Global perspectives and compounding problems

Editorial Consultant, HPE

Pharmacists were the most helpful group of health professionals that contributed to shaping the law when the Clinton administration was drafting healthcare reform legislation, according to former President Bill Clinton in his keynote address. Healthcare is profoundly important to the health and well-being of both citizens and the economy, he continued. The US spends 18% of its outgoings on healthcare whereas no other country spends more than 11%. Examining the breakdown of costs, he said that 20% of expenditure was due to administration costs and rather more than 20% was rooted in diseases related to “lifestyle choices”. For example, type-2 diabetes, which accounts for more than US$150 billion annually, was now being diagnosed in children as young as nine years old. A further 40% of expenditure is related to the ways healthcare is delivered in the US. The remaining 15% goes on other items, including care for people in the last six months of life. In this context, President Clinton said that “making a living will would be a very good thing”.

In the US, life expectancy has continued to rise in recent years for all groups in the population except for non-Hispanic whites with little education. For this group, there has been a four-year fall in life-expectancy. Major contributory factors included increased smoking, increased obesity and overdoses of prescription drugs.

Three huge challenges now face the world, said President Clinton. First, there is too much inequality for social cohesion. Disparities in income, access to employment, education and healthcare were prime examples. Moreover, in half the world, people live on less than two dollars per day and often lack sanitation, clean water and food. Too much inequality slows economic growth and a better balance is needed, he said. Second, there is too much social instability. Some instability is helpful but too much can lead to “financial shutdown”. The third challenge is that of unsustainable energy consumption and climate change. In the US, some political parties still question the reality of climate change whereas Sweden, for example, has tackled the issue and has built one of the most energy-efficient countries in the world.

Turning to healthcare reform, President Clinton called on pharmacists to help implement the new Affordable Care Act properly, and “if it’s wrong, improve it”, he suggested. He also urged pharmacists to help to ensure that the advances in pharmaceuticals actually make people better and are coupled with improvements in lifestyle and healthy habits. Baby-boomers need to stay healthy, otherwise they will bankrupt the system, he commented. Lastly, he noted that deaths of young people due to recreational use of prescription drugs such as oxycodone was an area where pharmacists’ help was desperately needed, to educate people better about drug effects.

Faced with an ageing population, growing disparities between what needs to be done and the resources available in healthcare, increasing urbanisation and higher incidence and prevalence of chronic diseases, the profession of pharmacy is globally poised to make a difference to these issues and to be accountable for collective and individual actions to our communities and nations, said Henri Manasse [Professional secretary and Chair, Steering Committee for FIPed, International Pharmaceutical Federation (FIP)], recipient of the 2012 Francke Medal for significant contributions to international pharmacy practice.

Dr Manasse, who served as Chief Executive Officer of ASHP from 1996–2011, described some of his insights into the global evolution of pharmacy. The global challenges for the profession are significant, real and often rooted in the “less than optimal education that pharmacists receive at national level”. There is often a divergence between the skills and talent that a nation needs from its pharmacy workforce and what is taught in universities. Fortunately, leaders and organisations in pharmacy are tackling these challenges and a recent FIP Declaration, signed by 126 national pharmacy organisations, will help to take this forward.

The practice of pharmacy and its scientific endeavours in other countries could serve as important models for the US to consider, said Dr Manassse. Important examples include government/private sector initiatives in drug development in The Netherlands, the management of ambulatory care patients with certain diseases in Spanish hospitals and the design and image of community pharmacies in most of Europe. In addition, the granting of prescribing privileges to suitably qualified pharmacists in the UK and Canada represented a change in the status quo in the interests of patients and profession alike.

Pharmacy needs effective leaders and “engaged followership” for its ongoing development. The profession gains its franchise from satisfying the special needs of the communities that it serves, but it also needs to work with other professions and the local political infrastructure. FIP can help through its links with the World Health Organisation (WHO) and the United Nations’ Education, Social and Cultural Organisation (UNESCO) by gathering collective wisdom and expertise. It also advocates the critical role that pharmacy can play in advancing the health status of individuals. However, it can only do this when universities are preparing pharmacists for these roles and governments allow for appropriate scope and quality of practice in all settings where patients are cared for and where medicines are manufactured, distributed and sold, he concluded.

Each of the seven billion people on earth is exposed to no fewer than 14,000 doses of medicines during a lifetime, Claire Anderson (Professor of Social Pharmacy, University of Nottingham, UK) told the audience. This means that there is a huge opportunity for pharmacy services but, unfortunately, there is a critical shortage of pharmacists, she continued. Places that have poor access to essential and affordable medicines, such as sub-Saharan Africa and South America, are also short of pharmacists. This is important because the lack of adequate human resources for health threatens to undermine all efforts to strengthen health systems and improve healthcare. Pharmacy education provides the capacity, leadership and mechanisms for innovation and delivery of all pharmacy services, including science, research and development, policy, medicines’ expertise and supply, she argued. For these reasons, FIP and WHO had a special interest in pharmacy education. One current initiative is the FIP–WHO Global Survey of Pharmacy Schools. This aims to provide evidence-based information on the status of pharmacy education worldwide. Since 2010, data have been collected from surveys sent to countries in the six geographical regions identified by WHO, that is, the Western Pacific, Europe, Africa, the Eastern Mediterranean, Southeast Asia and the Americas. However, the database is still incomplete and Dr Anderson appealed to colleagues to contact FIP at [email protected] if they are able to connect the team to data associated with local pharmacy schools.

