Meeting the FDA’s Emerging SPL (Standard Product Labeling) Requirements
Classic "Build your own" vs. outside services analysis to meet changing requirements in a changing environment

Meeting the FDA’s requirement for XML formatted data for Structured Product Labeling (SPL) submissions fall into three main categories: service, hosted and enterprise. Which is best for you? Asks DCL's Don Bridges.

What is SPL?

Structured Product Labeling is an example of cooperation between regulatory agencies and industry on a wide scale to improve information flow that's needed for public safety. The standard was initially set up by representatives from a wide variety of pharmaceutical companies, and adopted by the FDA as an approach that would solve a problem. The issues of implementation and the question of building your own infrastructure vs. outsourcing and using services is a question that applies to many other situations, and the discussion here is relevant to them as an approach.

For several years the Pharmaceutical regulatory compliance community has been submitting Package Inserts (PIs) in SPL (XML) format. That mandate will be expanded to OTC, Veterinary, and Vaccines in June 2009. Quite a leap from Adobe's PDF™ format that has been the standard. The FDA is asking sponsors to shift from an "appearance is everything" approach to one where data is standardized. This data can then be extracted accurately as it gets communicated through computers to the various bodies that need it.

The road has been difficult for most. A new lingo (e.g. XML, DTDs, schemas, stylesheets, etc.) was the easy part. The hard part has been trying to identify an approach that in the short-term meets the FDA’s regulatory requirements and pharmaceutical manufacturers' business requirements, while not precluding future needs. Journal articles have documented the issues and sometimes suggested solutions. But we are less than six months before the deadline for XML submissions and one thing has become clear: there is no one right approach.

Looking into the future, SPL is only the first of many expected FDA-driven XML initiatives within the regulatory environment. The FDA has made no secret of its desire for a greater communication interchange and increased public accessibility to information. XML appears poised to be the vehicle to facilitate these goals.

The requirements relative to Electronic Common Technical Document (eCTD) are expected to pick up momentum. And it is probable that a mandate to provide XML based Core Data Sheets, New Drug Applications (NDA’s), and other regulatory materials will follow.

Viability of Outsourcing Conversion of Labels

There have been concerns that outsourced conversions can't be as good as those done in-house. These concerns are typically based around three areas: Accuracy, security and schedule. These are valid concerns, but most professional conversion bureaus have built in processes that specifically account for and address these issues. When it comes to accuracy most conversion bureaus agree that it is not possible to have 100% accurate conversion of SPL materials with software alone. For this reason, DCL recommends you look for a conversion vendor that places a premium on getting it right first time by combining software with human intervention and insuring the XML instances that you receive are correct. Regarding confidentiality concerns, it is important to be sure your prospective vendor has experience in dealing with sensitive materials and has safeguards in place to insure that your materials are secure. And, of course, you want your conversion done on time, so when looking for a conversion service, make sure the vendor places a premium on the schedule, and has a history of meeting schedules. (Data Conversion Laboratory meets all these requirements).

Within the SPL arena itself, the exact detail of supplying information in XML is ever changing. In late 2004, the SPL schema was in Version 1. Industry has worked through Versions 2 and 3 and faces Version 4 which introduces more information to what constitutes an SPL submission.

XML is here to stay, and will likely turn out to be the core technology that you use to transmit information to the regulatory authorities. The good news is that implementing an XML system will in many cases eventually reduce the cost of creating, maintaining, and distributing your information. So for many organizations it’s not really an issue of if but when they will have this technology in-house. Just as you can’t imagine a world without MS Word, someday you’ll probably feel the same about XML (you heard it here first.)

XML Systems

For those considering an internal implementation, there are three main components to an XML environment: management, authoring and distribution. These components are illustrated in the figure below. At the heart is content management, sometimes (mistakenly) referred to as "document management".* For pharmaceutical organizations, this function is often met by Documentum™ software from EMC, which can also handle XML (just as it currently handles MS Word processing based information and Acrobat™ files).

Authoring is the second aspect of an XML system, and it consists of creating new information and revising already existing information. The third aspect is delivery, which can include regulatory submissions (in XML format to the FDA in the SPL schema), HTML (for posting information to an Intranet or the Internet), PDF (for a paper representation of the information) and EPS (Electronic Post Script) for use by a printer to print the carton or label). Of course this is a simplified view and there are many more aspects to a full XML implementation.

* Document Management differs from Content Management in the granularity of information stored within the system. Content Management is much more sophisticated software in that it manages "chunks" of information and can dynamically reassemble smaller chunks into larger documents and larger books. This capability is critical when implementing a content reuse strategy.

Approaches

For some organizations, the immediate implementation of an internally-developed XML system is a prudent path. For others, outside services can buy time while the various options clarify and mature. Yet others will see outside services as a good long-term option.

So how do you make a decision that keeps you in conformance with FDA mandates and in good graces with your CFO? Well, there are three main options available to you:

• Conversion (and possibly revision) of current labels into SPL as a service.
• Hosted SPL environments.
• Enterprise SPL environments.

