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By Stephen S. Dallas

That was the theme of the 21st annual DIA Conference for Electronic Document Management (EDM) hosted in Philadelphia on February 5 through 8. The goal of this year’s conference was to focus on grass roots; getting back to basics and best practices. While the intent was not specifically about the transformation to an electronic ‘state’ and the associated evolving standards, it was evident many attendees still want to know how to get there. The overarching theme for the conference was the “Never-ending Process”.

If your profession involves the management of electronic information in the Life Sciences industry, then the annual DIA Conference for Electronic Document Management conference is for you. This year’s conference afforded attendees vast opportunities for knowledge exchange and more importantly the ability to provide input and feedback to industry leaders and government regulators.

DIA President Ron Fitzmartin stressed the importance of this particular conference reminding the audience of the overall DIA mission, which states, “…sharing information that optimizes the process of drug development and lifecycle management.” The statement itself does not include the words ‘document’ or ‘electronic’ in it however it does infer best practices, collaboration, and the overall process. This is truly grass roots and indeed never-ending. In my opinion, the conference succeeded in meeting its stated goals, while keeping within the spirit of the DIA’s mission.

There was a broad spectrum of speakers from industry, technology and service providers, and FDA. The provider area included the anticipated mix of firms partnering, competing, and sometimes both to promote their business values.

There were four main themes permeating this year’s EDM Conference, including
Best Practices, Standards, Regulatory Trends and Metadata.

Everybody wants Best Practices and the conference was full of them, however many resulting from years of experience and hard work by individuals or small groups. More can be done to compile Best Practices across the industry to include a broader base and objective evidence. This would facilitate wider acceptance and expedite implementation across organizations.

A lot has been done. If you are of the opinion that standards and best practices are related, initiatives like the Electronic Common Technical Document (eCTD) have proven effective. One speaker made an interesting point that good standards allow authors more time to spend on content.

Standards were also discussed extensively, especially as they relate to Health IT initiatives, both during opening day on Wednesday and on ‘FDA Day’ Thursday. In fact, a lot more was mentioned about Health Care related issues than I expected to hear at a DIA conference, with Interoperability of Health IT systems mentioned as an area of growing concern. The question was raised, “If we advance technology for interoperability, Who should pay? Who would benefit? What would be the business case?”

FDA representatives were surprisingly vocal at the conference. The agency acknowledged that there are fewer employees with an increasing amount of work to do with an IT infrastructure in need of an update. Michael Fauntleroy, Dir. Electronic Submissions, CDER, jumped off the stage and into the audience to talk about the Gateway, Validation Checks, Waiver Policy, and other topics regarding how to submit an electronic dossier to FDA. This was practical and valuable information. His delivery was a real treat, effective, and kept us wide awake.

FDA representatives talked about the agencies drive to provide industry with guidance as a means to drug safety, as opposed to instilling fear with the actual power they possess. This point was illustrated by two images; “Mr. Rogers” versus “The Terminator”. A bit extreme but gets the point across. That’s getting back to basics, human communication basics.

We were reminded that when FDA reviews an application, in fact there are two human beings communicating. So when you assemble your dossier, put yourself in the shoes of the person who will have to review it. This idea was cited in several discussions regarding hyper-links and bookmarks in an eCTD. Someone asked how much is enough. The answer was, “If you had to review it, what would make your job easier?” By the way, the larger the document, the more useful the links can be.

While there are obvious benefits to EDM in reducing the product development lifecycles and thereby getting drugs to market faster, the FDA is still dealing with the challenge of doing more with less people and less paper.  Although electronic submissions do not guarantee shorter review cycles, shifting to eCTDs is of special importance, since we learned at the conference that CDER’s paper repositories are full. 

Naturally there was a significant focus on eCTD. I attended the Electronic Odyssey tutorial on Tuesday. During the session, the point was driven home regarding the interdependence of EDM Systems (EDMS) and eCTD. A successful EDMS implementation must be created with the end in mind. A key “Lesson Learned” was that large organizations should not aim to have a single, monolithic EDMS/eCTD system. This overarching strategy, although interesting from a consolidation standpoint, doesn’t seem to work in practice. Instead, companies should look at federated systems linked with ‘connectors’. When you take into consideration the current trend toward outsourcing and information coming from 3rd party partners, federation is even more appealing.  Regardless of the implementation strategy, EDMS output should be displayed with the understanding of how a reviewer will need to consume it.

