International Packaging Submissions: Exploring the

1
International Packaging Submissions Exploring
the Regulatory Requirements for Pharmaceutical
Packaging and Ingredients in Other Countries

• Donna Jackson
• HSE Technical Representative
• EASTMAN

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in Other
Countries

• EUROPE - EMEA Marketing Authorization Role of
  European Pharmacopoeia Monographs
• CANADA - Drug master file system - Therapeutic
  Products Programme
• PEOPLES REPUBLIC OF CHINA - Import Drug Permit
• AUSTRALIA - Regulatory process used by
  Therapeutic Goods Administration

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients inEUROPE

• European Agency for the Evaluation of Medicinal
  Products (EMEA)
• Council Directive 65/65/EEC, as amended, and
  Regulation (EEC) No. 2309/93 requires a marketing
  authorization be issued either by a Member State
  authority or by the EMEA for a drug to be
  marketed

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients inEUROPE

• General explanation
• National authorizations
• Community authorizations
• (Trade) Name of Medicinal product
• Centralized procedure
• Mutual recognition procedure
• Independent national procedures
• Community referrals

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients inEUROPE

• Rules Governing Medicinal Products in the
  European Union
• (http//pharmacos.eudra.org/F2/eudralex/index.ht
  m)

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• Guideline Plastic Primary Packaging Materials -
  February 1994
• (http//pharmacos.eudra.org/F2/eudralex/vol-3/pdfs
  -en/3aq10aen.pdf)
• This note for guidance concerns the application
  to plastic primary packaging materials of Part 2,
  sections A, C, and F of the Annex to Directive
  75/318/EEC as amended, with a view to the
  granting of a marketing authorisation for a new
  medicinal product. The provisions of Community
  legislation relating to plastic materials
  intended to come into contact with foodstuffs, in
  particular Directive 90/218/EEC should be taken
  into account.

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• 3.2.1.Information concerning the plastic material
  used for packaging
• pharmaceutical products
• A. General information
• The following information should be provided for
  plastic materials used in the container,
  including those already described in the
  pharmacopoeia where the monographs authorise the
  use of several additives from which the
  manufacturer may choose one or several (within
  certain limits).
• The name and grade given by the manufacturer
  of the material.
• For ophthalmic and parenteral preparations,
  the name of the
• plastic manufacturer.
• The chemical name of the material.
• The chemical name(s) of any monomer used.

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• The complete qualitative composition of the
  plastic material is required where an interaction
  between the container and the contents occurs.
  The qualitative composition covers all
  substances, including additives such as
  antioxidants, stabilisers, catalysts,
  plasticisers, lubricants, solvents and/or dyes
  (comprising the colour index number and/or the EC
  number). If the material has not been approved
  for use for packaging of food, toxicological data
  should be provided. In addition, toxicological
  information is required for plastics normally
  approved for use in food packaging, if they are
  used for parenteral or ophthalmic medicinal
  products.

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• B. Technical information
• Characteristics - Description of the material,
  its solubility in various solvents.
• Identification of the material generally by
  infrared absorption spectrophotometry, with
  indication of the position of characteristic
  absorption bands. The infrared spectrum of the
  reference material should be provided other
  methods of identification may be appropriate.
• Identification of the main additives, in
  particular those which are likely to migrate into
  the contents (such as antioxidants, plasticisers,
  catalysts, initiators, etc.... and, for PVC,
  phthalates, adipates and organic tin compounds).

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• Identification of dyes by using chromatographic
  or any other appropriate method.
• Tests
• General tests
• Mechanical tests
• Physical tests an extraction test should be
  performed where the plastic material is used as
  primary packaging material for liquid and
  semi-solid preparations. The choice of solvent
  for this test depends on the composition of the
  product. The test should investigate the level of
  extractives (antioxidants, plasticisers).

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE3AQ10a ___________________________________
_________________________Summary presentation of
the documentation of plastic containers and
packaging material
Routine tests The studies of suitability
toxicity and compatibility content-container and
migrations are carried out during the
development and not for routine test.
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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• European Pharmacopoeia Monographs applicability
  to resins used in drug packaging applications
• Primary packaging materials direct contact,
  i.e. closures, seals, containers - strict
  compliance with EP containers and materials
  monograph is not a legal requirement, however, EU
  authorities view compliance favorably
• Secondary packaging materials demonstrate
  compliance with EU requirements for food-contact
  materials

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• European Pharmacopoeia Monographs
• 1.3 General Chapter
• Containers ..General names used for materials,
  particularly plastics materials, each cover a
  range of products varying not only in the
  properties of the principal constituent but also
  in the additives used The test methods and
  limits for materials depend on the formulation
  and are therefore applicable only for materials
  whose formulation is covered by the preamble to
  the specification The use of materials with
  different formulations and the test methods and
  limits applied to them are subject to agreement
  by the competent authority.

