QUALITY ASSURANCE IN FISH DISEASE DIAGNOSIS

Olga Haenen1*, Eva-Maria Bernoth2*, and David Groman3*


1 ID-DLO Institute for Animal Science and Health, Fish Diseases Laboratory, P.O. Box 65, 8200 AB Lelystad, The Netherlands; e-mail: o.l.m.haenen@id.dlo.nl (6th September 199 onwards - o.l.m.haenen@id.wag-ur.nl)
2Aquatic Animal Health Unit, National Office for Animal & Plant Health, Department of Agriculture, Fisheries & Forestry, GPO Box 858, Canberra, ACT 2601, Australia; e-mail: Eva-Maria.Bernoth@affa.gov.au
3 Aquatic Diagnostic Services, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PEI, Canada C1A 4P3; e-mail: groman@Upei.CA


Contents of this Page


SUMMARY


1. INTRODUCTION

2. QUALITY GOALS


3. INTERNAL QUALITY ASSURANCE AT A FISH DIAGNOSTIC LAB


4. EXTERNAL QUALITY ASSURANCE AT A FISH DIAGNOSTIC LAB (proficiency testing)


5. QUALITY OF OPERATIONS AND RESOURCES RELATED TO INTERNAL AND EXTERNAL QUALITY


6. DOCUMENTATION OF QUALITY


7. EVALUATION OF LAB PROCEDURES AND VALIDATION


8. WHAT STEPS DOES QA TAKE AND WHAT ARE THE COSTS?


9. HYPOTHESIS

10. CONCLUSIONS


11. FURTHER READING/LITERATURE


ANNEXES: 1 - 3 : Costs: some examples


ANNEX 4: QA/QC , an American Fisheries Society Approach

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Summary


A workshop on Quality Assurance in Fish Disease Diagnosis was held during the 9th International Conference of the European Association of Fish Pathologists (EAFP) in Rhodes Greece, from 19th - 24th September 1999. In this workshop, a working document on how to standardize your work, and one step further, how to gain accreditation (ISO 9001, EN 45001, USDA) of diagnostic testing was discussed, together with a plan for interlaboratory quality assurance (QA), with respect to fish diagnostic laboratories.

It has resulted in a practical guide, about the steps required to reach these goals. The guide was published in an issue of the EAFP Bulletin (Vol 19(6) 1999) and is made available here for reference.

Eva-Maria Bernoth acted as chairperson for the Workshop

Apart from the discussion, a number of formal presentations were made:


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1. INTRODUCTION (from Bellamy, 1999)



Human laboratories are legally required to follow a set of quality assurance procedures. Although there are few regulatory requirements for quality assurance in veterinary laboratories, the quality of laboratory results is just as important and would be expected in any legal challenge to decisions based on laboratory results. Every veterinary laboratory, whether it is a full service regional facility or a practioner's office laboratory, should have a quality assurance program.

A quality assurance program in a veterinary laboratory is important to the laboratory, to the veterinarians who use the laboratory, and to the public. A laboratory quality assurance program has one overall objective - to provide confidence in the validity of the laboratory's test results and services. Veterinarians who receive timely laboratory results and are confident in their accuracy and reliability are more likely to make valid medical decisions on their patients. The public in turn will have increased satisfaction with the quality of veterinary health care.

The specific components of a quality assurance program will vary between laboratories, depending on the extent and complexity of the tests conducted, however, a quality assurance program for a veterinary laboratory should usually address the following: quality goals, internal quality assurance, external quality assurance, quality of operations and resources, and documentation of quality.

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2. QUALITY GOALS



"Each lab should define a set of measurable quality goals. The most important goals to set initially are specific quality goals for the accuracy and precision of a test aimed at reducing analytic errors to the minimum required for a valid veterinary application of the test" (from: Bellamy, 1999).

2.a What is Quality Assurance (QA)?


When we just look at the words themselves: "the guarantee for quality". For a fish diagnostic lab it means, that the results of the used test are correct. These results may be used to make a diagnosis of a disease outbreak, or to confirm absence of a disease, and are based on qualitative investigations. This implies that there should be standard operating procedures (SOPs) at the laboratory for every test.

