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Defence Mechanisms

Small children are more at risk of being involved in an accident in the home than on the road. Of every 100,000 children aged under five who died in Germany in 2011, 4.2 were killed in household accidents, while only 1.3 were killed in road accidents (1). One of the biggest risks to children in the home is unintentional poisoning with household chemicals, cosmetics or pharmaceutical drugs. Emergency hotlines in Germany receive around 94,000 calls every year about children under 15 years of age who may have poisoned themselves, and 19,000 of these children actually do demonstrate symptoms of poisoning (2).

The results of surveys conducted in the US provide a similar picture. A study by the Consumer Product Safety Commission (CPSC), for example, shows that over 85,000 children were treated at public hospitals in 2004 due to poisoning. That corresponds to almost 430 cases per 100,000 children. In just under 60 per cent of cases, the children had consumed oral prescription drugs, over-the-counter (OTC) medications or food supplements. When medications for external application are also taken into account, the figures are even higher (3).

Established Standard

It is therefore no wonder that the number of packaging products with child-resistant (CR) closures continues to increase in Europe and the US. High-risk household chemicals such as drainpipe cleaners, oven cleaners and methylated spirits, which often come in bright, coloured packaging that appeals to children, have long had CR closures as standard.

Regulatory authorities prescribe high standards for manufacturers of prescription drugs and of pharma primary packaging products, and CR packaging has been mandatory for many liquid and solid prescription drugs for years. These drugs generally have packaging closures that require specific action sequences to open which small children, in particular, are unable to perform. To open the packaging, a combination of simultaneous or sequential actions is generally necessary.

The popular ‘squeeze and turn’ closures have to be activated simultaneously in order to open them; pressing the cap at defined positions distorts its shape so that the locking elements are released. In addition to the combination of two actions, packagings often have large caps which hinder small children’s hands from pressing the two diametrically opposed release points at the same time. ‘Push and turn’ closures have to be simultaneously pushed and turned before they can be screwed off. In this action sequence, the downward pressure releases the locking elements. Packaging products with flip-top lids or pump sprays incorporate other safety features relating to the opening or trigger mechanism.

Recent Trends


New regulations have been introduced for OTC products over recent years in addition to the longstanding regulations for prescription drugs. The CPSC has recently introduced a new Guideline, according to which all prescription and OTC drugs with more than 0.08mg of imidazolines must have CR packaging. Imidazolines (tetrahydrozoline, naphazoline, oxymetazoline and xylometazoline) are vasoconstrictors indicated for ophthalmic irritation or nasal congestion. Accidental ingestion by children can cause serious adverse reactions, such as central nervous system depression, decreased heart rate and depressed ventilation. According to the CPSC, between 1997 and 2009, 5,675 children younger than five suffered injuries after ingesting products containing imidazolines, especially eye drops.

The Guideline, which came into effect in December 2013, is based on the Poison Prevention Packaging Act (PPPA) of 1970, and requires drug manufacturers and packagers using more than 0.08mg of imidazolines to make their primary packaging immediately compliant. Even before the decision had been taken, some customers in the human and animal health industries had already made the switch to CR packaging. For the producers of primary packaging, time has therefore become a big issue.

The new requirements have already resulted in a lot of activities related to the production of dropper bottle systems, nebulisers and nasal sprays. The CPSC has proposed a one-year implementation period from the Guideline’s effective date, but on behalf of the pharma industry, the Consumer Healthcare Products Association has requested a longer transition period. It argues that drug manufacturers and packers need at least two years to design, develop and test CR packaging in order to ensure continued consumer access to eye drops, nasal decongestants and other products with imidazoline ingredients.

The marketplace for primary packaging is not well represented with standard CR packaging solutions for this type of product, and fundamental design development is therefore likely to be required. Few suppliers of ophthalmic primary plastic packaging have standard CR solutions or CR closures that can be adapted to customers’ existing bottles. In this line of business, many aspects have to be considered to meet the market demands of today and tomorrow.

