Medical Device Link.

Some medical device manufacturers see documentation as nothing more than jumping through hoops for FDA. Certainly, meeting FDA requirements is essential, but if documents are developed only for that reason, then they’re not truly serving their purpose. Documents should not be dusted off for inspection when the auditors come by and then be hidden away; they should be used every day by employees.

What to Expect during an FDA Audit

An inspection or audit is an evaluation of conformance to a particular standard or set of standards. FDA conducts inspections to enforce the Federal Food, Drug, and Cosmetic Act. For the medical device industry, this includes the following regulations:1

• Quality system (QS) (21 CFR Part 820).

• Medical device reporting (MDR) (21 CFR Part 803).

• Medical device tracking (21 CFR Part 821).

• Corrections and removals (21 CFR Part 806).

• Registration and listing (21 CFR Part 807).

Figure 1. (click to enlarge) FDA’s inspection process follows the 10 steps outlined above.

FDA follows a disciplined inspection process (see Figure 1). Generally, an FDA investigator from the local district office contacts the responsible site person a short time before the audit to set a visit date. The investigator may become suspicious if there are attempts to delay the visit more than 10 days. (Keep in mind that FDA can also show up unannounced—even more reason to have effective and accurate documents in place that employees use.) The investigator may request copies of the quality policy and high-level quality system procedures (including management review procedures), the quality manual, the quality plan, or equivalent documents to review prior to the inspection. A company is not required to provide these, but they may help facilitate the on-site audit.

Once the audit date is determined (usually three to five days from contact), taking the following steps will help a company prepare:

• Notify key staff of the impending visit.

• Assign a site facilitator to assist the investigators.

• Reserve adequate workspace for the investigator and make sure a copier is available.

• Review how to appropriately answer questions.

Because most FDA audits are done with little or no notice, it is necessary to be in substantial FDA compliance at all times. Effective documentation is essential to ensuring this compliance, because it would be nearly impossible to achieve consistency across locations, shifts, and individuals without thorough and specific documents.

Indeed, ensuring compliance is the whole point of short- or no-notice audits. Telling FDA, “you caught me on a bad day” just doesn’t work. Most regulatory audits of a device company examine items such as instrument calibration; documentation practices; handling of out-of-specification results, raw data, and traceability of data; training records; handling and audits of data; standard operating procedures (SOPs); change control; validations; and log books—all of which need careful documentation. The inspection is heavily focused on management responsibility and oversight of functions.2

Upon arrival, the investigator(s) display credentials (e.g., photo ID) and FDA Form 482, Notice of Inspection. The inspection is conducted during normal business hours and may involve up to three investigators. After some brief introductions, the investigators may want to tour the facility. They will then start requesting documents that support the area being investigated. The area generally focuses around a fairly small target, such as a product, a new filing, a portion of the company’s SOPs such as corrective and preventive actions.

Be sure to keep a copy of everything the investigators take with them to facilitate future communications about the inspection—and to make sure your employees still have documents from which to reference their work. Do not provide financial data such as salary or budget information except as specifically required for items such as clinical investigations. Also, do not provide personnel data except for documents that indicate individuals’ qualifications and their training.

Investigators may also wish to interview employees associated with the area being inspected, although they may question any employee during an inspection. The investigators may use the compliance program guidance manual as an interview guide.1 Appropriately answering questions includes being polite and cooperative. It’s perfectly acceptable to ask for clarification if needed—don’t guess or speculate on what the inspector may be seeking. Answer factually and briefly—don’t elaborate or answer more than was asked. Refer to an SOP to find an answer. Answer honestly when you don’t know an answer or when you need to do some additional research. Reference appropriate documentation for help in answering questions about complex operations. Answer only questions that are within your area of responsibility. Certainly do not answer anything off the record.

At the end of each inspection day, the investigators review their findings with site representatives. At the completion of the inspection they conduct an exit interview to review the findings, clarify misunderstandings, and describe any deviations. If there are significant findings, the investigators leave an FDA Form 483, Notice of Observations. Some of the most common negative observations can be avoided with proper documentation.3 Diligent respect to the following activities can ease any audit experience:

• Adhere to protocol.

• Keep adequate and accurate records.

• Report adverse effects.

• Follow SOPs.

• Specify, maintain, and follow procedures.

Table I. (click to enlarge) Three types of classification and the corresponding letters that result from an FDA inspection.

After returning to the district office, the investigators write an Inspection Report and forward it to FDA headquarters for evaluation. FDA then classifies the inspection and sends a letter to the site. Table I describes the three types of classification and the corresponding letters. Table II compares data from random 483 letters, highlighting those with problems related to documentation.