The level of quality (QA) can differ:

2.b Where and for whom should QA be practiced?


From the local fish diagnostic lab to the EU reference lab, each at their own level. Who would be interested in your lab working to standard procedures, and possibly being accredited? The costumer, the vet, the fish farmer and the government officer because they can count on quality of your diagnosis or experiments. It makes your position as a lab stronger, because you can demonstrate that you deliver quality work, and you may print a "Q" on your letters. There should be some economic reason, otherwise the costs would be easily be too high.

2.c Why QA?


It is important to prove to a client that you "did what you "said" (wrote down in your protocol), and you "say what you did" (write down in your log book or on the form) what you did. For the employee, QA gives more insight into its their work.
Overall, it means that you have to work strictly to a regime, which you describe beforehand. To start with intralaboratory QC you write down the way you have worked until now, and make this the standard way. If your lab crew changes, the test is still well described and can be taken over by another technician staff member who has passed the working-introductory program, as laid down in documents.

Why would you accredite your fish diagnostic tests? To be certain that the test results are right, not only within your lab and according to your knowledge, but also related to reference samples from other labs and according to experts from other labs. In this way you can standardize your tests, and demonstrate that the results of your tests are always the same for a certain sample, independent of the day, technician staff member, weather conditions, mood, or whatever. It implies a lot of validation work, dependent on whether the test is a qualitative or a quantitative test: how specific is the test, how sensitive, etc.

2.d How can you reach this abstract form of quality?


You are not the first lab to do so, so there are guidelines present in this paper (see references), but also at the accrediting firms. It takes a big effort in the start, but the advantages in QA can soon be seen. For a minimum QA you could standardize your tests: write down how you do your test, make this the standard way, and double check results of the test by a second person. Use reference samples (virus, bacteria etc., preferrably from other labs) as positive controls. For accreditation: see 3-8.

2.e What system of accreditation should you choose?


If you have a small fish diseases lab with few samples per year, and carry out some research in fish diseases, you should probably choose intralaboratory QC or ISO 9001. It means that the first step of QA is reached, but the accreditation agency is not checking the scientific contents of your tests. As an example, they do not assess: why do you use this cell line instead of that one. Therefore, you show that you use your tests reliably and in a consistent manner, but you do not actually show that you are using the most appropriate test.

This latter assessment is the case with European Norm (EN) 45001: they critically look into the set up of your test or experiment, and ask for a strong validation of your test: for example prove that the cell line is always susceptible to the virus, test the specificity of the test, test that the temperature fluctuations of the incubator do not influence the test results, etc.. You could also consider partly accrediting your lab tests according to EN 45001. Necropsy is always difficult to objectively standardize, but, for instance, virus isolations methods for export releated certification on notifiable diseases can be easily standardized, based on the regulations of the European Commission.

Example: At AAHL (Geelong, Australia) they have laboratory accreditation (to ISO/IEC Guide 25) for Veterinary Testing under the NATA Veterinary Testing Laboratory scheme, and certification to the quality management standard ISO 9002.
Note : Of the quality management standards that apply to laboratories the standard ISO 9001 would apply if research activities were included in the certification ( i.e. design, development). Standard ISO 9002 can be used if research activities are not included in the certification. We do not further go into ISO 9002 here.

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3. INTERNAL QUALITY ASSURANCE AT A FISH DIAGNOSTIC LAB



3.a ISO 9001 criteria Internal QA


* What steps are undertaken to develop the end product (f.i. diagnosis) out of the delivered products or services? Standard Operating Procedures (SOPs) have to be worked out.

* How do you judge good or wrong related to the product? How can you trace back the process if the product was wrong?

* Describe the process of production or service (in SOPs)

* Define controls at the start, during the process, and at the end (including positive and negative controls, double checks of results reading etc.)

3.b Internal QA according to EN 45001


Make SOPs of your tests and reagents, based on the example SOP of the QA handbook
Use a log book, to document all relevant actions during lab testing, like titre calculations, which are not in the SOP or the result form. The procedure on how to use it should be composed and available.


