The FDA is in a real dilemma. Stagnant budgets, decreased man-power, more regulated
industries, EU harmonization and a new (well not so new) GMP. So the FDA has to figure a
way to get more out of less and still provide the proper consumer protection.
The FDA is looking into two inspectional strategies, one that I explained in the July
Insight report (#7) - HACCP (Hazard Analysis & Critical Control Points), and now the
other called the QSIT - the Quality System Inspection Technique. This new inspectional
approach was outlined in a draft guideline in October.
The FDA calls the QSIT a "top-down" subsystem inspectional approach. The FDA
has keyed 5 areas of the GMP (QS) to be used to determine if a company has met the
requirements of regulations. These areas are: Management Control, Design Controls
Subsystems, Corrective and Preventative Actions (CAPA), Production and Process Controls
Subsystems (P&PC), and Sterilization Process Controls. The FDA has also outlined a
Sampling Plan for reviewing controlled documents. The FDA feels that if these areas are
focused on by the investigators, they will be able to efficiently and effectively
evaluated a company's quality system.
In this draft guideline the FDA has also setup a Decision Flow Chart for the each of
the keyed areas to provide guidance for the investigators hoping to provide uniformity to
this inspectional approach.
The FDA has always used what they now call the "bottom-up" approach to
conducting inspections. For example, they would look at complaints or corrective actions,
find problems and then zero in on specific problems, and evaluating the firm's actions
relating to those problems. With the "top-down" approach, the FDA will look at
the firm's systems for addressing quality before actually looking at specific quality
problems. The FDA plans to "touch-bottom" in each of the listed subsection by
sampling records, rather than starting with record review and working backwards towards
procedures.
In assessing the QSIT, it appeared that the FDA had used this or a similar approach in
the past to evaluate GMP compliance before the FDA went to implementing the
"bottom-up" approach. The bottom-up approach was implemented to try to reduce
the inspectional time and to key into problem areas.
This "top-down" approach is in reality the same approach that is used by the
ISO auditor during their certification inspections. In reviewing each subsection the FDA
does use this top-down inspectional approach except for the Production and Process
Controls subsection where the FDA suggests that when the investigator selects a process
for review it should be based on "CAPA indicators of process problems." This
appear that the FDA would recommend that a bottom-up approach be used for reviewing this
section.
It is the FDA's expectation that it would take 1 man-day for the FDA to review each
subsection or 5 days for an inspection. If the FDA accepted the HACCP inspectional
approach it is estimated be that time could be cut in halve.
Another thing that makes this QSIT inspectional approach look more and more like an ISO
audit is that the FDA investigator will request a copy of the company's Quality Policy,
the high level Quality System Procedures (including Management Review Procedures), Quality
Manual, and a copy of the Quality Plan or equivalent documents to preview prior to the
pre-announced inspection (though the firm will not be required to supply these). These
documents will be returned to the firm at the time of the inspection.
The following is the highlights of each of the subsections.
Management Control
There are 6 areas to be examined in this section.
1. Verify that a quality policy, management review have been defined and documented.
2. Verify quality policy has been implemented.
3. Review organizational structure to assure it includes responsibilities, authorities
and necessary resources.
4. Appointment of a management representative.
5. Verify management reviews are being conducted.
6. Verify quality audits are being conducted.
Design Controls Subsystems
As you could surmise, this section would have the largest amount of inspectional
objectives, 15. If you are familiar with the FDA inspectional guideline for review Design
Control, (Inspecting Design Control), then the objectives are very similar.
The FDA's stated "Purpose/Importance" of the Design Control section is a
follows:
"xxx to control the design process to assure that devices meet user needs,
intended uses, and specified requirements. Attention to design and development planning,
identifying design inputs, developing design outputs, verifying that design outputs meet
design inputs, validating the design, controlling design changes, reviewing design
results, transferring the design to product, and compiling a design history file help
assure that resulting designs will meet user needs, intended uses and requirements.xxx
Corrective and Preventive Actions(CAPA)
This section has 10 inspection objectives which are as follows:
1. Verify the CAPA system procedures address the requirements of the quality system
regulation and have been defined and documented.
