Estimating the Uncertainty of Structured Pharmaceutical Development and Manufacturing Process Execution Risks Using a Prospective Causal Risk Model (PCRM)
by Mark F. Witcher
Volume 18, Open Access (Sep 2019)
While many risk analysis methods describe how execution or performance risks originate and propagate through pharmaceutical and biopharmaceutical manufacturing processes and systems, few provide methods for efficiently estimating the uncertainty of an execution risk’s occurrence. This article describes prospective causal risk modeling (PCRM) for estimating the risk’s uncertainty of failures associated with executing processes, particularly when little process performance information or data is available. Building upon a basic unit of risk, the process-based system risk structure (SRS) approach is combined with PCRM to provide a method of carrying out quality risk management (QRM) exercises that properly assess both the severity and uncertainty of process execution risks. After the risks are structured using an SRS, PCRM provides a straightforward and effective method for using subjective human judgement and thought experiments to evaluate the risk process’s causal mechanisms for analyzing, evaluating, and controlling the uncertainty, including its likelihood of occurrence, of significant risks associated with developing and manufacturing pharmaceuticals. Using an SRS/PCRM-based QRM exercise, a wide variety of process execution risks can be efficiently evaluated and accepted or rejected so that important risks requiring mitigation can be identified for additional evaluation, control, and eventual acceptance.
Citation:
Witcher M. Estimating the uncertainty of structured pharmaceutical development and manufacturing process execution risks using a prospective causal risk model (pcrm). BioProcess J, 2019; 18. https://doi.org/10.12665/J18OA.Witcher
Posted online Sep 18, 2019.
Fetal Bovine Serum – Country of Origin, Geographic Relevance, and Labeling
by Percy W. Hawkes, Ole Bødtker Nielsen, and Marc Wintgens
Volume 18, Open Access (Aug 2019)
With an ever-increasing number of countries involved in the collection, processing and marketing of serum, it is necessary to understand the relevance and rules relating to geographic region of origin. This article reviews and discusses the safety and quality of FBS, rules of origin, consumer market-motivated misinformation, and how mislabeled serum can be detected. The article concludes that high-quality serum needed for scientific research and biopharmaceutical products can originate from any country, as long as it is collected, imported, and processed following all the applicable regulatory and industry requirements...
Citation:
Hawkes P, Nielsen OB, Wintgens M. Fetal bovine serum – country of origin, geographic relevance, and labeling. BioProcess J, 2019; 18. https://doi.org/10.12665/J18OA.Hawkes.0819
Posted online Aug 28, 2019.
Fetal Bovine Serum – Geographical Origin and International Trade
by Jennifer A. Murray and Rosemary J. Versteegen
Volume 18, Open Access (Aug 2019)
It is a common belief that fetal bovine serum (FBS) collected from certain geographical regions, such as New Zealand, is of superior quality to material collected from South America. Whilst it is true that origin does have an impact on the price of serum, it does not affect the quality or biological performance of the product. FBS collected under similar conditions from any geographical region will demonstrate comparable ability to support cell growth. For FBS, the term “quality” is frequently confused with “health status.” It is the health status of the geographical region from which the serum is collected that will dictate its potential use, the availability of material for import, and eventually, the price. It should be noted that health status should be considered a result of more than just the geographical source of the material, but also the regulatory infrastructure and how well regulations are enforced by the countries within that region...
Citation:
Murray JA, Versteegen RJ. Fetal bovine serum – geographical origin and international trade. BioProcess J, 2019; 18. https://doi.org/10.12665/J18OA.Murray
Posted online Aug 28, 2019.
