Acronyms can add a layer of complexity, since they can be very similar with only slight variations on each other, such as cGMP, GMP, GAMP and GxP. Fortunately, there are some standard letters that are used, which makes deciphering some of these acronyms a bit easier. For example, ‘G’ is often used for Good and ‘P’ for Practice or Practices. Another commonly featured letter is the lowercase ‘c’ which stands for Current if it’s at the beginning of the acronym. When ‘A’, is found in the middle of the acronym it’s for Automated, followed by the area that is represented, such as ‘M’ for Manufacturing, ‘C’ for Clinical and ‘L’ for Laboratory. Collectively these are all known as GxP, where the ‘x’ in the middle indicates there are many different unique areas the overriding methodology can be implemented into.

When you get further into your project you will likely need to enforce control and manage change by utilizing either Software Development Implementation and Maintenance (SDIM) or Systems/Software Development Lifecycle (SDLC). They both include a detailed Computer Systems Validation and a Change Control process to ensure safe and efficient management. Both SDIM and SDLC cover the full project lifecycle from the initial idea through design, test, deployment, (including any iteration for change) and the final phase. The change management process has its own set of relevant terms, starting with Continuous Improvement, Kaizen or Six Sigma, all of which aim at long term improvements in an operational or manufacturing process. If an issue is uncovered, a different set of tools and techniques can be used to investigate and remove or rectify the issue. These include Root Cause Analysis, Corrective and Preventative Action (CAPA), and Poke-Yoke (Japanese technique also called Error Proofing).

A Quality Assurance and/or a Quality Management System will help you deal with the overall aspects of planning and control and should incorporate the relevant GxP methodologies as well as some tools and techniques used within the change management process. Relevant accreditations, for example ISO, will fall into this area.
Have you managed to successfully navigate the methodology minefield? Do you have experience with SDIM or SDLC? Share your advice here.

These guidelines are focused on the use of electronic records and electronic signatures for life sciences companies, such as Pharmaceutical, Medical Device, Biotech, Biologic, Clinical or Contract Research Organizations as well as other FDA-regulated industries. In short, life sciences companies need to implement controls for software and systems involved in processing electronic data that include audits, system validations, audit trails, electronic signatures and documentation. Companies that need to comply are those that ‘manufacture’ in or wish to ‘import goods’ into the United States.

The guidelines go on to define the criteria under which electronic records and electronic signatures are considered to be trustworthy, reliable and generally equivalent to paper records and handwritten signatures. The FDA states that Part 11 applies to records in electronic form that are created, modified, maintained, archived, retrieved, or transmitted under any records requirements set forth in Agency regulations.
The relevant records, as well as documentation for the systems, must be available for inspection by the FDA. In order to pass inspection:

• Signatures need to be two part (username and password)
• Relevant validation documentation needs to be in place
• Labels and data need to be strictly version controlled
• Relevant SOP’s must be in place
• An audit history of actions needs to be maintained and secure
• Actions within the system need to be permission based

Of course, if you don’t want to deal with Part 11 and all its components, the alternative is to keep “hard copies” of all required records. If you choose this option, the paper documents are considered to be the authoritative document for regulatory purposes so the computer system doesn’t have to meet the Part 11 requirements.

Any tips on how you are working within the FDA 21 CFR Part 11 guidelines? Have you been through an FDA inspection? Share your thoughts with us!

Economic pressures have had an effect on the way pharmaceutical companies and medical device companies sell their products. There is a lot more emphasis on total cost of treatment, and that makes it increasingly difficult for these companies to differentiate themselves in the U.S. and other established markets. In response, pharmaceutical companies and device manufacturers have started venturing outside of their home countries. Emerging markets, especially China and India but also Brazil and Russia, are adding one billion new patients into the global healthcare system.

While the economy has made things more difficult for the industry, technology has made life a little bit easier and can actually aid in saving costs. Online services, whether it’s ordering supplies, managing product lifecycles or tracking clinical trials data, have become more efficient with the use of tablets, such as the iPad. Health professionals have embraced tablets for their ease of use, portability, and range of uses from data entry, to viewing medical images, to accessing online reference materials and databases. For clinical trials they are already being used for electronic data capture as well as journal entries.

The last area we will look at – compliance – will continue to be top of mind for the healthcare industry, as companies face the threat of potential fines and scrutiny from regulatory bodies. The evolving regulatory environment has impacted the way these companies do business – from labeling requirements and barcodes, to tracking and tracing medical devices and pharmaceuticals through the various distribution channels. As new guidelines come out and deadlines creep closer, this struggle to keep counterfeit drugs and products off the market will continue to shape how the healthcare industry manufactures, labels, packages and distributes its products.

