Best Practices for Analyzing Pesticides and Their Metabolites in Environmental Samples

When a company wishes to commercialize a new pesticide, they must conduct environmental studies and develop analytical methods capable of detecting the pesticide, and its metabolites, in soil and water samples. The methods must be robust and rugged, for easy use in routine analysis. James Stry, a principal investigator at FMC Agricultural Solutions, recently talked to LCGC about best practices he and his team have established for developing such methods, including approaches to meeting a variety of requirements of regulatory bodies, simplifying sample preparation, dealing with matrix effects, choosing an ionization method, and streamlining method development.

When you are developing environmental methods for the registration or re-registration with the U.S. Environmental Protection Agency (EPA) of a new pesticide, what exactly do you have to demonstrate?

We must demonstrate that the methods we develop extract the environmental residue of concern from soil or sediment and that the residue is accurately quantified. To demonstrate the performance of the extraction method, we treat soil samples with radiolabeled compounds and age them in conditions representative of the environment. Aging the treated soil or sediment allows for the environmental metabolites to form and for the soil to become representative of a sample collected from the environment. We then extract the aged samples and analyze the radioactivity in the extract and the amount of radioactivity remaining in the soil. We test different extraction solvents, extraction techniques (for example, bead mill, sonication, or microwave), and the number of extractions conducted until close to all of the significant residue is extracted from the sample.

Once we have an extraction method, we fortify untreated control soil or sediment samples with known amounts of the analytes of interest. We then extract and analyze these samples and compare the concentration determined using the method to the known amount added to the control samples. The amount determined must be between 70% and 120% of the amount added for the method performance to be acceptable.

In addition to meeting the requirements of the U.S. EPA, do you also have to meet requirements for other regulatory bodies, such as those of other countries, if your products will be sold abroad, or of individual states within the United States? If so, how do you balance meeting all the requirements?

In an attempt to minimize additional method development work, we develop our methods to meet the most conservative requirements and test our methods on soil collected from all parts of the world. Currently, the European Union (EU) has some of the most conservative requirements for environmental methods. These requirements are described in the SANCO 825 Revision 8.1 guidance document (1). Once validated, the environmental methods can be sent to support compound registrations anywhere. An example is the residue method for chlorantraniliprole in crops (2). This method was validated on 21 different crops at a limit of quantitation of 0.010 mg/kg. This method has been accepted by regulatory agencies around the world for data collection and maximum residue limit (MRL) enforcement.

What are typically the biggest challenges in developing methods for detecting a pesticide and its metabolites in soil or sediment? What are the biggest challenges for detecting them in water?

Minimizing matrix effects is a major challenge when developing environmental methods. Since our methods are intended to analyze samples from grower fields, a suitable control sample will not always be available. Therefore, preparing standards in untreated control extracts may not always be an option. Moreover, the U.S. EPA prohibits the use of matrix-matched standards in all monitoring and enforcement methods (3).

Developing selective cleanup steps is one way to deal with matrix effects. However, the number and diversity of metabolites in the methods and the low limit of quantitation (1.0 µg/kg or below) makes method development a challenging task. The diversity of metabolites makes it difficult to develop one cleanup procedure capable of removing co-extracts while keeping all of the analytes of interest in a single extract. Keeping all of the compounds in a single extract limits the selectivity of the cleanup procedure.

Developing chromatographic separations using ultrahigh-pressure liquid chromatography (UHPLC) columns or solid-core particles can help minimize matrix effects as well. The sharp peak shape these columns produce lowers the instrument detection level, allowing additional dilution of the extracts. Dilution is perhaps the best way to minimize matrix effects. Instrument manufacturers continue to produce faster, more sensitive, and more-rugged instruments that have allowed us to simplify and streamline our methods. The speed of the newest generation of instruments allow for positive–negative switching without significant loss of sensitivity. This capability has removed the need to separate positive- and negative-ionizing compounds chromatographically or to analyze them in multiple chromatographic runs.

Water samples, although less complicated than soil or sediment, can be just as challenging. Water methods usually have a limit of quantitation of 0.10 µg/L or lower. For methods that include many metabolites, the analytes may need to be extracted from the water samples using solid-phase extraction (SPE) or a liquid–liquid partition step. Once the extract is concentrated, a solvent-exchange step may be needed before analysis. At the low levels analyzed in these methods, minor water contaminants can complicate quantitative analysis.

Over the years, have you developed best practices or streamlined approaches to developing these methods?

When developing the extract purification procedures, we tend to use a systematic approach. Before extracting any samples, we test evaporation and reconstitution steps, liquid–liquid partitions, and SPE procedures. When developing SPE procedures, we filter the analytes through columns in a variety of solvents to determine when they are retained and when they are eluted. Once we retain the analytes on a cartridge, we wash the cartridges with progressively stronger solvents until we have a complete profile of the properties for all analytes. Having all of this information allows us to understand how the analytes behave and to piece together an efficient and effective cleanup procedure.

We prefer to include all of the known metabolites in the methods. If the compound is not detected in the terrestrial field soil dissipation studies or if it does not show any adverse ecotoxicology effects, it can be removed from the method. We refer to this approach as comprehensive method development. We validate our methods in this manner because the addition of a new metabolite to an existing method often results in completely reworking the method, which can be time- and resource-intensive.

In environmental analysis, a challenge is often the complex matrix, which requires effective sample cleanup and preparation. Do you have “go-to” sample cleanup or preparation approaches for certain classes of products?

When developing our methods, we usually start with the most difficult soil or water samples. The idea is that if the method works for the most complex samples it will perform well for the other samples. For soil samples, we start with a high clay, high organic matter soil. We have found this combination results in an extract that is very difficult to purify and analyze. For water samples, we usually start with a pond-water sample.

The methods developed are based on the analytes included in the analysis. When developing methods for polar metabolites, some of the reversed-phase polymer SPE cartridges can be very effective at concentrating the sample extracts. We usually try to develop cleanup procedures that complement the separation and detection methods. If we are using reversed-phase LC we will try to develop an ion-exchange cleanup. If we are using an alkyl SPE cartridge (such as C18 or C8) for the cleanup step, we will develop a separation using a phenyl or biphenyl column. The overall goal is to minimize matrix effects by taking advantage of multiple physical-chemical properties of the analytes.

What percentage of your methods use gas chromatography (GC) and what percentage use LC? Has there been any change in recent years in that balance?

Almost all of the methods we develop are LC methods. Many of our active ingredients are thermally labile, limiting the use of GC analysis. The inclusion of multiple metabolites to these methods also limits the amount of GC analysis we conduct. Often, the metabolites we are analyzing are small polar alcohols or weak acids that are not amenable to GC analysis without derivatization. Although derivatization procedures can be developed, they can be time consuming and add complexity to the methods. It is also worth mentioning that relative to LC analyses, we have generally observed more severe matrix effects when conducting GC analyses.

What type of mass spectrometry (MS) detection do you typically use?

We typically use LC–MS/MS detection on triple-quadrupole instruments. Given that we are analyzing a limited number of known compounds using a reference standard, we can set up several multiple-reaction monitoring (MRM) transitions at the retention time of each analyte. In addition to being very sensitive, this approach allows for confirmation and quantitation during a single analysis. An added benefit is the availability of triple-quadrupole instruments in contract and monitoring laboratories. Using similar equipment allows for our methods to be transferred and revalidated at the laboratories performing the analysis with minimal modifications.

When do you use atmospheric pressure chemical ionization (APCI) MS, rather than electrospray ionization (ESI)?

When developing a new method, we usually start with ESI because often it is more sensitive than APCI. If we determine matrix effects are affecting method performance, we attempt to develop a cleanup procedure that is efficient and effective at minimizing the matrix effects. If, because of the number or diversity of the analytes, the cleanup procedure is not effective, is not rugged, or is very complicated, we switch to the APCI ion source. Although less sensitive, APCI usually does not exhibit the same degree of matrix effects as ESI. Given the reduced sensitivity of APCI, we adjust the injection volume, aliquot factor, or the sample’s final volume to reach the required detection level (2). Not all of the compounds we monitor can be ionized using APCI because of the increased temperature of the ion source and the gas-phase ionization mechanism. For compounds that are not amenable to APCI we return to ESI and look for new extract cleanup steps or better chromatographic separations until a robust method is developed.

How do you balance the need for sample preparation methods that are effective but not overly complicated or time consuming?

