ESTP International Expert Workshop
Friday afternoon 29th September and Saturday morning 30th September
The ESTP International Expert Workshop will be organized in the Hyperion Hotel in Basel.
Messeplatz 12, Basel, Switzerland 4058
T: +41 61-560-4000
Designed to stay yet do no harm: Safety assessment of Long-Acting Injectables and the evaluation of the injection site. The ESTP International Expert Workshop will take place on 29th September PM and 30th September AM.
The content of the workshop will be brought to the participants as presentations, highlighting the discussion that the experts conducted during the preparation, including interactive sessions with voting options and time for discussion, questions, and answer sessions.
In-life/study design will cover the Preclinical development of LAI including optimal study designs for evaluation of Local tolerance, Good practices for tolerability studies, Harmonization of Clinical observations for injection site reactions.
The Post-mortem parts (sampling/nomenclature) will include species comparison and selection criteria, assessment of these injection sites including both the acute and chronic response to SC/IM injection of LAIs and their recovery, and recommendations on the collection and trimming of SC/IM injection sites in different species. The available CDISC/SEND and INHAND nomenclature for histological description of these lesions will be discussed, and proposed updates to the current INHAND nomenclature will be presented with examples.
Tolerability section will cover its assessment in local tolerance studies and systemic toxicity studies. Terminology and proposed criteria based on case examples and Communicating the clinical risk of ISR from LAI drugs.
The main reason for the development of novel “long-acting injectable” (LAI) depot formulations, is to meet the needs of chronic or life-long disease therapy. The long-term treatment of diseases such as psychiatric conditions (e.g., schizophrenia) and infectious diseases (e.g., HIV), is often hampered by the fact that patients do not adhere to their daily (oral) medication. In many instances, the slow drug-release provides steady plasma exposures, eliminating the “peak and trough” kinetics of repeated daily dosing. Evaluation of LAI related injection site reactions in animal studies is a key component for risk assessment.
Currently, some important details of study designs, such as the collection and processing of injection sites, or the terminology and interpretation of injection site observations for these compounds are not well defined. This workshop will contain interactive elements, recommendations, and practical examples for the safety assessment of LAIs at the injection sites. In this workshop we aim to discuss and share our recommendations for the evaluation of LAI injection site reactions in local tolerance studies.
For the study design of in-life portion of the studies we will include species and administration site comparison for subcutaneous (SC) and intramuscular (IM) administration of long acting injectables. Currently the evaluation of clinical observations is often based on the “Draize score”, adopted from ocular/dermal evaluations. Because the current Draize scoring scale might not be suitable for depot formulations, we will also provide recommendations for an adapted scoring system and terminology, including examples.
Many long-acting injectables are formulated in a poorly soluble depot or a device, from which the active agent is slowly released over time. Assessment of these injection sites should include both the acute and chronic response to SC/IM injection of LAIs and their recovery. We will share our recommendations on the collection and trimming of SC/IM injection sites in different species. The available CDISC/SEND and INHAND nomenclature for histological description of these lesions will be reviewed, and proposed updates to the current INHAND nomenclature will be presented with examples.
We aim to provide criteria for pathologists to assess the local tolerance of LAIs, based on clinical observations and injection site histopathological findings. We will present case studies to discuss tolerability of LAIs, their translatability to the clinic and impact on drug label.
Finally we consider that the outcome of this workshop will also be useful to other studies using parenteral routes.
Friday, 29 September
14.00-14.10 | Introduction | Marjolein van Heerden & Bhanu Singh
14.10-15.45 | In-life/study design | Marjolein van Heerden
•Preclinical development of LAI including optimal study designs for evaluation of Local tolerance | Lorenz Kempeneers
•Good practices for tolerability studies | Laure Penard
•Subcutis species comparison | Najla Ayadi
•Harmonization of Clinical observations for injection site reactions | Bianca Feyen
15.45-16.15 | Coffee break
16.15-18.00 | Post-mortem sampling | Keith Nelson
• In-Life Factors in LAI Studies Affecting Post-Mortem Evaluation | Elodie Drevon-Gaillot
• Post-Mortem Sample Collection and Processing in LAI studies | Keith Nelson
• Subcutaneous Injections in the Minipig: A Local Tolerability Study Example | Keith Nelson and Rikke Kirk
• Post-Mortem Evaluation Approaches for LAI studies | Maurice Cary
• Nomenclature for Macroscopic Observations of LAI Injection Sites: A Suggested Glossary | Keith Nelson
Saturday, 30 September
08.30-10.15 | Post-mortem nomenclature | Anna-Lena Frisk
• Histopathology - Nomenclature: Terminology and General Considerations | Lars Mecklenburg, Charlotte Keenan
• Nomenclature (Case Studies) | Anna-Lena Frisk, Duane Belote, Lars Mecklenburg
• Survey Responses from the Poster “Macroscopic and Microscopic Evaluation of Injection Sites for Long- Acting Injectables– Proposed Guidelines on Terminology” | Keith Nelson
• Particle Size in Long Acting Injectable (LAI) Crystalline Drug Suspensions drives Cellular Response | Marjolein van Heerden
10.15-10.45 | Coffee break
10.45-13.00 | Tolerability | Bhanu Singh
• Communicating the clinical risk of injection site reactions from long-acting injectable drugs | John Vahle, Bernd Riebesehl
• Points to consider for determination of local tolerability in nonclinical studies | Bhanu Singh, Vijay Kale
• Development of a long acting subcutaneous injectable for seasonal malaria chemoprotection-Evaluation of tolerability at the injection site (Case Study) | Jean-Rene Galarneau
• Tolerability of Intra-Articular Long-Acting Injectables (Case Study) | Esther Sutter
• Local Tolerance of Silica-Based Vehicle (Case Study) | Marjolein van Heerden
• Closing remarks | Marjolein van Heerden, Bhanu Singh
The expert panel of the 10th ESTP Workshop
Anna-Lena Frisk, Janssen Pharmaceutica*
Bernd Riebesehl, Novartis
Bhanu Singh, Gilead Sciences Inc.*
Bianca Feyen, Janssen Pharmaceutica
Charlotte Keenan, C.M. Keenan ToxPath Consulting
Duane Belote, Labcorp
Elodie Drevon-Gaillot, Charles River Lyon SA
Esther Sutter, Novartis
Jean-Rene Galarneau, Novartis
John L Vahle, Lilly
Keith Nelson, Inotiv
Lars Mecklenburg, Labcorp
Laure Penard, Charles River
Lorenz Kempeneers, Janssen Pharmaceutica
Luann Mckinney, Office of New Drugs, USFDA
Marjolein van Heerden, Janssen Pharmaceutica*
Maurice Cary, Pathology Experts GmbH
Najla Ayadi, MedinCell
Raphaela Hiltrop, University Ghent
Rikke Kaae Kirk, Novo Nordisk
Vijaykumar Kale, Bristol Myers Squibb
Expert Meeting € 150
Prices are incl. 7,7% Swiss VAT
The registration fee includes
• Admission to the Expert Meeting
• Coffee break
How to register
In order to register for the Expert Meeting and / or the ESTP congress please register online and be sure to submit your registration. Upon receipt of your completed registration form and payment, you will receive an email confirmation of your registration.