This year's Extractables & Leachables Europe features a never been seen before session dedicated to what the pharmaceutical industry can learn from the food contact industry. As part of the session, Pete Watts, Director of Toxicology at Bibra, will present on 'Migrant Health Risk Assessment and Supporting Toxicity Data Sources' so we spoke to him to find out more about what learnings can be had, why it's an important topic to discuss and how the information can be used to shape the industry in the future.
What learnings can the pharma industry take from looking at the food contact industry and case studies? Are there similarities in methodology?
I'd say there is significant expertise and awareness, in both sectors, that the contact between product and processing equipment, packaging and delivery devices can result in the transfer of chemicals into the product and subsequent delivery to the patient/consumer. In both sectors, there are requirements to undertake safety evaluations to ensure that any migration/leaching does not occur in quantities that significantly alter the safety, identity or quality of their end product.
Others will no doubt better address the regulatory aspects, but we can perhaps think about when the pharma industry can benefit from an understanding of extractable profiles of food packaging materials - as they already do, for example in their selection of 'food-grade' packaging materials for oral pharmaceuticals.
The question of risk-benefit is an interesting discussion. The pharma industry typically caters for specific subgroups (often age- and disease-specific) and can carry out focused health risk assessments. The food industry is aimed at healthy consumers (but patients have to eat too!) but has little control over which population subgroups partake of the foodstuff, or how much. The toxicologists can assess the health risks but are not necessarily the best professionals to judge benefits and make the overall calls. In the Pharma industry, there are (we hope) significant benefits associated with the API. The benefits of eating and drinking are obvious.
There are similarities for the two sectors in methodology, both in the analytical phase (determining the extent of migration/leaching) and in the toxicological phase (assessing health risk). In each sector, the analytical phase involves extraction of the manufactured materials with a range of standard solvent systems under certain (rigorous) conditions. In the food-contact sector, there is a relatively high level of standardisation over appropriate solvents and extraction conditions, with the extent of migration being critically dependent upon where the contents lie on the aqueous-fatty scale. For the pharma sector, very useful guidance on extraction methods exists, but there is little in the way of legislative rules or harmonisation (which, of course, allows for a greater degree of flexibility in study design).
Where the sectors do differ in methodology is that the food-contact sector relies heavily on the migration “simulation” studies (what pharma calls “extractables” studies) because detecting and quantifying low levels of migrants in many actual foodstuffs (equivalent to the pharma “leachables” investigation) is generally too challenging, due to the complex nature of the food-based contents. The pharma industry often has the chance to better define “real” exposures by analysing the relatively simple drug products themselves.
In the food-contact sector, there are established regulatory limits for (a) overall migration and (b) specific migration for a certain range of migrating species. These have been set based on derivations of tolerable daily intakes (TDIs) together with default figures for food/drink consumption, packaging area/food weight ratios, and a default population body weight. These can be seen as helpful or restrictive, depending upon circumstances. In the Food-contact area, daily lifetime consumption is the default assumption; in the pharma area, many treatments are short-term.
While the food sector need only concern itself with ingestion, pharma sector products may be administered by oral, dermal, inhalation or injection routes. This diversity of exposure routes poses additional challenges for the risk assessors in the pharma sector. For example, oral exposure to polymers is generally of very low concern due to a lack of systemic absorption – but who wants to be infused with a metabolism-resistant molecule that is too large for the kidney to excrete?
Your presentation will look at migrant health risk assessment and supporting toxicity data sources, why is this an important topic to discuss at E&L Europe 2017 and what will your presentation cover?
The issue of migration into food is very important because of its invisibility to us as consumers. Food labelling legislation provides us with a considerable amount of detail on the contents – e.g. weight, price, ingredients, additives, nutritional information (total calories, calorie distribution between fat, carbohydrate, protein), carbohydrate distribution (sugars, etc.) and even percentages of daily recommended allowances. Thus we, as consumers, are in a strong position to make informed choices in selecting foods and drinks. In contrast, information on the nature of the packaging and potential migrants in the foodstuffs is lacking from the label. In that respect, the consumers are totally reliant on processors, packaging manufacturers and legislators to protect their health. Post manufacture of food-contact materials, there may be residual levels of reactive chemicals that might migrate into the edible contents, so it is crucial to ensure these pose no threat to human health.
