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Research, Teaching and Testing Organisations

Summary of Review Report

Conformance with ACVM Legislation

Introduction

To gain a better understanding of how research, teaching and testing organisations (RTTOs) are working within the agricultural compounds and veterinary medicines (ACVM) legislation, the Approvals and ACVM Group Director commissioned the New Zealand Food Safety Authority’s (NZFSA) Compliance and Investigation Group (CIG) to carry out a ‘slice of life’ review.

Aims of the review were to:

• provide information on control of user programmes and their performance

• determine in broad terms where gaps in ACVM Group policy, standards and procedures might lead to lower than desirable levels of risk management under the legislation, or where regulatory intervention is excessive

• indicate where a formal audit might be warranted

• ascertain the level of awareness of approved codes of practice and standards

• assess the level of usefulness of the approved codes of practice and standards in developing operational procedures that ensure the conditions of prescription animal remedy (PAR) registration or exemption are being met

• highlight areas where common best practice is not being achieved.

Legislative regime

The review considered requirements laid down in the following legislation, standards and code of practice:

• Agricultural Compounds and Veterinary Medicines Act 1997

• ACVM Standard for Prescription Animal Remedy Veterinary Medicines

• ACVM Standard for Unregistered Veterinary Medicines Requiring Veterinary Overview

• ACVM Operational Procedures Standard 1: The Use of Veterinary and Human Medicines by Non-veterinarians for Research, Testing and Teaching Purposes

• Code of Practice for the Use of Veterinary and Human Medicines in Research, Testing and Teaching Organisations (Sponsor:The Royal Society of New Zealand)

Background

There are broadly three main types of RTTOs: university medical schools, biological schools and allied research institutes where animals are kept for research purposes.

RTTOs that operate within the umbrella of veterinary schools or commercial veterinary drug research, development and manufacturing companies have a long history of employing veterinarians for direct overall control of all research procedures, treatments and welfare issues involving the use of live animals. The same is true for state-owned research enterprises (SOEs), which have traditionally formed the backbone of pastoral agricultural research endeavours on behalf of various stakeholders within the government, farming and commercial arenas.

Until the 1970s, or more recently in some instances, it was not the practice in many other RTTOs to have a direct full-time veterinary presence. Traditionally, non-veterinarian researchers (known as Senior Technical Officers and trained in human medicine, biology and zoology) were in charge of the day-to-day treatment and management of the welfare of animals. In some situations a part-time veterinarian or a locally practicing veterinarian would be used on an ‘as needs’ basis for prescribing and dealing with animal welfare issues.

Change in legislation in the areas of both animal welfare consideration and drug use in animals has prompted these organisations to employ more full-time veterinarians to assist in compliance with the legislative requirements.

REVIEW

Sample

The sample of six RTTOs selected for this review cover the three types of organisations described above.

• Two universities with medical schools and schools of biological science where animals are used for research, testing and teaching. Both of these universities operate departments in multiple geographic sites and have a full-time veterinarian employed as Animal Welfare Officer/Director. Both also have other departments, e.g. psychology and physiology, where PARs are used.

• One university that is an RTTO using PARs in the school of biological sciences and also the psychology faculty at this location. This university did not have a full-time veterinarian employed. Locally practicing veterinarians were used on an ‘as needs’ basis for prescribing PARs and dealing with animal welfare issues.

• One company that provides contract research and is closely affiliated with an agricultural university institute. This company did not have a full-time veterinarian employed at the time of the review. However, this position had only recently become vacant and was being advertised.

• One multinational commercial drug research and testing organisation that manufactures PARs. There is some ectoparasiticide research and testing performed under the supervision of a full-time veterinarian. This multinational has also recently purchased a New Zealand-owned PAR research testing and manufacturing company which produces a range of large animal biological and hormonal vaccines. The research work done on these types of vaccine products is contracted to a major SOE’s subsidiary RTTO. This subsidiary RTTO has a full-time veterinarian working as Study Director.

