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Allergen management in the food industry
16 Allergen management in the food industry R. W. R. Crevel, Safety & Environmental Assurance Centre, Unilever Colworth, UK
16.1 Introduction Epidemiological studies published in the last 10 to 15 years indicate that significant proportions of the population of most countries surveyed suffer from food allergy. Early studies by Young et al. (1994) in the United Kingdom estimated a population prevalence of 1.4–1.9%, while more recent studies suggest figures of the order of 3.5–4% in the industrialised world (Kanny et al., 2001; Sicherer et al., 2004). The prevalence among children is generally accepted to be higher, of the order of up to 8% (Sampson, 2005). Such figures equate to upward of 10 million people with the condition in regions such as the EU or USA, and therefore a significant burden of ill-health and reduced quality of life. Avoidance of the offending allergen is currently the only treatment for food allergy and an immediate consequence of this is that having a member with food allergy affects the whole family and, to a lesser extent, the social circle of the allergic individual. Over the last two decades food allergy has thus evolved from a problem for the food-allergic individual to one of significant public health importance. This recognition has led to initiatives by public authorities and subsequently legislators in response. Stages in this development include the proposal by the Nordic countries in the early 1990s to amend the Codex Alimentarius’s 25% rule, leading to the FAO–WHO consultation in 1995 which identified eight major foods or food groups as important causes of food allergy (FAO/WHO, 1995). These early stages were followed in the early years of the 21st century by legislation in
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many countries and regions, including Australia, New Zealand, Japan, the European Union (Directive 2003/89/EC) and the United States of America (FALCPA, 2004). In parallel, many food manufacturing companies recognised the importance of food allergy and their responsibilities to their food-allergic consumers. Experience in the food industry, now going back a decade or longer, has demonstrated that allergen management shares many of the principles underlying management of other risks, such as toxicological or microbiological ones. In particular, safety cannot be ensured through end product testing, but must be built upon the careful analysis of the hazards at each stage of the product cycle. A key principle is therefore the development of an integrated approach that considers each stage of manufacturing, from the raw materials to the product that is delivered to the consumer, and involves all levels within a food company, as reflected in recently published guidelines (European Commission, 2006). However, responsibility for the management of food allergy does not rest solely with the food industry, but is a responsibility shared by other stakeholders, including health professionals, regulators and the allergic patients or their carers themselves. This chapter will consider the main issues associated with the principles underlying allergen management, its objectives, common issues and the application of allergen management.
16.2 Principles Allergen management systems form part of a family of food safety management systems, which include general toxicological and microbiological food safety. The requirements of allergen management may sometimes be at variance with those of other food safety systems. For instance, wet cleaning of dry mix lines would be a very effective way of removing allergenic residues, but at the risk of subsequent microbiological contamination. Allergen management therefore needs to be integrated into the overall food safety management system, a fact now explicitly recognised in new international guidance documents such as ISO 22000: 2005. Allergen management systems must meet both minimum statutory requirements and those that the company itself may have defined, after considering its objectives in this area of safety. These company requirements will arise from its own understanding of its operations and of the needs of its allergic consumers. An allergen management system must also balance a number of other requirements, the main one being to ensure a high degree of food safety with respect to allergens without impairing other aspects of food safety, but also without putting at risk the economic viability of the manufacturer. This can only be achieved if it is based on a clear set of objectives and clear criteria for action. Such systems will therefore need to take into account a number of factors as described below:
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16.2.1 Nature of food manufacturing operations Food manufacturing is typically a complex operation, which for purposes of allergen management, may be divided into several stages. These include the following: • Raw material selection and specification: depending on the operation, raw materials range from primary, minimally processed ingredients e.g. wheat flour, to complex formulated ingredients. The specification of these raw materials will limit what can be achieved in terms of residual allergen content. • Manufacturing operations: these vary considerably in complexity, depending on the type of products that are made at the facility. However, in almost all operations, many different products with different formulations are made on the same lines, with a constant risk of inadvertent transfer of residues from the previous formulations onto the following ones. An added complexity is that some equipment can be extremely difficult to clean down between production runs because of its design or the characteristics of the product made. Thus allergen management in dry mix plants, where water or aqueous solvents cannot usually be used, poses challenges which differ from those in wet process lines. Similarly, thermal treatments of the product often alter the ease with which allergenic residues can be removed by sanitation procedures. • Delivery to the consumer: most food manufacturers will deliver through retail or other outlets. In terms of allergen management, the manufacturer will need to consider how relevant information will be conveyed to the final consumer in such a way that it retains its integrity. In addition, food safety needs to be integrated into product development and innovation, such that new products do not degrade inadvertently the safety of existing operations when they are introduced. 16.2.2 Clinical and biological characteristics of food allergy Typically the minimum doses which elicit reactions in food-allergic individuals vary over many orders of magnitude. For peanut, for instance, this may be as much as 4 to 5 orders of magnitude among patients which have been challenged. Furthermore the reactivity of patients varies over time, depending on extraneous factors such environment, concurrent activity etc. Although reliable information is beginning to emerge on the distribution of minimum eliciting doses within selected population groups, little information is available on how symptoms in any one individual vary with the amount of allergen to which they are exposed. Thus it is difficult to define the safety margin between the dose provoking a slight reaction, which does not pose a threat to health and a dose which provokes a severe reaction. Development of an allergen management system could proceed through the following series of steps: • Definition of objectives. Defining objectives forms a key stage and merits careful consideration. Without clear objectives, an allergen management plan
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will be difficult both to communicate to those who must apply it operationally and to other stakeholders. It will also make it difficult to evaluate success and compliance. Absence of explicit objectives does not mean that no objectives exist, only that they are implicit. Such a situation poses a risk that objectives could be externally imposed without consideration for their achievability. Clear objectives also provide a company with a defensible position in the event of challenge. • Setting out a policy. Once objectives have been defined, these can be set out in a policy which will be a statement of what the company aims are and an outline of how they are to be achieved. It can also set out broad responsibilities for ensuring these aims are achieved. The policy enunciates the commitment of the company through its senior management. It also provides the basis for defining subsidiary objectives and mechanisms which will ensure compliance. • Drawing up guidelines. As indicated above, the policy document is not a dayto-day working document. Guidelines fulfil this purpose by detailing mechanisms and procedures to implement the broad objectives at a practical level. Guidelines will therefore cover detailed operations at all levels of the organisation. They will be adapted to cover the diversity of the company’s operations, including raw material types and sourcing, types of operation, etc.
16.3 Objectives Risk management of food allergens, as of other hazards, requires a clear definition of objectives. These need to recognise and balance the sometimes divergent interests of different stakeholders, a process which is often difficult to make explicit in the absence of formal mechanisms. In this context, the concept of Food Safety Objectives, analogous to those proposed by the ICMSF (2002) for microbiological hazards and as elaborated by the Codex Alimentarius Commission (Codex Alimentarius Commission, 1999), could form a useful basis for eliciting a consensus. The primary objective behind allergen risk management must be to prevent adverse reactions in food-allergic individuals, while not limiting their food choices unnecessarily. However, the apparent simplicity of this statement hides a number of complex issues. Firstly, in a matter of public health such as allergen management, the interests and needs of different stakeholders, which may diverge, must be balanced. These stakeholders include not only the allergic population, but also the general population, as well as the food industry and health professionals. Most common food allergens play an important nutritional role in the diet of the population as a whole, and it is not practicable, let alone desirable to eliminate them from products. Furthermore, the majority of the population is not exposed to any risk from food allergens, irrespective of the amounts to which they may be exposed. This situation differentiates food allergens from other food hazards, such as chemical or microbiological contaminants, from which no individual derives any benefit, and where the whole population is potentially at risk. This has two
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implications: firstly, the general population derives no direct benefit from allergen control measures, and indeed must indirectly bear their cost; secondly, because most product lines are shared, the adventitious presence of specific residual allergens will be inevitable in many products. The threshold of reactivity to allergenic foods ranges over many orders of magnitude while allergic reactions to foods span a considerable range of severity, from the barely noticeable to life-threatening anaphylaxis. There is thus a small and poorly defined fraction of the allergic population who react severely to very small amounts of allergenic food. Procedures to reduce unintentional presence of allergens may not be sufficient to protect such people, and other allergen management measures will be required to protect them. These observations underline the importance of setting clear objectives for allergen risk management, and ensuring they are clearly communicated to stakeholders. These objectives should define who the risk management activities aim to protect and against what. They can then serve to evaluate the effectiveness of measures taken to achieve them.
16.3.1 Who are we trying to protect and against what? Food allergy differs from most other adverse responses to foods. Within the susceptible population, the range of allergenic reactivity, expressed as the smallest amount of an allergenic ingredient able to trigger a reaction, spans many orders of magnitude (Taylor et al., 2002). Knowledge of minimum eliciting doses (thresholds), and the proportion of the population reactive to very small amounts, remains currently very limited and may be impossible to establish experimentally. Furthermore, a small, although unquantified proportion of the susceptible population can react severely to small amounts of allergenic protein (of the order of milligrams). Under those circumstances, the concept of protecting the whole allergic population against all reactions, however mild, is unrealistic. Design of food allergen management plans must therefore consider what level of protection they purport to provide, or in other words what can be considered a tolerable risk. Defining the tolerable risk level involves considering the probability of an adverse event, as well as its consequences in terms of severity. The two aspects are clearly related, inasmuch as the tolerable frequency for severe adverse events will be much lower than the tolerable frequency of all adverse events, among which events of low severity will predominate. Establishing the tolerable level is a societal issue, but little explicit guidance exists in the area of food allergy itself. One approach would be to consider the disease burden attributable to the less common food allergens, which are not subject to statutory regulation. This burden of disease could be considered to be that tolerated implicitly by society. In practice, however, information is lacking on the disease burden attributable to common, regulated allergens, let alone the less common ones, making this approach impracticable. Another approach might be to look to other situations analogous to food safety. The safety of drinking water shares characteristics with the protection of foodallergic people. In particular, any risk posed by drinking water is imposed on those
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who consume it and, for practical purposes, is usually impossible to avoid. The World Health Organisation has debated drinking water standards and proposed draft guidelines for drinking water quality, which translate to a probability of disease for any one individual of 10–3 per year or approximately 1 in 10 over a lifetime (WHO, 2003). This figure, of course, refers to all disease, irrespective of severity, so cannot be applied without qualification to allergic reactions to food. However, it can provide a basis for discussion among stakeholders.