I had the opportunity to discuss the topic of eCTD, with a “Big-Pharma” executive. We discussed what worries him most about eCTD. He amply replied, “It’s not the format of the eCTD, but rather getting the content compiled, complete, and accurate.” There are no new content requirements of eCTD over CTD.

Metadata also took the spotlight with an entire tutorial dedicated to the topic. Implementing a successful EDM used to prepare eCTDs requires careful metadata management. If you don’t, it can be hard or impossible to change metadata downstream. Pfizer presented a nice system for RA document archiving. It was created by first collecting metadata using carefully thought out methods and then leveraging that metadata to build the system. The result has no folder structure! This is the essence of metadata. It is a commendable task for such a large company because the more users, the harder that ‘shift’ can be. A lengthy discussion ensued about folders and how hard it is to get away from them.  Microsoft said even though Windows will be folder-based for the foreseeable future, one can eliminate them in a well designed EDMS. Finally, one attendee pointed out that a well thought-out folder structure can actually be directly used to create a metadata-only design.

The transformation to fully electronic data management is still uncertain, complex, and indeed ongoing. With such a complex field come silos of knowledge. Nobody knows everything, so the ‘sharing’ part of the conference was highly valuable. This is the 21st conference of its kind. One might think after decades, we might have it all nailed down, etched in granite. Yet this is not nearly the case. There is still a lot of uncertainty, many failed attempts to build a good working systems upon, and of course ever-evolving technologies and regulations.

The theme of getting back to grass roots was a good one for this year, and to that end I would like to propose a new acronym, LSIM, for Life Science Information Management. Who needs the ‘E’, it’s implied by now. We talk of Records, Content, Documents, Data, and this year a lot about Metadata; all of it is Information. Whether you interact with this information through an LCD or paper, generate it in the lab or from a study, create it or consume it, you must always remember that you are communicating information from one human to another.

Stephen S. Dallas is an independent consultant providing EDM Project Management services to Life-Science companies. Over the last ten years, he has managed the implementation and validation of Enterprise Content Management systems across a wide variety of pharmaceutical companies, ranging from startups to those in the Fortune 100.

Stephen can be reached at (484) 995-6396.

By Gregory P. Brummett, Esq.

In its February 20, 2008, decision in Riegel v Medtronic, Inc., the U.S. Supreme Court ruled that The Medical Devices Act of 1976 (“MDA”) was sufficient to preempt any State law that purported to “establish or continue … any requirement … which is different from, or in addition to, any requirement” under relevant federal law.  The MDA, passed in response to widespread lawsuits over the Dalkon shield, provides for Food and Drug Administration (“FDA”) oversight of medical devices with the degree of scrutiny depending on the type of device at issue.  The most extensive oversight is applied to those medical devices designated as Class III devices.  Such devices are subject to a premarket approval process during which the FDA reviews their design, labeling, and manufacturing specifications and determines whether or not those specifications provide a reasonable assurance of safety and effectiveness of the device.  Once a medical device has been approved, the manufacturer may not make changes that would affect the safety or effectiveness of the device until they have obtained permission for the change from the FDA.

Charles Riegel was injured when a Medtronic catheter ruptured during a 1996 coronary angioplasty in response to a myocardial infarction caused, in part, by a right coronary artery that was diffusely diseased and heavily calcified.  During the surgery, Riegel’s doctor inserted the Medtronic balloon catheter into Riegel’s diseased coronary artery and attempted to dilate the artery, despite device labeling warning that such use was contraindicated for patients, like Riegel, having diffuse or calcified stenoses.  Although the label further warned that the catheter should not be inflated beyond its rated burst pressure of 8 atmospheres (just over 117 psi), Riegel’s doctor inflated the catheter five times, to a pressure of 10 atmospheres (147 psi).  During the fifth inflation, the catheter ruptured, resulting in a blockage that necessitated emergency coronary bypass surgery.

Although the catheter was a Class III device that had passed FDA’s most rigorous premarket approval and was used in a manner inconsistent with the device labeling, Riegel filed suit in New York alleged that Medtronic’s device was designed, labeled, and manufactured in violation of New York common law and that he was entitled to recover damages on claims of strict liability, breach of implied warranty and negligence in the design of the catheter.  In disposing of the lawsuit, the U.S. District Court noted that Riegel’s claim was not based on any allegation that Medtronic had violated federal law and dismissed Riegel’s state law claims as being preempted by the MDA.  On appeal, the U.S. Circuit Court for the Second Circuit affirmed the lower court’s decision.

