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Lowes S.,Advion BioServices Inc. | Jersey J.,Agilux Laboratories | Shoup R.,AIT Bioscience | Garofolo F.,Algorithme Pharma Inc. | And 34 more authors.
Bioanalysis | Year: 2012

The Global CRO Council for Bioanalysis (GCC) was formed in September 2010. Since then, the representatives of the member companies come together periodically to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. The 4th GCC Closed Forum brought together experts from bioanalytical CROs to share and discuss recent issues in regulated bioanalysis, such as the impact of coadministered drugs on stability, some differences between European Medicines Agency and US FDA bioanalytical guidance documents and lessons learned following recent Untitled Letters. Recent 483s and agency findings, as well as issues on method carryover, were also part of the topics discussed. © 2012 Future Science Ltd.


Nomanbhoy T.K.,ActivX Biosciences | Sharma G.,Agilux Laboratories | Brown H.,ActivX Biosciences | Wu J.,ActivX Biosciences | And 6 more authors.
Biochemistry | Year: 2016

Palbociclib is a cyclin-dependent kinase (CDK) 4/CDK6 inhibitor approved for breast cancer that is estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative. We profiled palbociclib in cells either sensitive or resistant to the drug using an ATP/ADP probe-based chemoproteomics platform. Palbociclib only engaged CDK4 or CDK6 in sensitive cells. In resistant cells, no inhibition of CDK4 or CDK6 was observed, although the off-target profiles were similar in both cell types. Prolonged incubation of sensitive cells with the compound (24 h) resulted in the downregulation of additional kinases, including kinases critical for cell cycle progression. This downregulation is consistent with cell cycle arrest caused by palbociclib treatment. Both the direct and indirect targets were also observed in a human tumor xenograft study using the COLO-205 cell line in which phosphorylation of the retinoblastoma protein was tracked as the pharmacodyanamic marker. Together, these results suggest that this probe-based approach could be an important strategy toward predicting patient responsiveness to palbociclib. © 2016 American Chemical Society.


Lowes S.,Advion BioServices Inc. | Jersey J.,Agilux Laboratories | Shoup R.,AIT Bioscience | Garofolo F.,Algorithme Pharma Inc. | And 40 more authors.
Bioanalysis | Year: 2011

The Global CRO Council (GCC) for Bioanalysis was formed in an effort to bring together many CRO leaders to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. © 2011 Future Science Ltd.


Woolf E.J.,Merck And Co. | McDougall S.,Covance | Fast D.M.,Covance Laboratories Inc. | Andraus M.,ChromAnalysis | And 27 more authors.
AAPS Journal | Year: 2014

Consensus practices and regulatory guidance for liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) assays of small molecules are more aligned globally than for any of the other bioanalytical techniques addressed by the Global Bioanalysis Consortium. The three Global Bioanalysis Consortium Harmonization Teams provide recommendations and best practices for areas not yet addressed fully by guidances and consensus for small molecule bioanalysis. Recommendations from all three teams are combined in this report for chromatographic run quality, validation, and sample analysis run acceptance. © 2014 American Association of Pharmaceutical Scientists.


The 9th GCCClosed Forum was held just prior to the 2015 Workshop on Recent Issues in Bioanalysis (WRIB) in Miami, FL, USA on 13 April 2015. In attendance were 58 senior-level participants, from eight countries, representing 38 CRO companies offering bioanalytical services. The objective of this meeting was for CRO bioanalytical representatives to meet and discuss scientific and regulatory issues specific to bioanalysis. The issues selected at this years closed forum include CAPA, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, and ELNs. A summary of the industrys best practices and the conclusions from the discussion of these topics is included in this meeting report.