16.3.2 Hazard- versus risk-based approaches The simplest way to protect allergic consumers would be to ensure that the allergenic ingredients to which they are reactive are either declared on the product label in all circumstances or are totally excluded. This hazard-based approach is broadly appropriate to deliberately added ingredients, and indeed has been adopted in several pieces of legislation regulating allergens (e.g. Directive 2003/89/EC). However, food-allergic individuals are also at risk from small amounts of residual allergen inadvertently carried over from other products because of the sharing of manufacturing lines, or because of admixture into raw materials such as grains during storage and transport. The hazard-based approach focuses on the presence of the allergen and does not recognise the existence of an amount of allergenic protein below which there is virtually no risk. As a result, it provides no mechanism to decide on the magnitude of the danger that the presence of residual allergen constitutes. It is arguably therefore not the most effective way to protect the vast majority of food-allergic people while balancing the interests of different stakeholders. At the limit, it leads to declaration of the presence of allergen in amounts which present little or no risk to health. Application of a hazard-based approach thus decreases the food choices of the allergic population and increases the likelihood that they will suffer nutritional deficiencies, as well as reducing their quality of life (Avery et al., 2003). When applied to cross-contact allergens it is reflected in excessive use of precautionary (‘may contain’) labelling. While such a label on an individual product may well add to the protection of allergic individuals, the uncontrolled proliferation of such labels is likely to decrease it, as trust in the label reduces and it is ignored. The possibility also exists that some allergic people will misinterpret such a label, if they consume the product and fail to react, wrongly concluding that they are no longer allergic. The theoretical diagram in Fig. 16.1 attempts to illustrate these observations. Maximising public health outcomes thus ineluctably leads to a risk-based approach to allergen management. Risk can be defined as the probability that a hazard will become manifest, and is often expressed as a function of the intrinsic hazard and the exposure to that hazard. This definition is sometimes expanded to include severity of the resulting adverse effect. Thus, risk is defined in ISO/IEC Guide 51 as the combination of the probability of occurrence of harm and the severity of that harm (ISO 22000:2005). The key concept is therefore that of probability. In line with that concept, risk management does not seek to eliminate the risk, which is generally regarded as
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Fig. 16.1 Illustration of the efficacy of precautionary labelling against frequency of use.
impossible unless there is no exposure, but to reduce the probability of harm to a level which is considered tolerable. What is tolerable will be determined by a societal decision, which will reflect the balance of different stakeholder interests.
16.3.3 Risk assessment principles for allergens in food manufacturing Risk assessment as a process begins with hazard identification, followed by hazard characterisation, exposure assessment and risk characterisation to scope the overall risk to the population (FAO/WHO, 1997). Translating this to food allergens, the hazard itself is already defined as their intrinsic allergenicity, in this context their ability to provoke an allergic reaction. Beyond this, risk assessors require information about the characteristics of the hazard, which in this context can mean the response characteristics of the population at risk (distribution of minimum eliciting doses – thresholds, dose–response), the size of the population at risk, and the extent of exposure. In ideal circumstances, risk assessors could calculate the number of reactions that would occur for any given level of residual allergen in a food product if people allergic to that food consumed it. In practice, information on all the elements required for a risk assessment remains extremely limited. Studies to describe the reactivity of the allergic population in terms of minimum eliciting doses (thresholds) are still largely limited to selected populations, such as clinic patients, and further work is needed to map their reactivity onto the general allergic population. It is also limited to certain allergenic foods. Most available information is based on studies undertaken for other purposes, further limiting their value for establishing minimum eliciting doses because of the type of data generated. Only anecdotal information is available on the relationship between the dose of allergen to which an individual is exposed and the severity of the reaction
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experienced, as obtaining that information systematically presents considerable ethical difficulties. Further complexities arise from differences in the extent to which allergenic proteins are released from different food matrices, and become available to be recognised by the immune system. Uncertainty also exists over the size of the population at risk, given that epidemiological data are scarce for most regions. In most countries, there is also a surprising lack of detailed information about the incidence of reactions, even severe and fatal ones. Minimum eliciting doses (thresholds) clearly form a key piece of information for risk assessors. A recent report by FDA-CFSAN identified four ways in which they might be determined: analytically-based, statutorily derived, using a safety assessment approach and using a risk assessment approach. They indicated a preference for the risk assessment approach on the grounds that it was the most scientifically robust, as well as transparent, an important consideration in communicating with other stakeholders. Of those four approaches, only the safety and risk assessment ones use biological data on the reactivity of allergic patients, generated under controlled conditions. The safety assessment approach applies an uncertainty factor to either the highest dose of allergenic protein observed not to provoke a reaction or to the lowest one which does provoke a reaction (depending on what is available). Recently, we proposed an approach that aims to define the expected number of reactions from exposure to specified amounts of allergenic ingredient in a product and use it as a basis for risk assessment (Crevel et al., submitted), subsequently aiding risk management and communication. This approach is based on modelling statistically the dose–distribution data obtained from food challenge studies, to gain insights into the likely incidence of reactions to very low amounts of residual allergen, lower than can be practicably tested experimentally. The approach takes the following steps: 1. Good quality data from well-controlled challenge studies constitute the foundation of the approach. Such studies should be conducted using the agreed protocol proposed by Taylor et al. (2004). 2. A tolerable limit for the proportion (p) of allergic individuals who might react is established for the allergens of interest. The level p is defined in consultation with other stakeholders (regulators, patients, industry, clinicians). This part of the process requires other factors to be accounted for such as the prevalence of allergy to the allergen of interest, the actual rate of reported reactions, and their severity. 3. Data from a challenge study are analysed and a statistical distribution is fitted to the study data. The model is used to predict the EDp and the lower confidence interval on the EDp for the p defined in step 2. Precedents from other areas of food safety support this approach, although there are distinct differences, related to the type of data that are available or can be generated in each case. Thus Buchanan et al. (1997) estimated a conservative dose–response relationship for listeriosis using surveillance data on the number of
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cases, together with food sampling data on Listeria contamination of a food responsible for most such cases. In our approach, we use statistical distributions to describe data from clinical challenge studies performed under carefully controlled conditions. In microbiological terms, such data are more akin to controlled feeding studies with defined numbers of microorganisms in human volunteers. Inevitably, the populations tested in these studies contain an element of bias. Firstly, they will tend to exclude individuals who have suffered life-threatening reactions, as these may be less willing to participate and the clinicians more reluctant to accept them in a study on account of the risks. Perhaps more significantly, the process of selecting for challenge studies will result in a bias towards the more severely affected of the allergic population, other than the category previously mentioned. This arises because volunteers are chosen from the population which attends tertiary referral clinics, and who are therefore sufficiently motivated by the impact of their condition to visit a clinical expert. Limitations also exist when using such data as a basis for risk management, because they do not take into account some of the factors which modulate the allergic response, such as alcohol intake, exercise, etc. However, it can be argued that compared to other areas of toxicology, these data present the major advantage of being generated in the species of interest. Currently available data do not permit a direct application of the methods proposed in Buchanan et al. (1997). Specifically, data on the incidence of even severe allergic reactions to foods are not reliable, and usable published data on the distribution of undeclared allergen in food are very limited. Nevertheless, the next step in the development of this approach is to validate the predictions by comparing the number of predicted reactions with the number actually observed. Development of allergen management policies and procedures by food manufacturers contributes significantly to protection of allergic consumers by ensuring that the inadvertent presence of allergenic ingredients in products is minimised (Hefle and Taylor, 2004; Huggett et al., 1998; Crevel, 2005). However, the nature and complexity of food manufacturing operations imposes limits on such approaches, which can only be overcome at significant cost. These considerations have led significant numbers in the food industry towards the concept, and in many cases the use, of defensive (precautionary) labelling. This type of labelling, while initially welcomed by allergic consumers, has become devalued through perceived over-use and inconsistent application. In addition, such labelling is not justified for levels which would not cause effects. Indeed it now presents the allergic consumer with a dilemma: observe the labelling and face much decreased choice or ignore it and risk a reaction to the food.
