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Creative Biogene offers a series of analytical testing service for biopharmaceutics, pharmaceutics and clinic products. With leading-edge instruments and an excellent platform, our scientist team bring clients professional services with high quality results. Our analytical testing service help manufacturers ensure the biosafety of their products according to specifications and meet international standards. In addition, our experienced scientist team will always work closely with our clients to meet their needs. Custom analytical service is welcome.

The purpose of this publication is to show how an elemental impurities excipient database can be used in assisting the execution of a drug product elemental impurities risk assessment as required by the ICH Q3D guidelines. As a result of this exercise, we have demonstrated that the database, used in conjugation with other sources of information, is a credible source of elemental impurity levels in excipients therefore, a valuable source of information in completion of drug product risk assessments. This useful collection of data helps to reduce the burden of analytical testing for elemental impurities in excipients.

Adeno-associated virus (AAV) vectors, which contain a DNA transgene packaged into a protein capsid, have shown tremendous therapeutic potential in recent years. An inherent characteristic of the manufacturing process is production of empty capsids that lack the transgene and are therefore unable to provide the intended therapeutic benefit. The effect of empty capsids on clinical outcomes is not well understood, but there are immunogenicity and efficacy concerns, and these empty capsids are considered a product-related impurity. Therefore, empty capsids should be controlled during the manufacturing process and monitored through analytical testing, but there are limited techniques available that are capable of quantifying capsid content and even fewer that are amenable to validation and implementation as registered release tests in a regulated environment. In addition, there is currently not a widely accepted gold standard technique for quantifying capsid content, and the understanding of how the results compare between different orthogonal technologies is limited. The current study utilizes a comprehensive assessment to evaluate diverse analytical techniques for their ability to quantitate capsid content., Graphical abstract, A comprehensive study was performed to evaluate various analytical techniques for their ability to quantify the capsid content of adeno-associated virus vectors.

Rubber stoppered glass vial systems are widely used as primary containers for storing and delivering therapeutic protein products to patients. Addressing concerns and regulatory expectations related to the risk to biologic drug product quality and patient safety from rubber stoppered glass vial systems requires implementation of an extractable and leachable evaluation program based on material understanding, risk assessment, literature review, and a comprehensive scientifically sound analytical testing methodology. The extractable and leachable study design consisted of twelve drug products filled in twelve different size glass vials capped with laminated and nonlaminated rubber stoppers made from three different rubber formulations. Design of the model solvents was successful as they had little to no analytical interference and mimicked the formulation conditions and generated representative extractables capable of predicting leachables. The extraction conditions of time and temperature were appropriate as not to degrade the test materials or the extractable compounds, and yet generated significant quantities for identification of the extractable compounds with confidence. The extractables testing results were capable of predicting the leachable profiles of the twelve drug products. In each case, the leachable profile was a subset of the extractable profile. The organic and elemental impurities of the leachable profiles of drug products were the end-to-end verification of the quality of the glass vials, rubber stoppers and drug product lifecycles. Overall, the holistic approach was fully successful in the qualification of different vial systems as primary containers and delivery systems for different biotherapeutic products to ensure product quality and patient safety.

A biosimilar is a biological medicinal product whose active substance is a version of an active substance of the previously authorised biological medicinal product. The approach taken to develop biosimilar products is fundamentally different from the one used for a new biological medicinal product because the main efforts are directed towards reproducing the original active substance to the greatest possible extent. The biosimilarity concept recognises that it is impossible to reproduce the original biopharmaceutical in full. Thus, it allows for certain differences if they do not cause a significant negative impact from the clinical point of view. To show biosimilarity, an extensive analytical testing program should be implemented where all detected differences are then evaluated in the functional assays. The subsequent non-clinical or clinical tests are needed to demonstrate that the biosimilar delivers the same clinical effect as the reference biological product, but not to prove, yet again, the safety and efficacy of the biological active substance per se by reproducing the development program of the reference biologic.

