De-Risking Tech Transfer: A Smarter Path to Faster, More Reliable Outsourcing Outcomes

Tech transfer is conceptually a straightforward process, but it is fraught with minutiae and unknowns that can introduce delays, unplanned costs, and batch failures. When working with a CDMO like AGC Biologics, an approach that executes technology transfer in stages is designed to speed up the process while simultaneously mitigating the risks of making decisions before a complete process fit is worked out. There are two main scenarios to consider below.

CDMO lab to CDMO manufacturing facility

This scenario holds the promise of fit decisions being made during process development. Materials can be adjusted to accommodate vendor shortages, secondary vendors can be identified and validated, and equipment-related capital expenditure (CAPEX) can be avoided by developing the process to operate within the receiving facility’s manufacturing equipment ranges.

Client lab/client facility to CDMO manufacturing facility

This scenario can entail an early- or late-stage project scaling up for larger batches (e.g., clinical or commercial production), or it can be a late-stage project being redeveloped to yield higher productivity.

Stage 1: Request for Proposal (RFP)

The first stage is the request for proposal (RFP), where the CDMO proposes how it would execute a high-level process description in its facility. The RFP culminates in a signed agreement between the client and the CDMO.

Common challenges of the RFP stage are:

• Inadequate understanding of the process requirements by the CDMO

• Determination of CAPEX equipment purchases to meet project lead times

• Determination of long lead time chemicals, media, resins, and consumables

• Matching customer timeline needs to the CDMO’s schedule

Providing a CDMO with in-depth information to ensure a detailed fit is essential. The best fits are produced when client scientists are able to communicate directly with the CDMO’s manufacturing science and technology (MSAT) engineers.

Stage 2: Detailed Process Fitting

Process fit starts at a low level of detail and simplified information then after iterations to an in-depth, highly detailed process description. Each unit operation must be understood in terms of its purpose and operating requirements. Every facility has operating ranges and practices known to be reliable. Attempting to match client expectations to a facility’s known safe operating range inevitably exposes gaps that must be defined (in terms of scope and impact) and addressed.

Sometimes, the solution requires additional CAPEX, changes in work practices, or reevaluation of the process at lab scale. In most cases, a transfer to a CDMO is accompanied by batch-size scale-up, which can introduce new complexities.

Here are some tools AGC Biologics employs to manage a tech transfer’s complex and diverse activities:

1. Risk Registers

In almost all transfers, some risks must be taken by the CDMO or the client. A risk register maintained during process fit activities helps ensure risks aren’t overlooked.

2. Process Models

This is the output of a process fitting, which captures the process’ operating parameters, batch size, and timing. AGC Biologics divides each process into upstream and downstream, with harvest being the last upstream unit operation.

3. Master Process Instructions (MPI)

This document captures and describes the operating parameters and essential information for all unit operations. The MPI is a governing document used to author the master production record (MPR).

4. Master Production Record

The MPR contains detailed instructions for each unit operation, acting as a repository where data is recorded during batch execution. It may be used to capture procedural and equipment specific instructions outside the MPR.

5. New Product Introduction (NPI) Change Request

This formal quality document assesses the safety and cleanability of incoming molecules, cell lines, and other materials used in the manufacturing process.

6. Document Timing Calendar

A schedule for drafting, reviewing, and approving change requests, MPIs, and MPRs needed for manufacturing.

7. Bill of Materials (BoM)

First prepared during the RFP stage, this document is continuously refined as the process is fitted to the facility.

Stage 3: First Run at Scale (FRAS)

Depending on the client’s timelines, resources, and confidence, the FRAS can either be a non-GMP engineering run or a GMP production batch. The FRAS is the culmination of several components, including:

• Cell line introduction

• BOM ordering

• Material release

• Production scheduling

• Document authoring

• Operator training

• Automation method authoring

• Documentation issuing

• Material dispensing

These activities enable a manufacturing team to successfully execute the product recipe. Following the FRAS there is a cycle of review and adjustment, where improvements are investigated and applied to make the process more robust.

A successful technology transfer sets the stage for GMP production and opens the door to Process Performance Qualification (PPQ) campaigns and commercial licensure. That success depends on prompt, accurate communication between the customer and the CDMO, as well as transparency. For effective communication to occur, it is critical that the customer and the CDMO form consensus on who needs to be involved in every discussion. Each partner must strive to make those individuals available when they are needed, producing efficient decision-making and confidence in any agreed-upon solutions (i.e., everyone with relevant expertise or thoughts on the issue has weighed in).