PBPK

Draft revised consolidated 3-year work plan for the Methodology Working Party (MWP)

Retrieved on: 
Wednesday, February 14, 2024

Industry level .................................................................................................. 13

Key Points: 
    • Industry level .................................................................................................. 13

      Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 2/14

      1.

    • A reflection paper
      (RP) on the clinical pharmacology package for oligonucleotides is a prioritised activity in the MWP work

      Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 3/14

      plan, and it is envisaged that something similar may be needed for other emerging treatment
      modalities (e.g., peptides).

    • Guideline work led by other working parties
      ?

      Revision of the guideline on the requirements for clinical documentation for orally inhaled
      products (CPMP/EWP/4151/00 Rev.

    • Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 4/14

      The planned concept papers (CPs) will formulate problem statements for potential workshops and
      subsequent guidance documents will be informed and enriched by the outcome of discussions of
      workshops to be held in 2024.

    • Guideline work led by other working parties and committees
      ?

      Revision of Guidance on the investigation of medicinal products in the term and preterm
      neonate (EMEA/536810/2008).

    • There is a need for
      Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 5/14

      new guidance in these areas to ensure these novel approaches meet the required evidentiary
      standards and facilitate their evaluation.

    • Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 6/14

      ?

      Revision of Guideline on clinical evaluation of diagnostic agents (CPMP/EWP/1119/98/Rev.

    • Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 7/14

      ?

      Provide appropriate support to the EU network for generic and hybrid medicines including
      product-specific requirements.

    • Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 8/14

      2.3.

    • ?

      Cross disciplinary work with Quality Working Party and other stakeholders on physiologically
      based biopharmaceutics modelling (PBBM).

    • Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 9/14

      ?

      In order to support adequate evaluation of all methodology MWP will aim to facilitate an
      increase in presence and visibility in relevant committees of methodological expertise from
      across the EU network such as CHMP, PRAC, PDCO, CMD(h), ETF and CAT.

    • Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 10/14

      ?

      Product Specific Bioequivalence Guidelines (PSBGLs) (multiple) in liaison with CMD(h): for
      2024, azacitidine, budesonide (LALA GIT), trametinib, dabrafenib, paliperidone palmitate (3M
      depot) and melatonin have been prioritised as the next in series for drafting.

    • Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 11/14

      4.2.

    • ?

      Cross disciplinary work with Quality Working Party and other stakeholders on PBBM model
      assessment.

    • Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 12/14

      ?

      To deliver an improved access to raw data (e.g.

    • ?

      Propose regulatory research priorities for funders in across the activities of Methodology
      Working Party, including in the big data area.

    • ?

      Establish key communication points in national competent authorities and build a resource of
      key messages and communication materials on regulation and methodology.

    • The timing of workshops may need to be arranged according to the

      Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 13/14

      specific needs of the guidance ? either before the guidance is finalised to gather views and
      expertise; or once it is finalised for training purposes.

    • Revised consolidated 3-year work plan for the Methodology Working Party (MWP)
      EMA/CHMP/58124/2023

      Page 14/14

Reflection paper on investigation of pharmacokinetics in the obese population - Scientific guideline

Retrieved on: 
Wednesday, February 14, 2024

Reflection paper on investigations of pharmacokinetics in

Key Points: 
    • Reflection paper on investigations of pharmacokinetics in
      the obese population
      Table of contents
      1.
    • References .............................................................................................. 9

      Reflection paper on investigations of pharmacokinetics in the obese population
      EMA/CHMP/535116/2016

      Page 2/12

      1.

    • This is considered
      a shortcoming that is potentially compounded by obese patients often being poorly represented in
      clinical studies.
    • The specific aims of this reflection paper are to:
      ?

      describe how the effects of obesity can be investigated during clinical medicinal product
      development.

    • ?

      provide recommendations on when investigations of the effect of obesity on the PK of a
      medicinal product should be particularly considered.

    • Reflection paper on investigations of pharmacokinetics in the obese population
      EMA/CHMP/535116/2016

      Page 3/12

      ?

      discuss how to reflect PK (and/or PK/PD) findings in weight/weight-based dosing
      recommendations.

    • Absorption
      Reduced rate of absorption linked to locally reduced blood flow (8) is reported for the subcutaneous
      and transdermal routes in obese subjects.
    • Distribution
      The distribution of medicinal products is driven by body composition, regional blood flow and binding to
      tissue and plasma proteins.
    • Obese subjects have a larger absolute lean body weight (LBW) as well as fat mass.
    • The physicochemical properties of a medicinal product (lipophilicity, polarity, molecular size, and
      degree of ionization) influence its distribution in the body.
    • In BMI class III obese
      subjects, the blood flow per gram of fat is significantly lower than that observed in class I obese or
      lean subjects (4).
    • Reflection paper on investigations of pharmacokinetics in the obese population
      EMA/CHMP/535116/2016

      Page 4/12

      An increased amount of alpha-1-acid-glycoprotein (AAG), linked to a chronic inflammatory state, is
      reported in obese individuals.

