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U.S. Department of Health and Human Services

Medical Devices

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8. Quality System

INTRODUCTION

DESIGN CONTROLS

DEVICE MASTER RECORD

DOCUMENT CONTROL

INCOMING AND IN-PROCESS ACCEPTANCE ACTIVITIES

PROCESS VALIDATION

PROCESS CONTROLS

FINISHED GLOVE ACCEPTANCE ACTIVITIES

NONCONFORMING PRODUCT

LABELING AND PACKAGING

COMPLAINT HANDLING

STERILIZATION

QUALITY SYSTEM AUDITS

EMPLOYEE TRAINING

EXHIBIT #1 SAMPLE GLOVE SPECIFICATION (DEVICE MASTER RECORD)

EXHIBIT #2 SAMPLE COMPONENT RECORD (INCOMING CONTROLS)

EXHIBIT #3 SAMPLE IN-PROCESS RECORDS (IN-PROCESS CONTROL)

EXHIBIT #4 IMPACT OF MANUFACTURING PROCESSES (PROCESS CONTROL)

EXHIBIT #5 MONITORING AND PROCESS PARAMETER CONTROL RECORD

INTRODUCTION

Quality System Regulation

Manufacturers of medical gloves must meet the requirements of the Quality System regulation for medical devices (21 CFR part 820). The Quality System regulation at 21 CFR 820.5 states that “each manufacturer shall establish and maintain a quality system that is appropriate for the specific medical device...manufactured.” This system must meet the requirements of the Quality System regulation.

Proper quality control procedures help to control or eliminate manufacturing defects, such as pinhole defects. FDA also believes that compliance with the Quality System regulation and implementation of design controls will minimize water soluble proteins, chemical residues, and other problems common to the manufacture of medical gloves.

This chapter provides guidance that is particularly relevant to the manufacture of medical gloves and other natural rubber latex medical devices. This chapter does not cover all requirements of the Quality System regulation. We recommend that you use this chapter as a supplement to the Medical Device Quality Systems Manual.

Medical Device Quality Systems Manual: A Small Entity Compliance Guide

DESIGN CONTROLS

The design control requirements are basic controls needed to ensure that the device being designed will perform as intended when produced for commercial distribution. Although surgeon’s gloves are subject to design control requirements (21 CFR 820.30(a)(2)(ii)), patient examination gloves are not.

Design Input for Medical Gloves

When developing design inputs for a new or modified glove design, you should answer questions pertaining to the intended use of the device as well as the needs of users and patients. The questions and answers will vary for different types of gloves and accessories. Some typical design input questions include:

  • Where will the new glove be used?
  • Who will use the new glove?
  • How will the new glove be used?
  • With what devices will the new glove be used?
  • Does the glove need to be resistant to certain chemicals?
  • How long will the new glove be used?
  • What is the appropriate labeling and packaging?
  • What are the regulatory requirements for the glove and any performance claims?
  • Are there any other questions that are specific to the glove you are developing?

Design input requirements should identify all of the desired performance, physical, safety, and compatibility characteristics of the proposed glove design. Design input also includes requirements for labeling, packaging, and manufacturing. You should consider shelf life under design input as part of the activities to meet user and patient needs. FDA considers shelf life to be a significant factor in meeting user needs. The design input requirements are ultimately converted to the specifications for the finished glove.

You must have a design input requirement procedure (21 CFR 820.30(c)) in order to develop the glove specifications. The specifications, among other factors, should address:

  1. Performance and efficacy;
  2. Human factors, fatigue, donning, color, and odor;
  3. Length, cuff, size, and thickness;
  4. Chemical safety;
  5. Allergenicity (protein levels);
  6. Pinhole AQL;
  7. Biocompatibility;
  8. Glove compatibility with blood, saline and any intended chemical contact;
  9. Environmental compatibility;
  10. Packaging (in a separate specification document);
  11. Labeling (which may provided in a separate document or in the glove primary specification, as appropriate);
  12. Special labeling claims;
  13. Any other regulatory requirements; and
  14. Professional associations’ recommendations.

The final glove specifications should cover all significant glove characteristics. The glove specifications may refer to other specifications or standards. Specifications should address characteristics or factors such as biocompatibility (chemicals and proteins), barrier integrity, packaging protection, shipping stability, and shelf life, if applicable.

Design Verification

You must establish and maintain procedures for verifying the device design (21 CFR 820.30(f)). Design verification confirms that the device design meets the design input requirements. You should verify the design of gloves, packaging, and any subsequent changes by testing parameters such as tensile strength, elongation, barrier integrity (pinholes), protein residues, chemical residues, biocompatibility, correct labeling, and shelf life. We recommend that you use test methods provided in recognized consensus standards for your verification testing whenever possible.

Design Validation

While design verification confirms that the device design (outputs) meets the design requirements (inputs), design validation is conducted to determine whether the device meets user needs. The difference between design verification and design validation is illustrated in the following diagram:

This Design and Development diagram depicts the flow of the design process as well as the difference between design verification and design validation. The design process begins with user needs, follo

 

Validation for medical gloves may include use under real or simulated conditions. Validation assures that the donning ability, strength, thickness, feel, size, shape, texture, holding ability, tactile sensitivity, lack of fatigue, lack of irritation, color, and odor of the gloves are satisfactory to users.

Generally, clinical testing is not required for gloves that are substantially equivalent to gloves legally marketed in the U.S. However, if clinical testing is conducted, e.g., testing for skin sensitization to chemicals, you should perform appropriate laboratory and animal verification (e.g., performance, reliability, and biocompatibility) testing prior to human clinical or simulated use testing.

