Setting a blistering pace

BS8404 is about to hit the blisterpack industry, and there is new EU legislation in the pipeline. Blisterpack packers and the pharma manufacturers met to discuss the issues

For almost four decades, the blisterpack has offered a cost-effective and practical method of delivering unit dose packaging. According to the Proprietary Association of Great Britain (PAGB), there has been no increase in the rate of accidental poisonings over the years, despite the increased use of strips and blisters.

Furthermore, since 1989, the majority of the pharmaceutical industry has adhered to a code of practice designed to impart a degree of child-resistance to blisters. This incorporates measures such as the use of opaque substrates and limiting pocket sizes to minimise the rattle.

It is estimated that there are in excess of 1,000 pharmaceutical blister machines in the UK, many of which have been installed in the last decade as a result of government initiatives to promote original pack dispensing.

The current moves towards legislation were prompted by an incident of child poisoning in September 2000, which is believed to have involved products in a non-opaque blister.

BS8404, the standard relating to child-resistance of non-reclosable pharmaceutical packs, was published in December 2001. The consultation letter issued by the Medicines Control Agency (MCA) ; the body responsible for incorporating BS8404 into UK law ; followed a year later and the closing date for responses has now passed. Legislation could be implemented as early as October this year, with transitional arrangements running for a 12-month period thereafter.

current drafts

A further cause for concern is the imminence of EU legislation, a draft of which is currently being voted on by Member States. Once implemented, this will supersede any national laws, raising the possibility that pharmaceutical manufacturers will have to repeat the exercise to ensure EU compliance in the foreseeable future.

The current draft is similar to the German DIN standard and BS8404 but should amendments be incorporated along the path to the statute book, the relicensing process could become hugely complex.

At the invitation of machinery manufacturer Romaco, a cross-section of the UK pharmaceutical industry, representing ethical, generic and contract manufacturers and packers, the relevant trade associations, and machinery, materials and format parts suppliers, convened in Huntingdon recently to discuss the most practical and sensible approach to implementing BS8404. Brian Moore, managing director of Romaco UK, said the aim of the meeting was to put together an overall picture of the effects of the proposed legislation on the industry.

'This is a significant measure and we wanted to provide a forum for pharmaceutical producers to hear from the various trade associations who have been working with the regulators on this, as well as to talk to their equipment and materials suppliers about the solutions on offer.

'Measures introduced over the last 25 or so years have reduced significantly the incidence of accidental poisonings. The challenge facing the industry is how to achieve child-resistance, while limiting the frustration for the elderly in accessing their medication ; a possible consequence of over-ambitious implementation of any new legislation,' he added.

Dieter Janek, one of the pioneers of blister packing having joined machinery manufacturer Uhlmann in 1963, said that the concept of child-resistance in blisters began in the US in 1970 with the Poison Prevention Packaging Act. This produced many variations of the blister, including some that are extremely complex, both to produce and to open. As a result, only 20% of products in the US are packed in blisters and the vast majority of these are oral contraceptive pills, which are rarely, if ever, implicated in accidental poisoning.

Germany has had a DIN standard for pharmaceutical packs in place since 1979, which features more user-friendly solutions based primarily on variations in the lidding material and the use of perforation. Specifications were discussed for both push-through and peel-push blisters, which appear to have achieved their aims (table 1), indicating that less extreme measures than those in the US were in order.

license variation

The commitment to maximising child safety notwithstanding, wide-ranging concerns about the practicability of the legislation as currently proposed were raised by those present.

There is just one laboratory in the UK equipped to carry out child panel testing and its maximum capacity is 50-60 tests per year, covering both reclosable and non-reclosable packs.

Even if European laboratories are employed, there is still not sufficient capacity to fulfil the requirement. With up to 200 children aged 42-51 months and 100 adults aged 50-70 involved in each test, the requirement for test subjects is potentially huge. This is set against a background of increasing reluctance among parents to allow their children to take part in product testing.

