Vaccine Formulation

Lab Solutions for Testing, Quality Control, and Development of Vaccines

Overview
Publications
FAQ
Relaterade produkter
Mer information

What Is Vaccine Formulation?

Vaccines exploit the natural defense mechanism of the body to “teach” the immune system to build protection against specific foreign pathogens, primarily bacteria and viruses. They are traditionally employed to prevent or reduce the transmission of infectious diseases; however, some emerging vaccines may aid in the elimination of existing cancerous or otherwise diseased tissues.

Vaccine formulation is the process of developing and producing vaccines. Vaccines generally combine primary and secondary vaccine components to achieve high bioavailability and bioactivity of target substances while exhibiting the proper type and degree of immune stimulation. Secondary ingredients are added to ensure transport stability and shelf-life. Efficient manufacturing processes are required to meet high regulatory standards.

Development of a Vaccine Formulation – Main Formulation Components

Vaccine formulations typically contain an antigen, which can be equated to the active pharmaceutical ingredient (API), along with one or more adjuvants, which aim to enhance the immunogenic action of the antigen. Excipients are then added to help with formulation stability and storage.

Current Vaccine Antigen Types

There is a wide variety of vaccine categories, and they are usually classified as live or non-live to distinguish vaccines containing attenuated replicating strains of the pathogen from those containing only components of the pathogen or killed whole organisms.

Viral vaccines. The two main approaches to whole virus vaccines are:
- Live attenuated vaccines, which use a weakened form of the virus that can still replicate without causing illness.
- “Killed” vaccines, which use viruses that cannot replicate but still trigger an immune response since the antigens present in the viral structure are kept.

Recombinant viral vector vaccines. Viral vector vaccines use an unrelated attenuated virus (adenovirus) to hijack cellular machinery and give host cells instructions to produce antigens that trigger an immune response.

Subunits/Recombinant protein vaccines. Recombinant proteins vaccines or protein subunits vaccines use pieces of the pathogen produced using recombinant DNA technology.

Toxoid vaccines. Toxoid vaccines are prepared from attenuated toxins secreted from bacteria. The technology is matured and vaccines of this type are used for diseases such as tetanus and diphtheria worldwide.

Bioconjugate vaccines. Bioconjugate vaccines modify or combine two or more different vaccine components by mechanical, chemical, or biocatalytic (enzymatic) processes.

mRNA vaccines and pDNA vaccines. Nucleic acid vaccines include mRNA and pDNA (circular plasmid DNA) vaccines. These vaccines use genetic material, either RNA or DNA, to provide cells with the instructions to make an antigen. Once inside a human cell, mRNA or pDNA vaccines use the cells’ protein machinery to make the antigen that will trigger an immune response.

Type of vaccine	Vaccines using this technology
Live attenuated	Smallpox, measles, mumps, rubella, oral polio vaccine, BCG (tuberculosis), influenza
Killed whole organism Whole-cell Inactivated	Pertussis Polio
Subunit Recombinant protein Purified proteins from the organism Polysaccharides	Hepatitis B (HBV) Acellular pertussis Pneumococcal
Toxoid	Diphtheria Tetanus
Viral vectored	Ebola
Nucleic acid (mRNA)	SARS-CoV-2 (Comirnaty and Spikevax)

Table 1: Different types of vaccines and how they are used

The manufacturing workflow is similar for all vaccine classes. An antigen is identified, produced, purified, and formulated. Nowadays, most antigens are produced through bioprocessing following the steps below:

Upstream processing uses bacteria, yeast, or cell cultures to produce an antigen (virus, bacteria, recombinant proteins, attenuated toxin) or to amplify the pDNA necessary for mRNA vaccines. Online monitoring of parameters such as the pH, dissolved oxygen content, and percentage of CO₂ in culture media is necessary to optimize culture conditions and yields.
Downstream processing begins to isolate and purify the compound of interest (antigen, pDNA) from the bulk environment. The compound of interest can be further processed if necessary (e.g. virus inactivation, pDNA linearization, and mRNA transcription).
In formulation the antigen is combined with some adjuvants, stabilizers, and excipients to improve vaccine efficacy and storage.

