The plasma fractionation industry has undergone significant consolidation in recent years through mergers and acquisitions. Major pharmaceutical companies have exited the industry, while dedicated plasma companies like CSL have increased their market share through acquisitions. The industry faces rising plasma and production costs and falling prices for major products like IVIG. There remains potential to develop new plasma-derived products and improve yields from existing fractionation processes to generate more revenue per liter of plasma. New separation technologies may enable more efficient fractionation beyond the standard Cohn process.
most controversial topic in the field of transfusion medicine, most of the transfusions worldwide are associated with the deleterious effects of immunomodulation, simplified for PG students with latest article support
most controversial topic in the field of transfusion medicine, most of the transfusions worldwide are associated with the deleterious effects of immunomodulation, simplified for PG students with latest article support
Curso Canto Gregoriano - Gregorian Chant tutorial in portugueseAltair Costa
Curso de canto gregoriano em Power Point, versão em inglês e tradução para o português.
Não sei quem é o autor deste curso que encontrei na Internet.
I don`t know the author.
Visite minha página página de canto gregoriano / Visit my gregorian site: www.gregoriano.org.br
Curso Canto Gregoriano - Tutorial In Gregorian ChantAltair Costa
Curso de Canto Gregoriano - Gregorian Chant course.
Não conheço o autor / I don`t know who is the author.
Veja a minha página sobre canto gregoriano / see gregorian chant site: www.gregoriano.org.br
Música: Alleluia, lapis revolutus est cantada pelo Coral Gregorian de Belo Horizonte, onde canto.
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LF Energy Webinar: Electrical Grid Modelling and Simulation Through PowSyBl -...DanBrown980551
Do you want to learn how to model and simulate an electrical network from scratch in under an hour?
Then welcome to this PowSyBl workshop, hosted by Rte, the French Transmission System Operator (TSO)!
During the webinar, you will discover the PowSyBl ecosystem as well as handle and study an electrical network through an interactive Python notebook.
PowSyBl is an open source project hosted by LF Energy, which offers a comprehensive set of features for electrical grid modelling and simulation. Among other advanced features, PowSyBl provides:
- A fully editable and extendable library for grid component modelling;
- Visualization tools to display your network;
- Grid simulation tools, such as power flows, security analyses (with or without remedial actions) and sensitivity analyses;
The framework is mostly written in Java, with a Python binding so that Python developers can access PowSyBl functionalities as well.
What you will learn during the webinar:
- For beginners: discover PowSyBl's functionalities through a quick general presentation and the notebook, without needing any expert coding skills;
- For advanced developers: master the skills to efficiently apply PowSyBl functionalities to your real-world scenarios.
Smart TV Buyer Insights Survey 2024 by 91mobiles.pdf91mobiles
91mobiles recently conducted a Smart TV Buyer Insights Survey in which we asked over 3,000 respondents about the TV they own, aspects they look at on a new TV, and their TV buying preferences.
Accelerate your Kubernetes clusters with Varnish CachingThijs Feryn
A presentation about the usage and availability of Varnish on Kubernetes. This talk explores the capabilities of Varnish caching and shows how to use the Varnish Helm chart to deploy it to Kubernetes.
This presentation was delivered at K8SUG Singapore. See https://feryn.eu/presentations/accelerate-your-kubernetes-clusters-with-varnish-caching-k8sug-singapore-28-2024 for more details.
Epistemic Interaction - tuning interfaces to provide information for AI supportAlan Dix
Paper presented at SYNERGY workshop at AVI 2024, Genoa, Italy. 3rd June 2024
https://alandix.com/academic/papers/synergy2024-epistemic/
As machine learning integrates deeper into human-computer interactions, the concept of epistemic interaction emerges, aiming to refine these interactions to enhance system adaptability. This approach encourages minor, intentional adjustments in user behaviour to enrich the data available for system learning. This paper introduces epistemic interaction within the context of human-system communication, illustrating how deliberate interaction design can improve system understanding and adaptation. Through concrete examples, we demonstrate the potential of epistemic interaction to significantly advance human-computer interaction by leveraging intuitive human communication strategies to inform system design and functionality, offering a novel pathway for enriching user-system engagements.