Changes to the packaging of pharmaceutical products require an amendment to the product licence to be submitted to and approved by the MCA.

According to the MCA's own statistics, there are currently 140 Marketing Authorisations (MAs) for aspirin products affecting 52 Marketing Authorisation Holders (MAHs), 348 MAs for paracetamol products affecting 87 MAHs and 51 MAs for iron products affecting 30 MAHs.

The time and resource required to process up to 539 licence variations, as will be required by the new legislation, will be considerable.

real dangers

Statistics show that the majority of incidents involving medicines occur in places other than the child's own home. The need for continuing education of all adults in regard to the safe storage of medicines is therefore essential.

The products covered by the proposed legislation ; aspirin, paracetamol and iron ; are in many cases extremely low-margin. Delegates at the meeting feared there is a real danger that the additional materials cost (estimated to be in the region of 30-40%) coupled with lower outputs could render some products uneconomical. The potential repercussions include reduced availability/higher prices for the end user.

Prices of generic medicines in the UK are already comparatively low, typically a third of those in countries such as France and Germany.

Manufacturers present at the meeting said that this had been achieved through the high levels of efficiency in the sector, both in terms of operating practices and the quality of modern packaging machinery, specifically blisterpackers. Legislation introduced a few years ago specified pack sizes of eight and 16 units for otc packs of aspirin and paracetamol, for which blisterpacks are the only cost-effective solution.

If UK-based suppliers were to cease production of some of these medicines, there could be significant consequences, including downsizing in the manufacturing sector, as well as knock-on effects on equipment and materials suppliers. The most likely alternative sources of these products would be India and the Far East, creating logistical problems for the MCA, which is responsible for policing GMP compliance and product quality.

If, as seems most likely, the German model is followed, the probability is that blister sizes will increase. Using higher gauge or different substrates and perforation of lidding foil will require a doubling of the minimum workable space between pockets, while for some base substrates the pocket angle will need to be shallower, contributing to a significant increase in overall blister size. Materials costs downstream will increase, with larger cartons and cases required, ultimately affecting transport, storage and distribution functions for both suppliers and retailers.

If blister machines are not already equipped to produce child-resistant blisters, substantial and costly modifications will be required. These might include new feeding systems, forming and sealing formats, lidding foil pre-heating, perforation stations, and die-cutting formats. Format and feeding parts on cartoning machines will also need to be modified.

The use of alternative or higher gauge substrates will reduce line speeds through increased heating, forming and sealing dwell times.

high costs

One solution suggested by the DoH in its announcement accompanying the publication of MLX291 was the overlabelling of blisters. While certainly simplifying the process, the key steps of panel testing and relicensing ; both potential sources of logjams in bringing amended pack formats to market ; would still be necessary.

Every pharmaceutical product must be put through stability testing to ensure that its packaging will provide adequate levels of protection and preservation for the duration of its declared shelf life. These may be carried out either in-house or through an external laboratory, but the cost per product is typically £20,000.

The combination of the above factors means that the potential timeline for implementation set out in MLX 291 ; October 2003 ; is of serious concern to producers. The proposed transitional arrangements mean that existing licence holders will need to achieve compliance within 12 months of the date of implementation. Estimates of the time required for material sourcing and testing, stability trials and revalidation of packaging lines vary, but a typical duration would be three years. This is without the complication of the limited testing and relicensing resource.

provisional agreement

The meeting agreed that the most positive and practical course of action in view of the limited time available was to seek the acceptance of type approval for DIN-standard materials.

Discrepancies exist between the DIN and BS test models, such as age specifications for the adult panel test and the possibility for materials producers rather than licence holders to commission tests. Provided these are borne in mind, the meeting agreed that type approval would be the most acceptable means of proceeding for all concerned, going some way to preventing the exposure of huge numbers of children to panel testing. Other initiatives, such as the development of mechanical testing facilities were also to be encouraged.