History

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.