Beyond SOPs: Janssen talks tech transfer complexities

Successfully transferring manufacturing tech to a second facility or CMO relies on site readiness and sponsor oversight, says Janssen.

In so many cases a pharma product’s development and production site are separate or – when using a contract manufacturing organisation (CMO) – operated by a different company, principal scientist at Janssen Supply Chain Chiali Liu told delegates at Biotech Week Boston last month.

“Very often when we think about tech transfer we think about scale-up, batch record, SOP [standard operating procedures] review, transfer investment, transfer process, making sure equipment is working well, and compliance with quality.”

But while these are all important, “success of production is contingent to site readiness,” she said.

“What can break or fail in production is not down to how good your process knowledge is transferred, but whether the site is ready.”

Janssen's third party manufacturing case studies:

Problem #1: A ‘side sample’ required with a drug substance shipment was missing

  • Root cause: ‘Side sample’ lack of mention in the SOP for packaging and manufacturing at the drug substance site. Furthermore, the SOP and the site had not been reviewed by Janssen.
  • Lessons learned:  Site SOP should be reviewed before it is implemented. Packaging/shipping should be observed when executed the first time

Problem #2: Shortage of QC test reagent

  • Root cause: Reagent supplier did not inform manufacturing site until last minute of an industry-wide test reagent, while on site QC consumed more reagent than expected on qualifying an assay
  • Lessons learned:  Confirm required quantity is already received and available on site prior to production, while issues on method qualification need to be communicated early

Citing a number of examples from Janssen – the pharma subsidiary of J&J – of when problems occurring at a third-party site have affected production creating a quality or regulatory impact, she stated none were related to the process or product knowledge.

Instead they were caused by communication and review errors, something Liu said is now a key area that Janssen focuses on to ensure similar issues do not reoccur.

“Preparation before production is necessary but not sufficient [alone]. Continued monitoring throughout production is required to make sure things go well. We are talking about so many tasks and putting together so many functions.”

Tech transfer tasks

Therefore Janssen – the biopharma subsidiary of Johnson & Johnson (J&J) – has a specialised core team which works across many functions in order to ensure site readiness in all its tech transfers

According to Liu, the key to site readiness, and thus a successful tech transfer comprises of the following tasks:

  • Transfer of process and product requirements
  • Transfer of analytical test methods
  • Raw material specifications
  • Cleaning validation
  • Equipment validation and verification
  • Material and inventory management
  • Shipping of products and samples
  • Long-term operation
  • Quality systems and oversight
  • Cultural aspects

Liu stressed the importance of the latter, as Janssen works with suppliers and manufacturers across the globe.

“Knowing the habit and culture of a region is very important if you are going to an international site,” she said, as something as basic as the staff’s working hours and habits can create difficulties in ensuring a smooth transfer.