We need to strike a balance between the amount of sample cleanup, the time required to conduct the analysis, and the overall method performance. Cleanup can be time consuming and tedious work. However, without adequate cleanup, a method will perform well for only a limited number of sample types because of matrix effects or could result in false positives as a result of coeluted peaks. Reducing sample cleanup in favor of longer chromatographic separations limits the number of samples that can be analyzed per instrument each day.

Because of the large sample size (2–5 g) required to produce a representative soil or sediment sample, we have not implemented the 96-well format or other automated sample preparation approaches. We have seen significant improvements in efficiency using bead mill extractors, however. Bead mill extractors show excellent extraction efficiency of incurred residues and require less solvent per sample, and all of the equipment used is disposable, reducing the probability of sample contamination. The biggest advantage of bead mill extractors is the amount of time required to perform an extraction. An extraction requiring 20–30 min on a wrist action shaker or in a sonicating bath can be completed in 2–3 min using a bead mill.

Our goal is to develop a method with an efficient and rugged cleanup procedure and a set of chromatographic conditions that allow for adequate sample throughput without compromising the accuracy of the analysis.

References

(1) European Commission, Directorate General Health and Consumer Protection. “Guidance Document on Residue Analytical Methods,” SANCO/825/00 rev. 8.1, November 16, 2010.

(2) J. Grant, C.A. Rodgers, C.D. Chickering, S.J. Hill, and J.J. Stry, J. AOAC Int. 93(4), 1293–1301 (2010).

(3) U.S. EPA Ecological Effects Test Guidelines: OCSPP 850.6100: Environmental Chemistry Methods and Associated Independent Laboratory Validation.

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Scaling LC Methods Using Superficially Porous Particle Stationary Phases

The use of ultrahigh-pressure liquid chromatography (UHPLC) is now commonplace among pharmaceutical laboratories. However, until depreciation cycles replace traditional high performance liquid chromatography (HPLC) systems that operate at a maximum pressure of 400 bar, the advantages of UHPLC cannot be realized worldwide. Thus, product methods developed using UHPLC capabilities cannot directly transfer these methods to receiving laboratories without qualified UHPLC availability. As scaling methods from traditional LC to UHPLC has been popular in recent years, the desire exists to address this LC limitation by potentially transferring methods back from UHPLC to available LC systems. This capability has not been shown to be effective on traditional LC columns. Today, pharmaceutical chromatographic methods often use superficially porous packed particle columns that enable UHPLC-like separation under 400 bar. Unlike traditional stationary phases, which use a range of particle sizes with associated column dimensions, superficially porous particle stationary phases often use the same particle size in differing column dimensions. As the particle size now remains the same, this study looks to see if reverse scaling of chromatographic profiles of interest to the pharmaceutical industry can be routinely achieved.

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Liquid chromatography (LC) instrumentation operating at greater than 400 bar is becoming more commonplace as newer equipment is making its way into commercial laboratories. Although these ultrahigh-pressure liquid chromatography (UHPLC) systems are becoming more prevalent, the industry still relies on transferring chromatographic methods throughout the world and, as such, the issue that not all receiving laboratories routinely operate with LC systems that are compatible with UHPLC methods still needs to be addressed.

Since its inception, scaling low-pressure methods to UHPLC conditions has been prevalent. Many companies have scaling calculators available on their websites (1). Scaling of LC is becoming less of an issue as depreciation cycles replace laboratory LC systems with higher pressure capabilities. Yet, the issue of low-pressure systems still exists in pharma when using smaller contract and worldwide laboratories. With proper considerations for flow, injection, and system void volumes, methods developed on <400-bar systems are often made much more efficient using UHPLC conditions (2–4). However, the scaling is not perfect, and the UHPLC method should be revalidated before use. Although resolution may improve, the required lower injection volume may not place enough analyte on the column to detect low-level impurities. In addition, as demonstrated in our laboratory, columns may not behave identically as scaled (5). We found that scaling from UHPLC back to high performance liquid chromatography (HPLC) is not advantageous for impurity methods because of potential selectivity and performance issues. This observation makes sense; we don’t road test a Formula I automobile to race with a street car.

After publication of our reverse-scaling study, columns packed with superficially porous particles (SPPs) have become prevalent for pharmaceutical applications. Columns packed with these particles are often referred to as core–shell columns. Core–shell columns have the advantage of exhibiting near-UHPLC separations but at lower pressures (6). This capability enables laboratories to shorten their separation run times and efficiencies on traditional, non-UHPLC, instrumentation. Relevant to scaling interests, core–shell columns are often packed with the same particle in differing column dimensions. Unlike in the original reverse-scaling studies, core–shell columns enable the same particle to be used in the differing column dimensions. This characteristic may allow separations to reverse scale more effectively from UHPLC to HPLC conditions and pressures. The original intent of this study was to only look at vertical scaling, but the data showed right off the bat that this approach would not work. The investigation moved to horizontal scaling as a follow-up series of experiments to further investigate core–shell column scaling. In this study, a representative separation profile using commercially available drug substances was used to investigate reverse scaling with SPP columns.

Experimental

Instrumentation

The LC data reported in this study was generated using a Thermo Fisher Scientific Ultimate 3000 system equipped with a photodiode-array detector. System volume changes are critical in method scaling. A single instrument platform was used to negate this affect. Using a single system for all column investigations allowed us to operate at both traditional and UHPLC conditions and normalize the system effects and void volume differences that we would have using different systems. Thus, this study focused solely on column differences. The LC system was controlled and the resulting data were processed using Atlas Version 9.00.0.10711 (Thermo Fisher Scientific).

LC Conditions and Samples

Mobile phases and LC conditions were consistent with those used in a previous study (11). A single vendor for the traditional phase UHPLC column and two separate vendors for the SPP phases were used. All target analytes and mobile phases were prepared with chemicals purchased from Sigma-Aldrich. The LC column dimensions that were used are listed in Table I.

Scaling Calculator

Scaling calculations were calculated as described in the manuscript and correlated with spreadsheets received from Grace Discovery Sciences. The use of method translation calculators was recently reviewed by Majors (8).

Results and Discussion

Scaling Calculations

Scaling calculators were created for projecting the run conditions moving from traditional HPLC column formats to UHPLC column formats. In this regard, the calculators work well in speeding up run times from traditional HPLC methods and oftentimes improving, or at least maintaining resolution, throughout the profile (2,3). Because many laboratories still use equipment limited to the traditional HPLC platform, laboratories have attempted to scale back from UHPLC to HPLC with the goal of rapid HPLC method development on the UHPLC platform and transferring the method on traditional platforms that are still being used. Webster and Elliott showed why this approach may not be a good idea (5). This issue is limited in scope as depreciation cycles equip more and more laboratories with UHPLC-compatible instruments. Scaling calculators are designed with the conversion from HPLC to UHPLC in mind. The critical parameters in scaling from UHPLC to HPLC include column length, particle size, and injection volume (5,9–11). Neue and colleagues (12) demonstrated the scaling of separations using 5-µm, 15-cm columns to 1.7-µm, 5-cm columns. Dramatic changes should be made only if the chromatographic profile and resolution of the critical pair is maintained (13).

Scaling calculations are based on standard chromatographic concepts (14). The primary equations used by the scaling calculators are

Injection volume:

where I is the injection volume for methods 1 and 2; d _c is the column diameter used in methods 1 and 2; and L is the column length used for the method 1 and 2 columns.

Flow rate:

where F is the flow rate for methods 1 and 2; d _c is the column diameter used in methods 1 and 2; and d _p is the particle size used for the method 1 and 2 columns.

Gradient time:

where T is the gradient time for methods 1 and 2.

The calculations are designed to provide starting chromatographic conditions followed by further optimization. The critical parameter in reverse scaling is whether these conditions yield a pressure under the pressure maximum for HPLC. Most traditional HPLC platforms tolerate pressure of up to 400 bar. A UHPLC method that is to be converted to an HPLC platform must first be optimized to run at conditions that project that the new method pressure will remain under 400 bar. This often entails slowing down the optimized UHPLC method (5,14).

Figure 1: Study profile on traditional and superficially porous particle phases: (a) traditional UHPLC (50 mm × 2.0 mm, 1.5 µm), (b) Core–shell A (50 mm × 2.1 mm, 2.6 µm), and (c) Core–shell B (50 mm × 2.1 mm, 2.7 µm). Gradient conditions are given in Table II. Peaks: 1 = furosemide,2 = carbamazepine, 3 = naproxen, 4 = valsartan, 5 = ibuprofen, 6 = indomethacin.

