Labeling of LDPE Containers:

Options for Improving Identification for

Prevention of Medication Errors

Rick Schindewolf

Patrick Poisson

May 5, 2004

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Cardinal Health

• Cardinal Health is a Fortune 25 corporation that provides distribution, manufacturing, research and management solutions to the healthcare industry

• Cardinal Health Woodstock produces approximately 1 billion sterile units annually using Blow/Fill/Seal technology for a variety of pharmaceutical partners

• Cardinal Health Woodstock’s product portfolio includes NDA, ANDA, 510(k) and USP Monograph sterile aqueous products for respiratory, ophthalmic, topical and catheter flush applications

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Blow/Fill/Seal Technology

• Advantages– Advanced Aseptic Process (USP XXV) for increased sterility

assurance

– Flexibility in container design

– Cost effective approach to producing high volume sterile products (one raw material: plastic)

• Limitations– LDPE is a semi-permeable material

– Heat sensitive products

– Labeling

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Current Industry Practice

• Labeling and Packaging: General Industry Approach with LDPE UDVs– Emboss or deboss containers to display requisite

labeling information• Product Name, Concentration, Manufacturer, Lot Number, Exp.

Date, with critical phrases (i.e. “not for injection”, “for oral inhalation only”)

– Packaged in secondary overwrap (multiple/single) printed with additional product information to provide protection against chemical contaminants (vapor permeation of hydrocarbons) and small volume water vapor loss

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Current Guidance Specific to LDPE

• Draft Guidance Inhalation Drug Products Packaged in Semipermeable Container Closure Systems (July 2002)– LDPE vials are permeable to some volatile chemicals

– Recommends against paper labels due to past evidence of chemical contamination

– Recommends embossing/debossing or other means to display the requisite labeling information

– Recommends protective secondary packaging (i.e. multi-laminate foil)

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Primary Vial Labeling• Embossing/Debossing Approach to Primary Vial

Labeling– Advantages:

• Provides immediate tamper evident identification of the product at the time of manufacturing

• Eliminates the potential for chemical contamination that could occur with a paper label

• Provides ease of label copy control in the manufacturing process

– Limitations:

• Clear LDPE does not provide a contrasting background to aid legibility

• Does not provide bar code readable print

• Vial size affects legibility of print - based on current content requirement

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Options for Improvement

• Enhancements for Product Identification1. Reduce content requirement to allow an

increased text size

2. Addition of physical/tactile identifiers for generic product groups

3. Alternative label approaches (Sleeve Label)

4. Color code UDVs for generic product groups

5. Individual secondary overwrap of UDVs

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Options for Improvement

1. Increased text size– Limited surface area on container available for

embossing/debossing due to mold cavity limitations

– Text size can be significantly increased however some currently required information must be removed

– Does not change container materials or process. No impact on product chemistry

– Can be implemented in 8-10 weeks pending regulatory approval of label change

– One time minimal cost investment in tooling

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Increase Text Size Concept

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Options for Improvement

2. Physical/tactile identifiers added to container design

– Provides a easily recognizable/legible symbol on a container that represents a product type• Examples: A for Albuterol Sulfate, I for Ipratropium Bromide, C

for Cromolyn Sodium, etc.

– Currently being implemented on products manufactured by Cardinal Health for our customers

– Does not change container materials or process. No impact on product chemistry

– Can be implemented in 8-10 weeks pending regulatory approval of label change (CBE 30?)

– One time minimal cost investment in tooling

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Symbol Concept w/ Increased Text Size

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Symbol Concept w/ Increased Text Size

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Symbol Concept w/ Increased Text Size

Contrasted with standard vial design

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Options for Improvement

3. Sleeve Label– Redesign extended tab area to make amenable for non-

paper label on non-product contacting surface

– Cardinal Health has designed a LDPE vial (patent pending) capable of receiving a shrink wrap sleeve

– Label provides contrasted background for enhanced legibility and provides bar code readable print

– No changes to product contact surface of container. Shrink or pressure sensitive label attached to vial appendage. No adhesives adjacent to product contact surfaces

– Increase in manufacturing cost (equipment, labor, materials)

– Implementation 12-14 months following regulatory approval (stability testing)

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Sleeve Label Concept

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Options for Improvement

4. Color Coding– Products could be color coded to aid in identification.

Similar in approach to AAO recommendations for cap/label color for topical ophthalmic medications Container Closure Systems for Packaging Human Drugs and Biologics (May 1999)

– Provides a contrasting background to aid legibility of embossing/debossing

– Could impact product chemistry (leachables & extractables)

– Slight increase in product cost (raw materials)

– Implementation 6-9 months following stability and regulatory approval (stability and extractable/leachable testing)

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Colored Vial Samples

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Options for Improvement

5. Individual Secondary Overwrap– Individual UDV secondary overwrap provides enhanced

labeling opportunities including bar code readable print

– Overwrap can/will be separated from product prior to use. Legibility/identification issues still exist at the time of use

– Significant manufacturing cost increase (equipment, labor, raw materials)

– Implementation 12-14 months following regulatory approval of packaging change (stability testing)

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Summary

• Improvements in identification of LDPE containers to prevent medication errors can be made

• Each alternative should be assessed based on impact to the product, speed of implementation, ease of regulatory approval and cost to the patient

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Recommendation• Increase label information font size on

individual vials

• Add tactile symbol for generic identification– Advantages

1. Quickest approach for immediate improvement in product recognition

2. No impact on product chemistry or stability

3. No impact on patient cost

• Hospital dispensed UDVs - add sleeve label to accommodate bar coding

Biotechnology and Sterile Life Sciences