# Presentation: 528624

## FDA/Industry Container Closure Guidance Training SessionOctober 26, 1999

- BULK CONTAINERS
- Melissa J. Maust
- CDER

## Outline

- Types of bulk packaging systems
- Applicable CGMPs
- Description information
- Suitability information
- Quality control information
- Stability information
- Summary

## Types of Bulk Packaging Systems

- For drug substance (storage, shipping, or marketing)
- For drug product (storage, shipping,  marketing, or pharmacy bulk package)

## Bulk Packaging Systems for Storage

- In-process manufacturing storage
- Long term storage prior to packaging
- Storage prior to shipping to repackager or contract packager

## CGMP 211.65(a)

- Equipment construction
- Applies to containers used to hold any in-process materials by the manufacturer of the finished dosage form
- Applies regardless of holding time

## CGMPs

- 211.94:  Containers and closures for finished product
- 211.100:  SOPs for all drug processing operations
- 211.110(c):  Testing of in-process materials, as appropriate
- 211.111:  Qualification of holding times for in-process storage

## Repackager 

- Buys drug product from the drug product manufacturer or distributor and repackages it for sale under a label different than that of the manufacturer
- The repackager is responsible for the quality and stability of the repackaged drug product

## Contract Packager

- Retained by the applicant to package a drug product
- Applicant remains responsible for the quality and stability of the drug product during shipping, storage, and packaging

## Repackaging of Biologics

- CBER considers repackaging a part of manufacture
- Biologics repackagers must be licensed under 21 CFR 600.3(u) and 21 CFR 601

## Bulk Packaging Systemsfor Shipping

- Should be treated as a market package when shipping to a repackager
- Should provide adequate protection
- Should provide adequate mechanical strength

## Bulk Packaging SystemsFor Marketing

- Should meet the same requirements for protection, compatibility, safety, and performance as a smaller market package
- Should be included in the stability studies for application approval

## Pharmacy Bulk Package

- Considered a market package
- Described in USP <1> as the “container of a sterile preparation for parenteral use that contains many single doses”
- Should be shown to be suitable for the intended use

## Typical Bulk Packaging System for a Solid Drug Substance/Drug Product

*Container:*  fiber board drum, HDPE pail, stainless steel canister with double LDPE bags or PET laminate
*Closure for Liners:*  heat sealed or closed with a twist tie
*Desiccants:*  may be placed between the liners

## Typical Bulk Packaging System for a Liquid Drug Substance/Drug Product

*Container*:  plastic, stainless steel, glass- or epoxy-lined metal
*Closure*:  rugged and tamper resistant

## Bulk Packaging Systems for Compressed Medical Gases

- 21 CFR 210 and 211
- Regulated by US Department of Transportation
- Refer to CDER Compressed Medical Gas Guideline (February 1989)

## Descriptive Information 

- General description of the assembled packaging system
- Identity and description for each  component
- Identity of the materials of construction for each component
- Description of any additional treatments

## Suitability Information

- Protection
- Compatibility
- Safety
- Performance

## Suitability and Storage

- The length of time the product will spend in the bulk container may be a factor in determining the level of detail of the suitability information

**Notes:**
Well, who were they all?

## Protection

- Protection from all factors liable to cause a decrease in the quality of the product over its shelf life
- Examples:  absorption of water vapor, loss of solvent, microbial contamination, exposure to light and exposure to reactive gases

**Notes:**
Well, who were they all?

## Compatibility

- Packaging components should not interact and cause unacceptable changes to the quality of the drug substance/drug product or the packaging component
- Examples:  loss of potency due to absorption or adsorption, degradation, discoloration, or physical changes to a packaging component

## Safety

- Reference to appropriate indirect food additive regulations is *typically* considered sufficient to establish the safety of the materials of construction used in the packaging components for solid oral products
- For “non-solid” and “non-oral”  products, refer to the appropriate sections of the guidance

## Performance

- Ability to function in the	manner designed
- Usually not a concern for bulk packaging systems

## Quality Control Information

- Physical characteristics
- Chemical composition
- Adequate vendor validation program
- Incoming tests and acceptance criteria for release

## Stability Information

- Establish the retest period
- 	for a drug substance
- Establish the expiration date
- 	for a drug product
- In certain situations, simulated smaller versions of the packaging system
- 	may be used (not for pharmacy bulk packages)

## Stability Information (cont’d)

- “The ultimate proof of the suitability of the container closure system and the packaging process is established by full shelf life stability studies” 1
- 1  Container Closure Systems for Packaging Human Drugs and Biologics, Chemistry, Manufacturing, and Controls Documentation, May 1999, Section III.B.

## Summary

- Different types (with examples)
- Applicable CMGPs
- Suitability Information
- Quality Control
- Stability