Following a paperless paper trail

There is a change coming in the way new drugs are developed, documented and approved in the United States. This change is driven by the 21 Code of Federal Regulations Part 11, or simply 21 CFR Part 11, and it ultimately benefits everyone who uses medicine in this country. It is the most important and demanding regulation to hit the pharmaceutical industry in the last 20 years, and it started with the laudable goal of speeding up the process to approve new drugs. The accelerator is a shift from paper-based to computer-based record keeping for drug development and approval.

Consumers, drug manufacturers and the Food and Drug Administration (FDA) all want new medicines to become available as quickly as possible for the relief of the people who need them. Understandably, drug manufacturers and patients with serious illnesses are frustrated by the deliberate pace of the FDA approval process. This pressure to release drugs quickly is balanced by the FDA's mandate to protect the public from unsafe medications and unwanted side effects.

To help speed the lengthy drug development process the Pharmaceutical Manufacturing Association (now called the Pharmaceutical Research and Manufacturers of America) asked the FDA for approval of electronic signatures, or signatures that are applied by computer, rather than traditional hand-written signatures. Electronic signatures use encrypted algorithms with an individual's password to create a signature as unique as one scrawled with a pen. Such signatures are used on numerous documents that are reviewed by the FDA during the application process for new drugs. The FDA agreed to allow electronic signatures but took the additional step of creating new rules governing the handling of all drug development records by computer. The situation was summarized by former FDA inspector Martin Browning: "The industry wanted to have a rule on electronic signatures, but what they got was a rule on electronic records."

Supporting computer-based research and development

Pharmaceutical companies perform large amounts of electronic, or computer-based, research to develop new drugs. The documentation of this research is what supports a company's claim that a drug safely does what it is intended to do. Obviously, accurate records are an important part of the drug development and application process. Keeping good records of the research proves the validity of the conclusions reached by the scientists, and helps prevent bias in the interpretation of studies.

The 21 CFR Part 11 rule, enacted in 1997, sets minimum requirements for electronic records used in submissions to the FDA. The key areas addressed by the rule are data security, data integrity, audit traceability and signature authenticity. Data security is assured by limiting access to pharmaceutical companies' computer systems. Data integrity is protected by preventing changes to research data and linking data and outcomes so original results can be reproduced at any time. Audit traceability is achieved by computer-controlled, operator-independent documentation of who did what to the results and when.

The challenge for pharmaceutical companies

Applying the new standards for data security, integrity, and traceability in pharmaceutical development is a very difficult task. Data security requires implementing controls on physical access to the computer--known as operating a closed system--or using security codes as barriers to entry into the system. Data integrity and traceability require specialized software that records which test equipment was used and who operated each piece of test equipment, and then stores the equipment settings and data evaluation parameters for each experiment. Additional security software prevents uncontrolled and undocumented changes from being made to the data at a later time. This stored data must be able to be retrieved and replayed for FDA inspectors for up to 10 years (and in some cases more than 10 years). It is clear that responding successfully to the challenges posed by 21 CFR Part 11 requires cooperation between pharmaceutical manufacturers and the companies who provide them with the high-technology they need.

Agilent's response to 21 CFR Part 11

Through a unique combination of product features and professional services, Agilent is helping its customers meet these new demands and bring the next miracle drug to market. Agilent helps their customers comply with 21 CFR Part 11 through its vendor assistance program. Vendor assistance provides services vital to companies performing drug research such as writing equipment specifications, installing and certifying equipment, and providing standard operating procedures for qualification tests.

An example of 21 CFR Part 11 compliant software is part of Agilent's ChemStation Plus. The ChemStation's database module, ChemStore C/S, ensures compliance through:

• Limited and authorized systems access through logical security controls

• Limited and authorized access to selected tasks and applications

• Secure, operator independent electronic time stamped audit trail with information on who changed what

• Generation of electronic signatures with authenticated attachment to relevant records

For existing ChemStations, the Security Pack add-on software module is available to bring equipment in the field up to 21 CFR Part 11 standards.

For more information

Agilent is dedicated to developing technologies that accelerate the pace of drug discovery and research. To learn more about some of our 21 CFR Part 11 compliant products please visit the ChemStation Plus Security Pack section of our Web site.

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