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Lifting systems determine whether your operators work safely and ergonomically with drums, big bags and containers, or whether you risk back and shoulder injuries, product loss and downtime. In pharmaceutical, chemical, food and battery production, staff lift loads every day that far exceed the ergonomic limit without assistance. This pillar shows how HECHT lifters automate powder and drum handling, which safety standards apply and how to combine ergonomics with containment.

Why lifting systems are indispensable

A drum of powder easily weighs 50 to 200 kg, a big bag 500 to 1000 kg. Tilting, lifting or emptying by hand is physically demanding and error-prone. Lifting systems take over that load, position the product accurately above a discharge point and prevent spillage. The result: less absenteeism, higher throughput and a reproducible process that does not depend on the physical strength of the operator.

Types of lifters for powder and drum handling

The right lifter depends on your load type, height and process step.

• Drum lifters: lift, tilt and empty drums in a controlled way above a mixer or hopper.
• Big bag lifters: hoist and position big bags for dust-free emptying, often with a discharge station.
• Container and IBC lifters: dock to IBCs for charging process installations at height.
• Mobile lift tables and column lifters: bring products to working height and bridge level differences in the line.
• Vacuum lifters: lift sacks and packages without mechanical clamping force, ideal for varying formats.

Ergonomics as a design principle

Ergonomics is not a side issue but a design requirement. Good lifting systems bring the discharge point to the correct working height, eliminate reaching and bending and let the operator steer with minimal force. Match the operating height, tilt angle and speed to the task. A lifter that follows ergonomic guidelines measurably lowers the risk of musculoskeletal complaints and keeps your people deployable longer.

Integration with containment and dust-free working

Lifting and containment belong together. For active or hazardous powders you couple the lifter to a dust-free discharge, for example via a liner, a docking station or a split butterfly valve. This prevents the lifting moment itself from causing dust emission. Combine the lifter with a closed transfer to secure operator protection and ergonomics in a single action.

Safety, ATEX and standards

Lifting systems fall under strict safety rules. In zones with explosive dust the lifter must be ATEX-compliant, with spark-free design and correct grounding. The Machinery Directive and requirements for safe loading, emergency stop and fall protection also apply.

• ATEX: spark-free, certified design for dust explosion hazard zones.
• Machinery Directive: CE conformity, risk assessment and safe operation.
• Load safety: validated maximum working load, overload protection and stable pick-up.
• GMP/EHEDG: hygienic design and cleanable surfaces for pharma and food.

Material and hygienic design

In pharma and food the hygienic design determines suitability. Choose stainless steel 316L, crevice-free welds and surfaces that comply with EHEDG and GMP. This prevents product build-up, eases cleaning and keeps cross-contamination out. For corrosive chemicals you select materials resistant to the specific medium.

Return on investment and total cost of ownership

For procurement, more counts than the purchase price. Factor in the saving on absenteeism, the higher throughput and the lower product loss from spillage. A lifting system that speeds up changeover and eliminates manual steps often pays for itself within a few years. Moreover, automating handling lowers the risk of costly process errors and recalls.

Frequently asked questions about lifting systems

What load can a drum lifter handle?

That depends on the configuration, but standard drum lifters handle drums up to around 200 kg; heavier configurations are available to specification.

Are lifting systems suitable for ATEX zones?

Yes, provided you choose an ATEX-certified, spark-free design with correct grounding for zones with explosive dust.

How do I combine lifting with dust-free working?

By coupling the lifter to a closed discharge via a liner, docking station or split butterfly valve, so the lifting moment causes no dust emission.

Do lifters comply with GMP and EHEDG?

HECHT lifters are available in stainless steel 316L with crevice-free, hygienic design that meets GMP and EHEDG for pharma and food.

What does a lifting system deliver?

Less absenteeism through ergonomics, higher throughput, less product loss and a reproducible process, lowering total cost of ownership.

Related guides

• Big bag handling
• Drum & barrel discharge
• Bulk material handling

Tailored advice from HECHT

Want to know which lifting system fits your load type, working height and containment requirements? HECHT engineers lifters that combine ergonomics, safety and dust-free working. Request a no-obligation consultation and receive a proposal tailored to your line.

Our products

• Lifting equipment
• Barrel lifting aid

Screw conveying is one of the most reliable methods for moving powders and bulk materials in a controlled way. A rotating screw inside a closed trough or tube pushes the product from inlet to outlet at a constant, dosable rate. For engineers, buyers and QA in pharma, chemical, food and the battery industry, screw conveying offers a robust, low-dust and highly controllable solution. HECHT designs screw conveyors and dosing screws tailored to your product, capacity and hygiene requirements.

How screw conveying works

A screw conveyor consists of a helical screw shaft rotating inside a housing. The rotation moves the product axially towards the outlet. Through speed control, the screw acts as both a conveyor and a precise dosing device. This makes screw conveying ideal for processes that require a constant, adjustable mass flow.

Because the product is fully enclosed, dust emission stays minimal and the working environment remains clean and safe.

Types of screw conveyors

The right design depends on product, capacity and layout.

• Trough screw — open or closed trough, suited to larger volumes and horizontal transport
• Tube screw — fully enclosed tube, dust-tight and suitable for inclined transport
• Dosing screw — short, precise screw for gravimetric or volumetric dosing
• Shaftless screw — for sticky or fibrous products without a central shaft
• Vertical screw — for conveying powders upward in compact layouts

Precise dosing with screw technology

Screw conveying excels at dosing. Coupling the rotation speed to a weighing system creates a gravimetric dosing screw that holds the mass flow within tight tolerances. This is critical for recipe formulation, continuous production and filling of critical ingredients.

