Published in the September 2014 issue of Biologicals

Adventitious agents in viral vaccines: Lessons learned from 4 case studies

Since the earliest days of biological product manufacture, there have been a number of instances where
laboratory studies provided evidence for the presence of adventitious agents in a marketed product.
Lessons learned from such events can be used to strengthen regulatory preparedness for the future.

Four case studies where an adventitious agent, or a signal suggesting the presence of an agent, was found in a viral vaccine, are presented in this paper. The lessons learned from each event are discussed.

Based in part on those experiences,certain scientific principles have been identified by WHO that should be considered in regulatory risk evaluation if an adventitious agent is found in a marketed vaccine in the future.



Invitation to Join Brighton Collaboration


Read more


Career opportunities

The International Alliance for Biological Standardization (IABS), located in Geneva, Switzerland, is a non-profit association recognized as an NGO by WHO. The mission of IABS is to contribute to the scientific and medical advancement of biologicals by facilitating the communication among those who develop, produce and regulate biological products for human and animal health.

16-18 September, 2015 - The Netherlands PDF Print



The Consistency Approach and Alternative Methods: Towards Non-Animal-based Testing in Vaccine Development and QC


Date: September 16-18, 2015

Venue: Hotel Zuiderduin, Egmond aan Zee, The Netherlands


Scope and objective:

Vaccine development and quality control include models based on studies in laboratory animals, substantial numbers of which are used. Increasingly, however, regulations on animal experimentation and testing now urge the use of non-animal methods, reduction of animal numbers in tests still being performed and refinement of animal procedures and animal husbandry practices; the principle which is generally known as the 3Rs.


This need for humane science aligns with a broad wish to make vaccine development and quality control more science based, more economic and less time consuming.


Substantial progress in 3Rs implementation in vaccine development and quality control has been achieved; several non-animal models are being validated and a new testing strategy which integrates analytical tools, in vitro assays and quality systems; the consistency approach, is now under study.


The IABS conference will be the focal point for well recognised experts presenting the latest developments on the most important 3Rs topics in vaccine development and quality control. The conference will be THE platform for exchange of information on the 3Rs and testing strategies with representatives from industry, academia, guideline bodies and regulatory authorities. There will be a mix of presentations and interactive sessions offering an excellent opportunity for all those who are interested in state of the art vaccine quality control in the context of improving animal welfare.


For more information, please visit

Register here

29-30 September, 2015 - Rockville, Maryland PDF Print




2nd Statistical and Data Management Approaches for Biotechnology Drug Development


Date:29-30 September, 2015

Venue: US Pharmacopeia Conference Center, Rockville, Maryland

Co-sponsored by: IABS anad FDA


Scope and objective:

This meeting is to bring together regulators, scientists, academia and industry to help resolve existing challenges in ensuring the quality of biotechnology medicinal products and to bring high quality medicines to patients. Guidance on how to use statistics for a variety of activities required during biotechnology product development such as method development, improvement and replacement, product comparability, biosimilarity exercises and stability program development. In addition, the complexity of the types of data and the volume being analysed is ever increasing and how best to manage such data will be discussed. The meeting will bring the right experts together to discuss the issues and through roundtables attempt to reach conclusions that will be valuable globally to public health.


Among the challenges that will be explored :

  • Statistical Challenges with showing Comparability and Biosimilarity (Equivalence, small data sets, tolerance intervals etc.)
  • Using statistics for Assay Methods (Statistics for development, qualification, validation and transfer of methods)
  • The use of statistics and modelling when using Quality by Design (DoE, Bayesian, partial least squares, prior knowledge data sets)
  • Managing large and/or complex data sets (Large data sets for monitoring variation, complex analytical methods – Mass Spec, NMR, historical data sets)


View the Draft Agenda

Register here

12-13 November, 2015, Rockville, Maryland PDF Print



2nd Progress and Challenges in Protein Particles and Immunogenicity of Biotherapeutics 2015: Filling in the Gaps in Risk Evaluation and Mitigation