Testing for Geographic Origin of Fetal Bovine Serum
by Rosemary Versteegen, PhD, Olya Shatova, PhD, Sam Lind, PhD, and Kate Linterman
Volume 18, Open Access (May 2019)
Since its inception in 2006, the International Serum Industry Association (ISIA) has been focused on providing a more informative characterization standard for animal sera. A fundamental aspect of this effort has been the development of a program focused on product traceability from abattoir to end-user. This goal has been achieved in part by implementing the ISIA-sponsored audit program. Serum vendors determined to be compliant with all audit requirements are awarded ISIA Traceability Certifications. In conjunction with Oritain Global Ltd, ISIA has developed and implemented a method for establishing geographical origin of serum products. The method and its capability of determining geographical origin are described in this paper...
Citation:
Versteegen R, Shatova O, Lind S, Linterman K. Testing for geographic origin of fetal bovine serum. BioProcess J, 2019; 18. https://doi.org/10.12665/J18OA.Versteegen
Posted online May 15, 2019.
Gamma Irradiation of Animal Serum: General Regulatory Environment and Process Controls
by Greg Hanson, Bart Croonenborghs, Mara Senescu, Huw Hughes, Raymond Nims, and Rosemary Versteegen
Volume 18, Open Access (February 2019)
This is the sixth and last in a series of articles describing and demystifying the processes involved in the gamma irradiation of serum. This serum treatment is intended to mitigate the risk of introducing adventitious contaminants into cell cultures. In this article, we discuss the regulatory environment under which gamma irradiation of serum is performed, and provide additional details on best practices for documentation of the irradiation process, selection of the contract irradiator, evaluation of risk versus benefit needed to arrive at the radiation dose range to be used, as well as an understanding of the level of remaining risk following irradiation at that dose range. Gamma irradiation should not be viewed as a means of totally eliminating risk, but rather as a means of reducing the risk of introducing adventitious agents into cell cultures. A balance must be achieved between the desire to eliminate all adventitious contaminants, and the need to retain the desired performance characteristics of the serum, once irradiated...
Citation:
Hanson G, Croonenborghs B, Senescu M, Hughes H, Nims R, Versteegen R. Gamma irradiation of animal serum: general regulatory environment and process controls. BioProcess J, 2019; 18. https://doi.org/10.12665/J18OA.Hanson
Posted online February 11, 2019.
Evaluation of a Single-Use Benchtop Process Development System to Optimize Cell Growth and Scale-Up of Veterinary Vaccine Production
by Lídia Garcia, Mercedes Mouriño, Alicia Urniza, and Sandra Juanola
Volume 18, Open Access (February 2019)
In the past 20 years, mammalian cell lines have been utilized to produce many viral veterinary vaccines. Cell lines such as baby hamster kidney (BHK)-21, Vero, and Madin Darby canine kidney (MDCK) are widely used because they help facilitate shorter manufacturing lead times and tighter process controls. As compared to other biotech products, viral vaccine manufacturing processes present some specific constraints linked to the cell substrates used. With the global veterinary vaccine market value predicted to be almost $7 billion per year by 2021[2], to remain competitively priced as well as profitable, bioprocess scientists are under pressure to develop methods for faster and more cost-efficient cell culture production. This has led to a shift from the use of expensive, two-dimensional T-flask and roller bottles to single-use, stirred tank bioreactors with microcarriers, or the adaptation of attachment-dependent cell lines such as BHK-21 for suspension culture. This requires time-consuming optimization and scale-up development experiments, which are real drawbacks. However, utilizing automated, single-use mini bioreactors as a scale-down model can enable more efficient use of time and optimization of media, feed, and culture conditions to de-risk upstream process development. In this article, single-use, mini bioreactors are evaluated to determine if they are geometrically comparable to benchtop bioreactors (both glass and single-use vessels) and pilot-scale, single-use bioreactors for effectively modelling mammalian cell culture at 2 L and 50 L scale...
Citation:
Garcia L, Mouriño M, Urniza A, Juanola S. Evaluation of a single-use benchtop process development system to optimize cell growth and scale-up of veterinary vaccine production. BioProcess J, 2019; 18. https://doi.org/10.12665/J18OA.Garcia
Posted online February 11, 2019.
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