3.c Internal QA according to USDA guidelines


Will be added prior to the workshop.

3.d Canadian recommendations on QA (Dept of Fisheries and Oceans Canada)


It is essential in aquatic animal health certification programs that disease diagnostic tests be consistent and reliable. The results of tests can have a significant economic impact on an aquaculturist by determining whether a facility can sell products to other provinces or countries. Data from these diagnostic tests are also used to determine whether zones are free of specific diseases or not. The disease designations for zones are, in turn, important when assessing disease risks of proposed transfers of aquatic organisms.

To improve and enhance the consistency and reliability of diagnostic tests, it is proposed that a new Quality Assurance (QA) Program be implemented for finfish disease diagnostic laboratories. This program will be developed by Department of Fisheries and Oceans, and written up as a separate Quality Assurance Manual.
The Manual will be a policy document, outlining the intent of the QA Program. The main purpose of this program will be the production of high quality, or reliable laboratory results. Reliable in this case means accurate and precise results of appropriate sensitivity and specificity for the use to which the test has been put and for the test itself. In addition, a function and goal of the QA Program is to provide evidence of this quality, not only to the diagnostician but also to clients and to program managers.

Reference Laboratories

A key element of the QA/QC program will be the identification of reference laboratories for specific finfish diseases and disease agents. The basis for this recognition will be the presence of expertise and specialized equipment to test for the specific diseases or disease agents.
Reference laboratories will be available to confirm the detection of diseases or disease agents by other diagnostic laboratories, and investigate the identification of new diseases or disease agents.

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4. EXTERNAL QUALITY ASSURANCE AT A FISH DIAGNOSTIC LAB (PROFICIENCY TESTING)



An example is the inter-laboratory proficiency testing scheme for EU National Reference Laboratories for fish diseases. It is based on the Coucil Directive 91/67/EEC. In the last EAFP Conference Dr. N.J. Olesen presented a paper about it (Hastings, 1997). In short, coded lyophilized preparations with or without virus from naturally or experimentally infected fish tissues are sent to participating laboratories, accompanied by written procedures and recording protocols. The labshave to titrate the samples on standard cell lines and identify them. The aim is to obtain uniformity between the reference labs. Apart from this aim, this type of QA is useful to evaluate methodologies. The interlaboratory variation is calculated and the median of the test results.

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5. QUALITY OF OPERATIONS AND RESOURCES RELATED TO INTERNAL AND EXTERNAL QUALITY



5.a. Quality of Operations and resources related to ISO 9001

The following subjects have to be documented:

5.b Quality of Operations and resources related to EN 45001

The following subjects have to be documented:


5.c Quality of Operations and resources related to USDA guidelines

The following subjects have to be documented: text will be added prior to the workshop.

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6. DOCUMENTATION OF QUALITY



6.a

In practice, the quality book for ISO 9001 of our lab (ID-DLO, Lelystad) has the following contents:


6.b Documentation of EN 45001 (Sterlab):


General working documents and procedures:
For instance: use of a log book, organization of the tasks in the primary process, internal audits, management of quality documents at department or lab, ordering materials, example of standard operating procedure (SOP), model document for method of preparation, procedure of non standard activities, validation of immunodiagnostic and virological tests, external quality control of immune diagnostic tests, management and archiving samples and reports

Organization of the lab:
Organization scheme with persons, description of each job, task matrix of the lab, cv's per person, settlement program per person

Standard Operating Procedures (SOPs):
Each with the set-up: title, aim, definition/declaration, principle, precision (validation), requirements, procedure, results interpretation and registration, storage of samples and other materials, registration, remarks, references, annexes

Results of tests:
The results of each sample should be read by one person, and the result should be checked by a second person. The data of each sample tested at the lab should be well documented, preferrably on standard forms. The results of samples tested at the lab should be well documented, preferrably on standard forms. EN 45001 wants extra control of each reading. If the standard operating procedure is altered, this should be written down and explained with reason in the log book and the standard form. It should be proven that this other method is not negatively influencing the result of the test. The report with the results should also be checked by a second person. All notes, forms and letters should be kept in store for at least 5 - 10 years.

