FDA Webinar on the Infant Formula Packaging Requirements

good afternoon and welcome to the U.S Food and Drug administration's webinar series to discuss infant formula food ingredients and packaging requirements I'm Lieutenant Commander Janisha robs with the fda's center for food safety and Applied Nutrition Communications and public engagement staff and I will serve as your moderator today's webinar will focus on regulatory requirements and considerations for infant formula Packaging the FDA plays a critical role in

ensuring the safety and nutritional adequacy of infant formula in the United States the FDA also works to ensure that infant formulas sold in the United States meets the required safety and nutritional standards specified in section 412 of the federal Food Drug and cosmetic act and in the fda's implementing regulations at 21 CFR Parts 106 and 107. the webinars in this series are part of the fda's

ongoing efforts to help improve the safety and resiliency of the U.S infant formula Supply and provide educational resources for infant formula manufacturers in a moment I will turn the call over to Dr Patricia Hansen deputy director of Sif Sans office of nutrition and food labeling to provide opening remarks then you will hear from Dr Jessica herbalis regulatory review scientists and Sif Sands office of food additive

Safety Division of food contact substances to provide information on U.S regulation of food contact substances and considerations for infant formula after the presentation we will move to the question and answer portion of the webinar where Dr herbalis will answer questions we received through the registration process with that I will now turn the call over to Dr Patricia Hansen deputy director of Sif Sands office of nutrition

and food labeling thank you Tanisha and welcome welcome back for many to the sixth webinar in this series in this webinar Dr Jessica herbalis a chemist and Regulatory review scientist in the office of food additive safety will provide you with important information on fda's requirements and recommendations regarding infant formula packaging information as I mentioned in the previous webinars the requirements for new infant formula submissions are

the same whether a manufacturer and its products are eligible to pursue the path outlined in our infant formula transition plan guidance published in September of 2022 or a manufacturer is making a nuance and formula submission to our regular established process this includes the packaging requirements now in the second webinar of this series Dr Kerry assar provided an overview of the entire landscape of fda's new infant

formula submission requirements and our recommendations including Packaging you might find it helpful to review that webinar again as a refresher after this one today Dr herbalis will take us on a deeper dive into fda's requirements and recommendations regarding infant formula packaging including some very important legal and Regulatory context on food packaging and through contact materials generally and we hope that all of you regardless of the

pathway you may be on and whatever your role may be in the process will find us more information helpful the information in this webinar may be especially useful to those involved in product development materials procurement and Regulatory Affairs and now to turn things over to Dr herbalis thank you Dr Hansen for that introduction and thank you all for joining us today as Dr Hansen just mentioned

the goal of today's talk is to discuss how food contact substances in the U.S are regulated and considerations for infant formula Packaging but first I will provide some background on the history and legal basis for fda's authority of food contact substances and then discuss how a manufacturer can determine if their material is authorized for its specific intended use afterwards we turn the focus to infant formula

packaging and an overview of the information that we recommend to include in an infant formula notification in order for FDA to confirm that all components of the packaging or food contact material are authorized for their intended use so to begin food safety is one of the responsibilities of the center for food safety and Applied Nutrition or sip San the office of food additive safety is tasked

with ensuring the safety of substances added to food and food contact materials and while there is some overlap and cross-divisional work the vast majority of food additives that are directly added to food are evaluated by the division of food ingredients while indirect food additives are evaluated by the division of food contact substances as this Symposium is focused on infant formula we can simplify these distinctions to

say that the division of food ingredients evaluates infant formula ingredients while the division of food contact substances evaluate substances used in infant formula packaging and other materials that contact infant formula if you have any questions regarding infant formula ingredients I would encourage you to consult the webinar conducted by my colleague Dr Rachel Morrissette who gave an overview of the regulations and recommendations for infant formula ingredients

as for today we will focus on food contact materials and their use in infant formula Packaging to understand how FDA looks at food additives it might be helpful to understand a bit of our history and authorities in 1938 Congress passed the original Food Drug and cosmetic act this act included some food Provisions particularly as it relates to food adulteration however the food additives Amendment passed in