16.4 Issues associated with allergen management The increasing number of recalls triggered by regulatory inspections (Vierk et al., 2002), by consumer complaints (Hefle and Lambrecht, 2004), or by system failures, which result in the presence of undeclared allergen at hazardous levels,
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indicate that unresolved issues exist with allergen management systems. A report commissioned by the US FDA as part of a review of Good Manufacturing Practices in the food industry summarised issues arising from the operation of allergen management systems. These issues spanned the whole manufacturing supply chain as follows: • Raw materials. Adventitious presence of allergen was a problem, with incomplete knowledge of the formulation of ingredients used as raw materials, and the use of reconditioned ingredients and raw materials. Suggestions for overcoming these issues included developing a close working relationship with suppliers and performing regular audits. Training for the supplier could also be considered to improve understanding of the issues. Rework, which could be classed as a raw material, should be handled according to a defined and documented plan. • Manufacturing processes and procedures. The presence of undeclared allergen in a product was found to result from a multiplicity of sources and during manufacture, including inadequate cleaning, lack of physical separation at cross-over points in production lines, lack of separation between production runs, carry-over of allergen from shared storage equipment or from maintenance tools. The report recommended that allergens should be included in an overall hazard analysis, using a system such as the Hazard Analysis Critical Control Point approach or equivalent. Specific recommendations included cleaning to an appropriate degree of thoroughness, recognising that this may exceed what is required to assure microbiological safety. If appropriate, cleaning should include disassembly of the equipment. Cleaning protocols may need to be validated analytically. Other measures included production scheduling, building in physical barriers to prevent allergen ingress at cross-over points and providing dedicated storage facilities and maintenance equipment for specific allergenic materials. • Labelling or packaging. The report found that many companies failed to review their labelling, as a result of which ingredient declaration could be inaccurate. Recommendations included regular label reviews, together with policy to ensure old labels cannot be re-used. • Equipment design. The report identified old equipment as an important issue, either because it is difficult to clean, for instance because it cannot be dismantled, or because it lends itself to allergen accumulation which cannot be readily detected by inspection. Hygienic design should overcome much of this problem as old plant is renewed. • Effective training of employees. The report identified training as one of the areas where effectiveness was perceived to be lowest. Issues included training of the wrong people, not training enough people and not providing enough training. A key point made was that training should be delivered by people familiar with the plant, rather than by consultants.
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16.5 Application 16.5.1 From policy to guidelines: the need for an integrated approach Allergen management policies establish principally intent, but guidelines are required to set out the detailed mechanisms whereby this intent is made operational. As already mentioned, allergen management requires consideration of all the elements of the life cycle and production of a product from its design, through selection of raw materials to production processes and finally delivery to the consumer. This marks out allergen management as an activity which requires commitment throughout a company from senior management all the way to those working on production lines. Procedures that are put in place for allergen management may also impinge on other aspects of food safety. Effective delivery of such commitment therefore requires that allergen management be integrated into overall food safety management and encompass all stages of the life cycle of the product from the raw materials to the end product which the consumer buys. This has recently been recognised in external standards for food safety management systems such as ISO 22000:2005 and the EU’s DG Sanco HACCP guidance, 2005. As already discussed, this integrated approach starts with the development of policies, which provide the framework for the operation of the allergen management plans. Typically, such policies will specify the aims of the plan, indicate what will be done to achieve those aims, and define major responsibilities for their fulfilment. Policies thus enshrine the corporate commitment to the plan. However, implementation requires more detailed guidance documents, which can be tailored to specific operational requirements and provide practical advice to individual manufacturing units. Guidelines will therefore differentiate between different types of food processing, such as dry mix lines and wet lines, but will also cover elements such as the cleaning of specific pieces of equipment within a factory. This approach ensures that a high minimum standard exists for the handling of allergens throughout the company. Existing food safety management systems can be helpful in applying these principles operationally.
16.5.2 Food safety management systems and food allergens A number of formal systems have been developed to deal with food safety hazards, of which the best known are Good Manufacturing Practices and Hazard Analysis Critical Control Point (HACCP) systems. More recently, the International Standards Organisation (ISO) has published ISO22000:2005, which describes a fully integrated approach to food safety management. Good manufacturing practice Good Manufacturing Practice (GMP) regulations (Code of Federal Regulations 21 Pt 110, 2001) are probably the earliest food safety management systems. These evolved originally to counter chemical contamination, adulteration and misrepresentation of products to the consumer. The current content of these regulations reflects these origins, as well as the later focus on microbiological
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safety. Many aspects of the current GMPs relating to human food production contain elements with application to allergen management. They thus cover provisions for personnel, including health, education and training, and supervision arrangements, provisions for buildings and facilities, including construction, layout, maintenance, sanitary operations and facilities, provisions for equipment design, construction and maintenance, in particular with regard to sanitation. The GMPs also cover production and process controls, including raw materials as well as manufacturing operations. Main requirements are as follows: • Personnel. Personnel working in food handling or processing facilities are required to be free of disease, to maintain adequate cleanliness to avoid contamination of the food, to take other necessary precautions to avoid contamination. If they are responsible for identifying food contamination, they must have an adequate level of education and training. Furthermore, responsibility for compliance must be assigned to suitably competent supervisory personnel. • Buildings and facilities. Plant buildings and structures must be of sufficient size, and adequate construction, and design to facilitate maintenance and sanitary operations for food-manufacturing purposes. The guidelines lay particular emphasis on sufficient size to ensure adequate separation of operations to avoid contamination. Facilities must also have adequate arrangements for cleaning of equipment, as well for employees to clean their hands. • Equipment. Equipment must be designed to be cleaned adequately and must be properly maintained. • Production and process controls. All operations from the raw material selection and handling to the final product must be conducted in accordance with adequate sanitation principles. Again, stress is laid on the requirement for adequate supervision. The regulations require that ‘All reasonable precautions shall be taken to ensure that production procedures do not contribute contamination from any source’. Even a cursory consideration of the requirements of current GMPs shows that, although they are heavily focused on microbiological control, their principles should constitute a good starting point for allergen management. The original US regulations date from 1986, when food allergy was not deemed a significant public health problem. A report commissioned by the FDA into modernisation of the GMPs recommended revision to incorporate, among other elements, guidance on allergen control (FDA-CFSAN, 2005). This recommendation was endorsed by many of those who offered comments during the consultation phase on the report (FDA-CFSAN, 2005). Hazard analysis and critical control points (HACCP) HACCP, unlike GMP, is not a system of regulations which specify what must be done. Instead, it is a set of principles which can be applied as part of an approach to food safety management. It was originally proposed by the Codex Alimentarius Commission, and is now considered by various regulatory authorities (e.g.
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European Commission, 2004) to be an appropriate tool to control hazards in food businesses. In contrast to GMP, HACCP is process-specific, and indeed can be considered complementary to GMP. The structure of HACCP means that it can be applied to almost any hazard. HACCP consists of the following seven stages: 1. hazard analysis: identify any hazards that must be prevented, eliminated or reduced to tolerable levels 2. identify the critical control points 3. establish critical limits at critical control points 4. establish and implement effective monitoring procedures at critical control points 5. establish corrective actions when monitoring indicates that a critical control point is not under control 6. establish procedures to verify that the measures outlined in paragraphs 1 to 5 are working effectively 7. establish documents and records commensurate with the nature and size of the food business to demonstrate the effective application of the measures outlined in steps 1 to 6. Some regulatory authorities, rather than defining GMPs, have mandated the use of HACCP principles as part of food safety management. Thus EU Regulation 852/ 2004 on the hygiene of foodstuffs requires the application of HACCP principles. However, the guidance document (European Commission, 2005) also stresses the flexible application of the concept, commensurate with the complexity of the business. ISO 22000:2005: Food safety management systems ISO 22000:2005 starts from the premise that the most effective food safety systems are established, operated and updated within the framework of a structured management system and incorporated into the overall management activities of the organisation (ISO 22000:2005). The standard aims to provide the structure for a comprehensive food safety management system, integrated into other management systems (e.g. quality management systems, such as ISO 9001:2000). Key elements, which it highlights, include the following: • Role of management. The standard recognises the essential role of senior management commitment, demonstrated by definition of the food safety policy, its documentation and its communication within and beyond the company. It also details a requirement for operation of the policy to be reviewed periodically by senior management, and for attribution of key responsibilities. • Communication. The standard lays considerable stress on communication, both within the company to promote its effective application, but also beyond to suppliers, retailers and consumers. • Resources. Compliance with the standard can only be achieved if adequate resources both in equipment and trained personnel are available.
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• Documentation. The safety management system must be documented, both in terms of its different elements (e.g. HACCP plans) and by evidence that it is being adhered to (e.g. audit results). • Non-conformity. Plans to deal with breaches of the policy (e.g. product nonconformity) need to be documented, including a system for managing recalls. • Evaluation. The food safety management system must be evaluated periodically to ascertain whether it continues to cover the company’s requirements and takes into account the most recent information on the food safety hazards subject to control. The principles of HACCP, as enunciated by the Codex Alimentarius Commission and outlined in the previous section, form an integral part of ISO 22000:2005. The standard differs from the GMP Regulations in that it provides a framework for companies who do not have a food safety management system to develop and implement one. It also permits those who have already implemented such a system to review it against the standard and, if appropriate, to update or add elements to it. It does not provide detailed guidance, for instance, on how to design and operate a factory to minimise the risk of allergen cross-contact. The standard links to GMPs through the requirement that Prerequisite Programmes – covering, for instance, hygiene – are in place prior to implementation of the system.