UiPath Test Automation using UiPath Test Suite series, part 3DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 3. In this session, we will cover desktop automation along with UI automation.
Topics covered:
UI automation Introduction,
UI automation Sample
Desktop automation flow
Pradeep Chinnala, Senior Consultant Automation Developer @WonderBotz and UiPath MVP
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
Le nuove frontiere dell'AI nell'RPA con UiPath Autopilot™UiPathCommunity
In questo evento online gratuito, organizzato dalla Community Italiana di UiPath, potrai esplorare le nuove funzionalità di Autopilot, il tool che integra l'Intelligenza Artificiale nei processi di sviluppo e utilizzo delle Automazioni.
📕 Vedremo insieme alcuni esempi dell'utilizzo di Autopilot in diversi tool della Suite UiPath:
Autopilot per Studio Web
Autopilot per Studio
Autopilot per Apps
Clipboard AI
GenAI applicata alla Document Understanding
👨🏫👨💻 Speakers:
Stefano Negro, UiPath MVPx3, RPA Tech Lead @ BSP Consultant
Flavio Martinelli, UiPath MVP 2023, Technical Account Manager @UiPath
Andrei Tasca, RPA Solutions Team Lead @NTT Data
The Art of the Pitch: WordPress Relationships and SalesLaura Byrne
Clients don’t know what they don’t know. What web solutions are right for them? How does WordPress come into the picture? How do you make sure you understand scope and timeline? What do you do if sometime changes?
All these questions and more will be explored as we talk about matching clients’ needs with what your agency offers without pulling teeth or pulling your hair out. Practical tips, and strategies for successful relationship building that leads to closing the deal.
PHP Frameworks: I want to break free (IPC Berlin 2024)Ralf Eggert
In this presentation, we examine the challenges and limitations of relying too heavily on PHP frameworks in web development. We discuss the history of PHP and its frameworks to understand how this dependence has evolved. The focus will be on providing concrete tips and strategies to reduce reliance on these frameworks, based on real-world examples and practical considerations. The goal is to equip developers with the skills and knowledge to create more flexible and future-proof web applications. We'll explore the importance of maintaining autonomy in a rapidly changing tech landscape and how to make informed decisions in PHP development.
This talk is aimed at encouraging a more independent approach to using PHP frameworks, moving towards a more flexible and future-proof approach to PHP development.
SAP Sapphire 2024 - ASUG301 building better apps with SAP Fiori.pdfPeter Spielvogel
Building better applications for business users with SAP Fiori.
• What is SAP Fiori and why it matters to you
• How a better user experience drives measurable business benefits
• How to get started with SAP Fiori today
• How SAP Fiori elements accelerates application development
• How SAP Build Code includes SAP Fiori tools and other generative artificial intelligence capabilities
• How SAP Fiori paves the way for using AI in SAP apps
UiPath Test Automation using UiPath Test Suite series, part 4DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 4. In this session, we will cover Test Manager overview along with SAP heatmap.
The UiPath Test Manager overview with SAP heatmap webinar offers a concise yet comprehensive exploration of the role of a Test Manager within SAP environments, coupled with the utilization of heatmaps for effective testing strategies.
Participants will gain insights into the responsibilities, challenges, and best practices associated with test management in SAP projects. Additionally, the webinar delves into the significance of heatmaps as a visual aid for identifying testing priorities, areas of risk, and resource allocation within SAP landscapes. Through this session, attendees can expect to enhance their understanding of test management principles while learning practical approaches to optimize testing processes in SAP environments using heatmap visualization techniques
What will you get from this session?