1958 provided FDA with the authority over food additives the amendment formally defined a food additive and created the food additive petition process for sponsors to petition FDA for pre-market authorization of New Uses of food additives the amendment also established the standard of safety for food additives and which says the food additives are automatically unsafe unless they're used in a way that FDA has authorized and the

food containing the unauthorized additive is deemed adulterated the FDA modernization Act was later passed in 1997 and this act defined a subset of food additives called food contact substances it also created a pre-market notification process called food context substance notifications or fcns that allowed for more expedited review of these types of substances compared to the food additive petition process so what makes something a food additive

the legal definition says all substances the intended use of which results or may be reasonably be expected to result directly or indirectly and they're becoming a component of food or otherwise affecting the characteristics of any food additives require pre-market authorization for their use which is evaluated through the food additive petition process and regulated by title 21 of the code of federal regulations or CFR as I

previously mentioned the FDA modernization act also defined a food contact substance or FCS which is any substance intended for use as a component of materials used in the manufacturing packing packaging transporting or holding food if such use is not intended to have any technical effect in such food contact substances that are expected to become a component of food under its conditions of use also require pre-market

authorization and they are primarily evaluated through a food contact census notification or fcn contrary to the listings in the CFR effective fcns are manufacturer-specific and therefore only authorize a substance and its intended use for the manufacturer or supplier listed in the notification FDA reviews fcs's as individual components of food contact articles meaning the review is not for whole packaging or whole products some examples of food

contact substances are monomers in a polymer or a polymer itself or different kinds of additives such as colorants and antioxidants but what does that all mean in the context of food packaging reconsider food packaging to be one type of food contact article which is made up of food contact materials these are materials that contact food such as Coatings adhesives polymers or paper board in addition to

food packaging food contact materials include those used in food processing such as lubricants and conveyor belts or other articles intended to hold or transport food because food contact materials are made up of food contact substances the regulatory status of a food contact material is based on the regulatory status of each individual component that comprises the material in this context the regulatory status is the means by

which that substance is authorized for its specific intended use as stated in 21cfr 106.40b any substance used in packaging material for infant formula that is reasonably expected to become a component of food as a result of its intended use must be authorized or exempt for its intended use by one or more of the following a food additive regulation an issued threshold of Regulation or tour exemption

have generally recognized as safe or grass status be prior sanctioned or the subject of an effective fcm I will provide additional detail on several of these in a moment but first the intended use is important to note here for example just because a substance is authorized for use by a food additive regulation in paper board packaging does not also mean that it is authorized for use

in polyolifin films in addition the regulatory status of a food contact article is dictated by the most restrictive component of the article for instance if all if most components are authorized for use under conditions of use a through H but one component is limited to condition of use C through H the final article can only be used based on the more restrictive limitation of conditions of

use C through h foreign now as I mentioned previously the food additive regulations are established in response to food additive petitions food additives including food contact substances are listed in 21 CFR Parts 170 to 189. the authorization stated in the regulations are applicable to all manufacturers provided that the substance and its use complies with the regulation for example the regulation may include criteria on the identity

of the substance such as the cats reg number specific molecular weight starting material or ratio of monomers as well as end tests to demonstrate compliance regulations May State specific conditions of use for the substance such as its function or its use level the regulation may also provide for specifications with respect to the use of the substance in a material in contact with certain food types or

time and temperature limitations a food contact substance may also be exempt from regulation as a food additive by an issued threshold of Regulation or tour exemption like food additive regulations tour exemptions are also applicable to all manufacturers or suppliers provided that the substance meets the intended use in any limitations stated in the exemption there are several criteria listed for a tour exemption and they are listed

in 21 CFR 178.39 most notably that the dietary exposure of the substance resulting from its intended use is below 0.5 parts per billion and the FCS itself is not a known carcinogen FDA review of tour exemption submissions may be completed in less than 120 days an issued tour exemptions are listed in an inventory on our website for your consultation our website has a similar inventory for