DEVICE MASTER RECORD

Title 21 CFR 820.3(j) states a “Device master record means a compilation of records containing the procedures and specifications for a finished device.” A Device Master Record (DMR) is a comprehensive record of all of the procedures and instructions required to manufacture each type of glove. A DMR contains or refers to the location of documents for manufacturing and processing activities, such as procurement, processing, labeling, test and inspection, and packaging. The DMR also contains information on the design, formulation, specifications, complete manufacturing procedures, quality assurance requirements, acceptance criteria, packaging, and labeling of a finished glove.

A DMR for medical gloves manufactured by complex processes, such as latex dipping, usually consists of many documents. For convenience, many medical glove manufacturers generate an index or table of contents which lists all of the documents in a DMR. The DMR should contain a glove (device) specification. Generally, a medical glove specification will include the following: 

  • product trade and common name(s)
  • intended use(s)
  • performance characteristics, such as tensile strength and elongation
  • regulatory classification
  • physical characteristics, such as cuffs, thickness, length, and size
  • environmental limitations and product shelf life or expiration date
  • user safety characteristics such as a pinhole and chemical residue limits
  • water-extractable protein limit
  • powder/particulate/debris limit
  • packaging and labeling specifications

Exhibit #1 provides a sample specification for inclusion in the Device Master Record.

A DMR should contain specifications for the content and design of labeling. Labeling claims should match glove characteristics and contain required labeling. Gloves that have false or misleading labeling are misbranded under section 502 of the Act. (See chapter 4 on labeling.)

Record Retention

The Quality System regulation at 21 CFR 820.180(b) states “All records required by this part shall be retained for a period of time equivalent to the design and expected life of the device, but in no case less than 2 years from the date of release for commercial distribution by the manufacturer.” You should retain records for most medical gloves for two years or for as long as the labeled expiration/shelf-life date, whichever is longer.

DOCUMENT CONTROL

Many written documents are needed to manufacture gloves. Written procedures should cover the following areas:

  • glove design
  • processes
  • components, coagulants, dewebbers, donning lubricants
  • labeling and packaging
  • colorants, flavors, odorants, antimicrobials, anti-ozonants, anti-oxidants
  • environmental control, facilities, employee practices
  • production and measuring equipment
  • manufacturing materials

Specifically, we recommend that written procedures address the following:

  • cleaning tanks and equipment in accordance with a schedule
  • preventing or reducing of air bubbles during compounding
  • ball milling chemicals to yield proper size and prevent contamination
  • filtering compounded polymer solutions
  • inspecting formers on and off line for defects and debris
  • washing formers each (or as designated) line cycle
  • protecting wet formers from dust and other debris
  • controlling the environment by screening or closing doors and windows
  • protecting dipping tanks from dust and other debris
  • maintaining covers, shields, and ledges to reduce debris falling into processing tanks
  • controlling the use of grease and oil to eliminate drips into the processing tanks,
  • inspecting lines, tumblers, etc., to assure there are no protrusions, vibrations that could cause product defects
  • cleaning equipment
  • cleaning floors
  • maintaining floor or other waste material drains
  • controlling leach tanks function
  • controlling protein wash/rinse tanks function (i.e., manufacturing material is being removed)
  • controlling chlorination and neutralization
  • identifying and controlling finished gloves to prevent mix-ups
  • analyzing defective gloves (when acceptance criteria are not met) to determine the cause of the problems,
  • personal hygiene, such as hand washing

You should establish and maintain procedures to control all documents (21 CFR 820.40). Whenever there are changes to standard operating procedures, quality assurance procedures, data forms, and product specific documentation, the review and approval must come from individual(s) in the same function or organization that reviewed and approved the original (21 CFR 820.40(b)). See the Quality System manual for additional information on change control.

INCOMING AND IN-PROCESS ACCEPTANCE ACTIVITIES

Components and Manufacturing Materials

Components are materials used during manufacturing that are intended to be part of the finished gloves. Examples of such products are latex concentrate, various chemicals that are mixed with the latex or polymer during compounding (such as antioxidants), and donning lubricant.

Manufacturing materials are substances used to help in the manufacturing process but are not intended to become part of the finished gloves. Examples include ingredients contained in the dipping compound (such as accelerators), former release chemicals, and any detergents that are used to clean the formers. Corn starch (powder) is also a manufacturing material if it is added and then removed for “powder-free” gloves.

Component Qualification

Qualification is the determination of suitability of components and consists of verifying through documented testing, evaluation, and review that a manufacturing ingredient or component will reliably perform its function. Well characterized manufacturing ingredients or components that are used in their normal application may need minor testing. New products, such as donning lubricants, protein modified latex, or new accelerators, will require substantial testing.

For surgical gloves, you should maintain a design history file of any qualification (verification) testing of components, raw materials, and manufacturing materials. This record should include the product identity, testing methods that were used, who performed the testing, date, and the actual test data and results.

Specifications for Incoming Components

Specifications for components and manufacturing materials should state essential properties to assure the quality of the finished product. The specifications should adequately describe the characteristics, dimensions, design, chemical purity, performance, and any other feature or parameter necessary to assure receipt of the product desired. For some components, such as donning powder, the specifications should include a limit on microorganism contamination. Component and material specifications should be part of the device master record.

Natural rubber latex is a biologically produced substance that may vary considerably depending on climate, season, local environmental factors (including soil composition), and specific tree varieties. Therefore, you should have as many applicable specifications for the incoming latex as feasible in order to reduce some of the inherent variability in this component. You should be aware that various applicable standard tests and specifications are included in documents, such as ASTM D1076-02, Standard Specification for Rubber-Concentrated, Ammonia Preserved, Creamed, and Centrifuged Natural Latex.