The Athlete Biological Passport (ABP) is an indirect approach which provides a complementary and more sophisticated strategy to traditional analytical testing in an effort to scientifically gather evidence of possible doping in sport. The ABP is one tool in a kit of intelligent anti-doping practices meant to deter and detect the use of prohibited substances in sport. In 2013, the WADA Athlete Biological Passport Guidelines introduced a second module, the Steroidal Module, which became operational since January 1, 2014. The Steroidal Module monitors an athlete’s steroidal variables over time that may be indicative of steroid abuse. This paper summarized the details of samples requested for confirmation on GC/C/IRMS in year 2015 & 2016 to understand the pattern of generation of Atypical Passport Finding Confirmation Procedure Request (ATPF-CPR). Interestingly, out of total 26 cases of ATPF-CPR received by NDTL, three samples with normal steroid profile showed exogenous origin of endogenous steroids on GC/C/IRMS analysis, which proves the effectiveness of Steroidal Module. In this context, monitoring of steroid passport through steroidal module represents the new paradigm in detection of exogenous origin of endogenous steroids. Keywords: ABP, Steroid Profile, SSPCPR, ATPFCPR, Endogenous, Exogenous.

The COVID-19 pandemic has prompted hundreds of laboratories around the world to employ traditional as well as novel technologies to develop vaccines against SARS-CoV-2. The hallmarks of a successful vaccine are safety and efficacy. Analytical evaluation methods, that can ensure the high quality of the products and that can be executed speedily, must be in place as an integral component of Chemistry, Manufacturing, and Control (CMC). These methods or assays are developed to quantitatively test for critical quality attributes (CQAs) of a vaccine product. While clinical (human) efficacy of a vaccine can never be predicted from pre-clinical evaluation of CQA, precise and accurate measurements of antigen content and a relevant biological activity (termed “potency”) elicited by the antigen allow selection of potentially safe and immunogenic doses for entry into clinical trials. All available vaccine technology platforms, novel and traditional, are being utilized by different developers to produce vaccines against SARS-CoV-2. It took less than a year from the publication of SARS-CoV-2 gene sequence to Emergency Use Authorization (EUA) of the first vaccine, setting a record for speed in the history of vaccine development. The largest ever global demand for vaccines has prompted some vaccine developers to enter multiple manufacturing partnerships in different countries in addition to implementing unprecedented scale-up plans. Quantitative, robust, and rapid analytical testing for CQA of a product is essential in ensuring smooth technology transfer between partners and allowing analytical bridging between vaccine batches used in different clinical phases leading up to regulatory approvals and commercialization. We discuss here opportunities to improve the speed and quality of the critical batch release and characterization assays.

The article considers the aspects of increasing the competitiveness of an agricultural enterprise in modern conditions with the use of innovative management methods. Ensuring the country's food security is impossible without intensive cultivation of agricultural crops, based on the achievements of scientific and technological progress. The solution of this problem requires a large number of investments in the conditions of limited land resources and the instability of agro-industrial production.

Food fraud is of high concern to the food industry. A multitude of analytical technologies exist to detect fraud. However, this testing is often expensive. Available databases detailing fraud occurrences were systematically examined to determine how frequently analytical testing triggered fraud detection. A conceptual framework was developed for deciding when to implement analytical testing programmes for fraud and a framework to consider the economic costs of fraud and the benefits of its early detection. Factors associated with statistical sampling for fraud detection were considered. Choice of sampling location on the overall food-chain may influence the likelihood of fraud detection.

This article is part of a longer research-analytical work, because it outlines the results and conclusions of the study according to the main topic of the research and the applies method. The central theme of the research is the dynamic stiffness of machine tools and the various methods for their determination. After analytical testing, we will deal with another method, because we also use CAE software to perform previous tests in the form of simulations. The results obtained are compared with the values previously determined analytically.

