A Critical Process Parameter (CPP) is a term used in pharmaceutical production for process variables which have an impact on a critical quality attribute (CQA) and, therefore, should be monitored or controlled to ensure the drug product obtains the desired quality.
- CPP & CQA of Tablets & Hard gel Capsules
- CPP & CQA of DPI
- CPP & CQA of Ophthalmics
- CPP & CQA of Ampoules
- CPP & CQA of FFS
- CPP & CQA of LVP
- CPP & CQA of Ointments
- CPP & CQA of Oral Liquids
Key CQA’s by Dosage Form
| Dosage Form | Main CQAs (Critical Quality Attributes) |
|---|---|
| Tablets | Identity, Assay, Content uniformity, Dissolution, Degradation products, Hardness/friability (if impacts performance), Water content, Microbial limits, Appearance (chipping, capping, spots) |
| Hard Gelatine Capsules | Identity, Assay, Fill weight, Content uniformity, Dissolution / disintegration, Degradation products, Moisture (shell & fill), Shell integrity/brittleness, Microbial limits, Appearance (cracks, splits, printed text) |
| Soft Gelatine Capsules | Identity, Assay, Fill volume, Content uniformity, Dissolution / disintegration, Degradation products, Moisture content, Leak test / seam integrity, Peroxide value (for oils), Microbial limits, Appearance (shape, sticking, oil leakage) |
| Sachets (Powder/Granules) | Identity, Assay, Fill weight, Content uniformity (per sachet), Dissolution / reconstitution, Particle size (if performance related), Moisture content, Degradation products, Microbial limits, Foil/seal integrity, Appearance (caking, lumps) |
| DPI (Dry Powder Inhaler) | Delivered dose uniformity, Emitted dose, Aerodynamic particle size distribution (fine particle fraction), Assay, Moisture content, Degradation products, Microbial limits, Device performance (actuation, dose counter), Content per blister/capsule, Appearance (powder flow) |
| Ophthalmics (Sterile) | Sterility, Bacterial endotoxin, Assay, Degradation products, pH, Osmolality/tonicity, Particulate matter, Preservative content (multi-dose), Viscosity, Drop size, Clarity, Container-closure integrity |
| Ampoules / LVP (Parenteral solutions) | Sterility, Bacterial endotoxin, Particulate matter (visible & sub-visible), Assay, Degradation products, pH, Osmolarity, Clarity, Container-closure integrity, Fill volume, Leachables (if applicable) |
| Ointments / Creams | Assay, Content uniformity (uniformity of dosage units), Degradation products, Microbial limits (topical) / Sterility (ophthalmic), Particle size (grittiness), Viscosity/spreadability, Phase uniformity (no separation), Appearance, pH (for creams/gels) |
| Oral Liquid Syrup/Suspension | Assay, Content uniformity, pH, Degradation products, Microbial limits, Preservative content, Viscosity, Clarity (solutions), Redispersibility (suspensions), Sedimentation volume, Organoleptic properties (colour, taste, odour), Appearance (no precipitation) |
Use this as a master CQA list when you build your QTPP–CQA–CPP mapping.
CCP / Critical Steps – by Dosage Form
These are process steps that are “CCP-like” – where failure can critically impact CQAs and often can’t be fully corrected later.