WILMINGTON, Mass.--(BUSINESS WIRE)--Charles River Laboratories International, Inc. (NYSE: CRL) today reported its results for the fourth-quarter and full-year 2016 and provided guidance for 2017. For the quarter, revenue from continuing operations was $466.8 million, an increase of 31.9% from $353.9 million in the fourth quarter of 2015. Revenue growth was driven primarily by the Discovery and Safety Assessment and Manufacturing Support segments. Research Models and Services revenue also increased. The acquisitions of WIL Research, Agilux Laboratories, Blue Stream Laboratories, and Oncotest contributed 20.9% to consolidated fourth-quarter revenue growth, both on a reported basis and in constant currency. The addition of a 53rd week at the end of 2016, which is periodically required to align to a December 31st calendar year end, contributed approximately 5.1% to reported fourth-quarter revenue growth. The impact of foreign currency translation reduced reported revenue growth by 2.4%. Excluding the effect of these items, organic revenue growth was 8.3%. On a GAAP basis, net income from continuing operations attributable to common shareholders was $44.7 million for the fourth quarter of 2016, an increase of 36.4% from $32.8 million for the same period in 2015. Fourth-quarter diluted earnings per share on a GAAP basis were $0.93, an increase of 34.8% from $0.69 for the fourth quarter of 2015. On a non-GAAP basis, net income from continuing operations was $58.3 million for the fourth quarter of 2016, an increase of 23.3% from $47.3 million for the same period in 2015. Fourth-quarter diluted earnings per share on a non-GAAP basis were $1.21, an increase of 21.0% from $1.00 per share for the fourth quarter of 2015. Both the GAAP and non-GAAP earnings per share increases were driven primarily by the acquisition of new businesses, notably WIL Research, as well as higher revenue for legacy operations. A gain from the Company’s venture capital investments contributed $0.02 per share in the fourth quarter of 2016, compared to a negligible impact for the same period in 2015. James C. Foster, Chairman, President and Chief Executive Officer, said, “Our fourth-quarter results provided a strong finish to an exceptional year in which we met our long-term revenue goals for all of our businesses except Discovery, and our long-term operating margin targets for the three business segments. We were very pleased that three of our businesses, Safety Assessment, Microbial Solutions, and Biologics Testing Solutions, reported low-double-digit organic revenue growth for the full year. Client demand for our unique portfolio of essential products and services remained strong across each of our client segments, particularly for our biotechnology clients, who were the primary driver of our revenue growth in 2016.” “Our continued investments to broaden our early-stage portfolio, the scientific expertise of our staff, our focus on productivity and efficiency initiatives, and our ability to offer flexible partnership structures are the primary reasons that we are the partner of choice for many of our clients. Based on our view of the opportunities in 2017, we believe we will again deliver high single-digit organic revenue growth and earnings per share growth at a faster rate than revenue,” Mr. Foster concluded. Revenue for the RMS segment was $124.7 million in the fourth quarter of 2016, an increase of 9.5% from $113.8 million in the fourth quarter of 2015. Organic revenue growth was 5.7%. Revenue growth was driven primarily by higher sales of research model services, and sales of research models also increased. In the fourth quarter of 2016, the RMS segment’s GAAP operating margin increased to 26.7% from 24.1% in the fourth quarter of 2015. On a non-GAAP basis, the operating margin increased to 27.3% from 25.4% in the fourth quarter of 2015. Both the GAAP and non-GAAP operating margin increases were due primarily to higher sales volume and the benefit of efficiency initiatives. Revenue from continuing operations for the DSA segment was $241.7 million in the fourth quarter of 2016, an increase of 50.6% from $160.5 million in the fourth quarter of 2015. Growth was driven primarily by the acquisitions of WIL Research, Agilux Laboratories, and Oncotest, which contributed 41.6% to DSA revenue growth. Organic revenue growth was 7.9%. Low-double-digit growth in the legacy Safety Assessment business was partially offset by lower revenue for the legacy Discovery Services business, which declined due primarily to softer demand from global clients for Early Discovery services. Robust demand from biotechnology clients continued to drive revenue growth in the DSA segment. In the fourth quarter of 2016, the DSA segment’s GAAP operating margin declined to 18.1% from 23.1% in the fourth quarter of 2015. The margin decline was due to costs associated with the evaluation and integration of acquisitions, including amortization of intangible assets, as well as the benefit from a tax law change in Quebec in the fourth quarter of 2015. On a non-GAAP basis, the operating margin decreased to 23.8% from 27.1% in the fourth quarter of 2015, due primarily to the tax law change in Quebec, which benefited both the GAAP and non-GAAP DSA operating margin by approximately 230 basis points in the fourth quarter of 2015. The acquisition of WIL reduced the fourth-quarter operating margin by approximately 100 basis points, and foreign exchange benefited the DSA operating margin by approximately 80 basis points due primarily to a weaker British pound. Revenue for the Manufacturing segment was $100.3 million in the fourth quarter of 2016, an increase of 26.2% from $79.5 million in the fourth quarter of 2015. The acquisitions of Blue Stream Laboratories and WIL Research’s contract development and manufacturing (CDMO) services contributed 9.2% to Manufacturing revenue