News & Events

22 March, 2017
New article on future use of modern approaches and methodologies in a regulatory context

In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation: Future Use of Modern Approaches and Methodologies in a Regulatory Context.
Lennernäs H, Lindahl A, Van Peer A, Ollier C, Flanagan T, Lionberger R, Nordmark A, Yamashita S, Yu L, Amidon GL, Fischer V, Sjögren E, Zane P, McAllister M, Abrahamsson B.
Mol Pharm. 2017 Mar 1. doi: 10.1021/acs.molpharmaceut.6b00824. [Epub ahead of print]
 

07 March, 2017
Recent progress in understanding and predicting oral absorption

OrBiTo will organise a one day short course about “Recent progress in understanding and predicting oral absorption” at FIP Pharmaceutical Sciences World Congress in Stockholm 21 May. Registration is open to 1 april! More information can be found at the FIP PSWC 2017 webpage.

06 December, 2016
Orbito Progress update June 2016

Below is a brief summary of Orbito achivements July 2015 to June 2016.

  • OrBiTo has had its most productive year so far by means of submission of about 40 manuscripts to international high impact pharmaceutical journals with contribution from all work packages (accepted papers listed on www.orbitoprojects.eu).
  • There has also been extensive dissemination through presentations by invited and short presentations at international scientific meetings with a dedicated OrBiTo session at the major pharmaceutics conference last year, American Association of Pharmaceutical Sciences (AAPS) annual meeting, a meeting that gathered several thousands of participants.
  • There has been focused interactions with European and US regulatory bodies regarding possible future use of predictive tools and approaches developed within OrBiTo for example to reduce number of clinical bioequivalence studies. A paper has been submitted on this topic with contribution both by OrBiTo scientists and leading scientists at regulatory bodies. A series of webinar has also been started where OrBiTo results are presented for scientists at European and US regulatory authorities which has generated very positive feed-back from regulators.
  • “Young OrBiTo”, consisting of PhD students and post-docs in the project, has successfully been organising webinar sharing “hot off the press” new science within OrBiTo as well as a poster session at the annual OrBiTo face to face meeting. Finally, three research awards were granted to “Young OrBiTo scientist” at the AAPS annual meeting!
  • A brief survey among EFPIA partners has revealed a significant number of examples of early implementation of OrBiTo deliverables in the industrial process. For example, the standardised experimental protocols developed in WP1 and 2 have been implemented in several companies.  Enhanced physiological understanding generated in WP3 has been used for refinement of internal in vitro test and in silico modelling approaches.  The database generated in WP4 has been used for internal validations and as a source to enhance the learnings from experience. Finally, the output from OrBiTo has also been used to increase knowledge internally and build confidence with stakeholder regarding replacing in vivo studies with in vitro/in silico based predictive tools.
16 August, 2016
Journal of Pharmaceutical Sciences September 2016 issue dedicated to Marcus Brewster

Marcus E. Brewster helped to initiate the Oral Biopharmaceutics Tools project (OrBiTo) and became a key member. Marcus served as coordinator of the work package In Vivo Methods in Oral Drug Absorption and also served on the Executive Committee Board. Marcus passed away unexpectedly 15 September 2014, which was a major loss not only for OrBiTo, but for the whole pharmaceutical sciences community.

In order to honor Marcus, the Editorial Team of the Journal of Pharmaceutical Sciences (JPharmSci®) decided to dedicate a special issue to Dr. Marcus E. Brewster. This has now been published as the September 2016 issue of JPharmSci, and its content can be found on http://www.jpharmsci.org/issue/S0022-3549(16)X0010-X ; this issue includes contributions from many OrBiTo-partners.

In addition, Marcus has been included among the "TRUE GIANTS" in the pharmaceutical sciences website  http://www.jpharmsci.org/giants-of-pharmaceutical-sciences

15 August, 2016
OrBiTo Scientists Present Novel Data on Gastrointestinal Physiologies in Fasted and Fed States in Humans

The physiological conditions of the gastrointestinal (GI) tract can largely affect the in vivo performance of orally administered dosage forms during bioavailability and bioequivalence studies. Various parameters within the GI tract such as pH value, pressure activity, temperature, transit times as well as composition of intraluminal contents can influence the liberation and extent of absorption of drug substances.

Work package 3 within the OrBiTo consortium sets as its goal to facilitate model development by providing approaches and data to better understand the in vivo systems and systems biology impacting drug formulation behavior and drug absorption. Thus new and established in vivo tools for better in vivo prediction of the in vivo dosage form behavior can be assessed.

Even today the effects of food on the dosage form in vivo are not well understood. It is obvious that this effect of food on the dosage form can be the result of changed GI conditions. Such effects by co-ingested food can be caused by various reasons such as the delay of gastric emptying, the enhancement of solubility, the binding to food components, or the change of GI pH values and can contribute to the (unwanted) intra- and inter-individual variability of response to drug therapy.

