7.3 Distribution Controls

This page will address various regulatory issues related to this section of the GMP Institute framework.  Click below to view the issues that are relevant to you.

Is it acceptable for repackagers to assign a single lot number to two or more co-mingled lots of bulk finished product repacked during the same run? 

What types of failures must a batch of new drug product exhibit to trigger a field alert report?

Is it acceptable for a firm to export expired drugs for charity?

Is the sale of expired OTC drugs by a retailer a violation of the Food, Drug and Cosmetic Act?

Is it acceptable for repackagers to assign a single lot number to two or more co-mingled lots of bulk finished product repacked during the same run? 

References: 
See 21 CFR 210.3(b)(10) and(11), Definitions, and 
211.130(c), Packaging and labeling operations

No. Co-mingling of bulk lots during repackaging, even if repackaging records clearly identify the co-mingled lots, would cause the finished, repackaged product to be in violation of the CGMP regulations which define a "lot" as "a batch or a specific identified portion of a batch," (but not more than a single batch). Further, the CGMP regulations specify that the lot identification on finished product allow for, "the complete history of the manufacture, processing, packing, holding and distribution of a batch," and such would not be the case when product lots are co-mingled. Moreover, identifying problem lots or batches in the event of a complaint or finding of defective product, the use of appropriate expiration dating assignments, and the collection of representative samples, are additional concerns when product from different lots or batches are co-mingled.

Contact for further info: Barry Rothman, HFD-325, 301-594-0098, e-mail: rothmanb@cder.fda.gov

Reprinted from: FDA's HUMAN DRUG CGMP NOTES (Volume 6, Number 1) March, 1998.

What types of failures must a batch of new drug product exhibit to trigger a field alert report?

References: 
21 CFR 211.192, Production record review, and 
21 CFR 314.81(b)(1), Other postmarketing reports, Reporting
Requirements, NDA-Field alert report.

21 CFR 211.192 requires a thorough investigation of, among other things, a failure of a batch to meet any of its specifications. This is required whether or not the batch has been distributed. The meaning of distribution here is distribution of the batch in whole or in part. 

21 CFR 314.81(b)(1) requires the submission within three working days in a Field Alert Report (FAR) of information concerning any failure of a distributed batch to meet any of the specifications established in an application. This is required when the drug product is both the subject of any type of application and when the batch has been distributed, in whole or in part. 

For both of the above requirements, a failure includes any test result which falls outside of an established specification, and which has not been invalidated (e.g., found to be laboratory error). (A failure also includes other developments which are not discussed here). 

The required FAR should be submitted within the three day time period after the information becomes known or after distribution, whichever occurs later. An initial report should be filed while any investigation is ongoing and which extends beyond the three day period. The FAR, initial and follow-up as necessary, is required even though a batch may have been released after consideration of the failed test result which falls outside of an established specification along with all data which may be generated by the investigation and the information in the drug product production and controls records reviewed and approved in accordance with 21 CFR 211.192. 

Contact for further info: Nicholas Buhay, HFD-325, 301-594-0098; e-mail: buhay@cder.fda.gov .

Reprinted from FDA's Human Drug CGMP Notes, (Volume 4 Number 3), September, 1996.
This text is also reprinted in Framework section 7.2.

Is it acceptable for a firm to export expired drugs for charity?

Reference: 
21 CFR 211.137(a) and (d), Expiration Dating

No. While we recognize the dire need for drugs in distressed parts of the world, once the expiration date has passed there is no assurance that the drugs have the safety, identity, strength, quality and purity characteristics they purport or represent to possess. As such, expired drugs are adulterated within the meaning of section 501 (a)(2)(B) of the FD&C Act, and section 301 of the Act prohibits the introduction or delivery for introduction into interstate commerce any drug that is adulterated.

Firms may wish to extend the labeled expiration date, thus making them suitable for export, provided that any extension of the expiration dating is supported by appropriate stability studies. Any extension of the expiration dating should be of sufficient duration to ensure that the drugs do not again reach their expiry before their anticipated use.

Reprinted from FDA's Human Drug CGMP Notes, (Volume 4 Number 1), March, 1996.

Is the sale of expired OTC drugs by a retailer a violation of the Food, Drug and Cosmetic Act?

We have received calls from both FDAers and state agencies inquiring as to what violation can be charged against a retailer found to be selling expired OTC drugs. We have been told of instances where retailers were found to be selling expired OTC drugs at a discounted price. Some retailers apparently feel that as long as they openly disclose to customers that the drugs being offered for sale are expired, they can be sold legally. Some state and local agencies have indicated they lack authority under their laws to pursue legal action against purveyors of expired OTC drugs, and therefore seek support for a legal action under the FD&C Act.

We regard expired drug products to be adulterated within the meaning of Section 501(a)(2)(B) of the Food, Drug and Cosmetic Act, which states that drugs must be manufactured, processed, packed, and held in conformance with current good manufacturing practice. The holding of drug products past their expiration dates supports the 501(a)(2)(B) charge. It should be noted that it would not be appropriate to cite a retailer for deviations from the CGMP regulations in 21 CFR Parts 210 and 211, because the CGMP regulations apply to drug product manufacturers. Additionally, openly disclosing that the drugs are expired is not any basis for an exemption from the Act. From a public health standpoint, there is no assurance that drug products held past their expiration dates are safe and effective, even if they are OTC drugs.

Contact for Further Info: Barry Rothman, HFD-325, 301-594-0098, e-mail: rothmanb@fdacd.bitnet.