Date: 12-13 November, 2015

Venue: US Pharmacopeia Conference Cente, Rockville, Maryland

Co-sponsored by: IABS and Health Canada


Scope and objective:

The efficacy of therapeutic proteins can be compromised by patients' immune response to the proteins, resulting in antibody-mediated alteration of the proteins' activity or bioavailability. It is well established that highly repetitive motifs, such as those that would occur in large protein aggregates in therapeutic protein products, can enhance immunogenicity and can be produced during the pharmaceutical manufacturing process. While particles greater than 10 µm in size are monitored by light obstruction test in combination with the visible appearance test, the presence of sub visible particles (0.1-10 µm), large assemblies containing thousands to millions of protein molecules, in therapeutic protein products is not routinely monitored or controlled.

In 2009, IABS and FDA cosponsored a conference which focused on

a) The mechanism of protein folding

b) The characteristics of sub visible and visible protein particles that may influence immunogenicity including the size, type (reversible, protein class), composition, amount, and conformational status);

c) The risks associated with the propensity to generate immune responses including the route of administration, dose, and frequency, duration of administration and indication;

d) The factors that influence the formation of large protein aggregates and methods to reduce protein aggregation (approaches in formulation, and protein design) including case studies of occurrence of these particulates in manufacturing;

e) Analytical methods that are useful in quantifying these particles and approaches to the design of suitable control strategies that mitigate the risk to product quality.

One key outcome of that meeting was the realization that further study was required to improve our knowledge of how sub visible protein particles form, how they are accurately quantitated and characterized, and how they evolve over the shelf life of the drug product. There was consensus that standardization of quantitation technology was needed. While there was evidence that some types of particles might relate to immunogenicity, there were also clear gaps in understanding how this happened and whether this applied to all types of protein particles in all biotherapeutics. It was also unclear how this information related to developing a control strategy for each product during development.

It is now better understood that virtually all protein drug products possess some level of sub visible particles. IABS will cosponsor another meeting on 12-13November 2015 at the USP, Rockville, Maryland, USA to revisit these topics in light of what has been learned in the past 6 years. Progress in understanding the science of protein particle formation, the evolution of the analytical technologies for characterization and measurement of sub-visible protein particles, the advances in standardization of protein particle measurements, and their possible relationship of protein particle attributes to safety and efficacy of biotherapeutics will be highlighted. The goal of the meeting is to assess the progress of the past half-decade, and its implications for risk management during biotherapeutic product development.


IABS launches its European affiliate: IABS-EU

This is a landmark event in the history of IABS and will open the way for greater participation with EU partners in scientific activities. The objective of the Association IABS-EU is to support the mission and projects of the International Alliance for Biological Standardization and to enhance its image and develop its outreach within the European Union. The Association will contribute to scientific and medical advancement of biologicals, by facilitating communication among those who develop, produce and regulate biological products for human and animal health. More specifically, it will focus on issues concerning the regulation and standardization of biological products that are intended for market use.


A unique feature of IABS is that it acts as a neutral meeting point for the major stakeholders - regulators, academia, and industry- to consider the impact of regulatory requirements on innovation, with the objective of identifying sections that may require modification.


IABS-EU is officially recognized by French authorities as a nonprofit organization.


You will be hearing more about IABS-EU in the months ahead.


Founding Members :

Read more:


A few words from the President


As we start the new year, I’d like to review our 2014 accomplishments and hi-lite what we have planned for 2015.

Read more


Veterinary Scientific Committee

Read more about Alternatives to Antibiotics, Challenges and Solutions in Animal Production

Read more

IABS has signed an MoU with the following organizations:

Fondation Mérieux

Brighton Collaboration


Who's Online

We have 124 guests online
International Alliance for Biological Standardization, Coordinated by Dodet Bioscience