Evidence that Contamination (Adventitious Agents) ARE Being Taken Seriously

[JT1024]

I posted this on another thread but felt it deserved attention on it's own. The full Agenda to this meeting held last fall is attached.

PDA/FDA Adventitious Agents and Novel Cell Substrates: Emerging Technologies and New Challenges

November 2-4, 2011
Hilton Hotel | Rockville, Maryland
Program Agenda

Wednesday, November 2, 2011

Welcome and Opening Remarks
Arifa Khan, PhD, Senior Investigator, CBER, FDA

Plenary Session 1: Opening Keynote Presentation
Moderator: Arifa Khan, PhD, Senior Investigator, CBER, FDA

Based on past experience, this talk will present potential safety concerns associated with the use of biological raw materials, including cell substrates, and also focus on risk assessment for adventitious agents in biologicals.

Plenary Session 2: Adventitious Agent Testing and Emerging Methods Part I

This session will begin with an overview of the current assays that are used for virus detection with an emphasis on their benefits and limitations, and describe how those limitations have generated a need for new technologies. This will be followed by a broad talk on one of the new technologies, Next-Gen sequencing, in which the principles behind the technology and the various platforms available will be described.

Risks Associated with Retroelements: Lessons from Mammalian Systems
Jonathan Stoye, PhD, Head of the Division of Virology, MRC National Institute for Medical Research

Plenary Session 12: Adventitious Agents and Raw Materials Part I
Moderators: Zenobia Taraporewala, PhD, CMC Reviewer, CBER, FDA and Mark Plavsic, PhD, Senior Director and Corporate
Biosafety Advisor, Genzyme a Sanofi Company

As long as therapeutics and vaccines are produced in biological systems, there is the risk of product contamination by adventitious agents, mainly through the use of raw materials of animal or non-animal origin in the manufacturing processes. Manufacturers control for this risk by careful raw material selection, vendor qualification, raw material and cell bank testing, and raw material risk assessments. However, recent incidents with the detection of adventitious agents in commercial products have highlighted the practical hurdles manufacturers face with the detection and identification of adventitious agents in raw materials due to low level contamination, lot-to-lot variation, limited sampling, assay sensitivity, and sample ‘matrix’ effect. This session will discuss safety issues associated with the use of animal and certain non-animal derived raw materials, and ways to mitigate the risk of contaminationby adventitious agents. In the session, speakers will address challenges in adventitious agent screening/testing and reduction strategies for raw materials used in banking and batch production

 

[JT1024]

Another example is the MIT Consortium described below:

Powerpoint presentation here: http://www.slideshare.net/mewiebe/pda-annual-mtg-2012-caacb-talk

From the powerpoint:
Virus Contaminations: Company’s Have Learned Primarily From Their Contamination Event(s)
●Many companies have not publically disclosed virus contamination events
●No obligation to disclose unless the contamination results in a “material change” to the business
●Motivated by concerns for negative publicity.
●This is well known in the industry.
●Some companies do not notify regulatory authorities
●Companies that have disclosed rarely describe the event in sufficient detail to be of significant value
●Companies are only really able to learn from their own contamination events.


MIT link here: http://cbi.mit.edu/research-overview/caacb/
The Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB)

Safe and Reliable Manufacture of Biotherapeutics

One challenge in the safe and reliable production of biopharmaceuticals is mitigating the risk of cell culture contamination by adventitious agents such as viruses or mycoplasma. Currently, industrial knowledge about contaminating adventitious agents and successful approaches to combat these specific agents is largely limited to each company’s individual experience. As such, a central database of accumulated industry knowledge and experience does not exist. The collection, analysis and dissemination of the full body of industry experience would enhance the reliable manufacture and supply of such safe and effective medications.
Purpose and Outcome of the CAACB

The MIT CBI, along with several founding member companies, has launched the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB). The goals of the consortium are: the confidential collection and analysis of industry adventitious agent contamination data; and the dissemination of the most effective industry practices used to combat contaminations during the reliable manufacture of life-saving biotherapeutic medications. MIT is an ideal venue to host this initiative due to MIT’s existing track record with industrial collaborations and its strong faculty experience in solving complex systems engineering problems.
A comprehensive analysis of adventitious agent contamination data will be highly valuable as an industry “lessons learned” exercise. Such information should inform the industry on the best practices to mitigate the risks that lead to adventitious agent contamination. Specifically, the CAACB seeks to develop a comprehensive understanding of adventitious agents encountered, the source of such agents, and a risk-based analysis of the most effective barriers to contamination. The collection, analysis and dissemination of this information should enhance the uninterrupted supply of vital, safe and effective biotherapeutic medications. This is a goal shared by both the biopharmaceutical manufacturing industry and the CAACB as we strive to combat disease.

Consortium Members and Collaborators (*Consortium Members)

Aetna
Alnylam Pharmaceuticals*
Amgen*
Baxter*
Biogen Idec*
BioMarin*
Boehringer Ingelheim*
Bristol-Myers Squibb*
Brookings Institution
Cntrs. for Disease Cont. and Prev. (CDC)
Dana Farber Cancer Institute
EMD Millipore*
Eur. Medicines Agency (EMA) Merrimack Pharmaceuticals
Genentech*
Genzyme*
Georgetown University
Health Canada
Health Sci. Authority of Singapore (HSA)
Inno Biologics Sdn. Bhd.*
Johnson & Johnson*
KEW Group
Life Technologies*
Massachusetts General Hospital
MedImmune*
Memorial Sloan-Kettering
Merial*
Merrimack Pharmaceuticals*
Metabolix*
Millennium Pharmaceuticals*
National Institutes of Health (NIH)
Natl. Inst. of Standards & Technology (NIST)
NICE
Novartis Pharma AG*
Novartis Vaccines & Diagnostics
Pfizer*
Quintiles*
sanofi*
sanofi pasteur*
Shire*
University of Prince Edward Island
US Food & Drug Association (FDA)