Validation testing:
Validation of tests is a separate chapter (see 7). All SOPs and test results related to validation have to be well documented. Also, calculations of validation data have to be accessible in the log-book or another file.

Temperature data of fridges, incubators etc.:
Every day or other time span the temperature of the apparatus which are used for the tests at the lab have to be registered. For that we use digital thermometers, which give the minimum and maximum temperature in the last period since last resetting. In that way you can note malfunctions of the apparatus, and understand why for instance the cell line is killed during the weekend at too high temperatures, and take measures. In your SOP you note the temperature tolerance limits of the fish cell lines, bacteria etc., and in the documentation of the apparatus you define the accepted temperature range.

Technical apparatus and maintenance data:
The frequency of maintenance check of each apparatus (from pipetting apparatus to incubator) by the technical service should be defined in a SOP, and the maintenance reports should be documented and kept for control.

Storage forms of samples and reference samples etc. etc.:
From each sample it should be easy to find out through forms, if it is stored, and if so, where (what box no. etc.), at what site (fridge, -20oC or -70oC for instance). If a vessel container is removed, its' number should be crossed out and a stripe should be made through it in the storage overview forms, so that you know at all times from the documentation what is in store. The reference samples should also be stored at defined places. The results of testing the reference samples at your lab, and the origin of these samples should be well documented. They are needed as controls, especially for the validation of your tests.

Safety regulations:
General safety procedures should be known to all employees, and documented at a central place per department or laboratory.

6.c Documentation of Quality: Canadian recommendations (Dept. of Fisheries and Oceans):

The Quality Assurance Manual and related operations documentation will contain the following:
* a quality policy statement, including objectives and commitments; the organization and management structure of the laboratory, its place in any parent organization and relevant organizational charts, and the relations between management, technical operations, support services and the quality system;
* the laboratory╠s scope of test activities; the control and maintenance of the quality manual and related operating procedures documentation
* job descriptions of the key management and technical staff or reference to them;
* identification of the authorized signatories for certificates and reports;
* validation of test methods used at the laboratory;
* sampling procedures;
* the handling of test items (samples);
* records and a descriptive listing of the major items of test equipment and on any reference measurement standards, including reference materials, used;
* reporting the test results;
* monitoring the test results;
* feedback and corrective actions whenever discrepancies are detected, or departures from documented policies and procedures occur;
* departures, in exceptional circumstances and for valid technical reasons, from the laboratory╠s documented policies and procedures, or from standard specifications;
* dealing with feedback from customers;
* protecting confidentiality and proprietary rights, both the laboratory╠s own data and know-how, and information derived from clients;
* internal audits and management reviews.
* Qualifications and training of the staff to ensure compliance with the quality system and related operating procedures;
* the retention of records;
* if work has to be subcontracted, procedures to ensure that subcontractors are competent and comply with the requirements of this Guide;
* procurement of support services and supplies;
* customer service including the control over communications with the customer.

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7. EVALUATION OF LAB PROCEDURES AND VALIDATION


One way to evaluate lab procedures is by internal and external audits. They are held for instance once a year. The auditor checks whether the implementation of the QA documents is correct at all levels of the process, and for instance, if whether the vessels containers with virus no. X can indeed be found in the freezer at the site, which was documented in the forms. The internal auditor is a colleague from the same institute, the external auditor is someone from an official accreditation agency. In both cases, a report is made of the audits, and action points are formulated to improve QA. If the quality appeared to be too low, the external agency may withdraw the approval of the test.