Study

The goal of this study was to evaluate whether columns packed with core–shell particles reverse scale more effectively than traditional column packings. A separation based on earlier work (5) was used for actual UHPLC separation using compounds that vary in their chemical nature. In that study, the UHPLC column in a traditional particle format was used as the basis to investigate scaling back to HPLC.

Horizontal Scaling from UHPLC to Core–Shell Particles

Our first attempt is looking at UHPLC to short SPP columns. In Figure 1a, the rapid resolution of varying drug substances on a traditional UHPLC phase is presented. If we cannot scale a representative profile from traditional UHPLC to core–shell UHPLC phases, going to core shell phases packed in traditional lower pressure column dimensions is not warranted. Using the horizontal scaling conditions from Table II, the resulting profile for the 2.6-µm Core–shell A phase is shown in Figure 1b. In this separation, a peak reversal for the carbamazepine and furosemide pair is seen as well as a loss in resolution. Additionally, ibuprofen is coeluted with the indomethacin peak. It is not possible to conclude that scaling yielded an equivalent profile with the Core–shell A column and conditions. Looking at the results obtained using a second core–shell column (from a different manufacturer) in Figure 1c, the resulting profile again exhibits peak reversal and loss of resolution for the carbamazepine and furosemide peak pair. In addition, a coelution of the ibuprofen and indomethacin peak pair can be seen in the profile. Again, an equivalent profile was not produced. The effect of scaling may not be the culprit here as much as the older, traditional stationary phase (type A silica) likely has more exposed silica. It should be noted that using calculators specifically from the Core–shell A and B vendors for their phases did not solve this issue. Looking into this stationary phase effect a little further, the mobile phase was changed from formic acid to trifluoroacetic acid to investigate whether the addition of an ion-pairing reagent would improve the core–shell profile. Figure 2a is the resulting profile adding 0.1% trifluoroacetic acid in place of formic acid used with the traditional phase UHPLC column. Essentially the same profile is produced. However, the profile improves for both SPP phases (Figures 2b and 2c). The ibuprofen peak resolution with the core shell particles remains unacceptable. It is likely with further optimization that the profile could be obtained on the SPP phases. Method optimization is not direct method scaling of the separation. What this data shows is not so much that scaling cannot be achieved, but in more-complex separations the differences in stationary phase chemistries still remain significant. As with all LC separations, the nature of the stationary phase and the chemistry of the analytes must be considered. The United States Pharmacopeia (USP) may traditionally allow the substitution of one C18 column for another, but this equivalence is seldom realized in industrial pharma (16).

Figure 2: Study profile using trifluoroacetic acid on traditional and SPP phases: (a) Traditional UHPLC (50 mm × 2.0 mm, 1.5 µm), (b) Core–shell A (50 mm × 2.1 mm, 2.6 µm), and (c) Core–shell B (50 mm × 2.1 mm, 2.7 µm). Gradient conditions are given in Table II. Peaks: 1 = furosemide,2 = carbamazepine, 3 = naproxen, 4 = valsartan, 5 = ibuprofen, 6 = indomethacin.

Vertical Scaling with Core–Shell Particles

One of the advantages of superficially porous particles, according to their vendors, is that because the same particle is used in different column dimensions, scaling with these phases should be straightforward. Rather than looking at a horizontal scaling from the UHPLC short column as we did before, now we are changing the optimal core–shell conditions and scaling back to traditional HPLC column dimensions. We are going to start with the separation on the short SPP column and see how it vertically scales back to columns with dimensions compatible with lower pressure systems (Table III). Figure 3a is our initial separation for the Core–shell A phase. Ibuprofen was left in the sample matrix to see if the conditions applied will ultimately resolve this peak from the indomethacin peak. Increasing column dimensions, shown in Figures 3b–3e, effectively maintains the original profile. Interestingly, going down to the 1.7-µm particles did not enhance resolution of the original profile. The resolution data for the separations is presented in Table IV and the relative retention times (RRT) are listed in Table V. The RRTs are close, but not acceptably equivalent to say that the profiles scaled equivalently for both the 2.6- and 5-µm particles. From this data, we conclude that the scaling was a good estimate of the conditions needed for the different column geometries. However, there is still enough error in particle composition and packing differences so that direct method scaling was not achieved.

Figure 3: Vertical scaling on Core–shell A SPP phases. (a) 50 mm × 2.1, 2.6 µm, (b) 150 mm × 3.0 mm, 2.6 µm, (c) 150 mm × 4.6 mm, 2.6 µm, (d) 150 mm × 4.6, 5 µm, and (e) 250 mm × 4.6 mm, 5 µm. Gradient conditions are given in Table III. Peaks: 1 = furosemide,2 = carbamazepine, 3 = naproxen, 4 = valsartan, 5 = ibuprofen, 6 = indomethacin.

The vertical scaling study was repeated with columns from a second core–shell column manufacturer, designated as the Core–shell B phase (Table VI). Again, illustrated in Figure 4a, an initial resolution profile for this phase was established. The increasing column dimensions seen in Figures 4b–4e actually improve the profile for the carbamazepine and furosemide peak pair as well as the indomethacin and ibuprofen peak pair to a lesser extent. The resolution and RRT data for this study are presented in Tables VII and VIII. The RRT data are much improved with this series of profiles. It remains difficult to argue that the scaling profile was maintained.

Figure 4: Vertical scaling on Core–shell B SPP phases. (a) 50 mm × 2.1, 2.7 µm, (b) 150 mm × 3.0 mm, 2.7 µm, (c) 150 mm × 4.6 mm, 2.7 µm, (d) 150 mm × 4.6, 5 µm, and (e) 250 mm × 4.6 mm, 5 µm. Gradient conditions given in Table VI. Peaks: 1 = furosemide,2 = carbamazepine, 3 = naproxen, 4 = valsartan, 5 = ibuprofen, 6 = indomethacin.

Conclusion

Column scaling in liquid chromatography is an interesting concept that may work for series of analytes with consistent chemistry. However, the real value in scaling chromatographic methods is attempting to improve challenging lower-pressure separations using UHPLC capability. In our laboratory we have not seen stationary phases scale theoretically with column dimension. Scaling has not proven to be an achievable opportunity for most complex pharmaceutical separations. It is our suggestion to improve chromatographic efficiencies using core–shell and UHPLC technologies in a standalone fashion that can be optimized using scaling principals. However, revalidation is required to establish equivalence because direct scaling is not adequate in the cases studied.

Disclosure

This project was supported by AbbVie, Inc. AbbVie, Inc. participated in the interpretation of data, writing, reviewing, and approving the publication. Gregory K. Webster is an employee of AbbVie and Matthew A. Gragg is a contractor with AbbVie, Inc.

References

(1) Sigma, https://ift.tt/2HMGXUb, Sciences Analytiques: https://ift.tt/2G6XyF0; ACD Labs: https://ift.tt/2G07QDw.

(2) J.W. Dolan, LCGC North Am. 32(2), 98–102 (2014).

(3) J.W. Dolan, LCGC North Am. 32(3), 188–193 (2014).

(4) M. Swartz, “HPLC to UPLC Method Migration: An Overview of Key Considerations and Available Tools,” presented at the Pittsburgh Conference & Exposition on Analytical Chemistry and Applied Spectroscopy (Pittcon), Chicago, Illinois, 2007.

(5) G.K. Webster and A. Elliott, Am. Pharm. Rev. 14, 32–40 (2011).

(6) V. González-Ruiz, A.I. Olives, and A. Martín, TrAC, Trends Anal. Chem. 64, 17-28 (2015).

(7) I. Baranowska and B. Kowalski, Water Air Soil Pollut. 211, 417–425 (2010).

(8) R.E. Majors, LCGC North Am. 29(6), 476–484 (2011).

(9) D. Guillarme, D.T.T Nguyen, S. Rudaz, and J.L. Veuthey, Eur. J. Pharm. Sci. 66, 475–482 (2007).

(10) D. Guillarme, D.T.T Nguyen, S. Rudaz, and J.L. Veuthey, Eur. J. Pharm. Biopharm. 68, 430–440 (2008).