Project Stage/Target Completion
Develop data collection instrument, questionnaire, and process/Complete
Raw data collection from participating members & partners/In Progress
Anonymous data pooling, annotated and collated/2012
Preliminary report to member companies/2012
Analysis of processed data; Interpretation from CAACB forum (MIT Team & Industry Member Companies)/2012
Full research report to member companies; to include all methods, data analyses, findings, recommendations/2013
Publication of Research Summary Report: Major findings & recommendations/2013+
Continuous Updates & Expansion of Data: Collection & Analysis/2013+

 

[JT1024]

http://www.ibclifesciences.com/ViralSafety/agenda.xml

IBC's 9th Annual Viral Safety for Biologicals
Strategies, Technologies and Regulatory Perspectives for Detection, Prevention and Remediation in Upstream, Downstream and Manufacturing Operations

February 27 - 28, 2012 · Hilton San Diego Bayfront Hotel · San Diego, CA

Integrated Strategies for the Risk Mitigation of Adventitious Virus ContaminationAdventitious viral contamination is a high impact risk to any biopharmaceutical organization that produces products from mammalian cell lines. Although the biotech industry has an excellent viral safety record in supplying patients with recombinant protein products, rare events of viral contamination have caused severe impact to the companies on product supply, production facility downtime and significant business loss. This presentation discusses a proactive risk management strategy integrated throughout an entire organization from research and development to production operations with examples of associated opportunities and challenges.Yuling Li, Ph.D., Fellow, Process Biochemistry, Biopharmaceutical Development, MedImmune

Risk-Based Measures for Adventitious Agents in Developing Viral VaccinesRoya Ravanbakhsh, Director, Quality Assurance, PaxVax, Inc.

Regulatory Perspective

Ensuring Safety of Viral Vaccines - A Regulatory Perspective

Santosh Nanda, Ph.D., Microbiologist/Primary Reviewer, Division of Vaccines and Related Products Applications, Office of Vaccine Research and Review, CBER, US FDA

Methods for the Identification and Reduction of Adventitious Agent Risks in Raw Materials for Live Virus Vaccine Manufacturing

Adventitious agents in vaccine and biological products have been an area of concern to regulatory agencies, manufacturers, and public health officials since the issue first arose in the early 1900s.

While vaccines and the raw materials used during vaccine production are manufactured and tested in compliance with current regulations; quality control tests are broad, non-specific, and may not be capable of detecting novel or emerging adventitious agents.



The possibility of adventitious agent contaminations of licensed products has recently been brought to light through the use of new analytical technologies. Such non-biased, highly sensitive technologies have been able to detect adventitious agent contaminations where conventional methods have failed to detect them. In response to these events, vaccine manufacturers have had to re-evaluate adventitious agent risks in their manufacturing processes.

Legacy live virus vaccine processes are dependent on animal derived raw materials; removing animal derived raw materials from these processes, if possible, can take >10 years to realize. As such, Merck & Co. has developed a systematic approach to evaluate adventitious agent risks associated with the use of animal derived raw materials in live virus vaccine manufacturing. This approach includes the combination of FMEA and the development of a novel raw material screening program to identify adventitious agent risks in animal derived raw materials. Potential strategies for remediating the identified adventitious agent risks are also presented.

Tara Tagmyer, Ph.D., Process Scientist, Vaccine Manufacturing Sciences & Commercialization, Merck & Co.

 

[natasa778]

Not sure if this has been posted before, one of the authors/presenters above is leading the FDA programme ...



Investigating Viruses in Cells Used to Make Vaccines; and Evaluating the Potential Threat Posed by Transmission of Viruses to Humans


The emergence of pathogenic virus infections like influenza and HIV have created an urgent need for new vaccines.

Virus-based vaccines are made in living cells (cell substrates). Some manufacturers are investigating the use of new cell lines to make vaccines. The continual growth of cell lines ensures that there is a consistent supply of the same cells that can yield high quantities of the vaccine.

In some cases the cell lines that are used might be tumorigenic, that is, they form tumors when injected into rodents. Some of these tumor-forming cell lines may contain cancer-causing viruses that are not actively reproducing. Such viruses are hard to detect using standard methods. These latent, or "quiet," viruses pose a potential threat, since they might become active under vaccine manufacturing conditions. Therefore, to ensure the safety of vaccines, our laboratory is investigating ways to activate latent viruses in cell lines and to detect the activated viruses, as well as other unknown viruses, using new technologies. We will then adapt our findings to detect viruses in the same types of cell substrates that are used to produce vaccines. We are also trying to identify specific biological processes that reflect virus activity.

These methods will enable FDA scientists to help manufacturers to determine whether their specific cell substrate is safe to use for vaccine production. The methods our laboratory are developing and testing will help to ensure the production of safe and effective vaccines in two ways: 1) FDA will be able to develop testing guidelines for manufacturers who use new cell substrates for producing vaccines; and 2) FDA will publish the new methods it develops in peer-reviewed scientific journals, thus making them readily accessible to all manufacturers.

We are also evaluating the risk of retrovirus infections in humans. ... http://www.fda.gov/biologicsbloodvaccines/scienceresearch/biologicsresearchareas/ucm127327.htm

 

[currer]

Good posts JT1034 and Nastasa.

Just co-incidence I suppose with the "XMRV" saga being publicly wound up that all this is going on on the quiet.
Very timely.

None of the adventitious agents they are concerned about are likely to be "XMRV" But thats OK because we know we dont need to worry about XMRV any more.