growth in the fourth quarter of 2016. Organic revenue growth was 12.9%, primarily driven by robust growth in the Microbial Solutions and Biologics Testing Solutions businesses. In the fourth quarter of 2016, the Manufacturing segment’s GAAP operating margin increased to 31.0% from 23.7% in the fourth quarter of 2015. The GAAP operating margin increase was primarily driven by lower acquisition costs related to Celsis, as well as leverage from higher revenue in the Microbial Solutions business. On a non-GAAP basis, the operating margin increased to 34.2% from 33.8% in the fourth quarter of 2015, driven by operating margin improvement in the Microbial Solutions business as a result of higher revenue and the benefit of efficiency initiatives. For 2016, revenue increased by 23.3% to $1.68 billion from $1.36 billion in 2015. Organic revenue growth was 7.7%. On a GAAP basis, net income from continuing operations attributable to common shareholders was $154.5 million in 2016, an increase of 2.8% from $150.3 million in 2015. Diluted earnings per share on a GAAP basis in 2016 were $3.22, an increase of 2.2% from $3.15 in 2015. On a non-GAAP basis, net income from continuing operations was $218.9 million in 2016, an increase of 22.1% from $179.3 million in 2015. Diluted earnings per share on a non-GAAP basis in 2016 were $4.56, an increase of 21.3% from $3.76 in 2015. For 2016, RMS revenue was $494.0 million, an increase of 5.0% from $470.4 million in 2015. Organic revenue growth was 4.1%. On a GAAP basis, the RMS segment operating margin increased to 27.6% in 2016 from 25.7% in 2015. On a non-GAAP basis, the operating margin increased to 28.4% in 2016 from 27.1% in 2015. For 2016, DSA revenue was $836.6 million, an increase of 36.7% from $612.2 million in 2015. Organic revenue growth was 8.9%. On a GAAP basis, the DSA segment operating margin decreased to 16.5% in 2016 from 19.9% in 2015. On a non-GAAP basis, the operating margin decreased to 22.7% in 2016 from 23.3% in 2015. For 2016, Manufacturing revenue was $350.8 million, an increase of 25.0% from $280.7 million in 2015. Organic revenue growth was 11.3%. On a GAAP basis, the Manufacturing segment operating margin increased to 29.8% in 2016 from 26.6% in 2015. On a non-GAAP basis, the operating margin increased to 33.8% in 2016 from 32.6% in 2015. Charles River completed the divestiture of its CDMO business on February 10, 2017, to Quotient Clinical, a portfolio company of specialist healthcare investment adviser GHO Capital Partners LLP, based in London, England, for $75.0 million in cash, subject to certain post-closing adjustments. The CDMO business, which represented approximately 1% of Charles River’s 2016 consolidated revenue, provides services to support the formulation design and manufacture of oral drug dosages for biopharmaceutical clients, specializing in high-potency compounds. Charles River acquired the CDMO business in April 2016 as part of the acquisition of WIL Research. Following a strategic review, Charles River determined that the CDMO business was not optimized within Charles River’s portfolio at its current scale, and that the capital could be better deployed in other long-term growth opportunities. The Company is providing the following revenue growth and earnings per share guidance for 2017. This guidance reflects the divestiture of the CDMO business. Earnings per share in 2017 are expected to benefit from both higher revenue and operating margin expansion. The benefit is expected to be partially offset by foreign exchange, which is expected to reduce 2017 earnings per share by approximately $0.10, and lower gains from the Company’s venture capital investments. The Company’s 2016 earnings per share included a $0.13 gain on venture capital investments, and 2017 guidance includes an estimated $0.04 gain on these investments, consistent with the Company’s expected return on invested capital. Footnotes to Guidance Table (1) The contribution from acquisitions reflects only those acquisitions which were completed in 2016. (2) Organic revenue growth is defined as reported revenue growth adjusted for acquisitions, the divestiture of the CDMO business, the 53rd week, and foreign currency translation. (3) GAAP earnings per share guidance does not include the expected net gain and tax impact related to the divestiture of the CDMO business because the disposition accounting has not yet been finalized. (4) These charges relate primarily to the Company’s planned efficiency initiatives in 2017, including site consolidation costs, asset impairments, and severance. Other projects in support of the global productivity and efficiency initiatives are expected, but these charges reflect only the decisions that have already been finalized. (5) These adjustments are related to the evaluation and integration of acquisitions and the divestiture of the CDMO business, and primarily include transaction, advisory, and certain third-party integration costs, as well as certain costs associated with acquisition-related efficiency initiatives. Charles River has scheduled a live webcast on Tuesday, February 14, at 8:00 a.m. ET to discuss matters relating to this press release. To participate, please go to ir.criver.com and select the webcast link. You can also find the associated slide presentation and reconciliations of GAAP financial measures to non-GAAP financial measures on the website. Charles River will present at the Leerink 6th Annual Global Healthcare Conference in New York on Thursday, February 16, at 9:30 a.m. ET. Management will provide an overview of Charles River’s strategic focus and business developments. A live webcast of the presentation will be available through a link that will be posted on the Investor Relations section of the Charles River website at ir.criver.com. A webcast replay will be accessible through the same website approximately