Acceptance Criteria, Testing, and Documentation

To the extent feasible, you should have specific acceptance criteria for components and manufacturing materials. Acceptance criteria are the attributes of a product that determine its acceptability, such as appearance, color, dimensions, mechanical stability, percent solids, preservative levels, protein levels, viscosity, purity, pH, or performance characteristics.

You should document the inspection, testing, and acceptance or rejection of raw materials, manufacturing ingredients, and components. Exhibit #2 provides a sample record for receiving incoming latex.

If you use a contract laboratory to test components, materials, and manufacturing materials, the laboratory becomes an extension of the glove manufacturer’s quality system. The glove manufacturer is responsible for assuring that the contractor’s test and inspection procedures and quality system are acceptable. Typically, you can obtain this assurance by documented audits.

Component Storage

You should store components so that they are protected from moisture, dirt, and insects. You should store components or materials, such as latex and starch, in a manner that retards the growth of microorganisms. FDA suggests that you store components and manufacturing materials under conditions that prevent their deterioration. You may store ceramic formers and other items not affected by the environment in sheds or outside.

In-Process Testing

You should perform in-process testing on the dipping compound as well as the glove to determine if the manufacturing process is on target to meet your specifications. In-process testing may include testing of the uncured compound, the cure status of the dipping compound (whether the compound is ready to dip), and thickness, tensile strength, length, and water leak testing of the glove. Also, you should test for powder, if it is a powder-free glove. You can find a sample of an in-process record, Analysis of Latex Compounding, in Exhibit #3.

PROCESS VALIDATION

Process validation is a means by which the manufacturer establishes that its manufacturing process is capable of consistently producing a product that conforms to the specifications as outlined in the device master record. Process validation is a key element in developing process controls. A properly validated and controlled process will reduce scrap and rework resulting in increased efficiency. Examples of processes that should be validated include compounding, dipping, leaching, chlorination, sterile packaging, and sterilization.

If there is an increase in nonconforming product or process deviations occur, you should review and evaluate the process, and you should perform revalidations where appropriate. Changes to the manufacturing process, such as new equipment or a new compound, may require revalidation prior to implementation of the change.

FDA provides guidance on process validation in the Medical Device Quality Systems Manual. The Global Harmonization Task Force (GHTF) provides guidance in the following document:

Quality Management Systems – Process Validation Guidance

PROCESS CONTROLS

Each manufacturer must establish production and process controls, as appropriate, to ensure that a device conforms to its specifications (21 CFR 820.70(a)). These controls should reflect the ranges of parameters established during the previously conducted process validation.

You should consider process controls for the following processes: compounding, maturation, dipping, curing, bleaching, drying, powdering or removal of powder, and rinsing. Also, you should control vibration which causes air bubbles in the dipping tanks. Exhibit #4 shows a table providing the impact of processes that affect the finished glove characteristics. The table provides examples of parameters for each process that you should consider for process controls. Exhibit #5 provides a typical example of a monitoring and process parameter control record.

Inadequate process control can lead to nonconforming product. For example, patient exam gloves were insufficiently dried and subsequently packaged and distributed in a moist condition. The lot was later tested and found to have Aspergillus and Fusarium molds and recalled from the market. One way this situation may have been prevented is if the firm had monitored in-process controls during the manufacturing process. Monitoring the humidity and/or moisture content during the drying cycle could have revealed the problem. At this stage, the firm may have been able to rework (re-dry) the gloves which could have avoided the product recall.

Manufacturing Materials

Under the definition in 21 CFR 820.3(p) of the Quality System regulation, manufacturing materials include “concomitant” or by-product constituents. Concomitant constituents are substances that are unavoidably present in the components and manufacturing materials but are not intended to be present in the finished device. These include water-soluble natural rubber proteins present in the latex concentrate. These proteins do not contribute to the glove barrier, because they are not bound into the latex film but readily leach out. By-products are substances formed during mixing by reactions between various components and manufacturing materials. These also include various calcium salts.

Manufacturing materials such as mold release compounds, cleaning agents, lubricating oils, by-products, and other substances used to facilitate manufacturing are procured and received the same as components. You should establish, maintain, and document procedures for the removal of manufacturing materials when they could reasonably be expected to have an adverse effect on product quality. You should remove manufacturing materials or limit them to an amount that does not adversely affect the quality of the glove. Because natural rubber latex proteins can adversely affect the safety of medical gloves, you should establish and validate procedures to reduce the water soluble proteins to ensure that it is removed or limited to an amount that does not adversely affect the gloves's safety.

Control, Use, and Removal of Manufacturing Materials

You should carefully consider manufacturing materials that may adversely affect the finished glove. You should design each process to use a minimum amount of adverse chemicals to reduce costs and removal efforts and increase the safety of the glove.

For medical gloves, processing of raw latex, and leaching and washing processes are commonly used to reduce or remove natural water-soluble proteins and remove adverse materials, such as processing chemical residues. When residues from sterilization agents such as ethylene oxide need to be removed, instructions for aeration are necessary.

When you add starch to medical gloves to expedite handling and then remove it during further processing (for example, during the production of some “powder-free” gloves), the starch becomes a manufacturing material. You should use a written processing and test/inspection procedure to assure that powder residues on the finished gloves meet finished device specifications.

Water-Soluble Proteins. Water-soluble proteins on latex gloves may be a potential cause of allergic reactions. Processing controls should include the reduction of water-soluble proteins. You should remove them by:

  • reducing or removing the proteins in the raw latex,
  • using and controlling pre-cure leaching and post-cure washing processes,
  • assuring that the leaching tanks and spray or washing tanks use water that is flow-controlled and continually refreshed to avoid protein saturation, and
  • leaching and washing for an appropriate time.

You should perform washing before and after curing, because proteins become more water-soluble and/or move to the surface of latex gloves during heat curing. This allows you to remove the protein more efficiently. You should complete the washing before you apply the final donning powder or lubricant, if applied.