• One large SOE organisation with sites spread through out New Zealand. This SOE produces significant quantities of animal products for human and animal consumption in tandem with performing comprehensive research and testing work on animals kept on its farms. This SOE employs a full-time veterinarian as Animal Ethics Committee Animal Welfare Officer. There has been a vacancy for a clinical veterinarian at this site for some time. Because the SOE operates from a variety of sites, several veterinarians may be involved in prescribing PARs.

The review included all selected parties and individuals involved in the purchase, storage, dispensing, training and use of agricultural compounds, veterinary medicines and unregistered veterinary and human medicines requiring veterinary overview in animals within the spheres of RTTO activity.

Special emphasis was placed on the documented training, recognition and recording of competence of non-veterinarians who use PARs under prescription advice and/or direct supervision of the prescribing veterinarian. All interviewees were advised prior to the review that these records would be examined.

Operational procedures and training

The nature of the RTTO environment means that risks attendant with the use of prescription veterinary medicines are heightened. These heightened risks are compounded where there is not a full-time employed veterinarian who has direct and overall control of the prescribing, dispensing and training of the end users of PARs. One prescribing veterinarian may have dozens if not hundreds of RTTO staff and students using PAR I and, more importantly, PAR II medicines without direct physical veterinary supervision. Therefore, the prescribing veterinarian relies heavily on robust and foolproof systems to provide assurance that prescription use is compliant.

As set out in the Introduction of the ACVM Operational Procedures Standard 1: The Use of Veterinary and Human Medicines by Non-veterinarians for Research, Testing and Teaching Purposes, “the Operational Procedure must be robust enough to provide a level of control over the administration of the medicines equivalent to that achieved if the veterinarian were present in the room”.

An RTTO needs to ensure that the prescribing veterinarian is provided with adequate staffing and delivery resources to ensure training of non-veterinarian staff (and students if appropriate) in the legislation and correct use of prescriptions. Training must be available for every new staff member or student before they become involved in the use of drugs on animals. Such training wherever PARs are prescribed is a requirement set out in several of the review documents:

• The ACVM Operational Procedures Standard 1: The Use of Veterinary and Human Medicines by Non-veterinarians for Research, Testing and Teaching Purposes states: “Where institution specific qualifications are nominated as appropriate levels of training these should be veterinarian-endorsed as appropriate and available for audit (section 4.2).

• The Code of Practice for the Use of Veterinary and Human Medicines in Research, Testing and Teaching Organisations (Sponsor: The Royal Society of New Zealand) states: “Skills or qualifications required must be at least the minimum necessary to enable competent use of medicines on animals, as directed by the veterinarian (section 4.2).

At each of the six locations visited the reviewer examined the training of non-veterinarian staff (and, where present, students) in the requirements of the ACVM Act as it applies to the use of veterinary, human and compounded medicines on animals in RTTOs.

One location provided full-time, seven module ‘on line’ training and competency assessment. (This training programme was being developed to such a high level of compliance that other competing RTTOs and a Government Department involved in wildlife research had purchased components of, or the entire training package.) At the completion of each module the participant completed the competency assessment, which was marked with an outcome of pass or fail. The physical dispensing controls in place at this location were linked to this ‘on line’ competency register and blocked the provision of prescription drugs to persons not recognised as competent. All staff and students at this location were required to undertake the training programme to various levels within the seven module system. Due to the development of the training system ‘on line’ it was available to authorised participants 24 hours/ 7 days per week.

At other locations training was provided on an intermittent basis. At one location this training was done once at the beginning of a calendar year. This system did not ensure that individual staff or students who arrived subsequent to a training session were trained and recognised as competent. At another location two out of three staff involved in the management and use of prescribed and dispensed PAR II had either not been trained or evidence of training could not be supplied to the reviewer.

At five of the locations visited there were various serious deficiencies found that could have been avoided with the provision of better training. These deficiencies ranged from a complete lack of individual training records, to inadequate reconciliation of PAR class II drugs by a Dispensing Drug Control Officer, to inadequate security of PAR I and II products. Three out of the six locations visited were found to have untrained, or inadequately trained, staff involved in the use or control of PAR II products.