16.5.3 Food allergen management in Unilever Unilever, in parallel with other large food companies, identified food allergy as a public health issue long before it was addressed in international and regulatory documents dealing with food safety. Although its approach thus evolved separately, it contains many of the elements which have now been identified as key to food safety management. Unilever thus has a policy for dealing with allergens, which states that it shall declare the presence in its products of any allergen which is a common cause of allergic reactions. At a minimum, any allergen required by local regulations will be declared. However, beyond that, the allergenic risk from foods not considered commonly allergenic may be assessed if clinical or epidemiological data indicate the need. If then classed as a common cause of allergic reactions in accordance with the company’s criteria, this food component would then be declared on labels and included in allergen management plans. Unilever also undertakes to inform any consumer on request about the presence of uncommon allergens in specific products. The custodian of this policy, as of all Unilever policies, is the Executive Committee, thereby demonstrating senior management commitment. This approach enables the company to react more rapidly to emerging allergens than if it relied solely on reacting to external regulation. The policy, however, is made operational through specific guidelines, which exist for dry mix plants, wet savoury plants, ice-cream factories and other operations. Allergen management guidelines need to ensure that allergens are correctly and intelligibly declared in products, but also to make sure that allergen is not present
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inadvertently at levels likely to cause adverse health effects. Such guidelines need to address all stages in the product life cycle, from its design, through the sourcing of ingredients to manufacture, labelling and distribution. Specifically, they need to deal with: • Innovation. The product developer needs to consider whether the allergenic ingredient plays a functional role in the product or whether an equivalent nonallergenic ingredient could serve as well. Similarly, could an ingredient already present in the product replace an allergenic one; for instance, could wheat flour be used as a carrier for a flavour in a product already containing wheat? A further question that needs consideration is whether use of the allergenic ingredient in a product would alter the risks arising from existing operations, for instance by bringing a new allergenic ingredient into a plant. • Supply chain. Control of allergens in the supply chain requires a close relationship with suppliers, so that they understand the needs of the manufacturer and can meet its requirements. Typically, within Unilever, the starting point of the supplier assessment will be a questionnaire about allergens handled and precautions in place to avoid cross-contact, including the existence of a Hazard Analysis Critical Control Point (HACCP) plan. This is backed up by periodic audits of the suppliers’ facilities. Taking together, the resulting information will permit an assessment of the risk that an allergen is present inadvertently through the raw materials, and will form the basis for risk management measures, which might include a change of supplier. Additionally, where applicable, suppliers are required to seek agreement to any change in the formulation of the ingredient they supply. • Manufacturing protocols. The main considerations are the inclusion of common allergens in HACCP plans, production scheduling to minimise crosscontact, validated cleaning procedures and clear labelling and separation of specific allergenic ingredients within the factory. Procedures need to cover rework, where sound product is not packaged but ‘recycled’. Finally, the same degree of attention is needed whether the company’s own manufacturing facility is concerned or that of co-packers. • Training. Staff at all levels need to understand the importance of allergen control procedures and their own role in ensuring compliance. Training is thus vital and improves support for what could otherwise be perceived as irksome restrictions. • Packaging, promotion and advertising. Packaging carries the label and therefore the allergen information. Care is required to ensure that information remains with the product until it reaches the consumer: the allergen management plan needs to assess the probability that packs containing multiple individually packed items will be split, and the outer packaging separated from the product. Other considerations include the use of warnings if the formulation has changed to include an allergenic ingredient previously not present. • Retailers. Generally, the manufacturer’s allergen information will be
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sufficient. However, situations such as in-store promotions require care to ensure that the consumer is fully informed. Sound product, which fails to meet all standards for general sale, may be repackaged and sold on in specialised outlets or even in a different market. The manufacturer needs to ensure that appropriate allergen information is retained and available to the ultimate consumer. • Food professionals. Most allergic reactions to foods occur outside the home, in conditions where the product is often not labelled and even when asked, food professionals fail to provide correct information. Where pre-prepared food is provided to that sector, the manufacturer has a responsibility to ensure that accurate allergen information is provided and conveyed to the consumer. This brief summary of the elements of allergen management in Unilever illustrates the close parallels between the evolution of thinking within the company and the emerging consensus in the food safety management community. Although implementation in Unilever has characteristics specific to the company, with the key elements of a system integrated with other safety management systems, and the ultimate responsibility lying with the senior leadership of the company, it is more striking by its similarities to that consensus than by its differences from it.
16.6 Future trends Two main trends will drive developments in food allergen management. The first derives from current developments and application of risk assessment methodologies in food allergy. Several elements will contribute to hasten these developments. Data on both the prevalence of food allergy and the distribution of minimal eliciting doses will emerge from international projects in food allergy such as the European Union Integrated Project Europrevall. In parallel, risk assessment methodologies are being investigated for their applicability to food allergen risks. These developments will permit objectives for food allergen management to be based on improved understanding, and should facilitate the move from hazard- to risk-based approaches. These could mirror those in the area of microbiological safety and result in Food Safety Objectives related to food allergens. The requirements and demands of allergic consumers are the second element that will likely influence allergen management practices. Allergic consumers demand safe food products and as little limitation of choice as possible. Many food manufacturers have recognised these legitimate needs, and this has spurred developments in the risk-based approach. However, precautionary (may contain) labelling remains used to a considerable extent and is increasingly disliked by allergic consumers. This could impel public health authorities to develop regulation to control its application.
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16.7 Sources of information and advice Trade association guidelines Food and Drink Federation (UK): www.fdf.org.uk Confederation of the Food and Drink Industries of the European Union (CIAA): www.ciaa.be/ Food Safety Authorities guidelines Food Standards Agency (UK): http://www.food.gov.uk
16.8 References AVERY N J, KING R M, KNIGHT S, HOURIHANE J O (2003), Assessment of quality of life in children with peanut allergy, Pediatr Allergy Immunol, 14: 378–82. BUCHANAN R L, DAMERT W G, WHITING R C, SCHOTHORST M V (1997), Use of epidemiologic and food survey data to estimate a purposefully conservative doseresponse relationship for Listeria monocytogenes levels and incidence of listeriosis, J Food Prot, 60(8): 918–22. CODE OF FEDERAL REGULATIONS TITLE 21 PART 110 (2001), Current Good Manufacturing Practice In Manufacturing.Packing, Or Holding Human Food. www.access.gpo.gov/ nara/cfr/waisidx_01/21cfr110_01.html CODEX ALIMENTARIUS COMMISSION (1999), Hazard Analysis And Critical Control Point (Haccp) System And Guidelines For Its Application. ftp://ftp.fao.org/docrep/fao/005/ Y1579e/Y1579e.pdf CREVEL R W R (2005), Industrial dimensions of food allergy, Proc Nutr Soc, 64(4): 470–4. CREVEL R W R, BRIGGS D, HEFLE S L, KNULST A C, TAYLOR S L (2006), Hazard characterisation in food allergen risk assessment: the application of statistical approaches and the use of clinical data, Fd Chem Tox. DIRECTIVE 2003/89/EC OF THE EUROPEAN PARLIAMENT AND COUNCIL (2003), O.J. European Union L308/15, 25.11.2003. europa.eu.int/eur-lex/pri/en/oj/dat/2003/l_308/ l_30820031125en00150018.pdf EUROPEAN COMMISSION AND PARLIAMENT (2004), Regulation (EC) No 852/2004 of the European Parliament and of the Council of 29 April 2004 on the hygiene of foodstuffs. europa.eu.int/eur-lex/pri/en/oj/dat/2004/1_139/1_13920040430en00010054.pdf EUROPEAN COMMISSION (2005), Guidance on implementation of Regulation 852/2004. www.fsai.ie/legislation/food/eu_docs/Food_hygiene/EU_Guidance_852.pdf EUROPEAN COMMISSION (2006), Guidance document on the implementation of procedures based on the HACCP principles, and on the facilitation of the implementation of the HACCP principles in certain food businesses. www.fsai.ie/legislation/food/eu_docs/ Food_hygiene/EU_Guidance_HACCP.pdf FAO/WHO (1995), Application of Risk Analysis to Food Standards Issues, Report of the Joint FAO/WHO Expert Consultation, Geneva, Switzerland, 13–17 March 1995, WHO/ FNU/FOS/95.3. World Health Organisation, Geneva. http://www.who.int/fsf/Documents/ applira.pdf FAO/WHO (1997), Risk Management and Food Safety, Report of a Joint FAO/WHO Consultation, Rome, Italy, 27–31 January 1997, FAO Food and Nutrition Paper 65. Food and Agriculture Organisation of the United Nations, Rome. http://www.fao.org/docrep/ W4982E/W4982E00.htm FDA-CFSAN (2005), Approaches to establish thresholds for major food allergens and for gluten in food, http://www.cfsan.fda.gov/~dms/alrgn.html FDA-CFSAN (2005), Food CGMP modernization – A focus on food safety. http:// www.cfsan.fda.gov/~dms/cgmps3.html
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FOOD ALLERGEN LABELING AND CONSUMER PROTECTION ACT OF 2004 (Title II of Public Law 108–282) s.741–15–21. http://www.cfsan.fda.gov/~acrobat/alrgact.pdf HEFLE S L, LAMBRECHT D M (2004), Validated sandwich enzyme-linked immunosorbent assay for casein and its application to retail and milk-allergic complaint foods, J Food Prot, 67(9): 1933–8. HEFLE S L, TAYLOR S L (2004), Food allergy and the food industry, Curr Allergy Asthma Rep, 4(1): 55–9. HUGGETT A C, HISCHENHUBER C (1998), Food manufacturing initiatives to protect the allergic consumer, Allergy, 53 (Suppl 46): 89–92. INTERNATIONAL COMMISSION ON MICROBIOLOGICAL SPECIFICATIONS FOR FOODS (2002), Microbiological Testing in Food Safety Management (Microorganisms in food 7). Chapter 2: Evaluating risks and establishing a food safety objective, pp. 23–43. Kluwer Academic/Plenum Publishers, New York. INTERNATIONAL STANDARD 22000:2005. Food safety management systems – Requirements for any organization in the food chain. 1st edn 2005–09–01. International Standards Organisation, Geneva, Switzerland. KANNY G, MONERET-VAUTRIN D A, FLABBEE J, BEAUDOUIN E, MORISSET M, THEVENIN F (2001), Population study of food allergy in France, J Allergy Clin Immunol, 108(1): 133– 40. SAMPSON H A (2005), Food allergy – accurately identifying clinical reactivity, Allergy, 60 Suppl 79: 19–24. SICHERER S H, MUNOZ-FURLONG A, SAMPSON H A (2004), Prevalence of seafood allergy in the United States determined by a random telephone survey, J Allergy Clin Immunol, 114(1): 127–30. TAYLOR S L, HEFLE S L, BINDSLEV-JENSEN C ET AL. (2002), Factors affecting the determination of threshold doses for allergenic foods: How much is too much?, J Allergy Clin Immunol, 109: 24–30. TAYLOR S L, HEFLE S L, BINDSLEV-JENSEN C ET AL. (2004), A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?, Clin Exp Allergy, 34(5): 689–95. VIERK K, FALCI K, WOLYNIAK C, KLONTZ K C (2002), Recalls of foods containing undeclared allergens reported to the US Food and Drug Administration, fiscal year 1999, J Allergy Clin Immunol, 109(6): 920–2. WHO (2003), Guidelines for drinking-water quality, 3rd edn, Geneva, World Health Organisation. YOUNG E, STONEHAM M D, PETRUCKEVITCH A, BARTON J, RONA R (1994), A population study of food intolerance, Lancet, 343(8906): 1127–30.