Each manufacturer should establish the temperature of the leaching and washing water because the temperature needed varies based on the parameters of the overall compounding, dipping, and curing methods. Studies indicate that the purity (flow rate) and agitation of the leach water and total leaching time are more important than water temperature.

Surface treatment of the cured latex glove with chlorine or similar agents denatures surface constituents such as water-soluble proteins. These treatment processes also wash and rinse away proteins and manufacturing residues. Chlorine is an adverse manufacturing material which can cause deterioration of the gloves. You should remove it from the gloves after chlorination by washing, neutralization, or other appropriate methods. The chlorination process includes process control and validation.

You should test water-soluble proteins during routine production. You may test protein levels using the FDA-recognized standard, ASTM D5712, Standard Test Method for the Analysis of Aqueous Extractable Protein in Natural Rubber and Its Products Using the Modified Lowry Method, or an equivalent consensus standard.

Trained personnel should develop, validate, document, implement, and control the processes used to control water-soluble proteins and manufacturing materials (see 21 CFR 820.25).

Manufacturing Chemicals. You should remove manufacturing chemicals, such as vulcanization accelerators and detergents, to the extent that they do not adversely affect the finished glove. Reports of type IV sensitivity reactions have been associated with gloves that contain residual amounts of these manufacturing chemicals.

You can remove manufacturing chemicals by some of the same methods used to remove protein. You should develop leaching, washing, surface treatment, or other processes for removing adverse manufacturing materials. You should also validate, document, and continuously control the processes in order to meet the established specifications.

Maintenance and Inspection of Equipment

According to 21 CFR 820.70(g)(1), you must establish and maintain a schedule for the adjustment and cleaning of equipment. For example, you should periodically strip and clean the maturation tank of any residue to avoid contamination. The formers should have a routine cleaning schedule because build up of residues can cause thin spots and holes in the gloves. In addition to the in-line cleaning, you may need periodic maintenance of formers to remove the build up of residues. You should lift, or remove and repair, or replace defective formers. Because lubricant for production equipment can fall into dipping tanks, you should inspect the equipment for excess lubricant and periodically clean the equipment.

To properly maintain equipment, manufacturers should:

  • establish a written schedule for performing these activities,
  • post the schedule or make it readily available to employees,
  • document the activities, the individuals conducting the activities, and the date,
  • audit the activities and document the audit, and
  • keep maintenance records for each piece of equipment.

When adjustment is necessary to maintain proper operation due to deterioration of parts or other reasons, post the inherent limitations and allowable tolerances of the equipment or make these readily available to personnel responsible for making adjustments.

Contamination Control

For each area in the building where you process components and gloves, you should control any element that you determined might cause contamination. The contaminants include dust, paint chips, rust, starch residues, protein residues, microorganisms, humidity, temperature, and static electricity. If sources of contaminants are located above the manufacturing equipment, you should consider covering or enclosing portions of the dip line or any other area that could be affected by debris. You should clean equipment as needed by methods that will reduce or prevent contamination of tanks, formers, and gloves with dust and other debris.

Buildings should be appropriately constructed to prevent, reduce, and control contamination, and support the manufacturer’s environmental control program. For example, controlling dust may require that you pave driveways and parking lots. Floor sweeping and floor polishing scatter dust can contaminate wet formers, coagulant dipping tanks, latex/polymer dipping tanks, and finished gloves. You should clean floors and equipment by methods that minimize the amount of debris released into the environment.

You should perform all manufacturing and labeling operations for low protein or synthetic gloves in a separate area to avoid protein contamination by latex gloves. Synthetic polymer gloves, polymer-coated latex gloves, or any gloves with a labeled or controlled protein level should not be dipped in any tank (particularly starch slurry tanks) or tumbled in dryers where regular protein coated latex gloves have been produced, unless you clean the tanks thoroughly before the production of the low- or protein-free gloves. FDA recommends that manufacturers dedicate lines specific to the manufacture of synthetic gloves to avoid protein contamination.

Environmental Control

Where environmental conditions could reasonably be expected to have an adverse effect on product quality, you must establish procedures to control the environmental conditions (21 CFR 820.70(c)). You should establish and maintain an appropriate system for regular monitoring and documenting the control of environmental factors that apply to your specific situation.

You should consider environmental factors, such as lighting, ventilation, temperature, humidity, static electricity, insect and pest control, and particulates. If you use rodenticides, insecticides, or similar agents, you should establish written procedures for limiting their use and removing them from work surfaces. These procedures are to prevent any adverse effect on the manufacturing process or the device. You should cover finished gloves, solution tanks, and other appropriate items during the application of pesticides to the room.

You should store packaging and starch in a clean, dry, insect-free area. You should preserve latex to prevent bacterial growth. You should store components such as starch that support bacterial growth in a controlled environment such as sealed containers or bags. You should not use unfiltered air to dry washed formers or coagulant-coated formers, because the resulting contamination may cause pinholes. You should not use unfiltered factory air to cool or dry finished surgeon’s gloves. You should have screens in open windows, and doors should be screened to control insects.

Bioburden Control

Bioburden is an environmental factor that needs to be controlled for sterile surgeon’s gloves, but it is also important in the manufacture of nonsterile gloves. The failure to control bioburden may result in mold on the finished product.

Medical gloves, particularly those powdered with starch, can support the growth of micro-organisms. Appropriate processing controls should include:

  • purchasing starch with a low bioburden,
  • properly storing the starch until it is used,
  • applying starch per established procedures,
  • cooling the starch slurry and/or using an antimicrobial in the starch slurry tanks,
  • sampling finished gloves to assure that excessive starch is not applied,
  • keeping the finished gloves clean,
  • establishing and meeting a dryness specification for finished gloves, and
  • protecting finished gloves from the environment.

