HDA UK Media And Political Bulletin – 21 June 2017
|Use of Freezers
MHRA Inspectorate, Terry Madigan, 20 June 2017
This post describes the main issues seen when freezers are used by pharmaceutical wholesalers and provides an MHRA GDP inspectors’ view on possible ways to address them. Members should also refer to the GDP Green Guide and the inspectorate blog posts about refrigerators posted by MHRA GDP Senior Inspector Steve Todd.
Financial Times, David Crow and Barney Jopson. 20 June 2017
The FT reports that lobal sales projections for the pharmaceuticals industry in the United States have been cut by forecaster EvaluatePharma amid signs rampant drug price inflation is starting to ease after years of public pressure. “The continued political and public scrutiny over pricing of both the industry’s new and old drugs is not going to go away and we are starting to feel the impact now,” said Antonio Iervolino, head of forecasting at EvaluatePharma. Many in the industry are expecting President Donald Trump to issue an executive order on drug prices in the near future following a White House meeting of administration officials to discuss the issue.
Pharmaphorum, Andrew McConaghie, 19 June 2017
Pharmaphorum reports on the beginning of talks between the UK Government and the European Union negotiating team on Brexit. Despite a change in the UK Government’s rhetoric and signals that the UK was willing to compromise, Philipp Hammond insisted on reiterating the threat that the country would not be manipulated by the EU in entering a bad deal. Hammond signalled that he was in favour of an extended transitional arrangement, to help the UK avoid the ‘cliff edge’ Brexit which most economists agree would be hugely damaging to the country’s economy.
There is no Parliamentary coverage today.
|Use of Freezers
MHRA Inspectorate, Terry Madigan, 20 June 2017
This post describes the main issues seen when freezers are used by pharmaceutical wholesalers and provides an MHRA GDP inspectors’ view on possible ways to address them.
Most of the problems seen with use of freezers also apply to refrigerators and I do not intend repeating what has been written but refer the reader to the GDP Green Guide and the inspectorate blog posts about refrigerators posted by MHRA GDP Senior Inspector Steve Todd. What follows applies to pharmaceutical wholesalers; requirements specific to pharmaceutical manufacturers or those involved with laboratories or clinical trials should refer to specific MHRA inspectorate groups for advice.
When buying a new freezer the user should consider what it is to be used for and how they intend using it. This may appear obvious but the use of freezers that are not fit for use and unsuitable operating practices are regularly seen.
The most common use of freezers by wholesalers is for storing and conditioning cold packs for inclusion in passive transport containers and so I have included some information below on this topic. There may also be a need to store frozen medicinal products such as some vaccines, although the range of medicines that require to be stored frozen is small.
The intended use will determine the extent to which a particular freezer design meets your needs, or if any special measures need to be put in place. Consideration should be given to what temperature range you require, with a diversity of freezer models being available that maintain a variety of frozen temperatures. Storage conditions for specific medicines may be found by reference to packaging details or the Summary of Product Characteristics available from the manufacturers’ medicines regulatory authority or from the manufacturer. Topics you may wish to consider are presented in Table 1.
Prior to use the freezer should be fully qualified in line with GDP qualification requirements and the exercise documented both for small freezers, in which case qualification may be very simple, and large freezers installed by external specialists. Installation of the freezer should include risk assessment of the impact of the installation, e.g. effect of heat generation by the freezer on the surrounding area. Personnel should be instructed on how to use the freezer, and there should be notification to staff who are restricted from using it.
As with all equipment (including freezers and cold packs), don’t just rely on qualification data from the marketing brochure or sales rep., make sure qualification fully meets YOUR needs.
Domestic freezers are unlikely to have adequate power to rapidly freeze cold packs from room temperature but are designed for storage of ready-frozen product. This is shown in figure 1 where a single 500mL water-filled plastic container took over 24 hours to reach -18oC and in below in figure 3 where several packs took 7 days to reach acceptable temperature.