• Volumetric dosing — constant speed delivers a fixed volume per revolution
• Gravimetric dosing — feedback from weighing corrects density variations
• Loss-in-weight — continuous weighing of the supply hopper for maximum accuracy

Product-friendly conveying

Not every powder tolerates the same handling. Break-sensitive granules, sticky substances and segregation-prone mixtures call for an adapted screw design. The pitch, profile and speed of the screw determine how gently the product is moved. HECHT matches the geometry to the break sensitivity and flow properties of your product.

Containment and operator protection

For highly active powders, a closed screw system is an effective containment strategy. Combined with split-butterfly valves at inlet and outlet, the product stays isolated from the environment and operator exposure is limited. Depending on the OEB band, seals, bearings and feed-throughs are validated for leak-tightness, verified to SMEPAC.

Hygienic design: GMP and EHEDG

In pharma and food, a screw conveyor must be fully cleanable. GMP and EHEDG-compliant designs have polished surfaces (Ra ≤ 0.8 µm), no dead zones and disassembly-free CIP/WIP cleaning. Stainless steel 316L and FDA-compliant seals prevent cross-contamination between batches and product changeovers.

ATEX and safety

For combustible powders, the screw conveyor must be ATEX-compliant. Earthing, spark-free bearings, temperature monitoring and correct zoning prevent ignition. For oxygen-sensitive products such as battery powders, the system can be run inert with nitrogen.

Frequently asked questions about screw conveying

What is the difference between a conveying screw and a dosing screw?

A conveying screw moves large volumes; a dosing screw is optimised for accuracy and delivers a controlled mass flow.

What accuracy does a gravimetric dosing screw achieve?

With loss-in-weight weighing, accuracies within a fraction of a percent are achievable, depending on product and capacity.

Is screw conveying suitable for sticky products?

Yes, with a shaftless screw or an adapted pitch; HECHT selects the geometry based on the flow properties.

Can a screw conveyor operate dust-free?

A closed tube screw with the right seals operates virtually dust-free and is suitable for containment up to high OEB bands.

How is a screw conveyor cleaned?

Via CIP or WIP, or for fast product changeovers through an easily disassembled design, depending on your hygiene requirements.

Related guides

• Dosing guide
• Vacuum technology
• Bulk material handling
• Drum & barrel discharge

Tailored advice from HECHT

A screw conveyor that suits your product starts with an analysis of your powder, capacity and dosing requirement. HECHT designs, tests and supplies screw conveying that is reliable, low-dust and hygienic, and integrates seamlessly with your dosing and filling systems. Contact us for a conveying analysis and a tailored proposal.

Our products

• Feeding screw
• Feeding screws

What is controlled release?

Controlled release (CR) is a pharmaceutical formulation strategy in which the active substance is not released immediately after intake, but dosed over time or at a specific location in the body. The goal: more stable plasma concentrations, fewer side effects, lower dosing frequency and improved treatment adherence. Synonymous terms include modified release (MR), sustained release (SR), extended release (ER) and delayed release (DR) — each with a specific meaning in the pharmacopoeia.

Types of modified release formulations

Extended release (ER/SR)

The active substance is released over 8–24 hours. Peak plasma concentrations are reduced, troughs are raised — ideal for APIs with a narrow therapeutic index (carbamazepine, metformin, nifedipine). Mechanism: diffusion through a matrix polymer or membrane, erosion of a matrix, or osmotic drive.

Delayed release (DR)

Release is delayed until a specific location in the gastrointestinal tract — typically the small intestine or colon. Enteric coating is the best-known example: the coating dissolves at pH >5.5 (small intestine) and protects gastric-irritating APIs or acid-labile biologics.

Pulsatile release

Multiple release moments over time, triggered by colon bacteria (polysaccharide coatings), pH switches or pressure-sensitive systems. Application: chronopharmacology (antihypertensives for nocturnal blood pressure peaks).

Targeted release

Release at specific anatomical locations via ligand-receptor binding (nanoparticles with targeting ligands), mucoadhesion or local implants. Strongly growing segment driven by oncology and biologics.

Technology platforms for controlled release

Matrix tablets

The API is embedded in a polymer matrix (HPMC, ethylcellulose, Carbopol). Release via diffusion through the matrix and/or erosion of the polymer. Simple to produce via direct compression or granulation. Most widely used CR platform for oral solid dosage forms.

Reservoir systems

An API core surrounded by a rate-limiting membrane coating (ethylcellulose, Eudragit RS/RL). Release rate determined by membrane thickness and pore properties. Higher production precision required, but excellent release control.

Osmotic systems (OROS)

The OROS tablet (Alzet-type) uses osmotic pressure as the driving force: water penetrates through a semipermeable coating, builds up pressure and pushes the API out through a laser-drilled orifice. Release rate is near zero-order — virtually independent of GI motility and pH. High manufacturing precision required (laser orifice, coating thickness).

Lipid-based systems

Wax matrices (carnauba wax, beeswax, glyceryl behenate) for low-solubility APIs. Release via lipase-driven erosion. Applied to lipophilic APIs that are poorly soluble in aqueous media.

Regulatory aspects: IVIVC and bioequivalence

For modified release products, the FDA and EMA require an In Vitro-In Vivo Correlation (IVIVC) — a mathematical relationship between the in vitro release profile (dissolution) and in vivo pharmacokinetics. A level A IVIVC (point-to-point correlation) makes it possible to justify formulation changes without new clinical studies. Bioequivalence studies for CR products generally include tests in the fed and fasted state.