Available Vaccine Adjuvants

Besides antigens, which are considered the API and induce the adaptive immune response, most vaccines also contain adjuvants, which help to simulate a stronger immune response.

There are six main classes of adjuvants:

Aluminum salt adjuvants: Aluminum salts are typically precipitated and require particle engineering control.
Oils or other emulsion substances: These can originate from numerous sources and require characterization of impurities and particle size engineering after extraction and purification.
Liposomes or other lipid nanoparticles: These particles may be produced by chemical synthesis of core lipid components or through biocatalysis or bacterial fermentation.
Bacterial adjuvant products: These adjuvants are made from either semi-crude or purified recombinant components.
Immunostimulatory complexes (ISCOMS): These vaccine adjuvants are essentially fully structured or fragmented cytokine proteins, other proteins, or peptides produced through traditional upstream and downstream bioprocessing methods before being combined with the primary vaccine antigen(s).
Oligonucleotides: These specialized nucleotides are made through solid-phase oligonucleotide synthesis in a separate workflow before formulation with the primary vaccine adjuvant.

Adjuvant effectiveness is typically evaluated during clinical efficacy trials. Therefore, it is important to establish quality attributes for vaccine adjuvant formulations early in the clinical development phase.

Vaccine Stabilizers and Excipients

Vaccines can be fragile. Different formulations commonly show different stabilities to corresponding temperature conditions.

While live attenuated vaccines in liquid solutions are sensitive to freezing, inactivated viruses, subunits or toxoids are more sensitive to heat. Stabilizers or excipients are added to the formulation to minimize damage due to freezing or heat exposure, or to protect the antigen against shear and dehydration during drying.

Mannitol, dextran, lactose, L-leucine, and trehalose are commonly used as protective excipients. The choice of stabilizer depends on the type of vaccine formulation and requires careful optimization of formulation parameters in the first stage of product development to assess which excipient or combination of excipients best stabilizes the antigen in a vitrified status.

Combining Vaccine Components

Two key points in the formulation of vaccines are the addition of adjuvants to increase the immunogenicity of the antigen and the addition of excipients to improve the stability of the final product, which influences storage conditions.

Usually, live-attenuated vaccines are the only vaccines that do not require additional adjuvants in the formulation to increase immune response. However, their storage conditions demand a well-kept cold chain.

Various characterization and screening steps and processes can help to ensure final vaccine formulations deliver required performance once combined. The steps of choosing an adjuvant and preparing formulations is described below.

Screening and selection of adjuvants must often balance contradicting clinical and manufacturing needs. E.g. when using a recombinant, sub-unit antigen, which typically is matched to an aluminum salt adjuvant, critical quality attributes (CQA) such as small adjuvant microparticle sizes with high surface-area-to-volume ratios and antigen adsorption capacity promote high bioactivity. Yet, small particles are notoriously challenging for final drug product yield control, filtration efficiency, and vial fill-finish.

Chemical and physical attributes, as well as process parameters such as temperature, mixing dynamics, concentration control, reagent dosing rates, mass transfers, and particle and reaction kinetics need to be considered when choosing the adjuvant. Efficient and repeatable characterization of process parameters and the transformations that result can enable the definition and control of the desired attribute. Automated laboratory reactors are highly useful for investigating the effect of chemical and physical parameters on adjuvant preparation.

Antigen and adjuvant interactions and screening.

Antigens adsorb onto adjuvants such as AlPO4 and others by ligand exchange along with electrostatic, hydrophobic, or van der Waals interactions. Other adjuvants such as lipid nanoparticles may encapsulate the vaccine antigen.

During formulation studies of antigen-adjuvant interaction, it is important to assess the antigen-adjuvant interaction stability. Issues must be addressed such as:

Whether the interaction is permanent or reversible, as well as its strength and stability,
Kinetics of reactions or particle transformation mechanisms,
Intermediates or transformations of the antigen–adjuvant complex before it reaches an equilibrium, and
Whether formulations can quench and/or lock the antigen-adjuvant complex into a more stable configuration for improved bioactivity.

