European study of Neonatal exposure to Excipients (ESNEE)/Priomedchild Call/ERA-Net
Lead Research Organisation:
University of Liverpool
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
"Excipents are chemicals added to medicines to improve their quality. Sporadic reports indicate that some may be toxic for neonates and lead to significant morbidity or death. However, there is insufficient information about the risks generated by excipient exposure because systematic surveys have not been done and studies on babies have not been ethical in the past. Recent advances allow determination of excipient levels in very small blood volumes (50 microlitre) including dry blood spot methods and estimates of excipient exposures based on only 2-4 samples per baby. Hypothesis 1: information about exposures across the EU will promote reduction of neonatal exposure to excipients by highlighting opportunities for product substitution and priorities for reformulation.|Hypothesis 2: small volume blood samples can be used to generate models of systemic excipient exposure. Our consortium comprises researchers from Estonia, France and the UK with extensive experience in all aspects of the study. We will develop a platform of techniques to assess excipient exposure including: a questionnaire and point prevalence study of neonatal excipient exposure; systematic reviews of relevant literature; dried blood spot assays for high impact excipients; a cohort study to construct population excipient kinetic models (EK, analogous to active drug pharmacokinetics or PK) for high impact excipients. This work will lead to recommendations for the European Medicines Agency and other stakeholders about assessment of excipient exposure and underpin future work to relate exposures to outcomes.|"
People |
ORCID iD |
Publications
Mulla H
(2015)
An observational study of blood concentrations and kinetics of methyl- and propyl-parabens in neonates.
in Pharmaceutical research
Buckley LA
(2018)
Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients.
in International journal of pharmaceutics
Nellis G
(2014)
Comparison of two alternative study designs in assessment of medicines utilisation in neonates.
in BMC medical research methodology
Pandya HC
(2016)
Essential medicines containing ethanol elevate blood acetaldehyde concentrations in neonates.
in European journal of pediatrics
Pandya HC
(2016)
Ethanol in oral liquid iron and furosemide formulations is incompletely metabolised by neonates
in European Journal of Pediatrics
Turner M
(2012)
European Study for Neonatal Excipient Exposure (ESNEE)
in European Journal of Hospital Pharmacy
Graham Susan
(2011)
European Study of Neonatal Exposure to Excipients (ESNEE)
in Infant
Turner MA
(2013)
European Study of Neonatal Exposure to Excipients: an update.
in International journal of pharmaceutics
Lass J
(2012)
Hospitalised neonates in Estonia commonly receive potentially harmful excipients.
in BMC pediatrics
| Description | Citation in guidance document by European Medicines Agency |
| Geographic Reach | Europe |
| Policy Influence Type | Citation in other policy documents |
| Impact | Our data contributed to the risk-benefit analysis of commonly used excipients. Our findings confirmed in human neonates the suggestions from other sources that parabens are present at low concentrations following administration in existing medicines. The overall package of information supports the continued use of these excipients and avoids the need for costly reformulation of widely used medicines. |
| URL | http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/11/WC500196733.pdf |
| Description | EMA Advice |
| Geographic Reach | Asia |
| Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
| Impact | Summary data from the clinical studies in the project have been shared with the European Medicines Agency. We are told that this has informed their position on the risks associated with parabens in newborn babies. Their guidance is still in draft |
| Description | Interaction with European Medicines Agency |
| Geographic Reach | Europe |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Title | Assay development |
| Description | Assays for parabens in whole blood samples collected in dried blood spots have been developed by the Pharmacy Dept at Queens University Belfast |
| Type Of Material | Technology assay or reagent |
| Provided To Others? | No |