At another location where drugs prescribed by more than one veterinarian were stored together in dairy sheds there were no staff training records available. It was not possible to determine which veterinarian had prescribed which drugs. Individual drugs were not identified with the prescribing veterinarian’s details, which is a requirement of PAR labelling. Because individual prescriptions were unlabelled and unidentified it was not possible to define which veterinarian was responsible for the instructions and training of non-veterinarian staff for the use of these separate prescription drugs as required by the ACVM Standard for Prescription Animal Remedy Veterinary Medicines, which states: “the product is held by the user to be used according to the instruction and training provided by the veterinarian” (section 2.4.4).

At another location there were well developed training records but there needed to be retraining of non-veterinary staff in the recording, reconciling, and disposing of expired or surplus drugs.

The RTTOs reviewed showed a large variation in the availability, standard, and recording of training. Similarly there was inconsistent recognition of competency. Deficiencies observed in the provision of training and recognition of competence were highlighted in the individual site Location Findings report.

PAR storage

In regard to storage, the ACVM Operational Procedures Standard 1: The Use of Veterinary and Human Medicines by Non-veterinarians for Research, Testing and Teaching Purposes states: “All medicines used under an OP must be kept in a securely locked room, safe, box or cupboard with one nominated person responsible for access and security” (clause 8).

At two locations visited there was a substantial quantity of expired PAR II drugs held both in central storage and also at depots in a laboratory surgery and in a farm dairy location. Given that some of this PAR II, (Ketamine, Rompun and Pentobarb Barbiturate) had expired several years ago it was advised that urgent appropriate disposal methods for all expired drugs be undertaken and that a location wide audit be undertaken to facilitate containment and disposal of expired stock. At this farm dairy drug depot location there was also inadequate PAR II drug security and use records. Here PAR II barbiturate drug was kept on a shelf in an opened unlocked cabinet in a room with door opened to the outside environs. Use records of this drug had ceased in 2004.

Only one location stated in their Institutional Operating Plan that “Veterinary and Human Medicines that have passed their expiry date should not be used in animals”. At this location there were monthly audits and expired stock was destroyed under veterinary supervision. A second location did state in their SOP that a monthly check of the Animal Emergency Kit was to be done and that any expired stock was to be discarded. However, this check did not appear to have been done for 12 months and the procedure was occurring at the time of the reviewer’s visit.

Record keeping and audits

The ACVM Operational Procedures Standard 1: The Use of Veterinary and Human Medicines by Non-veterinarians For Research, Testing and Teaching Purposes 1 outlines the requirements for record keeping including the need for log book reconciliations to occur at least every six months plus the need for independent third party annual audits (section B9 and appendix).

The Code of Practice for the Use of Veterinary and Human Medicines in Research, Testing and Teaching Organisations (Sponsor: The Royal Society of New Zealand) states: “Records of all drug purchases and disposals must be kept by the organisation and periodically reconciled with the Controlled Drug Register -- this should be conducted every 2 months on a departmental basis, and every 6 months on an institutional basis” (section 9.2). Section 9.3 of this same document also states that “An independent party should conduct internal audits annually”.

There was a widespread lack of uniformity in the recording of drug usage. At several locations drug control registers were generic pocket notebooks, pages were not numbered and mandatory columns were non existent or, if partially present, were hand drawn. Overscribing previous twink use and erasing were evident in drug control registers at two locations.

All of these factors combine to make accurate reconciliations and audits impossible. Training in the correct rules and acceptable drug use recording practices needs to occur and if possible these requirements should be standardised at least within organisations to facilitate accurate audits. At one location there was heavy over scribing corrections of the quantities of use of a barbiturate in a drug control register. This activity made the registers unable to be audited.

At one location the Institutional Operating Plan stated that the Drug Control Officer sight and verify the accuracy of each Principal Investigator’s drug use registers prior to dispensing further PAR II products. This was not occurring and PAR II products were being re-dispensed without drug register checks.

At each location visited recent audit reports of drug control and usage were sought. There was inconsistent adherence to the stated frequencies that each organisation stipulated for internal and external audits. This inconsistency and in several cases lack of any audits compromises an RTTO’s ability to be an efficient self regulator in the management and use of ACVM Act requirements.

