Hospital Pharmacist
2008;15:25-27
January 2008

American Society of Health-system Pharmacists

Sharing recent advances in hospital pharmacy practice

Genomic medicine is likely to profoundly change the way we practise medicine, Robert Cook-Deegan, director of the Center for Genome Ethics, Law and Policy at Duke’s Institute for Genome Sciences and Policy, North Carolina, told conference attendees.

However, its use is being hindered by of a lack of policy to deal with the ethical issues involved. One concern is genetic discrimination. “The foremost reason that women do not get tested for breast cancer risk is that they fear that insurers … are going to discriminate against them or that they will be discriminated against when they are seeking a new job,” he explained.

There is a Bill currently going through the Senate to address this problem. Other concerns include privacy and confidentiality of people’s genetic information. “We still haven’t closed that gap between policy and what is happening in science. This constrains use of what is available,” he said.

Research needed

More research is needed about the practical application of DNA profiling, said Dr Cook-Deegan. He gave the example of the Amplichip, a diagnostic test that uses DNA profiling to determine a patient’s drug metabolism capability by cytochrome P450. This test predicts how patients will metabolise drugs such as antipsychotics and antidepressants, and thus help predict a patient’s response to therapy.

However, it is not certain how this information should be interpreted. “We need a formula for what doses should be given to what person,” he said. “This needs expensive, longitudinal clinical research.”

He raised the question of who would do this research. It is unlikely to be the company offering the test because it does not affect their reimbursement rate. “We do not have the incentive structure to drive the clinical decision paths the rest of the way to completion,” he said.

Commercial sequencing

DNA sequencing technology is getting faster and cheaper, said Dr Cook-Deegan. It currently costs between $300,000 and $1m to perform complete genomic sequencing for an individual. Over the next five years it is predicted that it will be possible to do this for just $100.

There is a big movement towards direct consumer testing that bypasses the healthcare system, he explained, and several companies believe there is a commercial market for providing people with their own genomic sequence. For example, US-based company Knowme offers customers whole-genome sequencing together with an analysis service to help them make sense of the information for $350,000.

There is a question about how such consumer models will affect the provision of care from healthcare professionals, said Dr Cook-Deegan. Furthermore, some policy makers are concerned that people will start to have unnecessary treatment.

Risk chart identifies cytotoxic risk to workers

A chart that enables pharmacy managers to identify the cancer risk level for workers according to the environmental levels of cyclophosphamide contamination has been developed by Paul Sessink, managing director of Exposure Control (a company which measures environmental contamination with cytotoxic drugs), Wijchen, The Netherlands.

He told conference attendees that the chart would enable pharmacy managers and staff to translate measurements of contamination and exposure into risk levels — terms that are understood by risk managers and hospital chief executives. It also shows when action should be taken and what monitoring is required.

The chart contains four levels, which are colour-coded for ease of use. The minimum acceptable level is “green” and requires no action. Low (yellow), medium (orange) and high (red) levels of contamination all require action to reduce risks to personnel. A “red” risk level requires immediate cessation of work.

The level of environmental contamination is measured using wipe samples of the working areas and the level of worker exposure is measured using urine levels of the drug. Results are compared with the ranges on the chart to determine the risk level.

The target for everyone should be the “green” minimum risk level, explained Dr Sessink. At this level, one extra case of cancer per million workers per year can be expected. The high risk (red) level is calculated to cause 100 extra cases of cancer per million workers per year.

A study of nurses in a hospital in the Netherlands showed that they were in the orange risk category — equivalent to 10-50 extra cases of cancer per million workers per year.

“We know that many hospitals in the US, Japan and Europe are currently in the red or orange risk categories,” Dr Sessink said.

Ensuring consistency of biosimilar drugs

Biopharmaceuticals (medicines derived from biotechnology) are expected to dominate the pharmaceutical market for the next few decades. Biosimilar products (ie, follow-on products produced when the original products are near their patent expiry) present special challenges for regulators and users, according to Roger Tredree, visiting professor, Kingston University, London.

In a session that explored the likely impact of biosimilar products, Professor Tredree explained some of the issues relating to the approval of these products in Europe.