1. Insights into SAP testing best practices
2. Heatmap utilization for testing
3. Optimization of testing processes
4. Demo
Topics covered:
Execution from the test manager
Orchestrator execution result
Defect reporting
SAP heatmap example with demo
Speaker:
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
UiPath Test Automation using UiPath Test Suite series, part 4
Plasma fractionation industry
1. FOCUS ON... BUSINESS
The Plasma
Fractionation Industry
New Opportunities To Move Forward?
John Curling and Christopher Bryant
S
hortly after the turn of
the millennium, Australian
fractionator CSL Ltd.
acquired the Swiss plasma
plant at ZLB, Bern (Central
Laboratory of the Swiss Red Cross
Blood Transfusion Service). Two
years later, the US plasma
fractionation industry entered the
year 2003 with an announcement
that the proposed merger between
Aventis Behring and Bayer’s plasma
operations would not happen. In
August 2004, soon after CSL
completed its acquisition of Aventis
Behring, the newswires buzzed with
speculation over Bayer’s long-
awaited divestment of its plasma
business in Clayton, NC. On 14
December 2004, Cerberus and
Ampersand agreed to acquire that
ANTHONY HERNANDEZ (WWW.ISTOCKPHOTO.COM) Bayer unit.
Such movements seem
COHN FRACTIONATION commonplace in an industry
sector that has endured consent-
The development of methods for plasma protein fractionation was driven by decrees, battled with product
a need for human albumin in World War II and the requirement to isolate shortages of both plasma-derived
diphtheria and tetanus antibodies from horse serum. and recombinant products, faced
E. J. Cohn and his many coworkers published their landmark paper describing dramatic drops in product pricing,
ethanol fractionation in 1946 (1). Their paper was 43rd in a series entitled and all but lost a market for
Studies on Plasma Proteins from Harvard Medical School. The first use of albumin. Raw material (plasma)
ethanol fractionated albumin was to treat casualties at Pearl Harbor in 1941. costs have risen significantly, and
The fractionation industry is now driven by the demand for IgG to treat processing costs rise with each
immune deficiencies and recombinant as well as plasma-derived Factor VIII incremental addition of safety
for hemophiliacs. Nonetheless, the industry standard backbone is still “Cohn measures such as inventory hold
fractionation” with chromatography and membrane technologies, integrated
with viral inactivation, dominating side-stream fractionation. and plasma pool testing.
However, CSL Ltd (www.csl.
REFERENCE com), now the holding company for
1 Cohn EJ, et al. Preparation and Properties of Serum and Plasma Proteins, IV: A System ZLB Behring and the world’s largest
for the Separation into Fractions of the Protein and Lipoprotein Components of Biological
Tissues and Fluids. J. Am. Chem. Soc. 62, 1946: 459–475. fractionator with a 25% market share
18 BioProcess International MARCH 2005
2. (with operations in Switzerland, PLASMA INDUSTRY CHANGES 2003 AND 2004
Germany, and the United States),
reported net profit after tax of 13% 2003
on revenues of US$1.65 billion for Bayer and Aventis halt plans for a merger of their plasma products
the past financial year, ending 30 businesses.
June 2004. Importantly, CSL’s cash
flow increased significantly, and R&D CSL announces preliminary negotiations with Aventis concerning the
expenditure was up 11% to over acquisition of Aventis Behring.
US$100 million. As another
important industry indicator, Baxter announces plans to close 26 of its 120 plasma collection centers in
approval of new plasma products the United States as well a 700,000-L plant in Michigan. Plasma collected
indicates no lack of innovation. New, and fractionated will drop from 4.6 million liters to 4 million liters, and
higher yielding side-stream processes 800 jobs will be eliminated.
also indicate innovation within limits,
Probitas Pharma completes acquisition of assets of Alpha Therapeutic from
intended or not, frequently set by
Mitsubishi Pharma.
regulatory authorities.
Octapharma completes acquisition of Mexican fractionator Probifasa SA
INDUSTRY CONSOLIDATION de CV.