A. Tablets
Key CQAs to protect: Assay, CU, Dissolution, Impurities, Hardness/friability, Appearance, Microbial limits
Typical CCPs / critical steps:
- Dispensing & Sifting
- Correct weight, segregation avoidance, foreign particle control → protects assay, CU, impurities
- Blending / Lubrication
- Blend time, speed, fill level, order of addition → content uniformity, assay
- Over-lubrication → poor dissolution, low hardness
- Granulation (Wet / Dry / Roller)
- Granulation endpoint (LOD, torque), binder solution addition, impeller/chopper speed → dissolution, hardness, CU
- Drying
- Product temperature, drying time, LOD → stability, dissolution, impurities
- Milling / Sizing
- Screen size, mill speed → flow, CU, dissolution
- Compression
- Compression force, pre-compression, turret speed, weight control → hardness, friability, thickness, CU, appearance
- Coating
- Inlet temp, pan speed, spray rate, atomization pressure, weight gain → stability, appearance, dissolution (for functional coat)
- Primary Packaging
- Blister/strip sealing temp & pressure, leak test → moisture-sensitive CQAs, stability
B. Hard Gel Capsules
Key CQAs: Assay, CU, Dissolution, Moisture (shell/fill), Shell integrity, Microbial limits
Critical steps / CCPs:
- Blend Preparation
- Similar to tablets – uniformity & flow → CU, assay
- Capsule Shell Storage
- Temperature & humidity control → prevents brittleness or softening → shell integrity, dissolution
- Capsule Filling
- Machine speed, dosing disk/pin setting, tamping force → fill weight, CU
- Metal check / sieving of filled capsules
- Foreign matter → patient safety
- Polishing / Dedusting
- Remove loose powder → appearance, cross-contamination risk
- Printing & Packaging
- Correct print, no mix-ups, proper blistering/bottling → identification, stability
C. Soft Gel Capsules
Key CQAs: Assay, CU, Fill volume, Dissolution, Moisture, Seam integrity, Leaks, Peroxide value, Microbial limits
Critical steps / CCPs:
- Gel Mass Preparation
- Gelatin grade, plasticizer ratio, temperature, deaeration → shell strength, elasticity
- Fill Formulation Preparation
- Temperature, viscosity, antioxidant level → assay, uniformity, stability
- Encapsulation (Rotary die process)
- Ribbon thickness, sealing temperature, timing, alignment → seam integrity, leak rate, fill volume
- Drying / Tumble Drying / Tray Drying
- Time, temperature, airflow, RH → moisture content, shell hardness, brittleness
- Leak Test / Weight Check
- Detection of micro-leaks & variation → CU, stability
- Packaging (Blisters / Bottles)
- Protection from moisture, oxygen, light → impurities, peroxide value
D. Sachets (Powder / Granules)
Key CQAs: Assay, CU per sachet, Fill weight, Moisture, Dissolution, Impurities, Microbial limits, Foil integrity
Critical steps / CCPs:
- Blend / Granules Preparation
- Uniform mixing, appropriate particle size → CU, flow, dissolution
- Environmental Conditions in Filling Area
- RH & temp control to avoid clumping, moisture uptake → moisture, dissolution, appearance
- Sachet Filling Operation
- Auger/volumetric filler setting, line speed, vibration → fill weight, CU
- Sealing
- Jaw temperature, pressure, dwell time → seal integrity, moisture ingress
- Online Checks
- Net weight, seal integrity, leak test → directly protect dose, stability
E. DPI (Dry Powder Inhalers)
Key CQAs: Delivered dose uniformity, Emitted dose, APSD/FPF, Assay, Moisture, Device performance
Critical steps / CCPs:
- API Micronization / Milling
- Mill type, speed, feed rate, classifier settings → particle size distribution, hence FPF, lung deposition
- Blending (API + Carrier like lactose)
- Blender type, speed, time, load → adhesion of API to carrier, CU, DDU
- Capsule/Blister Filling
- Low-dose filling accuracy, vibration, de-aeration → delivered dose uniformity
- Device Assembly
- Correct fit of components, piercing mechanism, dose counter → device performance, DDU
- Environmental Control
- Dry conditions to avoid agglomeration → flow, dose emission
- Packaging
- Moisture-barrier packs, desiccants → moisture-sensitive aerosol performance