Manufacturing challenges

Controlled release places higher demands on process control than immediate release. Coating uniformity (standard deviation <3% weight gain per tablet), polymer concentration and drying conditions determine the release profile. Scale-up from lab to production is critical: fluid bed coaters and perforated pan coaters behave differently at large scale. Containment is an additional challenge for CR formulations of highly potent APIs — combining coating equipment with an isolator or RABS integration.

Conclusion

Controlled release technology is one of the most valuable tools in pharmaceutical formulation development: better therapeutic profile, higher patient compliance and extended product life cycle. The choice of the right platform depends on API properties, desired release profile, production capacity and regulatory strategy.

More about pharmaceutical manufacturing engineering: hecht-technology.nl.

Hecht Technology: particle size precision for modified release

Controlled release depends on a precisely defined particle size distribution of the API and excipients. Hecht Technology's Jett Mill enables reproducible, accurate particle size reduction — a critical process parameter in the development and manufacture of modified-release formulations.

Our products

• Jett mill

Nanoparticles as a drug delivery platform

Nanoparticulate drug delivery systems are particles of 10–1000 nm that transport, protect and release APIs in a controlled manner at the desired location. The promise of nanoformulations is significant: improved drug solubility, extended circulation time, active tumour targeting and minimisation of systemic side effects. The mRNA vaccines from Pfizer/BioNTech and Moderna have given lipid nanoparticles (LNP) worldwide recognition as a manufacturing platform.

Liposomes: the oldest nanoplatform

Liposomes are spherical vesicles of one or more phospholipid bilayers enclosing an aqueous compartment. Hydrophilic APIs are encapsulated in the internal aqueous space; lipophilic APIs in the lipid bilayer. First FDA-approved liposome: Doxil (liposomal doxorubicin) in 1995.

Critical quality attributes of liposomes:

• Particle size (Z-average): typically 80–200 nm, measured via DLS
• Polydispersity index (PDI): <0.2 for a homogeneous population
• Zeta potential: indicator of stability; >+30 or <-30 mV for electrostatic stabilisation
• Encapsulation efficiency (EE%): percentage of API incorporated in the liposome vs. total added

Lipid nanoparticles (LNP): the mRNA revolution

LNPs are the most widely used formulation for nucleic acid delivery (mRNA, siRNA, ASO). Four lipid components work together:

• Ionisable lipid: positively charged at low pH (mRNA encapsulation) and neutral at physiological pH (reduced toxicity). Examples: DLin-MC3-DMA (Patisiran/Onpattro), SM-102 (Spikevax), ALC-0315 (Comirnaty)
• Helper lipid (DSPC/DPPC): structural stability of the lipid bilayer
• Cholesterol: membrane rigidity and fusogenicity
• PEG-lipid: steric stabilisation, extended circulation time, reduced MPS uptake

LNP production via microfluidics or T-junction mixing: the organic phase (lipids in ethanol) and aqueous phase (mRNA in acetate buffer) are mixed under a controlled flow ratio. Instantaneous nanoprecipitation yields LNPs of 80–120 nm.

Polymeric nanoparticles and micelles

PLGA (poly-lactic-co-glycolic acid) nanoparticles are the most studied biodegradable polymeric nanocarriers. PLGA hydrolyses in vivo into lactic acid and glycolic acid and is approved by the FDA/EMA as an excipient. Production via nanoprecipitation, emulsification-diffusion or double emulsion methods.

Polymeric micelles (block copolymer aggregates of 20–100 nm) are suitable for hydrophobic APIs dissolved in the micellar core. Advantage: small particle size, low critical micelle concentration, passive tumour targeting via the EPR effect.

GMP manufacturing of nanoformulations

Nanoformulations place special demands on GMP manufacturing: sterile filtration is not possible for liposomes and LNPs >200 nm (0.22 µm filters block particles that large); aseptic processing is then required. Scale-up from lab microfluidics to commercial production (Spark NanoAssemblr, Precision NanoSystems) is an active area of development.

Conclusion

Nanoparticulate drug delivery has grown from a laboratory curiosity into a clinically and commercially proven technology platform. Liposomes, LNPs and polymeric nanoparticles offer unprecedented possibilities for targeting and API protection — with accompanying manufacturing challenges in scale-up, sterile processing and characterisation.

More about biopharma manufacturing engineering: hecht-technology.nl.

Our products

• Jett mill
• Single-use isolator

The CTD dossier: universal structure for registration

The Common Technical Document (CTD) is the harmonised dossier structure used worldwide for drug registration with the EMA, FDA, Health Canada and more than 40 other regulators. The CTD consists of five modules: Module 1 (regional administrative information), Module 2 (summaries and overviews), Module 3 (quality data), Module 4 (preclinical data) and Module 5 (clinical data). Module 3 contains all pharmaceutical quality data: API specifications, formulation design, manufacturing method, validation data and stability studies. Electronic submission (eCTD) is mandatory with the FDA, EMA and various other authorities; eCTD software ensures correct XML structure and lifecycle management of the dossier.

EMA registration procedures in Europe

Four registration procedures are available in Europe: the centralised procedure (CP) via the EMA grants a Marketing Authorisation valid across all EU/EEA member states; the decentralised procedure (DCP) and the mutual recognition procedure (MRP) run via national authorities of multiple member states; the national procedure applies to registration in a single country. Biologics, oncology products and HIV medicines are required to use the CP; for other medicines the CP is optional but offers efficiency. EMA assessment time is a maximum of 210 active assessment days (with clock-stop periods excluded, typically 12-18 months total). PRIME (Priority Medicines) offers accelerated assessment for products with major therapeutic benefit for a condition without adequate treatment options.