Documentation to Develop

Table II. (click to enlarge) Data from eight random 483 letters to device manufacturers. As the table shows, some aspect of documentation was implicated in 78% of problems cited in these eight letters.

Documentation is probably the single most important aspect of an audit. As the saying goes, “if you didn’t write it down, you didn’t do it.” So, what all needs to be documented? Generally, there should be a fully documented, approved SOP in place for every operation related to the manufacture of the device. Typically SOPs include an introduction on how to write an SOP, as well as sections covering the creation of SOPs and change control training; instrument operation and calibration procedures; and sampling, receiving, testing, and disposition of raw materials, in-process materials, and finished products. They can also include analytical methods validation and use of analytical standards; specifications and validation; log book procedures; handling of tests, reserve samples, and records; and failure investigations and corrective actions, to name just a few.

The handling of one particular variety of SOPs, corrective and preventive actions (CAPA), has been, and is still, a hot topic. Regulatory auditors almost always look at how a device manufacturer handles and documents CAPA issues. The manufacturer must have a mechanism for CAPA investigation that strives to find root causes of problems, and that specifies what action or actions are to be taken as a result of that investigation. Improper handling of CAPA is a deficiency often cited on FDA-483 reports and can be avoided by having a sensibly written CAPA SOP.

Other essential documentation includes the log books, calibration records, test results, etc. that prove SOPs are being followed. Just having the documentation isn’t enough, though; each SOP must also be issued in a controlled manner, preferably electronically, using software that is compliant with 21 CFR Part 11. Issuing SOPs in a controlled manner means having a system in place that allows you to generate and modify SOPs. Such modification should include review and approval of each new or revised SOP. A controlled procedure also ensures that only the most recent version of an SOP is in use; all older versions should be appropriately archived. And be sure to track each document’s change history, including justification for each change.

Developing Great Documentation

Although some medical device companies may try to use their own employees to write SOPs and other documents, it’s better to work with documentation experts. The ability to organize information well is crucial for good documentation. More importantly, a third party can bring some distance, a critical eye, and specific expertise to preparing and writing documents. Such factors are especially important because those documents will serve as the first line of proof of regulatory compliance. Usually, employees’ skills are better used on the work for which they were hired, and at which they are experienced and adept. Individuals very close to a process may not be able to document it accurately. This might sound surprising, but those who follow a process routinely may leave out steps that seem obvious to them. However, explicit documentation would be necessary for someone who is new to the process. Highly organized documentation is also necessary for repeatability, which is essential to quality.

The key to a good audit is to have a sound CGMP program in place and to follow it judiciously. Doing so will ensure a regular and ongoing state of compliance. A third-party documentation vendor, in addition to providing an objective look at your system, can assist in developing or improving your site’s CGMP program.

A Closer Look at Documentation

Documentation experts can help members of management define, refine, and document their procedures. Hold joint meetings with key personnel and an independent FDA consultant early in the process to discuss and work out issues. No matter the type of document, the process is the same: asking lots of detailed questions, often raising issues that haven’t been considered before. Documentation experts need to know details of every procedure, i.e., how it is done, who does it, what the paper trail is, where the associated equipment comes from, how it is identified and traced, and so on, to ensure that critical steps and tasks are covered.

After a procedure or process has been defined, documentation should drive its performance. This can be difficult, because getting employees to follow documentation may require a paradigm shift. The key is to be consistent. Make sure documentation is out on the floor with the employees who need it. If employees don’t have easy access to documentation, then it will be worthless to them. Have documentation available in the language(s) your employees speak and understand. Use visual elements to communicate. Regardless of language, most people understand information better if it includes illustrations that augment text. If you have a large set of documents, make sure your employees understand how the documents fit together and what kinds of information can be found in each. Be concise—don’t repeat information across documents. Write clearly and unambiguously. Tell people what they need to do and what they need to know to do it—nothing more. Use indexes, tables of contents, sections, subheads, and other ways of arranging information so that it can be used easily. Replace unwritten rules with documentation. Have supervisors and senior employees use documents to answer questions. That will help to ensure consistent, accurate answers and reinforce the use of documentation.

Once processes are analyzed and documents accurately represent them, convince employees to actually use these documents. The goal is to improve production quality, increase inspection readiness, and raise company profits. Additionally, these documents can be used for training purposes. A document management system can help key personnel make changes to documents when needed.

Having a comprehensive set of documents in place not only meets FDA requirements, but also makes employees’ tasks go more smoothly and efficiently. Good documentation requires an investment in both time and money. But it’s an investment that can more than pay for itself in terms of productivity and profits.

Larry Elwell is director of engineering services at Prima Communications Inc. (Kalamazoo, MI).