Biopharmaceuticals are products that are made using recombinant technology. In contrast to traditional medicines they are large molecules for which the production processes are complex and can involve numerous steps.

At present, the important biopharmaceuticals are insulins, growth hormones, granulocyte colony stimulating factors and erythropoietin.

Product characteristics

Each biotechnology-derived protein is defined by its production process. The equipment, raw materials and process parameters all contribute to the characteristics of the final product. Thus, a biologics licence includes the product, the process and the facility (with technical and operational specifications), explained Professor Tredree.

Although these products are often heterogeneous they still have to be consistent. Since changes in the production process can alter the product, comparability of the final product (to a reference product) has to be demonstrated.

A good example of how a change in process can affect the product characteristics was the change in the formulation of Eprex SC (erythropoietin). When albumin was removed from the formulation a number of cases of pure red cell aplasia occurred as a result of the formation of neutralising antibodies to erythropoietin. It was then realised that simple changes to biological products can result in unpredictable immunological consequences, Professor Tredree said.

Eprex SC was withdrawn for the treatment of patients with renal anaemia in most countries. On this occasion the formulation change was made because the regulators advised manufacturers to remove human serum albumin from products, if possible, he noted.

In January 2006 the EMEA approved the first biosimilar growth hormone product, Omnitrope (Somatropin; Sandoz). For growth hormones, the EMEA requires clinical studies comparing the new product with a reference product and 12-month immunogenicity data before authorisation can be granted.

Currently several biosimilar growth hormone products are authorised in the EU and experience has shown that the EMEA guidelines can both be implemented and are realistic. In particular, all aspects of comparability are important and the reference product must be approved in the EU.

Future issues

Substitution of biosimilars will become an important issue as patents expire and this raises a number of concerns. The concept of generic equivalents will be difficult to apply to biosimilar products because of their complexity. When patents expire, branded biopharmaceuticals could become the norm, predicted Professor Tredree.

Therapeutic interchange, ie, switching to a product that produces the same clinical outcome, in collaboration with the prescriber, will be relevant to biosimilars as healthcare agencies seek best buys. A major consideration here will be immunogenicity, he noted.

In south London, a therapeutic tendering exercise was undertaken for erythropoiesis-stimulating agents. Tenders were received for four products and two companies were awarded contracts. The overall discount was about 70 per cent and the estimated annual saving to the local health economy will be about £5m.

Professor Tredree concluded that this type of interchange of biosimilar products can take place providing there is agreement with the prescribers and appropriate clinical control.

Pandemic flu — it’s not just about the antivirals

Common influenza still tends to be belittled by health care professionals, despite the significant mortality caused by the disease, said Michael Klepser, professor of pharmacy at Ferris State University, Kalamazoo, Michigan.

There is general “excitement” about the issues surrounding pandemic flu, he said, but it should be remembered that typical, annual flu is responsible for about 36,000 deaths every year in the US, and almost a quarter of a million hospital admissions due to secondary complications. Worldwide, a quarter of a million people die from flu every year, he added. Given that there is a relatively effective vaccine available for flu, this figure is unacceptable.

Turning to planning for a flu pandemic, Professor Klepser compared the clinical presentation of the H5N1 virus with typical influenza and emphasised how important it is that healthcare professionals recognise the difference.

Most patients infected with H5N1 need mechanical ventilation 48 hours after admission. “If you had an influenza pandemic which struck 100 patients in your community, and they all showed up at your doorstep, could you put them all on a ventilator?” he asked. “Even in a relatively small outbreak, we do not necessarily have the capacity to handle this.”

Another requirement is adequate stocks of antibiotics. Most deaths from flu are caused by complications secondary to bacterial infections that take hold when the hosts defences are weakened, especially those caused by Streptococcus pneumoniae and Staphylococcus aureus. Professor Klepser said it is important to be aware of these susceptibility patterns, and to hold sufficient stocks of antibiotics.

“It is going to be incredibly important that we do not get short-sighted in a pandemic just thinking about antivirals, and that we keep thinking about antibiotics,” he warned.