The increased use and applicability of Cannabis and Cannabis-derived products has skyrocketed over the last 5 years. With more and more governing bodies moving toward medical and recreational legalization, the need for robust and reliable analytical testing methods is also growing. While many stationary phases and methods have been developed for this sort of analysis, chiral stationary phases (CSPs) are unique in this area; not only can they serve their traditional chiral separation role, but they can also be used to perform achiral separations. Given that mixtures of cannabinoids routinely contain enantiomers, diastereomers, and structural isomers, this offers an advantage over the strictly achiral-only analyses. This work presents the separation of a 10-cannabinoid mixture on several polysaccharide-based sub-2 µm CSPs with both normal-phase and reversed-phase ultra-high-performance liquid chromatography (UHPLC) conditions. Along with the separation of the mixture, appropriate single-peak identification was performed to determine the elution order and reported where applicable.

Background: A spray pattern (SP) test is one of the most challenging in vitro tests for nasal spray products (NSPs) associated with a high degree of variation. The total results variation observed in such studies should be in major part representative of product performance to assure high confidence when making conclusions based on obtained results. Analytical methods should be developed in a way to minimize variation contribution of random factors. A systematic statistical assessment of sources of variation is encouraged to be performed during any method development. Methods: This study includes the development of a product-shaking procedure, definition of in vivo relevant actuation parameters, and the development of a robust SP method considering NSP behavior. The final SP method is tested on different days and in different laboratories to evaluate the contribution of individual factors and interactions to the observed variance in SP using a gauge repeatability and reproducibility (GRR) model. Results: It was found that the time lag between consecutive actuations significantly influences the variability of the SP area, suggesting the importance of determining a recovery period. Factor analyst was not found to be important. Factor day was found to have the potential to impact results, mostly through interactions with other factors, suggesting that one should pay attention when performing any comparative studies within the same laboratory on different days. Significant differences were observed when the same product was tested in different laboratories. Conclusion: Key random factors, which significantly contribute to total variation, were identified using a GRR approach. By applying an appropriate control strategy over these factors, one can assure that assessed total variation can be representative of product performance. The same general approach is not only applicable to development of SP method for NSP but to all types of analytical testing as well.

A solid oral dosage form (as a tablet) which is an immediate or extended-release dosage form which necessitates the scoring bisect of the tablet. This review discusses the quality attributes and interpretations for the split studies of the various tablet formulations using the analytical techniques. Each method of analysis for the evaluation of split-half tablets in terms of its critical quality attributes discusses in detail explanation of analytical methodology and challenges in formulation development. The results for quantitative analytical evaluation in terms of finished product/stability testing and release of the split-half drug product against the acceptance criterion and also discusses the flowchart guidance for the investigation of out of specification results. The present article provides an insight into the complete analytical evaluation of split-half drug product testing according to the requirements of tablet scoring as per US food and drug administration.

Gunshot residue, or GSR, can be a valuable tool in forensic science, but its importance depends greatly on how it is utilized during an investigation and applied in criminal courts. This comprehensive review defines what constitutes GSR resulting from a discharged firearm. Sampling methods and analytical testing instrumentation will be discussed along with data interpretation and limitations of analysis.

In the coagulation laboratory, much emphasis has been placed on rapid and accurate testing; however, spurious results that are inaccurate and do not reflect the actual status of the patient can potentially lead to an incorrect diagnosis and altered intervention. Errors in coagulation results and interpretation can occur at any point of the process from obtaining the specimen to interpretation and use of the result by the clinician. The main sources of error include the patient's biological and preanalytical variation, analytical testing, and postanalytical use of the reported result(s). This article reviews various sources of error leading to spurious results, providing methods to recognize these aberrant results and presenting solutions for minimizing their occurrence.

