# Presentation: 627013

## Labeling of LDPE Containers:Options for Improving Identification for Prevention of Medication ErrorsRick SchindewolfPatrick Poisson

- May 5, 2004

## 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

## 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

## 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

## 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- Draft Guidance *Inhalation Drug Products Packaged in Semipermeable Container Closure Systems* (July 2002)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)

## 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

## Options for Improvement

- Enhancements for Product Identification
- Reduce content requirement to allow an increased text size
- Addition of physical/tactile identifiers for generic product groups
- Alternative label approaches (Sleeve Label)
- Color code UDVs for generic product groups
- Individual secondary overwrap of UDVs

## 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

## Increase Text Size Concept

## 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

## Symbol Concept w/ Increased Text Size

## Symbol Concept w/ Increased Text Size

## Symbol Concept w/ Increased Text Size

- Contrasted with standard vial design

## 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)

## Sleeve Label Concept

## 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)

## Colored Vial Samples

## 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)

## 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

## 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

**Biotechnology and Sterile Life Sciences**