16.1 Introduction Epidemiological studies published in the last 10 to 15 years indicate that significant proportions of the population of most countries surveyed suffer from food allergy. Early studies by Young et al. (1994) in the United Kingdom estimated a population prevalence of 1.4–1.9%, while more recent studies suggest figures of the order of 3.5–4% in the industrialised world (Kanny et al., 2001; Sicherer et al., 2004). The prevalence among children is generally accepted to be higher, of the order of up to 8% (Sampson, 2005). Such figures equate to upward of 10 million people with the condition in regions such as the EU or USA, and therefore a significant burden of ill-health and reduced quality of life. Avoidance of the offending allergen is currently the only treatment for food allergy and an immediate consequence of this is that having a member with food allergy affects the whole family and, to a lesser extent, the social circle of the allergic individual. Over the last two decades food allergy has thus evolved from a problem for the food-allergic individual to one of significant public health importance. This recognition has led to initiatives by public authorities and subsequently legislators in response. Stages in this development include the proposal by the Nordic countries in the early 1990s to amend the Codex Alimentarius’s 25% rule, leading to the FAO–WHO consultation in 1995 which identified eight major foods or food groups as important causes of food allergy (FAO/WHO, 1995). These early stages were followed in the early years of the 21st century by legislation in
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many countries and regions, including Australia, New Zealand, Japan, the European Union (Directive 2003/89/EC) and the United States of America (FALCPA, 2004). In parallel, many food manufacturing companies recognised the importance of food allergy and their responsibilities to their food-allergic consumers. Experience in the food industry, now going back a decade or longer, has demonstrated that allergen management shares many of the principles underlying management of other risks, such as toxicological or microbiological ones. In particular, safety cannot be ensured through end product testing, but must be built upon the careful analysis of the hazards at each stage of the product cycle. A key principle is therefore the development of an integrated approach that considers each stage of manufacturing, from the raw materials to the product that is delivered to the consumer, and involves all levels within a food company, as reflected in recently published guidelines (European Commission, 2006). However, responsibility for the management of food allergy does not rest solely with the food industry, but is a responsibility shared by other stakeholders, including health professionals, regulators and the allergic patients or their carers themselves. This chapter will consider the main issues associated with the principles underlying allergen management, its objectives, common issues and the application of allergen management.
16.2 Principles Allergen management systems form part of a family of food safety management systems, which include general toxicological and microbiological food safety. The requirements of allergen management may sometimes be at variance with those of other food safety systems. For instance, wet cleaning of dry mix lines would be a very effective way of removing allergenic residues, but at the risk of subsequent microbiological contamination. Allergen management therefore needs to be integrated into the overall food safety management system, a fact now explicitly recognised in new international guidance documents such as ISO 22000: 2005. Allergen management systems must meet both minimum statutory requirements and those that the company itself may have defined, after considering its objectives in this area of safety. These company requirements will arise from its own understanding of its operations and of the needs of its allergic consumers. An allergen management system must also balance a number of other requirements, the main one being to ensure a high degree of food safety with respect to allergens without impairing other aspects of food safety, but also without putting at risk the economic viability of the manufacturer. This can only be achieved if it is based on a clear set of objectives and clear criteria for action. Such systems will therefore need to take into account a number of factors as described below:
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16.2.1 Nature of food manufacturing operations Food manufacturing is typically a complex operation, which for purposes of allergen management, may be divided into several stages. These include the following: • Raw material selection and specification: depending on the operation, raw materials range from primary, minimally processed ingredients e.g. wheat flour, to complex formulated ingredients. The specification of these raw materials will limit what can be achieved in terms of residual allergen content. • Manufacturing operations: these vary considerably in complexity, depending on the type of products that are made at the facility. However, in almost all operations, many different products with different formulations are made on the same lines, with a constant risk of inadvertent transfer of residues from the previous formulations onto the following ones. An added complexity is that some equipment can be extremely difficult to clean down between production runs because of its design or the characteristics of the product made. Thus allergen management in dry mix plants, where water or aqueous solvents cannot usually be used, poses challenges which differ from those in wet process lines. Similarly, thermal treatments of the product often alter the ease with which allergenic residues can be removed by sanitation procedures. • Delivery to the consumer: most food manufacturers will deliver through retail or other outlets. In terms of allergen management, the manufacturer will need to consider how relevant information will be conveyed to the final consumer in such a way that it retains its integrity. In addition, food safety needs to be integrated into product development and innovation, such that new products do not degrade inadvertently the safety of existing operations when they are introduced. 16.2.2 Clinical and biological characteristics of food allergy Typically the minimum doses which elicit reactions in food-allergic individuals vary over many orders of magnitude. For peanut, for instance, this may be as much as 4 to 5 orders of magnitude among patients which have been challenged. Furthermore the reactivity of patients varies over time, depending on extraneous factors such environment, concurrent activity etc. Although reliable information is beginning to emerge on the distribution of minimum eliciting doses within selected population groups, little information is available on how symptoms in any one individual vary with the amount of allergen to which they are exposed. Thus it is difficult to define the safety margin between the dose provoking a slight reaction, which does not pose a threat to health and a dose which provokes a severe reaction. Development of an allergen management system could proceed through the following series of steps: • Definition of objectives. Defining objectives forms a key stage and merits careful consideration. Without clear objectives, an allergen management plan
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will be difficult both to communicate to those who must apply it operationally and to other stakeholders. It will also make it difficult to evaluate success and compliance. Absence of explicit objectives does not mean that no objectives exist, only that they are implicit. Such a situation poses a risk that objectives could be externally imposed without consideration for their achievability. Clear objectives also provide a company with a defensible position in the event of challenge. • Setting out a policy. Once objectives have been defined, these can be set out in a policy which will be a statement of what the company aims are and an outline of how they are to be achieved. It can also set out broad responsibilities for ensuring these aims are achieved. The policy enunciates the commitment of the company through its senior management. It also provides the basis for defining subsidiary objectives and mechanisms which will ensure compliance. • Drawing up guidelines. As indicated above, the policy document is not a dayto-day working document. Guidelines fulfil this purpose by detailing mechanisms and procedures to implement the broad objectives at a practical level. Guidelines will therefore cover detailed operations at all levels of the organisation. They will be adapted to cover the diversity of the company’s operations, including raw material types and sourcing, types of operation, etc.
16.3 Objectives Risk management of food allergens, as of other hazards, requires a clear definition of objectives. These need to recognise and balance the sometimes divergent interests of different stakeholders, a process which is often difficult to make explicit in the absence of formal mechanisms. In this context, the concept of Food Safety Objectives, analogous to those proposed by the ICMSF (2002) for microbiological hazards and as elaborated by the Codex Alimentarius Commission (Codex Alimentarius Commission, 1999), could form a useful basis for eliciting a consensus. The primary objective behind allergen risk management must be to prevent adverse reactions in food-allergic individuals, while not limiting their food choices unnecessarily. However, the apparent simplicity of this statement hides a number of complex issues. Firstly, in a matter of public health such as allergen management, the interests and needs of different stakeholders, which may diverge, must be balanced. These stakeholders include not only the allergic population, but also the general population, as well as the food industry and health professionals. Most common food allergens play an important nutritional role in the diet of the population as a whole, and it is not practicable, let alone desirable to eliminate them from products. Furthermore, the majority of the population is not exposed to any risk from food allergens, irrespective of the amounts to which they may be exposed. This situation differentiates food allergens from other food hazards, such as chemical or microbiological contaminants, from which no individual derives any benefit, and where the whole population is potentially at risk. This has two
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implications: firstly, the general population derives no direct benefit from allergen control measures, and indeed must indirectly bear their cost; secondly, because most product lines are shared, the adventitious presence of specific residual allergens will be inevitable in many products. The threshold of reactivity to allergenic foods ranges over many orders of magnitude while allergic reactions to foods span a considerable range of severity, from the barely noticeable to life-threatening anaphylaxis. There is thus a small and poorly defined fraction of the allergic population who react severely to very small amounts of allergenic food. Procedures to reduce unintentional presence of allergens may not be sufficient to protect such people, and other allergen management measures will be required to protect them. These observations underline the importance of setting clear objectives for allergen risk management, and ensuring they are clearly communicated to stakeholders. These objectives should define who the risk management activities aim to protect and against what. They can then serve to evaluate the effectiveness of measures taken to achieve them.