Conversion of labels into XML as a service means you can prepare and update labels the way you always did and simply submit your labels to a service provider to be converted, whenever you have an FDA submission requirement. With some organizations you can subscribe to a service that will convert your label(s) as often as required on an annual basis; and you can always ‘mix and match’ one-time and annual revision services.

With this solution you can:

• Continue to use your current infrastructure to create and revise labels.
• Upload (or check-in) your labels via a secure web interface.
• Download approved XML documents for submission.

The service will:

• Convert/revise your documents to XML.
• Likely require that your environment maintain all versions of the document(s).
• Provide reports for review of your labels for validation.

Final review remains your responsibility, although most service bureaus will guarantee that the XML instance meets FDA requirements for structure. Concerns that this type of service adds a lengthy schedule impact on your submission process are unfounded as some service bureaus guarantee turnaround in as little as four hours. Organizations offering this class of solution include Data Conversion Laboratory, Intagras, and Reed. This solution costs less than the hosted solution, and buys you time to evaluate the options as they develop. And for some it might be a viable long-term option.

Hosted SPL environments means that you basically outsource the document preparation functions related to label production, and possibly more. This approach can be used long-term or for an interim period, buying you time until you are ready to make the jump to an in-house solution. You may opt for hosted SPL because you are waiting (a) for the FDA requirements to stabilize; (b) for additional XML requirements to be finalized or (c) for your product inventory and/or distribution to grow. With this solution, a company will host your labels in their environment and you will have access to your XML based labels via a secure web connection. You would have most of the functionality of an in-house system (including revision control and multiple output format capability (including PIM and PDF); and would continue to create and revise documents in XML in the hosted system. The big advantages are short implementation times and minimal capital investment.

Hosted SPL environments enable you to:

• Upload (or check-in) your labels via a secure web interface.
• Download validated XML documents for submission.

The host will:

• Convert/revise your documents to XML (initially).
• Provide a web based interface for validation.
• Provide a web based interface for updating.
• Maintain all versions of the document(s).

Organizations offering this class of solution include Thin Spring. Hosted SPL is a more extensive service option, but does not require immediate capital expenditure. For the short-term, it would be expected to cost less than an in-house solution, but may not tie in with the long-term content management strategy of the company.

Enterprise SPL environments are packaged offerings that integrate management software with authoring and distribution software. These systems offer a one-stop solution to meeting SPL requirements (as a near term solution) and follow-on XML requirements (as a long-term solution). It should be mentioned that for this type of solution there remains the issue of migrating your current labels to an XML format, although this would be a one-time requirement.

By using this type of solution you can:

• Procure and configure a system that meets your needs.
• Migrate your legacy materials into an XML repository (potentially utilizing content reuse).
• Train your staff on the system in general and XML in particular.
• Submit XML instances to the FDA using a normal output mechanism.

Organizations offering this type of solution include Glemser, i4i, Quark (In.vision) and Virtify. All have expertise in the intricacies of CFR 21 Part 11 compliance. These solutions are seen as the ‘total’ solution to address all regulatory requirements both now and in the foreseeable future. Entry level pricing ranges from $10,000 to well over six figures depending on your requirements.

Evaluation Considerations

We have identified eight different criteria to help you evaluate which solution is best:

Criteria	Service	Hosted Solution	Enterprise Solution
Expected Costs	Less than $500 per label	Varies widely based on business model and requirements	$10,000 up to $150,000+ capital costs, plus operational costs
In-house XML Expertise Needed	None	Moderate	Extensive
Risks	Competency of the Service Provider	Competency of the Service Provider	1) Time to implement – will it be ready? 2) Cost overruns; 3) Competency of internal personal, turnover, etc.
Volume	Cost is proportionate to number of labels; you use only what you need.	Very flexible plans and can be cost effective across a wide volume range for organization that want to outsource large portions of the process	Fixed capital investment in getting started, and a maintenance cost over time. Above this minimum, the cost per label should be lower than a service
Long Term vs. Short Term	Often considered an interim solution, but may be a long-term solution for organizations that would rather not build up the internal staffing	Often considered an interim solution, but may be a long-term solution for organizations that would rather not build up the internal staffing	For organizations investing in a complete document management solution, production of labels should be part of the solution
Timeframe	Less than one week	Less than one month	Typically 12 – 18 months
Turnaround Schedule	Normally 2-3 days; Can be as little as 4 Hours	Normally 2-3 days; Can be as little as 4 Hours	Dependant on internal resources and staffing
Impact of Change	None – other than reviewing the SPL output before submission, this addition should be transparent	This is usually included in outsourcing other parts of the process and may require some process change	Usually a major change requiring careful and thoughtful implementation

Analysis

A few things become clear when analyzing the advantages and disadvantages:

1. Organizations with many products and dedicated staff will likely implement an enterprise system sooner than organizations that only have a handful of products.
2. International organizations will likely implement an enterprise system sooner than domestic-only organizations because of the additional requirements of international regulation.
3. Regardless of your size or reach, a conversion service or hosted solution can buy some time until you are ready to implement an enterprise solution.
4. Even if you implement an enterprise solution, a conversion service may be very useful in allowing you to hit ROI targets on time.

DCLnews Editorial
Feb 15th, 2009