1980Õs: Expansion of Demand

In 1982, a massive increase in capital expenditure took place. At around £60 million, it allowed a large, modern manufacturingunit capable of greater production of blood products to be built.The size of the BPL site increased when Sir William Maycock soldhis house and grounds (which included an orchard). The factoryhad to be designed so that it fitted into the local Ôgreen beltÕ ofleafy Hertfordshire7.

Norman Fowler, the Minister of Health at that time, laid thefoundation stone and the new, state-of-the-art factory was openedby HRH the Duchess of Gloucester on 29th April 1987, providingus with the highly recognisable wedge-like landmark structure wesee today.

The mid-1980s also saw a growth in staff number from about 200to around 400 employees representing a variety of administrative,financial and scientific disciplines. Many staff were drawn from thenearby towns of Borehamwood and Watford. A further staffincrease to around 500 took place by the late 1990s and industrialrelations developed into one of ÔpartnershipÕ between BPLÕsExecutive and the trade union MSF (later Amicus).

A greater focus on Quality Assurance became a priority and arange of specialist functions were introduced such as a dedicatedmicrobiology department to test the quality of the manufacturingenvironment.

There were also key changes to the manufacturing process with a greater emphasis on patient safety, improved aseptic fillingoperations and sterile filtration of the product.

1990Õs Commercial Development

In 1990, following the establishment of the internal market in theNHS, Blood Products Laboratory changed its name to BioProducts Laboratory, although the ÔBPLÕ acronym was retained.At the same time the Government introduced a chargingmechanism for BPL products to NHS customers which allbecame licensed and BPL became subject to medicalinspectorate visits.

In 1991, BPL received a special mention in the House ofCommons for its role in the Gulf War through providing specialimmunoglobulin products as part of ÔOperation GranbyÕ inassociation with the Chemical Defence Establishment at Porton Down.

In 1993, the CBLA was dissolved and BPL became part of thenewly formed ÔspecialÕ Health Authority: the National BloodAuthority (NBA). This brought BPL and IBGRL together with theblood transfusion centres and donor collection service -previously under Regional Health Authority control - to form theNational Blood Services. This change was to allow for greaterre-sourcing and national strategy.

The 1990s saw improved techniques for viral removal andinactivation. A specially designed area of the factory — the ViralSecure Area (VSA) — was established and solvent detergentssteps added to destroy a spectrum of blood borne viruses.

Further investments into buildings took place and dedicatedbuildings for Engineering, laboratories and R&D were built in theearly 1990s.

In 1998 the theoretical risk of transmission of nvCJD resulted ina major change for BPLs operations. The factory underwent amajor sanitisation exercise and plasma was purchased fromblood centres in the USA.

Bio Products Laboratory Dagger Lane, Elstree, Hertfordshire, WD6 3BX UK Tel: +44 (0) 20 8258 2342 Fax: +44 (0) 20 8258 2604 Web: www.bpl.co.uk

The FutureThe future for BPL will be both consistent and constantlychanging. BPL will continue primarily as a plasma fractionator to supply IgG to the patient population. This will continue to beBPLs biggest growth area as there is a shift away frommanufacturing Factor VIII and albumin at previous levels.

The next decade will see BPL operating in Europe and in theUSA, which will keep BPL evolving and adapting in response to change.

The future holds much to look forward to and much to achieve.

AcknowledgementsThis booklet was written by Tim Sandle. Those who assisted with the preparationwere: Iain Bradbury, Shruti Shah, Sarah Kingsland and Steve Davies.Thank you to all BPL staff, past and present, who provided information andphotographs.

1 Source material: http://www.lister-institute.org.uk/scientific.htm

2 Source material: http://www.bath.ac.uk/ncuacs/guidei-k.htm#KekwickRA

3 Source material: BPL Staff Handbook, 1992

4 Source: Blood - An Epic History of Medicine and Commerce; Douglas Starr;London: Little, Brown, 1999; ISBN 0316911461

5 Source: http://www.bloodbook.com/trans-history.html

6 Source: Alice Kidd in ÔThe CrestÕ, Summer 1990

7 Source: Blood Products Laboratory: Long Term Management Plan, April 1987,Building Design Partnership

CELEBRA TING FIFTY YEARS OF ACHIEVEMENT50

BPL 50 Year Brochure 4 22/3/04 5:10 pm Page 1

What is BPL

Lister Institute of Preventative Medicine1

The Early Years

BPL is a Ônot-for-profitÕ organisation of the NHS and produces arange of plasma derived therapeutic products.