16.3.1 Who are we trying to protect and against what? Food allergy differs from most other adverse responses to foods. Within the susceptible population, the range of allergenic reactivity, expressed as the smallest amount of an allergenic ingredient able to trigger a reaction, spans many orders of magnitude (Taylor et al., 2002). Knowledge of minimum eliciting doses (thresholds), and the proportion of the population reactive to very small amounts, remains currently very limited and may be impossible to establish experimentally. Furthermore, a small, although unquantified proportion of the susceptible population can react severely to small amounts of allergenic protein (of the order of milligrams). Under those circumstances, the concept of protecting the whole allergic population against all reactions, however mild, is unrealistic. Design of food allergen management plans must therefore consider what level of protection they purport to provide, or in other words what can be considered a tolerable risk. Defining the tolerable risk level involves considering the probability of an adverse event, as well as its consequences in terms of severity. The two aspects are clearly related, inasmuch as the tolerable frequency for severe adverse events will be much lower than the tolerable frequency of all adverse events, among which events of low severity will predominate. Establishing the tolerable level is a societal issue, but little explicit guidance exists in the area of food allergy itself. One approach would be to consider the disease burden attributable to the less common food allergens, which are not subject to statutory regulation. This burden of disease could be considered to be that tolerated implicitly by society. In practice, however, information is lacking on the disease burden attributable to common, regulated allergens, let alone the less common ones, making this approach impracticable. Another approach might be to look to other situations analogous to food safety. The safety of drinking water shares characteristics with the protection of foodallergic people. In particular, any risk posed by drinking water is imposed on those
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who consume it and, for practical purposes, is usually impossible to avoid. The World Health Organisation has debated drinking water standards and proposed draft guidelines for drinking water quality, which translate to a probability of disease for any one individual of 10–3 per year or approximately 1 in 10 over a lifetime (WHO, 2003). This figure, of course, refers to all disease, irrespective of severity, so cannot be applied without qualification to allergic reactions to food. However, it can provide a basis for discussion among stakeholders.
16.3.2 Hazard- versus risk-based approaches The simplest way to protect allergic consumers would be to ensure that the allergenic ingredients to which they are reactive are either declared on the product label in all circumstances or are totally excluded. This hazard-based approach is broadly appropriate to deliberately added ingredients, and indeed has been adopted in several pieces of legislation regulating allergens (e.g. Directive 2003/89/EC). However, food-allergic individuals are also at risk from small amounts of residual allergen inadvertently carried over from other products because of the sharing of manufacturing lines, or because of admixture into raw materials such as grains during storage and transport. The hazard-based approach focuses on the presence of the allergen and does not recognise the existence of an amount of allergenic protein below which there is virtually no risk. As a result, it provides no mechanism to decide on the magnitude of the danger that the presence of residual allergen constitutes. It is arguably therefore not the most effective way to protect the vast majority of food-allergic people while balancing the interests of different stakeholders. At the limit, it leads to declaration of the presence of allergen in amounts which present little or no risk to health. Application of a hazard-based approach thus decreases the food choices of the allergic population and increases the likelihood that they will suffer nutritional deficiencies, as well as reducing their quality of life (Avery et al., 2003). When applied to cross-contact allergens it is reflected in excessive use of precautionary (‘may contain’) labelling. While such a label on an individual product may well add to the protection of allergic individuals, the uncontrolled proliferation of such labels is likely to decrease it, as trust in the label reduces and it is ignored. The possibility also exists that some allergic people will misinterpret such a label, if they consume the product and fail to react, wrongly concluding that they are no longer allergic. The theoretical diagram in Fig. 16.1 attempts to illustrate these observations. Maximising public health outcomes thus ineluctably leads to a risk-based approach to allergen management. Risk can be defined as the probability that a hazard will become manifest, and is often expressed as a function of the intrinsic hazard and the exposure to that hazard. This definition is sometimes expanded to include severity of the resulting adverse effect. Thus, risk is defined in ISO/IEC Guide 51 as the combination of the probability of occurrence of harm and the severity of that harm (ISO 22000:2005). The key concept is therefore that of probability. In line with that concept, risk management does not seek to eliminate the risk, which is generally regarded as
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Fig. 16.1 Illustration of the efficacy of precautionary labelling against frequency of use.
impossible unless there is no exposure, but to reduce the probability of harm to a level which is considered tolerable. What is tolerable will be determined by a societal decision, which will reflect the balance of different stakeholder interests.
16.3.3 Risk assessment principles for allergens in food manufacturing Risk assessment as a process begins with hazard identification, followed by hazard characterisation, exposure assessment and risk characterisation to scope the overall risk to the population (FAO/WHO, 1997). Translating this to food allergens, the hazard itself is already defined as their intrinsic allergenicity, in this context their ability to provoke an allergic reaction. Beyond this, risk assessors require information about the characteristics of the hazard, which in this context can mean the response characteristics of the population at risk (distribution of minimum eliciting doses – thresholds, dose–response), the size of the population at risk, and the extent of exposure. In ideal circumstances, risk assessors could calculate the number of reactions that would occur for any given level of residual allergen in a food product if people allergic to that food consumed it. In practice, information on all the elements required for a risk assessment remains extremely limited. Studies to describe the reactivity of the allergic population in terms of minimum eliciting doses (thresholds) are still largely limited to selected populations, such as clinic patients, and further work is needed to map their reactivity onto the general allergic population. It is also limited to certain allergenic foods. Most available information is based on studies undertaken for other purposes, further limiting their value for establishing minimum eliciting doses because of the type of data generated. Only anecdotal information is available on the relationship between the dose of allergen to which an individual is exposed and the severity of the reaction
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experienced, as obtaining that information systematically presents considerable ethical difficulties. Further complexities arise from differences in the extent to which allergenic proteins are released from different food matrices, and become available to be recognised by the immune system. Uncertainty also exists over the size of the population at risk, given that epidemiological data are scarce for most regions. In most countries, there is also a surprising lack of detailed information about the incidence of reactions, even severe and fatal ones. Minimum eliciting doses (thresholds) clearly form a key piece of information for risk assessors. A recent report by FDA-CFSAN identified four ways in which they might be determined: analytically-based, statutorily derived, using a safety assessment approach and using a risk assessment approach. They indicated a preference for the risk assessment approach on the grounds that it was the most scientifically robust, as well as transparent, an important consideration in communicating with other stakeholders. Of those four approaches, only the safety and risk assessment ones use biological data on the reactivity of allergic patients, generated under controlled conditions. The safety assessment approach applies an uncertainty factor to either the highest dose of allergenic protein observed not to provoke a reaction or to the lowest one which does provoke a reaction (depending on what is available). Recently, we proposed an approach that aims to define the expected number of reactions from exposure to specified amounts of allergenic ingredient in a product and use it as a basis for risk assessment (Crevel et al., submitted), subsequently aiding risk management and communication. This approach is based on modelling statistically the dose–distribution data obtained from food challenge studies, to gain insights into the likely incidence of reactions to very low amounts of residual allergen, lower than can be practicably tested experimentally. The approach takes the following steps: 1. Good quality data from well-controlled challenge studies constitute the foundation of the approach. Such studies should be conducted using the agreed protocol proposed by Taylor et al. (2004). 2. A tolerable limit for the proportion (p) of allergic individuals who might react is established for the allergens of interest. The level p is defined in consultation with other stakeholders (regulators, patients, industry, clinicians). This part of the process requires other factors to be accounted for such as the prevalence of allergy to the allergen of interest, the actual rate of reported reactions, and their severity. 3. Data from a challenge study are analysed and a statistical distribution is fitted to the study data. The model is used to predict the EDp and the lower confidence interval on the EDp for the p defined in step 2. Precedents from other areas of food safety support this approach, although there are distinct differences, related to the type of data that are available or can be generated in each case. Thus Buchanan et al. (1997) estimated a conservative dose–response relationship for listeriosis using surveillance data on the number of
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cases, together with food sampling data on Listeria contamination of a food responsible for most such cases. In our approach, we use statistical distributions to describe data from clinical challenge studies performed under carefully controlled conditions. In microbiological terms, such data are more akin to controlled feeding studies with defined numbers of microorganisms in human volunteers. Inevitably, the populations tested in these studies contain an element of bias. Firstly, they will tend to exclude individuals who have suffered life-threatening reactions, as these may be less willing to participate and the clinicians more reluctant to accept them in a study on account of the risks. Perhaps more significantly, the process of selecting for challenge studies will result in a bias towards the more severely affected of the allergic population, other than the category previously mentioned. This arises because volunteers are chosen from the population which attends tertiary referral clinics, and who are therefore sufficiently motivated by the impact of their condition to visit a clinical expert. Limitations also exist when using such data as a basis for risk management, because they do not take into account some of the factors which modulate the allergic response, such as alcohol intake, exercise, etc. However, it can be argued that compared to other areas of toxicology, these data present the major advantage of being generated in the species of interest. Currently available data do not permit a direct application of the methods proposed in Buchanan et al. (1997). Specifically, data on the incidence of even severe allergic reactions to foods are not reliable, and usable published data on the distribution of undeclared allergen in food are very limited. Nevertheless, the next step in the development of this approach is to validate the predictions by comparing the number of predicted reactions with the number actually observed. Development of allergen management policies and procedures by food manufacturers contributes significantly to protection of allergic consumers by ensuring that the inadvertent presence of allergenic ingredients in products is minimised (Hefle and Taylor, 2004; Huggett et al., 1998; Crevel, 2005). However, the nature and complexity of food manufacturing operations imposes limits on such approaches, which can only be overcome at significant cost. These considerations have led significant numbers in the food industry towards the concept, and in many cases the use, of defensive (precautionary) labelling. This type of labelling, while initially welcomed by allergic consumers, has become devalued through perceived over-use and inconsistent application. In addition, such labelling is not justified for levels which would not cause effects. Indeed it now presents the allergic consumer with a dilemma: observe the labelling and face much decreased choice or ignore it and risk a reaction to the food.