To validate the SOPs at your lab, there are schemes highlighting which data need to be collected. Table 1 presents roughly, what validation should take place in which case (data from ID-DLO, Lelystad, The Netherlands)

Table 1. Validation of qualitative and quantitative tests for EN 45001
1 = always needed
2 = if relevant
3 = not necessary


Quantitative method#
Qualitative method*

Low concentation level
High concentration level
Test:

New
Method

Standard
Method

Changed
Method

New
Method

Standard
Method

Changed
Method

Correctness
1
1
1
1
1
1
3
Repeatability
1
1
1
1
1
1
3
Reproducibility
1
1
1
1
1
1
3
Range of detection
1
2
2
3
3
3
1
Range of determination
1
2
2
3
3
3
3
Linearity
3
3
3
1
3
3
3
Selectivity
1
3
3
1
3
3
1
Robustness
1
3
3
1
3
3
1

(#) Like ELISA or Serum neutralisation assay
(*) Like virus isolation and typing by IFT


Validation is important to determine and prove the quality of your test. First define the confidence level you want to reach (f.i. 95%).

Correctness:
The correlation between the mean from a set of tests (10 samples f.i.) and the individual data. It can be determined comparing your sample with certified reference samples, for instance your standard control sera with positive and negative control sera from another reference lab. It can also be determined by participating in a proficiency test (see chapter 4). Related to a changed method, this change can be validated by comparing the results of a set of samples from the original and changed test. it also can be used for recovery experiments, in which the to be tested component is added to the sample.

Repeatability:
This is a measure for the variance between results of testing identical samples with the same methods at exactly the same circumstances. In practice: the variation in test results of 10 times the test by one person at the same day at one lab. For an ELISA for instance, use sera with a low, medium and a high titer, and test them each 6 times. It is calculated by CV% = SD/X (mean) * 100%.

Reproducability:
Are the results of a certain sample tested at your lab the same when tested at other labs? It can be calculated from results within the laboratory (internal reproducability) or between labs (proficiency tests), see 4. It tells something about especially systematical failures in a method. The variable circumstances can be for instance: different technicians, different apparatus, different days etc.. For an ELISA for instance: test sera with a low, medium and high titer each 6 times. It is calculated from the relative standard deviation, with CV% = SD/X (mean) * 100%.

Range of detection:
Are the results of a certain sample tested at your lab the same when tested at other labs? It can be calculated from results within the laboratory (internal reproducability) or between labs (proficiency tests), see 4. It tells something about especially systematical failures in a method. The variable circumstances can be for instance: different technicians, different apparatus, different days etc.. For an ELISA for instance: test sera with a low, medium and high titer each 6 times. It is calculated from the relative standard deviation, with CV% = SD/X (mean) * 100%.

Range of determination:
3*range of detection.

Linearity:
For instance how linear is the titration result in your ELISA? It can be determined by linear regression

Selectivity or specificity:
aHow selective is your agar medium to the pathogen you want to isolate? How selective is the antiserum related to the different viruses? What is the influence of metabolites of a certain chemical component on the result? The specificity is calculated by deviding the no. of negative samples in a test by the real no. of negative samples.
Example ID-Lelystad: selectivity of the IIFT serum: tests all relevant fish viruses in your test: there should be no cross reaction, and no repeats are necessry.

Robustness:
What happens with the test result if one of the procedure steps is forgotten, or, if the temp of the incubator has been 5 degrees too high etc.. It has to be defined for all critical possibilities of failure in a test. It cannot be calculated, but you can add a table with the consequences of abnormalities related to the test related to the test result. This should be one of the first validations to make in a new test.
Example ID-Lelystad: what is the influence of :
* concentration of media: test each ingredient at 3 concentrations (0.1, 1 and 10x), in trplo per cell line
* incubation time of the test (0.5, 1 and 2x)
* medium exchange, like culturing the cell lines with EMEM instead of HMEM
* temperature of incubation: test all cell lines in triplo at 15, 20, 26, 30 and 37÷C.

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8. WHAT STEPS DOES IT TAKE AND WHAT ARE THE COSTS?


* Identify customers/stakeholders that may be interested in your lab being accredited.

* Get a vision of where your lab may be in the next five years (does it need accreditation; are the customers going to change; will you be doing fully-cost recoverable contract work; will you have to compete for work?)

* Choose what system you may usefully apply.