In the present study*, temperature, pH and pressure profiles of nine healthy human volunteers were investigated after ingestion of the SmartPill® under clinical fasting conditions and compared to the same subjects who received the SmartPill® under fed conditions as recommended by the Food and Drug Administration (FDA). Since large non-digestible objects are mainly emptied during phase III of the interdigestive migrating motor complex, the gastric residence time of the SmartPill® was found to be clearly shorter under fasting conditions. Intragastric pH values during the initial 5 min were comparable with mean values of pH 4.2 under fasting and pH 4.6 under fed conditions. Interestingly, the lowest observed intragastric pH values in fasted state were about one pH unit higher than under fed conditions. Highest pressure activity was observed within the stomach, in relation to gastric emptying. In the fasted state, pressure values upon gastric emptying varied strongly between 30 mbar and 304 mbar, whereas in the fed state, values of at least 240 mbar could always be observed. The data showed highly variable gastrointestinal parameters even under clinical fasting conditions which must be considered when evaluating clinical studies and developing biorelevant in vitro test methods.

Figure: Pressure, pH and temperature profile of a subject obtained after fasted state (left) and fed state (right) ingestion of the SmartPill®. GE – gastric emptying, CA – colon arrival.


*Felix Schneider, Michael Grimm, Mirko Koziolek, Christiane Modeß, Anne Dokter, Tarek Roustom, Werner Siegmund and Werner Weitschies: Resolving the physiological conditions in bioavailability and bioequivalence studies: comparison of fasted and fed state. Submitted for publication

12 November, 2015
OrBiTo project gathers significant interest in scientific community according to latest IMI bibliometric report!

Predictive oral biopharmaceutics tools as provided by OrBiTo project gathers significant interest in scientific community according to latest IMI bibliometric report!!

06 November, 2015
OrBiTo gets multiple awards at AAPS annual meeting, the worlds largest pharmaceutics conference!

OrBiTo researchers received multiple awards at the AAPS annual meeting. AAPS is the worlds largest pharmaceutics conference and the winners were:

  • Andrés Olivares-Morales (Manchester) : AAPS Graduate Student Research Achievement Award in PK, PD, and Drug Metabolism and Clinical Pharmacology and Translation Research
    • Predicting the higher bioavailability observed for oxybutinin’s OROS formulation compared to the immediate-release (IR) tablet using a novel simplified absorption PBPK model
  • Philip Jonas Sassene (Copenhagen): AAPS Lipid-Based Drug Delivery Graduate Student Award
    • In vivo precipitation of poorly soluble drugs from lipid based formulations
  • Bart Hens (Leuven): AAPS Oral Absorption Focus Group Graduate Student Award
    • Precipitation of posaconazole upon entry in the upper small intestine in man

In addition, OrBiTo overall were very visible at the meetng with 7 posters and a symposium on PBPK in the plenary lecture also was live streamed.

15 October, 2015
Summary of Regulatory Session on OrBiTo Open Science Day, 1st July 2015.

The regulatory session was an initiative proposed by Anders Lindahl and Anna Nordmark from the Swedish Medical Products Agency with the aim to communicate on the scientific research within OrBito and to facilitate a face to face discussion with regulatory representatives from US, EMA and Japan on research activities within OrBito which are envisaged to have a future regulatory impact. In addition to the regulatory presenters on site, other members of the global regulatory stakeholder group joined the session by WEBEX.

As with previous OrBiTo annual meetings, day two was an open science day, supported by APGI, and was attended by a number of delegates who were not part of the OrBiTo consortium. In addition to sharing key updates from the on-going research within the OrBiTo work packages, the open science meeting brought together key representatives from regulatory agencies to discuss the implementation of biopharmaceutics tools in regulatory submissions.

The presentations and discussions will be summarised in a manuscript to be published in Molecular Pharmaceutics.

 

01 September, 2015
Young OrBiTo on YouTube

At the 2015 annual meeting in France our PhD-student and Postdoc community, Young OrBiTo, took the opportunity to shoot some footage in order to create a Young Orbito aftermovie. The movie is now available on YouTube via the link below.

https://www.youtube.com/watch?v=MxPLrKQurDc

02 March, 2015
OrBiTo Open Science Day July 1 2015

In connection with the 2015 annual OrBiTo meeting in Chilly Mazarin France, an Open Science Day is planned for the 1st of July. The Open Science Day will have a regulatory focus: “Beyond the BCS based biowaivers” and the agenda will shortly be avialable at http://www.apgi.org/


Confirmed speakers include:

Anders Lindahl (Swedish MPA), Achiel Van Peer (Janssen) et al.: Survey results from the current biopharm issues from EFPIA

Robert Lionberger (U.S. Food and Drug Administration): Impact of Modeling and Simulation on Generic Drug Development and Review

Anna Nordmark (Swedish MPA): The European regulatory perspective on the use of PBPK

Yamashita Shinji (Setsunan University, Japan): IVIVC or Quality Control?  Japanese status

Lawrence Yu (U.S. Food and Drug Administration): Title tbc.

Gordon Amidon (University of Michigan): FDA funded initiative for biorelevant dissolution – An Update

Volker Fischer: (AbbeVie, IQ Member) The Growing Impact of PBPK on Pharmaceutical Drug Development: Recipe for Success


 

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