Future Thinking


The use of CR packaging is likely to be extended beyond prescription and OTC drugs to food supplements, such as vitamins and minerals. Overdoses of food supplements can also lead to serious health problems; they pose a particular risk because they are often stored in the kitchen, where children have easy access to them, rather than the medicine cabinet.

Regulatory requirements, responsibilities and standard procedures for food supplements vary to a far greater extent from country to country and company to company than those for pharma drugs. In the US, the Food and Drug Administration (FDA) failed in its attempt to make PPPA-based CR packaging mandatory for preparations with more than 30mg of iron per dose (4). However, this was not due to doubts about the harmful effects of an overdose of the food supplement, but because of uncertainty as to whether this was an issue within the FDA’s remit.

In light of this, primary packaging manufacturers will play a pioneering role in bringing about greater child safety. In addition to obligatory compliance with regulatory requirements, it is in their interest to develop efficient solutions for patient health and product safety – firstly because it is also in the interest of patients (as end-users of their products) and, secondly, because this will provide them with a means of differentiating themselves from competitors.

Innovative Solutions


Even though the use of CR packaging is becoming more widespread, it does not solve every problem. Government authorities are well aware that although these safety measures improve child safety, they cannot guarantee it. The CPSC has emphasised that there is no such thing as CR packaging. It therefore recommends that product packaging – CR or otherwise – is not viewed as the primary protective measure, but as the last line of defence.

There is another problem associated with CR packaging – namely that it is often less effective at withstanding the energetic efforts of a four-year-old than attempts by elderly citizens or people with limited motor skills to open it. The trend of tighter regulatory requirements therefore conflicts with the requirements of senior citizenfriendly packaging – a need which is becoming increasingly relevant globally due to the ageing population.

Associations which work against agerelated discrimination are demanding ergonomic packaging that facilitates patient adherence and, in some cases, they oppose child protection association demands to optimise the efficiency of CR mechanisms. It is currently standard practice to develop CR packaging which strikes a balance between safety and ergonomics. This is reflected in CR packaging tests, which are predominantly oriented around PPPA requirements. The PPPA defines a target range which permits a fixed percentage of negative results for children and senior citizens. This means that only a certain number of children (aged between 42 and 51 months) should be able to open the packaging, while only a certain number of elderly citizens (aged 50 to 70) should be unable to open it (5).

Primary packaging manufacturers will therefore have to collaborate closely with their pharma manufacturing customers. There is a need to develop innovative closures which more effectively combine CR and senior citizen-friendly features than the statistical compromise achieved with the widely-used ‘push and turn’ or ‘squeeze and turn’ closures.

References

1. Federal Statistics Office statistics on cause of death, 2011
2. Figures provided by the Federal Ministry for the Environment
3. Franklin RL and Rodgers GB, Unintentional child poisonings treated in United States hospital emergency departments: national estimates of incident cases, population-based poisoning rates, and product involvement, Directorate for Economic Analysis, US Consumer Product Safety Commission, Bethesda, Maryland, Pediatrics 122: p1,244, 2008
4. Nutritional Health Alliance versus FDA, 318 F.3d 92 (2d Cir), 2003
5. Dlugi P and Ost D, Anforderungen an kindergesicherte pharmaverpackungen, Pharm Ind 60(10): pp883-888, 1998

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Marek Miszczak is R&D Manager and European R&D Coordinator for Gerresheimer Plastic Packaging. He oversees various business areas, particularly new product development of pharma plastic packaging within ophtalmics, parenterals, liquid formulations and solid dosage. Formerly Product Development Manager of medical devices, Marek has worked for Gerresheimer for 13 years.

Christina Desirée Holder is Head of Business Development Sales, and formerly Product Manager, for the European sites of Gerresheimer Plastic Packaging, covering the business areas of pharma plastic packaging within solid dosage, liquid formulations, ophthalmic applications and plastic bottles for personal care. Christina has worked for Gerresheimer for 11 years and has also held managerial positions within Customer Care Management and Marketing.
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Marek Miszczak
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Christina Desirée Holder
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