On 30 & 31 March, Nelson Labs Leuven hosted its virtual symposium on Small Volume Parenteral Packaging from an Extractable & Leachable perspective. The PDFs of the presentations from this two-day seminar are now available.
Contact [email protected] for more information.
Day 1 – March, 30
Session I
Introduction Nelson Labs.
Speaker: Eric Meyers, Senior Vice President EMEAA Operations
Company: Nelson Labs
Nelson Labs is a global leader in microbiological and analytical chemistry testing and advisory services for the medical device and pharmaceutical industries. Nelson Labs serves over 4,000 customers across 15 facilities in the United States, Mexico, Asia, and Europe. We have a comprehensive array of over 800 laboratory tests supporting our customers from initial product development and sterilization validation, through regulatory approval and ongoing product testing for sterility, safety, and quality assurance. We are regarded as a best-in-class partner with a strong track record of collaborating with customers to solve complex issues.
Based in Belgium, Nelson Labs Europe specializes in providing premium Extractables & Leachables testing services to the pharmaceutical and medical device industries. We also support pharmaceutical companies across the globe in developing worldwide compliance testing strategies to qualify container/closure applications and pharmaceutical production equipment from an Extractables & Leachables perspective.
Learn more about Nelson Labs at www.nelsonlabs.com Safeguarding Global Health® – with every test we complete.
Download the presentation slides here.
Session 2
Manufacturing an SVP Drug Containment Solution: Quality by Design.
Speaker: Daniel Martinez, Product Manager – Syringes & Analytical Services
Company: Stevanato Group
Considerations that need to be taken into account when choosing, designing, and manufacturing an SVP drug container solution. The drug product, route of administration, and life cycle management play an important role in the selection of the primary container, the manufacturing process, and the components chosen to safeguard the drug and the patients. An insight into the different manufacturing capabilities and controls to manufacture the required container.
Download the presentation slides here.
Session 3
Rubber Manufacturing and Composition of Pharma Rubbers.
Speaker: Tine Hardeman PhD, Manager Material Development Healthcare
Company: Datwyler
Rubber closures are often used in the primary packaging system of small volume parenterals. This presentation aims to provide more insight into the manufacturing process and basic composition of rubber compounds used for pharma applications. Additionally, it will discuss how the properties of rubber can be adjusted to match specific requirements and how to ensure that the rubber meets all the relevant criteria for safe use in the final application.
Download the presentation slides here.
Session 4
Polymer-based, Pre-filled Syringes designed to Minimize the Aggregation Risk of Sensitive Biodrugs.
Speaker: Philippe Lauwers, Technology Development Director
Company: Terumo
Biopharmaceutical drugs offer new therapeutic solutions to numerous human diseases and conditions. However, with this comes the risk of efficacy loss due to protein interactions potentially leading to immunogenicity impacting the patient’s safety and therapeutic outcome. Terumo’s PLAJEX™ pre-fillable syringes (PFS) are designed to meet the needs of a wide variety of types of drugs including those requiring low reactive containers.
In this presentation, we will highlight some of the main values our PLAJEX™ PFS offer as well as the experience we have built over two decades with processing our primary containers on our own fill-and-finish lines in Japan.
Download the presentation slides here.
Session 5
E&L Testing of Single-Use Systems for Production.
Speaker: Karen Pieters, Study Director
Company: Nelson Labs
Leachables in pharmaceutical products could originate from manufacturing items (filters, bioreactors, etc.) used in the pro duction process. With the increasing use of disposables in the pharma industry, the concern in E&L has also developed considerably. Biopharma industry groups (BPSA, BPOG) have published recommendations when and how to perform E&L studies for these materials. More over, the USP has released chapter <665> and <1665>, which ad dress E&L for production materials in the (bio) pharmaceutical industry.
The different steps in the assessment of the E&L impact of a production line will be outlined In this presentation. In addition, the recommendations of BPOG and USP for these materials will be discussed.
Download the presentation slides here.
Session 6
Glass Delamination: Choosing the Right Glass Container for your Drug Product.
Speaker: Serena Panighello PhD, SG Laboratory Scientist
Company: Stevanato
Corrosion propensity of pharmaceutical glass is affected by the combination of several factors, starting from the manufacturing process to the storage of the final product. Drug stored in glass primary containers risk losing efficacy and safety when not properly tested. Our risk-based approach to improve product quality and reduce testing is presented through case studies:
• Choosing the correct glass container early in development and when dual sourcing
• Impact of processes and treatments
• Functional testing for early-stage development
Download the presentation slides here.