Background: A biosimilar is a biological medicine highly similar to another already approved biological medicine (reference product). The availability of biosimilars promotes competition and subsequently lower prices. Changing the current biosimilar clinical comparability trial requirements may lead to lower biosimilar development costs that potentially could increase patients’ access to biologics. Objective: The aim was to determine the perceptions of industry and medicines agency regulators regarding the value, necessity, and future developments of the European biosimilar clinical comparability trial requirements for establishing biosimilarity. Methods: Semi-structured interviews were conducted with eight European national medicines agency regulators and 17 pharmaceutical company employees or consultants with experience in biologics between September 2018 and August 2019. Data were subjected to content analysis. Results: In general, the participants expected that clinical comparability trial requirements will continue to be reduced, in particular based on advancements in analytical testing and knowledge generated from prior biosimilar approvals. However, there are also competing issues at play, such as competition, physician’s trust, and ethical considerations. Participants also reported that any new initiative to reduce or waive biosimilar clinical requirements needs to be scientifically sound and could potentially lower biosimilar development costs. Conclusion: The main findings are that biosimilar clinical comparability trial requirements are likely to change in the near future. Clarity is needed on how to ensure adequate correlation between physicochemical data, pharmacokinetic/pharmacodynamic studies, and the drugs’ performance in the clinic, as well as how to continue sufficient immunogenicity assessment. Obtaining this clarity can facilitate regulatory assessment of the next biosimilars.

There is an increasing need in decentralized high-performance analytical testing in many fields, including human healthcare, environmental, food and water monitoring, to name a few. High-performance testing has mostly remained so far limited to bulky and expensive analytical equipment in centralized labs. Smartphone are able to break that paradigm by providing a quantitation equipment (e.g. a smartphone camera) attached to portable digital platform. This chapter provides an overview on the opportunities and challenges for smartphone-based testing in modern point-of-need applications.

In this chapter, we describe an LC-fluorescence (FLR)/MS-based method for released N-glycan analysis in the development of biotherapeutic proteins. The method includes enzymatic release and labeling of N-glycans with a signal-enhancing tag, LC-MS data collection, and data interpretation. Using the given protocol, up to 24 glycan samples can be prepared within 1 h, while the LC-FLR/MS data can be collected and analyzed using an established data processing method in a semi-automated manner.

Grains and cereals provide a great deal of the global population’s calories and are immensely important to many countries’ economies. Much of the adulteration that takes place in different grain crops is primarily of economic concern, such as varietal or species substitution, organic fraud, and genetically modified organism adulteration. However, some issues exist that also have human health implications, namely, the adulteration of protein products with toxic melamine, or the mixing of gluten-containing cereals with nongluten products (a threat to celiac individuals). Several different analytical methods have been evaluated for grain quality control, including spectroscopies, analyte separation techniques, types of mass spectrometry, stable isotope measurements, immunosorbent assays, DNA methods, or combinations thereof. When industry combines appropriate analytical testing with preventative risk mitigation plans that are based on known vulnerabilities to fraud, quality grain products can make it from the farm to the hands of consumers.

Analytical quality by design (AQbD) has now been considered as an indispensable element for the analytical testing and development of robust analytical methods. Since the inception of the concept, it has proven its worth in developing the drug products with robust performance. Notwithstanding the benefits of AQbD in product development, it has versatile applications in analytical development. Within analytical science, the liquid chromatographic methods are increasingly used for routine pharmaceutical analysis and quality assessment of the drug products. Such methods primarily include high-performance liquid chromatography, ultra-performance liquid chromatography, and ultra-fast liquid chromatography. The critical understanding of the analytical method performance essentially requires systematic optimization of the critical method parameters for attaining enhanced robustness and performance to support the product development through the life cycle. AQbD typically provides benefits by reducing the time, resources, and efforts for developing robust liquid chromatographic methods with applicability in the analysis of drug substances, degradation products, impurities, and metabolites.

