Onshoring drug manufacturing: the tech transfer and validation path to a US site

Why it is on every agenda

The push to make more medicines in the United States, from policy, from supply security and from customers asking where a product is made, has sponsors moving products to domestic sites and CDMOs adding capacity to receive them. The receiving site is often new, or new to the product, and the transfer lands on a quality and CMC team that is already busy.

For an approved product, a new manufacturing site is a post-approval change. In the United States it normally goes to FDA as a prior approval supplement, and FDA may inspect the site before approving it. The transfer plan therefore has two customers from the start: the receiving site, which has to make the product, and the agency, which has to be shown that the product is the same.

The critical path

• Gap analysis between sending and receiving sites: process, equipment and scale, materials, methods, procedures and people, with each gap given an owner and a closure plan
• Facility, utilities and equipment qualification where the suite is new, or a documented assessment where it is already qualified for similar products
• Analytical method transfer with comparative testing, so the receiving laboratory's results can be trusted before the first batch is tested
• Engineering batches that find the equipment and scale differences before they appear in a PPQ batch
• Process performance qualification, with the number of batches justified from the process knowledge and its variability rather than taken as three by habit
• Stability on the PPQ batches, the supplement, and a site that can show an inspector its records on request

What makes the timeline slip

• Method transfer started after qualification instead of alongside it, so the laboratory is the last thing ready
• Equipment differences discovered during a PPQ batch rather than in an engineering run
• No comparability protocol agreed with the sending site, so the data from the two sites cannot be compared when the supplement is written
• A PPQ batch count with no justification on file, which an inspector reads as a process nobody understands
• Documents written for the submission rather than from the batch records, so the narrative and the evidence disagree

How QLogixCMC helps

QLogixCMC engineers run the gap analysis with both sites, write the transfer and comparability protocols, and are on the receiving site's floor for qualification, engineering batches and PPQ execution. The supplement, the method transfer reports and the PAI readiness work run remotely or on site as the deliverables require, and the quality unit of the receiving site approves every protocol and report.