The plasma is fractionated by a process which separates out theplasma components into different product groupings. Theseproducts include coagulation factors for the control of haemophilia(A and B) and other inherited bleeding disorders; specific and non-specific immunoglobulins (antibodies) for the treatment of peopleborn with weak immune systems; and albumin for those who needa restoration of their circulating blood volume.

These products are distributed around hospitals in England andWales, with any excess sold on a global market with all proceedsreturned to the NHS.

The plasma is separated and purified by a process called PlasmaFractionation. Plasma arrives at BPL frozen. After quarantine, theplasma is sent for processing. The first product (cryoprecipitate) isseparated and is used to process the clotting factors. This isperformed by separating plasma from individual packs; crushing

In 1902 Dagger Farm in Aldenham, Hertfordshire, was sold to theLister Institute of Preventative Medicine. It was located along theappropriately called Dagger Lane, where a nineteenth centurymurder by stabbing had infamously occurred.

Joseph Lister had established his world famous Institute in 1891 toundertake scientific research into the causes, prevention andtreatment of disease and to prepare and supply protective andcurative materials such as vaccines and antitoxins.

The 35 acre Elstree site was used to house various farm animalswhich were used to develop life saving vaccines for the treatment ofthen serious illnesses like diphtheria and scarlet fever. QueensburyLodge, built in 1886 and currently BPLÕs administration centre, wasthe location of the research laboratories.

A number of eminent scientists worked at the Lister Instituteincluding Harden (the discoverer of co-enzymes) and themicrobiologist MacConkey.

In 1954, the Lister Institute shared the Elstree site with the newlyformed ÔBlood Products LaboratoryÕ. In 1978, due to financialpressures and a decline in the demand for smallpox vaccines, theLister Institute was forced to leave due to financial problems and BPLtook sole control of the site.

Work in the development of blood products continued. In the1950s, Kekwickdeveloped a method of fractionating out afibrinogen fraction rich in Factor VIII, the anti-haemophilic globulin.This led to the first clinical use of Factor VIII in treating haemophiliain 1957 and the need for large scale plasma fractionation, whichBPL provided5.

In 1959, a group led by Pool discovered that cryoprecipitate - thecold, insoluble globulin precipitate formed during the slow thawingof plasma — contained a five-fold higher concentration of FVIIIcompared to that of plasma.

By 1964, it was shown that cryoprecipitate could be separated bycentrifugation and stored frozen. Because cryoprecipitate containedother proteins, such as fibrinogen, albumin and immunoglobulins,these needed to be extracted through the process of fractionationusing ethanol. The use of fractionation had been developed by theAmerican Doctor Edwin Cohn in the 1940s.

Fractionation also allowed the amount of Factor VIII to beconcentrated to over 400 times the natural concentration found inblood plasma. By the late 1960s the process of freeze-drying(lyophilisation) was used to produce, concentrate and preserveFactor VIII products.

Some of the other proteins extracted through fractionation could bedeveloped into different blood products. The first major non-coagulation factor to be developed was the Anti-D immunoglobulinfor treating rhesus-negative mothers.and thawing under controlled conditions, and extracting the clotting

factors from the thawed material. Following purification andconcentration, the finished bulk solutions are sterile filtered andaseptically filled.

After the clotting factors have been separated, the remaining liquidis bulked in large capacity vessels and centrifuged in sub-zeroconditions. Proteins are separated by the addition of ethanol andother reagents. The precipitates are further processed to removeresidual alcohol and processed as albumins or immunoglobulins.These products are also sterile filtered and aseptically filled.

During processing a number of quality checks are performed byBPLs Quality Assurance and Quality Control departments.

19541967

19861968

19781964

1985

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A lot has happened in that time and you might characterize ourhistory as either constant or constantly changing. In the lattercategory you may recall the fact that BPL came to Elstree as aguest of the Lister Institute and eventually took over the site. Wehave the evolutions in the product range with the additions ofspecial coagulation factors and immunoglobulins, the introductionof new steps to make purer product, the introduction of steps toeliminate viruses and to make safer product. Great strides, greatchange.

A variety of external events, however, have thrown BPL and, indeedthe whole industry, into turmoil from time to time. Few will everforget the advent of non-A, non-B hepatitis and the emergence ofvariant CJD, to name but two.

