The U.S. Pharmacopeia is asking for your help as it revises its guidance on Good Distribution Practices. 

In the June 23 Webcast, “USP General Chapter (GC) <1083> Good Distribution Practices—One Global Document Under Consideration,” Mary G. Foster, PharmD, Chair of the USP Expert Committee on Packaging, Storage, and Distribution, told the audience that the committee is preparing General Chapter <1083> Good Distribution Practices (GDPs), which when final will replace two official USP General Chapters on GDP: 1) on drugs, <1079> ; and, 2) <1197> for excipients. 

The USP has been working on GDPs for the last 10 years, and most recently began discussion with the World Health Organization and the European Medicines Agency in an effort to create one standard document and approach to distribution practices globally. The initial discussions began in October 2014 and are intended to include the US FDA, Health Canada, and other regulatory bodies. Each country would maintain their own regulatory guideline but could use a GDP standard as the focal point, Foster tells PMP News.

Foster emphasized the real need to standardize as more and more countries write regulation and guidance. The prospect of one global document could be of real value to the end-user whether that involves a drug manufacturer, an API supplier, a third-party logistics provider, or an airline, she says.

“If you’re in this industry long and in shipping and distribution programs, you know how many different documents there are that you have to keep tabs on, and the regulations are changing pretty frequently,” she says. “And while the FDA is on top of this and providing the industry with new guidance meeting its time table, which goes out several years, from the USP Expert Committee perspective, we’re looking at how to make the next practical step for the end-user right now.”

The Committee has also been working with other USP Expert Committees as well as with other stakeholders and subject matter experts to get as many different perspectives on GDPs as possible, Foster said. “It’s very important that every medicinal product [professional] understand their need to protect the identity, strength, quality, and purity of their product. We cover radioactive products, reagents, dietary supplements, so it’s just about every product we could assess with the exception of medical gases, and this was the only area for which we didn’t have subject matter expertise, so ring my bell if you do--we would appreciate having that expertise on board."

The scope of the GDP GC will be all individuals and organizations involved with packaging materials, processes, and products. Foster said that the feedback the committee has gotten so far from stakeholders is that USP’s “‘scope is great and we love it being wide, but tell us why some of the things are happening and be more specific,’ so that’s what we are going to work on.”

“Now is a great time (for USP readers) to let us know what needs to be written,” Foster said. “I am hoping you have read [the proposed chapter] in the Pharmacopeia Forum, but if you haven’t, please do so and give us feedback. We read every word that comes back to us.” She also encouraged participation from subject matter experts who can offer input pertaining to any container that holds a drug product.

USP is aligning its approach with FDA’s, Foster explained. “Our intent is not to supersede FDA, not to override, but to work as a partner with FDA and delete information if FDA choses to write guidance on any subject we have official or are in the process of writing,” she said.

The proposed GC, GDP <1083> includes an introduction, four pillar subjects forming sub-chapters and, to date, five new subchapters covering subjects that were deemed the most important:

<1083.1> Quality Management System
<1083.2> Environmental Conditions Management
<1083.3> Importation & Exportation Management
<1083.4> Supply Chain Integrity & Security
<1083.5> Finished Drug Products
<1083.6> Excipients
<1083.7> Active Pharmaceutical Ingredients 
<1083.8> Packaging Components & Materials
<1083.9> Clinical Trial Materials

Future topics under consideration to be covered in separate sub-chapters include validation (shipping process) and risk management (distribution issues). “We have had feedback that validation should be prospective,” and more should be covered because not all USP end-users are from large pharma or established firms but rather may be start-ups, virtual, or outside the direct drug manufacturing process such that they would appreciate further guidance in these areas," says Foster. 

Also, “we’re hearing a lot about risk, so we will go into more depth than we originally planned, explaining exactly who [is responsible] and the risk [itself],” she said. For instance, consider medications left in a mailbox all day, she added.

USP has been getting requests for more information on specific topics. One is biologics, and industry wants more information on agitation/drop studies and freeze-thaw cycles, she says. “It may not be as critical with an oral solid or a liquid, but it may be with a biologic,” she says. “We’re also getting requests about CO2 ingress on shipping materials, radiation effects from air transportation.  All subjects that would help the end-user better understand what to do.

“Let’s not just talk cold-chain. In fact, we are not using that term anymore,” she continues, “because all temperature conditions need to be considered because all drugs must be temperature controlled. We have received feedback that you should be monitoring all materials that are being held through an SOP, using shipping protocols and a Master Validation Plan for shipping. And, there’s not just temperature, there’s also humidity-feedback per regulatory agencies, so how are we going to write about it, what direction should we take? This is where subject matter experts are needed.”

In terms of covering excursions, questions have been raised about mean kinetic temperature (when to use it and how) and when to read temperature loggers, she said. "Feedback from one agency covered the fact that data loggers should be read immediately upon receipt because sending them back to be read can lead to destruction of the data logger during its transport, leaving the process and outcomes with an investigation that may be hard to complete."

Also, "we have learned that most companies ship outside labeled storage conditions," Foster says. "This may be because there is data supporting or other control mechanisms in place. The question for the Expert Committee becomes how to address this for all end-users of the GC."

In the context of the following sentence: “The ability to maintain the product within specific labeled environmental conditions, especially during transportation…” the one word “specified” in relation to temperature controls can be hard to follow, Foster notes. "Change it to a word like 'established,' and the end-user may have a workable guidance to follow (recent conference feedback). I hope you can see the need for the subject matter experts to be sure we get this right!” she says.

The revision will also address a number of emerging issues, such as re-importation and re-exportation in consideration of the FDA refusal of admission of products. The USP Expert Committee is working to be predictive and wants to provide the end-user with future-thinking concepts, Foster tells PMP News. “How do we take what we know and sync it to the future?” she asked during the event. “How do we get ahead of this and help the end-user of GDPs and the USP?”

Another issue to address is the supply agreement. “Supplier contractual agreements cover GDPs, but how are firms covering every license, registration, customs clearance, returns, and reuse of product?” she asked.

Training must also be considered. “All staff who touch the supply chain should be trained,” said Foster. “Repackaging has to be covered in this regard; all the touch points handling the product. We’ve got to get everything into the 21^stcentury.”

Foster is a pharmaceutical/biologic consultant with 30 years of industry and is currently managing director of The Foster Group LLC. She has served on the USP Packaging, Storage, and Distribution Expert Committee since 2005 and as Chair for the past five year cycle and for the 2015 – 2020 new cycle; and has served on the USP Governance Committee from 2013-2015. To reach Foster, please e-mail her at [email protected]. 

The Webcast was sponsored by UPS.