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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Production and Process Controls (P&PC)

Production 

and 

Process Controls 

Subsystem 


 

 

Production and Process Controls

Inspectional Objectives

1. Select a process for review based on:

a. CAPA indicators of process problems;
b. Use of the process for manufacturing higher risk devices;
c. Degree of risk of the process to cause device failures;
d. The firm's lack of familiarity and experience with the process;
e. Use of the process in manufacturing multiple devices;
f. Variety in process technologies and Profile classes;
g. Processes not covered during previous inspections;
h. Any other appropriate criterion as dictated by the assignment

Note: If the process chosen is sterilization, evaluate the process according to the "Sterilization Process Controls" chapter of this handbook.

2. Review the specific procedure(s) for the manufacturing process selected and the methods for controlling and monitoring the process. Verify that the process is controlled and monitored.

Note: Control and monitoring procedures may include in-process and or finished device acceptance activities as well as environmental and contamination control measures.

3. If review of the Device History Records (including process control and monitoring records, etc.) reveals that the process is outside the firm's tolerance for operating parameters and/or rejects or that product nonconformances exist:

a. Determine whether any nonconformances were handled appropriately;
b. Review the equipment adjustment, calibration and maintenance; and
c. Evaluate the validation study in full to determine whether the process has been adequately validated.

4. If the results of the process reviewed cannot be fully verified, confirm that the process was validated by reviewing the validation study.

5. If the process is software controlled, confirm that the software was validated.

6. Verify that personnel have been appropriately qualified to implement validated processes or appropriately trained to implement processes which yield results that can be fully verified.

 

 

Production and Process Controls

 

Production and Process Controls

Narrative

Purpose/Importance

The purpose of the production and process control subsystem is to manufacture products that meet specifications. Developing processes that are adequate to produce devices that meet specifications, validating (or fully verifying the results of) those processes, and monitoring and controlling the processes are all steps that help assure the result will be devices that meet specifications.


checkmark1. Select a process for review based on:

a. CAPA indicators of process problems;
b. Use of the process for manufacturing higher risk devices;
c. Degree of risk of the process to cause device failures;
d. The firm's lack of familiarity and experience with the process;
e. Use of the process in manufacturing multiple devices;
f. Variety in process technologies and profile classes;
g. Processes not covered during previous inspections;
h. Any other appropriate criterion as dictated by the assignment

Note: If the process chosen is Sterilization, evaluate the process according to the "Sterilization Process Controls" chapter of this handbook.

In order to meet the Production and Process Control requirements of the Quality System Regulation, the firm must understand when deviations from device specifications could occur as a result of the manufacturing process or environment.

Discuss with the Management Representative (or designee) the firm's system for determining whether deviations from device specifications could occur as a result of the manufacturing process or environment. The firm may accomplish this requirement via Product and Process Risk Analyses.

chainlinkImportant linkages for these activities include 820.20 Management Responsibility and 820.30 Design Controls.

Select for evaluation a manufacturing process where deviations from device specifications could occur as a result of the process or its environment. The selection of the manufacturing process for evaluation should be based upon one or more of the criteria listed above.

chainlinkImportant linkages to consider at this point include 820.30 (g) Design Validation (risk analysis) and 820.100 Corrective and Preventive Action.

checkmark2. Review the specific procedure(s) for the manufacturing process selected and the methods for controlling and monitoring the process. Verify that the process is controlled and monitored.

Note: Control and monitoring procedures may include in-process and or finished device acceptance activities as well as environmental and contamination control measures. 

All processes that may cause a deviation to a device's specification and all validated processes must be monitored and controlled in accordance with established procedures. Just because a process is validated, does not mean verification activities utilized to monitor and control the process are unnecessary. Examples of some verification activities associated with validated processes include review of process parameters, dimensional inspections, package performance tests, sterility and EO residual testing.

For the process chosen, confirm that the established Process (and where applicable Environmental and Contamination) Control, Monitoring and Product Acceptance Procedures maintained by the shop floor are the most current approved revision contained within the Device Master Record (DMR). Most firms maintain a "Master List" of the most currently approved documents. This list can be verified against the DMR and brought to the shop floor to compare with the currently available documents.

Verify that the building is of suitable design and contains sufficient space to perform necessary operations.

Verify that the control and monitoring activities demonstrate that the process is currently operating in accordance with the DMR. This should be done on the shop floor by reviewing work instructions, product acceptance criteria and results, control charts, etc.

While on the shop floor, make note of one significant piece of process equipment and one significant piece of inspection, measuring or test equipment (preferably from a finished device acceptance activity). Prior to concluding the inspection, confirm that applicable maintenance activities (preventive maintenance, cleaning, adjustment etc.) are performed as scheduled for the chosen piece of processing equipment. Also confirm that the piece of inspection, measuring or test equipment was controlled and calibrated.

NOTE: Control and monitoring procedures may include in-process and/or finished device acceptance activities as well as environmental and contamination control measures.

Once you've reviewed the process control and monitoring activities on the shop floor, use the sampling tables and select for review a number of Device History Records (DHR's including monitoring and control records, etc.) from recent production runs. If the process is run over more than one shift, your review should include DHR's from all shifts. Verify that the product was manufactured in accordance with the Device Master Record.

This verification must include a review of the purchasing controls and receiving acceptance activities regarding at least one component or raw material (preferably determined essential for the proper functioning of the device).

In addition, this verification must include a review of in-process and final finished device acceptance activities and results as well as environmental and contamination control records (if applicable). Verify that sampling plans for process and environmental control and monitoring activities are based upon a valid statistical rationale.