(11) M.M. Dittmann, “Approaches Towards Method Compatibility Between HPLC and UHPLC Systems,” Paper 1970-6, presented at the Pittsburgh Conference & Exposition on Analytical Chemistry and Applied Spectroscopy (Pittcon), Orlando, Florida, 2010.

(12) U.D. Neue, D. McCabe, V. Ramesh, V. H. Pappa, and J. DeMith, Pharmacopeial Forum 35, 1622–1626 (2009).

(13) G.K. Webster and C.L. Basel, LCGC North Am. 21(3), 286–294 (2003).

(14) G.K. Webster, T.F. Cullen, and L. Kott, Ultra-High Performance Liquid Chromatography and Its Applications, (Wiley Interscience, 2013), pp. 31–54.

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Gregory Webster is a senior principal research scientist in Development Sciences at AbbVie, Inc. Dr. Webster received his PhD in analytical chemistry at Northern Illinois University in 1991. Prior to joining Abbott/AbbVie in 2007, he worked at Alpharma, Chemsyn Laboratories, Bayer Corporation, and Pfizer.

Matthew Gragg is currently a chemist working within the NCE Analytical R&D – LC group at AbbVie, Inc. He graduated with a BS in Chemistry from Truman State University in 2015.

Direct correspondence to: [email protected]

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Guardant Health to Present Validation Data for the GuardantOMNI™ assay

Guardant Health developed GuardantOMNI in partnership with several leading pharmaceutical companies. The assay, launched last year, is designed to accelerate clinical trials and the research of targeted cancer drugs and immunotherapies by enabling profiling of patients across an unparalleled number of clinical trial targets with a simple blood draw, allowing low-risk, real-time monitoring of tumor genomics, drug response and tumor evolution, and enabling retrospective analyses of banked samples for target identification.

The validation study demonstrates that, across SNVs, CNVs, fusions, and indels, the performance of the 500-gene GuardantOMNI assay is comparable to the performance of the 73-gene Guardant360® assay, the leading clinical comprehensive liquid biopsy.

“Advances we’ve made sequencing tens of thousands of clinical Guardant360 samples have allowed us to improve the performance of our underlying technology platform to achieve an assay that has 10 times the footprint of Guardant360 without compromising on performance,” said Guardant Health Co-Founder and President AmirAli Talasaz. “We believe this assay can play a unique role in accelerating clinical and pre-clinical programs across the biopharma industry.”

Guardant Health and its collaborators will present eight total abstracts at AACR, demonstrating advances in the understanding of cancer biology and innovations in bioinformatics. A complete list is available here.

About Guardant Health

Guardant Health is focused on conquering cancer by using its breakthrough blood-based assays, vast data sets, and advanced analytics. Using both molecular and digital tools, Guardant Health is addressing challenges across the cancer care continuum. The company has raised more than $500 million from leading investors. Its first product, the Guardant360 assay, came to market in 2014, and is now the most widely ordered comprehensive liquid biopsy commercially available and available in more than 30 countries. In 2016, it announced Project LUNAR, an effort to apply Guardant Health’s technology platform to early detection, recurrence monitoring, and assessing minimal residual disease. Guardant Health and Guardant360 are registered trademarks of Guardant Health, Inc. Learn more at www.guardanthealth.com.

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Microbiology In-Depth Focus 2018 – European Pharmaceutical Review

In this In-Depth Focus; specificity in the recombinant factor C test for endotoxin, the latest trends in pharmaceutical microbiology, and the changing environment in pyrogen and endotoxin testing.

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Method Development and Validation for Assays Supporting Testing of Biologics (San Francisco, CA – June 21-22, 2018) – ResearchAndMarkets.com

DUBLIN–(BUSINESS WIRE)–The “Method
Development and Validation for Assays Supporting Testing of Biologics”
conference has been added to ResearchAndMarkets.com’s
offering.

Biologics continue to be a steadily growing component of the
pharmaceutical industry. The advent of large molecule therapeutics
requires a different perspective on the assays needed to support
development through preclinical and clinical testing.

This 2-day seminar is designed to offer a broad overview of developing
and validating a range of assay methodologies for biologics with
specific key analysis of cell culture, assay variability, and DOE.
Specifically, this seminar covers essential concepts related to
cell-based potency methods, ELISA, and other methods supporting
biologics. In addition to potency methods this seminar addresses
immunogenicity methods for preclinical and clinical studies. The format
of the seminar offers an examination of current best practices as well
as time to dissect examples of documentation with emphasis on beneficial
systems to consider. Scientists who attend this 2-day seminar will gain
knowledge that will be beneficial in helping to achieve well-controlled
validated methods.

Learning Objectives:

• Understanding the different requirements for small versus large
  molecules
• Mapping appropriate timelines with decision points
• Designing, developing, optimizing, and validating key methods
• Potency methods, other release and stability methods
• Preclinical and clinical methods
• Use of DOE and statistical analysis
• Handling of critical materials
• Process monitoring concepts
• Assessment of orthogonal methods
• Assessing readiness for validation
• Defining the validation protocol with real-time capture of data
  analysis
• Maintaining quality through documentation

Who Should Attend:

Below titles working in biopharmaceuticals, pharmaceuticals, natural
products/botanicals will be benefited by attending this seminar:

• Validation Scientists
• QA/QC
• Regulatory Affairs
• Laboratory Managers
• Assay Development Specialists
• Statistician
• CMC Titles
• Bio Assay

For more information about this conference visit https://ift.tt/2vcczBc

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Box Strengthens Product Offering With Major Product Updates – April 12, 2018

Box, Inc. (BOX – Free Report) introduced Admin Insights Dashboard, a major update to Box admin experience. The latest feature will enhance visibility, productivity and simplify processes.

Along with this, Box also unveiled advanced retention policies related to metadata in Box Governance.

The latest move will help Box to further strengthen its product portfolio. The advanced features are likely to boost the client base of the company which will drive the top-line growth.

Coming to the price performance, shares of Box have returned 19.5% over a year, underperforming the industry’s rally of 35.2%.

 

More on the headlines

Admin Insights Dashboard ensures data protection by providing flexibility, scalability, control and security insights. The latest dashboard helps in tracking usage of Box like upload, download, preview, login and edit, across the world. Also, admins can study the user behavior and implement it in personalized training sessions, which will drive the adoption rate of Box.

Extended power enterprise visibility ensures business efficiency and team productivity which is highly in demand.

Moreover, the new retention policies will allow businesses to transform their governance strategy by easily retaining content and unstructured data in the cloud. It will also lower dependency on legacy enterprise content management systems.

Robust Product Portfolio — Key Growth Driver

Box has an innovative product portfolio which will continue to help the company in attracting more customers and clients to its platform and generate higher revenues.

Recently, Box announced first-of-its-kind data processing addendum which is a simple self-serve solution for global data privacy preparedness.

In January 2018, Box introduced Box GxP Validation, which allows validation and operation of GxP compliance standard to its pharmaceutical, biotechnology and medical device business clients.

Late last year, the company launched Box Transform which provides a Box Consultant to business clients to develop customized solutions from their business insights.

Moreover, the company’s strategic partnership with Google Cloud and Microsoft’s Azure is helping it to integrate its platform. This has added enhanced features such as artificial intelligence, machine learning and image recognition capabilities to Box’s cloud products and services.

Growing Cloud Market

Box is well positioned to take advantage of the emerging trend of shifting traditional business model to a cloud based model due to massive amount of data.

Moreover, Box’s strong focus toward innovation and product portfolio expansion will continue to reap benefits from the rising demand for cloud content management products.

Per a report from Markets and Markets, the global cloud enterprise content management market is expected to reach $34.42 billion in 2022 by growing at a CAGR of 28.6% between 2017 and 2022.

Last quarter, Box generated revenues of $136.7 million which was mostly attributed to growing add-on products and strong clientele.

Courtesy to the current cloud market scenario, we believe the company’s market share will continue to gain momentum by winning clients.

 

Zacks Rank & Stocks to Consider

Currently, Box carries a Zacks Rank #3 (Hold).

Investors interested in the broader technology sector can consider some better-ranked stocks like Paycom Software (PAYC – Free Report) , Twitter (TWTR – Free Report) and Veeva Systems (VEEV – Free Report) . All the three stocks sport a Zacks Rank #1 (Strong Buy). You can see the complete list of today’s Zacks #1 Rank stocks here.

Long-term earnings growth rate for Paycom Software, Twitter and Veeva Systems is currently pegged at 24.75% and 21.5% and 17%, respectively.

