Gotta give the FDA some credit here. In addition to its transparency initiative we’ve talk about before, the agency is also trying to remove some of the mystery about how it handles inspections and other inner workings at the FDA. From where I sit, it appears to be a sincere effort and I believe it is helping outsiders better understand what the FDA is trying to do – and how it is trying to do it.

For example, at the second in a new series of monthly online webinars, FDA’s Michael C. Rogers, deputy director, Office of Regional Operations, said today (March 25, 2010)  tried to outline how an FDA inspection tends to work, and what drives inspectors before, during and after an inspection.

As an aside, Rogers also said that the agency currently has about 1,800 total inspectors across its full portfolio, though food gets the bulk of the bodies. He also said there will be more foreign inspections this year, and that the number should continue to grow.

Inspections are based on risk, Rogers said. In other words, the riskier the potential drug, device or food item, the more likely they will be inspected.

Most inspections are unannounced, Rogers said. Before they go on-site, the inspector on inspection team will look at previous inspection reports and identify what corrective actions were promised during prior inspections. They also prepare inspection tool kits with sampling equipment, info to drive inspection based on guidance documents and the Investigation Operations Manual. They also carry a camera to document evidence.

They also conduct “for cause” inspections driven by consumer complaints or other outside activity.

Typically, the inspection begins with a discussion with management to explain the purpose of the inspection, and they try to learn about the corporate structure and any changes made since last inspection. They also ask about complaints, positive tests or returns. Answers to those questions help FDA inspectors focus their on-site efforts.

Next, they go to the physical manufacturing area. They try to observe and understand the on-site process. They ask about acceptance criteria and want specifics on failures, especially the reasons.

Inspectors also draw a diagram of the facility showing the manufacturing process from start to finish. They’re looking for problems in the system and looking to identify critical control points in the manufacturing process.

FDA inspectors then identify procedures in place and assess if company is actually following them. They also look for controls in place to mitigate any contaminated products.

They also look at training and cleaning programs. They also watch employees while they are actually making the product.

If they find evidence of an adulterated product, they collect evidence based on inspector observations and collect samples to prepare their case for possible legal action in court.

At conclusion of inspection, the FDA team meets again with management. They then inform the top company official what is in the official Form 483. That form documents observations during the inspection but does not include final recommendations. They also ask for the firms corrective actions planned or in place to get into compliance.

These corrective actions are taken into account as agency formulates official recommendations.

After the inspection at the firm, the inspector develops a report back at the home office. It includes evidence collected and what the firm has already agreed to do about any shortcomings.

In some cases firms can offer voluntary corrections. But sometimes the agency decides it needs enforcement action such as a warning letter, and can also impose civil and/or monetary penalties.

The webinar was extremely popular. In fact, it “sold out” so many who tried to join it could not get in to the live event. There will be a recording available on Monday March 29.

UPDATE: Slides are now available from this event here in PDF format.

Ken Miles, a 28 year veteran of the FDA, is today a widely-respected industry consultant to the medical device industry. He draws on his extensive experience to help firms effectively and efficiently comply with FDA requirements. Ken’s expertise includes evaluating Good Manufacture Practice (GMP) and Good Laboratory Practice (GLP) compliance, Quality System Regulations, and QSIT certification inspections (Management, Design, Process Controls, and CAPA).

In this multi-part series, we talked with Ken about FDA inspections, CAPA, quality systems, audits, training and more.

Q: When you were with the FDA, what did you look for during onsite inspections at medical device facilities?

A: What I primarily looked for was a robust quality management system that covered all of the key areas: CAPA, internal quality audit findings, training, MDRs and complaints, supplier quality, etc.   Supplier audits are also very important, and they should always tie back into CAPA and management review findings.

Q: You mention training as part of the overall quality management system –  what kind of problems did you see in that area?

A: The most common problem with training is that programs are often inadequate. Oftentimes procedures are either nonexistent or very poorly written. You need to have stringent management commitment and oversight, while also removing irresponsible people who can seriously damage the business. Procedures, management review and training are the primary areas that should generally be addressed through a CAPA program to make it work.

Q: Digging deeper, what were the CAPA-related issues you saw most often during inspections?

A: The one thing I saw often was that companies did not prioritize their CAPA items. You need to prioritize them using a risk-based approach. The highest priority ones should be put at the top of the list. Sounds like an obvious thing, but a lot of companies just throw all CAPA related issues into one bucket with no priority or even closure dates. If you don’t have some sort of prioritization system, you might become weighed down with too many assignments with no end in sight. Prioritize by low, medium and high priority, as well as severity of consequences. That would also imply that you have a target date, or closure date once you implement that program. A lot of companies don’t do that.

Q: You stress the importance of prioritizing and setting due dates for CAPA. Can you give us some examples of what you looked for during your inspections?