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• European Pharmacopoeia Monographs
• 3.1 Materials used for the manufacture of
  containers
• Definition
• Production
• Characteristics
• Identification
• Tests
• Supplementary tests

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• European Pharmacopoeia Monographs
• 3.1.1.1 PVC materials for containers for blood
• 3.1.1.2 PVC for tubing for transfusion of blood
• 3.1.3 Polyolefins
• 3.1.4 Polyethylene without additives for
  containers for
• parenteral and opthalmic
  preparations
• 3.1.5 Polyethylene with additives
• 3.1.6 Polypropylene for containers and closures
  for
• parenteral and opthalmic use

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• European Pharmacopoeia Monographs
• 3.1.7 Poly(ethylene-vinyl acetate) for
  containers and
• tubing for total nutrition
  preparations
• 3.1.8 Silicone oil as a lubricant
• 3.1.9 Silicone elastomers for closures and
  tubing
• 3.1.10 Materials based on PVC for containers for
  non
• injectable aqueous solutions
• 3.1.11 Materials based on non-plasticized PVC
  for
• containers for dry dosage
  forms for oral
• administration

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• European Pharmacopoeia Monographs
• 3.1.12 Rubber for closures for containers for
  aqueous
• parenteral preparations and
  for powders for
• freeze-dried products
• 3.1.14 Materials based on plasticized PVC for
  containers
• for aqueous solutions for
  intravenous infusion
• 3.1.15 Polyethylene terephthalate for containers
  for
• preparations not for
  parenteral use

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• European Pharmacopoeia Monographs
• 3.2.1 Glass containers for pharmaceutical use
• 3.2.2 Plastic containers and closures for
• pharmaceutical use
• (defines the different types of containers and
• discusses how to select
  plastics for containers
• there is no testing listed.)
• 3.2.3 Sterile plastic containers for human blood
  and
• blood components
• 3.2.4 Empty sterile containers for human blood
  and
• blood components

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
EUROPE

• European Pharmacopoeia Monographs
• 3.2.5 Sterile containers of PVC for human blood
  and
• blood components with an
  anticoagulant
• 3.2.6 Sets for the transfusion of blood and
  blood
• components
• 3.2.2.1 Plastic containers for aqueous solutions
  for
• parenteral infusions (applies
  to LDPE, HDPE, PP,
• PVC)
• 3.2.8 Sterile single use plastic syringes
• 3.2.9 Rubber closures for containers for aqueous
• preparations for parenteral use

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
CANADA

• Therapeutic Products Programme
• Similar to U.S. FDA process
• DMF system
• No legal requirement
• Authorization by holder for review
• Same content

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
CANADA

• Therapeutic Products Programme
• Differences
• Type II for packaging materials
• Filing fee 350 Cdn and 50 Cdn fee for each LOA
• No statement of commitment on compliance with
  environmental laws
• Biannual updates

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
PEOPLES REPUBLIC OF CHINA

• State Drug Administration
• Drugs, including bulk pharmaceutical chemicals
• Application form for Import Drug License
• Recommend authorizing an Applicant Agent in China
• Chinese Translation
• Certificates issued by govt authority in country
  of manufacture (notarized, legalized by Chinese
  embassy), i.e., production, free sale,
  exportation, patent, GMP inspection
• Data Composition, production process,
  specifications, test methods for finished
  product, raw materials, excipients, primary
  packaging materials, samples, COA, toxicity, etc.

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
AUSTRALIA

• Therapeutic Goods Administration
• http//www.health.gov.au/tga email
  tga-information-officer_at_health.gov.au
• Pre-market evaluation and approval of registered
  products intended for supply in Australia
• Licensing of manufacturers in accordance with
  international standards under GMP
• Post-market monitoring
• Development, maintenance and monitoring of the
  systems for listing of medicines
• Assessment of medicines for export

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
AUSTRALIA

• Therapeutic Goods Administration
• Therapeutic Goods Act 1989 requirements for
  listing or registering all therapeutic goods in
  the Australian Register of Therapeutic Goods
  (ARTG)
• Therapeutic Good a good which is represented
  in any way to be, or is likely to be taken to be,
  for therapeutic use, unless specifically excluded
  or included under Section 7 of the Act.
• Preventing, diagnosing, curing or alleviating a
  disease, ailment, defect or injury Influencing,
  inhibiting, or modifying a physiological process
  Testing the susceptibility of persons to a
  disease or ailment Influencing, controlling or
  preventing conception Testing for pregnancy
  Replacement or modification of parts of the
  anatomy

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
AUSTRALIA

• Therapeutic Goods Administration
• ARTG all medicines manufactured for supply in
  Australia must be listed or registered, unless
  they are specifically exempt or excluded
• Listing/registering in ARTG depends on
  ingredients, dosage form of product, and the
  promotional or therapeutic claims made for the
  product
• Listed medicines well known established
  ingredients TGA assesses only for quality and
  safety but not efficacy medicines self-selected
  by consumers and used for self-treatment - lower
  risk than registered medicines

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
AUSTRALIA

• Therapeutic Goods Administration
• Registered medicines sponsors required to
  provide comprehensive safety, quality and
  efficacy data (non-prescription registered or
  prescription registered)
• Complementary medicines (or traditional or
  alternative medicines such as vitamins, mineral,
  herbal, aromatherapy, and homoeopathic products)
  may be listed or registered depending on
  ingredients and their claims

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Exploring Regulatory Requirements for
Pharmaceutical Packaging and Ingredients in
Other Countries

• List of Internet Websites
• (copies available upon request)