| Impact | Assays are currently being applied to 500 samples from 150 babies recruited in our clinical studies |
| Title | Assay development, ethanol |
| Description | The Pharmacy Department at Leicester have developed an assay for ethanol and 3 of its metabolites from microsamples of plasma (50 micro litres) |
| Type Of Material | Technology assay or reagent |
| Provided To Others? | No |
| Impact | This assay is being applied to 150 samples from 50 babies recruited to the clinical study. |
| Description | Belfast |
| Organisation | Queen's University Belfast |
| Department | School of Pharmacy |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Clinical trials expertise; project management |
| Collaborator Contribution | Assay expertise |
| Impact | Not yet |
| Start Year | 2009 |
| Description | Leicester |
| Organisation | University of Leicester |
| Department | Leicester Medical School |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Expertise in clinical trials; project management |
| Collaborator Contribution | Pharmacokinetic expertise, review of clinical materials |
| Impact | Not yet |
| Start Year | 2010 |
| Description | Paris |
| Organisation | Robert Debre Hospital |
| Country | France |
| Sector | Hospitals |
| PI Contribution | Clinical trials expertise; project management |
| Collaborator Contribution | Expertise in literature review |
| Impact | Not yet |
| Start Year | 2010 |
| Description | Paris 2 |
| Organisation | Antoine Beclere Hospital |
| Department | Pharmacy Antoine Beclere Hospital |
| Country | France |
| Sector | Hospitals |
| PI Contribution | Clinical trials expertise; project management |
| Collaborator Contribution | Pharmacy expertise |
| Impact | Not yet |
| Start Year | 2010 |
| Description | Tartu |
| Organisation | University of Tartu |
| Department | Department of Paediatrics |
| Country | Estonia |
| Sector | Academic/University |
| PI Contribution | Clinical trials expertise; project management |
| Collaborator Contribution | Survey expertise |
| Impact | Not yet |
| Start Year | 2010 |
| Title | Clinical study of excipient kinetics |
| Description | Excipients are widely used in medicines given to neonates but their circulating concentrations have never been evaluated. |
| Type | Management of Diseases and Conditions |
| Year Development Stage Completed | 2013 |
| Development Status | Closed |
| Clinical Trial? | Yes |
| Impact | Our study of excipient kinetics examined three excipients. This is the first time this has been done in neonates. The use of dried blood spots was novel. The results have been published and presented to the regulatory authorities. |
| URL | http://www.isrctn.com/ISRCTN31837223 |
| Description | 21st European Neonatology workshop |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Keynote/Invited Speaker |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Towards a systematic approach to risk assessment in neonates: a case study from the european study of neonatal exposure to excipients Profile of study raised |
| Year(s) Of Engagement Activity | 2013 |
| Description | Belfast presentation USA |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Keynote/Invited Speaker |
| Geographic Reach | International |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | S. Yakkundi 2013. Application of LC-MS/MS to Determine the Exposure to Methyl and Propyl Parabens in Preterm Neonates using Dried Blood Spot (DBS)",61ST ASMS Conference on Mass Spectrometry and Allied Topics, Minneapolis, USA, June 2013 Raising profile of study |
| Year(s) Of Engagement Activity | 2013 |
| Description | CI poster ESPR |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Poster Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | M.A. Turner, S. Yakkundi, T. Metsvah, H.Varendi, G. Nellis, J.Windrow, S.Graham, H.Mulla, H.Pandya, S.Tapscott, N.Caldwell, J.Duncan, I.Lutsar, T.Nunn, J.McElnay 2013. Methyl and propyl paraben concentrations in preterm neonates exposed to clincially indicated medicines fall within safety margins for oestrogenic effects of these anti-microbial excipients. 54th Annual meeting ESPR, Oct 10-14, 2013, Portugal Findings from study with regards to safety margins of methyl & propyl concentrations in neonates |
| Year(s) Of Engagement Activity | 2013 |
| Description | Dried Blood Spots Editorial |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Health professionals |