FDA NDA and ANDA: US registration

In the US, innovative medicines are registered via a New Drug Application (NDA) under 21 CFR Part 314. FDA review time for a standard NDA is 10 months, for Priority Review (serious conditions) 6 months. Important FDA expedited designations are: Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review. The Prescription Drug User Fee Act (PDUFA) funds FDA review capacity through annual fees from manufacturers; the PDUFA fee for an NDA is approximately 4 million dollars. Pre-submission meetings (Type A, B, C) with the FDA are strategically valuable to reach alignment on clinical programme design, endpoints and the registration plan.

Orphan drug and breakthrough therapy designations

Orphan Drug Designation (ODD) offers incentives for medicines targeting rare conditions (fewer than 5 per 10,000 in Europe; fewer than 200,000 patients in the US): 10 years of market exclusivity (EU) or 7 years (US), reduced registration fees and development guidance. Breakthrough Therapy Designation at the FDA is intended for products with preliminary clinical evidence of substantial benefit versus existing therapy; it offers intensive FDA guidance and can lead to accelerated approval based on surrogate endpoints. The EMA equivalent PRIME (Priority Medicines) offers comparable benefits in Europe. Combining designations maximises the chance of an efficient, patient-focused development route.

Post-approval changes and variations

After market authorisation, changes to manufacturing, specifications, formulation or site require formal notification or approval via the variation procedure system. In Europe, variations are classified as Type IA (minor, 30-day notification), Type IB (minor, 30-day approval), Type II (major, 60-day review) and extensions (Major Change). The FDA distinguishes Prior Approval Supplements (PAS, 6-12 months), Changes Being Effected (CBE-30, 30 days) and Annual Reports. Post-approval change management requires that the impact on product quality be assessed through risk analysis and, if needed, additional studies. SUPAC guidelines (Scale-Up and Post-Approval Changes) provide FDA-specific criteria for which type of supplement is required for manufacturing and formulation changes.

Conclusion

Regulatory strategy and drug registration are complex disciplines requiring in-depth knowledge of international CTD structures, review procedures and post-approval change management. A well-considered regulatory strategy shortens time-to-market and reduces the risk of rejections or additional data requirements. Hecht Technology supports pharmaceutical companies in setting up CTD dossiers, regulatory gap analyses and registration strategies for Europe and the US.

Hecht Technology: process equipment for validation dossiers

A strong registration dossier relies partly on demonstrably validated production equipment. Hecht Technology supplies GMP- and ATEX-certified systems with complete IQ/OQ documentation, such as the single-use isolator, which support the quality substantiation of your CMC dossier for EU and FDA registration.

Our products

• Single-use isolator

Polymorphism: definition and pharmaceutical importance

Polymorphism describes the phenomenon whereby a chemical substance exists in multiple crystalline solid-state forms that share the same molecular composition but differ in their three-dimensional arrangement within the crystal lattice. For pharmaceutical APIs, polymorphism is of critical importance because different crystal forms can differ substantially in solubility, by factors of 2 to more than 100 times, in melting point by up to 30 degrees Celsius, and in physical stability and processability. The best-known example is ritonavir, whose discovery of polymorphic form II in 1998 led to the product being recalled because the new form had 4 times lower solubility and the capsule formulation was no longer therapeutically effective. Pseudo-polymorphs, or solvates and hydrates, are crystal forms in which solvent or water molecules are incorporated into the crystal lattice and likewise exhibit different physicochemical properties. Regulatory authorities require a complete polymorph characterisation report in registration dossiers and control of the polymorphic form in every production batch.

Crystal form screening

Polymorph screening identifies all relevant solid-state forms of an API via systematic crystallisation experiments across a broad range of solvents, temperatures and solvent concentrations. Automated high-throughput screening platforms such as Crystal16 and Crystalline from Technobis crystallise an API under 16 to 96 conditions simultaneously via temperature profiles and antisolvent additions. Screening methods include cooling crystallisation from solvent solutions, antisolvent precipitation, slurry methods in competing solvents, vapour diffusion and mechanochemical grinding of the solid material. Coordinated characterisation of all forms found via XRPD, DSC and TGA at an early stage makes it possible to fully map the polymorphic landscape before registration studies begin. Per project, typically 3 to 15 new crystal forms are found, of which 30 to 50% are pseudo-polymorphic solvates or hydrates in nature and require specific storage conditions.

XRPD and DSC characterisation

X-Ray Powder Diffraction (XRPD) and Differential Scanning Calorimetry (DSC) are the two primary techniques for solid-state characterisation of API crystal forms in pharmaceutical development. XRPD provides a unique diffractogram fingerprint of each crystal form via Bragg reflections at specific 2-theta angles, with the international Cambridge Structural Database (CSD) containing more than 1 million reference structures. Variable-temperature XRPD from 25 to 200 degrees Celsius monitors polymorphic transitions in situ and is essential for understanding the thermodynamic phase diagram of an API. DSC thermograms reveal the enthalpic signatures of phase transitions, melting points and dehydration processes: every endothermic or exothermic peak between 50 and 300 degrees Celsius represents a crystallographically significant event. Thermogravimetric analysis (TGA) combined with DSC distinguishes solvate desolvation from polymorphic transformation by simultaneously measuring weight loss upon heating, with a resolution of 0.1 microgram on modern TGA instruments.

Solubility and stability per form

The intrinsic solubility of different polymorphic forms differs due to the free energy of the crystal lattice and is related via the Ostwald rule of stages: less stable metastable forms have higher solubility. Solubility measurement via the shake flask method at pH 7.4 phosphate buffer distinguishes the thermodynamic solubility of all forms at 37 degrees Celsius in simulated intestinal medium. Metastable forms with higher solubility can create supersaturation in vivo and thereby increase bioavailability, but the risk of spontaneous conversion to the more stable form during processing or storage must be evaluated. Solid-state stability of polymorphs under accelerated storage at 40 degrees Celsius and 75% RH for 3 months shows whether the selected product form remains stable under normal storage conditions. DSC-based thermodynamic stability analysis via the enthalpy-entropy compensation principle can predict the thermodynamic solubility ratio of two polymorphs without experimental solubility measurements.

