38 GOOD CONTROL LABORATORY PRACTICE AND USE OF OUTSIDE LABORATORY SERVICES – Food and Drink – Good Manufacturing Practice, 7th Edition

38
GOOD CONTROL LABORATORY PRACTICE AND USE OF OUTSIDE LABORATORY SERVICES

Principle

A control laboratory should have appropriate premises, facilities and staff, and be so organised as to enable it to provide an effective service at all relevant times necessary to fulfil good manufacturing practice (GMP) requirements.

EU GLP

38.1 The Organisation for Economic Co‐operation and Development (OECD) Principles of Good Laboratory Practice (GLP) ensure that test data is reliable and avoid duplicate testing in the wider context of harmonising testing procedures for the mutual acceptance of data. The European Union (EU) has adopted these principles and the revised OECD Guides for Compliance Monitoring Procedures for GLP as annexes to the two GLP Directives. EC Directive 2004/9/EC lays down the requirements for the inspection and verification of good laboratory practice and 2004/10/EC lays down the requirements for the harmonisation of laws, regulations and administrative provisions relating to the application of good laboratory practice and the verification of their applications for tests on chemical substances. The OEDC defines GLP as ‘a quality system concerned with the organisational process and the conditions under which non‐clinical health and environmental safety studies are planned, performed, monitored recorded, archived and reported’.

Resources

38.2 The resources required will depend on the nature of the materials and/or products to be tested. It is essential that facilities are appropriate to the needs of the tests, whether chemical, physical, biological or microbiological. Staff should be properly trained, well motivated and well managed. Standards should be set at the highest level and maintained by careful attention to approved and agreed methods and method checks using, where appropriate, reliable outside expertise.

Premises

38.3 Control laboratories should be constructed, located, designed, equipped, maintained and of sufficient size with enough space to suit the operations to be performed in them. This will include provision for writing and recording of results and archive facilities for the storage of documents, facilities for ambient samples and refrigerated storage for samples, as required. Storage rooms should be separated from rooms where testing is undertaken and there should be adequate protection against contamination, material deterioration and pest infestation. Storage rooms should be adequate to preserve sample and reference material identity, purity and stability and the appropriate storage of hazardous materials (see 38.7). Archive facilities must ensure that the retrieval of materials and documents is timely and the contents are protected from deterioration. Storage time for documents and records needs to be defined (see Chapter 13).

To avoid contamination or loss of control of samples and test materials there should be separate areas for receipt and storage of test and reference items and it is important to check on receipt that there has been no mixing or contamination of test and reference materials.

38.4 Chemical, biological and microbiological laboratories should be separated from each other and from manufacturing areas. Separate rooms may be necessary to protect sensitive instruments from vibration, electrical interference, humidity and so on. Care should be taken to avoid contamination in either direction between laboratories (particularly microbiological laboratories, where access and exit controls should be strictly followed) and manufacturing areas, and reagents or materials that could cause taint should ideally be kept in a separate building. Provision should be made for the safe storage of waste materials awaiting disposal.

38.5 All services should be identified using colour coding according to standard documented procedures.

38.6 The UK legislation concerned with fire and explosion in laboratories falls under the process fire precautions, i.e. additional precautions that relate to workplaces such as laboratories. Laboratory practices need to comply with the Dangerous Substances and Explosive Atmospheres Regulations 2002 (DSEAR) and other relevant legislation as amended.

COSHH

38.7 In the UK, the Control of Substances Hazardous to Health (COSHH) Regulations 1994, SI 1994 No 3246 as amended by SI 1996 No 3138 Amended 2002, 2003 and 2004SI 2004/3386 affect the choice of safe laboratory working methods. All methods written up should include an assessment of the hazard of each of the chemicals used in the analysis and appropriate instructions to contain any hazard. If necessary, monitoring of the exposure to hazardous chemicals should be carried out. Advice on COSHH may be obtained (in the UK) from the Health and Safety Executive (HSE), among others.

Equipment

38.8 Control laboratory equipment and instrumentation should be appropriate to the testing procedures undertaken. Equipment must be suitably located, and have adequate capacity and appropriate design for the tests to be performed.

38.9 Equipment and instruments should be inspected, cleaned, maintained, serviced and calibrated at suitable specified intervals by an assigned competent person, persons or organisation in line with standard operating procedures. Calibration should, where appropriate, be traceable to national or international standards of measurement. Laboratories working to traceable national or international standards should in turn calibrate measuring inspection and test pieces used in the calibration process at intervals determined by risk assessment. Records of the calibration procedure and results should be maintained for each instrument or item of equipment or test piece. These records should specify the date when the next calibration or service is due (see Chapter 34).