Major structural changes of the
North American–European plasma Aventis Bio-Services sells 21 of its 80 plasma collection centers to
fractionation axis are shown in the International Bioresources.
“Plasma Industry Changes 2003
and 2004” box. Clearly, major Bayer initiates divestment of the plasma operations of its Biological
chemical-pharmaceutical companies Products Division. Plasma product sales were €679 in 2002. Bayer
are seeking to exit the business, employs 1350 people at its Clayton, NC, facility.
whereas dedicated plasma companies
such as CSL Ltd., which continues CSL and Aventis sign a definitive agreement, creating a new entity, ZLB
to divest non-core business, and Behring, for US$925 million. Aventis Behring generated €1.068 billion in
Probitas Pharma (Grifols) are eager sales in 2002 and employs 5800 people worldwide.
to consolidate and strengthen their
2004
positions. Increasingly, raw material
Baxter further reduces fractionation capacity by around 13% (400,000 L
(plasma) follows the laws of
annually and closure of further collection centers).
commodity markets as we witness
the acquisitions and divestments ZLB Behring, formerly Aventis Behring, closes 35 collection centers,
of collection centers across the reducing collection volume by one million liters and leaving 65 centers
United States. in operation. Plasma throughput at the Kankakee, MI, facility will be
Past and current chairs of the reduced, the Vienna plant closed, and production transferred to Marburg,
Plasma Protein Therapeutics Germany. ZLB Bioplasma’s facility will implement improved use, and the
Association (PPTA, www. combined capacity of CSL’s facilities will be reduced from 4.2 million to
plasmatherapeutics.org) have 3.1 million liters. CSL expects to save US$100 million in operating costs.
successfully differentiated the plasma
industry from the pharmaceutical Probitas Pharma is forced to suspend its IPO because of weak investor
industry. For example, raw material demand. The company expects to double its sales from US$1.26 billion
costs account for around 45% of the in 2003 over five years, achieving a 10% global market share.
units on an income statement in the
plasma industry compared with 5% Bayer’s short list of bidders for its plasma fractionation business includes
in the pharmaceutical industry (1). investment firms Bain Capital and Carlyle Group. Cerberus is also
Quality plasma costs have risen 40% bidding, and the American Red Cross is reported to have an interest. On
over the past seven years, and 14 December, Cerberus Capital and Ampersand Ventures agreed to buy
nucleic-acid testing alone adds the business for over US$590 million. The new company thus created,
US$5–15 per liter of plasma (2). NPS Biotherapeutics, Inc., will also incorporate Precision Pharma. Bayer’s
Although recalls and withdrawals plasma products generated sales of US$739 million with a pretax loss of
have declined dramatically, inventory US$426 million in 2003. Sales in FY2004 were €481 million.
hold costs the industry another
US$33 million per year (2). The Finnish Red Cross, which decided to discontinue fractionation in
In his 2004 analysis of the 2003, enters an agreement with Sanquin for the manufacture and supply
industry, the PPTA Chair Peter of plasma products for Finland’s market. Intermediates will be produced
Turner notes that “US and in the Belgian Red Cross fractionation facility and finished products
European demand for IVIG processed in Amsterdam.