Polymorph control in manufacturing

Control of the polymorphic form during commercial API manufacturing is a critical quality requirement that must be captured in the control strategy with in-process monitoring and finished-product analysis. In-process control via Raman spectroscopy or NIR monitoring of the crystallisation step detects polymorphic conversion in real time with a response time of 1 to 5 seconds, enabling rapid process intervention. Seeding with the desired polymorphic form at a relative supersaturation of 5 to 15% above the saturation curve initiates crystallisation of exclusively the desired polymorph, achieving a selectivity above 99%. Storage conditions for the API crystallisate and the finished product must be established and specified based on stability studies to prevent polymorphic conversion during long-term storage. XRPD finished-product analysis on every production batch, with a reference diffractogram and acceptance criteria for peak positions within 0.2 degrees 2-theta, is the legal minimum requirement for polymorph control per the Ph.Eur. monograph on API characterisation.

Conclusion

Polymorphism and solid-state characterisation are fundamental aspects of API development that directly affect therapeutic effectiveness, product stability and regulatory acceptance. Hecht Technology supports polymorph screening studies, characterisation and the implementation of polymorph control in API manufacturing processes in accordance with ICH Q6A and Ph.Eur. Contact us for a polymorphism assessment of your API development project.

Our products

• Jett mill

Micro-organisms and cell lines as production platforms

Upstream bioprocessing selects the most suitable production platform based on the desired product, the required post-translational modifications and the production titre. Escherichia coli is the most widely used bacterial expression system due to its rapid growth of 0.3 to 1.0 hour generation time, well-understood genetics and high production titre of over 50 g/L inclusion bodies. Saccharomyces cerevisiae and Pichia pastoris are suitable yeast expression systems for proteins requiring secretion or N-glycosylation, with titres of 3 to 10 g/L for simple proteins. Mammalian cell lines, with CHO (Chinese Hamster Ovary) as the dominant choice for more than 70% of approved biologics, offer correct human-like glycosylation for therapeutic proteins. Insect cell systems Sf9 and High Five via baculovirus infection and transient expression systems offer flexibility for small batches and rapid titre improvement in the early development phase. The production platform directly determines the upstream and downstream processing strategy across the full life cycle of the drug.

Bioreactor design and mixing

Bioreactor design is critical for controlling the cells' environmental conditions and optimising the mass transfer of oxygen and carbon dioxide. Stirred tank reactors (STR) are the most widely used bioreactor type in pharmaceutical production, with working volumes from 2 to over 25,000 litres, fitted with Rushton turbine or marine propeller impellers at an impeller-to-vessel diameter ratio of 1:3. The bioreactor's volumetric oxygen transfer coefficient (kLa) determines the maximum oxygen supply capacity of the culture: for CHO cells with a specific oxygen consumption qO2 of 1 to 10 mmol O2/g·h, a kLa of 2 to 20 h⁻¹ is required. Airlift bioreactors without mechanical agitation use air or gas bubbles for mixing and are suitable for shear-sensitive cell lines, where the Kolmogorov length scale of turbulence must remain above the cell diameter of 10 to 20 micrometres. Disposable bioreactors made from single-use materials offer advantages for clinical batch production: no cleaning, elimination of cross-contamination and faster turnaround between batches of 4 to 6 hours versus 48 to 72 hours for stainless steel.

Fed-batch and continuous fermentation

Fed-batch cultivation is the dominant process mode in pharmaceutical bioproduction and combines the benefits of high cell concentration with controllable product formation via a guided feed addition protocol. The fed components, typically glucose, amino acids and vitamins, are dosed based on online measurements of the glucose concentration below 1 g/L via enzymatic or NIR sensors to avoid overfeeding and catabolite repression. Fed-batch CHO cell cultures reach cell concentrations of 50 to over 100 million cells per mL and monoclonal antibody titres of 3 to over 10 g/L over process durations of 12 to 21 days. Continuous fermentation via perfusion culture circulates cell retention through a spin filter or alternating tangential flow filtration (ATF), with cell concentrations up to 200 million cells per mL and day-for-day productivity up to 3 times higher than fed-batch. Intensified bioprocessing via N-1 perfusion at the seed fermentation stage compensates for the longer start-up phase of production bioreactors and increases the facility's total annual productivity by 25 to 50%.

Process control: pH, DO and glucose

Process control in bioreactors monitors and regulates critical process parameters that directly affect cell growth and product formation via closed-loop control strategies. Dissolved oxygen (DO) control via a cascade controller to impeller speed and air supply maintains oxygen saturation between 30 and 50% of air saturation for optimal aerobic CHO cell culture; under-saturation below 20% causes metabolic stress and reduced productivity. pH control via addition of sodium carbonate solution or CO2 gassing maintains pH within 0.05 units of the setpoint of 6.95 to 7.20, depending on the cell line and desired metabolic profile. Glucose concentration measurement via an online YSI analyser or enzymatic flow cell with a response time of 5 to 15 minutes drives the fed-batch feed pumps and prevents glucose limitation at concentrations below 0.5 g/L. Process analytical technology (PAT) via online dielectric spectroscopy biomass sensor provides direct measurement of viable cell concentration every 15 seconds without sampling loss, enabling continuous process optimisation.