    • Fatty infiltrations are present in the liver for 90% of obese subjects, with the extent of the infiltrations
      being proportional to the degree of obesity.
    • In some cases, in particular for CYP3A4 metabolized medicinal products,
      bodyweight normalized clearance can be lower in obese patients (23).
    • Based on presently available data, it has been suggested that uptake transporters

      Reflection paper on investigations of pharmacokinetics in the obese population
      EMA/CHMP/535116/2016

      Page 5/12

      are downregulated while efflux transporters may be upregulated (31).

    • Platelet hyper-reactivity is also observed,
      which can impair the response to anti-platelet medicinal products in obese patients (42, 43).
    • Reflection paper on investigations of pharmacokinetics in the obese population
      EMA/CHMP/535116/2016

      Page 6/12

      3.

      the medicinal product properties and scientific literature indicate that obesity may lead to a
      marked effect on elimination and/or distribution or on the PK/PD relationship.

    • These
      models may aid in extrapolating the known efficacy and safety in the non-obese population to the
      obese population.
    • The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients
      Before and One Year After Bariatric Surgery.
    • Reflection paper on investigations of pharmacokinetics in the obese population
      EMA/CHMP/535116/2016

      Page 11/12

      41.

    • Reflection paper on investigations of pharmacokinetics in the obese population
      EMA/CHMP/535116/2016

      Page 12/12

Certara introduces Simcyp™ Biopharmaceutics software to increase efficiency of novel and generic drug formulation & development  

Retrieved on: 
Tuesday, November 21, 2023

PRINCETON, N.J., Nov. 21, 2023 (GLOBE NEWSWIRE) -- Certara, Inc. (Nasdaq: CERT), a global leader in biosimulation, today announced the introduction of Simcyp™ Biopharmaceutics software.

Key Points: 
  • PRINCETON, N.J., Nov. 21, 2023 (GLOBE NEWSWIRE) -- Certara, Inc. (Nasdaq: CERT), a global leader in biosimulation, today announced the introduction of Simcyp™ Biopharmaceutics software.
  • It is designed for use by biopharmaceutic, formulation, and CMC scientists to aid in formulating complex novel and generic small molecule medicines quickly and cost effectively.
  • Simcyp Biopharmaceutics software is part of the Simcyp Simulator biosimulation platform, which has supported label claims for more than 100 approved novel therapies .
  • Simcyp Biopharmaceutics software includes a VBE module that automates elements of trial design significantly enhancing opportunities for attaining biowaivers.

RedHill Announces FDA sNDA Approval for Talicia®

Retrieved on: 
Monday, September 18, 2023

RALEIGH, N.C. and TEL-AVIV, Israel, Sept. 18, 2023 /PRNewswire/ -- RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, announced the U.S. Food and Drug Administration's (FDA) approval of its supplemental new drug application (sNDA) for Talicia[3], allowing a change to a more flexible three times daily (TID), taken at least 4 hours apart with food, dosing regimen for H. pylori eradication. This differs from the previously approved dosing regimen (Q8H), which required dosing every eight hours with food, by enabling patients to follow a convenient "breakfast, lunch and dinner" dosing routine, which may support increased patient adherence and optimize the potential for successful H. pylori eradication.

Key Points: 
  • "H. pylori treatment can be challenging for patients as most regimens require different pills to be taken multiple times per day.
  • "This new dosing regimen further supports the value of Talicia as an empirically prescribed first-line therapy for H. pylori eradication.
  • "Talicia is unique in that it is the only FDA-approved rifabutin-based therapy for the eradication of H. pylori.
  • "RedHill is committed to advancing GI and infectious disease management through patient-focused innovation.

Simulations Plus Hosts First-of-its-Kind Virtual Summer Camp for Students and Professors

Retrieved on: 
Thursday, September 7, 2023

Simulations Plus, Inc. (Nasdaq: SLP), a leading provider of modeling and simulation solutions for the pharmaceutical and biotechnology industries, announced the successful completion of the inaugural University+ PBPK Summer Camp, an intensive eight-week course covering the theory and application of PBPK modeling using GastroPlus®.

Key Points: 
  • Simulations Plus, Inc. (Nasdaq: SLP), a leading provider of modeling and simulation solutions for the pharmaceutical and biotechnology industries, announced the successful completion of the inaugural University+ PBPK Summer Camp, an intensive eight-week course covering the theory and application of PBPK modeling using GastroPlus®.
  • More than 80 attendees across 26 countries satisfactorily finished all rigorous assignments and earned their certificates of completion.
  • The PBPK Summer Camp was offered as an enhancement to its University+ program , which provides software licenses to students and professors at accredited universities.
  • During the program, students successfully learned how to build, evaluate, and apply PBPK models to critical drug development questions.

Certara Simcyp™ Group Awarded Two New Grants from US FDA

Retrieved on: 
Tuesday, August 29, 2023

These capabilities will help enable safer, faster and more cost-effective product development of both complex generics and novel drugs.