Real-time and in situ process measurements via spectroscopic analysis and particle engineering PAT (process analytical technology) aid in characterizing antigen-adjuvant interactions.

Optimizing vaccine against a number of factors

As noted, vaccines can be fragile. Stabilizers or excipients are added to:

Minimize aggregation or degradation of a drug product during production,
Enhance the solubility of an active drug product,
Maintain proper pH,
Preserve stable conformation or secondary structure,
Retain high antigen-adjuvant adsorption, and
Extend shelf-life during long term storage.

Often excipient and stabilizer selection considers the final vaccine outcome as determined by offline analytical methods but may fail to adequately address or characterize the process or procedure itself. Understanding the kinetics, route mechanism or in-situ molecular interactions is critical to establishing robust process controls.

Up-concentration processes by ultrafiltration using tangential flow filtration (TFF), hollow fiber filters, or other methods are commonly used in formulating vaccines. Up-concentration can be performed independently or in tandem with diafiltration, also using similar filtration methods.

The need for greater throughput, process characterization, and control is a driver for real-time analytical technology in buffer exchange unit operations. Analyzing higher concentration protein, viral, or polysaccharide antigen solutions is an advantage for biologic processes measured with vibrational spectroscopy PAT tools, facilitating the real-time, simultaneous analysis of proteins and excipients in an aqueous solution.

Vaccines are commonly stabilized in powder form via freeze drying. The addition of cryo-protectants in vaccine formulation plays a huge role in developing a stable powder formulation.

A cryoprotectant stabilizes the vaccine molecule through vitrification and decelerates the aggregation of proteins or lipid membranes. The crystallization behavior of the excipient as well as the collapse temperature (Tc) and glass temperature (Tg) of the freeze-concentrated solution are significant variables influencing formulation stability. Determining these values using differential scanning calorimetry (DSC) prior to freezing gives indications of formulation stability and has the potential to determine the success of the entire freeze-drying process.

Challenges of Vaccine Formulation Development

Vaccine formulation development involves multiple duties and responsibilities. As such, the challenges faced in formulation development are varied and specific to the tasks at hand.

Core challenges shared across formulation steps include:

Formulation-specific design and handling. Each reaction and vaccine formulation method necessitates a specific design and handling, including conditions that may also be unique to each reaction scheme and require unique characterization.
Sampling as a bottleneck. Sampling typically becomes a critical bottleneck. HPLC and offline particle characterization are standard analytical methods used extensively throughout formulation development. Many thousands of samples are taken, most by hand, and these are manually prepared for offline HPLC or offline particle characterization techniques.
Lack of in-situ measurements. Reaction kinetics and antigen adsorption mechanisms are difficult to characterize without in-situ measurements.
Limited information from intermittent sampling. Similarly, intermediates or process events can easily go unnoticed with intermittent sampling and may fail to produce a true understanding of the process mechanisms.
Choosing the correct carrier vesicle to protect the payload that can not only withstand production and delivery conditions, but also be site-targeted

In-situ particle characterization, or PAT combined with characterization techniques such as spectroscopy, can help to address these challenges and streamline the development of effective vaccine formulations, which can be of critical importance when faced with an active outbreak of life-threatening illness.

Optimizing Vaccine Formulation Development

Optimizing vaccine development requires an in-depth understanding of immunology, bioprocessing, bioconjugation, adjuvant synthesis, antigen-adjuvant adsorption, excipients/stabilizers, up-concentrations, buffer exchange, and other process parameters. Various technologies help ensure success in vaccine development.