| Results and Impact | An editorial about the use of dried blood spots to study experient kinetics in neonates was published in December 2011 . Since this publication, there has been a lot of interest in the DBS excipient work. A couple of groups in the US and Mexico got in touch in order to discuss the paraben work. |
| Year(s) Of Engagement Activity | 2011 |
| Description | ESNEE - Estonian presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Paper Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Nellis, G.; Varendi, H.; Metsvaht, T.; Lutsar, I. (2012). Medicines used for neonates in Europe - the survey of the European study of neonatal exposure to excipients (ESNEE). In: Journal of Neonatal-Perinatal Medicine: 20th European Workshop on Neonatology, Tallinn, 27th - 30th June, 2012. IOS Press, 2012, (5; 2), 199. Discussion arose around the subject area & study |
| Year(s) Of Engagement Activity | 2012 |
| Description | ESPID Estonia presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Paper Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Metsvaht, T.; Nellis, G.; Varendi, H.; Graham, S.; Rieutord, A.; Storme, T.; Vaconsin, P.; Nunn, AJ.; McElnay, J.; Millership, J.; Yakkundi, S.; Mulla, H.; Pandya, H.; Turner, MA.; Lutsar, I. (2013). DOSING OF FREQUENTLY USED ANTIBIOTICS IN EUROPEAN NICUS: POINT PREVALENCE STUDY OF EUROPEAN STUDY OF NEONATAL EXPOSURE TO EXCIPENTS (ESNEE). In: 31th Annual Meeting of ESPID (European Society of Pediatric Infectious Diseases); Milan; 28.05.-01.06.2013 Raising profile |
| Year(s) Of Engagement Activity | 2013 |
| Description | Estonia Presentation blood concs |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Paper Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Nellis, G.; Lutsar, I.; Varendi, H.; Turner, MA.; Graham, S.; Rieutord, A.; Storme, T.; Vaconsin, P.; Nunn, AJ.; McElnay, J.; Millership, J.; Yakkundi, S.; Mulla, H.; Pandya, H.; Metsvaht, T. (2013). BLOOD CONCENTRATIONS OF METHYL AND PROPYL PARABENS IN NEONATES TREATED WITH GENTAMICIN AS THE MOST COMMONLY USED ANTIBIOTIC. 31th Annual meeting of ESPID (European Society of Pediatric Infectious Diseases) Milan, Italy; 28.05.-01.06.2013. Raising profile of study |
| Year(s) Of Engagement Activity | 2013 |
| Description | Ethanol Concentrations poster |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Poster Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Presentation at the 14th ESDPPP Congress, Salzburg 2013. M.Hubbard, R.Cordell, H.Pandya, P.Monks, M.A.Turner, H.Mulla. Circulating ethanol concentrations in neonates administered clinically indicicated medications: feasibility of microsampling methods as part of the european study of neonatal excipient exposure. Raising profile of study specifically with regards to ethanol sampling |
| Year(s) Of Engagement Activity | 2013 |
| Description | Journal Article with Estonian Team |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Publication of Hospitalised neonates in Estonia commonly receiving potentially harmful excipients in the BMC Pediatrics Journal The publication raised the profile of the ESNEE study in Estonia and resulted in sites expressing a wish to take part in the project |
| Year(s) Of Engagement Activity | 2012 |
| Description | Journal Article with French Team |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Publication of ESNEE in the European Journal of Hospital Pharmacy to raise the profile of the ESNEE study throughout the European pharmacy community The profile of the study was raised throughout Europe with many interested countries wishing to find out more information and to take part |
| Year(s) Of Engagement Activity | 2012 |
| Description | Magazine article (Infant) |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Health professionals |
| Results and Impact | Magazine article targeted at health care professionals who would support clinical aspects of the project Several new centres expressed an interest in participation, these centres are not part of our informal network of contacts |
| Year(s) Of Engagement Activity | 2011 |
| Description | Nellis Poster Presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Poster Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Antibiotic prescribing in European neonatal intensive care units: Service Evaluation Survey of the European Study of Neonatal Exposure to Excipients poster presentation at the 30th meeting of ESPID. The poster was read by other professionals and led to discussion of the project and work carried out Interest in the study rose |