16.4 Issues associated with allergen management The increasing number of recalls triggered by regulatory inspections (Vierk et al., 2002), by consumer complaints (Hefle and Lambrecht, 2004), or by system failures, which result in the presence of undeclared allergen at hazardous levels,
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indicate that unresolved issues exist with allergen management systems. A report commissioned by the US FDA as part of a review of Good Manufacturing Practices in the food industry summarised issues arising from the operation of allergen management systems. These issues spanned the whole manufacturing supply chain as follows: • Raw materials. Adventitious presence of allergen was a problem, with incomplete knowledge of the formulation of ingredients used as raw materials, and the use of reconditioned ingredients and raw materials. Suggestions for overcoming these issues included developing a close working relationship with suppliers and performing regular audits. Training for the supplier could also be considered to improve understanding of the issues. Rework, which could be classed as a raw material, should be handled according to a defined and documented plan. • Manufacturing processes and procedures. The presence of undeclared allergen in a product was found to result from a multiplicity of sources and during manufacture, including inadequate cleaning, lack of physical separation at cross-over points in production lines, lack of separation between production runs, carry-over of allergen from shared storage equipment or from maintenance tools. The report recommended that allergens should be included in an overall hazard analysis, using a system such as the Hazard Analysis Critical Control Point approach or equivalent. Specific recommendations included cleaning to an appropriate degree of thoroughness, recognising that this may exceed what is required to assure microbiological safety. If appropriate, cleaning should include disassembly of the equipment. Cleaning protocols may need to be validated analytically. Other measures included production scheduling, building in physical barriers to prevent allergen ingress at cross-over points and providing dedicated storage facilities and maintenance equipment for specific allergenic materials. • Labelling or packaging. The report found that many companies failed to review their labelling, as a result of which ingredient declaration could be inaccurate. Recommendations included regular label reviews, together with policy to ensure old labels cannot be re-used. • Equipment design. The report identified old equipment as an important issue, either because it is difficult to clean, for instance because it cannot be dismantled, or because it lends itself to allergen accumulation which cannot be readily detected by inspection. Hygienic design should overcome much of this problem as old plant is renewed. • Effective training of employees. The report identified training as one of the areas where effectiveness was perceived to be lowest. Issues included training of the wrong people, not training enough people and not providing enough training. A key point made was that training should be delivered by people familiar with the plant, rather than by consultants.
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16.5 Application 16.5.1 From policy to guidelines: the need for an integrated approach Allergen management policies establish principally intent, but guidelines are required to set out the detailed mechanisms whereby this intent is made operational. As already mentioned, allergen management requires consideration of all the elements of the life cycle and production of a product from its design, through selection of raw materials to production processes and finally delivery to the consumer. This marks out allergen management as an activity which requires commitment throughout a company from senior management all the way to those working on production lines. Procedures that are put in place for allergen management may also impinge on other aspects of food safety. Effective delivery of such commitment therefore requires that allergen management be integrated into overall food safety management and encompass all stages of the life cycle of the product from the raw materials to the end product which the consumer buys. This has recently been recognised in external standards for food safety management systems such as ISO 22000:2005 and the EU’s DG Sanco HACCP guidance, 2005. As already discussed, this integrated approach starts with the development of policies, which provide the framework for the operation of the allergen management plans. Typically, such policies will specify the aims of the plan, indicate what will be done to achieve those aims, and define major responsibilities for their fulfilment. Policies thus enshrine the corporate commitment to the plan. However, implementation requires more detailed guidance documents, which can be tailored to specific operational requirements and provide practical advice to individual manufacturing units. Guidelines will therefore differentiate between different types of food processing, such as dry mix lines and wet lines, but will also cover elements such as the cleaning of specific pieces of equipment within a factory. This approach ensures that a high minimum standard exists for the handling of allergens throughout the company. Existing food safety management systems can be helpful in applying these principles operationally.
16.5.2 Food safety management systems and food allergens A number of formal systems have been developed to deal with food safety hazards, of which the best known are Good Manufacturing Practices and Hazard Analysis Critical Control Point (HACCP) systems. More recently, the International Standards Organisation (ISO) has published ISO22000:2005, which describes a fully integrated approach to food safety management. Good manufacturing practice Good Manufacturing Practice (GMP) regulations (Code of Federal Regulations 21 Pt 110, 2001) are probably the earliest food safety management systems. These evolved originally to counter chemical contamination, adulteration and misrepresentation of products to the consumer. The current content of these regulations reflects these origins, as well as the later focus on microbiological
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safety. Many aspects of the current GMPs relating to human food production contain elements with application to allergen management. They thus cover provisions for personnel, including health, education and training, and supervision arrangements, provisions for buildings and facilities, including construction, layout, maintenance, sanitary operations and facilities, provisions for equipment design, construction and maintenance, in particular with regard to sanitation. The GMPs also cover production and process controls, including raw materials as well as manufacturing operations. Main requirements are as follows: • Personnel. Personnel working in food handling or processing facilities are required to be free of disease, to maintain adequate cleanliness to avoid contamination of the food, to take other necessary precautions to avoid contamination. If they are responsible for identifying food contamination, they must have an adequate level of education and training. Furthermore, responsibility for compliance must be assigned to suitably competent supervisory personnel. • Buildings and facilities. Plant buildings and structures must be of sufficient size, and adequate construction, and design to facilitate maintenance and sanitary operations for food-manufacturing purposes. The guidelines lay particular emphasis on sufficient size to ensure adequate separation of operations to avoid contamination. Facilities must also have adequate arrangements for cleaning of equipment, as well for employees to clean their hands. • Equipment. Equipment must be designed to be cleaned adequately and must be properly maintained. • Production and process controls. All operations from the raw material selection and handling to the final product must be conducted in accordance with adequate sanitation principles. Again, stress is laid on the requirement for adequate supervision. The regulations require that ‘All reasonable precautions shall be taken to ensure that production procedures do not contribute contamination from any source’. Even a cursory consideration of the requirements of current GMPs shows that, although they are heavily focused on microbiological control, their principles should constitute a good starting point for allergen management. The original US regulations date from 1986, when food allergy was not deemed a significant public health problem. A report commissioned by the FDA into modernisation of the GMPs recommended revision to incorporate, among other elements, guidance on allergen control (FDA-CFSAN, 2005). This recommendation was endorsed by many of those who offered comments during the consultation phase on the report (FDA-CFSAN, 2005). Hazard analysis and critical control points (HACCP) HACCP, unlike GMP, is not a system of regulations which specify what must be done. Instead, it is a set of principles which can be applied as part of an approach to food safety management. It was originally proposed by the Codex Alimentarius Commission, and is now considered by various regulatory authorities (e.g.
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European Commission, 2004) to be an appropriate tool to control hazards in food businesses. In contrast to GMP, HACCP is process-specific, and indeed can be considered complementary to GMP. The structure of HACCP means that it can be applied to almost any hazard. HACCP consists of the following seven stages: 1. hazard analysis: identify any hazards that must be prevented, eliminated or reduced to tolerable levels 2. identify the critical control points 3. establish critical limits at critical control points 4. establish and implement effective monitoring procedures at critical control points 5. establish corrective actions when monitoring indicates that a critical control point is not under control 6. establish procedures to verify that the measures outlined in paragraphs 1 to 5 are working effectively 7. establish documents and records commensurate with the nature and size of the food business to demonstrate the effective application of the measures outlined in steps 1 to 6. Some regulatory authorities, rather than defining GMPs, have mandated the use of HACCP principles as part of food safety management. Thus EU Regulation 852/ 2004 on the hygiene of foodstuffs requires the application of HACCP principles. However, the guidance document (European Commission, 2005) also stresses the flexible application of the concept, commensurate with the complexity of the business. ISO 22000:2005: Food safety management systems ISO 22000:2005 starts from the premise that the most effective food safety systems are established, operated and updated within the framework of a structured management system and incorporated into the overall management activities of the organisation (ISO 22000:2005). The standard aims to provide the structure for a comprehensive food safety management system, integrated into other management systems (e.g. quality management systems, such as ISO 9001:2000). Key elements, which it highlights, include the following: • Role of management. The standard recognises the essential role of senior management commitment, demonstrated by definition of the food safety policy, its documentation and its communication within and beyond the company. It also details a requirement for operation of the policy to be reviewed periodically by senior management, and for attribution of key responsibilities. • Communication. The standard lays considerable stress on communication, both within the company to promote its effective application, but also beyond to suppliers, retailers and consumers. • Resources. Compliance with the standard can only be achieved if adequate resources both in equipment and trained personnel are available.