In-situ particle characterization and spectroscopy PAT are often used in combination with automated laboratory reactors. The can eliminated the need for intensive and repetitive manual operations and accelerate process characterization. PAT can be used to support vaccine formulation development activities such as:

Stability studies. DoE (design of experiments)-based stability studies to assess temperature, hydrolysis, oxidation, deamidation, or degradation from light, as well as assessments of impurities or degradation by-products consequential to analysis are improved via inline characterization methods.
Critical process parameter (CPP) definition. Using PAT to define CPPs helps to accurately assess crucial transformations, microparticle formation kinetics, drug substance stoichiometry, uncontrolled transformations, molecular adsorption, antigen-binding, or unwanted secondary structure changes.
Analysis and data assessment. The reduction of sampling needs offered by PAT and automated reactors facilitates structured and searchable data and improve data analysis and handling.
Measuring process parameters and quality attributes. Attributes including particle size, agglomeration, antigen structure, antigen-adjuvant interactions, and solubility are easily assessed and characterized.

To help ensure the quality of the vaccine formulations in powdered form, the temperature of the formulation should never rise above its glass transition temperature during the drying process and during storage.

DSC analysis of the formulation prior to the drying steps will enable the determination of the glass transition temperature of a freeze-concentrated solution as well as that of the final powder, helping to optimize drying parameters as well as storage conditions.

Drying processes never remove 100% of the water contained in the sample. The remaining water influences the shelf life, physical and chemical stability, and overall quality of the vaccine. A moisture content that is too low can cause processing issues or aggregation, while a moisture content that is too high will lead to product degradation due to shelf life and storage instabilities.
The reference to measure residual moisture in pharmaceutical lyophilized products to ensure they remain stable and effective is coulometric Karl Fisher titration.

Challenges of Vaccine Quality Control

According to vaccine manufacturers, quality control and testing can take up to more than half of vaccine production time. The legal responsibility to maintain the effectiveness of products at every stage of production generally falls to the manufacturer. Hence, analysis of vaccine raw materials and the finished product becomes crucial. The following technologies help address quality control challenges in vaccine development and manufacture.

Among currently available analytical techniques, UV Vis spectrophotometry is considered a standard method for the concentration measurement of proteins and nucleic acid content. This is important because, e.g., mRNA vaccines require highly purified DNA/RNA to maintain potency.
UV Vis can also be used in the analysis of enzymes, nucleotides, and plasmids as well as in the purity/impurity profiles of raw materials such as ethanol and sucrose. This flexibility along with ease of analysis has made UV Vis an analysis of choice for the characterization of both final vaccines and various vaccine components across the development chain.

Many pharmaceutical ingredients are either hydrates or contain water in adsorbed form. Water can influence excipient behavior and vaccine shelf-life and stability. Analyzing moisture content and understanding how moisture influences the product is essential to the definition of vaccine specifications and limitations.
Karl Fischer titration is one of the most frequently used water determination methods. Water content determination is important to demonstrate compliance with pharmacopeia standards. One example where Karl Fischer’s titration is for the characterization of Polysorbate 80, a commonly used excipient in vaccine formulation.
The moisture content of excipients and of the final powder formulation can also be measured using a moisture analyzer where the monograph mentions a “loss on drying” method using a drying oven. These measurements will give information on storage conditions and shelf life.

Meeting Vaccine Development Regulations

The field of pharmaceutical analysis is highly standardized internationally. Vaccine manufacturers must supply information on the API content and additives present in their vaccine formulations, which requires rigorous testing.

Regulatory authorities publish specific guidelines that include assays to evaluate adjuvant and adjuvant-antigen complex stability to regulate adjuvant selection and quality control. The adjuvant alone and in the final formulation should also be subject to preclinical and clinical assessment to ensure its safety and efficacy, and to measure its ability to stimulate the immune system against a specific antigen.

Companies must adhere to local and/or global pharmacopeia compendial regulations that dictate the chemical composition of substances allowable for use in manufacturing products, and analytical techniques and methods used in quality control are defined in international test methods. Governing pharmacopeias can include the United States Pharmacopeia (USP), European Pharmacopeia, Japanese Pharmacopeia, Chinese Pharmacopeia, Indian Pharmacopeia, and the International Pharmacopoeia (issued by the World Health Organization), or pharmacopeias of other countries. Thanks to active efforts for global harmonization, regulations have become largely consistent among the different pharmacopeias.