Key Points: 
  • These capabilities will help enable safer, faster and more cost-effective product development of both complex generics and novel drugs.
  • “We are proud to collaborate with the FDA in developing innovative model-informed approaches for accelerating drug development of complex generic and innovator drugs,” said Rob Aspbury, President of Certara, Scientific Software.
  • “The Simcyp Simulator has already proved its ability to replace clinical studies in both VBE and dermal absorption.
  • Topical products undergo changes immediately upon application due to formulation metamorphosis, which may alter the critical characteristics of the formulations.

Simulations Plus Chief Science Officer Dr. Viera Lukacova Honored as Fellow by the American Association of Pharmaceutical Scientists (AAPS)

Retrieved on: 
Thursday, August 24, 2023

“Viera stands out as an eminent figure whose profound contributions have significantly shaped the landscape of physiologically based pharmacokinetics (PBPK) modeling,” said John DiBella , President of the SLP Division at Simulations Plus.

Key Points: 
  • “Viera stands out as an eminent figure whose profound contributions have significantly shaped the landscape of physiologically based pharmacokinetics (PBPK) modeling,” said John DiBella , President of the SLP Division at Simulations Plus.
  • “Her scientific insights have advanced the capabilities of software platforms like GastroPlus® , DDDPlus™ , and MembranePlus™ that scientists use every day to develop safe and effective treatments for patients worldwide.
  • A tireless advocate, her impact also extends beyond research into the realms of publication, presentation, and education.
  • Joining Dr. Lukacova as 2023 AAPS Fellows are Dr. Shaukat Ali, Dr. Ben Boyd, Dr. Maria Croyle, Dr. Otilia Koo, Dr. Xiuling Lu, Dr. Wellington Pham, and Dr. Patrick Ronaldson.

Simulations Plus Reports Third Quarter Fiscal 2023 Financial Results

Retrieved on: 
Thursday, July 6, 2023

Simulations Plus, Inc. (Nasdaq: SLP), a leading provider of modeling and simulation software and services for pharmaceutical drug discovery and development, today reported financial results for its third quarter of fiscal 2023, ended May 31, 2023.

Key Points: 
  • Simulations Plus, Inc. (Nasdaq: SLP), a leading provider of modeling and simulation software and services for pharmaceutical drug discovery and development, today reported financial results for its third quarter of fiscal 2023, ended May 31, 2023.
  • Strong execution on our strategic priorities this quarter resulted in profitable growth that keeps us on track to meet our stated goals for fiscal 2023.
  • Our clients are responding positively to this initiative, and we will continue the realignment process through the balance of 2023.
  • “As we enter the fourth quarter, our performance for the nine months gives us confidence in our previously stated guidance.

Simulations Plus Launches New Integrated Pulmonary Software and Services Package to Streamline Drug Development and Improve Patient Outcomes

Retrieved on: 
Wednesday, May 10, 2023

Simulations Plus, Inc. (Nasdaq: SLP), a leading provider of modeling and simulation software and services for pharmaceutical safety and efficacy, today announced the release of a new integrated pulmonary software and services package.

Key Points: 
  • Simulations Plus, Inc. (Nasdaq: SLP), a leading provider of modeling and simulation software and services for pharmaceutical safety and efficacy, today announced the release of a new integrated pulmonary software and services package.
  • This targeted package will support pharmaceutical companies by streamlining their pulmonary drug development processes, enabling them to make better-informed decisions and bring therapies to market faster.
  • The pulmonary package offered by Simulations Plus is founded on the industry leading GastroPlus® modeling and simulation platform, which can be used to predict localized exposure in the lungs.
  • Together, we can better understand lung absorption and efficacy, and find new treatments for respiratory disease.”
    Learn more about the newly released pulmonary package: https://www.simulations-plus.com/breatheeasy

RedHill Publishes New Talicia® Data on Generic Non-Bioequivalence in AP&T and Presents New Dosing Data at Digestive Disease Week

Retrieved on: 
Tuesday, May 9, 2023

RALEIGH, N.C. and TEL-AVIV, Israel, May 9, 2023 /PRNewswire/ -- RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, announced two distinct sets of new Talicia[3] data focused on generic non-bioequivalence and on dosing regimens. The first new dataset, published in the Journal Alimentary Pharmacology and Therapeutics (AP&T) showed that generically substituted regimens are non-bioequivalent to Talicia. The second set of data, presented at Digestive Disease Week (DDW), supports bioequivalence between Talicia TID (three times daily) and Q8H (every eight hours) dosing regimens for H. pylori eradication therapy.

Key Points: 
  • The first new dataset, published in the Journal Alimentary Pharmacology and Therapeutics (AP&T) showed that generically substituted regimens are non-bioequivalent to Talicia.
  • The second set of data, presented at Digestive Disease Week (DDW), supports bioequivalence between Talicia TID (three times daily) and Q8H (every eight hours) dosing regimens for H. pylori eradication therapy.
  • In eradicating H. pylori, previous work has shown the importance of antibiotic exposure at the site of the infection[4].
  • Given the potential for antibiotic resistance and treatment failure, the non-equivalence of generics shown by these data should be kept front of mind when prescribing first-line therapy for H. pylori eradication."