INPROCESS LSP

AdvancedAnalytics for Productsand Processes

InProcess-LSP offers advanced analytical services and solutions for pharma, food, life sciences and other related industries to support product and process development and manufacturing. Today’s products and manufacturing processes demand highest performance in terms of product quality, process robustness and efficiency. For high product quality and robust processes, in-depth product and process understanding is of utmost importance.

With a strong background in product and process development as well as in analytical sciences varying from microscopy and imaging to a wide range of spectroscopic and optical technologies, InProcess-LSP offers a unique combination of experience and knowledge.

Our services include contract research & troubleshooting to increase understanding of your products and processes, as well as PAT method development and implementation to monitor and control processes. If commercially available instrumentation cannot provide the desired solution, InProcess-LSP offer the opportunity to modify or optimize instruments or develop new instruments and software for your specific application.

ADVANCED ANALYTICS FOR PRODUCTS AND PROCESSES

Raw materials

Formulations

Processes

End products

WHY CHOOSE US?InProcess-LSP is an entrepreneurial organization providing advanced analytical services and solutions to support you with your product and process challenges. Our aim is to make a positive difference by offering high services and optimal solutions with a strong sense for pragmatism and business context. With our strong background in spectroscopy and process analytics as well as many years of academic and industrial experience you can rely on a highly skilled and experienced team of scientists and specialists. You will find in us a dedicated, reliable and enthusiastic partner. You can count on us.

MISSION AND VISIONWe provide advanced analytical solutions and expertise supporting our customers in development of high-quality products and well-controlled, and robust manufacturing processes. We envision helping our customers to achievethese goals by offering high services and customized solutions in the landscape of current quality driven product and process development and manufacturing.

PROCESS ANALYTICALTECHNOLOGY

Validation

GMP

Business casesupport

Process Development

DoETech Transfer

Upscaling

Process Dynamics

Troubleshooting

ParametricRelease

ProcessValidation

Filingsupport

QbD

Process E�ciency

Translation traditionalrelease requirements

Process Performance

Feed-back/forward loop

Process Robustness

Process Control Criteria

SPC

PROCESS CONTROLProcess Analytical Technology (PAT) can be effectively applied in process control to measure process variation and to stop or adjust processes in real time optimizing product quality and yield. InProcess-LSP can help you to develop and implement PAT solutions for process control in a pragmatic and result driven way.

REAL TIME RELEASEProcess Analytical Technology (PAT) can be effectively applied for real time release or reduced end product testing. Effectively recorded process data reflecting critical quality aspects may be used to eliminate or reduce the number of release tests at your QC department. InProcess-LSP can help you to build a business case driven solution to optmize your process efficiency.

PROCESS UNDERSTANDINGProcess Analytical Technology (PAT) can be effectively applied during process development, scale up and transfer to obtain a more in-depth insight into your process. PAT applications for process understanding purposes are often temporary projects, solely intended to provide specific answers to process or product related questions. InProcess-LSP offers full support, including equipment rental options, to select the right PAT method for your projects.

BENEFITS OF PAT• In-depth process insight and

understanding • Continuous process monitoring,

verification and improvement• Reduced impact of input material and

process condition variability• Time efficient development of robust

processes and design space studies• Effective upscaling and tech transfer • Upstream quality control enabling Real

Time Release • Efficient and data driven

troubleshooting

WHY PAT?Since input variables like raw material properties, process and environmental conditions will vary for most processes, the endproduct of the process will consequently show related variations in quality as well. If a process is designed as a fixed process, without the possibility to adjust or cope with varying input variables, process performance will be dependent on how well critical input variables can be controlled.

By applying PAT to measure critical process performance will depend on how well critical processes can be made variable

VARIABLEINPUT

VARIABLEINPUT

VARIABLEQUALITY

CONSTANTQUALITY

FIXEDPROCESS

VARIABLEPROCESS

PAT

by adjusting the process for variations in input variables. Once the relation between critical input variables is known and adjusted for by the variable process, this will result in a consistent end product quality and higher level of process performance.

