Sterile Pharmacy compounding services in hospitals

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Sterile Pharmacy compounding
services in hospitals:

Learning from the tragic lessons of the past
occurred in developed countries

Dr. Muhammad Tahir Aziz PhD
Associate Director Pharmaceutical and Ambulatory Services
Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore

After yet another widely broadcasted tragedy related to microbial contamination of compounded injections in the America, there is value in reviewing the long history of problems associated with sterile compounded medicines in the developed countries but above all there is a need to review the countries who even not think on these crucial services.
Aseptic services are the preparation and supply of sterile medical products, which require some dilution or other manipulation before administration. The preparation is carried out in the pharmacy aseptic service sub section by trained technicians, assistants and pharmacists under environmentally controlled conditions before being dispensed in a form ready for immediate use without further manipulation.
In response to the incident, US states appointed the Special Commission on Compounding Pharmacies, which was charged with developing recommendations for preventing similar occurrences. The final report of this commission contained more than two dozen recommendations. Key recommendations include :
* Directing the Board of Pharmacy to actively and continuously monitor the practice of compounding to minimize patient risk and allow for a rapid response to problems that arise
* board of pharmacy be granted the authority for oversight of free-standing pharmacies, hospital-based pharmacies, and physician offices
* The authority to establish content-specific expert advisory groups to address specialized areas of pharmacy practice
* Create specific licensing categories
* Establishing minimum requirements for pharmacy inspector training and education, and
* Enhancing pharmacy inspection schedules
Further, the US state was encouraged to strengthen the definitions, regulations, and continuing education requirements to ensure compliance to USP quality standards for compounding in all settings, including USP Chapter <795> Pharmaceutical Compounding: Non-sterile Preparations (USP <795>) and USP <797>.
The development and those who are running these services, the ultimate elimination of these problems must be built on an understanding of how they arrived at the situation we are in today. The purpose here is to aid that understanding by reviewing, in the context of hospital patient care, how the technology associated with injections has evolved, the major previous incidents of morbidity and mortality associated with compounded sterile medicines, non-availability of compounding services and the efforts made over the years to improve compounding practices. Pharmacy aseptic services are set to lead one of the most important improvements in patient safety for years. Significant investment may be needed, but pharmacists should not refrain from seeking it.
Pharmacy-based aseptic medicines preparation services are now a cornerstone of pharmaceutical care in all general hospitals of developed countries specifically in many hospitals across the Europe and United States of America. Estimates suggest more than six million ready-to-administer doses are supplied annually by these services in the UK only, supporting the care of some of the most critically ill patients in the health system. Specialist pharmacists and technicians in these services are contributing unique clinical and technical expertise to this care.
Advanced Pharmacy aseptic services now stand at the brink of leading one of the most significant improvements in patient safety seen for some years, with developments having application in the developed countries. Failing to grasp this opportunity will ring in the ears of hospital Pharmacist, health care providers and patients groups for years to come.

Recognizing clinical risk

As far back as 1976, developed countries identified serious failings in healthcare, with patients receiving intravenous treatments being exposed to unacceptable risk through contamination and error. Since then numerous reports, papers and studies have confirmed both this risk and the fact that patients are harmed as a result. Such cases include infection and cross-infection, particle contamination, errors in preparation, incorrect route or method of administration, drug confusion and incompatibility, and more. In the United Kingdom, 24% of all reported medicines-related adverse events and 58% of those causing serious harm or death concern injectable therapy.
These are risks which can be reasonably predicted - overworked nurses and doctors working in difficult conditions over long periods will make mistakes, particularly as therapies become more complex and patient’s conditions become more acute. Handling cytotoxic chemotherapy agents is an area of occupational risk for hospital staff. Chemotherapy agents include cytotoxic (cell-killing) agents, which are known to be occupationally hazardous. Non-cytotoxic agents are not proven to have occupational hazards, but should be handled with the same degree of precaution. Specific policies and procedures are needed to ensure quality patient care and optimal occupational safety during the administration of chemotherapy drugs.
Health worker preparing cytotoxic drugs without adequate precautions have been shown to contaminate themselves and their work environment. Reports of increased fetal loss and birth abnormalities in nurses, as well as anecdotal reports of other toxicities have been published. These reports relate to exposure occurring prior to the introduction of cytotoxic drug handling guidelines. The adoption of improved handling techniques and in particular the use of cytotoxic drugs safety cabinets has reduced exposure of cytotoxic drugs in health workers to levels that cannot be detected.