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New Jersey Firm Gets FDA Warning Letter

FDA sent a warning letter to Tris Pharma Inc. after investigators found the company had failed to properly investigate batch failures and establish quality control procedures.

FDA sent a warning letter, dated March 26, 2018, to Tris Pharma Inc. after investigators inspected the company’s Monmouth Junction, NJ facility and found deviations in current good manufacturing practices (CGMP). During the inspection, which was conducted Feb. 14 to March 20, 2017, inspectors found that the company had failed to properly investigate batch failures and establish quality control procedures.

Specifically, inspectors found that the company did not thoroughly investigate product failures, dissolution testing failures, and defect complaints. Root cause investigation and corrective actions and preventive actions (CAPA) were not “prompt and effective.” According to FDA, previous inspections conducted in 2011, 2012, and 2014 found similar problems.

“Your firm and Pfizer conducted a review of all changes to the manufacturing process and process controls initiated since NDA 202100 approval. You also performed an analysis of process capability. Your review found that one or more steps in the manufacturing process may contribute excessive variation that could cause the dissolution failures. A further assessment of process controls is also being conducted using Failure Mode and Effect Analysis. You expect to complete your process assessment work and perform new process validation studies by (b)(4),” the agency stated. “Your response is inadequate because you did not promptly and thoroughly investigate variables in the manufacturing process that may be responsible for inconsistent product quality (e.g., dissolution performance). You also did not fully address the quality of all in-date Quillivant XR lots on hold or released for distribution in the United States.”

The agency requested the company provide an update on the retrospective review of dissolution and assay failures, a risk assessment of the quality of distributed batches, and an update on the company’s CAPA plans.

An update on the company’s CAPA and risk assessment regarding complaints of leaking or under-filled bottles was also requested by FDA. “After this investigation, you attributed the leaks to a specific lot of caps that had cracks in their liners and remained in inventory for an extended time without retesting. Your response is inadequate. Defective product remained on the market for an additional eight months before you completed a thorough investigation and initiated a recall in July 2017,” the agency stated in the letter.

The agency also stressed the responsibility of the contract facility in ensuring the quality of drug products: “You and your customer, Pfizer, have a quality agreement regarding the manufacture of drug products. You are responsible for the quality of drugs you produce as a contract facility, regardless of agreements in place with application sponsors. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity … You are responsible for ensuring that your firm complies with all applicable requirements, including the CGMP regulations. You should immediately notify the drug application sponsor of changes to the manufacturing or testing of the drug product, and any relevant drug master file updates, so they can file an appropriate submission to the application (supplement or report in annual report). A major change should not be implemented until a prior approval supplement is approved by FDA.”

Source: FDA

 

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TraceLink Unveils EU FMD Express, a Purpose-Built Compliance Solution for Smaller Pharmaceutical

With far greater resource and budget constraints than their larger counterparts, many small pharmaceutical companies face extreme challenges with serialization, including master data management and data exchange with their contract manufacturing organizations (CMOs), making it difficult to meet the EU FMD deadline by February 2019. TraceLink’s EU FMD Express provides these companies with a simple approach to meet EU FMD compliance while controlling costs and minimizing business impact. With over 40,000 users regularly accessing the Life Sciences Cloud system, TraceLink’s EU FMD Express is a complete, easy to use solution that allows smaller manufacturers to comply with EU FMD and integrate with the EU Hub through a single, secure connection, while removing the burden of software maintenance and upgrades, and insulating companies from regulatory changes.

“Due to its size and vast number of companies spread across various countries, Europe is one of the largest and most complex markets, leaving hundreds of small companies grappling with how to achieve EU FMD compliance within the next 11 months,” said Shabbir Dahod, president and CEO, TraceLink. “As the market leader, we feel that is our responsibility to help every company comply, regardless of size, and therefore developed this cost-effective, easy to use offering to streamline the ability for smaller companies to become compliant on time, with no disruption to their business operations.  Through our investment in services and support in the EU and unique network architecture to accelerate company on-boarding, TraceLink is the only company positioned to provide such an offering for this market.”

EU FMD Express: Key Benefits for Small Pharmaceutical Companies
Designed specifically for smaller pharmaceutical companies with simple supply chains, EU FMD Express utilizes purpose-built templates and compliance modules for faster implementation and predictable costs. TraceLink executes the entire deployment, including system configuration and data entry.  Every EU FMD Express customer will benefit from:

• Easy to Use and Proven Solution That Is Purpose-Built for Smaller Companies – Enabling portal access for line management systems and CMOs with integration options available; access to TraceLink’s serial number and event repository; and direct integration into the EU Hub;
• Simplified Deployment, Set-Up and Configuration – TraceLink Services will help EU FMD Express customers define and manage their master data, on-board and train their CMOs, configure the EU compliance module, support for QA testing and validation, and user training.
• Ongoing Training and Education – All EU FMD Express users will have full access to TraceLink configuration templates for master data and serial number templates. TraceLink also provides an online collaboration workspace for companies to exchange customer configuration documents and full access to TraceLink University for tutorials and e-learning courses.

To learn more about EU FMD Express and see how TraceLink provides smaller pharmaceutical companies with unmatched flexibility and predictability while eliminating the uncertainty of high costs from CMO integrations and time-intensive implementations, please visit: https://ift.tt/2qotR8E.

About TraceLink

TraceLink is the World’s Largest Track and Trace Network for connecting the Life Sciences supply chain and eliminating counterfeit prescription drugs from the global marketplace. Leading businesses trust the TraceLink Life Sciences Cloud to deliver complete global connectivity, visibility and traceability of pharmaceuticals from ingredient to patient. A single point and click connection to the Life Sciences Cloud creates a supply chain control tower that delivers the information, insight and collaboration needed to improve performance and reduce risk across global supply, manufacturing and distribution operations. A winner of numerous industry awards including Deloitte’s Technology Fast 500 (ranked number 149 in 2016), the Amazon AWS Global Start-Up Challenge Grand Prize, and the Edison Award for Innovation in Health Management, the Life Sciences Cloud is used by businesses across the globe to meet strategic goals in ensuring global compliance, fighting drug counterfeiting, improving on-time and in-full delivery, protecting product quality and reducing operational cost. For more information on TraceLink and our solutions, visit www.tracelink.com or follow us on LinkedIn, Twitter and Facebook.

TraceLink is funded by Goldman Sachs, FirstMark Capital, Volition Capital and F-Prime Capital.

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New Labeling and Verification System Helps Pharmaceutical Companies Comply with Stricter Worldwide Serialization Regulations

METTLER TOLEDO PCE has launched a labeling and verification system that will help pharmaceutical manufacturers and contract manufacturing organizations (CMOs) meet stricter global serialization regulations. The new T2620 is a compact system for the Track & Trace labeling¬ of cartons in accordance with the Falsified Medicines Directive (FMD) in Europe, the Drug Supply Chain Security Act in the US, and other global regulations.

“We are bringing the T2620 to market in two model variants – for cartons with a width of up to 150 mm and those with a width of up to 250 mm,” says Reinhold van Acke-ren, Head of Marketing at METTLER TOLEDO PCE. “With both model variants, we are able to guarantee pharmaceutical manufacturers and CMOs fast delivery and in-stallation of the system with our standard configurations – increasingly important over
the coming weeks and months as the FMD deadline of February 9, 2019 approach-es.”

Flexible Solution
The T2620 system supports the Track & Trace-compliant printing¬ of data such as se-rial numbers, batch numbers, expiry dates and static product identifiers on the car-ton, together with a datamatrix code containing the same serialization information. The combined system then verifies the accuracy and¬ quality of the printed infor-mation using a camera.

The T2620’s compact design saves valuable production¬¬ space and the system can be easily integrated into new production lines or added to upgrade¬¬ existing¬¬ ones. The T2620 is compatible with all METTLER TOLEDO PCE software for data man-agement, serialization and aggregation, such as PLM and PLM Direct, and can be seamlessly integrated into existing ERP environments via the PCE Software Suite.

Minimal Equipment Setup Time, Maximum Availability
The T2620 system features the latest frame technology from the METTLER TOLEDO C33 Series of checkweighers, making it incredibly stable and vibration-free. It also ensures precise mechanical product transfer and a smooth and¬ secure product flow when interacting¬ with systems that are optimally aligned with each another. The T2620 takes the cartons requiring printing¬ directly from the cartoner by means of a transfer unit. Thanks to the convenient¬ user interface on the terminal for calling up stored¬ product data and the easy-to-use manual setting options, the system can be quickly adapted to new products and carton dimensions.

