Guidance for Industry
 
Container Closure Systems for 

Packaging Human Drugs 

and Biologics 

Questions and Answers 

U.S. Department of Health and Human Services
 
Food and Drug Administration
 
Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

May 2002 

CMC
  Guidance for Industry
 
Container Closure Systems for 

Packaging Human Drugs 

and Biologics 

Questions and Answers 

Additional copies are available from: 

Office of Training and Communications 

Division of Drug Information, HFD-240 

Center for Drug Evaluation and Research 

Food and Drug Administration 

5600 Fishers Lane 

Rockville, MD 20857 

(Tel) 301-827-4573 

http://www.fda.gov/cder/guidance/index.htm 

or

 Office of Communication, Training and 

Manufacturers Assistance, HFM-40 

Center for Biologics Evaluation and Research

 Food and Drug Administration 

1401 Rockville Pike, Rockville, MD 20852-1448

 http://www.fda.gov/cber/guidelines.htm 

Fax: 1-888-CBERFAX or 301-827-3844 

Phone: the Voice Information System at 800-835-4709 or 301-827-1800 

U.S. Department of Health and Human Services
 
Food and Drug Administration
 
Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

May 2002 

CMC
  1 
Guidance for Industry
Container Closure Systems for Packaging 

Human Drugs and Biologics 

Questions and Answers 

This guidance represents the Food and Drug Administration=s current thinking on this topic. It does not 
create or confer any rights for or on any person and does not operate to bind FDA or the public. An 
alternative approach may be used if such approach satisfies the requirements of the applicable statutes 
and regulations. 
This document provides questions and answers relating to the guidance on Container Closure 
Systems for Packaging Human Drugs and Biologics (the guidance).2 The questions are based on 
those posed to CDER by applicants. 
Q1: 	 Table 5 of the guidance (section III.E.2) provides information on the American 
Academy of Ophthalmology (AAO) uniform color coding system for the caps and labels 
of topical ocular medications. Is there a source for current information on this coding 
system? 
A1:	  Current information on the AAO color coding system can be found on AAOs Web 
site at http:///www.aao.org (type color coding in the  search entry box). 
Q2: 	 Section VI.B of the guidance states that container closure systems for on-site storage 
have generally been considered a Current Good Manufacturing Practices (CGMP) 
issue. However, the guidance goes on to state that if a firm plans to hold bulk drug 
products3 in storage, then the container closure system and the maximum storage time 
should be described and justified in the application. If this is a CGMP issue, does 
information need to be included in the application? 
                                                
1  This guidance has been prepared by the Packaging Technical Committee of the Chemistry, Manufacturing, and 
Controls Committee (CMCCC) in the Center for Drug Evaluation and Research (CDER) at the Food and Drug 
Administration (FDA). 
2 A notice of availability for this guidance published in the Federal Register on July 7, 1999 (64 FR 36694). 
3 A bulk drug product means finished dosage form that has not yet been packaged into the container closure systems 
intended for market and/or sale. 
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  A2:	  Information on container closure systems used for storage of bulk drug products, 
other than biologics or protein drug products, need not be included in the application. 
However, these container closure systems should be shown to be suitable for their 
intended use.  The suitability of the storage containers should be supported by data 
retained by the applicant and/or manufacturer and should be made available during 
FDA inspection upon demand.  Information as requested in section VI.B. of the 
packaging guidance should be included in the application on the container closure 
system for storage prior to packaging or shipping of biologics and protein drug 
products, including container closure suitability.  This information should be provided 
for biologics and proteins because, in general, there is greater potential for adverse 
effects on the identity, strength, quality, purity, or potency of biologics and protein 
drug products during storage or shipping. 
Q3: 	 Section VI.B of the guidance states that a container closure system for the 
transportation of bulk drug products to contract packagers should be described in the 
application; section VI.B also provides recommendations on information to include in 
the application. However, different recommendations are provided for holding bulk 
drug products in storage, and this situation appears to include shipping of bulk drug 
products between applicant-owned manufacturing sites and applicant-owned 
packaging sites. Why are the recommendations different for these similar situations? 
A3: 	 Information on container closure systems used for shipping (i.e., between applicant's 
own facilities or contract facilities) and bulk drug products, other than biologics or 
proteins, need not be included in the application.  However, these container closure 
systems should be shown to be suitable for their intended use. The suitability of the 
storage containers should be supported by data retained by the applicant and/or 
manufacturer and should be made available during FDA inspection upon demand. 
Information as requested in section VI.B. of the packaging guidance on the container 
closure system for storage (shipping) of biologics and protein drug products, 
including container closure suitability, should be included in the application. This 
information should be provided for biologics and proteins because, in general, there is 
greater potential for adverse effects on the identity, strength, quality, purity, or 
potency of biologics and proteins during storage or shipping. 
2