Approaches to risk reduction in pharmacy aseptic preparation

It is clear that pharmacy-based aseptic preparation services are ideally equipped to reduce or eliminate these risks. Most of the advanced pharmacies responded early in chemotherapy and nuclear-medicine services and in parenteral nutrition preparation, due to the high risks of staff exposure and product microbial contamination associated with these treatments. There is now no sanction for any manipulation of these treatments outside of controlled aseptic facilities. Expansion in favor of intravenous additive services will be a key part of the continued response. However, it is equally clear that capacity, organizational and financial constraints limit their scope for all injectable. A typical UK teaching hospital supplies some five million injection doses per year, with 40% requiring manipulation before administration.
The risk assessment approach should therefore be used to priorities existing pharmacy resources and secure funding for further development including :
* Compounding drugs specifically cytotoxic drugs must be prepared by Pharmacy personnel (including after-hours staff) who have undertaken appropriate training and validation in aseptic and cytotoxic drugs reconstitution and handling techniques
* Precise operating and safety procedures for the handling of compounding drugs and equipment must be established, documented and regularly reviewed
* The relevant drugs must be prepared in either a drug safety cabinet or in a pharmaceutical isolator cabinet
* Drug safety cabinet must be housed in a clean rooms and anterooms that comply with USP 797 or any international developed standard.
* Separate, clearly marked storage areas, including refrigeration must be available for all drugs
* Protective clothing must be worn by all personnel preparing cytotoxic drugs, cleaning cytotoxic preparation facilities, or cleaning cytotoxic spills.
* Contaminated waste generated during the preparations and the cleaning of spills must be segregated, packaged and disposed off in a manner such that personnel and environment are not contaminated.
* Procedures for transporting cytotoxic drugs within the medical facility must be prepared and maintained.
* Training, education, quality improvement and documentation is an integral part of compounding services.

Pharmacy-based aseptic preparation

Models where 100% preparation by pharmacy is the norm do exist in most of the countries. Although this is desirable from some viewpoints, it is unlikely to be achievable by most of the developing countries within their national resources.
Satellite aseptic services based near wards may be harder to staff due to contingency cover and skills needs, and may take additional infrastructure costs. However, such services support near-patient, short-lead-time care and allow specialist pharmacy staff to provide clinical pharmacy care as well as hold technical responsibilities. Economies of scale may be lost in favor of improved responsiveness and focus on one clinical specialism. This model particularly lends itself to cancer and nuclear-medicine services and the intensive/high-care environment.
Centralized aseptic services offer high-quality, high-capacity preparation for intravenous additives. These services may have a longer lead time but can smooth fluctuations in demand across the organization and better focus effort and skills. Parenteral nutrition is also best provided centrally due to the high levels of skill and control measures required and the wide range of wards served.
Outsourced supply can augment in-house services, and is particularly valuable for high-usage standard-dose products, leaving capacity in-house for the more specialist, shorter-lead-time or short-expiry drugs.

Aseptic Service development

As patient safety takes on a higher profile there is growing recognition that investment may be required to deliver it. Aseptic services should seek funding for service development, but should expect to bid for this in an increasingly competitive environment. Business cases will need to show:
* Robust financial modeling.
* Clear evidence to support the development.
* Strategic vision over the foreseeable future.
* Thorough option appraisal, including the non-pharmacy development options.
* Focus on the organizations objectives.
* Engagement and support from stakeholders and management.
The early involvement of planning specialists within the organization is important in following the often-complex business processes, and gaining support from likely user’s management will make the outcome of approval discussions more favorable.
While risk assessment will drive pharmacy-based preparation of high-risk injectable, there may be insufficient capacity or resources to transfer those assessed as at or below moderate risk. Additionally, not all high-risk drugs are suitable for pharmacy-based preparation. Aseptic specialist pharmacists have a key part to play in supporting wards to reduce this risk, using their unique combination of technical skills and clinical insight. Where pharmacists consider they lack this interface experience, it is vital that these skills are developed to improve service responsiveness and patient care. Potential ways to reduced risk with ward-based preparation; aseptic services pharmacists have a key role in leading with these examples.

Shaukat Khanum Pharmacy

Shaukat Khanum Memorial Cancer Hospital & Research Center Aseptic Pharmacy services, an exemplary standards and clinical experience, are ideally placed to reduce the real risks faced by patients from their injections - treatment intended to improve their health may instead lead to harm.

Why do it?

Aseptic services ensures medication management by the pharmacist right up to the point of administration thus improving the quality of care and reducing risk to patients in the following ways:
* Educed risk of microbial contamination
* Reduced risk of particulate contamination
* Ensures correct dilution
* Ensures stability and compatibility
* Ensures appropriate route and rate of administration
* Saves clinical staff time on the wards
* Reduces inappropriate use of expensive drugs

What preparations are supplied?

Cytotoxic injections are checked against the height, weight and surface area of the patient by the cytotoxic pharmacist against an agreed regimen signed by the consultant oncologist in accordance with the SKMCH&RC guidelines. The aseptic services section also prepares drugs for cytotoxic trials.
Total Parenteral nutrition distinguishes SKM Pharmacy from the rest to those patients who are not on natural diet. Parenteral nutrition is the administration of nutritional requirements by an intravenous route for those patients for whom the external route is not possible. The total requirements for 24 hours are supplied in a single infusion bag, which is prepared in the Aseptic Services section. The SKMCH&RC Pharmacy also provides this service to other hospitals, which do not have this facility.

Pre-filled syringes / Injectable 

Slow IV push syringes (bolus) are used at ward level wherever possible. These may only be administered by nurses who have completed the trust IV training course. ‘Continuous infusion syringes’ for use in a syringe pump are also prepared for use on the pediatric wards.

Intravenous drug additives

Some intravenous drugs require dilution in an infusion fluid before they can be safely administered. The Aseptic Services section provides a range of these drugs ready diluted in the correct volume of a compatible infusion fluid, labeled with the time for which it is stable and a recommended rate of administration.