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• Documentation. The safety management system must be documented, both in terms of its different elements (e.g. HACCP plans) and by evidence that it is being adhered to (e.g. audit results). • Non-conformity. Plans to deal with breaches of the policy (e.g. product nonconformity) need to be documented, including a system for managing recalls. • Evaluation. The food safety management system must be evaluated periodically to ascertain whether it continues to cover the company’s requirements and takes into account the most recent information on the food safety hazards subject to control. The principles of HACCP, as enunciated by the Codex Alimentarius Commission and outlined in the previous section, form an integral part of ISO 22000:2005. The standard differs from the GMP Regulations in that it provides a framework for companies who do not have a food safety management system to develop and implement one. It also permits those who have already implemented such a system to review it against the standard and, if appropriate, to update or add elements to it. It does not provide detailed guidance, for instance, on how to design and operate a factory to minimise the risk of allergen cross-contact. The standard links to GMPs through the requirement that Prerequisite Programmes – covering, for instance, hygiene – are in place prior to implementation of the system.
16.5.3 Food allergen management in Unilever Unilever, in parallel with other large food companies, identified food allergy as a public health issue long before it was addressed in international and regulatory documents dealing with food safety. Although its approach thus evolved separately, it contains many of the elements which have now been identified as key to food safety management. Unilever thus has a policy for dealing with allergens, which states that it shall declare the presence in its products of any allergen which is a common cause of allergic reactions. At a minimum, any allergen required by local regulations will be declared. However, beyond that, the allergenic risk from foods not considered commonly allergenic may be assessed if clinical or epidemiological data indicate the need. If then classed as a common cause of allergic reactions in accordance with the company’s criteria, this food component would then be declared on labels and included in allergen management plans. Unilever also undertakes to inform any consumer on request about the presence of uncommon allergens in specific products. The custodian of this policy, as of all Unilever policies, is the Executive Committee, thereby demonstrating senior management commitment. This approach enables the company to react more rapidly to emerging allergens than if it relied solely on reacting to external regulation. The policy, however, is made operational through specific guidelines, which exist for dry mix plants, wet savoury plants, ice-cream factories and other operations. Allergen management guidelines need to ensure that allergens are correctly and intelligibly declared in products, but also to make sure that allergen is not present
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inadvertently at levels likely to cause adverse health effects. Such guidelines need to address all stages in the product life cycle, from its design, through the sourcing of ingredients to manufacture, labelling and distribution. Specifically, they need to deal with: • Innovation. The product developer needs to consider whether the allergenic ingredient plays a functional role in the product or whether an equivalent nonallergenic ingredient could serve as well. Similarly, could an ingredient already present in the product replace an allergenic one; for instance, could wheat flour be used as a carrier for a flavour in a product already containing wheat? A further question that needs consideration is whether use of the allergenic ingredient in a product would alter the risks arising from existing operations, for instance by bringing a new allergenic ingredient into a plant. • Supply chain. Control of allergens in the supply chain requires a close relationship with suppliers, so that they understand the needs of the manufacturer and can meet its requirements. Typically, within Unilever, the starting point of the supplier assessment will be a questionnaire about allergens handled and precautions in place to avoid cross-contact, including the existence of a Hazard Analysis Critical Control Point (HACCP) plan. This is backed up by periodic audits of the suppliers’ facilities. Taking together, the resulting information will permit an assessment of the risk that an allergen is present inadvertently through the raw materials, and will form the basis for risk management measures, which might include a change of supplier. Additionally, where applicable, suppliers are required to seek agreement to any change in the formulation of the ingredient they supply. • Manufacturing protocols. The main considerations are the inclusion of common allergens in HACCP plans, production scheduling to minimise crosscontact, validated cleaning procedures and clear labelling and separation of specific allergenic ingredients within the factory. Procedures need to cover rework, where sound product is not packaged but ‘recycled’. Finally, the same degree of attention is needed whether the company’s own manufacturing facility is concerned or that of co-packers. • Training. Staff at all levels need to understand the importance of allergen control procedures and their own role in ensuring compliance. Training is thus vital and improves support for what could otherwise be perceived as irksome restrictions. • Packaging, promotion and advertising. Packaging carries the label and therefore the allergen information. Care is required to ensure that information remains with the product until it reaches the consumer: the allergen management plan needs to assess the probability that packs containing multiple individually packed items will be split, and the outer packaging separated from the product. Other considerations include the use of warnings if the formulation has changed to include an allergenic ingredient previously not present. • Retailers. Generally, the manufacturer’s allergen information will be
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sufficient. However, situations such as in-store promotions require care to ensure that the consumer is fully informed. Sound product, which fails to meet all standards for general sale, may be repackaged and sold on in specialised outlets or even in a different market. The manufacturer needs to ensure that appropriate allergen information is retained and available to the ultimate consumer. • Food professionals. Most allergic reactions to foods occur outside the home, in conditions where the product is often not labelled and even when asked, food professionals fail to provide correct information. Where pre-prepared food is provided to that sector, the manufacturer has a responsibility to ensure that accurate allergen information is provided and conveyed to the consumer. This brief summary of the elements of allergen management in Unilever illustrates the close parallels between the evolution of thinking within the company and the emerging consensus in the food safety management community. Although implementation in Unilever has characteristics specific to the company, with the key elements of a system integrated with other safety management systems, and the ultimate responsibility lying with the senior leadership of the company, it is more striking by its similarities to that consensus than by its differences from it.
16.6 Future trends Two main trends will drive developments in food allergen management. The first derives from current developments and application of risk assessment methodologies in food allergy. Several elements will contribute to hasten these developments. Data on both the prevalence of food allergy and the distribution of minimal eliciting doses will emerge from international projects in food allergy such as the European Union Integrated Project Europrevall. In parallel, risk assessment methodologies are being investigated for their applicability to food allergen risks. These developments will permit objectives for food allergen management to be based on improved understanding, and should facilitate the move from hazard- to risk-based approaches. These could mirror those in the area of microbiological safety and result in Food Safety Objectives related to food allergens. The requirements and demands of allergic consumers are the second element that will likely influence allergen management practices. Allergic consumers demand safe food products and as little limitation of choice as possible. Many food manufacturers have recognised these legitimate needs, and this has spurred developments in the risk-based approach. However, precautionary (may contain) labelling remains used to a considerable extent and is increasingly disliked by allergic consumers. This could impel public health authorities to develop regulation to control its application.
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16.7 Sources of information and advice Trade association guidelines Food and Drink Federation (UK): www.fdf.org.uk Confederation of the Food and Drink Industries of the European Union (CIAA): www.ciaa.be/ Food Safety Authorities guidelines Food Standards Agency (UK): http://www.food.gov.uk
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FOOD ALLERGEN LABELING AND CONSUMER PROTECTION ACT OF 2004 (Title II of Public Law 108–282) s.741–15–21. http://www.cfsan.fda.gov/~acrobat/alrgact.pdf HEFLE S L, LAMBRECHT D M (2004), Validated sandwich enzyme-linked immunosorbent assay for casein and its application to retail and milk-allergic complaint foods, J Food Prot, 67(9): 1933–8. HEFLE S L, TAYLOR S L (2004), Food allergy and the food industry, Curr Allergy Asthma Rep, 4(1): 55–9. HUGGETT A C, HISCHENHUBER C (1998), Food manufacturing initiatives to protect the allergic consumer, Allergy, 53 (Suppl 46): 89–92. INTERNATIONAL COMMISSION ON MICROBIOLOGICAL SPECIFICATIONS FOR FOODS (2002), Microbiological Testing in Food Safety Management (Microorganisms in food 7). Chapter 2: Evaluating risks and establishing a food safety objective, pp. 23–43. Kluwer Academic/Plenum Publishers, New York. INTERNATIONAL STANDARD 22000:2005. Food safety management systems – Requirements for any organization in the food chain. 1st edn 2005–09–01. International Standards Organisation, Geneva, Switzerland. KANNY G, MONERET-VAUTRIN D A, FLABBEE J, BEAUDOUIN E, MORISSET M, THEVENIN F (2001), Population study of food allergy in France, J Allergy Clin Immunol, 108(1): 133– 40. SAMPSON H A (2005), Food allergy – accurately identifying clinical reactivity, Allergy, 60 Suppl 79: 19–24. SICHERER S H, MUNOZ-FURLONG A, SAMPSON H A (2004), Prevalence of seafood allergy in the United States determined by a random telephone survey, J Allergy Clin Immunol, 114(1): 127–30. TAYLOR S L, HEFLE S L, BINDSLEV-JENSEN C ET AL. (2002), Factors affecting the determination of threshold doses for allergenic foods: How much is too much?, J Allergy Clin Immunol, 109: 24–30. TAYLOR S L, HEFLE S L, BINDSLEV-JENSEN C ET AL. (2004), A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?, Clin Exp Allergy, 34(5): 689–95. VIERK K, FALCI K, WOLYNIAK C, KLONTZ K C (2002), Recalls of foods containing undeclared allergens reported to the US Food and Drug Administration, fiscal year 1999, J Allergy Clin Immunol, 109(6): 920–2. WHO (2003), Guidelines for drinking-water quality, 3rd edn, Geneva, World Health Organisation. YOUNG E, STONEHAM M D, PETRUCKEVITCH A, BARTON J, RONA R (1994), A population study of food intolerance, Lancet, 343(8906): 1127–30.