Bioreactor scale-up

Scaling up from 2-litre lab scale to 200-litre pilot scale and 10,000-litre commercial scale requires preserving critical bioprocess parameters via dimensionless numbers and specific scaling criteria. Equal specific mixing or power input per volume (P/V) of 50 to 200 W/m³ is a common scaling criterion that ensures the turbulent micro-scale stays above the cell diameter to limit shear stress. Gas sparging via injection nozzles and ring spargers must be scaled based on equal gas holdup fraction, which amounts to 0.01 to 0.05 v/v, measured via the pressure differential method. Heat transfer calculations for biological heat generation (qheat) of 50 to 200 kW/m³ determine the cooling water requirements of the jacketed bioreactor at production scale. Volumetric production time (PT) of the bioreactor, defined as the annual production hours divided by the working volume, is a key parameter for comparing the economic efficiency of different bioreactor formats at comparable capital and operational costs.

Conclusion

Upstream bioprocessing is the technological foundation for the production of biologics, monoclonal antibodies and biotechnological medicines that are transforming the pharmaceutical industry. Hecht Technology provides expertise in bioreactor design, process control implementation, fed-batch optimisation and scale-up for biotechnological production processes. Contact us for support with your upstream bioprocessing project.

What do industrial fermentation facilities and GMP qualification cost?

Investment in a fermentation facility typically consists of CapEx (bioreactor, HVAC, sterilisation, monitoring, utilities) of approximately 1 to 5 million euros, OpEx of 500,000 to 2 million euros per year, and GMP validation costs of 200,000 to 1 million euros. For biologics with an annual market of 5 to 20 million euros, ROI is typically 3 to 5 years. Incremental scale-up — pilot, clinical, commercial — spreads the investment risk across the development phases.

Hecht Technology: single-use and containment in bioprocessing

Modern upstream bioprocessing increasingly employs single-use technology to prevent cross-contamination between batches and reduce validation time. Hecht Technology's single-use isolator supports this for contained transfer and sampling of biomass and media, while our columns and process towers are used for downstream separation and purification steps after fermentation.

Our products

• Single-use isolator
• Columns and process towers

What is a Dry Powder Inhaler (DPI)?

A Dry Powder Inhaler (DPI) is an inhalation device that delivers dry powder directly into the lungs without a propellant. The patient activates the dose by inhaling: the airflow through the device deagglomerates the powder and transports the active particles to the bronchioles and alveoli. DPI systems are widely used for asthma, COPD and lung infections (including inhaled antibiotics and vaccines).

The success of a DPI stands or falls with formulation and manufacturing process. Particle size, carrier particles, blend uniformity and moisture sensitivity together determine the Fine Particle Fraction (FPF) — the proportion of the dose that actually reaches the lungs.

The pharmacology of inhalation: why particle size determines everything

Only particles of 1–5 µm reach the deeper lung regions (bronchioles, alveoli). Larger particles (>10 µm) deposit in the oropharynx and are pharmacologically inactive. Particles <1 µm are exhaled. The aerodynamic particle size (MMAD, Mass Median Aerodynamic Diameter) is therefore the most critical quality parameter for inhalation formulations, measured via cascade impactor (NGI, Andersen).

DPI formulation strategy

Carrier-based formulation

The most widely used DPI formulation strategy combines fine API particles (1–5 µm) with coarse carrier particles of lactose (50–200 µm). The API adheres to the surface of the carrier and is released upon inhalation by turbulence within the device. Critical parameters:

• Lactose quality: morphology, specific surface area and moisture content determine API-carrier interaction
• Lactose fines fraction: small lactose particles (fines, <10 µm) compete with the API for carrier surface and improve the FPF
• Mixing order and intensity: determine adhesion uniformity and avoid excessive deagglomeration during production

Carrier-free formulation

For highly potent APIs or when no suitable carrier is available, carrier-free formulations are used: spray-dried or lyophilised porous particles with low density and aerodynamically favourable morphology. Higher production complexity, but superior FPF (up to >60%).

Micronisation and particle production

API micronisation for DPI formulation requires particle size control at sub-5µm level. Common methods:

• Jet milling (fluidised bed jet mill): air- or nitrogen-driven interparticle collisions, no thermal load, scalable to production volume
• Spray drying: solution or suspension evaporated in a hot air stream, produces spherical particles with controllable size and morphology
• Supercritical fluids (RESS, SAS): niche application for polymorph-sensitive APIs

Containment during micronisation of HPAPIs (OEB 4–5) is a critical engineering requirement: closed mills with integrated filter separation and negative pressure are standard for potent inhalation APIs.

Blend uniformity and mixing

DPI blends require extreme uniformity: Content Uniformity (CU) specifications of <5% RSD at dose level are common. This places high demands on:

• Deagglomeration of micronised material before mixing (via sieving or sonication)
• Mixing equipment (tumble blender, bin blender) and mixing parameters (rpm, fill degree, mixing time)
• Electrostatic charge management (use of grounded equipment, anti-static liners)

Moisture sensitivity and packaging

Inhalation powders are extremely moisture-sensitive: even at 40–60% RH, lactose-based blends can sinter or API crystallisation can occur, dramatically reducing FPF. Production under controlled conditions (RH <30%, T 20–22°C) and packaging in moisture-resistant blister packs (aluminium-aluminium) or capsules with desiccant are standard GMP practice.

Regulatory requirements and quality control

DPI products are characterised via: Aerodynamic Particle Size Distribution (APSD) via NGI, Fine Particle Fraction (FPF), Delivered Dose Uniformity, MMAD and GSD. ICH Q4B Annex 9 and EMA/FDA inhalation guidelines describe test methods and acceptance criteria. Device-formulation combination testing is mandatory for registration.