Session 7
Radiation Sterilization of SVPP: RTU and fill/finished. Do not default to 25 kGy – 40 kGy.
Speaker: Bart Croonenborghs PhD, Technical Director Irradiation EMEAA
Company: Sterigenics
Examples will be presented for radiation sterilization of RTU SVPP as well as terminal sterilization of fill/finished items. A critical aspect in validation of the irradiation processes is the Process
Definition step, where there is considerable benefit to not default to a specification of 25 kGy to 40 kGy.
Methods and practices for widening the specification will be discussed.
Download the presentation slides here.
Session 8
A Structured Approach to Selection of Container Closure Materials for Small Volume Parenterals – Pipe Dream or Necessity.
Speaker: Jason Creasy, Managing Director and Principal Consultant
Company: Maven E&L
This presentation will provide reasons why material selection for small volume parenteral container closures should be built upon well-defined attributes rather than a random selection or just previous use. It will explore some of the factors and attributes to consider such as compatibility, material extractables, dimensional stability, and regulatory expectations. It will answer
questions such as what is meant by combability and how might extractable testing design choices influence selection.
The presentation will explore how performance, quality, safety, and functionality are all interconnected and affected by the choices made. It will also lay out an ideal timeline for selection.
Download the presentation slides here.
Session 9
US Drug Delivery Combination Product Regulatory.
Speaker: Lee Leichter, RAC, MBA, President
Company: P/L Biomedical
This presentation will include a short summary of the types of Drug Delivery Combination products codified by US FDA regulation, and the types of other drug delivery products where the combination must be addressed. It will detail the current technical expectations for development, incorporating Design Verification approaches, including FDA Essential Performance Requirements (EPRs), recently updated ISO 11608 series, and FDA and IEC requirements for addressing Human factors; and GMP/System requirements required under FDA 21 CFR Part 4 regulations.
Among other areas, the presentation will touch on requirements for clinical requirements and unique challenges for generic products.
Download the presentation slides here.
Session 10
SVP Packaging – NB Persepective on CE-marked Medical Devices versus Article 117 MDR Combination Products.
Speaker: Christiana Hofmann PhD, Regional Manager Focus Topics (Article 117 & Annex XVI)
Katharina Weidmann PhD, Expert Biocompatibility
Company: TüV SüD
This presentation will provide an overview of considerations regarding biological risks from primary packaging materials for CE marking of combination products.
Furthermore, combination products falling under the Art 117 MDR requiring a NBOp (regulatory background and common pitfalls) will be discussed.
Download the presentation slides here
Session 11
SVP Packaging – NB Persepective on CE-marked Medical Devices versus Article 117 MDR Combination Products.
Speaker: Christiana Hofmann PhD, Regional Manager Focus Topics (Article 117 & Annex XVI)
Katharina Weidmann PhD, Expert Biocompatibility
Company: TüV SüD
This presentation will provide an overview of considerations regarding biological risks from primary packaging materials for CE marking of combination products.
Furthermore, combination products falling under the Art 117 MDR requiring a NBOp (regulatory background and common pitfalls) will be discussed.
Download the presentation slides here.
Day 2 – March, 31
Session 1
Primary Packaging Considerations from a Biologics Product Development Perspective.
Speaker: Prof. Hanns-Christian Mahler PhD, CEO
Company: ten23 health AG
In this presentation, Dr. Mahler will give an overview of biologics product development, with a specific emphasis on how primary packaging for parenteral biologics drug products are being chosen and appropriately qualified.
This presentation is not available
Session 2
Essential Principles of Chemical Characterization (Extractables and Leachables) Applied to Small Volume Parenterals (SVPs).
Speaker: Dennis Jenke PhD, Principal Consultant
Company: Nelson Labs
During their production, storage/distribution and administration, small volume parenteral drug products leach chemicals from their manufacturing, packaging, and delivery systems. These foreign impurities (leachables) can potentially have a significant effect on the quality of the SVPs and may affect the efficiency with which the SVP is produced. To establish the effects of these impurities, drug products are profiled for leachables and manufacturing, packaging, and delivery systems are tested for extractables (as probable leachables).