Health agencies and regulatory bodies like FDA and EMA are typically interested in product and processing quality risks related to input variables. PAT will help to increase understanding, efficiency and control of your processes and products.

InProcess-LSP helps customers with complete services and solutions in the areas of (process) analytical application development, analytical support and data analysis. With extensive experience in pharmaceutical and life-science industry, we support customers with analytical support projects in the areas of Process Development and Improvement and troubleshooting and offer consultancy on Quality by Design, Process Analytics and filing strategy. We pride ourselves in offering high scientific standards and strive to add value and understanding to customers’ processes, beyond mere measurements.

If desired solutions cannot be achieved effectively by existing available instrumentation, InProcess-LSP also develops dedicated instruments and / or software specifically to fulfill all your application needs.

OUR SERVICES

APPLICATION METHOD DEVELOPMENT

ANALYTICAL SERVICE

PROCESS DEVELOPMENT& IMPROVEMENT

INSTRUMENTS & SOFTWARE

TRAINING

PAT METHOD DEVELOPMENT• Blend Uniformity Assessment• Liquids / Suspension processing• Content Monitoring• Drying• And more…

OFF-LINE / LAB METHOD DEVELOPME• Moisture content• Assay / Content• Composition• Residual Solvents

CONTRACT RESEARCH• Spectroscopy (NIR, Raman, UV-VIS)• (NIR) Imaging, Microscopy and Morphology• Reology• Modelling and data analysis• Nanoparticle sizing studies by NanoFlowSizer

TROUBLESHOOTING• In-depth product studies and root cause

analysis support

QBD, SIX SIGMA, RISK ASSESSMENT• Facilitation and support of product and process

related Risk Analysis• DoE studies, Monte Carlo Simulations, Process

Performance

COMMERCIAL INSTRUMENTS• NanoFlowSizer (www.nanoflowsizer.com)

DEDICATED INSTRUMENTS & SOFTWARE• Optimization or development of instruments• Software development to meet your specific needs

CUSTOMIZED AND OPEN TRAININGS• PAT strategies, Blend uniformity by NIR, Particle Sizing, Rheology and more

InProcess-LSP develops inline/online/at-line and offline methods using nondestructive, optical and spectroscopic tools. Our services vary from consultancy and feasibility testing, to validation and implementation of inline or offline methods for application in development or manufacturing environments. With well equipped laboratory facilities and an extensive network of suppliers of instruments, InProcess-LSP perform feasibility studies and most of the development and validation work in-house, limiting interruption of customers’ process development activities or operations.Key areas of expertise and services our customers benefit from:

Evaluation of adequate method performance and process behavior during routine manufacturing is important to assure consistency in quality and provides a solid basis for continuous improvement. InProcess-LSP provides tailor made maintenance solutions for applications according to customer needs.  Analytical Instrument Quali fication for PAT instruments or offline analyzers may be required for applications in GMP regulated environments. InProcess-LSP advises customers on instrument qualification and supports compilation of qualification documents, system management and maintenance procedures specifically for your system in accordance with current guidance and regulations.

• Extensive experience in Process Development• Broad knowledge of PAT technologies and independent

advice• Fit for purpose solutions• Experience in development/validation and

implementation strategy• Full method validation, regulatory filing support• Instrument Qualification support

ANALYTICAL METHOD DEVELOPMENT

ACTIVITIESInProcess-LSP

CUSTOMERINPUT

Intake & AdviceObjective(s) & Possibilities,

Role InProcess-LSPNeed, Purpose

FeasibilityStudy

Business case, Optimal technology& Design study, Feasibility study,

Guidance and Regulations,Final design and Strategy

Requirements,Costs

ApplicationDevelopment

Experimental setup, Sampling,Modeling, Measurements,Simulation, Con�guration

ImplementationInstallation, Training and

Procedures, Filing support

Evaluation& Maintenance

Periodic Performance / dataveri�cation & adjustment if

required

Validation

Risk based validationaccording to guidance and

regulations, Statistical evaluation,Performance simulation

Proof of ConceptDecision

DeliveryApplication

Decision

Customer feedback:

“very systematic and scientifically sound”

Blend UniformityInline monitoring or control of powder blending processes provides major advantages in terms of process understanding, efficiency, cost saving and risk reduction in process development, tech transfer and manufacturing. InProcess-LSP develops complete solutions in this area, either based on qualitative (rate of change) or quantitative

Liquid ProcessingIn-line content monitoring during liquid processing offers several benefits in process development & manufacturing. InProcess-LSP provides customers with tailor made solutions using NIR/Raman/UV-Vis and related methods. As example we developed a dedicated ATR-UV method for monitoring a high absorbance compound in a complex solution, assuring content uniformity in the final product.

Offline NIR/RamanAt-line (near your process) or offline (at your laboratory) analysis by UV/VIS, NIR or Raman can provide very valuable information of your intermediate or end-products. No or limited sample preparation in combination with fast analysis times make at-line and offline methods very efficient for monitoring product and process quality. Providing the desired information instantly, without time cconsuming logistics transferring and analyzing samples at different

methods for uniformity assessment. By applying efficient development and validation strategies in combination with in-house capabilities to develop and validate blend uniformity methods, InProcess-LSP assures a highly efficient and high quality approach for you as a customer.

location, makes these methods attractive from time and cost perspective. Typical application areas are moisture content of various sample types including lyophilized cakes, powders, tablets etc. Composition or content of one or more ingredients, or residual solvents for instance can often be measured within one minute by dedicated calibration models. InProcess-LSP has a wide experience in this field and can support you finding the optimal solution.

CONTRACT RESEARCHInProcess-LSP offers Contract Research and Troubleshooting services to reveal important information of your products and processes. We apply PAT or offline analysis to your processes and products either in our lab-facilities or directly at your process if required. Contract research can typically vary from one day to weeks for the larger projects.

In-depth studies related to process performance and product quality are performed by pre-defined and agreed work-packages against fixed pricing offers. If your analytical questions require a dedicated and typically non-routine approach. Contact us to discuss possibilities.

ANALYTICAL SERVICES

TROUBLESHOOTINGIn case product quality or process performance does not meet expectations this could have serious impact on your business. InProcess-LSP can effectively support your root cause finding studies by applying advanced analysis methods to your products and processes. Since we fully understand the necessity of fast feedback and often aggressive timelines for troubleshooting projects, you can count on our full commitment and flexibility as a professional partner.

On-site UV-Vis monitoring of gelatin compounding allowed rapid DoE studies for process development.

Spectroscopic and optical offline analytical methods offer cost-effective and rapid alternatives to chemical analyses, with a range of direct benefits to process development, understanding and troubleshooting. Since these methods require no (or very limited) sample preparation, undesired sample disturbance is avoided and the relevant product characteristics are measured directly and rapidly. The in-house techniques we offer include:

• Near Infrared, Raman and UV/VIS spectroscopy• Microscopy and NIR Imaging• Powder Flow and Physical properties• Morphology studies• Reology • Optical Coherence Tomography• Nanoparticle sizing studies• Various data analysis and calibration• Design of Experiments• Modelling and Simulation

Products or intermediates we analyze for our customers range from tablets, powders, freeze dried products, complex liquids and creams to capsules and polymeric devices.

In close collaboration with our customers we define the study set-up providing answer to their process or productrelated questions. Using our extensive network combined with broad expertise in spectroscopic, imaging and optical techniques, InProcess-LSP also supports customers with lab analysis and analytical consultancy in areas such as infrared and terahertz spectroscopy, fluorescence or Raman (confocal) microscopy, particle size analysis, SEM as well as rheology.