Filthy or contaminated water may also be a major source of microbes on finished gloves. You should monitor and appropriately treat water used in processing the glove, especially near the end of the manufacturing process, such as post-cure washing, to control the bioburden on the glove.

You should refer to ANSI/AMMI/ISO 11737-1:1995, Sterilization of Medical Devices—Microbiological methods—Part 1: Estimation of Population of Microorganisms on Product for guidance on bioburden testing.

Personnel Practices

You should establish and maintain procedures for personnel to follow to reduce contamination and any other adverse effects on the gloves. Procedures should include hand washing requirements. Personnel should not wear jewelry or have sharp fingernails. Additionally, eating and smoking may adversely affect the finished glove. You should confine these activities to designated areas.

FINISHED GLOVE ACCEPTANCE ACTIVITIES

Finished glove acceptance procedures should demonstrate that the gloves meet the manufacturer’s acceptance criteria. The finished device evaluation should include inspection and testing of samples of packaged gloves. A manufacturer’s evaluation of finished glove lots usually includes appropriate in-process inspection and testing performed on representative samples. You should record the evaluation data for finished glove lots in the device history record (DHR). You should review and accept the DHR before releasing the lot for distribution.

Glove evaluation may include the following parameters:

  • barrier integrity, including pinholes and embedded debris,
  • length, width, thickness,
  • weight,
  • elongation and tensile strength,
  • cuffs/beads,
  • powder and/or lubricant level,
  • measurement or indication of manufacturing material residues,
  • measurement or indication of proteins or allergens,
  • moisture content or dryness level,
  • fisheyes, webbing, or folds,
  • package integrity,
  • bioburden count,
  • labeling,
  • visual tests, such as color and material uniformity.

Your quality system procedures should describe the finished device test methods and acceptance criteria, including sampling procedures and AQL. You should reference any standard test methods that are used. Information on test methods for water leak testing, protein, tensile strength, and powder residue is available in consensus standards. See Chapter 10, Voluntary Standards, for more information on consensus standards. For water leak testing, FDA uses the methodology in 21 CFR 800.20 for its regulatory testing of all medical gloves (of all materials).

NONCONFORMING PRODUCT

If a lot of gloves or product does not meet specifications, you should properly identify the containers of rejected gloves and place them in a separate quarantine area or in a specially identified area to prevent mix-ups. If nonconforming product is investigated, you should add the results to the corrective and preventive actions (CAPA) system. According to 21 CFR 820.90(b)(1), you must document the disposition of nonconforming product. The records should state whether you returned or scrapped the gloves, components, materials, or other products.

Reworked Gloves

You must establish and maintain procedures for rework to include retesting and reevaluation of reworked nonconforming product (21 CFR 820.90(b)(2)). Reworked product should meet the original specifications. You should evaluate reprocessing to assure that gloves will not be adversely affected and you should document the results of the evaluation.

Procedures for reworking should specify the types of nonconformances that may be reworked. These procedures should document the specific tests and processes to be performed. You should base these procedures on studies that measure the effects of reprocessing operations.

Reworked product is nonconforming product until it meets all finished device acceptance criteria. You should identify reworked product to distinguish it from acceptable product and components. 

LABELING AND PACKAGING

The Quality System regulation has specific requirements for labeling and packaging design, as well as for labeling and packaging operations (21 CFR 820.120, 820.130)). Labeling includes dispenser box labels, case labels, package labels, and directions for use, such as caution statements.

Area Separation and Inspection

You should separate all labeling and packaging operations performed at the same time, as necessary, to assure there are no mix-ups between similar labels or various sizes or types of gloves. Before beginning any packaging and labeling operation where a mix-up could occur, you should examine the production area and equipment to make certain that you have removed any glove and labeling materials from previous operations. You should destroy unused labeling that contains a pre-coded manufacturing date, expiration date, or lot number; you should not return it to the label storage area.

A designated individual should examine the labeling for accuracy, in accordance with the device master record, prior to initiating the labeling operation. The examination should include the expiration date.

Packaging

An effective primary package for a medical glove should be designed and developed along with the product by considering glove characteristics, contamination control, sterilization process, sealing, labeling, secondary packaging, shipping, environment, shelf life (expiration date), end use, and FDA regulations. The primary package and the shipping container should protect gloves adequately under all reasonable conditions from original packaging to final use. For sterile gloves, you should validate the packaging operation. You should either compile complete storage and stability data for packaging for sterile gloves or obtain the data from the packaging supplier.

Shipping for Further Processing

It is common industry practice for non-sterile gloves labeled as “sterile” to be shipped to a contract sterilizer. You should conspicuously mark each pallet, carton, or other designated unit to show its non-sterile nature when it is introduced into and is moving in interstate commerce. See Sterilization for additional information.

COMPLAINT HANDLING

Each manufacturer must process complaints from all sources according to its complaint handling procedure (21 CFR 820.198(a)). You should assure that personnel in marketing, sales, engineering, and manufacturing report complaints. You should make these employees aware of this Quality System requirement through formal training and note the training in their training records.

Because FDA believes that customer complaints are underreported, user reporting for tears and leaks are considered low. Therefore, even small increases in the rate of complaints may be significant.

