Food Contact Compliance:

1
Food Contact Compliance

• How relevant is it for drug packaging?
• March 25, 2002
• Waylon Jenkins
• Eastman Chemical Company

2
Outline

• Food contact clearances
• Types
• How food contact evaluations are performed
• New food contact substances
• Drug packaging
• Comparison of food and drug packaging
  requirements
• Establishing suitability of drug packaging
• Pharmacopeial tests compared to food contact
  regulations
• Conclusion

3
Types of Food Contact Clearances

• Regulations (21 CFR 170-199)
• Prior sanctions
• GRAS
• Not a food additive
• Food contact notifications

4
Factors Affecting Food Contact Status

• Chemical composition
• Function
• (base polymer, additive, colorant, etc.)
• Conditions of use
• (e.g. food type, time and temperature of contact)
• Compliance requirements
• (e.g. concentration limitation, physical
  properties, extraction tests, etc.)

5
21 CFR Regulations of Food Packaging

• Regulations according to the use
• Examples
• 21 CFR 175.300 Resinous and polymeric coatings
• 21 CFR 175.320 Coatings for polyolefins
• 21 CFR 176.170 Components of paper and paperboard
• 21 CFR 177.1210 Closures with sealing gaskets
• 21 CFR 178.2010 Antioxidants
• 21 CFR 178.3297 Colorants

6
21 CFR Regulations of Food Packaging

• Regulations according to substance
• Examples
• 21 CFR 177.1520 (PE, PP and polyolefin
  copolymers)
• 21 CFR 177.1630 and 177.1315 (PET and similar
  copolymers)
• 21 CFR 177.1640 Polystyrene
• 21 CFR 177. 1580 Polycarbonate

7
Other Routes to Food Contact Compliance

• Prior sanctions
• Authorized by FDA before 1958
• GRAS
• Generally Recognized As Safe for the intended use
  by qualified experts
• Some listings in 21 CFR parts 182, 184, and 186
• GRAS notifications
• Self-determined GRAS

8
Other Routes to Food Contact Compliance

• Not reasonably expected to become a component of
  food
• Threshold of regulation (http//www.cfsan.fda.gov
  /dms/opa-torx.html)
• Food contact notification (FDAMA 1997)

9
Food Contact Notifications

• FCN No. 1 March 1, 2000
• Similar to regulations, but are limited to the
  notifier (and customers of the notifier)
• Many include references to regulations
• Do not go through formal rulemaking and are not
  published in the CFR
• Are published on internet in numerical order
  (http//www.cfsan.fda.gov/dms/opa-fcn.html)

10
How are new food contact substances evaluated?

• Safety Risk assessment related to the intended
  use
• Estimate exposure
• Estimate migration (of monomers, oligomers,
  additives, etc.) for the intended use
• Migration experiments and/or calculations
• Migration testing with food simulating solvents,
  e.g. water/ethanol mixtures and olive oil, corn
  oil, or synthetic triglycerides
• Calculate exposure based on the intended use
• (http//www.cfsan.fda.gov/dms/opa-pmnc.html)
• Evaluate toxicology relative to exposure estimate
  (http//www.cfsan.fda.gov/dms/opa-pmnt.html)
• NEPA (environmental impact)

11
Some default assumptions for food contact
substances

• 10 g of food per in2
• In contact with 5 of the diet
• Different polymer types have different food type
  distributions that may be used to further refine
  the exposure estimate
• 3000 g of diet per day (considers foods and
  beverages)
• 60 kg body weight

12
Some observations on migration

• Migration is generally very low. Some regulations
  have limits of 0.5 mg/in2, but typical migration
  is far less.
• Migration potential generally increases with
  temperature and/or presence of low molecular
  weight species.
• Migration can vary widely from one food type to
  another, due to differences in solubility of
  migrants and possible swelling of the polymer.

13
Technical Suitability of Food Packaging

• Technical suitability must be determined by
  users. Issues including the following must be
  considered
• Shelf life (light transmission, oxygen barrier,
  etc.)
• Organoleptic properties (resulting from migration
  and/or scalping)
• Necessary physical properties for packaging,
  shipping and storage

14
Drug Packaging

• Evaluated as part of the drug
• No broad premarket approvals for drug packaging
• Some materials are listed in USP and/or European
  Pharmacopoeia

15
Some considerations

• Drug manufacturers must consider possible impacts
  on efficacy in addition to safety of migrants and
  organoleptic issues.
• Drug manufacturers may need to consider routes of
  administration other than oral.
• In most cases, exposure per day and over a
  lifetime will be far less than exposure to foods.

16
USP and EP

• USP lt661gt has general requirements for containers
  and some specific tests for containers made from
  certain materials.
• European Pharmacopoeia has some specifications
  for materials.
• In both cases, in relation to materials, the
  listings are intended to characterize similar
  materials.
• In neither case do the listings indicate
  suitability for specific drug products.

17
Conclusions

• In general, food contact compliance should be
  relevant to support safety for similar use in
  packaging of drugs with physical properties
  similar to foods.
• Migration from packaging is generally very low
  and typically involves species of relatively low
  reactivity.

18

• As with foods, technical suitability of drug
  packaging in relation to shelf life and
  organoleptics must be determined on a case by
  case basis.
• Extra consideration may be appropriate for other
  routes of administration or for drugs that are
  not well represented by conventional food
  simulating solvents.