Conclusion

DPI formulation is one of the most complex areas in pharmaceutical product development. Particle size, carrier interaction, micronisation process, blend uniformity and moisture control must all be optimised simultaneously for a robust product. The process steps require specialised equipment for both production and containment.

More about inhalation powders and DPI production equipment: hecht-technology.nl.

Our products

• Jett mill
• Single-use isolator

Granulation: from powder to processable granulate

Granulation is the process in which fine powder particles are combined into larger, stable agglomerates (granules). The goal is to improve the processing properties of the powder: better flowability for dosing systems and tablet presses, higher bulk density for more compact storage and transport, improved compressibility for tableting, and reduced dust formation with hazardous substances. Granulation is a central step in pharmaceutical solid dosage form production and is also applied in food, chemistry and fertiliser production.

Wet granulation: the most widely used granulation technique

In wet granulation, powder particles are combined by adding a binder solution (granulation liquid). The binder (gelatine, PVP, HPMC, hydroxypropyl cellulose) forms bridges between particles that yield stable granules after drying. Wet granulation takes place in:

• High-shear mixer-granulator: intensive mixing and granulation in a single vessel; short process time (10–20 min); suitable for APIs requiring robust granulation
• Fluid bed granulator: powder is suspended in a fluidised bed while binder solution is sprayed on; gentler process; simultaneous granulation and drying
• Twin-screw granulator: continuous processing; high formulation flexibility; suitable for continuous manufacturing lines

Wet granulation is not suitable for moisture-sensitive or thermolabile APIs.

Dry granulation: for moisture-sensitive products

In dry granulation, powder particles are compressed together without adding liquid. The two most commonly used methods are:

• Roller compaction: powder is compressed between two counter-rotating rollers into compact ribbons, which are then milled into granulate. Scalable, continuous processing, broadly applicable
• Slugging: powder is first compressed into large tablets (slugs) and then milled. Less efficient than roller compaction; increasingly less used

Fluid bed technology: granulating and drying in one step

Fluid bed processors can granulate, coat and dry in the same equipment. An upward airflow keeps the material suspended while a spray nozzle applies binder or coating. Fluid bed technology offers high process flexibility but requires precise control of air volume flow, temperature and spray rate.

Selection criteria for granulation technology

• Moisture sensitivity of the API: moisture-sensitive → dry granulation or fluid bed
• Thermolability: thermolabile → low-temperature fluid bed or dry granulation
• Batch vs. continuous production: continuous production → twin-screw or roller compaction
• Desired granule properties: particle size, density, porosity
• Scale: from gram-scale lab to ton-scale production

Hecht Technology supplies bulk handling systems for granulate processing lines: contained transfer, dosing and transport of granulates for pharma and food. More information: hecht-technology.nl.

Hecht Technology: downstream processing after granulation

After granulation, the granulate often still needs to be dried and brought to the correct particle size. Hecht Technology supplies Nutsche filter dryers for drying moist granulates in a closed, GMP-compliant environment, and the Jett Mill for fine milling or adjusting the particle size distribution after granulation.

Our products

• Nutsche filter dryers
• Jett mill

Powder characterisation: the key to predictable process behaviour

The properties of a powder determine how it behaves during transport, dosing, mixing, granulation and tableting. Powders with identical chemical composition can be processed fundamentally differently if their particle size, shape, bulk density or flowability differ. Systematic powder characterisation is therefore essential in process design, scale-up and troubleshooting in the pharmaceutical, food and chemical industry.

Particle size distribution (PSD): the most critical powder property

Particle Size Distribution (PSD) describes what percentage of the particles has a given size. PSD directly affects: API dissolution rate, mixing quality, flowability, capsule and tablet fill time, filterability and pneumatic transport behaviour.

Common measurement methods for PSD:

• Laser diffraction: fastest method, measurement range 0.1–3500 µm, wet or dry dispersion, standard in pharma and food
• Sieve analysis: simple, low-cost, suitable for particles >45 µm; less suitable for cohesive powders
• Dynamic image analysis (DIA): also measures particle shape alongside size; valuable for anisotropic particles (needles, flakes)
• Electrical sensing zone method (Coulter counter): high accuracy for narrow distributions in liquid

Bulk density: poured and tapped

Bulk density is measured as poured bulk density and tapped bulk density. The difference between the two provides information about the powder's compressibility. The Carr Index and Hausner Ratio are derived measures:

• Carr Index = (tapped - poured) / tapped × 100%. Values <15% = good flowability, >35% = poor flowability
• Hausner Ratio = tapped / poured. <1.25 = good flow, >1.4 = cohesive powder

Flowability and cohesiveness: process-relevant parameters

A powder's flowability determines whether it flows spontaneously and reproducibly from a silo, hopper or dosing device. Cohesive powders form bridges and rat holes. Measurement methods for flowability include the angle of repose test, the flow function (Jenike shear cell) and dynamic flowability (powder rheometer such as the FT4).

Flow improvers such as silica (Aerosil), magnesium stearate or talc are added to improve cohesive powders — but affect other product properties and generally require formulation validation.

Powder characterisation across the production cycle

Powder characterisation takes place at four points: at procurement (raw material specification), at process design (scale-up from lab to production), during deviation investigation (OOS results or process disruptions) and during regular trending as part of process analytical technology (PAT). Hecht Technology supplies process equipment designed for powders with widely varying characteristic properties. More information: hecht-technology.nl.

Read also

• Powder transport in closed systems 7-step guide
• CIP systems for powder transport: what you need to know
• Bulk handling machine selection
• Powder processing & transport: product overview

Weighing and batch dosing: the foundation of reproducible bulk production

Accurate weighing and batch dosing are the foundations of quality assurance in industrial production. Whether it concerns pharmaceutical API formulation, food ingredients or chemical reactors — every batch starts with the correct weight of the correct components. Inaccurate dosing directly leads to product quality problems, raw material waste and compliance risks. In GMP environments, deviations of more than 0.5% of the batch weight are often grounds for batch rejection.

