Leveling the Playing Field with recent Draft Guidance

Review and Update of Device Establishment Inspection Processes and Standards, a draft guidance document from the FDA, establishes uniform processes and standards for FDA’s Inspection Process of both domestic and foreign medical device firms. The FDA’s plan is outlined in a short, six-page document released March 29, 2019. The goal is to bring more consistency to the inspection process.

Consistency in investigators’ approaches may better help medical device firms to prepare for inspections and to establish baseline communication and timing expectations. The 2017 FDA Reauthorization Act (FDARA) Section 702(b)(1), introduced section 704(h)(1) of the Federal Food, Drug, and Cosmetic Act (FDCA), which directs the FDA to adopt uniform processes and standards describing how the agency should pre-announce inspections, provide a reasonable estimated timeline for inspections and ensure regular communication with device makers.

FDA investigators use the Quality System Inspection Technique (QSIT) to look at the most important compliance issues and ask questions linked to four major quality system subsystems: management controls, corrective and preventive action (CAPA), design controls, and production and process controls.

Most investigators typically meet the QSIT timeframe for foreign-based inspections where travel time is limited to a set number of consecutive days. However, the QSIT timeframe has not always been followed for domestic audits, which causes prolonged investigations.

As mandated by the FDARA, the FDA reviewed the processes and standards related to medical device inspections and identified uniform processes and standards. The draft guidance establishes the following processes and standards:

• Pre-announcement notice and communication

An FDA inspector will notify establishments by telephone prior to surveillance or preapproval inspections. The FDA retains the authority to conduct unannounced, for-cause inspections. For domestic firms, the announcement will be no less than five calendar days before the inspection. Due to requirements of particular country clearances, the announcement may be more than five days before inspection of foreign firms. Per the guidance, notifications should generally include information regarding the type and nature of the inspection. When possible, the FDA should provide device makers with advance notice of records that may be requested by inspectors.

• Standard inspection time frame

Typically, a reasonable time frame for an inspection ranges from three to six days. The guidance indicates that the FDA will share estimated durations for each inspection at the time of pre-announcement. The duration of inspection may change depending on factors such as the complexity of operations, availability of knowledgeable staff and nature of observed issues. The guidance cautions that inspections may need to be extended for a number of reasons, such as follow-up on postmarket safety information. However, unless an investigator identifies a reason for additional time and communicates it verbally to the device maker, inspections should take place within a standard time frame over consecutive business days.

• Communication during inspections

When able, inspectors should “make every reasonable effort” to discuss with the firm’s management all observations as they are observed or on a daily basis. Such communications may be recorded by the FDA or the firm, so long as there is advance notice and mutual consent.

This new draft guidance appears to be levelling the inspection playing field for domestic medical device firms. Until now, domestic firms might have received a phone call the night before a ‘scheduled’ FDA inspection, saying ‘Hello, we’re coming to inspect your facility tomorrow.’ (Or, they might simply receive a knock on their door.) Once the FDA arrived at a domestic firm, inspectors could take their time (anywhere from a week to month) to conclude their inspection. Now foreign and domestic medical device firms will all be in the same boat.

Industry Feedback

The FDA invited stakeholders to comment on the published draft guidance until May 28, 2019 at https://www.regulations.gov/document?D=FDA-2019-D-0914-0002. On that day (due to industry request), they provided a 30-day extension for additional comments. The Advanced Medical Technology Association (AdvaMed), the world’s largest association representing manufacturers of medical devices, diagnostic products, and medical technology, took the opportunity to provide written feedback on the FDA’s draft guidance.

AdvaMed’s member companies range from the largest to the smallest medical product innovators and manufacturers, with nearly 70 percent of their members generating less than $100 million in annual sales. AdvaMed’s member companies produce innovations that transform health care through earlier disease detection, less invasive procedures, and more effective treatments.

The association’s main concern with the draft guidance for FDA’s Inspection Process is that it does not explicitly recognize the risk-based process for device inspections. The association fears the new guidance might “lead some to believe that a different principle or principles are to be followed in inspections in the future.”

AdvaMed recommended that the draft guidance “be modified to include specific criteria to clearly explain when exceptions to the uniform processes and standards can be made. In addition, FDA’s internal procedures should require supervisory review of any decision to deviate from these uniform processes and standards.”

The following is a brief overview of some of AdvaMed’s proposed changes to the draft guidance:

• Add “If the call is not answered, FDA shall wait for acknowledgement from the establishment, within reason.” Phone calls may be missed to company holidays, personnel vacation, wrong telephone number, etc.
• Add additional means of communication such as e-mail to ensure that companies are appropriately notified
• Add a description of the document types FDA will request during the inspection to the required communication in order to aid in preparation for the inspection and contribute to its efficiency
• Develop a protocol for situations where the primary contact is unavailable (i.e. call is not received and no response is received).
• Change the wording of ‘calendar days’ to ‘business days’ to allow companies sufficient notification to gather requested documents and ensure that key personnel are present
• Develop a standard list of information that will be included in the inspection notification. This should include name of inspector/s, date of inspection, type of inspection, and duration of inspection.
• Add “…whether the inspection will be abbreviated, comprehensive, pre-approval, if “for cause” or not.”
• Add a requirement that communications recorded either by FDA or a manufacturer will not be disclosed to other parties.

Additionally, AdvaMed strongly recommended that “the FDA establish goals for the Agency with respect to consistency and uniformity of inspection of device establishments and regularly review and publish these metrics.” These metrics would enable the Agency and the public to track the FDA’s performance in meeting the goals of FDARA in order to determine whether the revised inspectional process was successful.

To summarize the goals of FDARA as it relates to medical devices:

• follow a risk-based schedule for inspection
• consider the participation of the establishment in international device audit programs
• provide a reasonable estimate of the time frame for the inspection
• provide advance notice of some records that may be requested
• establish regular communications during the inspection
• provide non-binding feedback on inspectional responses as requested

Although Advamed suggested wordsmithing that could help to clarify procedures, having a consistent approach to inspections will benefit everyone in the long run.

StarFish Medical feels that this new draft guidance for FDA’s Inspection Process is definitely a step in the right direction.