effective fcns unlike food additive regulations or tour exemptions fcns or manufacture specific meaning that they are only effective for the manufacturer or supplier listed in the fcn and are only effective for the specific substance and intended use described in the notification there is also a statutory 120-day review time frame for scns for listings for effective fcns are similar to those for issued tour exemptions in that

they specify the substance intended use and any limitations or specifications for its use however fcns also include the effective date and the name of the manufacturer or supplier for which the fcn is effective it's important to note that the standard of safety is the same for food additive regulations and fcms the standard is based on safety only meaning there is no risk benefit analysis conducted for

the use of a substance instead it requires a reasonable certainty of no harm in the minds of competent scientists under its conditions of use it does not and cannot require proof Beyond any possible doubt that no harm will result under any conceivable circumstance built into this reasonable certainty of no harm is the Delaney clause which does not allow for the authorization of a food additive with

known carcinogenicity in humans or animals the assessment of safety is based primarily on two joining factors it is dependent on the dietary exposure of the substance and that in turn is determined by the intended use of the substance how the FCA assesses the safety of an FCS is by evaluating consumer dietary exposure to the substance from its intended use and ensuring that the probable dietary exposures

are supported by available toxicological information in simplistic terms we often use the rubric that the intended use of the FCS May generally be considered safe if the cumulative EDI is less than the ADI the ADI or acceptable daily intake is the estimate of the amount of an FCS that may be consumed daily over a lifetime with reasonable certainty of no harm the ADI value of a

substance is determined from robust toxicological data the estimated daily intake or EDI is calculated by estimating the amount of an FCS that may be consumed daily by an individual from its intended uses to estimate the EDI we first need to determine how much of the FCS May migrate to the food under its intended conditions of use to do so we review the amount of migration of

the substance from the packaging or other article into the food itself notifiers May conduct migration studies under conditions that reflect intended use to provide estimates of the highest probable migration levels of the FCS or other components into food the amount of migration is reported in relation to the food context surface area and migration values are calculated using the amount of food in the packaging to determine

concentrations or levels of the FCS in the food such as microgram of FCS per kilogram of food the migration levels in food obtained from either migration data as previously discussed or a 100 migration calculation are then used to calculate consumer dietary exposure to the FCS in all of its impurities and breakdown products when an FCS is used in single-use food packaging calculations may be refined using

packaging information the packaging information includes packaging factors such as food type distribution factor and a consumption Factor these factors answer the questions of how much of each food type will contact the food contact article and how much of the daily diet will contact the food contact article the combination of the packaging information in the migration levels leads to the consumer dietary exposure estimates for the specific

use of the FCS in Packaging now as a note for an FCS intended for use in infant formula packaging we do not include packaging factors in the dietary exposure estimate because we assume the infant formula is the sole source of the infant's diet and not a fraction thereof and when calculating dietary exposure for infants in an fcn submission there are additional safety factors in place infants

aged 0 to 6 months typically consume human milk and or infant formula exclusively and consume higher amounts of food in relation to their body weight than adults this contributes to a higher albeit temporally limited exposure to Potential migrants from the FCS for this reason as well as the known differences in metabolism between infants and the adult population FDA published a guidance document in 2014 that describes

the specific information needed in an fcn submission to calculate and support the dietary exposure estimates for the infant population for example the guidance describes the recommended stimulants of 10x for powder or 50 ethanol for liquids to mimic migration of an FCS used in an article that is intended to contact infant formula or human milk this includes articles such as packaging or baby bottles and nipples the

guidance also provides additional information regarding how to calculate the resulting dietary exposure estimates using values of body weight and food consumption that are specific to the infant population so now that we've covered how the safety of food contact substances are evaluated by FTA we can now transition to information specific to food contact substances used in infant formula Packaging for the remainder of the talk we will

discuss the type of information we recommend to support the packaging component of an infant formula notification or ifn how to determine if your food contact material is authorized for its intended use and how to submit this information to FDA for review let's first start with what type of packaging information is reviewed in an infant formula notification I will go into these categories in Greater detail but