Justice Scalia, writing for an 8-1 majority, held that the MDA preempts the imposition of liability under state laws for Class III devices that have passed the FDA’s approval process, the most rigorous of the FDA’s testing procedures.  Scalia reasoned that allowing juries to award damages when something goes wrong would be unfair because patients “would suffer without new medical devices if juries were allowed to apply the tort law of 50 states to all innovations.”

Justice Ginsburg dissented, arguing that Congress had not intended the preemption clause “to effect a radical curtailment of state common law suits seeking compensation for injuries caused by defectively designed or labeled medical devices” and that she doubted Congress meant leave no remedy to consumers injured by FDA-approved devices that “nevertheless prove unsafe.”  She further noted MDA’s “failure to create any federal compensatory remedy for such consumers” as evidence that Congress did not intend the MDA to preempt all state common-law suits alleging deficiencies in FDA-approved medical devices.

Gregory P. Brummett of the Capitol Patent & Trademark Law Firm is a patent attorney with 15 years experience in the drafting and prosecution of patent applications before the USPTO in a wide range of technologies including, in particular, chemical and semiconductor processes. 

He may be reached at (703) 266-3330 or gbrummett@cappat.com.

By Daniel R. Matlis

Lately, I have been getting a lot of questions regarding the state of Outsourcing in Life-Sciences.  Most recently, I shared my thoughts during interviews with Medical Product Outsourcing and InTech Magazine.

When I started working in Life-Sciences, nearly two decades ago, going offshore meant moving operations to a company owned facility in Puerto Rico. This was the heyday of Section 936. Established in 1976, Section 936 of the Internal Revenue Code provided U.S. firms operating in Puerto Rico with tax-free income. Lower wages and the security of being home (Puerto Rico is a free associated state of the US) made the island a hub of Life-Science activities. 

By the mid 90’s, Life-Science Companies began moving manufacturing operations to Mexico. The shift was a consequence of a sunset provision in Section 936 and the ratification of the North American Free Trade Agreement (NAFTA)

In the past five years, the trend to offshore manufacturing has evolved into outright outsourcing.

Life-Science Executives tend to a pretty conservative bunch. This is not surprising given the highly regulated nature and high risks associated with Life-Science products. Consequently, it is not surprising that the outsourcing shift in our industry follows decades of successful outsourcing across industries such as consumer electronics, high-tech and automotive. This cross industry success has paved the way for the rapid uptake and growth of outsourcing in Life-Sciences.

In fact, Life-Science outsourcing has grown from working with certified suppliers of basic raw material, excipients, packaging and components, to comprehensive contract manufacturing, clinical trial management, and product research, development and engineering.

Recently, a number of leading Life-Science companies made groundbreaking announcements around their outsourcing initiatives:

• Pfizer aims to outsource 30% of its manufacturing, largely to Asia.
     Source: The Wall Street Journal, November 30, 2007  
• AstraZeneca has begun to outsource production of some of its bestselling medicines to low-cost manufacturers in the Far East.   
     Source: Times of London, October 22, 2007

Although much of the recent outsourcing buzz has focused on China, so have some of the outsourcing problems.

• A Chinese Supplier could be the source of a potentially deadly allergic reaction experienced by hundreds of U.S. patients infused with Baxter International Inc.’s blood thinner heparin.
     Source: Chicago Tribune February 14, 2008
• FDA Advises Consumers to Avoid Toothpaste From China Containing Harmful Chemical 
     Source: FDA, June 1, 2007

To make it clear, geographic location has little to do with product quality. It does not matter whether you outsource to the India or Indianapolis, People’s Republic of China (PRC) or Puerto Rico (PR).  What’s important is that you ensure the presence and enforcement of tight controls over critical to quality parameters (preferably of a proactive, not reactive nature) at your outsourcing partner. It is critical that license holders ensure that outsourcers have in place - and can provide documented evidence of - systems that ensure product quality.

Outsourcing is here to stay, and although its benefits are relative, one thing is certain: outsourcing is not a strategy for “Liability Transfer” or “Risk Management”.  The fact is that there is no such thing when it comes to FDA regulations or the court of public opinion. If your name is on the product, you are ultimately responsible, regardless of who makes it for you.

When outsourcing, “Trust but Verify” is not just a saying but a way of life.