Physiologically Based Models in Regulatory Submissions: Output From the ABPI/MHRA Forum on Physiologically Based Modeling and Simulation
Open accessAbstract
Under the remit of the Ministerial Industry Strategy Group (MISG), the Association of the British Pharmaceutical Industry (ABPI) and Medicines and Healthcare products Regulatory Agency (MHRA) hosted a meeting to explore physiologically based pharmacokinetic modeling and simulation, focusing on the clinical component of regulatory applications. The meeting took place on 30 June 2014 with international representatives from industry, academia, and regulatory agencies. Discussion topics were selected to be complementary to those discussed at an earlier US Food and Drug Administration (FDA) meeting. This report summarizes the meeting outcomes, focusing on the European regulatory perspective.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NASA, the FDA, and other regulatory bodies have developed standards to assess the credibility of computational models.
“Due to the increasing importance of computational models in scientific discovery, the National Aeronautics and Space Administration (NASA), the FDA, and other regulatory bodies have developed standards to assess the credibility of models [4, 8, 9].”
From Adapting modeling and simulation credibility standards to computational systems biology (2023) · cites this paper as [9]
The European Regulatory Viewpoint (page unavailable) reports a published European PBPK concept paper and plans for a guideline on model qualification and reporting. It mentions an earlier FDA workshop, but does not say the FDA developed credibility standards; the Discussion Topics section says PBPK system-model qualification standards were not yet agreed. Our copy does not mention NASA. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe European Medicines Agency issued its Guideline on the Reporting of Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation in 2018.
“Of particular relevance for the field of systems biology is The European Medicines Agency’s (EMA) Guideline on the Reporting of Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation issued in 2018 [9, 65].”
From Adapting modeling and simulation credibility standards to computational systems biology (2023) · cites this paper as [9]
The European Regulatory Viewpoint says an EMA PBPK concept paper had been published and was expected to lead to a European guideline on qualification and reporting. The References identify that concept paper, but this 2015 paper does not establish that the guideline was issued in 2018. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThere is a mismatch in terms and definitions used between the computational science and MIDD communities, including 'qualification,' 'validation,' and 'verification'.
“To add complexity, there is also mismatch in terms and definitions used between the computational science and MIDD communities (including “qualification,” “validation,” and “verification”).21”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Zhao, P. (2017) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12166 · Cited by 45 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Reference to FDA meeting report in same CPT edition
- Understanding the Potential of Systems Pharmacology. Unpublished paper written by G Mirams (University of Oxford, UK), D Gavaghan (University of Oxford, UK), M Davies (AstraZeneca, UK) for the Medical Research Council
Cited by
Sorted by citations
Applied Concepts in PBPK Modeling: How to Build a PBPK/PD Model
Kuepfer, L., Niederalt, C., Wendl, T., Schlender, J., Willmann, S., Lippert, J., Block, M., Eissing, T., & Teutonico, D. (2016) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12134 · Cited by 425 · see citing works
Jamei, M. (2016) · Current Pharmacology Reports · doi:10.1007/s40495-016-0059-9 · Cited by 244 · see citing works
Kuemmel, C., Yang, Y., Zhang, X., Florian, J., Zhu, H., Tegenge, M., Huang, S., Wang, Y., Morrison, T., & Zineh, I. (2020) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12479 · Cited by 177 · see citing works
“21 Regardless of the vocabulary used across the MIDD community currently, if the goal is to assure a common starting point for dialogue on the evidentiary standards needed for acceptance of a model for a given regulatory purpose, then the terminology used for model credibility assessments needs to…”
Parrott, N. J., Yu, L. J., Takano, R., Nakamura, M., & Morcos, P. N. (2016) · The AAPS Journal · doi:10.1208/s12248-016-9957-3 · Cited by 77 · see citing works
Zhao, P. (2017) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12166 · Cited by 45 · see citing works
Adapting modeling and simulation credibility standards to computational systems biology
Tatka, L. T., Smith, L. P., Hellerstein, J. L., & Sauro, H. M. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04290-5 · Cited by 25 · see citing works
- Authors
- Shepard, T., Scott, G., Cole, S., Nordmark, A., & Bouzom, F.
- Affiliations
- Medicines and Healthcare products Regulatory Agency (GB)
- Takeda (United Kingdom) (GB)
- Medical Products Agency (SE)
- Technologie Servier Orleans France
- Corresponding author
- Shepard, T
- ORCID
- Venue
- CPT: Pharmacometrics & Systems Pharmacology
- Publisher
- Wiley
- Published
- 2015-04
- Volume
- 4
- Issue
- 4
- Pages
- 221-225
- ISSN
- 2163-8306 (ISSN-L)
- PMC
- PMC4429575
- OpenAlex
- W1550666041
- Cited by
- 75
- References
- 2
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 9 · 2020: 6 · 2019: 4 · 2018: 7 · 2017: 13 · 2016: 15 · 2015: 3
- FWCI
- 12.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- CPT Pharmacometrics & Systems Pharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- physiologically based pharmacokinetic modeling, regulatory submissions, drug regulation, clinical pharmacology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