as an overview the packaging information of an ifn should cover three main points the first of which is a summary of the packaging information or other food contact article this can mean a list of all components of the packaging material that are subject of the ifn second identity and Regulatory status information this section should contain information to certify that each component is authorized for its specific

intended use it may include Declarations of compliance from the manufacturers used for each material and third in the case where the ifn is not for completely new packaging but rather for a change in packaging a summary of any proposed changes should be clearly stated and accompanied by any relevant supporting information for the proposed change the summary of packaging information may include a description of the packaging

and all packaging materials that are the subject of the ifm meaning if this is a submission for a new infant formula or formula with new packaging the description should include all components of the packaging in a comprehensive depiction for example a composite cam would include the components of the can all liners adhesives lid and scoop multi-layer materials should also have clear descriptions as to the order

packaged in various forms it is also important to provide the intended use of the materials for example is the material in contact with dry or liquid infant formula and is it used at room temperature or sterilized at high temperature conditions there may also be instances where other types of food contact articles may be included for example materials used in transport storage or holding the infant formula

once you have the list of all the food contact materials that are subject of the ifn the next step is to provide the identity and Regulatory status of each substance that makes up that material when we say regulatory status it essentially means describe how the substance is authorized for its specific intended use in your food contact article each substance should meet the specifications of a regulation

for its identity and use or be authorized or exempt from pre-market authorization by either an issued tour exemption be considered grass for the intended use the prior sanctioned or subject of an effective fcm one way to provide this information is using a declaration of compliance from the manufacture of the material Declarations of compliance or manufacture specific because an FCS may be authorized according to specific identity

and intended use limitations both of which may be varied between manufacturing processes as an example here's the type of information that supports the proposed use of a blue scoop in infant formula Packaging the information provided should include the identity of each substance that comprises the scoop including the chemical name and cast red number its intended use in the scoop such as for use as a colorant

or stabilizer in reference to the corresponding food additive regulation or other means such as the number of an effective fcn that authorizes that substance for that specific intended use in the article the key concept for these submissions is that every food contact substance used in infant formula packaging must be authorized or be exempt for its specific intended use that is to say an infant formula notification

is not the appropriate Avenue to obtain authorization for use of a food contact substance so what if you determine that your packaging contains an unauthorized FCS then you may need to submit an fcn for pre-market authorization an fcn is needed for a new FCS or if the specific intended use of the substance is not authorized by one of the means listed previously in addition if the

FCS is the subject of an effective SCM a new fcn may be needed if the FCS is from a different manufacturer or supplier if there is a new intended use of the FCS or a change in its manufacture impurity profile or dietary exposure estimate resulting from its intended use if you have any questions about whether your substance is authorized for its intended use or questions regarding

fcn submissions we encourage you to contact the division of food contact substances here at FDA as I mentioned before there may be instances where a full dossier of the packaging components is not necessary to include in an ifn if the ifn includes a packaging change to material previously reviewed by FTA for the same infant formula manufacturer a summary of the packaging changes may be sufficient in

order to avoid duplicative review the ifn does not need to include all of the identity and regulatory information of the complete packaging but rather just the information pertaining to the specific change requested this type of information may include a summary of the changes proposed in a submission for instance a change in the material used in an article of the packaging or a change in a component

of that article such as a new resin colorant or new grade of an existing material in support of the proposed change additional information may be needed namely Declarations of compliance for manufacturers new identity information intended use and Regulatory status and a scientific rationale for the change when applicable lastly reference to previous ifns for which the other components of the packaging were reviewed should be included to

demonstrate the additional review is not needed for these materials let's go through another example in this instance there is proposed change to the colorant used in the polymer lid the packaging information should therefore include the chemical identity of the substance both old and new the intended use and the corresponding regulatory status a description of the change would include the summary of the proposed change and clarify

that no other changes are to be implemented in either the lid or other components of the packaging included are references to the ifn number where the lid was previously reviewed as well as the ifn number or numbers where the rest of the packaging was reviewed this enables us to quickly verify that all components were previously reviewed by FDA and allows us to focus our review on