Inline Validation and Product Rejection
The printer unit prints the serialization data and codes on the front or rear side of the cartons. Cartons with data successfully¬ verified by the camera system are stored in an internal database with the status ‘commissioned’. The logs created at the same time serve as the proof of quality required by GMP. Cartons that do not meet the re-quirements of ISO 15415 during the inline validation of the print quality of the data matrix
code, or that are otherwise defective or illegible, are ejected into the reject bin by means of a precision air nozzle or an optional pusher.

Model Variants
The T2620 system has a belt speed¬ of up to 80 meters per minute for throughput¬ rates of up to 400 cartons per minute. While the T2620-150 model variant supports the processing of cartons¬ with a width of up to 150 mm and a fill weight¬ of up to 300 g, the T2620-250 model provides a solution for cartons with a width of up to 250 mm and a fill weight of up to 1100 g. Both models are available immediately.

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AstraZeneca licenses Ionis’ NASH drug in $300m deal

PBR Staff Writer
Published 10 April 2018

AstraZeneca has licensed a fatty liver disease treatment IONIS-AZ6-2.5-LRx (AZD2693) from Ionis Pharmaceuticals in a deal that could fetch up to $300m for the California firm in milestone payments.

IONIS-AZ6-2.5-LRx has been designed by the US company to inhibit an undisclosed target for the treatment of patients having nonalcoholic steatohepatitis (NASH).

AstraZeneca and Ionis had previously entered into a partnership focused on tapping the antisense technology of the latter to discover and develop antisense therapies for cardiovascular, metabolic and renal diseases.

The licensing of the drug follows its advancement from target validation into the development stage. It is now the third drug under the Ionis-AstraZeneca collaboration to have entered into development with the milestone enabling Ionis an upfront license fee of $30m.

AstraZeneca will now take care of the further development and commercialization of the NASH drug.

As per the terms of the licensing deal, Ionis will be eligible to get up to $300m in the form of additional development and regulatory milestone payments along with tiered royalties from sales of the NASH drug.

Ionis Pharmaceuticals chief operating officer, antisense drug discovery and translational medicine senior vice president Brett Monia said: “IONIS-AZ6-2.5-LRx incorporates many of the advancements we have made in antisense technology, including our LIgand-Conjugated Antisense (LICA) and Generation 2.5 chemistry, and is the second drug in our collaboration to incorporate both modifications.

“By combining Generation 2.5 and LICA, we generate drugs that have the advantages of both higher affinity chemistry and efficient cell-specific targeting.”

Monia further said that the Generation 2.5 and LICA combination helps in developing drugs that are more potent than the two individual constituents. Also, the combination supports administration of infrequent, very low doses, and even allows the possibility for oral dosing, said Monia.

Ionis and AstraZeneca have also formed a partnership to discover and develop antisense drugs for the treatment of cancer.

Last month, Ionis licensed the global rights to inotersen and AKCEA-TTR-LRx (formerly IONIS-TTR-LRx) to Akcea Therapeutics in a deal potentially worth around $1.7bn.

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Image: AstraZeneca UK Sales and Marketing Horizon Place, United Kingdom. Photo: courtesy of AstraZeneca.

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EyeGate Receives FDA Feedback on Investigational Device Exemption Amendment for Second Pilot Study of Ocular Bandage Gel Nasdaq:EYEG

WALTHAM, Mass., April 09, 2018 (GLOBE NEWSWIRE) — EyeGate Pharmaceuticals, Inc. (NASDAQ:EYEG) (“EyeGate” or the “Company”), a clinical-stage, specialty pharmaceutical company with two proprietary platform technologies for treating diseases and disorders of the eye, today announced that it has received a letter from the U.S. Food and Drug Administration (FDA) responding to the Company’s amended investigational device exemption (IDE) application for a second pilot study of the Company’s lead product, EyeGate Ocular Bandage Gel (EyeGate OBG), a cross-linked thiolated carboxymethyl hyaluronic acid (CMHA-S) platform being developed for the acceleration of re-epithelialization of large corneal epithelial defects in patients having undergone photorefractive keratectomy (PRK).

In its letter, the FDA identified four deficiencies in the Company’s submission, requesting additional information on the manufacturing processes associated with the EyeGate OBG product. The primary comment relates to the validation of the filter specifically used for sterilization of the CMHA material, while the remaining comments include a request for clarification to the previously submitted data and modifications to the manufacturing process documents.

“We are pleased that our first IDE amendment addressed the majority of the 13 issues raised in the FDA’s initial response, and believe that the clarity of feedback provided in this letter gives us a clear path to approvability of the application,” said Stephen From, President and Chief Executive Officer of EyeGate. “We are now in the process of addressing the various points raised in the letter, mainly the validation of the sterile filtration of the CMHA material. According to the agency, one of the three filters used for validating the filter required for sterilizing the CMHA material did not pass the validation step by definition. To address this deficiency, our plan is to work with the manufacturer of the filter to complete the validation work using a different filter. We anticipate completing this work in the coming months, and are targeting the submission of a second amendment to the IDE application in July 2018. Assuming this next amendment is approved by the FDA, we would look to initiate the second EyeGate OBG pilot study in PRK patients later in the third quarter, with top-line data reported in Q4.”

The IDE seeks approval for a proposed second pilot study of EyeGate OBG, enrolling up to 45 subjects undergoing a bilateral PRK procedure in a reading center masked trial. The goal of this study is to compare EyeGate OBG to the current standard of care, bandage contact lens (BCL) plus artificial tears. The primary endpoint will be the percentage of subjects achieving complete wound healing (based on staining) on day 3. Subjects enrolled in the study will be randomized into three arms: EyeGate OBG administered four times daily (QID) for 14 days, EyeGate OBG administered eight times daily for three days, followed by QID administration for 11 days, and BCL with QID administration of artificial tears for 14 days.

In March 2018, the Company submitted an amended IDE comprising of the validation data on the manufacturing processes and bioburden tests related to production of EyeGate OBG, as well as data related to the analytical methods to identify and quantify impurities and degradation products.

The amended IDE submission is subject to review by the Center for Devices and Radiological Health (CDRH) of the FDA, and must be approved prior to initiating this study. Once submitted, the FDA will have 30 days to review the amendment and either request additional data or approve the initiation of the study.

About EyeGate
EyeGate is a clinical-stage specialty pharmaceutical company focused on developing and commercializing products using its two proprietary platform technologies for treating diseases and disorders of the eye.

EyeGate’s CMHA-S platform is based on a cross-linked thiolated carboxymethyl hyaluronic acid (CMHA-S), a modified form of the natural polymer hyaluronic acid (HA), which is a gel that possesses unique physical and chemical properties such as hydrating and healing when applied to the ocular surface. The ability of CMHA-S to adhere longer to the ocular surface, resist degradation and protect the ocular surface makes it well-suited for treating various ocular surface injuries.

EGP-437, EyeGate’s other product in clinical trials, incorporates a reformulated topically active corticosteroid, Dexamethasone Phosphate that is delivered into the ocular tissues through EyeGate’s proprietary innovative drug delivery system, the EyeGate II Delivery System.  For more information, please visit www.EyeGatePharma.com.

EyeGate Social Media

EyeGate uses its website (www.EyeGatePharma.com), Facebook page (https://ift.tt/g8FRpY EyeGatePharma/), corporate Twitter account (https://twitter.com/EyeGatePharma), and LinkedIn page (https://ift.tt/2GKHSV6) as channels of distribution of information about EyeGate and its product candidates. Such information may be deemed material information, and EyeGate may use these channels to comply with its disclosure obligations under Regulation FD. Therefore, investors should monitor EyeGate’s website and its social media accounts in addition to following its press releases, SEC filings, public conference calls, and webcasts.  The social media channels that EyeGate intends to use as a means of disclosing the information described above may be updated from time to time as listed on EyeGate’s investor relations website.