Customer feedback: “....I worked with InProcess-LSP on a troubleshooting project using their advanced analytical methods. When the need arose for a technique currently not in their portfolio they rapidly connected to a provider and produced the data and interpretation we needed to understand the problem...”

Dr. Wim Oostra, Sr. Technical Manager Pharmaceutical Science & TechnologyAbbott

Optical Coherence Tomography (OCT)

FT-NIR

NIR Chemical Imaging

NANOPARTICLE ANALYSISThe NanoFlowSizer is an inhouse developed nanoparticle sizing instrument based on spatially resolved dynamic light scattering, offering unique capabilities to measure highly turbid nanosuspensions and emulsions without sample dilution or other sample preparation requirements. In addition, the NanoFlowSizer technology allows measurements in flow which allows direct inline measurement during processing or dynamic experiments. Since nanoparticle size characteristics can be obtained at high frequency in a continuous mode the NanoFlowSizer offers unique capabilities to study dynamic behavior of nanoparticles like growth or aggregation. Typical operational particle size range of is 10-1000nm.

For nanoparticle analysis by NanoFlowSizer typically input parameters like viscosity are important. InProcess-LSP can provide all necessary rheological properties of your samples as well (see rheological studies).

(see for more information www.nanoflowsizer.com)

NANOPARTICLE ANALYSISAND RHEOLOGY

RHEOLOGICAL STUDIESRheological properties such as viscosity, shear thinning and yield stress of liquids, polymers, gels or pastes are of vital importance both for successful processing and as final quality attribute of products. InProcess-LSP can support you with full rheological studies of your products using our state of the art instrumentation and our broad experience in rheological measurement and data-interpretation based on the composition of your formulation. The measurement spectrum we offer includes all standard tests (e.g. shearrate dependent viscosity, yield stress, storage and loss moduli, creep and their temperature dependence) as well as customized tests with tooling and protocols customized for your specific sample needs.

DEDICATED INSTRUMENTSInProcess-LSP will typically find the best possible solution for your analytical questions and objectives. In case existing technology and instrumentation does not meet your requirements, it is possible to consider development of a dedicated system. A dedicated system would typically be an optimized analysis system with software for your specific needs. Based on initial discussion and agreement of the User Requirements Specification, a dedicated instrument will be designed and manufactured in close collaboration with you as a customer. Instrument development projects will typically be divided in clear development phases with full transparency of required time and costs.

DEDICATED INSTRUMENTSAND SOFTWARE

Customer feedback: “....InProcess-LSP rapidly and competently analyzed the complex structure of our product by employing custom-made image analysis. The results added valuable information to our product characteristics and improved our product and process understanding...”

Bart van Ingen, MSc Technical Project Leader Cosun Biobased Products

DEDICATED SOFTWAREInProcess-LSP offers dedicated software solutions. Dedicated software may be of interest if direct translation of analytical (raw) data to meaningful information is required without the need for additional data processing. Dedicated software can typically provide the exact calculation and presentation of the desired information. Related statistics may be integrated as well to optimize the output information for your specific objective.

In principle, it is possible to provide dedicated software for any type of data processing. Whether you are interested in image processing, spectroscopic data processing or other types of data processing, please feel free to discuss your challenges and objectives with us.

DATA ANALYSIS Transforming raw measurement data into the relevant information on process performance or product properties is essential for successful application of PAT methods. It can be challenging for companies to find the required data-analysis expertise and resources along with the relevant knowledge of the analytical method, the process and the product.

InProcess-LSP supports customers with tailor-made advanced data analysis and modeling services. We offer chemometric calibration and multivariate/statistical analysis for spectroscopic and Process Analytical projects. In addition we offer advanced image analysis for any imaging technique, including chemical (hyperspectral) imaging. To support and improve customers’ process and product development with better mechanistic understanding, we also develop predictive physical/mechanistic models for process simulation in specific areas. In all cases we provide tailor made solutions using custom written analysis algorithms.

