Depressing Weekend: Eli Lilly Victim of Theft

Prozac and Cymbalta are among the products stolen from Eli Lilly and Co. over the weekend, the company reported today.  More than 30 lots of products were stolen from the company’s distribution operations in Enfield, CT.

“Since early Sunday morning, Lilly has taken quick and appropriate actions to ensure the safety of our medicines,” said Dr. Fionnuala M. Walsh, Lilly’s senior vice president of global quality, in a statement on the company’s Web site. “The U.S. pharmaceutical distribution system is tightly controlled and monitored, making it extremely difficult for stolen product to make it to patients through legitimate channels. However, we will continue to work closely with local and federal law enforcement authorities, the FDA, and our distribution partners to maintain the integrity of our drug supply chain.”

According to this statement, only partial lots were stolen. “Product from the affected lots which had been delivered from Lilly to retailers, wholesalers, or institutions prior to March 14 was approved for its intended use and is not affected by this event,” the company states. “Product containing these lot numbers has been distributed by Lilly within the United States, Puerto Rico, and its territories.” Lilly stopped distributing product with the affected lot numbers on Monday.

Suppliers to the pharma industry have pointed to the vulnerabilities of tracking drugs solely by lot number and continue to advocate item-level serialization or authentication technologies like taggants. Product movement cannot always pinpointed as precisely with lot numbers as it can with serial numbers or unique markers, they say.

FDA is under a FDAAA deadline to release its suggested Standardized Numerical Identifier for serializing prescription drugs this month.

Eli Lilly is putting its faith in the supply chain. Could that faith be shaken by articles like this one at Newser.com from the Associated Press that suggests stolen drugs could make their way back into the legitimate supply?

Daphne Allen

Posted in Uncategorized | No Comments »

Pinholes Found in IV Product Packaging

Pinholes may be at the root of a recall issued in February of nearly a thousand medical device products.

According to FDA, Teleflex Inc. offered an update on the Arrow International Inc. recall of all lots of its Arrow custom intravenous administration products (IV tubing sets and accessories) and certain Arrow arterial embolectomy catheters distributed prior to February 19, 2010.

“Testing revealed pinholes in some of the pouches in which the products are packaged, and it has been determined that product sterility cannot be guaranteed,” Teleflex reported. “No injuries have been reported to date. However, significant under-reporting of adverse events may have occurred.”

A 40-page list of affected products can be found on the company’s site.

An incredible number of kits and sets seem to be affected, including some with Alaris Medical Systems trademarked devices.

Daphne Allen

Posted in FDA, Recalls | No Comments »

Are You Terrific at Tracking?

If you are wondering what FDA is thinking these days when it comes to drug safety, you should read yesterday’s statement from Joshua M. Sharfstein, M.D., FDA’s principal deputy commissioner, before the Committee on Energy and Commerce, Subcommittee on Health, U.S. House of Representatives. You may not have all your questions answered, but you’ll get a good idea of the agency’s priorities.

First, FDA expects you to be in control of every part of your supply chain, regardless of where it begins or ends and who is involved. “In this day and age, companies should be able to effectively demonstrate that safety, quality, and compliance with international and U.S. standards are built into every component of every product and every step of the production process,” Sharfstein said.

Tracking your products–and all the ingredients, components, and tools you use to make your products–is imperative. “Some companies already do a terrific job at this, tracking where and how their products and their components are made and the path taken to reach our shores.  In fact, I have met with some companies that react with incredible swiftness to questions about the integrity of their supply chain,” Sharfstein noted. “Obviously they have a vital interest in ensuring confidence in the safety and quality of their products and their brand. These best practices need to become standard practice throughout industry.”

What are those best practices? Sharfstein said that “very shortly, FDA will issue a guidance establishing a standard for unique identification for prescription drug packages, which ultimately will help in identifying the whereabouts and authenticity of drug packages and distinguish them from counterfeits.” Will it be guidance or a requirement? It may not matter so much to FDA, because it is looking for “terrific” to become “standard.”

And what if you don’t implement those best practices? “FDA needs to access regulatory information quickly, hold all parties responsible for the quality of products in the supply chain, and have reasonable and reliable options for enforcement,” Sharfstein said, referencing statements made by Secretary of Health and Human Services Kathleen Sebelius when she appeared before this committee in February.