Customer complaints may include the following issues:

[ ] Pinholes, Tears, Thin Spots, Degradation ___________________________________
[ ] Expiration Date / Shelf Life ______________________________________________
[ ] Powder, Lubricant, Tacky _______________________________________________
[ ] Particulates: Type _________________ Location
[ ] Packaging __________________________________________________________
[ ] Sterility ____________________________________________________________
[ ] Labeling ___________________________________________________________
[ ] Thickness, Mold, Appearance, Attributes ___________________________________
[ ] Dermatitis __________________________________________________________
[ ] Allergic Reaction _____________________________________________________
[ ] Describe Other Defects ________________________________________________

Complaint Analysis

Each complaint needs to be reviewed by a designated unit and a decision made as to whether an investigation is needed. The analysis of the complaint typically includes the following information:

Sequential Complaint Number ________________
Glove Type ______________________________
Cat. Number _____________________________
Date of Complaint Report ___________________
Lot Number ______________________________
Name of Complainant ______________________
Nature of Complaint _______________________

ASSIGNEE EVALUATION & CONCLUSIONS:
______________________________________________________________________

______________________________________________________________________

______________________________________________________________________

______________________________________________________________________

[ ] Pinholes, Tears, Thin Spots, Degradation ____________________________________

[ ] Powder, Lubricant, Tacky ________________________________________________

[ ] Particulates __________________________________________________________

[ ] Labeling/Packaging ____________________________________________________

[ ] Non-Sterile ___________________________________________________________

Thickness, Appearance, Color Attributes of:

[ ] Fingers __________________________
[ ] Palm ____________________________
[ ] Crotch ___________________________
[ ] Cuff/bead _________________________
[ ] Elongation ________________________
[ ] Tensile ___________________________
[ ] Chemical Residues Above Spec. __________________________
[ ] Protein Level Above Spec. _______________________________
[ ] Improper Use _________________________________________
[ ] Shipping Damage _____________________________________
[ ] Describe Other Defects/Problems ________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________

ACTION: [ ] Recalled [ ] Replaced [ ] Credited [ ] Sales Follow-Up

[ ] Letter ______________________________________________________________________

Investigation needed [ ]Yes [ ]No

[ ] Referred To _____________________________________ for Further Investigation or Correction

[ ] NONE. Reason for no action ______________________________________________________

NOTES: _______________________________________________________________________
______________________________________________________________________________

FINAL DISPOSITION _____________________________________________________________
______________________________________________________________________________
______________________________________________________________________________

Reviewed by:Quality Assurance __________________________________ Date _______________

If requested:Engineering _______________________________________ Date _______________

Production __________________________________________________ Date ______________

Complaint Investigation

Each manufacturer must evaluate complaints to determine whether an investigation is necessary (21 CFR 820.198(b)). After an analysis of the complaint, if an investigation is needed, the failure investigation and analysis should determine the actual problem or actual failure mechanism to the level necessary to correct the problem. A failure investigation may include a review of the device history records and analysis of returned product. When you diagnose the same failure, contaminant, or other problem several times, you do not need to analyze all additional gloves that are returned with the same complaint.

Complaints Received by Distributors

When the manufacturer is located outside the U.S., the foreign manufacturer should provide the U.S. distributor with instructions to forward any complaints to the foreign manufacturer for review and analysis. You should consider the forwarding of complaints when developing contracts or other business arrangements with importers.

Medical Device Reporting

According to 21 CFR 820.198(a)(3), you must evaluate complaints to determine whether the complaint represents an event which must be reported to FDA under 21 CFR 803, Medical Device Reporting. Incidents in which a device may have caused or contributed to a death or serious injury must be reported to FDA under the Medical Device Reporting program. In addition, you must report certain malfunctions. (21 CFR 803.1.) An allergic reaction may be considered a reportable event.

The MDR regulation is a mechanism for FDA and manufacturers to identify and monitor significant adverse events involving medical devices. The goal of the regulation is to detect and correct problems in a timely manner. You can find additional information on the Medical Device Reporting process at: "Medical Device Reporting (MDR)".

 

STERILIZATION

Sterilization of medical gloves should meet a sterility assurance level (SAL) of 10 -6. This means that you should design the sterilization process so that the probability of a glove being non-sterile is 1 in 1,000,000, even if the gloves originally contained highly resistant microorganisms.

You should sterilize medical gloves with a validated sterilization process. Note that some glove materials are adversely affected by certain sterilization methods. Validation of the sterilization method should demonstrate that the sterilization process does not adversely affect glove safety and effectiveness.

Refer to the Quality System manual and applicable standards, such as AAMI or ISO, for validation of sterilization processes. AAMI and ISO standards for sterilization include the following:

  • ANSI/AAMI/ISO 11135- Medical devices - Validation and routine control of ethylene oxide sterilization
  • AAMI/CDV 11137 Sterilization of health care products – Radiation
  • AAMI/ISO Technical Information Report (TIR) 13409 Sterilization of health care products - Radiation sterilization

Additional AAMI standards are available at AAMI Database Search.

Contract Sterilization

It is common industry practice to ship non -sterile gloves labeled as sterile to a contract sterilizer. This practice is recognized in 21 CFR 801.150(e) which states, in part, “the Food and Drug Administration will initiate no regulatory action against the device as misbranded or adulterated when the non-sterile device is labeled sterile, provided all the following conditions are met:

  1. There is in effect a written agreement which:
    1. contains the names and post office addresses of the firms involved and is signed by the person authorizing such shipment and the operator or person in charge of the establishment receiving the devices for sterilization,
    2. provides instructions for maintaining proper records or otherwise accounting for the number of units in each shipment to insure that the number of units shipped is the same as the number received and sterilized,
    3. acknowledges that the device is non-sterile and is being shipped for further processing, and
    4. states in detail the sterilization process, the gaseous mixture or other media, the equipment, and the testing method or quality controls to be used by the contract sterilizer to assure that the device will be brought into full compliance with the Act.
  2. Each pallet, carton, or other designated unit is conspicuously marked to show its non-sterile nature when it is introduced into and is moving in interstate commerce, and while it is being held prior to sterilization. Following sterilization, and until such time as it is established that the device is sterile and can be released from quarantine, each pallet, carton, or other designated unit is conspicuously marked to show that it has not been released from quarantine, e.g., “sterilized—awaiting test results” or an equivalent designation.”