The cannabis market is expanding exponentially in the United States. As state-wide legalization increases, so do demands for analytical testing methodologies. One of the main tests conducted on cannabis products is the analysis for terpenes. This research focused on implementation of accelerated solvent extraction (ASE), utilizing surrogate matrix matching, and evaluation of traditional vs. more modern sample introduction techniques for analyzing terpenes via gas chromatography–mass spectrometry (GC-MS). Introduction techniques included Headspace-Syringe (HS-Syringe), HS-Solid Phase Microextraction Arrow (HS-SPME Arrow), Direct Immersion-SPME Arrow (DI-SPME Arrow), and Liquid Injection-Syringe (LI-Syringe). The LI-Syringe approach was deemed the most straightforward and robust method with terpene working ranges of 0.04–5.12 μg/mL; r2 values of 0.988–0.996 (0.993 average); limit of quantitation values of 0.017–0.129 μg/mL (0.047 average); analytical precisions of 2.58–9.64% RSD (1.56 average); overall ASE-LI-Syringe-GC-MS method precisions of 1.73–14.6% RSD (4.97 average); and % recoveries of 84.6–98.9% (90.2 average) for the 23 terpenes of interest. Sample workflows and results are discussed, with an evaluation of the advantages/limitations of each approach and opportunities for future work.

Metal building systems clad in masonry or precast concrete panels (hard walls) have been shown through analytical studies, shake table tests, and postearthquake reconnaissance to be suscept...

Within the pharmaceutical industry, it is a regulatory requirement to ensure that pharmaceutical drug manufacturing equipment is clean prior to use. Cleaning processes of manufacturing equipment are performed using a “validated” process and subsequently verified since inadequate cleaning can result in a contaminated or adulterated product. Historically, cleanliness of equipment within Drug Substance/Product/Active Pharmaceutical Ingredient (API) manufacturing is validated and verified using direct swabbing of the equipment and subsequent analytical testing of the swab extract. In this study, a novel approach has been evaluated using a number of innovative technologies and techniques to develop and validate a methodology based on an in situ hand-held Process Analytical Technology (PAT) to verify manufacturing equipment cleanliness and eliminate swabbing and associated off-line laboratory testing. Specular reflectance Mid Infrared (Mid-IR) spectroscopy was used to detect and quantify surface residue. It is expected that this analytical technique will allow the elimination or reduction of the number of swabs and subsequent off-line analytical testing required during cleaning verification of manufacturing equipment in the pharmaceutical and biopharmaceutical industry. This study was focused on the development and validation of a Mid-IR based calibration model. The results indicate that surface a residue of 0.19 μg cm−2 for a specific molecule is detectable using a specular reflectance Mid-IR technique.

Background A key component of laboratory medicine is the evaluation of specimen suitability for downstream analytical testing. Accurate identification and characterization of the impact of interferents on clinical chemistry analytes is important for patient care. To empirically assess the influence of hemolysis and lipemia on clinical chemistry tests analyzed on a Roche cobas® c701 system, we evaluated serum pools spiked with increasing concentrations of hemolysate and Intralipid®. Methods Using an interferent acceptance threshold of within ± 10% of the non-hemolyzed or non-lipemic results, 31 routine chemistry analytes were evaluated. Results The majority of analytes were determined to have the same or very similar acceptability thresholds as those listed in the vendor package insert. However, several analytes resulted in new thresholds that deviated from manufacturer recommendations (9 higher and 2 lower for lipemia, 7 higher and 6 lower for hemolysis). Samples with high enzyme activities (LDH, ALT, AST, ALP, and CK) were observed to tolerate higher levels of hemolysis, and tiered hemolysis thresholds were established for these enzymes. Independent evaluation of indices is recommended to enable thoughtful implementation of specimen quality criteria and to provide guidance to laboratorians and providers on the nature of these interferences.

The testing and rapid detection of pathogenic organisms is a crucial protocol in the prevention and identification of crises related to health, safety and wellbeing. Pathogen detection has become one of the most challenging aspects in the food and water industries, because of the rapid spread of waterborne and foodborne diseases in the community and at significant costs. With the prospect of inevitable population growth, and an influx of tourism to certain water bodies testing will become a requirement to control and prevent possible outbreaks of potentially fatal illnesses. The legislation is already particularly rigorous in the food industry, where failure to detect pathogenic materials represents a catastrophic event, particularly for the elderly, very young or immune-compromised population types. In spite of the need and requirement for rapid analytical testing, conventional and standard bacterial detection assays may take up to seven days to yield a result. Given the advent of new technologies, biosensors, chemical knowledge and miniaturisation of instrumentation this timescale is not acceptable. This review presents an opportunity to fill a knowledge gap for an extremely important research area; discussing the main techniques, biology, chemistry, miniaturisation, sensing and the emerging state-of-the-art research and developments for detection of pathogens in food, water, blood and faecal samples.