* Contact a consulting firm to advise you on details.

* Do a proper budgeting for the selected system.

* Do a cost benefit analysis.

* Decide whether you can 'afford' it.

Then you start with the 'real' work, getting the data together, see 3-7

The costs for QA can be very high, especially if external accreditation agencies are involved. In the appendix 1, 2 and 3 examples are presented on costs made by different institutes to accredite their tests. The cost benefit analysis is important. However, if your lab is known to be a qualitatively good one, it might pay back to some extent.

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9. HYPOTHESES


* Working to QA diminishes the scientific output of the organization, because it takes too much time

* Engaging on an accreditation process MUST be budgeted for in advance, both in staff resources (time) as well as real $$ figures.

* Motivation of each participant in the process is necessary to work with QA, and is more important than any written letter in the QA book

* If you want to talk about international QA the need of central production of standards (antisera, cell lines, pathogen batches, and other biologics) is unmissable, as is the regular interlaboratory proficiency testing.

* QA? Is it better to make the standard work for you rather than you work for the standard (J. Tanti).
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10. CONCLUSIONS



* QA is becoming more and more important in fish diagnostic labs
* There are many QA possibilities, from SOPs without accreditation until EN 45001
* QA is expensive, but might pay back because of the gained quality and status of the lab
* there is a need for a simple manual for small and bigger fish diagnostic labs, about how to start and work on QA, with practical examples
* the US and Canadian QA system and the QA system in Europe and Asia could be better coordinated and benefit from eachother
* as a result of the discussion during the workshop the EAFP Council will further focuson QA towards other legal authorities

Follow up:
From the discussion it is clear, that QA is alive as a new topic in fish diagnostic laboratories. The need for practical advice on how to start with and implement QA was unanymously expressed by the audience. Apart from the actions of the EAFP Council some volunteers are needed to pursue this further (see the note in this bulletin). Reactions can be sent to one of the authors of this working document.

Acknowledgements
The authors are grateful to the invited speakers of the QA workshop for their interesting lectures: Dr. D. Alderman from the Office International des Epizooties, Dr. S. LaPatra from the QA/QC Committee of the Fish Health Section of the American Fisheries Society, and Dr. Alex Thierman from US Department of Agriculture.

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11. LITERATURE/FURTHER READING


Bellamy, J., 1999. Re: Quality Assurance in Veterinary Laboratories. In: Update and Letters to the Editor. Vol 15 (1): 13-15. Published by The College of Veterinarians of Ontario, Canada.

Dybkaer R. et al., 1993. A quality manual for the clinical laboratory including the elements of a quality system. Proposed guidelines. Scan. J. Clin. Lab. Invest. 53: Suppl. 212: 60-84.

European Standard, 1989. EN 45001. General criteria for the operation of testing laboratories. CEN/CENELEC, The joint European Standards Institution, Brussels, Belgium, UDC 620.1.008.6.

European Standard, 1994. EN ISO 9001. Quality systems. Model for quality assurance in design, development, production, installation, and servicing. CEN, European Committee for Standardization, Brussels, Belgium. UDC 658.56:006.83.

Hastings, T.S., 1997. Quality Assurance in fish and shellfish disease work. Bull. E.A.F.P. 17,6: 261-263.

ISO 9001 : 1994 Quality systems - Model for assurance in design, development, production, installation and servicing. Available from the International Organization for Standardization (ISO), or the national Standards body in individual countries.

ISO 9002 : 1994 Quality systems - Model for quality assurance in production, installation and servicing. Available from the International Organization for Standardization (ISO), or the national Standards body in individual countries.

ISO 8402 : 1994 Quality management and quality assurance - Vocabulary. Available from the International Organization for Standardization (ISO), or the national Standards body in individual countries.

Laboratory Accreditation : ISO/IEC Guide 25 - 1990 General requirements for the competence of calibration and testing laboratories. (soon to be replaced by ISO 17025). Available from the International Organization for Standardization (ISO), or the national Standards body in individual countries.