Chemometric calibration

and model maintenance

Multivariate modelling and data analysis

Advanced Image analysis

Physical/mechanistic modeling and simulation

To apply Quality by Design and process design & improvement strategies effectively, throrough understanding of available tools and possibilities is required. Although overall principles are often known, practical execution may be challenging. Good design practice will undoubtly provide significant benefits in the areas of process risks, yield and quality. In addition, the current regulatory landscape increasingly demands in-depth knowledge and risk based validation of processes.

InProcess-LSP has broad expertise (black belt level) both in Six Sigma based improvement (DMAIC) and design (IDOV) projects, and in applying Quality by Design in process development. Our process development and improvement services typically include:

• QbD strategy and filing support• Risk Assessment strategy and facilitation• Six Sigma based design and improvement projects• Design of Experiments support • Monte Carlo Simulation• Process performance evaluation and statistics

PROCESS DEVELOPMENT & IMPROVEMENT

PROCESS DEVELOPMENT & IMPROVEMENT

Customer feedback:“....the company shows a professional way of performing process risk assessments together with our specialized teams based on a very good scientific approach...”

Dr. Marcel van Aar, Generics Project LeaderTeva Pharmaceuticals

Design tool

Based on linkagebetween variables andrequirements

Identication of CPP’s

Quality FunctionDevelopment

(QFD)

Risk Analysis tool

Based on risk scoringby matrix

Suitable when limitedproject specic knowledgeis available (early stage)

Identify risk areas

Risk Rankingand Filtrering

KNOWLEDGE

Detailed Risk Analysis tool

Suitable for denedprocess and su­cientproject experience

Challenge the process

FMEA

Objective(s) & Possibilities,Role InProcess-LSP

RISK ASSESSMENT STRATEGY AND FACILITATIONRisk Assessment is an integral part of Quality by Design. Risk analysis approaches and requirements in pharma are well described in ICH guidance documents. However, identifying and executing the optimal approach at different development stages for different complexities of processes may be difficult. InProcess-LSP facilitates risk assessments at early and later development stages and offers support to find the best solution for you as a customer.

InProcess-LSP offers dedicated and customized training courses specifically tuned to your requirements. The effectiveness is further enhanced by addressing typical customer applications and results. Addressing your theoretical and practical challenges, directly related to your products and processes, will help you to broaden your knowledge which can be directly applied into practice.  Different training ‘building blocks’ can be combined in order to create the most optimal training program, such as: • Process Analytical Technology strategies• NIR for blend uniformity assessment• Fundamentals of Near Infrared (NIR) Spectroscopy• NIR Imaging• Introduction in Chemometrics• Method Development and Validation of NIR methods (including regulatory aspects)• Multivariate Calibration of Spectral data• Basic Rheology• Advanced Rheology• Particle sizing overview course• Nanoparticle-sizing by spatially resolved DLS• Design of Experiments• Quality by Design in practice• Risk Assessment for process development Dependent on the training needs of the customer, a dedicated 1 to 3-day training program can be compiled. If you are interested in a dedicated training program, please contact us to discuss your needs and preferences. Formal training certificates and in-house developed training materials are always included.

Customer feedback:“....I attended the Basic NIR training at InProcess-LSP. It was a very effective and valuable training which I recommend to my employees...”

Peter Ebben, Quality ManagerFrieslandCampina

TRAINING

Enthusiastic& Comitted

Full Validation& Implementation

BusinessCase Driven

In-houseLab facilities

Access totechnologies& equipment

Fit-for-Purposemodeling

50 Year PAT experience

in Pharma

Criticalview

Creative

Aiming to exceed

expectations

TYPICALSTRENGTHS

Independent

INPROCESS LSPAdvanced Analytics for Products and Processes

Kloosterstraat 9

5349 AB Oss

The Netherlands

T: +31 412 211 002

info@inprocess-lsp.com

www.inprocess-lsp.com