F. Ophthalmic Products (Solutions/Suspensions – Sterile)
Key CQAs: Sterility, Endotoxin, Assay, Impurities, pH, Osmolality, Particulate matter, Preservative level, Viscosity, Drop size, Clarity, CCI
Critical steps / CCPs:
- Water & Raw Materials (Incoming)
- WFI quality, bioburden control → baseline for sterility/endotoxin
- Solution / Suspension Preparation
- Order of addition, mixing speed, temperature, pH adjustment → assay, stability, particulate matter
- Sterile Filtration (0.22 µm)
- Filter integrity test (pre & post), pressure, time → sterility, particulates
- Container Preparation
- Washing, siliconization (if any), depyrogenation/sterilization → particulates, endotoxin, sterility
- Aseptic Filling & Stoppering/Capping
- Grade A conditions, interventions control, line speed, stopper feed → sterility, particulates, CCI
- Terminal Sterilization (if used)
- Cycle parameters, F₀, heat distribution → sterility, degradation
- Preservative Efficacy (for multi-dose)
- Correct preservative concentration → antimicrobial effectiveness
- Visual Inspection
- Particles, container defects, fill volume → appearance, particulate matter
G. Ampoules & LVP (Large Volume Parenterals)
Key CQAs: Sterility, Endotoxin, Particulates, Assay, pH, Osmolarity, Clarity, CCI, Fill volume, Degradation products
Critical steps / CCPs:
- WFI Generation, Storage, Distribution
- Temp, recirculation, sanitization → bioburden, endotoxin
- Solution Preparation
- Order of addition, mixing, pH and osmolarity adjustment, temperature → assay, stability, clarity
- Glass/Ampoule/Vial Washing
- Washer settings, final rinse quality → particulates, endotoxin
- Depyrogenation (if applicable)
- Tunnel temperature and belt speed → endotoxin reduction
- Sterile Filtration
- Integrity tests & filtration parameters → sterility
- Aseptic Filling / Sealing
- Headspace control, flame sealing or stoppering, crimping → CCI, fill volume, sterility
- Terminal Sterilization (for SVP/LVP when applicable)
- Autoclave cycle, F₀, load pattern → sterility, degradation
- 100% Visual Inspection
- Particulate matter and container defects → patient safety
H. Ointments / Creams
Key CQAs: Assay, CU, Microbial limits (topical) / Sterility (ophthalmic), Particle size (grittiness), Viscosity, Phase homogeneity, Degradation products, Appearance
Critical steps / CCPs:
- Phase Preparation (Oil/Water)
- Heating & mixing temperature/time → emulsion stability
- Emulsification/Homogenization
- Shear rate, time, cooling profile → droplet size, uniformity, viscosity
- Addition of API & Heat-Sensitive Excipients
- Temperature at addition, mixing uniformity → assay, CU, stability
- Milling (if needed)
- Gap, speed, number of passes → particle size, grittiness
- Filling Operation
- Pump setting, nozzle design, crimping of tubes → fill weight, CU, CCI
- Microbial Control
- Use of preserved vs. sterile product, environmental controls → microbial limits
I. Oral Liquid Syrup / Suspension
Key CQAs: Assay, CU, pH, Microbial limits, Preservative content, Degradation products, Viscosity, Clarity / Redispersibility, Sedimentation, Organoleptic properties
Critical steps / CCPs:
- Water & Sugar Solution Preparation
- Heating, dissolution, filtration → clarity, microbial control
- API & Excipient Addition
- Order & rate of addition; mixing speed → assay, CU, suspension stability
- pH Adjustment
- Addition of acids/bases in controlled manner → stability, taste, preservative efficacy
- Homogenization (for suspensions)
- Speed, time → droplet/particle size, redispersibility
- Deaeration / Filtration
- Vacuum deaeration, inline filters → foaming, particulate matter
- Filling & Capping
- Volume control, torque for caps, induction sealing → fill volume, CCI
- Preservative Efficacy
- Correct preservative levels → microbial limits over shelf-life
GOOD WORK
Thanks
I like your draft and your documents are very help full .
thanks dear
CPPs & CQAs for DPI please
ok,
wait till sunday
kindly complete for other dosage like svp & lvp
ok dear
good
thanks