In addition, the demand for products has increased over the yearsas more and more patients are successfully treated and are able tolive normal lives. To cope with this, the BPL infrastructure hasdeveloped enormously to the state-of-the-art plant that we nowhave, together with the new R&D, Technical, Engineering andWarehouse buildings. As well as importing our basic raw materials,BPL now export products to all corners of the world.

Underlying these apparently never ending changes is the element ofconstancy. We remain on the same rather pleasant site in ruralHertfordshire. The raw material from which we make our productsis still fundamentally the same raw material, the process by whichwe break that raw material into its component parts and extract it isstill basically the same process.

The number of people at Elstree may have increased dramaticallyand while there is nobody is here today who was with BPL in 1954,but there remains certain unchanging values to which we all adhere- the desire to make products which are not only safe andefficacious but which in every case save lives and which make adifference, not just to the patients who receive them but to theirfamilies and friends as well.

For 50 years, BPL has been making that difference and willcontinue to do so into the future. Another 50 years? Who can tell,but however far the future of BPL stretches ahead, people who livethat future will be able to look back at an ever-lengthening history ofdevelopment, achievement and making a difference.

Happy Birthday BPL.

Foreword

New fa

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2004

BPL Today

BPLDuring the 1940s, Brinkhous and McFarlane discovered thattransfusions using whole blood or plasma provided a means of FVIIIreplacement. Applications using this early discovery were limiteddue to naturally low concentrations of this anti-haemophilic factor inblood and plasma and volume constraints in the circulatory system.

During this time, Professor R. A. Kekwick, working at the ListerInstitute undertook experimental and production work with A.S.McFarlane. The two scientists devised a process to clarify outdatedblood plasma to render it suitable for transfusion2.

In 1943, Kekwick was appointed Head of the ListerÕs BiophysicsDivision, Kekwick established the Blood Filtration Unit and he andhis team worked on methods of freeze-drying plasma and then ofseparating out proteins in blood plasma. These early products wereused to meet the needs of the Armed Services and civilianestablishments.

In 1948 the Blood Filtration Unit came under the joint managementof the Medical Research Council (MRC) and the Lister Institute, andthe name was changed to the Blood Products Research Unit. Itoccupied the newly built laboratories (or ÔBuilding 25Õ) and its aimwas directed towards the preparation of plasma fractions for clinicaluse3.

In 1954, the Government wished to establish a site for increasedproduction of blood products. This followed on from the importanceof blood in therapeutic medicine, the need for blood productsduring the Second World War (particularly the use of albumin4) andthe formation on 26th September 1946 of the National BloodTransfusion Service. It had also been discovered that a secondform of haemophilia (Haemophilia B) existed, which was treatablewith blood protein called Factor IX.

An agreement was reached between the Government, MRC andthe Lister Institute and the Blood Products Laboratory wasestablished with funding from the Ministry of Health. Enlargedfacilities for plasma fractionation and freeze-drying wereestablished.

In 1978, the Lister Institute sold the entire Elstree site to theGovernment. As a result, the distinction of the ÔscientistsÕ andÔtechniciansÕ dining in separate canteens was ended as BPL tooksole occupancy of the site. The average wage for a laboratorytechnician at BPL was £25.67 per week6.

The running of BPL was transferred to the North West ThamesRegional Health Authority as an interim measure. In 1982 a SpecialHealth Authority was created called the Central Blood LaboratoriesAuthority (CBLA). Which administered BPL, PFL, BiomedicalServices and the Bristol based International Blood Group ReferenceLaboratory (IBGRL) for approximately ten years.

PFLIn 1967 the Plasma Fractionation Laboratory (PFL) opened inOxford (at the Churchill Hospital, Headington). Staffed by a smallnumber of people, PFL was established as BPLs pilot plant and toproduce special products for the treatment of rare forms ofhaemophilia. The Oxford laboratories were a highly innovativeresearch centre - developing the first heat treatment process forFactors VIII and IX in the mid-1980s - until their closure in 1992when all operations and staff were transferred to BPL.

BPLDThe Blood Products Laboratory Diagnostics (BPLD) operation wasestablished in 1986 with the aim to provide a service for bloodgrouping tests, for the identification of correct blood groups ofdonors and patients, and diagnostic kits, such as screening cells,for various blood centres and hospitals.

Closed in 1995, BPLD its operations were transferred to differentcentres within the blood transfusion service.

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