This month will certainly be an exciting one, with FDA’s deadline under FDAAA for “development of standards for the identification, validation, authentication, and tracking and tracing of prescription drugs as a step towards further securing our nation’s drug supply.”

Sharfstein told the committee that the complex web of players in the supply chain “leaves weaknesses through which counterfeit, adulterated, and misbranded products might infiltrate the legitimate supply chain.”

Are you terrific at tracking your products through that web? Or are you terrified at the notion?

Daphne Allen

Posted in Compliance Packaging, Counterfeiting, Diversion, FDA, Hospital, Imports, Third Parties, security, serialization | No Comments »

Don’t Pass on Poststerilization Testing

FDA’s Quality System Regulation states that as part of “final acceptance activities. . . each manufacturer shall establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria.”

Why the regulation lesson? I just read today that Guidewire Technologies Inc. (Salem, NH) received a warning letter from FDA stating that “testing is not conducted after each sterilization process for your sterile packed guidewires. Your 510(k) submission states that finished Teflon coated guidewires will be free unless packaging is opened or damaged.”

I am not aware of the specific details, but poststerilization testing seems absolutely necessary. Of course, you must decide what tests to perform based on your processes and the risks presented to your products. Seal strength and package integrity seem givens, but there may be some gray areas. Common sense should prevail.

For instance, at HealthPack last week, emergency room nurses stated that they had some trouble reading package labels. So when Dave Olson, vice president of sales and marketing for Advanced Web, stated that a survey his firm conducted found that 73% of those label users surveyed evaluated label integrity poststerilization, I wondered whether any label troubles snuck past the remaining 27%.

I am not equating package integrity and label integrity. But as FDA’s regulation states, “each manufacturer shall establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria.”

Don’t let the rigors of sterilization escape your scrutiny.

Daphne Allen

Posted in FDA, Labeling, Testing | No Comments »

FDA: “We are not opposed to patient unit-dose packaging”

A while ago we shared a letter from the Healthcare Compliance Packaging Council to FDA regarding an FDA decision out of the Office of Drug Safety “that prohibits generic drug manufacturers from ‘calendarizing’ unit dose blister cards, strips, and other packaging formats.”

We hadn’t heard anything official from FDA, so I asked the agency for an update. Here is the official response, courtesy of two always helpful press contacts, Crystal Rice and Karen Mahoney:

“The Office of Surveillance and Epidemiology evaluates proposed labels and labeling from a medication error perspective.  We are not opposed to patient unit-dose packaging.  However, we want to ensure that the unit-dose pack is designed in a way that is not confusing to the patient or caregiver and makes sense for the dosage and administration of the product.  In certain instances, manufacturers wish to place the days of the week (calendarize) on the unit-dose packaging. However, calendarizing may not be suitable for all medications.  For example, medications that are given on an as-needed basis, or once or twice daily, as opposed to those with fixed doses.  Thus, we evaluate every proposal on a case-by-case basis to determine if the package design and proposal for calendarization makes sense for the dosage and administration of the product and does not contribute to confusion that could lead to dosing errors.”

The good news is that FDA is not opposed to unit-dose packaging, which could put to rest fears that FDA is banning all generic drug manufacturers from using calendarized packaging if the brand drug maker doesn’t.

But could the case-by-case process for reviewing package design and calendarization proposals make some generic drug makers reluctant to introduce something new?

The rush to market can be fierce. I hope that innovation won’t get trampled.

Daphne Allen

Posted in Blisters, FDA, Medical Errors, Safety | 2 Comments »

Whose Imports Are Being Shredded at the Border?

FDA is working to tighten U.S. borders when it comes to product safety. In February alone, import alerts for “Detention Without Physical Examination (DWPE)” have been issued for several medical device or drug-like items: unapproved new drugs, active pharmaceutical ingredients that appear to be misbranded, potentially defective medical gloves, devices that appear to be without approved PMAs or IDEs or without a 510k, and even bovine amniotic fluid from countries affected by foot-and-mouth disease. If you’ve got the time, peruse through FDA’s list for a snapshot of imports held at the border.

In February, FDA officially launched its new risk-assessment tool to ensure import safety, PREDICT. The web-based database-scouring system employs product codes to help FDA inspectors determine risk based on manufacturer, country of origin, recall history, and potential security risks. PREDICT will replace the admissibility screening function of OASIS, FDA’s legacy system. According to FDA, PREDICT “will assist entry reviewers in targeting higher-risk shipments for examination.” To learn more, click here.