the proposed change in the subject notification so now that we've gone through what information is pertinent to the packaging review of an ifn it may be helpful to show you the different ways that this information may be submitted to FDA most packaging information is submitted to FDA by the infant form of the manufacturer is part of the ifn submission itself if a packaging material manufacturer prefers

to send identity information of their components directly to FDA for review they may do so by submitting to ofas a food Master file or FMF through sifsand's online submission module or cosm alternatively information may be submitted via paper or CD-ROM directly to our address in Maryland as a note FDA does not accept submissions on USB drive across all of these Avenues we request any information provided

to ofas in support of an infant formula notification include the corresponding number of the submission so that we are able to ensure all supporting information is properly identified we also offer different ways to provide regulatory support to our stakeholders if you have a general question regarding an FCS or its regulatory status you may submit an inquiry to us at our pre-market inbox additionally many questions may

be answered by our website at how to determine the regulatory status of a food additive however if you would like to request more in-depth assistance regarding packaging information for an infant from the notification or future fcn you may do so by requesting a PNC or pre-notification consultation in which we would be able to conduct a pre-review or provide more tailor guidance before your future submission in

addition to those Avenues of support we also have a lot of information on our website pertaining to food contact substances the different ways they can be authorized for their use information for fcn submissions and the use of recycled Plastics and food packaging these links shown here will hopefully be helpful tools if you have questions regarding the topics discussed today of course if you have any additional

questions not answered in these resources please don't hesitate to contact us by one of the means listed previously lastly I would like to thank you all for your time and attention and for joining us today to discuss infant formula Packaging thank you Dr herbalis at this time we will begin the question and answer portion of the webinar and answer several of the questions we've received during

the webinar registration process our first question is can you confirm that food contact substances listed in the 21 CFR food additive regulations for example polymers adhesives Coatings may be used for infant formula Packaging yes these regulations authorize the safe use of these substances in contact with infant formula in accordance with any limitation or specification stated in the regulation the exception to this of course is when

regulations list limitations for the use of a substance in contact with specific food types for example a food contact substance may be limited to its use and contact with alcoholic Foods thereby excluding its use in contact with infant formula can you explain the bisphenol a or BPA restriction for use in infant formula Packaging in 2013 FDA amended its regulations to no longer provide authorization for the

use of bpa-based epoxy resins as Coatings and packaging for infant formula similarly in 2012 FTA amended its regulations to no longer provide for the use of vpa-based polycarbonate resins in baby bottles and sippy cups both of these actions were taken in response to food additive petitions which demonstrated that the use of these BPA resins in such articles have been abandoned as such because there is no

current authorized use of bpa-based epoxy resins in infant formula packaging any manufacturer who seeks to use this resin in the future would need to obtain pre-market authorization to demonstrate safety for its intended use and this would be the same process for any other new food contact substance what are the requirements for infant formula packaging that is a multi-layer structure without a functional barrier a food contact

substance May recently be expected to migrate to food from a multi-layer structure under its intended conditions of use in the absence of a functional barrier for example a metal foil layer therefore in the absence of a functional barrier all components of the multi-layer structure must be authorized for their intended use foreign last question is there an optimized format for submitting packaging information there is no standard

approach or specific form to submit to FDA for infant formula packaging information however our recommendation is to provide clear and concise submissions containing a summary of the materials subject to the review and clear descriptions of the identity of the substance its intended use and the corresponding U.S regulation or other authorization for that specific intended use we understand that a substance may be authorized for many different

intended uses and Declarations of compliance from suppliers often cite multiple regulations however providing only the applicable authorization for the specific intended use of the substance in the packaging or article helps expedite our review this type of information may be submitted by the infant formula manufacturer or directly from the packaging material supplier as a food Master file as discussed earlier in the webinar we've received additional questions

that were specified to a regulation or an experimental method we encourage stakeholders to submit these questions to us at pre-market p r e m a r k t at FDA .hhs.gov so that we may provide more individualized responses to better assist thank you to Dr Hansen and thank you Dr herbalis links to resources that were shared during today's presentation are also available in the YouTube description

box below this concludes today's webinar a recording will be available on fda's meeting web page shortly thank you and have a great day