The focus of production and repackaging activities in hospital pharmacies has changed dramatically over the past 40 years. In the early 1970s, it was common practice for even small district general hospitals to engage in a wide range of production activities.
History
The focus of
production and repackaging activities in hospital pharmacies has changed
dramatically over the past 40 years. In the early 1970s, it was common practice
for even small district general hospitals to engage in a wide range of
production activities. Non-sterile production would have typically included a
range of oral liquids and mixtures (often preserved with chloroform water),
antiseptic skin-staining solutions for use in theatre, sup-positories, creams,
ointments and powders. Many of the formulae for these products were obtained
from official literature such as the British Pharma-ceutical Codex, although a
number of formulations were ‘developed’ in house.
Many hospitals had
also realised the benefits of preparing stocks of com-monly used solid-dosage
forms as prepacks on a small-batch scale. These become known as ‘ward packs’
and were prepared using manual (for ex-ample, the tablet triangle) or
semiautomatic tablet- and capsule-counting systems. Labels were often preprinted
and batch-specific details were either hand-written or typed.
With few exceptions,
non-sterile manufacturing and prepacking occurred on an ad hoc, small-scale
basis, with little central coordination. Batch records, procedures and
production facilities were all extremely variable and little thought was given
to process validation, shelf-life assignment, QA and control.
The manufacture of
terminally sterilised products was also more wide-spread in the 1970s than is
currently the case. The presence of small autoclaves, dry-heat sterilisers and
steam baths was common in district general hospital pharmacies, and many
hospitals were self-sufficient in their provision of most sterile products,
buying only the bulk intravenous (IV) infusions from industry (for example,
0.9% sodium chloride and 5% glucose). The product range typically included
bladder irrigation solutions, multidose eye drops, antiseptic solutions and
oily preparations for sterile wound dressings. In some centres, specialist
injectables for IV, intramuscular and intrathecal administration were also
produced. In most cases, bulk solutions were prepared in uncontrolled or
perhaps ‘socially clean’ areas and were invariably filled into glass containers
which were sealed with a rubber stopper and screw cap arrangement. A basic
filtration procedure was usually incorporated for parenteral products and eye
drops; some of the more specialised units had ampoule sealing equipment which
was, at best, only semiautomatic. Sterilisation processes were poorly
controlled and rarely validated, particularly in the case of steam baths (for
heating with a bactericide) and dry-heat sterilisers. Quality control (QC) was
usually rudimentary, with only an inspection of the product for visible
par-ticulates and an examination of sterilisation cycle temperature–time charts
prior to batch release.
As the 1970s
progressed, sterile production became more organised with the emergence across
the UK of specialist sterile product units on a coord-inated, regional basis.
Many of these units concentrated on the production of sterile large-volume
irrigation solutions that were normally presented in semirigid plastic
containers (for example, Schubert containers). These units benefited from
considerable investment to fund automatic filling lines, hermetic sealing
technology and large double-ended autoclaves. A few UK centres were equipped to
fill flexible-film polyvinyl chloride containers for the manufacture of
large-volume IV infusions and small blow-moulded containers for eye drops. By
comparison with sterile and non-sterile manu-facturing, aseptic preparation was
a relatively minor component of hospital pharmacy work in the mid-1970s.
In 1976 the
Breckenridge report was published, recognising the hazards associated with
infusion preparation on hospital wards. This prompted the development of
embryonic CIVAS in a few of the larger teaching hospitals, which prepared TPN
and other infusions considered of insufficient stability to withstand terminal
sterilisation processes. As with other types of hospital production of that
era, facilities, controls and documentation were often neglected. The
preparation of radiopharmaceuticals at the time was largely confined to nuclear
medicine departments, where medical physics staff under the supervision of
medical staff carried out the work.
An attempt to
rationalise hospital technical services activities through the introduction of
rigorous costing policies was made in 1984 with the issue of health circular
HC(84)3 by the Department of Health. This circu-lar recommended that hospitals
should not produce pharmaceuticals that were commercially available and that
the economic viability of in-house manufacture should be assessed. This
included taking into account the full cost of staff, facilities, equipment,
maintenance, heating, lighting and depreciation when calculating the cost of
products. At the time, this health circular was not well received by technical
services pharmacists and, apart from encouraging further rationalisation
through regional production units, its impact was limited.
Of greater
significance was the loss from National Health Service (NHS) hospitals of Crown
immunity in 1990. Under new guidelines, manufacturing activities above
specified levels were required to be licensed by the Medicines Control Agency,
now known as the Medicines and Healthcare products Regulatory Agency (MHRA).
For many smaller production units, the cost of upgrading facilities to the
standards required to obtain a Medicines Control Agency specials manufacturing
licence was prohibitive. The loss of Crown immunity coincided with the
introduction of trust status for many NHS hospitals. The combination of new,
higher standards and a more cost-conscious environment in the NHS significantly
changed the emphasis of technical services activities. More recently, the issue
of guidance note 14 and enforcement by the MHRA have, in effect, eliminated
products made under a manufacturing specials licence where a licensed
equivalent is available. Although seeking to raise the standards of preparation
of medicines, this has led to concerns about intellectual property rights (IPR)
of hospital-developed formulations which can be copied by industry and sold
back to the NHS at high cost in a protected market. This guidance may also prevent
hospital manufacturing units responding to supply problems, now more prevalent
in the pharmaceutical industry.
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