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 | 1 Comment »

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 »

Shake and Bake Cookbook: Does It Exist?

Years ago, one of our editorial advisory board members (actually, more than one) told me that medical device manufacturers were seeking a cookbook-approach to medical packaging. Mix this, test that, age this, store that, and so on.

With the wonderfully detailed ISO 11607 and consensus-driven ASTM standards, we are getting pretty close to that cookbook approach. But MDMs still must ensure that  packaging development supports the safety and integrity of their medical devices and that ALL testing is appropriately matched to that packaging.

Such was the collective message at MD&M West’s day-long packaging track on February 8. Scott Levy of DDL, who spoke about ASTM D4169 and other performance testing standards, said that in order to select the most-appropriate testing method, you’ve got to know your distribution environment. “You have to look at what is going on in the real-world to understand common failures. What percentage of defects are you seeing?”

“It is important to mitigate the risks that happen in the real-world, not just the risks presented when testing to a particular method,” he added.

Mike Troedel of Troedel & Associates Inc., who spoke about several ASTM methods and joined Levy for an expert panel, advised attendees to perform “a thorough risk analysis so you have testing acceptance criteria established before you test.”

“You must have a strong technical justification upfront so if you see testing failures, they are probably happening in the real world,” Troedel added. Engineers can often be looked at testing for too severely, he intimated.

So, understand the standards and methods available to you, because they can help you follow best practices. (Plus FDA may have recognized them.)

But at the same time, base your testing decisions on what is appropriate for your given medical device and package. Otherwise, you may experience failures you’re not prepared to handle.

Daphne Allen

Posted in Testing | No Comments »

Pallet-Sized Shippers Target Global Transit

Growth in bio-engineered products more susceptible to variations in temperature and humidity. Emerging global markets that require packaging that will stand up to the handoffs, complexities, and climate variations of extended supply chains. The proliferation of guidelines and regulations from countries around the world promoting best practices for handling sensitive freight.

It all adds up to a “perfect storm” for manufacturers of thermal shipper solutions. 

Drug manufacturers’ requirements for new solutions in unit load devices (ULDs) has spurred innovation for stowing pallet-sized loads of various sizes in aircraft transport. 

“Customers are requesting a lot of international work, and looking for more payload capacity.  We are seeing a tremendous demand for longer duration shipments (in pallet-load sizes),” says Larry Gordon, president of Cold Chain Technologies. 

CCT plans to launch six new pallet-sized thermal shippers this year. A new GTS 6000 will handle product requiring room temperature conditions. Other of the company’s planned ULDs will feature smaller pallet dimensions for transit lanes served by planes that can’t accommodate full-sized pallets. 

EnviroCooler just launched a pallet-sized ULD designed to fill out an LD3-size cargo space, supporting more payload for the same transport cost. 

And leveraging its technology in ultra-low temperature containers for pharmaceutical product, Farrar Scientific is offering a ULD metal container with heating and cooling capacity. The PharmaPort 360 responds to customers’ concerns over ambient temperature extremes on global routes, reports Farrar Scientific president Scott Farrar. 

While improved packaging solutions go a long way, companies shipping to far flung destinations face exceptional challenges. Security check points in a post 9/11 world have added to the in-transit hurdles. 

Manufacturers are minimizing variability in supply chain logistics, streamlining supply chains with partners committed to best cold chain management practices. 

It will be interesting to see if quality assurance programs for sensitive drug cargo recently implemented by the airlines–perhaps in combination with new pallet load systems and thermal technology–will reduce the higher excursion risks historically seen in the air transport leg of shipment itineraries.

Dave Vaczek

Posted in Cold Chain | No Comments »

Covert Anticounterfeiting: Smart Strategy, or an Insult to Partners?

Patients in the United States are very lucky that drug and medical device counterfeiting has not caused the problems other global regions have seen. But as U.S. supply chains stretch around the world, especially pharmaceutical and medical device supply chains, will U.S. patient safety remain the norm?

According to a press release issued by BrandWatch Technologies, in 2009, U.S. Customs seized over $30 million in counterfeit medical products, including pharmaceuticals, personal care products, electronic components, and power systems. I searched the Web to verify this fact and found this statement “The U.S. pharmaceutical industry loses billions of dollars of annual revenues due to counterfeit medicines.  The average reported value of counterfeit medicines seized in 2008 was over $5 million” on the Web site of the Office of the United States Trade Representative.

Many numbers are being cited, but one thing is clear: Counterfeits threaten patient lives and corporate livelihoods. “The potential health risks to consumers aren’t the only dangers,” explains Steve Delepine, V.P. of Business Development for BrandWatch Technologies. “The effects of legal liabilities, negative branding, and revenue loss can ultimately bankrupt a company.”

Delepine is looking to help the medical device industry monitor for counterfeits particular, at several stages of the the product’s entire life cycle “from contract manufacturers, to healthcare administrators, all the way to the customer.” BrandWatch offers taggants for multiple uses, potentially in the inks, dyes, polymers, pulp, and paper used in packaging and labeling.

“Too many companies spend a lot of money on a security solution which will be duplicated or obsolete in six months,” Delepine warns. “A brand protection plan that doesn’t include an evolving design is no plan at all. Counterfeiters just move too fast.”

A security expert I recently spoke to (not from BrandWatch) indicated that as more and more companies outsource certain operations to contractors around the world, they are truly at the mercy of their partners. Of course, due diligence in selecting the right partner with a proven reputation should help eliminate risk.

But if a company is dealing with a new partner that may be outsourcing activities itself, would using covert protection unbeknownst to that partner provide extra protection? Is that a smart business strategy, or an insulting one, should your partner ever find out?

Daphne Allen

Posted in Counterfeiting, Healthcare Reform | No Comments »