Surface contamination with antineoplastic agents results from broken vials, leakage during preparation or administration, contamination of the exterior surfaces of vials during manufacture and transfer from contaminated gloves or equipment, explained Tom Connor (Research biologist, National Institute for Occupational Safety and Health, (NIOSH) Cincinnati). The phenomenon has been recognised for many years and, since the first publication in 1993, numerous studies have been reported. One factor that contributes to surface contamination is the nature of the drugs themselves.

Cyclophosphamide and ifosfamide persist for long periods – one study has shown that, after a spillage, it took six months for the levels of cyclophosphamide on the floor to return to previous low levels, noted Dr Connor. Other important factors include the amount of drug handled, cleaning procedures and the stability of the drug – some are degraded by ultra-violet light or detergents. Cytotoxic/aseptic handling technique is critical and those who handle the drugs frequently usually have good technique, he commented. Finally, a “working climate” that promotes safety and the use of personal protective equipment is important. “Patient safety and worker safety go hand in hand”, said Dr Connor. The risk of surface contamination is unlikely to decrease in the near future as new procedures involving hazardous drugs such as isolated limb procedures, bladder instillations and hyperthermic intraperitoneal chemotherapy (HIPEC) become more common.

Paul Sessink (Managing Director, Exposure Control, Sweden) made the point that it is important to understand and tackle the four main sources of surface contamination in the pharmacy: external vial contamination, spillage during preparation, contamination of the biological safety cabinet and disposal of waste. In addition, the patient can be a key source of contamination, he noted. This means that patients’ toilets can be heavily contaminated. He advised that both water and mops should be changed after cleaning patients’ toilets to avoid spreading cytotoxic drug contamination to other ward areas.

Since the problem of surface contamination had been recognised, recommendations had been published to combat the problem. However, studies in US hospital pharmacies had shown that, even after implementation of all the required engineering controls, considerable amounts of contamination were still detected on the airfoil of the biological safety cabinet and on the floor in front of the cabinet. The biggest difference was made by the introduction of closed system drug transfer devices (CSTDs). Robotic compounding appeared to contain contamination effectively but it was important to realise that, once the inside of the robot cabinet was contaminated, it would be difficult to remove.

Turning to the question of acceptable levels of contamination, Dr Sessink said that, after much discussion in The Netherlands amongst pharmacists, nurses, occupational hygienists and toxicologists, a pragmatic approach had been adopted. Cyclophosphamide was used as a marker because it is highly toxic, persistent and penetrates the skin easily. If surface contamination with cyclophosphamide is below 0.1ng/cm2, then no cyclophosphamide is detected in the urine of workers, indicating that there is no measurable exposure. Furthermore, in all the studies of cyclophosphamide contamination to date, 99% of samples have been below 10ng/cm2. On this basis, the following ‘traffic lights’ scheme has been adopted in The Netherlands: The target contamination level (of cyclophosphamide) is less than 0.1 ng/cm2 – designated ‘green’. Levels of 0.1–1.0 ng/cm2 and 1.0–10.0 ng/cm2 are designated yellow and orange, respectively, and indicate the need for more frequent monitoring and the introduction of measures to reduce contamination. Levels of more than 10.0ng/cm2, designated red, are associated with an increased risk of cancer amongst workers and indicate the need for immediate action. This model helps pharmacists to interpret and use surface contamination data. In the US most hospitals fall into the yellow and orange regions, although some are in the red, commented Dr Sessink.

The implementation of some of these findings remains challenging for many practitioners. During the discussion, Dr Connor acknowledged that there is as yet no standard method for evaluating CSTDs and no easy way to determine the level of surface contamination, although NIOSH is trying to develop a quick-wipe test.

Hospitals that purchased injections from the New England Compounding Company (NECC) that were not patient-specific broke the law in Massachusetts and will therefore have no insurance cover (for adverse events arising from faulty products), according to Carmen Catizone (Chief Executive Officer, National Association of Boards of Pharmacy (NABP)). In a special session devoted to the evolving regulatory landscape driven by the meningitis outbreak linked to products supplied by NECC, Mr Catizone described the measures that were to be put in place immediately and the likely future developments.

NECC had supplied injections that were contaminated with fungal organisms and these had been linked to 36 deaths (as of December 2012) and many seriously ill patients. Although only licensed to compound injections against individual prescriptions, NECC had been preparing and supplying large batches. The regulatory system, the pharmacy compounding system, collaboration between the Food and Drug Administration (FDA) and the system for purchasing of products all broke down in this case, said Mr Catizone. The primary problem, he suggested, was one of resources. The State Boards of Pharmacy, who are responsible for inspection of pharmacy compounders, do not have adequate resources to fund this activity. In some States, pharmacists are no longer employed as inspectors because they are too expensive; inspections are therefore carried out by the same people who inspect funeral directors and massage parlours, he said. It was noted that, since the NECC event, 26 other compounding pharmacies in Massachusetts have been inspected, three of which were closed down immediately because conditions were even worse than those reported at NECC.

Drug shortages had played a role in this situation. The purchase of the compounded products was a way of obtaining items that were otherwise difficult to source. Purchasers did not realise that the compounded injections were not of the required quality.

Past efforts to tighten regulation of pharmacy compounders and bring it under the aegis of the FDA have failed because compounders have repeatedly argued that it was unnecessary. In light of this episode, it was likely that the pendulum would swing towards federal regulation, he predicted. In the short term, the NABP is setting up an inspection service. As part of this initiative, it will create electronic profiles for non-resident pharmacies (pharmacies that provide medications across state lines), starting in Iowa, so that future purchasers will be able to check inspection reports easily.

In the meantime, Mr Catizone advised purchasers of compounded products to undertake due diligence to protect themselves and their patients – “see how many warning letters have been issued”, he said. “You will be surprised that some of the pharmacies that you’re purchasing from are among those entities that have disciplinary actions on the record”, he added.