MARCH 2005 BioProcess International 19
3. [intravenous immunoglobulin] Table 1: New, US, normal plasma and equivalent recombinant product approvals (BLA)
in 2002–2004
has been met, and prices have
Manufacturer Claimed Benefit/
fallen 20–25% in two years, the price Product Approval Date Indication Improvement
of albumin has halved in three years, Aralast Alpha Therapeutic API deficiency and First alternative to
substitution of recombinant Factor Alpha-1 Proteinase (now Baxter) evidence of Prolastin; patient choice
VIII for plasma-derived product Inhibitor (API) 23 December 2002 emphysema
continues, and there is greater access
to alpha1-protease inhibitor” (3). Crosseal Omrix Hemostasis in Ease of preparation and
In this climate, industry Fibrin Sealant (Distr.: American patients use
Red Cross undergoing liver
consolidation and realignment are 21 March 2003 surgery
understandable, but widely disparate
access to plasma protein therapies Zemaira Aventis Behring API deficiency and Purity (90%), safety,
Alpha-1- 8 July 2003 evidence of efficacy, convenience;
remains unaddressed across the Proteinase emphysema 15 min. infusion time
globe. Among the PPTA models Inhibitor (API) (cf 30 mins for other
for the future (3) are a products)
• Broad portfolio of high Advate Baxter Healthcare Hemophilia A Recombinant, no plasma
yielding products rFactor 25 July 2003 products used in MAb
• Global plasma reach selling VIII Plasma/ production or as
three–four products/liter of plasma Albumin Free additives; no prion risk;
• Efficient scale and competitive Method tolerability, hemostatic
efficacy; low inhibitor
cost structure. rate; easy to use
MORE PRODUCTS Gamunex Bayer Primary immune Unprecedented primary
IVIG, 10% by 27 August 2003 deficiency and ITP immune deficiency (PID)
PER LITER OF PLASMA Chromatography clinical results; anti-
Blood plasma is the most complex Process infective efficacy; new
human-derived proteome. It safety paradigm
contains 55–60% albumin and offers Flebogamma Instituto Grifols Primary immune Liquid, ready-to-use
an exceptional dynamic abundance IVIG (Probitas Pharma) deficiency
range (10 orders of magnitude) — 15 December 2003
from picograms/mL of interleukins Octagam Octapharma Primary immune Only liquid and double
up to 35–50 g/L range for albumin. IVIG 21 May 2004 deficiency virus inactivated IVIG
Despite the plethora of true plasma that can be stored at
proteins (secreted from solid tissues room temperature (2–
and immunoglobulins), tissue- 25 °C) up to 24 months;
free from stabilizers
leakage products, and temporary
plasma passengers, only 289 proteins
have been documented; about 100 It also appears that the established (6). Despite lower pricing for IVIG,
are used in diagnostic assays and industry is focused on highly this product is likely to remain an
fewer than 20 as plasma competitive markets in which industry driver, but added revenues
therapeutics, with three proteins products are differentiated by from plasma-derived Factor VIII
accounting for 80% of the revenue manufacturers and distributors and alpha1-protease inhibitor are
(4). Assessing opportunities for the rather than by therapeutic effect. mandatory for an industry that
future, Over (5) found only five new (That is changing, but on “benefit- needs to invest in both plant and
products in clinical trials in 2002. to-patient” attributes such as ease R&D. Net revenues (after the cost
However, 2003 was an exceptional of use, infusion time, shelf-life, and of plasma) from existing products
year for new approvals by CBER storage conditions.) The industry per liter of plasma dropped from an
(www.fda.gov/cber/products.htm), still tends to differentiate on safety, all-time high of about US$220 in
as shown in Table 1. advocating added or improved viral 1999 to barely over US$100 in
It is striking that all those clearance or prion safety as well as 2003 (3). Among the various
products are new variants of new manufacturing techniques. measures triggered by such a loss
established products and that they A quick review of a plasma has to be the development of truly
were launched in the US market as product distributor site — www. new products from plasma, not just
an attempt to expand market share, blooddiagnostics.com — illustrates incremental improvements to
competing against existing products. the competitive nature of the market existing ones. This involves a
Significantly, products new to the as well as the product offerings. paradigm shift and a new era of
market are absent from the list of Such an environment leads to price innovation that Christensen
approvals — such as plasmin, pressures and loss of revenue/liter describes as a “disruptive
fibronectin, and apolipoprotein A-1. of plasma as described by Rankin technology” path (7).
20 BioProcess International MARCH 2005
4. HIGH-YIELDING PROCESSES Table 2: Average process yields per liter of plasma from existing “Cohn” fractionation
facilities.