three hours after the presentation and will remain available for approximately two weeks. The Company reports non-GAAP results in this press release, which exclude often one-time charges and other items that are outside of normal operations. A reconciliation of GAAP to non-GAAP results is provided in the schedules at the end of this press release. In addition, the Company reports results from continuing operations, which exclude results of the Phase I clinical business that was divested in 2011. The Phase I business is reported as a discontinued operation. Use of Non-GAAP Financial Measures This press release contains non-GAAP financial measures, such as non-GAAP earnings per diluted share, which exclude the amortization of intangible assets, inventory purchase accounting adjustments, and other charges related to our acquisitions; expenses associated with evaluating and integrating acquisitions and divestitures, as well as fair value adjustments associated with contingent consideration; charges related to modifications of purchase options on remaining non-controlled equity interests, and re-measurement of previously held equity interests; charges, gains and losses attributable to businesses or properties we plan to close, consolidate or divest; severance and other costs associated with our efficiency initiatives; executive transition costs; a reversal of indemnification assets associated with acquisitions and corresponding interest; write-off of and adjustments to deferred financing costs and fees related to debt financing; gain on bargain purchase; and costs related to a U.S. government billing adjustment and related expenses. This press release also refers to our revenue in both a GAAP and non-GAAP basis: “constant currency,” which we define as reported revenue growth adjusted for the impact of foreign currency translation, and “organic revenue growth,” which we define as reported revenue growth adjusted for foreign currency translation, acquisitions, the divestiture of the CDMO business, and the 53rd week. We exclude these items from the non-GAAP financial measures because they are outside our normal operations. There are limitations in using non-GAAP financial measures, as they are not prepared in accordance with generally accepted accounting principles, and may be different than non-GAAP financial measures used by other companies. In particular, we believe that the inclusion of supplementary non-GAAP financial measures in this press release helps investors to gain a meaningful understanding of our core operating results and future prospects without the effect of these often-one-time charges, and is consistent with how management measures and forecasts the Company's performance, especially when comparing such results to prior periods or forecasts. We believe that the financial impact of our acquisitions and divestitures (and in certain cases, the evaluation of such acquisitions and divestitures, whether or not ultimately consummated) is often large relative to our overall financial performance, which can adversely affect the comparability of our results on a period-to-period basis. In addition, certain activities and their underlying associated costs, such as business acquisitions, generally occur periodically but on an unpredictable basis. We calculate non-GAAP integration costs to include third-party integration costs incurred post-acquisition. Presenting revenue on a constant-currency basis allows investors to measure our revenue growth exclusive of foreign currency exchange fluctuations more clearly. Non-GAAP results also allow investors to compare the Company’s operations against the financial results of other companies in the industry who similarly provide non-GAAP results. The non-GAAP financial measures included in this press release are not meant to be considered superior to or a substitute for results of operations prepared in accordance with GAAP. The Company intends to continue to assess the potential value of reporting non-GAAP results consistent with applicable rules and regulations. Reconciliations of the non-GAAP financial measures used in this press release to the most directly comparable GAAP financial measures are set forth in this press release, and can also be found on the Company’s website at ir.criver.com. This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate,” “believe,” “expect,” “intend,” “will,” “may,” “estimate,” “plan,” “outlook,” and “project,” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These statements also include statements regarding our projected future financial performance including revenue (on both a reported, constant-currency, and organic growth basis), operating margins, earnings per share, the expected impact of foreign exchange rates, and the expected benefit of our life science venture capital investments; the future demand for drug discovery and development products and services, including our expectations for future revenue trends; our expectations with respect to the impact of acquisitions on the Company, our service offerings, client perception, strategic relationships, revenue, revenue growth rates, and earnings; the development and performance of our services and products; market and industry conditions including the outsourcing of services and spending trends by our clients; the potential outcome of and impact to our business and financial operations due to litigation and legal proceedings, including with respect to our ongoing investigation of inaccurate billing with respect to certain government contracts; and Charles River’s future performance as delineated in our forward-looking guidance, and particularly our expectations with respect to revenue, the impact of foreign exchange, and enhanced efficiency initiatives. Forward-looking statements are based on Charles River’s current expectations and beliefs, and involve a