38.10 Written operating instructions should be readily available for each instrument.

38.11 Where practicable, suitable arrangements should be made to indicate failure of equipment or services to equipment. Defective equipment should be withdrawn from use until the fault has been rectified. Following identification of defective or broken equipment, a review should be undertaken by the quality control manager or designate to determine the potential impact of equipment failure on product safety, legality or quality. Actions taken as a result of the review should be documented and verified to determine their effectiveness.

38.12 As necessary, analytical methods should include a step to verify that the equipment is functioning satisfactorily.

Cleanliness

38.13 Laboratories and equipment should be kept clean in accordance with written cleaning schedules. Adherence to cleaning schedules and compliance with cleaning standards should be verified at routine intervals. Verification activities should be recorded.

38.14 At all times personnel should wear clean protective clothing appropriate to the duties being performed, especially eye protection.

38.15 The disposal of waste material should be carefully and responsibly undertaken by appropriate bodies and in compliance with legislation. Waste must be stored in appropriate, designated areas so that the integrity of testing is not compromised.

Reagents, Controls and Standards

38.16 Where necessary, reagents should be dated upon receipt or preparation.

38.17 Reagents made up in the laboratory should be prepared by persons competent to do so, following laid down procedures. As applicable, labelling should indicate the identity, concentration, standardisation factor, shelf life (i.e. an expiry date) and storage instructions. The label should be initialled or signed, and dated, by the person preparing the reagent. A date for restandardisation should be recorded if required.

38.18 In certain cases, it may be necessary to carry out tests to confirm that the reagent is suitable for the purpose for which it is to be used. A record of these tests should be maintained.

38.19 Both positive and negative controls should be applied to verify the suitability of microbiological culture media. The size of the inoculums used in positive controls should be appropriate to the sensitivity required.

38.20 Reference standards, and any secondary standards prepared from them, should be dated, and be stored, handled and used so as not to prejudice their quality.

Sampling

38.21 Samples should be taken in such a manner that they are representative of the batches of material from which they are taken, in accordance with written sampling procedures approved by the quality control manager. The sampling activities used are constrained by:

  • the resources and time available;
  • the planned frequency of verification activities;
  • the volume of data to be assessed;
  • any planned or unplanned sampling bias; and
  • the potential for deviation from the scope of the sampling protocol.

Sampling procedures should identify whether they are risk‐based or non‐risk‐based methods of sampling, that is, whether all batches have an equal probability of being sampled or whether, through a risk assessment process using screening criteria, the sampling is biased towards certain ingredients, products and potential food safety hazards. Consideration needs to be given to the homogeneity of the sample or of the criteria being tested within the food product as, for example, there may be more contamination on the surface of the food product than in the sample as a whole.

For example, materials associated with possible contamination such as mycotoxins (e.g. nuts) might be sampled at a higher frequency than those products that are not identified as having the potential to be so contaminated. Risk‐based sampling accepts the premise that resources are limited and that sampling must be economically viable and deliver benefits to the manufacturing business. Other screening criteria might be third‐party certification, provision of certificates of analysis, history of conformance with specifications and the volume of product utilised by the manufacturing business and thus the impact of failure.

The European Commission (19761 and 20062 ) distinguished between different types of food samples:

  • sampled portion: a quantity of product constituting ‘a unit’ having characteristics presumed to be uniform;
  • incremental sample: a quantity taken from one point in the sampled portion, lot or sublot; and
  • aggregate sample: an aggregate of incremental samples taken from the same sampled portion or the combined total of all the incremental samples taken from the lot or sublot.

It is therefore important to classify the type of sample being derived as this will impact on the results in terms of the amount of variability in the batches to be sampled and whether this is masked by an aggregate sample and whether contamination in one batch is ‘diluted’ by the use of aggregate sampling to a point where it is not detected or finally where traceability of a food safety hazard identified during sampling to a particular batch is no longer possible. The physical state of the material, that is, liquid, solid or particulates, will also influence the sampling protocols that can be effectively adopted. Sampling procedures should include:

  1. the method and rate of sampling, which should reflect the degree of homogeneity of the material being sampled;
  2. the equipment to be used, which must also be recorded on any testing records;
  3. the amount of sample to be taken;
  4. the instructions for any required subdivision of the sample;
  5. the type and condition of the sample container to be used;
  6. the storage requirements for the sample prior to testing;
  7. any special precautions to be observed, especially in regard to sterile sampling or sampling of noxious materials and the prevention of false positives; and
  8. the cleaning and storage of sampling equipment.

