Supporting Scientific information for UK SMIs
Technical limitations
Limitations of UK SMIs
The recommendations made in UK SMIs are based on evidence (for example sensitivity and specificity) where available, expert opinion and pragmatism, with consideration also being given to available resources. Laboratories should take account of local requirements and undertake additional investigations where appropriate. Prior to use, laboratories should ensure that all commercial and in-house tests have been validated and are fit for purpose.
Specimen containers (1-4)
UK SMIs use the term "CE-marked leak proof container" to describe specimen containers intended for the collection and transport of clinical specimens. Laboratories should ensure that specimen containers comply with applicable regulatory requirements and are suitable for their intended purpose.
In Great Britain, in vitro diagnostic medical devices are regulated under the UK Medical Devices Regulations 2002 (as amended) and associated MHRA guidance. In Northern Ireland and the European Union, in vitro diagnostic medical devices are regulated under Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR), which repealed Directive 98/79/EC (IVDD).
Previous editions of UK SMIs referenced the requirements of Directive 98/79/EC, and this terminology may remain in some documents (2).
Selective media in screening procedures
Selective media which does not support the growth of all circulating strains of organisms may be recommended based on the evidence available. A balance therefore must be sought between available evidence and available resources required if more than one media plate is used.
Avidity
Avidity measures antibody maturity by determining the binding strength of antibody-antigen interactions. IgG avidity tests may be used as an additional diagnostic tool especially in patients with IgM test reactivity. Avidity is initially low after primary infection and increases over time, usually about 3 months. High IgG avidity suggests that infection occurred over 3 months ago. Low or moderate IgG avidity results should not be interpreted as diagnostic of recently acquired infection, as low or moderate avidity antibodies may persist for many months following infection in some individuals. Health care providers and clinical laboratories involved in pregnancy care should be aware that avidity testing is an adjunct to the other tests and should be interpreted with consideration of the other serological tests and ideally earlier results.
Troubleshooting
When discrepant results are found these should be reviewed in accordance with the recommendations of the kit manufacturer. In certain instances, consideration should be given as to whether they should be referred to the MHRA.
Uncertainty of measurement (5)
Uncertainty of measurement expresses (attempts to quantify) the doubt that inevitably exists when any measurement is made. In most circumstances, this relies on statistical data from repeated measurements that allow one to state the degree of confidence that a measured value lies within a certain range. In order to provide a measure of confidence in results produced by a laboratory, it is necessary to identify all factors which may contribute to variation in a process and assess their potential to influence uncertainty. Once identified, these factors must be reduced or controlled to an acceptable level and a value for the range of acceptable uncertainty assigned where possible.
Note: laboratories should therefore seek to explain their process of ‘consideration of uncertainty’ in terms which technical assessors will understand. It is likely that unless the uncertainty of measurement is expressed in statistical terms, appropriate ‘consideration’ will lead to a conclusion that there are too many variables in the process to express the uncertainty in a meaningful way.
Safety considerations
Specimen collection, transport and storage (2-4,6-8)
For specimen collection, transport and storage you should:
- use aseptic technique
- collect specimens in appropriate CE-marked leak proof containers and transport in sealed plastic bags
- collect swabs into appropriate transport medium and transported in sealed plastic bags
Adhere to compliance with postal, transport and storage regulations is essential.
The above guidance should be supplemented with local COSHH and risk assessments.
Specimen processing (6,9-18)
Any laboratory procedures that give rise to infectious aerosols must be conducted in a microbiological safety cabinet.
As a minimum, it is recommended that the processing of any culture that may result in generation of aerosols should be processed in a microbiological safety cabinet in accordance with the relevant risk assessment, ACDP and HSE guidelines.
Processing of diagnostic specimens or cultures assessed as being at increased risk of containing Hazard Group 3 organisms must be undertaken under appropriate containment conditions, as determined by local risk assessment and current ACDP and HSE guidance. This will normally require Containment Level 3 (CL3) facilities.
Refer to current guidance on the safe handling of all organisms discussed in each UK SMI. The above guidance should be supplemented with local COSHH and risk assessments.
Notification to UKHSA or equivalent in the devolved administrations
The Health Protection (Notification) regulations 2010 require diagnostic laboratories to notify the UK Health Security Agency (UKHSA) when they identify the causative agents that are listed in Schedule 2 of the regulations (19). Notifications must be provided in writing, on paper or electronically, within 7 days. Urgent cases should be notified orally and as soon as possible, recommended within 24 hours. These should be followed up by written notification within 7 days.
For the purposes of the Notification Regulations, the recipient of laboratory notifications is the local UKHSA health protection team. If a case has already been notified by a registered medical practitioner, the diagnostic laboratory is still required to notify the case if they identify any evidence of an infection caused by a notifiable causative agent.
Notification under the Health Protection (Notification) Regulations 2010 does not replace voluntary reporting to UKHSA. The vast majority of NHS laboratories voluntarily report a wide range of laboratory diagnoses of causative agents to UKHSA, and many UKHSA health protection teams have agreements with local laboratories for urgent reporting of some infections. This should continue.
Note: Certain infections and organisms may be subject to separate statutory notification, surveillance or reporting arrangements. Laboratories should refer to current UKHSA guidance and relevant national reporting requirements.
