title: A survey on IVIVC/IVIVR development in the pharmaceutical industry - Past experience and current perspectives.
abstract: The present work aimed to describe the current status of IVIVC/IVIVR development in the pharmaceutical industry, focusing on the use and perception of specific approaches as well as successful and failed case studies. Two questionnaires have been distributed to 13 EFPIA partners of the Oral Biopharmaceutics Tools Initiative and to the Pharmacokinetics Working Party of the European Medicines Agency in order to capture the perspectives and experiences of industry scientists and agency members, respectively. Responses from ten companies and three European Agencies were received between May 21st 2014 and January 19th 2016. The majority of the companies acknowledged the importance of IVIVC/IVIVR throughout the drug development stages and a well-balanced rate of return on investment. However, the IVIVC/IVIVR approach seemed to be underutilized in regulatory submissions. Four of the ten companies stated to have an internal guidance related to IVIVC/IVIVR modelling, whereas three felt that an overall strategy is not necessary. Successful models mainly served to support formulation development and to provide a better mechanistic understanding. There was not yet much experience with safe-space IVIVRs as well as the use of physiologically based modelling in the field of IVIVC. At the same time, the responses from both industry and agencies indicated that there might be a need for a regulatory framework to guide the application of these novel approaches. The relevance of IVIVC/IVIVR for oral IR drug products was recognized by most of the companies. For IR formulations, relationships other than Level A correlation were more common outcomes among the provided case studies, such as multiple Level C correlation or safe-space IVIVR, which could be successfully used for requesting regulatory flexibility. Compared to the responses from industry scientists, there was a trend towards a higher appreciation of the BCS among the regulators, but a less positive attitude towards the utility of non-compendial dissolution methods for establishing a successful IVIVC/IVIVR. The lack of appropriate in vivo data and regulatory uncertainty were considered the major difficulties in IVIVC/IVIVR development. The results of this survey provide unique insights into current IVIVC/IVIVR practices in the pharmaceutical industry. Pursuing an IVIVC/IVIVR should be generally encouraged, considering its high value from both industry and regulators' perspective.
authors.affiliation: Institute of Pharmacy, Johannes Gutenberg University, Staudinger Weg 5, 55099 Mainz, Germany. Electronic address: nguyen@uni-mainz.de.
authors.forename: M A
authors.initials: MA
authors.lastname: Nguyen
authors.affiliation: AstraZeneca R&D, Alderley Park, Macclesfield SK10 4TF, United Kingdom. Electronic address: Talia.Flanagan@astrazeneca.com.
authors.forename: T
authors.initials: T
authors.lastname: Flanagan
authors.affiliation: Pharmaceutical Sciences and Quantitative Sciences, Janssen R&D, Tornhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: M
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authors.lastname: Brewster
authors.affiliation: Pharmaceutical Sciences and Clinical Supply, MSD, West Point, PA 19486, USA. Electronic address: filippos_kesisoglou@merck.com.
authors.forename: F
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authors.lastname: Kesisoglou
authors.affiliation: Technical R&D, Novartis Pharma AG, Novartis Campus, CH-4056 Basel, Switzerland. Electronic address: stefania.beato@novartis.com.
authors.forename: S
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authors.lastname: Beato
authors.affiliation: Pharmaceutical Sciences and Quantitative Sciences, Janssen R&D, Tornhoutseweg 30, 2340 Beerse, Belgium. Electronic address: JBIEWENG@its.jnj.com.
authors.forename: J
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authors.lastname: Biewenga
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authors.forename: J
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authors.lastname: Crison
authors.affiliation: Pharmaceutical Science and CMC Biologics, H. Lundbeck A/S, DK-2500 Valby, Denmark. Electronic address: RHOL@Lundbeck.com.
authors.forename: R
authors.initials: R
authors.lastname: Holm
authors.affiliation: Pharmaceutical Sciences, Pfizer Inc., P.O. Box 8012, Estern Point Road, Groton, CT, USA. Electronic address: rong.li@pfizer.com.
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.affiliation: Pharmaceutical Sciences and Quantitative Sciences, Janssen R&D, Tornhoutseweg 30, 2340 Beerse, Belgium. Electronic address: EMANNAER@its.jnj.com.
authors.forename: E
authors.initials: E
authors.lastname: Mannaert
authors.affiliation: Pharmaceutical Sciences, Pfizer Inc., Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom. Electronic address: mark.mcallister@pfizer.com.
authors.forename: M
authors.initials: M
authors.lastname: McAllister
authors.affiliation: Technical R&D, Novartis Pharma AG, Novartis Campus, CH-4056 Basel, Switzerland. Electronic address: martin.mueller-zsigmondy@novartis.com.
authors.forename: M
authors.initials: M
authors.lastname: Mueller-Zsigmondy
authors.affiliation: Global Chemical and Pharmaceutical Development, Bayer Pharma AG, 42096 Wuppertal, Germany. Electronic address: uwe.muenster@bayer.com.
authors.forename: U
authors.initials: U
authors.lastname: Muenster
authors.affiliation: R&D Pharmaceutical Sciences, Orion Corporation, Orionintie 1A, 02200 Espoo, Finland. Electronic address: krista.ojala@orionpharma.com.
authors.forename: K
authors.initials: K
authors.lastname: Ojala
authors.affiliation: Pharmaceutical Sciences, Pfizer Inc., Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom. Electronic address: sharon.page@pfizer.com.
authors.forename: S
authors.initials: S
authors.lastname: Page
authors.affiliation: GlaxoSmithKline, Research Triangle Park, 5 Moore Drive, NC 27709, USA. Electronic address: A.Parr.Bioceutics@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Parr
authors.affiliation: Pharmaceutical Sciences and Quantitative Sciences, Janssen R&D, Tornhoutseweg 30, 2340 Beerse, Belgium. Electronic address: SROSSENU@its.jnj.com.
authors.forename: S
authors.initials: S
authors.lastname: Rossenu
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, Reeds Lane, Moreton, Merseyside CH46 1QW, United Kingdom. Electronic address: peter.timmins@bms.com.
authors.forename: P
authors.initials: P
authors.lastname: Timmins
authors.affiliation: Pharmaceutical Sciences and Quantitative Sciences, Janssen R&D, Tornhoutseweg 30, 2340 Beerse, Belgium. Electronic address: AVPEER@its.jnj.com.
authors.forename: A
authors.initials: A
authors.lastname: Van Peer
authors.affiliation: Pharmaceutical Sciences and Quantitative Sciences, Janssen R&D, Tornhoutseweg 30, 2340 Beerse, Belgium. Electronic address: AVERMEUL@its.jnj.com.
authors.forename: A
authors.initials: A
authors.lastname: Vermeulen
authors.affiliation: Institute of Pharmacy, Johannes Gutenberg University, Staudinger Weg 5, 55099 Mainz, Germany. Electronic address: langguth@uni-mainz.de.
authors.forename: P
authors.initials: P
authors.lastname: Langguth
mesh_terms: D000818:Animals; D055808:Drug Discovery; D004345:Drug Industry; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D011795:Surveys and Questionnaires
keywords: Dissolution; In vitro/in vivo correlation; Modelling and simulation; Oral dosage forms; Pharmacokinetics; Regulatory