Weighing principles in industrial dosing installations

The most common weighing principles in bulk production are strain gauge load cells and electromagnetic force restoration (EMFR). Strain gauge cells are robust, cost-effective and suitable for capacities from a few grams to hundreds of tons. EMFR cells offer higher accuracy at lower capacities and are used in analytical precision dosing.

Load cells are configured in two main principles: gain-in-weight (GIW) — the receiving container stands on the load cell and is filled until the target weight is reached — and loss-in-weight (LIW) — the dosing source stands on the load cell and is dosed out while the weight decrease is measured. Both principles have specific application areas and accuracy profiles.

Gain-in-weight dosing: applications and benefits

With GIW dosing, the receiver is weighed during the filling process. Dosing stops as soon as the net target weight is reached. GIW is simple to implement, suitable for coarse dosing of multiple components into the same container, and requires less complex control technology than LIW. Typical accuracy: ±0.2–1.0% of the dosed weight.

GIW is the standard for: silo filling, big bag filling stations, batch weighing for mixers and reactors, and multi-component recipe dosing where the sequence and weight of each ingredient are recorded.

Loss-in-weight dosing: continuous precision

With LIW dosing, the supply hopper or feeder stands on the load cell. The control system calculates the actual mass flow as weight decrease per unit of time and adjusts the feeder to maintain the setpoint flow. LIW offers higher dynamic accuracy and is suitable for continuous processes. Typical accuracy: ±0.1–0.5% under stabilised operation.

LIW is the standard for: continuous pharmaceutical production, extruder feeding, blended raw material streams and processes where the dosing rate must remain constant regardless of product changes in the hopper.

GMP requirements for weighing and dosing systems

In pharmaceutical and food production, strict requirements apply to weighing and dosing systems. Load cells must be calibrated per OIML R 76 or USP chapter 41, with calibration certificates traceable to national standards. The installation requires IQ/OQ qualification, verifying measurement tolerance across the full dosing range. Electronic weighing data must be stored in an audit trail compliant with 21 CFR Part 11 or EU GMP Annex 1.

Integration with recipe management and MES

Modern weighing and dosing systems are fully integrated into the process automation ecosystem. Recipes are called up from the MES or ERP system, the PLC drives the dosing devices based on the weighing data, and the electronic batch record is generated automatically. This eliminates manual entry, shortens batch cycle times and enables real-time deviation alerts.

Hecht Technology supplies integrated weighing and batch dosing systems for pharma, food, chemistry and the battery industry — from standalone weighing stations to fully automatic multi-component dosing systems. More information: hecht-technology.nl.

Our products

• Weighing compensators
• Feeding screw

Bag filter or cartridge filter: the choice determines efficiency, maintenance and TCO

Bag filters and cartridge filters are both effective technologies for industrial dust separation, but they perform fundamentally differently with different dust types, particle sizes and process requirements. The wrong choice leads to increased maintenance frequency, excessive pressure drop or insufficient separation efficiency. A good selection guide starts with understanding filter operation and ends with Total Cost of Ownership.

Operating principle: how bag filters and cartridge filters separate dust

A bag filter (baghouse filter) uses long, cylindrical filter sleeves of woven or felted fabric. The dust-laden gas flows through the inside or outside of the bag, depending on the design. Dust adheres to the filter medium and forms a cake that actually increases filtration efficiency (primary filtration via the dust cake). Cleaning takes place via compressed air pulse-jet or mechanical shaking.

A cartridge filter uses pleated filter media — typically polyester, cellulose or PTFE — with a large filter surface area in a compact volume. The pleated structure provides 10 to 30× more filter surface per unit volume than a bag filter. Pulse-jet cleaning is standard.

When do you choose a bag filter?

• High dust concentrations (>5 g/m³): bag filters are designed for heavy dust loads and quickly form an efficient dust cake
• Coarse, abrasive particles (>10 µm): the robust fabric material withstands wear better than pleated cartridges
• Moist or sticky dust types: some fabric types (PTFE membrane) are better suited to sticky dust that would clog cartridges
• High-temperature processes (up to 260°C): fibreglass or PTFE bags are available for high-temperature applications
• Large volume flows: bag filters scale up more efficiently to large gas volumes

When do you choose a cartridge filter?

• Fine, dry dust types (<10 µm): cartridges offer higher filtration surface area and a lower A/C ratio for fine dust
• Low to moderate dust concentrations (<5 g/m³): cartridges are less suitable for heavy dust loads
• Limited installation space: the compact design fits into tight machine rooms or production floors
• Pharmaceutical and food applications: FDA-compliant filter material grades available, easier to clean and validate
• Frequent filter changeover: cartridges are quicker to replace than bags

Comparison overview: bag filter vs. cartridge filter

• Filter surface area per volume: cartridge filter > bag filter
• Suitable for high dust loads: bag filter > cartridge filter
• Compactness: cartridge filter > bag filter
• Temperature resistance: bag filter (specialised versions) > cartridge filter
• GMP cleanability: cartridge filter (easier) > bag filter
• Investment cost: comparable, depending on material and scale

Hecht Technology supplies both bag filters and cartridge filters for industrial dust separation in pharma, chemistry, food and the battery industry. More information: hecht-technology.nl.

Read also

• The different types of bag discharge systems and their applications
• The importance of integrated filters in bag discharge installations
• Benefits of mobile bag discharge installations for flexible production
• SE-H bag dumping cabinet