At three locations there was a failure by the RTTO to perform audits at the required frequencies stated in either their Institutional Operating Plan or SOPs. Some locations had not performed any audits. The prescribing, dispensing, training, drug reconciliation and drug disposal systems all need to be audited at the stated frequencies. Stated internal and independent third party audit frequencies must also be adhered to in a timely manner.

At one location there had not been any audits or any drug log register recording of the use of PAR II Ketamine in a 12 month period. A staff member was disposing of expired Ketamine stock from a drug emergency kit at the time of the reviewer’s visit. The amount of Ketamine contained in the kit was less than the log book indicated. The PAR II disposal methods were not secure at this site.

It was noted at three other locations that while the Institutional Operating Plans stipulated the frequency of drug register and/or Institutional Operating Plan audits, these were not being done. Drug register audits were incomplete and annual audits had not been done. In fairness, at one of these locations the annual audit was due around the time of the review visit.

At one location audits had been performed at the stated frequencies.

In conclusion, at five out of six locations visited there were deficiencies in the standards of records being kept that compromised the ability to perform an audit or audits were not being performed at stated frequencies. Where deficiencies in the control and use of drugs were observed the reviewer has made recommendations for corrective actions.

Disposal of carcasses

A consideration outside the Terms of Reference that was discussed with some interviewees regards secure disposal of animal carcasses. Operating plans sighted stated that production animals destroyed or euthanased prior to the expiry of drug withholding times must be securely stored until disposal by incineration or burial. (Animal products that could possibly enter the human or animal food chain and currently being used at the RTTOs visited include meats and offals of sheep, cows, pigs and fish plus dairy products. Rodents used in RTTOs could also possibly enter the animal food chain.)

Most locations did have procedures for secure holding of such carcasses. However, there was no evidence that such carcasses were physically or chemically denatured (as per the treatment of product condemned as unfit for human or animal consumption in a meat plant) in order to render them unable to be used for human or animal food. Urgent consideration needs to be given to ensure that the appropriate authorities ensure such carcasses are denatured.

Where RTTOs use animals that might enter the food chain there is a loophole in the security of disposal of animals that possibly needs to be brought into line with the disposal of condemned materials or materials that are deemed unfit for human or animal consumption under the Animal Products Act 1999.

It appears common practice that security within RTTOs until disposal is adequate. However, several of the institutions visited employed contractors to uplift non-denatured carcasses for disposal at other sites. The security afforded by contractors should not be relied upon. The recent incidence involving the untraceable origins of barbiturate contaminated meat being fed with fatal consequences to zoo tigers reinforces this viewpoint.

Conclusion

This review has highlighted several areas where compliance with the legislation is not being achieved. At only one major university RTTO and one commercial RTTO was the reviewer satisfied that compliance with the legislation was full and satisfactory.

Locations that did not have a full-time veterinary presence or had currently unfilled veterinary vacancies and were under-resourced for their relative size and complexity had more non- compliances. However, throughout the review where deficiencies have been highlighted and brought to the attention of interviewees there has been a universal response that corrections to procedures would be vigorously pursued.

Summary of Recommendations for NZFSA

1. Audit of RTTOs

It is a recommendation of this review that a full ACVM audit be performed by the appropriate authorities on a sample of RTTOs in the near future.

NZFSA response

An audit is planned to be undertaken in May - June 2007.

2. Denaturing of all carcasses

It is a recommendation of this review that the appropriate authority consider the need for mandatory denaturing of all carcasses disposed of by RTTOs that are either within the withholding period for PAR or PAR equivalent drugs or whenever euthanasia is performed using barbiturate overdose. This denaturing should be of sufficient efficacy to both physically and chemically render such carcasses unfit for human or animal consumption. This denaturing should be performed prior to the release of such carcasses from secure storage for transport to disposal by burial or incineration.

NZFSA response

This observation has been circulated to NZFSA New Zealand Standards for any further action. Their initial response sees the issue raised as a potential one rather than actual example. They note that there are a variety of situations where animals are moved to a premises or place for disposal without being denatured, eg collection of dead stock for rendering, fish which is going for animal consumption or rendering. Denaturing is pretty much limited to mammals (ie not fish or poultry) and occurs at slaughter plants.