The Cohn backbone process was
developed for albumin, so it is not Yield Yield Industry Industry
Target Protein Cohn trunk (%) Cohn total (%) Average (1) Average (2)
surprising that this protein is
obtained in high yield. Processes for Factor VIII by
40 18 140–270 IU ~200 IU
cryoprecipitation
other plasma proteins have been
developed either by addition of Factor IX — — — ~350 IU
(cryo-)precipitation or adsorptive
technologies before using ethanol
Immunoglobulin G 66 53 3–4 g ~3.5 g
fractionation or by mainly
chromatographic processing of Alpha1-protease
23 15 — ~0.2 g
fractions of the Cohn system, as inhibitor
in methods developed for alpha1-
antitrypsin. These processes are Albumin 95 86 22–28 g ~25 g
generally low yielding. Particularly,
Yield figures in % are calculated from industry sources. The “Industry average (1)” figures are from
the low yield of IVIG caused “Contract Fractionation”, World Federation of Haemophilia (reference 16). Industry average (2) estimates
(previously) major players Baxter are from the PPTA (reference 17).
and Bayer to implement significant
improvement to purification from
Affinity Chromatography: New
Fraction II + III. Considering the chromatography. This recently
technologies, which break the
data in Table 2, there should be reviewed (8) technique is already
“S-curve” (7) development scheme,
considerable room for improvement, used in many established process:
are unlikely to use differential
but that would necessitate a radical in the purification of coagulation
solubility as the driver of separation.
change of processing technology, factors, for example, and in new
They are far more likely to use
not generally attractive to an processes such as that for plasmin.
discerning technologies,
established industry bound by Such technologies allow for
commonplace in downstream
existing product licenses in the sequential adsorption, not
bioprocesses, such as affinity
United States and around the world. precipitation, from the main
FDA GUIDANCE FOR INDUSTRY:
SCREENING MATERIALS FOR HUMAN DONORS OF BLOOD AND BLOOD COMPONENTS
by James Reilly
In 2000, the American Association of Blood Banks Questionnaire.” The outcome of the task force and
(AABB) convened an Interorganizational Uniform workshop proceedings was a series of donor-history
Donor History Questionnaire Task Force at the request questionnaire (DHQ) documents, which when
of the US Food and Drug Administration. The Task implemented in their entirety effectively represent a
Force included a wide spectrum of constituents comprehensive donor history screening system.
including blood center staff, survey design experts,
In April 2004 the FDA published a draft guidance titled
an ethicist, and a statistician, as well as organizational
Acceptable Full-Length Donor History Questionnaire
members from AABB, America’s Blood Centers,
and Accompanying Materials for Use in Screening
American Red Cross, Plasma Protein Therapeutics
Human Donors of Blood and Blood Components,
Association, US Department of Defense, and liaisons
which fully incorporated the DHQ documents
from the FDA, Centers for Disease Control and
including
Prevention, and Canadian Blood Services. The goals
of the task force were to • Blood Donor Educational Materials
• Full-Length Donor History Questionnaire
• Provide major improvement in blood donor
• Medication Deferral List
screening
• Donor History Questionnaire
• Make the process more effective in capturing
• User Brochure (including glossary, flow charts, and
relevant blood-donor qualifying information
references).
• Simplify the screening process
• Enhance recruitment and retention without AABB DHQ DOCUMENTS
sacrificing the safety of transfusion recipients. Several important points need to be made regarding
In October 2000, the FDA and AABB cosponsored a the DHQ documents and the FDA draft guidance.
workshop on “Streamlining the Blood Donor History (continued)
22 BioProcess International MARCH 2005
5. stream and the design of a 91% of the world’s production of is a highly complex issue. The
backbone that targets the most pharmaceuticals (9). Plasma product InterAcademy Council (IAC,
needed plasma products. use is no exception to this. In 2000, www.interacademycouncil.net)
the Americas and Europe consumed notes that “the global reality is
GLOBAL ACCESS 83% of the plasma-derived Factor that many innovations fail to accrue
TO PLASMA PRODUCTS VIII and almost all the world’s to those who need them most.”