Forward-looking Statements

Some of the statements in this press release are “forward-looking” and are made pursuant to the safe harbor provision of the Private Securities Litigation Reform Act of 1995. These “forward-looking” statements include statements relating to, among other things, the commercialization efforts and other regulatory or marketing approval efforts pertaining to EyeGate’s products, including EyeGate’s EGP-437 combination product and those of Jade Therapeutics, Inc., a wholly owned subsidiary of EyeGate, as well as the success thereof, with such approvals or success may not be obtained or achieved on a timely basis or at all. These statements involve risks and uncertainties that may cause results to differ materially from the statements set forth in this press release, including, among other things, certain risk factors described under the heading “Risk Factors” contained in EyeGate’s Annual Report on Form 10-K filed with the SEC on March 02, 2018 or described in EyeGate’s other public filings. EyeGate’s results may also be affected by factors of which EyeGate is not currently aware. The forward-looking statements in this press release speak only as of the date of this press release. EyeGate expressly disclaims any obligation or undertaking to release publicly any updates or revisions to such statements to reflect any change in its expectations with regard thereto or any changes in the events, conditions or circumstances on which any such statement is based.

Contact:
Lee Roth / Janhavi Mohite
The Ruth Group for EyeGate Pharmaceuticals
646-536-7012 / 7026
lroth@theruthgroup.com / jmohite@theruthgroup.com

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Pharmaceutical Analytical Testing Services Market Slated to Grow at a Considerable Pace by 2025

Global Pharmaceutical Analytical Testing Services Market: Snapshot 

The global pharmaceutical analytical testing services market is poised to soar owing to the rising demand from pharmaceutical manufacturers and raw material suppliers. Delivering comprehensive pharmaceutical services in manufacturing and development have become the key concern of several companies. Numerous service providers are offering services such as pharma solutions, packaging, residual solvents, stability testing and storage, method validation, dissolution, raw material testing, leachable or extractable testing, and retrospective method validation.

A major trend observed in the global pharmaceutical analytical testing services market is outsourcing. Absence of the necessary set-up for performing every test in-house is one of the key reasons for outsourcing. The best method for handling tests such as process and facility validation, registration stability storage and testing, analytical testing that deploys expensive equipment, cleaning validations, and method development is outsourcing. Outsourcing to a specialty company provides experience and expertise in this domain. It also aids in bringing down the costs of maintenance, equipment, and validation. As a result, outsourcing is likely to contribute towards the expansion of the global pharmaceutical analytical testing market.

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The clinical bioanalytical testing segment is slated to grow at a considerable pace during the forecast period, attaining a significant share of the global market for pharmaceutical analytical testing services. The factors responsible for the growth of this region are stringent regulatory framework applicable to drug discovery and the rising number of clinical trials driven by the increasing incidence of diseases.

With the advent of several technological advancements, numerous new solutions are being developed. For example, in March 2017, a cost efficient system that enables pharmaceutical label-free ultra-high throughput screening has been launched by Bruker. The pharmaceutical industry has been increasingly deploying NMR fragment-based screening method, which has been incorporated into Bruker’s new software. Increased efficiency, productivity and reliability are some key features of this screening method.

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Pharmaceutical Analytical Testing Services Market: Comprehensive Overview

Pharmaceutical analytical testing services are services offered to several pharmaceutical manufacturers, product manufacturers, and raw material suppliers. The need for increased efficiency and cost reduction by pharmaceutical companies has led to the rising scope for outsourcing analytical testing services. Currently there are a number of companies focusing on providing comprehensive pharmaceutical manufacturing and development services such as manufacturing and packaging, pharmaceutical development, analytical testing services, and pharma solutions. Service providers are also offering several pharmaceutical analytical testing services, such as method development/ method validation, stability testing and storage, raw material testing, residual solvents, dissolution, retrospective method validation, and extractable/leachable testing.

The market for pharmaceutical analytical testing services has been analyzed by taking into consideration the revenue generated by various analytical testing services such as raw material testing, stability testing, and method validation and testing. The report gauges various trends in analytical services across four major geographies: North America, Asia Pacific, Europe, and the Rest of the World (RoW).

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Pharmaceutical Analytical Testing Services Market: Drivers and Restraints

The global market for pharmaceutical analytical testing services is driven by the growing need for the development and cost reduction of core competencies by pharmaceutical companies and the rising acceptance of outsourcing as a key business and growth strategy. Research studies have exhibited that in the year 2012, pharmaceutical and biotechnological companies spend an estimated US$190 mn on in-house analytical development as against the US$664 mn spent on outsourcing analytical testing services. This is likely to strengthen the growth of the market in the coming years.

On the other hand, the lack of skilled professionals and well-established healthcare infrastructure are some of the factors that threaten to hamper the growth of the pharmaceutical analytical testing services market. Apart from this, operational costs, fluctuations in good manufacturing practices (GMP), regulatory policies, and less turnaround times also impact the market growth.

Pharmaceutical Analytical Testing Services Market: Regional Outlook 

North America is one of the leading regions in the pharmaceutical analytical testing services market and is driven by familiarity with the regulatory scenario and the presence of well-established outsourcing infrastructure. The growth landscape of the Europe pharmaceutical analytical testing services market is slowly catching up, experts have observed.

Countries in Asia Pacific present significant growth potential thanks to the presence of a large pool of skilled professionals and relatively low operational costs. Rising investments in research is also a major factor driving the APAC pharmaceutical analytical testing services market. Investments in routine testing, multiplex protein profiling, biologics such as RNA sequencing, and others are likely to give Asia Pacific the boost it needs over the course of the forecast period.

Pharmaceutical Analytical Testing Services Market: Key Players

Some of the leading pharmaceutical analytical testing service providers are Pace Analytical Services, Inc., Intertek Group plc, Aptuit, Inc., and West Pharmaceutical Services, Inc. The vendor landscape of the pharmaceutical analytical testing services market has evolved over the recent past owing to rising mergers, strategic parternships, and downsizing in the pharma sector. In addition to this, increased focus on strengthening internal core competencies and the rising need and demand for faster analytical response fuel the market for pharmaceutical analytical testing services.

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Healthcare Analytical Testing Services Market Assessment – Latest Global Insights on Trends and Challenges – Healthcare News

HTF MI published a new industry research that focuses on Healthcare Analytical Testing Services market and delivers in-depth market analysis and future prospects of Global Healthcare Analytical Testing Services market. The study covers significant data which makes the research document a handy resource for managers, analysts, industry experts and other key people get ready-to-access and self-analyzed study along with graphs and tables to help understand market trends, drivers and market challenges. The study is segmented by Application/ end users [Pharmaceutical], products type [Method Validation, Environmental Monitoring, Bioanalytical Services, Stability & Microbial Testing] and various important geographies like United States, EU, Japan, China, India & Southeast Asia].

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The research covers the current market size of the Global Healthcare Analytical Testing Services market and its growth rates based on 5 year history data along with company profile of key players/manufacturers. The in-depth information by segments of Healthcare Analytical Testing Services market helps monitor future profitability & to make critical decisions for growth. The information on trends and developments, focuses on markets and materials, capacities, technologies, CAPEX cycle and the changing structure of the Global Healthcare Analytical Testing Services Market.

The study provides company profiling, product picture and specifications, sales, market share and contact information of key manufacturers of Global Healthcare Analytical Testing Services Market, some of them listed here are CRO. The market is growing at a very rapid pace and with rise in technological innovation, competition and M&A activities in the industry many local and regional vendors are offering specific application products for varied end-users. The new manufacturer entrants in the market are finding it hard to compete with the international vendors based on quality, reliability, and innovations in technology.

Global Healthcare Analytical Testing Services (Thousands Units) and Revenue (Million USD) Market Split by Product Type such as Method Validation, Environmental Monitoring, Bioanalytical Services, Stability & Microbial Testing. Further the research study is segmented by Application such as Pharmaceutical with historical and projected market share and compounded annual growth rate.
Geographically, this report is segmented into several key Regions, with production, consumption, revenue (million USD), and market share and growth rate of Healthcare Analytical Testing Services in these regions, from 2012 to 2022 (forecast), covering United States, EU, Japan, China, India & Southeast Asia and its Share (%) and CAGR for the forecasted period 2017 to 2022.

Read Detailed Index of full Research Study at @ https://www.htfmarketreport.com/reports/1069481-global-healthcare-analytical-testing-services-market-3 

Following would be the Chapters to display the Global Healthcare Analytical Testing Services market.