What do you think has had the biggest impact on the healthcare industry? Is it compliance and regulatory issues, a difficult economy or advances in technology? What do you think 2012 will bring?

If you are reading this blog you may also be familiar with Medical Device and Life Sciences specific acronyms for example IQ, OQ, and PQ. For those who are new to the very specific world of Life Sciences, we’ll try to debunk the myths around some of the terminology.

So what is meant by IQ, OQ, and PQ? They are terms that fall under the category of validation and verification.

IQ stands for “Installation Qualification”. The IQ records the installation of the software, and ensures that the installation follows the correct steps.

OQ stands for “Operational Qualification”. The OQ tests or qualifies that the solution is working using test data in general. This maps across to the requirements stated in the Functional Specification, and ensures the product or application meets all the predetermined requirements as stated.

PQ stands for “Performance Qualification” which means that the application, under real life conditions, consistently produces products which meet all predetermined requirements. The PQ is the final test before production (potentially the most important test document you will ever run), testing that the solution works fully in the live environment using live data, and should be based back on a workflow model from your User Requirements Specification.

On top of the IQ/OQ/PQ, you should ensure that you have other key documents including The Validation Master. This will form the detail and coverage of the documentation that you need.

Last thought for the day is that validation requires documented evidence, if the validation process is not documented then it cannot be proven to have occurred. Put another way, your regulatory body will view your validation process as solely a ‘rumour’.

An Untitled Letter is basically a way of citing a violation that does not meet the threshold of regulatory significance for a Warning Letter. A Warning Letter is the most serious of FDA letters, but it’s important to note that it’s not a form of FDA enforcement action. Instead a Warning Letter is just as the name suggests – a ‘warning’ that, if certain corrections or changes are not made, the FDA could take further action.

The intention of the letters is to bring about voluntary compliance without committing the FDA to taking enforcement action. Although there is no immediate enforcement on the part of the FDA, they do expect recipients to make the necessary changes and voluntarily comply with the law. Since Warning Letters are made public under the Freedom of Information Act, it can be helpful to review warnings given to others in an effort to avoid making the same mistakes.

If you do receive a Warning Letter, there is normally a short window (typically 15 days) in which to issue a response to the FDA. The response should include:

1. the steps that have been or will be taken to correct the violations and prevent similar violations;
2. the timeframe within which the corrections will be completed;
3. any reason the corrective action has not been completed within the response time; and,
4. any documentation that shows that correction is complete.

The amount of change that needs to take place to ‘close out’ a warning varies depending upon the violation. If the Warning Letter is in reference to misleading promotional activities, it could be as simple as discontinuing the use of an ad campaign. If, on the other hand, the violation has to do with the manufacturing process of a drug or medical device, there could be a long list of corrective actions that need to be taken. And it may take some time to address them all. In these cases the FDA may decide to withhold certain types of approvals until the issues have been rectified.

Once the violations have been corrected, a Close-Out Letter is issued. This is the official acknowledgement from the FDA that the violations outlined in the Warning Letter no longer exist.

We’d like to hear about your experiences with FDA letters. Have you ever received a Warning Letter? How long did it take before the issue was ‘closed out’?

First, let’s take at look at the Directive itself. It introduces a number of safety features including:

• Serial numbers and tamper-evident seals for safety packs
• Product traceability through the supply chain
• More stringent rules for the importation of active pharmaceutical ingredients (APIs), plus control and inspections of EU plants manufacturing APIs
• Extended control over the API and medicines supply chain, including improved scrutiny of brokers and traders
• Greater oversight of Internet sales, including an official logo for certified online pharmacies
• More stringent sanctions against counterfeiters

All EU member states have just 18 months to turn the Directive into national law. Manufacturers then have three years be compliant. Although the timetable has been set, there are still some details that need to be finalized. This includes specifics around the unique serial numbers that are required on medicine packs. There is some evidence that it will be the ECC200 2D Datamatrix barcode, but other barcode types and RFID are also being considered.

Whichever method is selected, having an identification and tracking system in place will be the foundation for success for the Directive. This will allow all parties – from manufactures to distributers to pharmacists – to check the authenticity of medication by scanning a unique serial number and checking it against a database. Any duplication of serial numbers or other discrepancies can be immediately flagged and investigated.

As with all previous measures, protecting patients is the fundamental goal of the new Directive. What are your thoughts around the new Directive? Do you think this will be a good way to enforce serialization?