Compliance with 21 CFR 801.150(e) may require two written agreements when importing pre-labeled “sterile” but not-yet-sterilized surgeon’s gloves. The two agreements are:

  • one between the importer and the glove manufacturer, and
  • one between the importer and the contract sterilizer.

Gloves that have been sterilized and shipped to the importer’s warehouse prior to final release of the product should be properly marked as not yet released. For example, pallets or other designated units may be marked “sterilized, awaiting test results,” or similar wording. The importer should have control of the gloves until final release. Prior to shipping, you should use either a highly controlled quarantine area or a label control system to prevent distribution of gloves marked “sterile,” but not yet released for distribution.

QUALITY SYSTEM AUDITS

Under 21 CFR 820.22, you must conduct quality audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system. Individuals who do not have direct responsibility for the area being audited must conduct the quality audits. You must take corrective action(s), including a reaudit of deficient matters, when necessary. You must document the results of each quality audit, (and reaudit(s), if necessary) in a report, and management responsible for the area audited must review the report (21 CFR 820.22).

You should establish written procedures for quality audits. You should document the dates and results of quality audits and reaudits.

EMPLOYEE TRAINING

Under 21 CFR 820.25, you must have sufficient personnel with the necessary education, background, training, and experience to assure that all activities required by the Quality System regulation are correctly performed. As part of their training, personnel must be made aware of device defects that may occur from the improper performance of their specific jobs. Personnel who perform verification and validation activities must be made aware of defects and errors that may be encountered as part of their job functions.

You must establish procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities. You must document employee training (21 CFR 820.25).

EXHIBIT #1 SAMPLE GLOVE SPECIFICATION (DEVICE MASTER RECORD)

*** SAMPLE DEVICE MASTER RECORD examination glove specification *** including some typical parameters.
You may modify this form and use it to meet your needs. Do not use this example as is.

C O M P A N Y L O G O Page 1 of 1
Title: Glove Specification SOP Number
Prepared by: Date Prepared
Approved by: Date Rev C
ECN notes: ECN 429 Protein limit added 8-1-96; no label claim -- no new 510k required; ECN 436 Rev B powder level changed to 10mg/decimeter2
ECN 438 Rev C protein reduced to 200 µg/decimeter2 by process improvement

COMPANY PRODUCT NAME: _________________

Trade Name: Patient examination gloves, non-sterile
Intended Use: Medical activities except surgery
U.S. FDA Status: Class I, Classification Number 80LYY; 510(k) marketing clearance required.
Should be manufactured under quality system program.
Material: Natural rubber latex    
Donning Lubricant: U.S.P. Absorbable corn starch    
Catalog Numbers: Crystal Touch 100S Crystal Touch 100M Crystal Touch 100L
Sizes: Small Medium Large
Conforms to following      
Standards: ASTM D3578, ISO 11193    
Overall Length: 240 mm minimum 240 mm minimum 240 mm minimum
Width: 80 +/- 10 mm 95 +/- 10 mm 111 +/- 10 mm
Palm Thickness: 0.10 mm minimum    
Finger Thickness: 0.10 mm minimum    
       
  BEFORE AGING at 70°C AFTER AGING at 70°C  
Tensile Strength: 18 Mpa minimum 14 Mpa minimum  
Ultimate Elongation: 650% minimum 500% minimum  
       
Orientation: Ambidextrous    
Cuffs: Yes    
Color: Natural    
Residual Powders 10mg/decimeter2 max.    
Protein Max. 200 µg/decimeter2 max.    
       
Packaging: 100 units in dispenser box by weight    
Disp. Carton Labeling: Per Packaging specification P-192 Rev. C    
Ship. Case Labeling: Per Packaging specification P-193 Rev. B    

Product Coding:

******************************* End **********************************

EXHIBIT #2 SAMPLE COMPONENT RECORD (INCOMING CONTROLS)

*** SAMPLE RECORD *** Page ___ of___

Do not use without modifying to meet your specific glove and operations.

RECEIVING LATEX TEST DATA PROCEDURE NO.*
SUPPLIER: Date Received
SOURCE: Date Sampled
LATEX GRADE: Lot
PARAMETER ACCEPTANCE CRITERIA RESULTS Tested by and date PASS/FAIL
% TOTAL SOLID CONTENT        
MST (sec)        
% DRY RUBBER CONTENT        
% NON-RUBBER CONTENT        
% ALKALINITY ( NH 3% )        
VFA NUMBER        
KOH NUMBER        
VISCOSITY        
pH VALUE        
OTHER:        
Remarks :
 
 
 
Reviewed by (signature): Date

EXHIBIT #3 SAMPLE IN-PROCESS RECORDS (IN-PROCESS CONTROL)

*** SAMPLE RECORD ***

Do not use without modifying to meet your specific glove and operations.

ANALYSIS OF LATEX COMPOUNDING
DATE SHIFT
Batch Number  
Compounding Tank No.  
Date & Time Compounded  
Date and Time of Test  
 

PROCEDURE*

NUMBER (Spec)

RESULTS BEFORE MATURATION

 

PASS/FAIL

1. pH      
2. TSC      
3. Precure test      
4. NH 3      
5. VISCOSITY      
6. OTHER      
 

PROCEDURE*

NUMBER (Spec)

RESULTS AFTER MATURATION

 

PASS/FAIL

1. pH      
2. TSC      
3. Precure test      
4. NH 3      
5. VISCOSITY      
6. OTHER      

Remarks:

 

*The test & acceptance activities performed & equipment used are described in the procedures

Tested by:

Signature:

 

EXHIBIT #4 IMPACT OF MANUFACTURING PROCESSES (PROCESS CONTROL)

This chart indicates the possible effects of various process parameters on the performance characteristics of gloves. It can be used as a checklist for the design of gloves and associated processes. It does not cover all possible parameters. It is in keyword form; therefore, it should be used by appropriately trained persons. Do not use this checklist without modifying it to meet your specific approach to glove and process design.