number of risks and uncertainties that are difficult to predict and that could cause actual results to differ materially from those stated or implied by the forward-looking statements. Those risks and uncertainties include, but are not limited to: the ability to successfully integrate businesses we acquire; the ability to execute our efficiency initiatives on an effective and timely basis (including divestitures and site closures); the timing and magnitude of our share repurchases; negative trends in research and development spending, negative trends in the level of outsourced services, or other cost reduction actions by our clients; the ability to convert backlog to revenue; special interest groups; contaminations; industry trends; new displacement technologies; USDA and FDA regulations; changes in law; continued availability of products and supplies; loss of key personnel; interest rate and foreign currency exchange rate fluctuations (including the impact of Brexit); changes in tax regulation and laws; changes in generally accepted accounting principles; and any changes in business, political, or economic conditions due to the threat of future terrorist activity in the U.S. and other parts of the world, and related U.S. military action overseas. A further description of these risks, uncertainties, and other matters can be found in the Risk Factors detailed in Charles River's Annual Report on Form 10-K as filed on February 12, 2016, as well as other filings we make with the Securities and Exchange Commission. Because forward-looking statements involve risks and uncertainties, actual results and events may differ materially from results and events currently expected by Charles River, and Charles River assumes no obligation and expressly disclaims any duty to update information contained in this news release except as required by law. Charles River provides essential products and services to help pharmaceutical and biotechnology companies, government agencies and leading academic institutions around the globe accelerate their research and drug development efforts. Our dedicated employees are focused on providing clients with exactly what they need to improve and expedite the discovery, early-stage development and safe manufacture of new therapies for the patients who need them. To learn more about our unique portfolio and breadth of services, visit www.criver.com. (1) Charles River management believes that supplementary non-GAAP financial measures provide useful information to allow investors to gain a meaningful understanding of our core operating results and future prospects, without the effect of often-one-time charges and other items which are outside our normal operations, consistent with the manner in which management measures and forecasts the Company’s performance. The supplementary non-GAAP financial measures included are not meant to be considered superior to, or a substitute for results of operations prepared in accordance with U.S. GAAP. The Company intends to continue to assess the potential value of reporting non-GAAP results consistent with applicable rules, regulations and guidance. (2) This item includes operating losses related primarily to the Company's Shrewsbury, Massachusetts facility. (3) These adjustments are related to the evaluation and integration of acquisitions, which primarily include transaction, third-party integration, and certain compensation costs, and fair value adjustments associated with contingent consideration. (1) Charles River management believes that supplementary non-GAAP financial measures provide useful information to allow investors to gain a meaningful understanding of our core operating results and future prospects, without the effect of often-one-time charges and other items which are outside our normal operations, consistent with the manner in which management measures and forecasts the Company’s performance. The supplementary non-GAAP financial measures included are not meant to be considered superior to, or a substitute for results of operations prepared in accordance with U.S. GAAP. The Company intends to continue to assess the potential value of reporting non-GAAP results consistent with applicable rules, regulations and guidance. (2) These amounts represent the reversal of an uncertain tax position and an offsetting indemnification asset primarily related to the acquisition of BioFocus. (3) The amounts relate to the acquisition of Sunrise Farms, Inc. and represents the excess of the estimated fair value of the net assets acquired over the purchase price. (4) The amount represents a $1.5 million charge recorded in connection with the modification of the option to purchase the remaining 13% equity interest in Vital River, partially offset by a $0.7 million gain on remeasurement of previously held equity interest in an entity acquired in a step acquisition. (1) Charles River management believes that supplementary non-GAAP financial measures provide useful information to allow investors to gain a meaningful understanding of our core operating results and future prospects, without the effect of often-one-time charges and other items which are outside our normal operations, consistent with the manner in which management measures and forecasts the Company’s performance. The supplementary non-GAAP financial measures included are not meant to be considered superior to, or a substitute for results of operations prepared in accordance with U.S. GAAP. The Company intends to continue to assess the potential value of reporting non-GAAP results consistent with applicable rules, regulations and guidance. (2) The contribution from acquisitions reflects only those acquisitions which were completed during fiscal year 2016 and 2015. (3) Organic revenue growth is defined as reported revenue growth adjusted for acquisitions, the 53rd week, and foreign exchange.


