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Building safety into the packaging of injectables


Richard Bateman
QA Specialist Pharmacist
East and South East England Specialist
Pharmacy Services, UK

In the UK, information on patient safety incidents has been gathered and analysed by the National Patient Safety Agency (NPSA). Between 2005 and 2007, 59,000 patient safety incidents involving medicines were reported to the NPSA. Of these, injectable medicines accounted for 25% of all incidents and 58% of the most serious resulted in harm or death. It was also reported that 33% of medication incidents were a result of confusion over packaging and labelling. The 2009 NPSA Report Safety in Doses further highlighted these issues.

The report considered data from the National Reporting and Learning System that covered all patient safety incidents. Of a total of 811,746 reports, 9% related to medicines. Overall, this was the third largest category. Although 96% of these incidents resulted in no or low harm, there were 100 reports of death or severe harm related to medicines. Of these incidents, 41% were errors in administration and 62% involved injectable medicines.

Within the specific area of hospital pharmacy practice in the UK, the National Aseptic Error Reporting Scheme (NAERS) has been collecting data on pharmacy compounding errors from regional pharmacy quality assurance (QA) specialists and has been analysing these data since 2003. The NAERS data are unique because they bring together information on all potential safety incidents, including in-process errors that do not reach the patient (i.e. near-misses). In fact, the majority of the NAERS errors were near misses and were detected before the product left the pharmacy. Although preparation error rates are much lower in pharmacy-controlled aseptic preparation units than in clinical areas, they do still occur. NAERS data identified contributory factors that led to the events occurring, and approximately 15% of reports related to the selection of the incorrect drug, strength or diluent.

Pack design is not the only issue influencing the risks associated with injectables but it is a key part of the overall medicines safety agenda.

Experience in England
NPSA Alert 20
In recognition of the ongoing safety issues associated with injectable medicines, the NPSA issued Safety Alert 20, entitled ‘Promoting the safer use of injectable medicines’ in March 2007. This required NHS organisations to:

  • Risk-assess injectable medicine procedures and products in all clinical areas and develop action plans to minimise high risks.
  • Ensure up-to-date protocols and procedures exist for prescribing, preparing and administering injectable medicines.
  • Ensure that essential technical information on injectable medicines is available and accessible at the point of use.
  • Implement a ‘purchasing for safety’ policy to promote procurement of injectable medicines with inherent safety features.
  • Train staff and ensure adequate supervision.
  • Audit medication practice with injectable medicines as part of the annual medicines management audit programme.

Purchasing for safety
The concept of purchasing for safety is not a new one, but NPSA alert 20 strengthened the requirements for this and increased the emphasis on the manufacture, procurement and use of injectable medicines in a ready-to-use or, ideally, a ready-to-administer presentation. It also reinforced the need to bring high-risk injection preparation activities carried out in clinical areas into pharmacy aseptic preparation units, where more stringent controls are in place to minimise the risks of errors.

QA assessment of medicines for use in secondary care
The requirements for purchasing for safety in NPSA Alert 20 built on risk-assessment systems that had been developed and implemented by members of the NHS Pharmaceutical Quality Assurance Committee and had been implemented within the NHS. This process aimed to identify, and document in advance, quality issues or risk factors relating to the medicine and its packaging that could have given rise to an increased risk of medication error or patient harm. This process is outlined below and has been set out in an approved national policy.
There are two components to the risk assessment:
1    Pharmaceutical quality assessment (PQA)
2    Assessment and evaluation of supporting technical data and identification of potential issues that could cause local implementation problems following a contract change, i.e. potential acceptability issues (PAI)

This part of the assessment is aimed at ensuring the medicine meets the required specification and is of appropriate quality. The assessment also incorporates medication error potential analysis (MEPA). This element of the assessment process is designed to identify the areas of risk associated with the medicines’ labelling and packaging, including user information, e.g. patient information leaflets and technical data.

During the assessment, the assessor might identify important information or issues that are useful to end-users. These issues might not pose a medication error risk or highlight a product quality issue, but they need to be identified because they could cause local logistical problems.

Good packaging design principles
There are a number of potential hazards associated with medicines and their packaging that can lead to medication errors. These hazards include:

  • Confusing one medicine with another because of poor labelling or packaging.
  • Confusing one medicine with another because of similar manufacturer’s packaging across its product range.
  • Confusing a medicine with another after it has been removed from its outer packaging.
  • Providing the incorrect dose because of complex manipulation or calculations before administration.
  • Health and safety risks to staff/patients because of poor packaging and labelling.
  • Patient acceptability problems related to changes in medicine formulation.

To aid this process, the PQA process comprises 10 sections. The NPSA also coordinated a project in conjunction with experts from the fields of pharmacy, medicine and nursing, and design experts from the Royal College of Arts. The resultant guidance document, entitled ‘Design for patient safety: a guide to the labelling and packaging of injectable medicines’, was published in 2008.

The report gave detailed guidance to manufacturers and users regarding the design principles that needed to be incorporated into the packaging of injectable medicines to ensure the delivery of products that not only met regulatory licensing requirements but that were also safe in use.

This described general arrangements regarding user testing and use of colour and general design requirements, and further built on this with specific, detailed sections for ampoules, vials, pre-filled syringes and infusion containers.

Risk issues identified in use
Availability of critical information at point of use
The risks associated with the preparation and administration of injectables can be mitigated by providing the right information to the user at the point of use.

What manufacturers and users must realise is that this is not necessarily the same as regulatory compliance. To facilitate the safe preparation and administration of an injectable medicine, it is vital that the user has specific instructions available as to how to manipulate and administer the product at the time and place of administration.

To achieve regulatory compliance this only needs to be in the Summary of Product Characteristics (SPC) and not the package insert.

In reality, however, it is unlikely that the user will have access to the SPC at the time and place of administration, so this information must be either in or on the pack to ensure safe administration.

Vial size and displacement values
Some products are formulated in vials where the full-stated volume of diluent cannot be added, which results in the user having to resort to a complicated multistage process.
In other cases, or where the volume added leaves no headspace, reconstitution becomes difficult and time consuming.

Providing information on displacement volumes for paediatric dose calculations might not be part of a licensing requirement (depending on
the licensed indications and doses for that product) but in reality this reflects how many products will be used in the real world.

To allow safe dose calculations to be made in these circumstances, users need to be able to obtain this information at the point of use.

Device compatibility
Some medicines, such as infusion fluids, are used in conjunction with medical devices such as administration sets. When considering the introduction of a new medicine in this category, or changing an existing supplier, compatibility issues with these associated devices must be assessed in advance and any risks identified documented and managed
with a supporting education and training programme.
Using incompatible devices and inadequate training to support changes is associated with risks of administration errors. In addition, there can be spillage hazards to patients and staff from hazardous drugs.

It is important that manufacturers, purchasers and users of injectable medicines understand the risks associated with their use. These risks can be mitigated by the application of good packaging design principles and rigorous risk assessment of the safety in use of injectable medicines before they are considered suitable for purchase.

Any identified residual risks need to be clearly communicated to users, and suitable risk management and education measures put in place.

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