Lloyd, W.E. & Stahr, H.M., 1980. Quality Assurance in laboratory practice [veterinary procedures]. Proceedings of Annual Meeting, American Association of Veterinary Laboratory Diagnosticians (USA), no. 23 : 417-419.

National Association of Testing Authorities (NATA) 1. Guide to the Development of a Quality System for a Laboratory. 2.General Requirements for Registration 1992. 3. Supplementary Requirements for Accreditation - Veterinary Testing. Available from NATA , Australia, 7 Leeds Street, Rhodes, NSW 2138.

Osuch, M.A.V., 1996. Preparing for your ISO quality management guideline audit and registration. Genetic Engineering News, Sept. 1996: 17.

Quality Management : ISO 9000 : 1993 Quality management and quality assurance Standards. Available from the International Organization for Standardization (ISO), or the national Standards body in individual countries.

Rohle, R., 1993. Externe Qualita tssicherung in Deutschland. CCKL bulletin, March 1993 8(1): 1-2.

Unites States Pharmacopeia XXII, 1989. National Formulary XVII, general chapter "Validation of Compendial Methods". The US Pharmacopeial Convention, Inc., Rockville, Maryland, p 1710.

WHO, 1993. Report meeting on "Quality Assurance related to health laboratory technology". April 21-23, 1993, Geneva.

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ANNEX 1 : EXAMPLE OF COSTS OF QA (in euro's)



QUALITY MANAGEMENT SYSTEMS -An Australian example

Compiled July 2, 1999

Relevant Facts Using Laboratory XXX as an Example

The following costs are for certification and accreditation of Diagnostic Services only.

Quality Management Systems


* Certification Standard: AS/NZS ISO 9002:1994

* National Association of Testing Authorities (NATA), Australia accreditation obtained: "Accredited Laboratory in the Field of Veterinary Testing"


Costs (euro's)

The process of registration and accreditation required approx. 24 months to complete.

Salaries:
1 QA Manager (25% for first 6 months in training - then full time for 18 months) and approximately 20 other staff members contributing approximately 10% of their time.

Total Salary Cost (2 Years): Salary + On-Costs (20%) = 88,503.-
Training (senior staff and internal auditors): 3,218.-
New Equipment (including computer software): 6,436.-
Registration and Certification: 3,218.-
TOTAL COST euro's 101,375.-

Maintenance Costs

QA Manager (50%: 30% on maintenance; 20% on development): 9,655.-
12 Staff Members contributing 5% of their time
(internal audits, equipment calibration and monitoring, document management):
9,655.-
External audits, annual registration fees: 1,609.-
TOTAL MAINTENANCE COSTS: euro's 20,919.-

Notes

The following consideration needs to be emphasised. Prior to accreditation and certification, Laboratory XXX had infrastructure, systems (engineering support) and many of the requirements for accreditation and certification already in place. Other institutes may not be starting off at the same level. Much of the process is concerned with documentation and maintenance of records. Establishment of computer systems to underpin this process is essential for an organisation of this size. Even with the level of sophistication present at Laboratory XXX the total time to complete the process was underestimated by 50%. Costs do not include overheads.


ANNEX 2 : EXAMPLE OF COSTS OF QA (amounts in euros)


A second example of veterinary institute Y

Relevant Facts Using Laboratory Y as an Example


The following costs are for certification and accreditation of Diagnostic Services and research.

Quality Management Systems


* ISO 9001: all research and related sustaining departments

* EN 45001 : 75 tests at 6 labs

* Good Laboratory Practice (GLP): animal experiments

Accredited Laboratory in the Field of Veterinary Testing

Costs (euro's)


The process of registration and accreditation required at least 48 months to complete.

Salaries:
2 QA Managers (full time) and approximately 8 other staff members contributing approximately 10% of their time.