With a supply crisis for IVIG an issue recombinant products (10). In the Furthermore, “stronger science
of the past, the overproduction of same report, Europe and North and technology capacity in the
albumin, and the availability of new- America accounted for about three developing nations is not a luxury,
generation Factor VIII presentations quarters of the IVIG. For all but an absolute necessity if these
and alternative alpha1-protease products, the use of plasma nations are to participate as full
inhibitor (API) products, the derivatives in Africa is only about partners in the world’s fast-forming,
majority of patients in North 1% of the total. With the current knowledge-based society” (13).
America, Europe, and other worldwide market for plasma- The debate attempting to resolve
developed countries generally receive derived products stable at US$5.8 issues related to plasma fractionation
the products they need. Exceptions billion, North America accounts for is not new with advocates of “self-
are that many hemophiliacs have yet 37% and Europe for 30% (11). In sufficiency” (those who advocate
to be on prophylactic treatment, and contrast, North America accounts local or national fractionation or
according to the Alpha-1 Foundation for 6.7% and Europe for 12% of the contract fractionation at a distant-
(www.alphaone.org), at least 90% of world population of just over six but-established fractionator). The
the 100,000 API-deficient patients in billion. Although the United States December 1997 Transfusion Today
the United States remain exports over 6.5 million liters of contains six short articles on the
undiagnosed and untreated — plasma (12), that is largely to subject (14), and the Gordian knot
indicating a market opportunity if facilities in Europe that either lack has not been untied over almost two
reimbursement policies would allow. sufficient collection structures or are decades. Central to the ability to
However, a very much larger and mandated not to use domestic produce safe and reliable plasma
more global issue must be tackled. sources because of possible vCJD products is the existence of an
The World Health Organization risk (as in the United Kingdom). adequate infrastructure for plasma
(www.who.int) estimates that 15% The state of science and collection, recently discussed by
of the world’s population consumes technology in developing countries Farrugia (15). This is a necessity
FDA GUIDANCE FOR INDUSTRY (CONTINUED)
Blood Donor Educational Materials: This document Medication Deferral List: The most significant
provides a first layer of safety by familiarizing donors improvement to this component of the donor screening
with the donation process and risks that result in process was combining the various FDA-required
deferral from donation. The document emphasizes the permanent and temporary deferrals for medications.
importance of accuracy and honesty in responses to The document includes a rationale for the deferral,
screening questions. written in terms that donors can understand, and
defines the period that a donor would be ineligible to
Full-Length Donor History Questionnaire: The
donate. This approach allowed the replacement of
questionnaire is significantly different from previous
multiple questions with a single question about
questionnaires and is designed to be either donor self-
medications in DHQ documents after review of the
administered or administered by direct oral screening,
list. Facilities, at their option, can supplement the list
or computer-assisted screening. However, staff must be
with additional medications that have been identified
readily available to help donors in all cases. The DHQ
as a result of local medical policies.
uses “capture” questions that require additional action
when a donor gives an unacceptable answer. Donor History Questionnaire User Brochure: The brochure
provides detailed instructions to facility screening
The questionnaire allows for addition of facility-
personnel regarding how to administer the overall
specific questions to meet local regulatory
documents and system. The glossary, flow charts, and
requirements and questions that respond to temporary
references provide follow-up questions to the “capture”
situations — such as those about severe acute
questions and explain the process.
respiratory syndrome (SARS). The DHQ documents
incorporate screening questions based on cancer; DHQ Document Evaluation and Review: The first donor-
organ, tissue, or bone marrow transplants; bone or skin screening questionnaire was developed in 1953.
grafts, and pregnancy (1). These go beyond the FDA
(continued)
requirements in 21 CFR Part 640.