A: Medium and serious CAPA issues should be closed out within 30 or 90 days at the most. I’ve seen situations where CAPAs are still hanging out there after two or three years! And I’ve even some that have never closed or resolved! In certain situations, I’ve also seen CAPAs that don’t even have a closure date. Unfortunately, that’s typical of spreadsheet based CAPA systems.

In the next part, we will delve deeper into actual situations, and discuss some of the more egregious things that Ken Miles experienced as an FDA inspector.

Click here for more detailed information about CAPA.

In a recent FDA presentation Foster City, CA, Mark Roh, Regional Food and Drug Director outlined the most common cited 483 items for both pharma and med device companies:

The most common Drug GMP FDA-483 (observational) items:

• Responsibilities and procedures of the Quality Control unit are not in writing
• Written procedures are not followed
• Control procedures not established
• Inadequate specificatons
• inadequate written procedures
• Inadequate failure analysis

The most common Medical Device GMP FDA-483 (observational) items:

• Deficiencies in complaint file system
• Inadequate CAPA procedures
• Lack of written MDR procedures
• Corrective and preventive actions not documented
• Inadequate process validation

This doesn’t mean you won’t be cited for anything not listed in the bullet items or nabbed for all of the above. These are the most common observations cited by FDA personnel during an inspection. So now you may want to go back and take a good hard look at your SOPs, quality management system, CAPA process, complaint handling/MDRs as well as your validation documentation. Obviously training your personnel in these procedures and processes is also key.

Of course, everyone’s goal is not to end up here…

Also, you may want to check out our previous blog entry “Don’t Ignore 483s…it’s in Your Best Interest to Respond in Writing“

The Royal Bank of Scotland (RBS Group) is one of the top 10 banking groups in the US and a principal supplier of corporate finance and debt capital markets services, with retail banking franchises stretching from New England to the Midwest.

In 2005, Juel McQueen, Assistant Vice President, Compliance, and her team in quality assurance needed a solution to track all corrective actions, periodic reviews and verification documents. Since resources for IT were already stretched, they decided to pursue a solution that was available as SaaS (Software as a service). After researching numerous vendors, Ms. McQueen and her team selected CATSWeb OnDemand with the blessing of their IT department because it suited their needs for security, functionality and versatility. CATSWeb is hosted at a SAS 70 Type II certified facility.

Prior to CATSWeb, the QA department was using Microsoft Word and Excel and routing files by email to solve their corrective actions and sign off on documents. Some of these attachments ended up being accidentally deleted or overlooked.  Now, instead of relying on file attachments in email, all users log into the CATSWeb system, view the tasks and documents assigned to them, and electronically sign off on them in a much more accurate and timely manner.

“AssurX helped me get started on the system with initial training, and now I do the necessary configuration changes myself,” said McQueen.

In addition to providing a centralized system for users, CATSWeb also generates executive reports for test results, findings and corrective actions.

The FDA has had many challenges and setbacks in the past few years. From budget cuts to high-level departures, the agency has also faced fury from lawmakers on Capitol Hill over high-profile device, drug and food recalls.

Off the record, current and former FDAers have told us that they know they’ve been understaffed and underfunded in recent years, and that their enforcement capabilities often weren’t up to the task.

Now with a new president and renewed focus on government regulation in Washington, it’s likely pressure from the White House and Capitol Hill will spur the agency to be more active this year and in the next several years, experts say.

In a new white paper from AssurX, you’ll learn why a FDA’s new Good Importer Practices draft guidance is putting the device industry on notice. The white paper explains that the FDA will:

• Hold those at the top accountable for any import problems for their
  products,
• Expect medical device manufacturers to be vigilant about quality, and;
• Increase its emphasis on device firms’ catching and correcting mistakes and
• complaints.

As this new guidance demonstrates, a revitalized FDA today demands that medical device manufacturers to build quality into their products from the very beginning, and to spot procedural problems very early in the product lifecycle.

At its heart, the FDA guidance wants device manufacturers to:

1) Establish procedures for developing corrective action plans, and for taking corrective and preventive actions if non-compliance with a U.S. requirement or a safety concern should arise.

2) Identify and investigate the root cause of non-compliance with U.S. requirements for products they import, or by foreign firms with which they do business.

3) Take steps to remediate and prevent harm from present and future shipments, and to ensure non-compliance and safety problems do not recur.

4) Work with the non-compliant firm to meet U.S. requirements, or stop conducting business with that firm.

“This is part of a broader effort, pushing responsibility for manufacturing on the manufacturer,” says Mark Mansour, an attorney with Bryan Cave LLP in D.C. While the FDA is saying it will inspect and enforce more, manufacturers are counted on as the “first line of defense,” he adds. “Device firms should take this very seriously,” Mansour said.

Request your copy of the FDA Importer Guidance for Medical Devices paper here.