The case fatality rate for typical annual flu is less than 0.1 per cent, but that for disease caused by the H5N1 virus is 56 per cent. This figure is likely to be an overestimate, Professor Klepser explained, because it consists of data from the most ill people (ie, those who were admitted to hospital).

However, this figure is still alarming considering that the case fatality rate for the pandemic flu of 1918 was 2.5 per cent.

Drug errors in neonatal intensive care units

Most potential medication errors in neonatal medicine are caught by pharmacists, nurses or parents before administration, according to John Chuo, director of the neonatal intensive care unit (NICU) at the University of Medicine and Dentistry of New Jersey.

However, the importance of the pharmacovigilance team cannot be overstated. The core members of the team are a “4C” champion (responsible for ensuring the correct medicine, correct patient, correct administration and correct culture — ie, attitudes to patient safety), a doctor, a nurse and a pharmacist.

Invited members include a respiratory therapist, a laboratory technician, a hospital administrator, a lecturer and a patient representative. The pharmacovigilance team reports directly to the NICU leadership team.

Dr Chuo went on to discuss the barriers to the reporting of incidents. The “blame culture” still persists in many hospitals, he said, and this needs to change fairly quickly if progress is to be made. Lack of leadership and inappropriate delegation of ultimate responsibility play a part, along with statutory professional rules relating to error reporting.

In addition, there is some ambiguity as to what needs to be reported. Positive feedback to the doctor immediately after an error has been identified is particularly important, Dr Chuo said.

Large numbers of reports require appropriate data management. Common file management programs enable data mapping to be carried out which helps to identify clusters of similar events.

However, the data are often incomplete and a pharmacist is employed to go through each report, filling in missing data and clarifying ambiguous information. This “data cleansing” is an essential part of the data management process, he explained.

Dr Chuo concluded by saying that the pharmacovigilance team must have influence over governance. It has to be multidisciplinary, work to defined processes and must overcome organisational culture challenges.

Safety strategies

Mary C. Binghay, paediatric clinical specialist at Shady Grove Adventist Hospital, Rockville, Maryland, discussed pharmacy strategies to improve medication safety in the 30-bed NICU at her hospital. Initially, a multidisciplinary team was set up to evaluate the risks, to create a culture of safety and to create a strategic plan for incorporating best practices for improved medication safety in the NICU. Strategies included:

• Dispensing unit dose oral and intravenous medicines (This was consistent with best practice but increased pharmacy staff requirements.)

• A pharmacy “double-check” process for all NICU medicine orders (Again, this is consistent with best practice and it increases accountability and safety awareness.)

• Involving pharmacists in NICU nurse orientation and training (This has led to improved communication with nurses and practice consistency.)

• A computerised program for total parenteral nutrition (TPN) orders (This has standardised the process and has had an immediate impact on reducing the number of TPN queries raised.)

• The introduction of “smart” IV pumps, making use of standard concentrations of IV medicines and protocols

• Improving the order entry process by developing protocol templates and an antibiotic dose calculator (This has reduced the number of queries relating to illegibly written orders and dosing problems.)

• Implementing point-of-care barcoding and electronic medication administration records

Dr Binghay believes that in addition to improving the safety of the patients in the NICU, at least two hours per day are saved by pharmacy personnel in not having to deal with clarification issues.

Mobile emergency pharmacy for disaster zones

Building on the lessons learned after hurricanes Katrina and Rita in 2005, the Veterans’ Administration in the US has produced a prototype mobile emergency pharmacy to help in similar situations in the future.

The mobile pharmacy is housed in a modified shipping container. The 40-foot long, seven-foot wide space houses a patient counselling area, a dispensary and living quarters for a four-person crew.

It is air-conditioned and carries a generator, water supply and waste water tanks. The interior has a fungus-resistant, washable coating. An awning and external power sockets are provided so that additional outdoor dispensing stations can be set up if required.

There are also robust laptop computers and a satellite connection to the VA’s main prescription database. This allows pharmacists to identify prescriptions accurately and deal with urgently-needed medicines promptly. Non-urgent medicines can be requested from the VA’s consolidated mail outpatient service (a central service delivering medicines by post).

The satellite link will also provide access to computerised information resources. The mobile emergency pharmacy is designed to withstand winds from a category three hurricane.