To ensure vaccine safety, effectiveness, and acceptance by the regulatory authorities, it is important to assess quality at every stage of development. METTLER TOLEDO provides instruments for critical in‐depth analytical characterization, quality assurance (QA), and quality control (QC) research and development.

Solutions for Vaccine Formulation Development and Quality Control

Vaccine formulation development requires the characterization of individual vaccine components, adjuvant-antigen complexes, process kinetics, molecular interactions, and other quality attributes. Differential scanning calorimetry (DSC). The DSC3+ from METTLER TOLEDO measures the enthalpy changes in samples due to changes in their physical and chemical properties as a function of temperature or time. Knowing the thermal characteristics of a vaccine formulation helps to define the vaccine drying parameters and to achieve higher stability.

Karl Fischer (KF) titration. The ability to determine the residual moisture content of a vaccine with acceptable accuracy is crucial for safety. With an increasing number of samples to analyze, scientists are under high time pressure to deliver results, while maintaining accuracy and safety. METTLER TOLEDO coulometric Karl Fischer titrators offer accurate and precise water determination with maximized throughput, efficient workflows, and traceable data that improves safety and productivity.

Monitoring the effect of process parameters in real-time on excipients, stabilizers, adjuvants, and antigen-adjuvant interactions is not feasible with classical offline analysis and characterization methods. Instead, DoE methods and their interdependent variables are best understood and optimized via technologies that measure the process in real-time as they exist in situ.

Thermostating systems. Easy-to-use thermostating improves temperature management, eliminating ice baths and other cumbersome handling to ensure that CPPS such as temperature, pH, mixing rate and dosing are accurately measured, enabling reproducible conjugation chemistry, adjuvant synthesis, and adsorption processes. METTLER TOLEDO EasyMax™, OptiMax™, and RX-10™ make these processes easier, more efficient, and more accurate.
In-situ spectroscopy. In-situ spectroscopy tracks and monitors key drug substances, excipients, or reaction species simultaneously and in real-time in both aqueous and organic solvents/buffers. Highly useful for characterizing unknown process intermediates, antigen secondary structure changes, percent adsorption, and other relationships between liquid and solid vaccine components, ReactIR™ and ReactRaman™ track rapid chemical and structural transformations without interference from suspended particles.
In-situ particle characterization. In-situ particle measurement systems characterize adjuvant or antigen particles which may be fragile or susceptible to change when measured by other techniques. They can also characterize, promote or prevent short-lived transformations that may affect vaccine particulate quality. ParticleTrack™ and EasyViewer™ easily monitor microparticle size, count, and distribution in heterogeneous suspensions.

METTLER TOLEDO iC Software Suite integrates the entire PAT experimental workflow, making it simple to visualize, interpret and report results. In each iC product, powerful algorithms and graphical representations are combined with a simple user interface enabling scientists to gain deeper process understanding with less effort. iC Software Suite automatically captures, prepares, and shares experimental data between teams building institutional knowledge as well as preserving crucial results for regulatory authorities.
These in-situ analytical techniques used in conjunction with automated reactors enable a thorough understanding of how reaction conditions and variables affect vaccine formulation and provide excellent platforms for scaling up challenging processes.

Various equipment and methods exist to assist in the accurate quantification of antigens, adjuvants, and excipients in vaccine manufacturing following the guidance of different pharmacopeias. Common techniques include liquid handling, weighing, titration, density, refractive index, UV/Vis spectrophotometry, melting point, pH, conductivity, and moisture determination.