In this presentation, the scientific and practical aspects and principles of the chemical characterization of SVPs and their related systems will be introduced; including a review of the relevant regulatory guidance, standards and best demonstrated practice recommendations. The presentation will provide suggested best practices (dos and don’ts) for the design, implementation, interpretation, and submission of E&L studies.
Download the presentation slides here.
Session 3
Setting up Extractables & Leachables Studies for Small Volume Parenteral Applications.
Speaker: Eyra Marien PhD, Study Director
Company: Nelson Labs
In this presentation, general extractables and leachables principles will be explained for small volume parenteral (SVP) applications including vials, cartridges, and pre-filled syringes—as these are the main container closure systems used in SVP applications.
Download the presentation slides here.
Session 4
The Necessity of Extractables and Leachables Qualifications for Lyophilized Drug Products: Some Fallacies Addressed.
Speaker: Sona Kovackova PhD, Study Director
Company: Nelson Labs
When selecting and qualifying the primary packaging for lyophilized drug products (LDPs), one of the obvious questions is How far should you go into the E&L-qualification process? As the drug product is in a solid state, you would expect that the interaction between the LDP and the components of its container would be low. But is this really the case?
The presentation will provide a view on the current status of regulatory requirements and will address some of the fallacies that exist in E&L qualifications for lyophilized drug products.
Download the presentation slides here.
Session 5
Rubber Oligomers.
Speaker: Piet Christiaens PhD, Scientific Director
Company: Nelson Labs
Rubber Oligomers, originating from the rubber closure (vial) or plunger (e.g., syringe or cartridge) are a class of compounds that needs an increased level of attention, especially when they are chlorinated or brominated. These halogenated oligomer compounds have shown to be reactive to the drug product under certain circumstances, and toxicity is potentially of high concern.
With this presentation, rubber oligomers’ structure will be discussed and how it pertains to their reactivity and toxicity. In addition, we will take a closer look at their formation and how you can detect these compounds and identify them in an extractable or leachable study.
Download the presentation slides here.
Session 6
Reactive Leachables.
Speaker: Paulo Forte, Study Director Extractables & Leachables
Company: Nelson Labs
The reactivity of leachables is an area of growing concern, especially for therapeutic proteins and peptides, not only because it can lead to undesirable immunogenic effects, but it can also compromise the quality and efficacy of the drug product. In a lot of cases, an evaluation of the chemical structure of the leachable can “predict” its potential reactivity.
This presentation will explain the experimental work that Nelson Labs performed to link the structural reactivity to experimentally observed reactivity, using Glargine (an Insulin peptide) as a marker compound.
Download the presentation slides here.
Session 7
N-Nitrosamines in Primary Packaging for SVP’s.
Speaker: Ward d’Autry PhD, Study Director Structural Elucidation
Company: Nelson Labs
Because of recent product recalls due to the unexpected presence of N-Nitrosamines, it is important to look at the formation of these amines on materials prominently used in the primary packaging of drug products.
The unanswered question is: do we know everything about the materials of construction of a container closure system and their ability to generate
N-Nitrosamines? It is commonly known that secondary amines (and potentially tertiary amines) are a precursor to N-Nitrosamine formation and that these need to be taken into consideration when evaluating the extraction pro file of materials of construction. The question however remains: should this raise a “red flag” in an N-Nitrosamine risk mitigation strategy?
Download the presentation slides here.
Session 8
Analytical Approaches used in E&L studies from Basic Instrumentation to High-End, State-of-the Art Equipment to Support Structural Elucidation.
Speaker: Ward d’Autry PhD, Study Director Structural Elucidation
Company: Nelson Labs
In this presentation we will visit the analytical laboratory where E&L studies are performed. We will show the kind of equipment we use, where it is used, what the analytical data looks like, and how it is evaluated. We will explain how we can estimate concentrations and identify extractables or leachables and how to avoid and mitigate mistakes?
We will also discuss if a compound is not identified after a first screening round, what are the next possibilities for structural elucidation? Welcome to the analytical lab.
Download the presentation slides here.
Session 9
The Challenges in Tox Assessments for Small Volume Parenteral Packaging System Applications.
Speaker: Koen van Deun PhD, External Toxicologist
The presentation will cover typical toxicological challenges in SVP E&L, including some examples. Further toxicological procedures and typical endpoints are discussed. Finally, possible hazard evaluation methods will be explained, followed by a conclusion on current toxicological assessment.
Download the presentation slides here.