| Year(s) Of Engagement Activity | 2012 |
| Description | Nellis Presentation UENPS |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Paper Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Abstract (Potentially harmful excipient in antibiotics prescribed to European neonates - ESNEE survey) accepted at the 3rd international congress of UENPS. Nellis G et al. Oral Presentation Raising profile of the study |
| Year(s) Of Engagement Activity | 2012 |
| Description | Poster Presentation (Belfast Team) (DBS to study excipient kinetics in neonates) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Poster Presentation |
| Geographic Reach | National |
| Primary Audience | Health professionals |
| Results and Impact | An ESNEE poster regarding the Dried Blood Sports (DBS) analysis of excipients at the Reid Bioanalytical Forum, Guildford, 2011. The poster created a lot of interest as this is the first of its kind in DBS area. The impact was that the ESNEE team were asked to submit an editorial for the Journal |
| Year(s) Of Engagement Activity | 2011 |
| Description | Potentially harmful excipients in antibiotics - Estonia |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Paper Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Potentially harmful excipients in antibiotics prescribed to european neonates - ESNEE survey. In: Acta Médica Portuguesa : 3rd International Congress of UENPS, 2012; Porto, nov 14-17. , 2012, (25; 2), 141. Nellis, Georgi; Varendi, Heili; Lass, Jana; Lutsar, Irja; Metsvaht, Tuuli Discussion arose with regards to the presentation |
| Year(s) Of Engagement Activity | 2012 |
| Description | Potentially harmful excipients in medicines - PPS - Estonia |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Paper Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Nellis, G.; Lutsar, I.; Varendi, H.; Lass, J.; Turner, MT; Metsvaht, T. (2013). Potentially harmful excipients in medicines prescribed to European neonates - ESNEE PPS. 54th Annual Meeting of European Society of Paediatric Research, Porto, Oct 10-14, 2013. Raising profile of study |
| Year(s) Of Engagement Activity | 2013 |
| Description | Probiotic use PPS - Estonia |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Paper Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Metsvaht, T.; Moor, R.; Nellis, G.; Varendi, H.; Lutsar, I. (2013). PROBIOTIC (PB) USE IN RELATION TO ANTIBIOTIC (AB) USE IN EUROPEAN NEONATAL INTENSIVE CARE UNITS (NICU): SUB-ANALYSIS OF ESNEE POINT PREVALENCE STUDY (PPS). 8th World Congress of the World Society for Pediatric Infectious Diseases; Capetown, South Africa; 20.-23. November 2013. Raising profile of study |
| Year(s) Of Engagement Activity | 2013 |
| Description | Probiotics Estonian presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Paper Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Moor, R.; Metsvaht, T; Nellis, G.; Varendi, H.; Lutsar, I. (2013). The use of probiotics in European neonatal intensive care units: sub-analysis of the ESNEE point prevalence study. 2nd Baltic Pediatric Congress; Pärnu 30.05.-01.06.2013. Raised discussion about the work carried out for project |
| Year(s) Of Engagement Activity | 2013 |
| Description | Turner Poster |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Poster Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Turner MA, Yakkundi S, Varendi H, Metsvaht T, Nellis G, Windrow J, Graham S, Mulla H, Pandya H, Tapscott S, Caldwell N, Duncan J, Lutsar I, McElnay J (2003). Methyl and propyl paraben concentrations in blood form preterm neonates exposed to clinically indicated medicines are lower than the concentrations of these anti-microbial excipients reported to affect cell physiology. raising profile of study |
| Year(s) Of Engagement Activity | 2013 |
| Description | Uni of Tartu presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Poster Presentation |
| Geographic Reach | International |
| Primary Audience | Health professionals |
| Results and Impact | Nellis G, Metsvaht T, Varendi H, Lass J, Turner M, Lutsar I European study of neonatal excipient exposure (ESNEE): Preliminary results of the Point Prevalence Survey Raising study profile |
| Year(s) Of Engagement Activity | 2013 |