Figure 1 – Freezing water-filled container in a domestic freezer (courtesy of Seer Pharma)
Storage of medicines
The range of medicines that require storage in a freezer is small, and storage equipment most often seen are small freezers holding a small quantity of medicine. There is often a temptation to use the same freezer for other purposes such as conditioning of cold packs. This increases risk to the stored medicines, as high temperature excursions are created either by unconditioned cold packs loaded in bulk or by increased access to the freezer to load or remove the cold packs. It is therefore recommended that freezers used for storing medicines are dedicated in use or otherwise demonstrated to be not adversely affected by freezing cold packs. If the volume of frozen medicines is very small then the wholesaler should consider whether
it is worth either not holding those lines or outsourcing the holding of cold chain medicines to a wholesaler better suited to storing them. Some companies compromise by using dual refrigerator/freezer units. Although less expensive and with a smaller footprint than separate units, if one unit becomes non-functional then the both units are compromised. In addition, if both units are served by a single compressor, then the ability of the equipment to maintain temperature in one unit may affect its ability to maintain the other unit. This may be a concern if frozen medicines are stored and the refrigerator is in frequent use, if regular defrosting of the refrigerator occurs or where the thermostat setting for one unit is adjusted. It should also be appreciated that some domestic freezers may struggle to condition cold packs in a practical timeframe due to having smaller compressors and fans and those with automatic defrost may cause temperature excursions much higher than with some pharmaceutical freezers.
The majority of frozen medicines require storage in the range of -15oC to -20oC, and the responsibility is on the wholesaler to ensure they know what frozen temperature is required for a particular product and that the freezer used can maintain this. Requirements to temperature monitor and map freezers for storing medicines or conditioning cold packs are the same as for refrigerators.
Not all frozen medicines require storage at the same frozen temperature.
Conditioning of cold packs
In order for cold packs to perform consistently several points need to be considered. The first is to ensure that the correct type of pack is used as they are designed to maintain different temperatures e.g. -80oC, -15oC, +5oC, +25oC. This is brought about by the use of different phase change materials (PCM) which are materials that change between liquid and solid phases at specific temperatures. One effect of this change in phase is that the pack maintains a stable temperature throughout the change. A pack designed for -15oC may therefore not be suitable for maintaining +5oC.
The packs should be used in accordance with either the manufacturers’ instructions or the conditions established through undertaking a qualification exercise. This is because all packs are not the same, for example some packs designed to be conditioned within a refrigerator may not be suitable for conditioning within a freezer, and some types are not suitable for multiple freeze/thaw cycling.
When is a cold pack fully conditioned?
It is important to follow each manufacturer’s instructions as not all packs turn solid – some are fully conditioned in a soft gel state. The following is therefore a generalisation and relates to packs that turn solid.
As illustrated in Figure 2, the cold pack is originally at room temperature (shown as “A”) and quickly cools to approximately 5oC. During this time the contents of the pack are liquid and as it approaches 5oC (shown as “B”) it enters the solidifying stage. Properties of the cold pack mean that the contents solidify over a period of time until all the contents are solid (“C”). Throughout this stage the temperature of the cold pack remains at approximately 5oC due to the heat loss being associated with the change in form from liquid to solid rather than causing a decrease in temperature.
Figure 2 shows the temperature of a cool pack designed for use at 5 celsius being conditioned in a freezer operating at -20 celsius. The conditioning process can be seen as having different stages.
Once all the contents of the pack reach 5oC there is no option other than for further freezing to cause a decrease in temperature (between “C” and “D”) referred to as supercooling. If the pack becomes supercooled then it needs to be thawed to its stable temperature (“C”) before use to prevent freezing medicines below the intended temperature. Some packs may become damaged by supercooling.
Ideally the cold pack would be used at point C, before it gets colder than required and where all contents are solid at 5oC thereby giving it the longest period before the contents thaw (“melt”). If the pack was not fully conditioned (e.g. only to half way between “B” and “C”) it may fully melt in use despite appearing solid when first used. It is therefore important to understand that checking if a cold pack is conditioned based only on whether it feels solid is a false test of conditioning. It should also be remembered that the packs freeze from the outside therefore the middle may not be fully frozen even when the outside is solid; and likewise packs thaw from the outside, so a supercooled pack may have the appearance of being at the desired temperature but may still cool below intended temperature when placed in an insulated container. The user should therefore be able to trace how long a specific pack has undergone conditioning, and to prevent mix-up between conditioned and unconditioned packs.
Increasingly medicines are designed to be more thermo-stable, less vaccines are required to be stored frozen. There is however still a risk to refrigerated medicines caused by inadvertent freezing. Reference: Umit Kartoglu and Julie Milstien, Tools and approaches to ensure quality of vaccines throughout the cold chain, Expert Rev. Vaccines 13(7), 843–854 (2014)
Figure 3 – Ice packs conditioned in a domestic freezer (courtesy of Seer Pharma)
Figure 3 illustrates the extent of variation in conditioning ice packs in a domestic freezer. The fast-freeze cycle takes the temperature below the standard freezer temperature (-18oC) and can lead to supercooling. The data does not show if spread of data is due to variation in individual ice packs, conditioning method or freezer loading.