Chapter 1, to describe Definition, Specifications and Classification of Healthcare Analytical Testing Services, Applications of Healthcare Analytical Testing Services, Market Segment by Regions;
Chapter 2, to analyze the Manufacturing Cost Structure, Raw Material and Suppliers, Manufacturing Process, Industry Chain Structure;
Chapter 3, to display the Technical Data and Manufacturing Plants Analysis of Healthcare Analytical Testing Services, Capacity and Commercial Production Date, Manufacturing Plants Distribution, R&D Status and Technology Source, Raw Materials Sources Analysis;
Chapter 4, to show the Overall Market Analysis, Capacity Analysis (Company Segment), Sales Analysis (Company Segment), Sales Price Analysis (Company Segment);
Chapter 5 and 6, to show the Regional Market Analysis that includes United States, EU, Japan, China, India & Southeast Asia, Healthcare Analytical Testing Services Segment Market Analysis (by Type);
Chapter 7 and 8, to analyze the Healthcare Analytical Testing Services Segment Market Analysis (by Application) Major Manufacturers Analysis of Healthcare Analytical Testing Services;
Chapter 9, Market Trend Analysis, Regional Market Trend, Market Trend by Product Type [Method Validation, Environmental Monitoring, Bioanalytical Services, Stability & Microbial Testing], Market Trend by Application [Pharmaceutical];
Chapter 10, Regional Marketing Type Analysis, International Trade Type Analysis, Supply Chain Analysis;
Chapter 11, to analyze the Consumers Analysis of Global Healthcare Analytical Testing Services;
Chapter 12,13, 14 and 15, to describe Healthcare Analytical Testing Services sales channel, distributors, traders, dealers, Research Findings and Conclusion, appendix and data source.

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What this Research Study Offers:

Global Healthcare Analytical Testing Services Market share assessments for the regional and country level segments
Market share analysis of the top industry players
Strategic recommendations for the new entrants
Market forecasts for a minimum of 5 years of all the mentioned segments, sub segments and the regional markets
Market Trends (Drivers, Constraints, Opportunities, Threats, Challenges, Investment Opportunities, and recommendations)
Strategic recommendations in key business segments based on the market estimations
Competitive landscaping mapping the key common trends
Company profiling with detailed strategies, financials, and recent developments
Supply chain trends mapping the latest technological advancements

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Reasons for Buying this Report
This report provides pin-point analysis for changing competitive dynamics
It provides a forward looking perspective on different factors driving or restraining market growth
It provides a six-year forecast assessed on the basis of how the market is predicted to grow
It helps in understanding the key product segments and their future
It provides pin point analysis of changing competition dynamics and keeps you ahead of competitors
It helps in making informed business decisions by having complete insights of market and by making in-depth analysis of market segments

Thanks for reading this article; you can also get individual chapter wise section or region wise report version like North America, Europe or Asia.

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HTF Market Report is a wholly owned brand of HTF market Intelligence Consulting Private Limited. HTF Market Report global research and market intelligence consulting organization is uniquely positioned to not only identify growth opportunities but to also empower and inspire you to create visionary growth strategies for futures, enabled by our extraordinary depth and breadth of thought leadership, research, tools, events and experience that assist you for making goals into a reality. Our understanding of the interplay between industry convergence, Mega Trends, technologies and market trends provides our clients with new business models and expansion opportunities. We are focused on identifying the “Accurate Forecast” in every industry we cover so our clients can reap the benefits of being early market entrants and can accomplish their “Goals & Objectives”.

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Validation of Horizon Technology Disk Extraction Technology for US EPA Wastewater Method 625.1

The US EPA monitors a variety of chemicals in water that may cause harm to humans or wildlife to minimize exposure. Method 625 was developed by the Office of Science and Technology in the Clean Water program to allow the monitoring of a large suite of semivolatile chemicals in wastewater for compliance with the National Pollution Discharge Elimination System (NPDES). NPDES is a system of permitting that defines the characteristics of water that is released into a waterway, defined by industrial category. The permitting levels are set depending on the waterway’s use. If the waterway is used for recreation or is an important wildlife habitat, the limit may be set lower.

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The original method was developed in the early 1980s and has been updated several times since then to allow the use of more modern technology. The latest update has taken place over the last few years and was proposed in a Method Update Rule (MUR) in 2015 which was just published in the Federal Register August 28, 2017 and became effective September 27, 2017 (1). The latest version of the method includes a larger suite of analytes (up to 364) and an extensive set of labeled surrogates to better monitor the method performance throughout the sample preparation and analysis step.

This application note will present the data collected as part of the demonstration of disk solid phase extraction validation for US EPA method 625.1. Nine different wastewater matrices were evaluated and tested against the criteria listed in Table 6 of the method. Sample preparation was performed using the Atlantic® One-pass system, where the water sample is passed through a solid phase extraction (SPE) disk and carbon cartridge once, rather than twice with a pH change between loadings. Automation of the process was achieved using the SPE-DEX® 4790 system (superseded by SPE-DEX 5000). Table I shows the matrix spike and matrix spike duplicate results for a centralized waste treatment point source (437 NPDES category) sample, for selected compounds. The spike recovery and agreement between the duplicates was within criteria for most all analytes. Method detection limits, initial demonstration of compliance, and other wastewater matrices are shown in the full application note (2).

References

(1) Method 625.1, December 14 revision, can be found in the MUR, February 19, 2015. Or downloaded here: https://ift.tt/2H7E83n

(2) Application Note 117, “Validation of Horizon Technology Disk Extraction Technology for US EPA Wastewater Method 625.1,” available from www.horizontechinc.com.

Horizon Technology, Inc.
16 Northwestern Drive, Salem, NH 03079
tel. (603) 893-3663
Website: www.horizontechinc.com

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Healthcare Analytical Testing Services Market Till 2024 Research Report – Industry Trends, Growth, Size, Share and Forecast

Healthcare Analytical Testing Services Market Report added by DecisionDatabases.com offers industry size, share, growth, trends and forecast analysis upto 2024. Healthcare Analytical Testing Services Market Report also covers top key players, porter’s five forces analysis and market segmentation in detail. The global healthcare analytical testing services market research report provides detailed information about the industry based on the revenue (USD MN) for the forecast period. This research study is a descriptive analysis of the healthcare analytical testing services market emphasizing the market drivers and restraints that govern the overall market growth. The trends and future prospects for the market are also included in the report which gives an intellectual understanding of the healthcare analytical testing services industry. Furthermore, the report quantifies the market share held by the major players of the industry and provides an in-depth view of the competitive landscape. The healthcare analytical testing services market is classified into different segments with detailed analysis of each with respect to geography for the study period.

The major market drivers are nutraceutical industry rising demand and growing recognition of the QBD (quality by design) approach in pharma research/manufacturing. The market growth might be restricted due pricing competition faced by major player and inadequate of expertise under the study period.

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The report offers a value chain analysis that gives a comprehensive outlook of the healthcare analytical testing services market. The attractiveness analysis of healthcare analytical testing services market has also been included so as to evaluate the segments that are anticipated to be profitable during the forecast period.

The healthcare analytical testing services market has been segmented based on types such as bioanalytical testing services, physical characterization services, method validation, raw material testing, batch release testing services, stability testing, microbial testing and environmental monitoring. The study incorporates periodic market estimates and forecasts. Each type has been analyzed based on the market size at regional and country levels.

The healthcare analytical testing services market has been segmented based on sample such as raw materials, finished products, in-process samples and environmental samples. The study incorporates periodic market estimates and forecasts. Each sample has been analyzed based on the market size at regional and country levels.

The healthcare analytical testing services market has been segmented based on end user such as pharmaceutical and biopharmaceutical companies, medical device companies and contract research organizations. The report provides forecast and estimates for each end user in terms of market size during the study period. Each end user has been further analyzed based on regional and country levels.

Major Table Of Contents:

1. 1. Introduction To The Healthcare Analytical Testing Services Market
2. Executive Summary
3. Market Analysis Of Healthcare Analytical Testing Services
4. Healthcare Analytical Testing Services Market Analysis By Type
5. Healthcare Analytical Testing Services Market Analysis By Sample
6. Healthcare Analytical Testing Services Market Analysis By End User
7. Healthcare Analytical Testing Services Market Analysis By Geography
8. Competitive Landscape Of Healthcare Analytical Testing Services Companies
9. Company Profiles Of Healthcare Analytical Testing Services Industry

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Geographically, the healthcare analytical testing services market has been segmented into regions such as North America, Europe, Asia Pacific and Rest of the World. The study details country-level aspects based on each segment and gives estimates in terms of market size.

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