If your review of the device history records reveals no anomalies proceed to Objective 4.

If evidence that the process or environment are not controlled and monitored (no control and monitoring activities, not operating within most currently approved parameters or reject limits, etc.) is observed, this may be a major production and process control deficiency.

Important linkages to consider at this point include Documents, Records & Change Controls, (820.40 Document Controls, 820.180 Records, 820.181 Device Master Record, 820.184 Device History Record,), Facilities and Equipment Controls (820.72 Inspection, Measuring, and Test Equipment), Material Controls (820.50 Purchasing Controls, 820.60 Identification, 820.65 Traceability, 820.80 Receiving, In-process, and Finished device acceptance, 820.86 Acceptance Status, 820.130 Packaging, 820.140 Handling, 820.150 Storage, 820.160 Distribution) and 820.250 Statistical Techniques.

checkmark3. If review of the Device History Records (including process control and monitoring records, etc.) reveals that the process is outside the firm's tolerance for operating parameters and/or rejects or that product nonconformances exist:

a. Determine whether any nonconformances were handled appropriately;
b. Review the equipment adjustment, calibration and maintenance; and
c. Evaluate the validation study in full to determine whether the process has been adequately validated.

If process or product nonconformance(s) are identified based upon these activities, determine whether the nonconformance(s) were recognized by the firm, handled appropriately and fed into its CAPA system. Review (if appropriate) the firm's nonconforming product control, review and disposition activities and any CAPA's indicated. If the firm's Quality System failed to recognize the process or product nonconformance(s) or take appropriate CAPA, this may be a major CAPA deficiency.

NOTE:

1. If the firm engages in a number of manufacturing processes, Investiga- tors should avoid repeatedly selecting the same process every time the firm is inspected.

2. If Device Labeling is the process chosen, include in your inspection coverage of the requirements of "820.120 Device Labeling".

Review the firm's equipment adjustment, maintenance and calibration records for the process and (if appropriate) comprehensively evaluate the Validation Study as described in the "Note" contained within the narrative discussion of Objective 4. These activities may provide further insight into the cause of the nonconformance. If the firm has recognized and implemented appropriate CAPA's regarding the observed nonconformance(s), then the quality system was effective. Proceed to Objective 5.

chainlinkImportant linkages to consider at this point include Corrective and Preventive Action, Material Controls (820.90 Nonconforming product), and Facilities and Equipment Controls (820.72 Control of inspection, measuring and test equipment).

checkmark4. If the results of the process reviewed cannot be fully verified, confirm that the process was validated by reviewing the validation study.

If the results of the process can be fully verified, proceed to Objective 5.

If the chosen process requires process validation, review the established Process Validation Procedure(s). The regulation does not require a general Process Validation Procedure. Therefore, separate procedures may be established for each individual Process Validation Study. Remember, the definition of "Product" contained within the regulation includes components, in-process devices and finished devices. Verify via a review of the Process Validation Study Summary (if available) and Approval, that objective evi-dence has demonstrated that the process will consistently generate a product or result meeting its predetermined specifications. With respect to process validation, an example of a "result" is a Sterility Assurance Level (SAL). If a Validation Study Summary and Approval is not available, a review of objective evidence within the validation study will be necessary.

NOTE:

If there are indications (via review of DHR's, the Process Validation Study Summary and Approval, the assignment, CAPA system, etc.) of unresolved, potential problems with a validated process, in addition to a review of process monitoring and control activities, a comprehensive validation study review should be conducted. This review should include determining whether: 1. The instruments used to generate the objective evidence were properly calibrated and maintained prior to the validation study; 2. Predetermined product specifications were established; 3. Test sample sampling plans were based upon a statistically valid rationale; 4. Objective evidence demonstrates predetermined product specifications were met consistently; 5. Process tolerance limits were challenged; 6. Process equipment was properly installed, adjusted and maintained; 7. Process monitoring instruments are properly calibrated and maintained; 8. Changes to the validated process were appropriately challenged; and, 9. Process operators are appropriately qualified.

If the objective evidence demonstrates that the process is not capable of consistently producing a product or result meeting its predetermined specifications, this is a major process validation deficiency. Important linkages to consider at this point include Management Responsibility (including 820.25 Personnel), Design Controls (820.30(h) Design Transfer), Corrective and Preventive Action, and Facilities and Equipment Controls (820.72 Inspection, Measuring and Test Equipment) and 820.250 Statistical Techniques.

checkmark5. If the process is software controlled, confirm that the software was validated.

If the process chosen is NOT controlled with software, proceed to Objective 6.

If the process chosen is automated with software, review the software requirements document, software validation protocol, software validation activities, software change controls and software validation results to confirm that the software will meet user needs and its intended use. If multiple software driven systems are used in the process, challenge one based upon significance.

An important linkage to consider at this point is Material Controls (820.50 Purchasing Controls). For example, for software developed elsewhere, confirm that appropriate software and quality requirements were established and provided to the vendor and that purchasing data (and validation results) support that the requirements were met.

checkmark6. Verify that personnel have been appropriately qualified to implement validated processes or appropriately trained to implement processes which yield results that can be fully verified.

Using the sampling tables, select a number of training and qualification records for process operators and employees conducting Q.C. activities related to the chosen process. Where a process is operated over more than one shift, training records from all shifts should be included within your review. Confirm that the employees are aware of the device defects that may occur as a result of improper performance of their assigned responsibilities. Confirm that employees conducting Q.C. inspections and tests are aware of the defects and errors that may be encountered while performing their assigned responsibilities.

An important linkage to consider at this point is Management Responsibility (820.25 Personnel).