It is unclear whether any of the above-listed items were detained through use of the new system. But according to a video on FDA’s site, inspectors at the Port of Los Angeles (reportedly the largest in the United States) have actually been using PREDICT for several months. Many products have already been destroyed at the border, reports the video.

Could your imports be flagged by PREDICT? Are you importing items from flagged countries of origin, or have any of your international vendors come under scrutiny?

Some imports could see faster trips across the border, but “only if accurate and complete data are provided by importers and entry filers,” FDA advises.

“We expect PREDICT to offer two major benefits to FDA import inspectors, to importers, and to the public,” explained FDA Commissioner Dr. Margaret Hamburg at a presentation before the Center for Strategic and International Studies on February 4. “First, the system will automatically flag potentially risky shipments. Second, the system will give lower risk scores to more innocuous materials, which can then be cleared through FDA inspection rapidly. This allows FDA inspectors to spend their time looking at the highest-risk items. It also means that carefully labeled products with good histories will be held up for shorter periods, which is better for everyone.”

Judging from the FAQs on FDA’s site, there are still several outstanding challenges. But it appears that product labeling and coding will be pretty essential to smooth importing.

Daphne Allen

Posted in Imports | No Comments »

Clinical Success Can Depend on Packaging

Polyethylene is commonly used for drug packaging. So who could ever have expected that it could result in a product’s clinical failure?

Biotec Pharmacon reported today in a press release that its candidate, SBG, used in a diabetic ulcer program, “may have been inactivated as a result of interaction with polyethylene in the product containers.” SBG “failed to show superiority over placebo in the phase III study for oral mucositis.”

Biotec Pharmacon reports that it plans to carry out accelerated stability studies of SBG with alternative containers. For months the company has been working to identify the root cause behind SBG’s failing the phase III diabetic ulcer program. “We’re clearly dealing with a systematic failure,” says CEO Lars Viksmoen in the release. “There is nothing wrong with our SBG manufacturing process or with the design and conduct of the clinical trials. However, we have early evidence that there has been an unexpected interaction between the product container and SBG that has led to inactivation of SBG over time. We need further confirmation of this theory, and are now planning to conduct similar analyses with the product used in the phase III oral mucositis studies since the same type of containers have been used in all these studies. We are also planning to initiate accelerated stability studies with a number of different containers.”

I don’t have any details on the alternative containers Biotec Pharmacon will be testing.  And since I am not an engineer, I certainly cannot offer any advice on how to proceed.

But I can tell you that over the years packaging technology providers have told me that oftentimes they aren’t contacted early enough during product development to help suggest new packaging materials. Usually the problem they run into is that packaging engineers are only given a short time before product launch to get packaging and labeling ready for market. Stability studies certainly help these engineers narrow material options, but these, too, may not be given enough time to fully explore material options. And because no packaging engineer wants to be blamed for delaying a launch, traditional materials are often selected.

So what can you as a packaging engineer do? Pay attention to new packaging material options, and don’t be afraid to ask the material providers for data that may help you justify use. And, while you certainly cannot afford to put every potential material option up on stability, it may not hurt to try a few promising options.

And ask to get involved as early as you can in product development!

Daphne Allen

Posted in Quality, clinical trials | 1 Comment »

Hospital Decided to Divert Drugs

I hope you read this news in today’s  PMP News.com Daily Newsletter: “Hospital makes a profit trading NHS drugs in Europe.”  Before you click to read it, though, I just want to share a few quick thoughts.

This story shocked me. We’ve reported instances of tampering and theft by healthcare professionals and others seeming to deserve our trust. But in this case, a business decision was made to ignore drug pricing agreements. As the story reports, “The Royal Surrey County hospital foundation trust had been trading in the pharmaceutical export market by buying up drugs at the cheap NHS price and selling them to a wholesaler for export.” It proceeded to do so “despite warnings from the government that such behaviour was unacceptable.”

The Royal Surrey’s finance director Paul Biddle told the Health Service Journal, the trade magazine which broke the story, that “yes, we did see this as an opportunity to make a margin.”

Such diversion reportedly threatens drug availability and could impact future discount negotiations between pharmaceutical companies and the NHS. Patient safety could certainly be an issue if drugs are in short supply. But what about handling integrity? Or labeling? If products were packaged and labeled for one market, could that packaging and labeling fail to support requirements in the market into which product is diverted?