24 BioProcess International MARCH 2005
6. independent of the volume of Handed down from the UN center responsible for the commercial
plasma made available for Millennium Development Goals production of plasma products.
fractionation and independent of (www.un.org) and embedded in If the gap between “have” and
where fractionation is carried out. WHO thinking are ambitious targets “have-not” nations is to be
However, another side of the coin is for maternal and child health, narrowed, the technology for such
that it must be possible within the infectious disease control, and an industry needs to embrace
healthcare system to diagnose, access to essential medicines. Many current, best biopharmaceutical
reach, and treat patients in need. mechanisms for achieving those goals practice and embrace high yielding,
Additionally, there needs to be depend on partnerships that serve to competitive, and economically
political will and a regulatory narrow the ever-widening gap beneficial processes. In plasma
environment to support provision between developing and developed product manufacturing, this is
of plasma products. nations. The IAC Report provides unlikely to be based on Cohn
Import of finished products, strong arguments and a framework fractionation technology, but to rely
although a possible short-term for local development (13). In on the standard unit operations of
necessity, is neither a long-term, countries that benefit from the bioprocessing: chromatography and
sustainable solution nor an realization that supply of plasma membrane separations together with
economically satisfactory resolution products is a biopharmaceutical the most recent and proven means
for making plasma products endeavor rather than an “altruistic” of viral inactivation. R&D efforts
available. The pros and cons of branch of blood transfusion, there will, therefore, probably be shared
contract fractionation available in is every reason to investigate between the technology providers
developing countries are well establishing a national and the local, transfer recipients.
discussed in a World Federation nongovernmental organization When product development occurs
of Haemophilia document (16). (NGO) or independent industrial at the local (national) level, patient
Neither solution encourages the venture. Creating world-class centers needs can be targeted in the setting
development and establishment of of excellence in biotechnology and where the products are to be used.
biopharmaceutical processing at a bioprocessing can embrace
local level. establishing a plasma biotechnology
FDA GUIDANCE FOR INDUSTRY (CONCLUDED)
Since that time, donor screening has become A SIGNIFICANT ADVANCEMENT
significantly more complex and time consuming. The Donor screening is one of the pillars of transfusion
DHQ documents represent a significant redesign and medicine and related biological therapies safety. The
modified process. They were evaluated and modified FDA DHQ documents, when implemented in their
as a result of testing that used a series of focus groups entirety, represent a significant advance in donor
and one-on-one cognitive interviews (2). screening systems.
Additional information and the DHQ documents can
REGULATORY REQUIREMENTS
be found at www.aabb.org, click on “Pressroom, AABB
The FDA draft guidance allows facilities to implement
Donor History Questionnaire.” The complete FDA
DHQ documents — if adopted in their entirety — with
Draft Guidance document can be found at www.fda.
notice to the FDA only as a part of their annual report.
gov/cber/guidelines.htm.
There are two exceptions: Facilities choosing to modify
the DHQ (except for deletion of certain questions not
REFERENCES
currently part of FDA requirements) must notify the 1 Blood Bank Transfusion Service Standards Program Unit.
FDA using the “Prior Approval Supplement” Standards for Blood Banks and Transfusion Services, 22nd edition.
submission process; and those wishing to use the AABB: Bethesda, MD, 2003.
computer-assisted interactive interview procedure 2 Orton SL, Virvos VJ, and Williams AE. Validation of Selected
Comprehension. Transfusion 40(11) 2000: 1407–1413.
should consider this a “moderate change” and use Donor-Screening Questions: Structure, Content, and
the “Changes Being Effective in 30 Days (CBE30)”
notice process. (Additional information on FDA
James Reilly is the director of Global Development, AABB
reporting can be obtained at www.fda.gov/cbergdlns/ Consulting Services, 8101 Glenbrook Rd. Bethesda, MD
donorhistques.pdf). 20814; jreilly@aabb.org
26 BioProcess International MARCH 2005
7. 7 Christensen CM. The Innovator’s 15 Farrugia A. Plasma for Fractionation:
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