Titration determines the quantity of a specific substance (analyte) contained in a sample by the controlled addition of a reagent (titrant) of known concentration. It is commonly recommended by monograph e.g. for the characterization the stabilizer tromethamine or to determine sodium acetate concentrations. Titration also characterizes fats and oils and provides the acid-, hydroxyl-, peroxide- and saponification values of excipients. The modular Titration Excellence line ensures that you are prepared to meet future analytical challenges with intelligent sensors for all application types.
pH is important to assess the stability and safety of the final vaccine formulation. It is also useful for verifying the quality of specific vaccine ingredients. Specialized InLab® sensors are available for specific biological applications.
Melting point, density, and refractive index are physical parameters used to characterize organic and inorganic compounds and to ascertain the purity of vaccine ingredients.
Thermal analysis with the DSC 3+ from METTLER TOLEDEO is used to measure the enthalpy changes in samples due to changes in their physical and chemical properties as a function of temperature and time. Knowing the thermal characteristics of a vaccine formulation helps to define the vaccine drying parameters and to achieve higher stability. Thermal analysis with DSC or TGA can be also used on separate substances to determine their purity. These methods can also determine the characteristics of separate substances from the final formulation.
Moisture analysis helps ensure the quality of excipients and final products. The ability to determine the residual moisture content of a vaccine with acceptable accuracy is crucial for safety. With an increasing number of samples to analyze, scientists are under high time pressure to deliver results, while maintaining accuracy and safety. METTLER TOLEDO Karl Fischer titrators and Halogen Moisture Analyzer offer accurate and precise water determination with maximized throughput, efficient workflows, and traceable data that improves safety and productivity.
- The HX204 Halogen Moisture Analyzer is ideal for samples with low moisture content and for highly regulated industries.
- Volumetric Compact Karl Fischer titrators accommodate a wide range of water content applications from 100 ppm to 100%.
- Compact Coulometric Karl Fischer titrators offer particularly fast and precise titration of samples with a low water content from 1 ppm to 5%.
UV/Vis spectrophotometric determination is considered a standard method for the concentration measurement of proteins and nucleic acid content. Spectrophotometer UV5 Nano is ideal for life science applications where micro-volumes are analyzed, while Spectrophotometer UV7 is ideal for regulated environments.

The variety of equipment in a pharmaceutical quality control lab often presents challenges in terms of collating and integrating data for recordkeeping compliance. METTLER TOLEDO offers a wide range of instruments and balances that, in combination with LabX™ software, help simplify and streamline FDA 21 CFR part 11 compliance activities.
All data from Excellence instruments and balances is automatically stored in a centralized database. LabX all but eliminates manual data recording and transcription risk, which helps labs and production sites meet FDA ALCOA+ data integrity requirements. Data can be accessed from anywhere 24/7. Customized reports are easily generated.
METTLER TOLEDO also offers accurate balances and scales to meet analytical and production needs. Learn more about how our instruments can accommodate various sample needs and process requirements, including intelligent dosing automation.

Publications

FAQ

How do vaccines work?

When a disease-causing organism (virus, bacteria, fungus, parasite) enters the human body, the immune system identifies it as harmful and triggers a response to overcome it. Pathogens are made of several specific parts that are usually unique to a specific pathogen and disease. The immune system recognizes these parts as foreign (antigen) and produces antibodies against them.

Antibodies are specific to the antigen detected. Antibodies to one pathogen, therefore, cannot detect and mark another pathogen for destruction. For every new antigen, our body needs to build a new specific antibody. When the same disease is encountered again, the immune system has a memory of the disease and is ready to react against it before symptoms can develop.

Vaccines contain part of the pathogen that work as an antigen to trigger the first immune response against a disease, creating a “memory” of it. In the ideal, if a vaccinated person encounters the disease later, the immune system “remembers” it and prevents infection, though other desired outcomes of vaccination include less dangerous infections and limiting transmission.

What is vaccine formulation?

Vaccine formulation is the process of development and production that combines primary and secondary components to achieve high bioavailability and bioactivity while exhibiting the proper type and degree of immune stimulation. It also seeks to produce excellent stability and shelf-life as well as an efficient manufacturing process that meets high regulatory standards.

Primary components (antigen or antigen precursors) serve as prophylactic or therapeutic modalities that elicit an adaptive immune response. Secondary components (adjuvants and other excipients) are used to increase the effectiveness of vaccines via immunostimulatory, immunomodulatory, or immunopotentiator effects.

Vaccines are traditionally employed to prevent or reduce infectious diseases, while some emerging vaccines may aid the elimination of existing cancerous or diseased tissues.

Can I use an infrared moisture analyzer to get reliable results for water content?