2. Determine if appropriate sources of product and quality problems have been
identified. Make sure the data is analyzed to assure that existing product and quality
problems have been identified that may require corrective actions.
3. Make sure trend analysis has been done and unfavorable trends found and addressed
with proper corrective actions.
4. Verify that the data received by the CAPA system are complete, accurate and timely.
5. Verify appropriate statistical methods are used.
6. Determine if failure investigation procedures are being followed.
7. Determine if appropriate actions have been taken when problems are identified.
8. Determine is corrective and preventive actions were effective and verified or
validated prior to implementation. Confirm that corrective and preventive actions do not
adversely affect the finished device.
9. Verify that corrective and preventive actions are properly identified.
10. Determine if information regarding non-conforming product and quality problems and
corrective and preventive actions has been properly disseminated, including to management
meetings.
Production and Process Controls (P & PC)
There are 6 inspectional objectives in this subsections:
1. How to select a process for review - which includes 8 criteria's to use in making
their selection. The top of the list is to review CAPA indicators of process problems,
then a high risk device processes, the degree of risk of the process which could cause
device failures as well as several other areas to base your selection on.
2. Verify that the process is controlled and monitored.
3. If the Device History Records reveal that the process is outside the firm's
tolerance for operating parameters and/or rejects or product non-conformances exist, the
investigator is to determine whether they are handled appropriately. Also in this area the
maintenance and calibration should be reviewed as well as process validation has been
conducted where necessary.
4. Review process validation studies.
5. Review process software validation.
6. Verify that personnel can perform process validation and/or appropriately trained to
implement processes.
Sterilization Process Controls
There are five inspectional objectives in this area. There are as follows:
1. Make sure that the sterilization has been validated.
2. Verify that the sterilization process is controlled and monitored.
3. If it is determined from the Device History Record review that the process is out of
specifications were the appropriate corrective actions taken. Also, review the equipment
adjustment, calibration and maintenance.
4. If software controlled was it validated.
5. Verify that personnel are appropriately trained.
In the narrative portion of this section in the Purpose/Importance preamble, the FDA
does go on and state that for the sterilization process, the primary device specification
is the desired Sterility Assurance Level (SAL). Other specifications may include sterilant
residues and endotoxin levels.
Sampling Plans
Now this is a new approach for the FDA, to outline their record sampling approach. The
FDA always had used a statistical method for picking up samples but never for reviewing
documents. In the most recent Compliance program the FDA outlines how to review complaint
file records but this statistical approach is new to the agency.
This section outlines the FDA Sampling Plans Instructions and the FDA provides tables
for the investigators use. There are two tables one for a Confidence limit of 95%
Confidence and another for 99% Confidence. It is up to the investigator to select which
table they will use.
QSIT vs ISO and HACCP
Were you to carefully review this QSIT approach, you would see that except for the new
sampling plan for record review, this in reality is not a new approach. This was the way
the FDA did their inspections prior to the FDA keying in on complaints and MDRs. The FDA
has always used the QSIT approach for foreign inspections.
Though the FDA would not like to admit it, this QSIT inspectional approach is very
close to the ISO9000 certification auditing method. The ISO audit followed the top down
approach all along determining the firm's quality system and then determining the
compliance to the procedures by reviewing records and documentation. The main difference
between the QSIT and the ISO is still the fact that the ISO audit is a management system
review while the FDA is still keying to the device specifications and assuring that only
devices meeting specifications are released and distributed.
The QSIT and the HACCP inspectional approaches are completely different, though,
probably the best inspectional approach to assure consumer protection would be a
combination of using both approaches.
The QSIT is a top down inspectional approach while the HACCP inspectional approach
using an extensive product and process review to determine what the company is doing to
assure that the device sold is safe and meets specifications.
In conclusion, the FDA likes to change it inspectional approach every few years based
on budgetary conditions as well as the Congressional makeup. Will the QSIT provide the
necessary safety that the American public expects from its regulatory agency is to be
seen? Will the QSIT inspectional approach win out over the HACCP approach should be an
interesting fight to watch? But, to come up with inspectional approaches to reduce
inspectional time, should be monitored closely to assure that all this time savings do not
end up costing the American public real concern for their safety.
The next month's Insight - Year in Review.