Mass serialization, of course, could be used to identify and root out such diversion. Pharmaceutical companies could therefore ensure that the pricing agreements they forge with certain entities do not affect supply in other markets. Pharmacies could also be assured of manufacturer-approved handling as well as market-compliant packaging and labeling.

Both assurances could certainly promote patient safety.

Daphne Allen

P.S. Click here if you are interested in receiving PMP News.com Daily Newsletter.

Posted in Diversion, Tampering, Theft, serialization | 1 Comment »

FDA Asks Drug Maker to Monitor ESA Prescribing

I have always heard that historically, FDA has pretty much just regulated the manufacture and marketing of the products it oversees (i.e., pharmaceuticals and medical devices, among others) but not the practice of medicine itself. Currently, though, FDA can mandate certain activities under a risk evaluation and mitigation strategy (REMS). A recent agency announcement shows that it can come pretty close to regulating practice—and in this instance it seems to be involving the drug manufacturer.

FDA is requiring Amgen, the manufacturer of certain Erythropoiesis-Stimulating Agents (ESAs), to develop a risk management program, which includes preparation of a medication guide explaining the risks and benefits of ESAs. Requirements for medication guides are increasing, so this is nothing new. (But it is a challenge for manufacturers to ensure that such guides are provided to all patients. Retail pharmacies have been known to miss a guide or two, especially when repackaging takes place.)

But FDA has also asked Amgen to develop the ESA APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs) Oncology program for healthcare professionals who prescribe ESAs to patients with cancer. FDA reports that under the ESA APPRISE Oncology program, Amgen will ensure that only those hospitals and healthcare professionals who have enrolled and completed training in the program will prescribe and dispense ESAs to patients with cancer. Amgen is also required to oversee and monitor the program to ensure that hospitals and healthcare professionals are fully compliant with all aspects of the program.

Is this unique? Is it realistic? Have other manufacturers had to work so closely with the practitioner environment to ensure safe product use?

Has packaging or labeling played a role in easing product use? It certainly can to ensure that medication guides are handy and available for dispensing to patients. Is that all that is needed, or can packaging and labeling play other roles?

I have put a call into Amgen to see what it may be doing with packaging and labeling. But I would love to hear from you, too, especially if you are being drawn into setting practice standards.

Daphne Allen

Posted in FDA, Hospital, Labeling, Medication Guides, REMS, Safety | No Comments »

Don’t Miss the Nurses!

Medical device packagers who have attended the last few HealthPack events still remember the valuable packaging feedback provided by nurses. From an advance survey to a live interactive panel, nurses have provided specifics on packaging preferences, challenges, and wish lists.

HealthPack 2010 will again feature nurse input during the morning session on Wednesday, March 3, in “Voice of the Customer—Part 1; A New and Expanded Nurses Survey.” Jennifer Neid Benolken of T.O. Plastics and Jennifer Blocher of Sealed Air Corp. will present the results of a detailed survey of nurse preferences and concerns.

Later that day, Jennifer Neid Benolken will facilitate “Voice of the Customer—Part 2,” which will consist of a live nurses focus group reviewing submitted packages. Following will be a live Q&A with nurse panel participants.

At last year’s event, nurses offered some eye-opening feedback on packaging. Nurses who responded to the survey appeared to favor double-entry trays for sterile medical devices. Maintaining sterility was a top concern, and the surveyed nurses seemed to feel most comfortable with a tray.

During the live panel, nurses expressed their concern over packages that were difficult or uneasy to open, and they worried about breaching the sterile field during their struggles.

At the same time, however, nurses fretted over minimal hospital storage as well as excess hospital waste.

Earlier this year, HealthPack organizers asked medical device manufacturers to send in actual packages for nurse reviews, so the upcoming exchanges should be just as compelling. Based on feedback we’ve heard from past HealthPack attendees, nursing advice has been taken seriously. Perhaps this next batch of packages will meet with rave reviews!

We look forward to the upcoming event, which also includes a full conference line-up from packaging experts. Of particular note will be the opening keynote address, “Global Standards’ Role in Medical Device Packaging,” to be presented by Charles Sidebottom, Chairman of the Board of Directors, Association for the Advancement of Medical Instrumentation (AAMI).

Hope to see you there!

Daphne Allen

Posted in Medical Devices | No Comments »