work. This methodology divides the technology transfer into gated stages which ensure that predecessor items are completed prior to moving forward with the next phase, because missed steps are the devil’s playground.
ProPharma Group has spent years aligning the methodologies in our gated approach to ensure the value of the technology transfer is directly translated into a successful process validation. Recent updates to the ICH Q12 have opened new opportunities to utilize multivariant analysis to truly understand manufacturing processes. Our gated technology transfer process applies requirements across multiple FDA and EMA guidance documents to ensure that the boundaries, critical process parameters, and risk analysis are developed appropriately to reduce the level of transferred process risk and to ensure a compliant process validation.
A key component to a successful tech transfer is the availability of strong analytics to demonstrate equivalence and to confirm that the process is performing correctly. The analytical portion of the technology transfer and analytical method validation starts with assembling a team. The team should include Quality Control analysts, Quality Assurance representatives, and purchasing and statistical support.
Analytical transfers start with a list of available tests, their status, and those that are needed. Next a list of equipment and materials are developed to support the transfer. Raw material finished product and in-process test procedures are exchanged. Technicians from the receiving site are sent to the sending site to run the bank of tests with the technicians and confirm the techniques are repeatable. The same process is repeated with technicians from the sending site going to the receiving site to confirm techniques, materials, and equipment are equivalent.
Analytical variability also needs to be assessed for the methods, materials, and analysts. The final step is to perform round robin testing to confirm equivalency with the same sample. Utilize virtual systems such as laboratory information management system (LIMS) to allow analytical team members to log on and evaluate the data remotely.
You must first define the full process to be transferred and the status of the existing process. Among the key items to evaluate are the storage conditions for raw materials, the classifications required for process steps, and the methodology for bringing personnel through the process. An equipment list, skill sets for resources, capacity requirements, and Chemistry Manufacturing and Controls (CMC) requirements all need to be defined. You also need to ensure that a quality by design (QbD) process is employed. Per the Juran Trilogy, a QbD process adheres to the following steps:
Next, you need to develop a team to implement an operation’s technology transfer with the goal of completing a compliant technology transfer and implementing process validation. The team is typically composed of personnel from the sending site/ development team and personnel from the receiving site. The team should include operators, maintenance, calibrations, cleaning, quality, engineering, validation, IT, and project management staff. Establishing a Microsoft Teams site or other virtual platform is important to allow population of data/files and review in a virtual space. You may need to work with the IT department to build needed folder structures and alerts.
The next step is to assign tasks to the team based on deliverables. Deliverables are laid out starting with identification of the finished product requirements, process flow, process controls, process risks, equipment, facilities, utilities, and raw materials.
QA teams need to review CAPAs and change controls and determine if the process is capable of being validated. My recommendation is to employ an Agile methodology for virtual teams to quickly review updates and provide feedback on how teams are performing against expectations. The process is simple, and all tasks are arranged into sprints.
Sprints are series of events which need to be completed to accomplish a deliverable. The tasks are divided into “to do”, “doing”, and “done”. Each task has an owner, a due date, and description of how it is related to the deliverable. Teams meet virtually on a phase specific period of time to review status and offer support. Project managers or team leads meet with leadership to align timelines, resources, and establishment of expectations and deliverable sequence.
Alignment through program policies allows teams and individual contributors to understand the path for their work while preserving the corporation’s ability to set boundaries and declare expectations. There are three reasons to establish programs, but I also want to stress the need to maintain flexibility within each program to allow the team to meet patient needs rather than bureaucratic needs.
Reason one is that regulatory agencies expect a company to utilize a documented program for both technology transfers and process validation. The program allows practices and processes to demonstrate how your company complies with regulatory guidance. I’ve never been a proponent of doing things because a regulatory body dictates something, but rather because these are the right things to do and provided by experts with years of experience supported by industry experience.
Reason two is speed. By starting with a documented technology transfer aligned with the process validation program it will substantially reduce the time it takes to bring products through the development phases. Several steps can run in parallel as well as the front loading of long-term constraints, such as specialty equipment, analytical methods, or materials that need to be developed.
Reason three is the financial impact. Without alignment of technology transfer and process validation programs, companies need to align testing and ensure that not only are you demonstrating equivalency but also building data to apply to the risk analysis, using multivariant analysis to confirm CPPs, and utilize as part of process validation. A solid technology transfer should utilize critical process parameters as the basis for the transfer fits cleanly into the process validation risk reduction. Ineffective and inefficient processes cost significantly more even in the short term than well structured, well controlled processes.
To learn more about how we can help you with your technology transfer, contact us today.
December 17, 2020
Quick, can you name the top 10 Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) of your bio-pharmaceutical manufacturing process? Well if you hesitated don’t feel bad. Most...
December 17, 2020
During product development some sponsors struggle to determine how their product will be regulated by the FDA. Will it be considered a drug, medical device, biologic, or combination product? Based...
December 17, 2020
If you have been following along, you now know that I have reviewed the first three gates to the Nine Gate Transfer Process for moving production from site to site. I have covered: Gate 1: Assessment...