In addition to public health notification requirements, laboratories holding specified dangerous pathogens and toxins must comply with the requirements of Part 7 of the Anti-terrorism, Crime and Security Act 2001(20). This includes notification to the relevant authorities and the implementation of appropriate security measures for pathogens and toxins listed in Schedule 5 of the Act. Further information is available from the Home Office guidance on notifying the intention to hold pathogens and toxins.
Other arrangements exist in Scotland (21), Wales (22), and Northern Ireland (23) under their respective public health legislation and notification arrangements.
Reference grading information
SIGN reference grading used by UK SMIs when assessing references
References used in the UK SMIs are assessed using the Scottish Intercollegiate Guidelines Network (SIGN) approach. UK SMI documents commencing review from August 2020 onwards will use SIGN. The tables below are a guide to what the grades indicate.
|
Grade |
Power of study |
|
1 |
Meta-analysis, systematic review, randomised controlled trial |
|
2 |
Non-randomised controlled trial, cohort studies, case-control studies, cross-sectional studies, prevalence studies |
|
3 |
Case reports/case series, consensus reports, descriptive studies, uncontrolled trials |
|
No number |
Not applicable |
|
Grade |
Quality of study |
|
++ |
Document has appropriate presentation, is relevant to the topic, lacks bias, has a suitable method, originates from a good source and contains timely, up to date information. |
|
+ |
Document is relevant to the topic but may have minor issues that impact the quality |
|
- |
Document is relevant to the topic but may have one or more serious issues that impact the quality |
Modified GRADE table previously used by UK SMIs when assessing references
Prior to August 2020, references used in UK SMIs commencing review were assessed using a modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Under this scheme, each reference is assessed and allocated a grade for strength of recommendation (A to D) and quality of the underlying evidence (I to VIII). A summary table that defines the grade is listed below:
References
- The Medical Devices Regulations 2002 (SI 2002/618), as amended; 2002. ++
- European Parliament. UK Standards for Microbiology Investigations (UK SMIs) use the term "CE marked leak proof container" to describe containers bearing the CE marking used for the collection and transport of clinical specimens. The requirements for specimen containers are given in the EU in vitro Diagnostic Medical Devices Directive (98/79/EC Annex 1 B 2.1) which states: "The design must allow easy handling and, where necessary, reduce as far as possible contamination of, and leakage from, the device during use and, in the case of specimen receptacles, the risk of contamination of the specimen. The manufacturing processes must be appropriate for these purposes". 1998. ++
- European Parliament and Council of the European Union. Consolidated text: Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (Text with EEA relevance). pages 176–332. 2025. ++
- Official Journal of the European Communities. Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices 1998. pages 1–37. ++
- British Standards Institute. ISO/TS 20914:2019 Medical laboratories. Practical guidance for the estimation of measurement uncertainty. BSI Standards Limited. 2019.
- Health and Safety Executive. Safe use of pneumatic air tube transport systems for pathology specimens. 2009. ++
- World Health Organization. Guidance on regulations for the transport of infectious substances 2025-2026: applicable as from 1 October 2025. 2026. ++
- Department for Transport. Guidance Note 17: Transporting infectious substances (17/2012 Rev. 7). 2013. ++
- British Standards Institution (BSI). BS 5726:2005 - Microbiological safety cabinets. Information to be supplied by the purchaser and to the vendor and to the installer, and siting and use of cabinets. Recommendations and guidance. 2005. pages 1–14. ++
- British Standards Institution (BSI). BS EN 12469-1:2025 Biological safety cabinets Classes and basic requirement 2025. ++
- British Standards Institution (BSI). BS EN 12469-2:2025 Biological safety cabinets. BSC class II 2025. ++
- British Standards Institution (BSI). BS EN 12469-5:2025 Biological safety cabinets. Installation, commissioning and routine testing 2025. ++
- Health and Safety Executive. Control of Substances Hazardous to Health Regulations. The Control of Substances Hazardous to Health Regulations 2002 (as amended). Approved Code of Practice and guidance L5 (sixth edition). HSE Books,. 2013. ++
- Health and Safety Executive. Bloodborne viruses (BBVs). Health and Safety Executive. ++
- Health and Safety Executive. Safe deliberate work with biological agents. ++
- Health and Safety Executive, Advisory Committee on Dangerous Pathogens. Management and operation of microbiological containment laboratories. HSE. 2019. ++
- Health Services Advisory Committee. Safe Working and the Prevention of Infection in Clinical Laboratories and Similar Facilities. HSE Books 2003. ++
- Advisory Committee on Dangerous Pathogens. The Approved List of Biological Agents. Health and Safety Executive 2026. pages 1–45. ++
- UK Health Security Agency (UKHSA). Laboratory reporting to UKHSA: a guide for diagnostic laboratories. UKHSA 2025. pages 1–35. ++
- Home Office. Anti-terrorism, Crime and Security Act. 2001. ++
- Scottish Government. Public Health etc. (Scotland) Act 2008. Implementation of Part 2: Notifiable Diseases, Organisms and Health Risk States. 2009. ++
- The Welsh Assembly Government. Health Protection Legislation (Wales) Guidance. 2010. ++
- Home Office. Public Health Act (Northern Ireland) 1967 Chapter 36. 1967. ++
The search strategy for any UK SMI document is available on request by emailing [email protected]