Figure 4 – Cold packs conditioned in a blast freezer (courtesy of Seer Pharma)
Figure 4 illustrates rapid cooling and less extent of supercooling of cold packs conditioned in a blast freezer and can be compared to the domestic freezer. The type of cold pack and freezer loading method are not necessarily comparable to that used in figure 3; however the main reason for the increased speed of cooling in the blast freezer is due to freezer design and power, 11.5kW compared to the domestic freezer 85W.
Selecting the type of cold pack to use
Apart from the temperature range, other considerations for selecting cold pack types include:
A few tips:
Figure 5 – Storage of cold packs in a small freezer.
Note that some packs are wrapped in paper (hygiene hazard), multiple types of pack are in use, and there is no indication of how long individual packs have been conditioned for.
Figure 6 – Poor storage practice.
Cold packs stored on the floor pose a hygiene hazard to the patient. They also risk getting damaged leading to leaking of contents in storage or in use that may corrode packaging, contaminate medicines or pose a handling risk
Pharmaphorum, Andrew McConaghie, 19 June 2017
Today marks the beginning of talks between the UK government and the European Union negotiating team on Brexit, with signs that both sides are willing to compromise.
Before the UK general election just over a week ago, British prime minister Theresa May was talking tough, signalling that ‘no deal was better than a bad deal’ – but this rhetoric has evaporated after her party lost their parliamentary majority.
The less Eurosceptic members of May’s Conservative party are now gaining the upper hand, including Chancellor Philp Hammond, who has now directly contradicted May’s earlier statement.
Yesterday he told the BBC’s Andrew Marr show: “No deal would be a very very bad outcome for Britain.”
Despite this signal that the UK was willing to compromise, Hammond insisted on reiterating the threat that the country would not be manipulated by the EU.
He added: “But there is a possible worse outcome, and that is a deal that is deliberately structured to suck the lifeblood out of our economy over a period of time.”
Hammond signalled that he was in favour of an extended transitional arrangement, to help the UK avoid the ‘cliff edge’ Brexit which most economists agree would be hugely damaging to the country’s economy.
However Hammond’s cabinet colleague David Davis is a more hardline Brexiteer, and will be leading negotiations with the EU, whose chief negotiator is French politician Michel Barnier.
David Davis said Europe should be in no doubt the UK is leaving the EU, a direct rebuttal of remarks made by France’s new president.
Emmanuel Macron has indicated that the “door remains open” for the UK to remain in the EU, comments which have been echoed by Germany’s finance minister Wolfgang Schäuble.
Despite the sudden – and seemingly terminal – decline in Theresa May’s reputation among the UK electorate, one poll shows she retains support to see the Brexit talks through.
A Survation poll for ITV’s Good Morning Britain programme put the opposition Labour party ahead by three points (44% to 41%), but also showed that 52% believed May was the best person to lead Brexit negotiations.
However the survey also showed a possible change of heart about Brexit: 51% said they would vote ‘Remain’ in a second referendum, with 49% supporting ‘Leave’.
As the political landscape has proven to be so unpredictable over the last year or more, no-one is confidently predicting the outcomes of the Brexit talks, however, especially because of their complexity.
The UK has quietly backed down from its earlier insistence on negotiating the terms of its withdrawal from the EU and a new trade deal simultaneously. The talks will commence with a focus on its withdrawal, including the disputed question of the money owed to the EU, and other wider issues such as rights of EU citizens to stay in the UK, and the future of the border between Northern Ireland and the Republic of Ireland.
One of the greatest fears for the countries remaining in the economic union, the EU27, was that Brexit could lead to more countries breaking away. However election results in the Netherlands and France have shown limited appetite for populist anti-EU policies, and the EU economic area looks set to outperform the UK in the next few years.
From Factory to Pharmacy
As part of our mission to build awareness, understanding and appreciation of the vital importance of the healthcare distribution sector, we developed an infographic explaining the availability of medicines. It identifies the factors that can impact drug supply, as well as the measures that HDA members undertake day in, day out to help mitigate the risks of patients not receiving their medicines.See the Infographic
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