A practical perspective on process understanding, technology transfer and sterile manufacturing readiness.
Written by David Cox, Site Director at Eramol
David has more than 20 years’ experience across engineering, technical functions, sterile manufacturing, technology transfer and pharmaceutical site operations.
Connect with David on LinkedIn
Across a career spanning engineering, technical functions, sterile manufacturing, technology transfer and site operations, one pattern becomes difficult to ignore.
When a sterile fill-finish programme runs into trouble, the cause can often be traced to a much earlier decision.
A programme may look ready. Drug substance has been manufactured, equipment selected, a quotation approved and a filling date discussed.
But are the foundations really in place?
Can the formulation pass through the proposed equipment without changing? Has the sterilisation route been justified? Is the container suitable? Are the analytical methods ready? Has enough material been allowed for testing, stability and process losses?
A programme can resemble a facility fitted out before the process has been fully understood. Everything looks complete, but the weaknesses appear once operations begin.
Is technology transfer more than paperwork?
The strongest transfers are rarely the ones with the largest document packs.
They are the ones where the receiving team understands why the process works.
A process description is like an equipment manual. It may explain which button to press, but not what to do when the equipment or product behaves differently.
This becomes harder when each function speaks its own language. Development may talk about product characteristics, engineering about equipment limits, operations about practical execution and Quality about control and evidence.
They may all understand their part, but do they understand the same process?
This is where the Britest approach can be valuable. Its focus on whole-process understanding and visual tools helps multidisciplinary teams turn their individual knowledge into a shared view of the process.
Creating that common language allows teams to explore what happens at each stage, what the product experiences and where control may be lost.
Early development will always contain gaps. The danger comes when a gap is treated as a fact.
Visible uncertainty can be managed. Hidden uncertainty tends to become delay.
How many vials are really needed?
A clinical study may require 500 vials, but does that mean the manufacturing requirement is also 500?
Material will be needed for testing, stability, retained samples and possible replacements. Product will also remain in vessels, filters, tubing and filling equipment.
It is similar to planning production from the equipment’s stated capacity rather than its proven output. The two figures are rarely the same.
The better question is:
“How many releasable vials can be produced from the material available?”
For scarce products, getting this wrong may affect more than cost. It may move the clinical timeline.
Has the correct process route been chosen?
Terminal sterilisation may offer a strong route where the product and container can tolerate it. Heat-sensitive products may require sterile filtration and aseptic processing.
The choice cannot be based only on which equipment is available.
That would be like selecting a production line before fully understanding the product. The line may run, but is it the right process?
A late change can affect the formulation, facility, equipment, validation, container and stability programme.
What first appears to be a manufacturing choice can quickly become a programme-wide issue.
Is the vial really just packaging?
A vial and stopper may be described as packaging, but the product could remain in contact with them for months or years.
Could the product stick to the surface? Could oxygen, light or silicone affect it? Could the closure lose integrity?
The container is less like a cardboard box and more like part of the process equipment. Its performance can directly affect the product inside.
Availability matters too. The technically correct component may become the wrong programme choice if it has a long lead time or cannot be supplied in the required quantity.
Early decisions preserve options. Late decisions narrow them.
What is quietly controlling the timeline?
The manufacturing date is easy to see.
Analytical readiness, component availability, quality agreements and QP review are less visible. Yet any one of them may determine when the product can actually be released.
Can testing rescue a weak process?
A sterility test cannot make up for poor bioburden control, unsuitable hold times or weaknesses in aseptic practice. Testing should confirm that the process worked, not try to rebuild confidence afterwards.
Bringing the QP into the programme only when the batch is ready for certification can create a similar problem.
It is like asking Quality to inspect a facility after construction has finished. Changes may still be possible, but they will be slower, harder and more expensive.
Is filling really the finish line?
After filling come inspection, packaging, labelling, QC testing, QP certification, storage and shipment.
Sterile clinical supply is closer to a relay race than a sprint. A strong performance during manufacture cannot recover time if the baton is dropped during testing, release or packaging.
The most useful plans work backwards from the patient:
Site delivery → packaging → QP release → testing → manufacture → material readiness
When these links are visible, the programme can be managed as one connected process rather than a collection of separate departments.
Final reflection
Readiness does not mean having every answer.
It means knowing which questions remain, what they could affect and who is responsible for resolving them.
It also means creating a common language around the process so that technical, operational and quality teams are discussing the same risks, assumptions and controls.
Good planning cannot remove uncertainty from early development. It can prevent uncertainty from remaining hidden until it becomes a delay, a deviation or a failed batch.
The GMP batch may be where the problem becomes visible.
It is rarely where the problem began.
Preparing an early-phase sterile programme?
Eramol supports sponsors in building a clear, practical route from product and process understanding through to sterile manufacture, testing, QP certification and clinical supply.
Speak with our team to review your formulation, batch requirements, container format, analytical readiness and proposed clinical timeline.
Discuss Your Sterile Fill-Finish Programme
References and further reading
- Britest Limited. What We Do: Mapped Whole-Process Understanding.
Britest describes a structured approach to whole-process understanding that uses visual methods to connect knowledge across technical, operational and organisational boundaries. This supports the article’s discussion of creating a shared process view between development, engineering, operations and Quality.
Explore the Britest approach - European Commission. EudraLex Volume 4, Annex 1: Manufacture of Sterile Medicinal Products.
The principal EU GMP guidance for sterile manufacture, covering contamination control, aseptic processing, sterilisation, process design, monitoring and the use of Quality Risk Management.
Read EU GMP Annex 1 - International Council for Harmonisation. ICH Q8(R2): Pharmaceutical Development.
Guidance on developing a scientific understanding of the product and manufacturing process, including the relationship between material attributes, process parameters and product quality.
Read ICH Q8(R2) - International Council for Harmonisation. ICH Q9(R1): Quality Risk Management.
Guidance on identifying, assessing, controlling, communicating and reviewing pharmaceutical quality risks throughout development, technology transfer and manufacture.
Read ICH Q9(R1) - European Commission. EudraLex Volume 4, Chapter 1: Pharmaceutical Quality System.
EU GMP guidance linking pharmaceutical development, technology transfer, investigational-product manufacture and commercial manufacturing within an effective Pharmaceutical Quality System.
Read EU GMP Chapter 1 - International Council for Harmonisation. ICH Q14: Analytical Procedure Development.
Guidance on developing analytical procedures that are scientifically sound, risk-based and fit for their intended purpose, supporting reliable testing and release decisions.
Read ICH Q14