Hougton R.,Quotient Bioresearch | Gouty D.,Intertek | Allinson J.,Icon Development Solutions | Green R.,Quotient Bioresearch | And 25 more authors.
Bioanalysis | Year: 2012

The 5th GCC in Barcelona (Spain) and 6th GCC in San Antonio (TX, USA) events provided a unique opportunity for CRO leaders to openly share opinions and perspectives, and to agree upon recommendations on biomarker bioanalytical method validation. © 2012 Future Science Ltd.


Tseng E.,Pfizer | Walsky R.L.,Astrazeneca | Walsky R.L.,EMD Serono, Inc. | Luzietti Jr. R.A.,Astrazeneca | And 7 more authors.
Drug Metabolism and Disposition | Year: 2014

Metabolism by cytochrome P4503A (CYP3A) is the most prevalent clearance pathway for drugs. Designation of metabolism by CYP3A commonly refers to the potential contribution by one or both of two enzymes, CYP3A4 and CYP3A5. The metabolic turnover of 32 drugs known to be largely metabolized by CYP3A was examined in human liver microsomes (HLMs) from CYP3A5 expressers (*1/*1 genotype) and nonexpressers (*3/*3 genotype) in the presence and absence of ketoconazole and CYP3cide (a selective CYP3A4 inactivator) to calculate the contribution of CYP3A5 to metabolism. Drugs with the highest contribution of CYP3A5 included atazanavir, vincristine, midazolam, vardenafil, otenabant, verapamil, and tacrolimus, whereas 17 of the 32 tested showed negligible CYP3A5 contribution. For specific reactions in HLMs from *1/*1 donors, CYP3A5 contributes 55% and 44% to midazolam 1′- and 4-hydroxylation, 16% to testosterone 6βhydroxylation, 56% and 19% to alprazolam 1′- and 4-hydroxylation, 10% to tamoxifen N-demethylation, and 58% to atazanavir p-hydroxylation. Comparison of the in vitro observations to clinical pharmacokinetic data showed only a weak relationship between estimated contribution by CYP3A5 and impact of CYP3A5 genotype on oral clearance, in large part because of the scatter in clinical data and the low numbers of study subjects used in CYP3A5 pharmacogenetics studies. These data should be useful in guiding which drugs should be evaluated for differences in pharmacokinetics and metabolism between subjects expressing CYP3A5 and those who do not express this enzyme. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

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