Total Salary Cost (per year):



1,089,072.-
Training (senior staff and internal auditors): 13,613.-
New Equipment (including computer software): 9,075.-
ESTABLISHING CERTIFICATION AND ACCREDITATION: TOTAL COST: euro's 1,111,760.-

Maintenance Costs
2 QA Managers (full time) 181,512.-
8 Staff Members contributing 10% of their time 72,604.-
External audits, annual registration fees:

ISO:
EN 45001


9,075.-
11,344.-
TOTAL MAINTENANCE COSTS : euro's 274,535.-


ANNEX 3: EXAMPLE OF COSTS OF QA (amounts in euros)


A third example

Here are estimates for QA costs for a lab, which would be classified as a moderate sized veterinary diagnostic laboratory at a university.

Total Budget including salaries: euro's 1,554,200.-

Cost for Establishing Certification/Accreditation year 1

Salaries 10% of budget
Training 5% of budget
New Equipment 5% of budget
Registration and Certifications 5% of budget
TOTAL COSTS 25% of budget

Maintenance Costs Yearly:


Salaries for QA (contribution by all personnel) 10% of budget
Internal audits, standards, calibration etc. 2.5% of budget
External audit programs and registration fees 5% of budget
TOTAL MAINTENANCE COST PER YEAR 17.5 % of budget

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ANNEX 4: QA/QC, an American Fisheries Society Approach


In September 1996, representatives from federal and state government, the private aquaculture industry and university researchers met in Denver to discuss the use of advanced technologies in aquatic animal medicine. The general consensus of the group was that the use of advanced technology was not a new topic but one in which concerns have intensified as a result of recent applications of extremely sensitive DNA test procedures. The test procedures were new enough to the aquatic animal health field that they may have lacked specificity validation and standardization regarding use, application, and interpretation of results. The results of these tests could result in economic loss to the aquaculture industry and loss of valuable fish stocks to the sport fishing industry. A series of questions were then sent to the states, fish health protection groups and private industry for response and thoughts on the use of advanced technologies.

In response to this letter the Great Lakes Fish Health Committee submitted a response to the American Fisheries Society Fish Health Section President JoAnn Leong voicing its concerns about the use of advanced technologies. The Great Lakes Fish Health committee requested that the American Fisheries Society Fish Health Section take the lead role in developing a unified approach to the following areas:


* Develop a QA/QC program for fish diagnostic laboratories;

* Develop a process through which new fish health technologies can be validated and incorporated into regular use;

* Develop guidelines for resolving inconsistent test results when multiple diagnostic techniques are used to detect the same pathogen 'Gold Standards'.

As a result of the letter from the Great Lakes Fish Health committee the American Fisheries Society Fish Health section developed a committee at first to deal with the issues of QA/QC and advanced technologies, but realized this chore was more than one committee should handle thus a second committee has now been established to develop means of testing and standardizing new methods for use within the diagnostic laboratory.

QA/QC


It is the intent of the Quality Assurance/ Quality Control committee to accomplish the following:

A special session was organized by the American Fisheries Society Fish Health Section to encourage dialogue on this issue as part of the 3rd International Symposium on Aquatic Animal Health. Topics included in this special session included:


Individuals from industry, research, Veterinary services, federal and state government were invited to give their viewpoints and participate in the discussion.

Several key points raised by the speakers were as follows:

In conclusion the area of Quality Assurance/ Quality Control is increasingly important as new more sensitive diagnostic assays are developed and used in aquatic animal medicine. Also there is a need for formal guidelines by which new methods must be compared with established benchmarks before they can become accepted as standards (the AFS/FHS has established a committee to begin work in this area). This is a huge task that needs to be addressed and worked on cooperatively with OIE, EAFP,FHS and JSFP to harmonize international standards for the validation and certification of fish disease diagnostic assays.


GLOSSARY


AFS American Fisheries Society
EAFP European Association of Fish Pathologists
EN 45001 European Norm standard no. 45001 (Sterlab)
FHS Fish Health section of the AFS
GCP good clinical practice
GLP good laboratory practice
GMP good management practice
GVP good veterinary practice
ISO International Organization for Standardization
OIE Office International des Epizooties
QA Quality Assurance
QC Quality Control
SOP Standard Operating Procedure
Sterlab see EN 45001
USDA Unites States Department of Agriculture

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Document Updated: 1st March 2000