Introduction Cannabis sativa L. (cannabis) is utilised as a therapeutic and recreational drug. With the legalisation of cannabis in many countries and the anticipated regulation of potency that will accompany legalisation, analytical testing facilities will require a broadly applicable, quantitative, high throughput method to meet increased demand. Current analytical methods for the biologically active components of cannabis (phytocannabinoids) suffer from low throughput and/or an incomplete complement of relevant phytocannabinoids. Objective To develop a rapid, quantitative and broadly applicable liquid chromatography-tandem mass spectrometry analytical method for 11 phytocannabinoids in cannabis with acidic and neutral character. Methodology Bulk diffusion coefficients were calculated using the Taylor-Aris open tubular method, with four reference compounds used to validate the experimental set-up. Three columns were quantitatively evaluated using van Deemter plots and fit-to-purpose performance metrics. Low (1.2 μL2 ) and standard (3.6 μL2 ) extra-column variance ultra-high pressure liquid chromatography (UPLC) configurations were contrasted. Method performance was demonstrated with methanolic cannabis flower extracts. Results Bulk diffusion coefficients and van Deemter plots for 11 phytocannabinoids are reported. The developed chromatographic method includes the challenging Δ8 /Δ9 -tetrahydrocannabinol isobars and, at 6.5 min, is faster than existing methods targeting similar panels of biologically active phytocannabinoids. Conclusions The bulk diffusion coefficients and van Deemter curves informed the development of a rapid quantitative method and will facilitate potential expansion to include additional compounds, including synthetic cannabinoids. The developed method can be implemented with low or standard extra-column variance UPLC configurations.

Influenza remains one of the major public health concerns because it causes annual epidemics and can potentially instigate a global pandemic. Numerous countermeasures, including vaccines and antiviral treatments, are in use against seasonal influenza infection; however, their effectiveness has always been discussed due to the ongoing resistance to antivirals and relatively low and unpredictable efficiency of influenza vaccines compared to other vaccines. The growing interest in vaccines as a promising approach to prevent and control influenza may provide alternative vaccine development options with potentially increased efficiency. In addition to currently available inactivated, live-attenuated, and recombinant influenza vaccines on the market, novel platforms such as virus-like particles (VLPs) and nanoparticles, and new vaccine formulations are presently being explored. These platforms provide the opportunity to design influenza vaccines with improved properties to maximize quality, efficacy, and safety. The influenza vaccine manufacturing process is also moving forward with advancements relating to egg- and cell-based production, purification processes, and studies into the physicochemical attributes and vaccine degradation pathways. These will contribute to the design of more stable, optimized vaccine formulations guided by contemporary analytical testing methods and via the implementation of the latest advances in the field.

Abusive business practices are increasingly evident in consumer packaged goods. Although consumers have the right to protect themselves against such practices, rapid urbanization and industrialization result in greater distances between producers and consumers, raising serious concerns on the supply chain. The operational complexities surrounding halal authentication pose serious challenges on the integrity of consumer packaged goods. This article attempts to address the progress and challenges associated with halal authentication. Advancement and concerns on the application of new, rapid analytical methods for halal authentication are discussed. The significance of zero tolerance policy in consumer packaged foods and its impact on analytical testing are presented. The role of halal assurance systems and their challenges are also considered. In conclusion, consensus on the establishment of one standard approach coupled with a sound traceability system and constant monitoring would certainly improve and ensure halalness of consumer packaged goods. © 2017 Society of Chemical Industry.

