Process Development & Characterisation
Process development is where the organisation stops asking "can we make it" and starts asking "do we understand how making it works". The quality-by-design frame of ICH Q8 supplies the grammar: a quality target product profile states what the product must be; critical quality attributes are identified from it; and systematic studies — risk assessments narrowing the variables, designed experiments mapping their effects — establish which process parameters are critical and across what ranges the process delivers quality. ICH Q11 extends the same thinking to the drug substance and, for biologicals, to the definition of a manufacturing process whose product is inseparable from it. The output is a control strategy: the planned set of controls, from material attributes through process parameters to specifications, that together assure quality.
What this page does not claim
Phases are an organising device, not a regulatory mandate — real programmes overlap them, and a medical device, a food product and a small-molecule drug traverse them differently. Each page says where the differences bite.
What happens in this phase
Process development is where the organisation stops asking "can we make it" and starts asking "do we understand how making it works". The quality-by-design frame of ICH Q8 supplies the grammar: a quality target product profile states what the product must be; critical quality attributes are identified from it; and systematic studies — risk assessments narrowing the variables, designed experiments mapping their effects — establish which process parameters are critical and across what ranges the process delivers quality. ICH Q11 extends the same thinking to the drug substance and, for biologicals, to the definition of a manufacturing process whose product is inseparable from it. The output is a control strategy: the planned set of controls, from material attributes through process parameters to specifications, that together assure quality.
This maps onto Stage 1 of FDA's 2011 process validation lifecycle — process design — and the quality of work here decides how much burden the later stages carry. Characterisation studies at small and pilot scale, with scale-down models justified against the commercial process, generate the proven ranges that qualification will confirm. Modern variants change the toolset without changing the logic: continuous manufacturing under ICH Q13 shifts control from end-of-batch testing toward real-time monitoring and material traceability through a dynamic system; process analytical technology moves measurement into the process; and analytical method development under ICH Q14 runs in parallel, because attributes only exist operationally once a method can see them.
The multi-industry framing matters here. Food safety runs this phase as HACCP and preventive controls: hazard analysis identifies biological, chemical, and physical hazards, and critical control points with validated limits — the food-safety plan under 21 CFR 117 — stand where the pharmaceutical control strategy would. Devices run it inside design controls, as design of both product and the processes that will make it, with process risk feeding the risk-management file. Cosmetics and veterinary products sit between, borrowing the pharmaceutical apparatus in proportion to risk. What is common is the deliverable: a documented, evidence-based understanding of how the process produces quality, owned before routine production begins, because everything downstream — validation, deviation investigation, change assessment — reasons from it.
- A defined product with a quality target product profile — or, for food, a product description and intended use grounding the hazard analysis.
- Candidate process knowledge from development or transfer, with initial risk assessments identifying the variables worth studying.
- Analytical methods able to measure the attributes under study, developing in parallel under ICH Q14 discipline.
- Representative materials and scale-down or pilot capability justified against the intended commercial process.
- Critical quality attributes and critical process parameters identified, with proven acceptable ranges supported by characterisation data.
- An approved control strategy — or validated food-safety plan — linking material attributes, process controls, and specifications to product quality.
- Process risk assessments completed and dispositioned, with residual risks explicitly accepted or carried into validation.
- A characterisation report package sufficient to design the qualification and validation stages against.
SPEQ synthesis. Phase boundaries and gate criteria are an organising device for planning and review, not a regulatory mandate. Real programmes overlap phases and re-enter them; treat these as the questions worth answering, not a compliance checklist.
- Chair the risk assessments that decide which variables are studied and which are dismissed — the dismissals need evidence too.
- Approve the control strategy and hold it to the characterisation evidence, not to precedent or convenience.
- Assure the integrity of characterisation data and the justification of scale-down models the conclusions rest on.
- Own the linkage from characterisation into validation planning, so Stage 2 confirms what Stage 1 established rather than discovering it.
- For food operations, own validation of the hazard analysis and the critical limits at each critical control point.
- Quality target product profile and the CQA identification rationale
- Process risk assessments and designed-experiment study reports
- Proven acceptable ranges for critical process parameters, with supporting data
- The approved control strategy — or the validated HACCP / food-safety plan
- Scale-down model justification linking study scale to commercial scale
- The process description and characterisation package that validation will confirm
- Characterising the easy parameters and asserting the hard ones, leaving the true edges of the process to be discovered by deviation.
- A control strategy written to match existing equipment habits rather than the characterisation evidence.
- Scale-down models never justified, so conclusions drawn at litres silently fail at thousands of litres.
- Analytical methods lagging process work, so attributes are "controlled" that cannot yet be reliably measured.
- Hazard analysis treated as a template exercise, so a real but unusual hazard — an allergen path, a novel impurity — is never on the list.
Derived from the 7 standards SPEQ maps to this phase, across 2 regulatory bodies: FDA, ICH.
FREQUENTLY ASKED
What is a control strategy, concretely?
The planned, documented set of controls that together assure product quality — derived from understanding rather than habit. Concretely it spans input material attributes and their specifications, process parameters and their ranges, in-process controls, facility and equipment conditions, and the finished-product specification, each linked to the quality attribute it protects. The linkage is the point: a control strategy is not a list of tests but a map from "what could go wrong" to "what stops it", which is why it becomes the reference for validation design, deviation impact assessment, and change evaluation for the product's entire life.
How does HACCP relate to pharmaceutical process development?
They are parallel answers to the same question: where can this process fail, and what controls the failure? HACCP runs hazard analysis across biological, chemical, and physical hazards, then establishes critical control points with validated critical limits, monitoring, and corrective actions — the architecture 21 CFR 117 builds preventive controls on. Pharmaceutical development runs risk assessment across quality attributes and establishes a control strategy. The vocabulary differs and so does the emphasis — food safety is hazard-driven, pharma quality attribute-driven — but a practitioner fluent in one recognises the other immediately.
Does quality by design mean more regulatory flexibility?
It can, but that is the by-product, not the purpose. Demonstrated process understanding — CQAs linked to CPPs, ranges supported by data, a control strategy with a rationale — gives regulators grounds to agree wider operating ranges and, under ICH Q12, a cleaner separation of what is binding from what is supportive, which reduces the transaction cost of change. But the primary return is internal: a process understood at this depth investigates its own deviations faster, assesses change impact credibly, and fails less often. Firms that pursue QbD purely for filing advantage tend to build the paperwork without the understanding.