REACTIONS / PHYSICAL PROPERTIES AND SURFACE CHARACTERISTICS

  a b c d e f g h i J k l m n o p q

 

 

 

 

 

COMPONENTS, PARAMETERS, AND PROCESSES

                                 
1. RAW LATEX - Non Rubber Solids; Ammonia;Copper & other metals; Centrifugation; Maturation     X X X             X         X
2. FORMULATION - Selection; Amount Added; Amount processed out (removed) X X X X X   X X X X X X   X   X X
3. CHEMICALS - Chemical purity; Microbial purity; Particle size; Supplier Change control X X   X X             X          
4. PRE-PROCESSING - Ball milling or grinding efficiency; Premixing X X X X X         X X X          
5. COMPOUNDING - Correct ingredients; Correct order; Cleanliness; Homogeneity; Maturation; Stir / Fill bubbles X X X X X     X X X X X          
6. FORMERS - Dimensions; Orientation; Length; Composition; Surface texture; Embossing; Cuff Width; Rotation; Dynamics; Age/wear       X     X     X       X X X  
7. COAGULANT - Composition; Agitation; Former temperature / dry; Agitation X X X X   X   X X X   X         X
8. LATEX DIP - Temperature; Agitation; Level; Dwell; Foam; Drip; Fallout       X           X             X
9. SET - BEAD (1)       X                 X   X X  
10. LEACH - Temperature; Water direction; Water speed; Dwell time; Depth; Fresh Water ratio; Water purity X X X X X   X X X   X       X (6)    
11. OVENS - Temperature Profile; Dwell; Air circulation; Humidity (2) X X X X X     X X X X X X        

12. POST-CURE RINSE POWDERED GLOVES

Purity; Volume; Duration; Exposure

X X X X X     X X                
13. POWDERED GLOVE SLURRY - antimicrobial; Surfactants; Ingredients; Temperature; Amount used; Agitation; Microbial growth; Clean out frequency (3) X X X         X X   X            
14. CHLORINATION POWDER FREEGLOVES - Concentration; Filtration; Duration; Load; Reversals; pH; Agitation; Drain efficacy and speed; Neutralization; Rinse Quality X X X X X   X X X X X X X   X X  


 

  a b c d e f g h i J k l m n o p q

 

 

 

 

 

COMPONENTS, PARAMETERS, AND PROCESSES

                                 
15. LUBRICANT - Type; Concentration; Distribution; Microbial Growth X X         X X X       X        
16. DRYERS - Delay; Temperature; Duration; Cross Contamination; Humidity; Filtration; Load / Space; Airflow X     X X     X X X X X          
17. PACKAGING - Line Clear; Clean up; Label control; Packaging material; Stack method; Sun / light exposure     X X X         X X X          
18. TRANSPORT / STORAGE - Temperature; Moisture; Protection; Insulation X     X X     X X X X X          
19. CLEANING - HOW? WHEN? - Formers; Filters / Screens; Tanks; Mop (no sweeping); Air / Surface; Line Change; Personnel; Chain guards X X X X X         X   X          
20. COATINGS - Laminates, Bound polymers (4) X X         X     X   X X X   X X
21. EXTRACT TREATMENTS - Enzymes, Protein binders X X X X X         X   X          

22. Other

(Add for your glove and processes)

                                 

 

GENERAL :

  • Line speed alters the dynamics of every step and process.
  • Environmental conditions impact barrier, quality, appearance, etc. Parameters, in general, are interdependent.
  • Standing water or wet glove on hold is a potential microbial problem.
  • Sterilization should be closely monitored with routine endotoxin and oxidation checks on glove and packaging bioburden.

Notes:

(1) Also affects drying inside the bead
(2) Can cause gloves to be brittle
(3) Slurry also affects powder distribution
(4) Delamination potential
(5) Refers to yellowing of latex
(6) Rolldown of hand or glove material

******************************* End *********************************

EXHIBIT #5 MONITORING AND PROCESS PARAMETER CONTROL RECORD

SAMPLE *** Do not use without modifying to meet your specific needs. ***

MACHINE DIP LINE PARAMETERS PER DAY

LINE: ____________________ SHIFT: ________________ DATE: _________________

OPERATOR: ______________________ SUPERVISOR: _________________________

 

ITEM OR PROCESS TIME & PARAMETER ACTION TAKEN
1. Acid tank 55-60 0 C.          
Level          
2. Rinse 45-50 0 C.          
Level          
3. Water 55-60 0 C.          
Level          
4. Wash oven 80-85 0 C.          
5. Coagulant 50-55 0 C.          
Level          
6 Coagulant oven 80-85 0 C          
7. Latex dip 27- 29 0 C.          
Level          
8. Tack oven 85-90 0 C.          
9. Beading          
10. Leaching 55-65 0 C.          
(1) Level in tank          
11. Leaching 55-65 0 C.          
(2) Level in tank          
12. Cure oven #1 temp.          
13. Cure oven #2 temp.          
14. Cure oven #3 temp.          
15. Protein Rinse operating          
Chain speed          
Line start time          
Line stop time          
~ items produced / hour          
Length of glove (23-24 cm)          
Weight of glove (gm)          
Reject weight (kg)          
Remarks