Food contact materials (FCM) contain chemicals which can migrate into food and result in human exposure. Although it is mandatory to ensure that migration does not endanger human health, there is still no consensus on how to pragmatically assess the safety of FCM since traditional approaches would require extensive toxicological and analytical testing which are expensive and time consuming. Recently, the combination of bioassays, analytical chemistry and risk assessment has been promoted as a new paradigm to identify toxicologically relevant molecules and address safety issues. However, there has been debate on the actual value of bioassays in that framework. In the present work, a FCM anticipated to release the endocrine active chemical 4-nonyphenol (4NP) was used as a model. In a migration study, the leaching of 4NP was confirmed by LC-MS/MS and GC-MS. This was correlated with an increase in both estrogenic and anti-androgenic activities as measured with bioassays. A standard risk assessment indicated that according to the food intake scenario applied, the level of 4NP measured was lower, close or slightly above the acceptable daily intake. Altogether these results show that bioassays could reveal the presence of an endocrine active chemical in a real-case FCM migration study. The levels reported were relevant for safety assessment. In addition, this work also highlighted that bioactivity measured in migrate does not necessarily represent a safety issue. In conclusion, together with analytics, bioassays contribute to identify toxicologically relevant molecules leaching from FCM and enable improved safety assessment.

Homemade explosive (HME) materials commonly take the form of binary, ammonium nitrate-based explosives, and are a challenge to detect due to the low volatility of ammonium nitrate, the great variation in fuel sources, and the complex environment in which detection takes place. Vapor detection in the form of detector canines overcomes these and other obstacles, and has proven to be a highly effective mode of detection. Due to inherent safety precautions associated with working with HMEs, experienced detector canines often lack the frequency of training on HME material necessary to remain proficient. For this reason, the Mixed Odor Delivery Device (MODD) was designed allowing canines to train on the odor of mixed explosives while keeping the HME components separate and unmixed, thus alleviating the safety requirements for handling, storing, and transporting explosives. Experiments across multiple investigative strategies were carried out to evaluate and characterize the vapor distribution in the MODD including computational modeling, analytical testing, and field trials. All testing indicated the MODD accurately provides uniformly mixed HME vapor at detectable levels from separated HME components.

Thrombin and fibrinogen powders are the active components of advanced surgical hemostasis products including the EVARREST Fibrin Sealant Patch. Measuring the enzymatic activity of thrombin in the presence of fibrinogen is challenging, as hydration of the powders in a neutral aqueous environment will cause the enzyme to rapidly react with the fibrinogen to form a fibrin clot, which in turn binds and entraps the enzyme thus preventing subsequent measurement of thrombin activity. A novel approach has been developed to overcome this challenge. After isolation of the mixture of powders, an alkaline carbonate solution is used to solubilize the proteins, while reversibly inhibiting the activity of thrombin and preventing clot formation. Once the powders have been fully solubilized, thrombin activity can be restored by neutralization in a buffered fibrinogen solution resulting in fibrin clot formulation. The rate of clot formation can be quantified in a coagulometer to determine the thrombin activity of the original powder. Samples coated with powders containing fibrinogen and varying amounts of thrombin were tested using the method described herein. The results demonstrated that the method could consistently measure the activity of (alpha) thrombin in the presence of fibrinogen over a broad range of thrombin activity levels. The test was successfully validated according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines and thus is suitable for use as part of a commercial manufacturing process. A method has been developed that enables thrombin activity to be measured in a mixture of fibrinogen and thrombin powders.

Across the globe, the wave of new cannabis and hemp legislation for growing and exportation, medicinal use programs, and adult recreational use of marijuana and cannabinoid products has grown tremendously. Analytical testing defined in the U.S. and Canada includes cannabinoid quantitation, pesticides and mycotoxins analysis, heavy metals analysis, residual solvents analysis, terpene profiling, and microbial screening. Conventional food testing assays like water activity, moisture content, and “filth” may also be regulated in the various regions. This chapter will describe the required chromatographic analytical testing platforms needed to perform these tests with an emphasis on cannabinoid quantitation, residual pesticide analysis, and residual solvent analysis. Any of these methods described in this chapter are translatable to hemp and hemp products since hemp and cannabis are the same plant differentiated only by total THC content.