Any sampling by production personnel should only be done by competent personnel in accordance with these approved procedures. Training records should be maintained to demonstrate that staff are competent.

38.22 Each sample container should bear a secure and indelible label indicating its contents, with the batch or lot number reference and the date of sampling. It should also be possible to identify the bulk containers from which samples have been drawn.

38.23 Sampling equipment should be cleaned after each use and stored separately from other laboratory equipment.

38.24 Care should be taken to avoid contamination or causing deterioration whenever a material or product is sampled. Special care is necessary when resealing sampled containers to prevent damage to, or contamination of or by, the contents.

Methods

38.25 Methods should be chosen with care to fulfil the needs of the analyses. For quality control purposes, the chosen method should be that most efficacious for the accuracy and speed of results needed, and the skill of the staff concerned. When possible, methods acceptable to any enforcing authority, or which are internationally acceptable, should be used. In all cases, method checks need to be incorporated into any analytical scheme to ensure reproducibility, repeatability and operator independence. Reviews of the methods used should be undertaken at predetermined intervals or at times appropriate to a developed need.

Documentation

38.26 All test facilities should have a documented quality assurance programme to assure that testing undertaken is performed in compliance with the principles of GLP. An individual should be designated by the manufacturer to ensure that the quality assurance programme for testing is consistently complied with. Laboratory documentation should be in line with the general guidance given in Chapter 13. When electronic or magnetic recording methods are used, see also Chapter 39.

38.27 Retention samples should be regarded as part of the laboratory records.

38.28 It is useful to record test results in a manner that will facilitate comparative reviews of those results and the detection of trends. To assist this process, ‘commodity files’ may be established.

Records of Analysis

38.29 Details to be recorded on the receipt and testing of starting materials, packaging materials and intermediate, bulk and finished products are indicated in Chapter 13. Analytical records should contain:

  1. the name of the product or material and its code reference;
  2. the date of receipt and sampling;
  3. the source of the product or material (including supplier and country of origin);
  4. the date of testing;
  5. the batch or lot number;
  6. an indication of tests performed;
  7. reference to the methods used;
  8. results;
  9. any decision regarding release, rejection or other status; and
  10. the signature or initials of the analyst, and the signature of the person taking the above decisions.

38.30 In addition to the above records, analysts’ laboratory records of the basic data and calculations from which the test results were derived should also be retained (e.g. weighing, readings, recorder charts).

Specifications

38.31 Specifications approved by quality control and including analytical parameters should be established for all raw materials and bulk, intermediate and finished products (see Chapter 13).

Testing

38.32 The persons responsible for laboratory management should ensure that suitable test methods, validated in the context of available facilities and equipment, are adopted or developed.

38.33 Samples should be tested in accordance with the test methods referred to, or detailed, in the relevant specifications. The validity of the results obtained should be checked (and, as necessary, any calculations checked) before the material is released or rejected.

38.34 In‐process control work carried out by production staff should proceed in accordance with methods approved by the person responsible for quality control.

38.35 Microbiological testing should be carried out in appropriate facilities and with due consideration to the handling, storage and disposal of samples and tested materials.

Contract Analysis

38.36 Although analysis and testing may be undertaken by a contract analyst, the responsibility for quality control cannot be delegated to him/her.

38.37 The nature and extent of any contract analysis to be undertaken should be agreed and clearly defined in writing, and procedures for taking samples should be set out as discussed in 38.21–38.24.

38.38 The contract analyst should be supplied with full details of the test method(s) relevant to the material under examination. These will need to be confirmed as suitable for use in the context of the contract laboratory.

38.39 Formal arrangements should be made for the retention of samples and of records of test results. Protocols must be in place for timely reporting of the results that identify product non‐conformance for product safety, legality and quality to the quality control manager or designate.

Accreditation

38.40 Where control laboratories are located within factories that are applying for third‐party certification, the laboratory is likely to be considered as part of the quality control system assessment. Adherence to GLP should meet the technical standards demanded, although the documentation of the system will need to conform to the needs of the assessors. In the UK, many food laboratories will wish to seek accreditation under the UK Accreditation Service (UKAS) accreditation scheme. Third‐party laboratories used for testing should be accredited by a competent national authority, such as UKAS, to ISO/IEC 17025 or an equivalent standard. This is often a requirement for third‐party certification of a manufacturer. Approval may be withdrawn from any laboratory if standards in any of the accreditation schemes are not maintained. Proficiency testing schemes are available for laboratories to monitor and give confidence in laboratory methods. Participating laboratories will take part in the Food Analysis Performance Assessment Scheme (FAPAS) testing (see https://fapas.com for further details).

Notes