A moisture analyzer using either infrared or halogen heating technology may be able to provide water content, depending on the analytical goal and sample character.

A thermogravimetric moisture analyzer measures evaporative weight loss caused by sample heating (i.e., “loss on drying”). If a sample contains only water as a volatile, a moisture analyzer will provide the water content. If other volatiles are present, it will provide moisture content. Moisture analyzers can therefore also be used to easily determine the solid content of solutions.

If the goal is to determine the water content of a sample that contains other volatiles, Karl Fisher titration will be a more appropriate method.

What is the benefit of PAT in vaccine development?

By collecting highly repeatable analytical data at regular intervals throughout each experiment, scientists and engineers get the best understanding and complete investigations in less time. Obtaining accurate and frequent samples reveals fundamental insights and leads to quick, well-informed decisions.

Which parameters should be monitored during a fermentation and why?

Process analytics during fermentation serves to maintain ideal living conditions for the suspended cells. This includes monitoring and control of the physicochemical environment such as pH, dissolved oxygen, and dissolved carbon dioxide. By sustaining perfect growth conditions, product quality can be kept high, yield can be improved, and fermentation run time can be reduced.

What are sensor requirements for inline monitoring of a fermentation?

To be suitable for use in bioprocess engineering, inline sensors must be sterilizable, should exhibit low drift, and need to operate reliably over days or even weeks. Preferably, sensors should require simple, infrequent maintenance so that valuable technician time is not unnecessarily spent on measurement point maintenance.

Can lab automation equipment help me ensure regulatory compliance?

In a word, yes. Laboratories that are subject to audit work to ensure compliant results through tight control over their analytical workflows. When using automated laboratory instrumentation, instruments themselves are selected and installed with care. Their history of use, routine testing, and service is typically tracked in detail.

Accompanying software is monitored with similar rigor to verify that it meets regulations concerning the completeness and security of data records, as well as fulfilling other applicable requirements: e.g., restricting users' access to an assigned set of devices and/or methods.

METTLER TOLEDO supports compliance by offering guidance on instrument choice, installation location, and setup, as well as appropriate service packages. We also provide traceable weights and certified reference substances for routine testing, modular software packages that secure data and accommodate new processes, and SOP creation that can help reinforce results quality.

Learn more about service and routine testing solutions such as CarePacs^®, CertiRef™, and LinSets or review our Good Measuring Practices to assess current process accuracy and more.

How can I be sure that my balance meets the accuracy requirements of my tests?

It is important to be aware of balance performance in relation to specific applications. A specific balance may be suitable for one application but not another. METTLER TOLEDO's Good Weighing Practice^™ (GWP^®) can help you determine if a balance is fit-for-purpose.

For accurate results, weigh within a safe weighing range. The upper limit of this range is the balance capacity, and the maximum sample weight should never exceed it. The lower limit is determined through a combination of balance minimum weight, process tolerances and the application of a safety factor. The smallest weighed weight must not be less than the lower limit of the safe weighing range.

A balance's minimum weight can be determined at the point of use by a service technician, and the safety factor applied varies according to application criticality. For more information on the safe weighing range, download the guide "Safe Weighing Range Ensures Accurate Results".

What are your service and preventive maintenance offerings?

We support and service your measurement equipment through its entire lifecycle, from installation through calibration, preventive maintenance, and repair. We help you ensure accurate results and compliance with all industry standards and regulations by offering a quality management system and global calibration standards.

All our technicians use the same software, which ensures full traceability. METTLER TOLEDO Service plans are tailored to your needs and your industry-specific requirements. For example, we offer a fast response time and preferential intervention with the Extended Care package, as well as a testing plan and fit-for-purpose confirmation of the instrument.

With METTLER TOLEDO training, you ensure operators and technical staff have the knowledge and confidence to operate your equipment efficiently and effectively. Our service technicians bring your team up to speed and prepare them for the tasks ahead.

Sökförslag

Vaccine Formulation

Lab Solutions for Testing, Quality Control, and Development of Vaccines

What Is Vaccine Formulation?