The presentation will describe standard methods of assessing health risks from chemical exposures. These methods would be applicable to evaluating whether food-contact migrants pose any significant health risks to those who consume the contents, just as they are applicable to assessing health risks associated with leachables in the Pharma sector. As robust health risk assessments are critically dependent upon capturing all key toxicity information on a migrant/leachable, valuable toxicity data sources will be briefly described in the talk.
Where do you foresee the industry is headed in the next 5 years and why? Or have you seen any particular areas of growth within the industry and why do you think this is?
Others are much better placed to tackle the question of where the food-contact sector is heading. Clearly, a company operating on a global scale must be fully conversant with a wide range of regulatory requirements and these are constantly changing. Colleagues suggest that the US FDA may change the Food Contact Notification system, assessing food safety in a more sophisticated way – moving from specific migration limits to a more probabilistic approach – based on how likely something is to be in the diet, and use of a consumption factor. We will no doubt see continued consultations on EU national regulations for non-harmonised FCMs, and uncertainty regarding FCM regulations in the United Kingdom post ‘Brexit’. How will the industry comply with the new Chinese Standard GB-9685-2016 and anticipated new Japanese and South American (Mercosur) regulations? I see the toxicologists’ role as one of partnership. The person ready and able to bring a specific skill set into play for any sector when those skills are applicable. Consequently, the toxicologist’s role is responsive more than proactive (in my opinion).
In terms of health risk assessment, EFSA has turned its attention to a group of FCMs that have not traditionally been evaluated for safety; papers, inks and coatings used in food packaging. Although not designed to contact foodstuffs directly, evaluation of these chemicals has already prompted changes to good manufacturing practice (GMP) in the sector and may have implications for equivalent manufacturers and suppliers in the pharmaceutical industry.
Increasing regulation and requirements for risk assessment of FCMs without unnecessary laboratory animal testing has led, and will continue to lead, to the development and utilisation of sophisticated computation methodology, alongside more traditional approaches to hazard and risk characterisation i.e. Matrix web-based tool for risk assessments performed under Article 19 of Commission Regulation (EU) No 10/2011 on plastic materials and articles intended to come into contact with food.
We are likely to see increasing use of nanomaterials in food packaging. ‘Active’ packaging involves the use of nanomaterials to interact directly with the food or the environment to allow better protection of the product and ‘smart’ packaging nanomaterials are designed to sense biochemical or microbial changes in the food to alert to the potential for spoiling and wastage. Whilst undoubtedly innovative, the health risk assessment of nanomaterials presents a challenge in all sectors.
It also seems likely that individual chemicals will continue to face challenges to their status. For example, the Bisphenol A (BPA) saga still has legs. In Europe, the current tolerable daily intake (TDI) for BPA is now as low as 4 µg/kg bw/day, set in 2015 by EFSA’s Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF). However, due to ongoing low-dose concerns for reproductive, neurological, immune and / or metabolic toxicity, EFSA intends to reassess the TDI in light of new data published since 2013 and following the publication of the US NTP 2-year study on BPA later this year. EFSA’s draft BPA hazard assessment protocol was published for public consultation on the 14th June 2017 to this end.
While certain substances might well be worthy of Expert Group scrutiny and subsequent control action, it’s also the case that a buzz word or two on “hazard” from a researcher can quickly rebirth as “risk” in the media, leading to consumer resistance and pressure to remove from the market. Any mention of endocrine disruption potential, for example, is likely to focus attention on a substance. Accurate and understandable communication is an elusive quality.
What are you most looking forward to at E&L Europe 2017 in Lyon in November?
For me, E&L conferences provide an ideal opportunity for education, because they bring together an international array of individuals with an impressive sweep of expertise. Listening to and learning from the experts can only have a positive impact on one’s own job performance. The conferences provide valuable insights into where an individual player fits into the overall process, stimulating ideas for instigating more efficient working procedures and better communication. The conferences help individuals to better understand and appreciate the challenges faced by others who play a different role in the overall effort. The format allows excellent opportunities for networking and building relationships. One key element is the chance for dialogue with the regulators.
Smithers Rapra will also be presenting on 'What Can We Learn From Food?' as part of the session this November. You can book your ticket to hear from the experts and join AstraZeneca, Mylan, Sonceboz, Solvias, Bayer, Novo Nordisk and more below.
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