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Cytostatics contamination: cleanroom clothing or chemical protective clothing.

Any work with cytostatics requires the effective protection of workers from the effect of such drugs, which can have various carcinogenic, mutagenic and reprotoxic outcomes. At the same time, it is important to protect the product against contamination from people. Workers are therefore required to wear suitable protective clothing. This article specifically addresses personal protection, discussing its requirement and possible solutions in the form of disposable protective clothing.

Cytostatics are used as drugs in cancer therapy (chemotherapy) to inhibit the multiplication of tumour cells and are also increasingly being used to treat other diseases. However, their toxicity not only affects tumour cells, but also healthy ones as well. Cytostatics often have a carcinogenic effect themselves (causing cancer), as well as being potentially mutagenic (changing a person's genetic material) and reprotoxic (endangering reproduction). They are therefore known as CMR substances. Upon direct skin contact, some cytostatics may also have an irritating or sensitizing effect. Based on research involving patients with a long history of exposure to high-dose cytostatics, as well as animal trials, the International Agency for Research on Cancer (IARC) in Lyon, France (a special organization that forms part of the World Health Organization) has classified cytostatics into three carcinogenic categories (Table I). (1,2) In Germany, a list of substances classified as carcinogenic, mutagenic or reprotoxic under categories 1, 2 and 3 can be found in TRGS 905 and is based on solid scientific findings. (2) This document contains national assessments from AGS (Hazardous Substances Committee) and seeks to provide health and safety specifications for employees in the workplace, thus enabling employers to take the required precautions.

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Employee Protection is Mandatory

To prevent staff exposure while handling cytostatics, a range of appropriate precautions must be taken. What applies to the handling of hazardous substances in general is also true for cytostatics; that is, the highest priority must be placed on the full use of all technical and organizational measures (Table II). For instance, care must be taken to prevent the formation of cytostatic aerosols and dust and to avoid cytostatic contamination during the production, preparation, provision, disposal, storage and transportation of such substances. Potential health hazards can result from even low-level contact with cytostatic substances. If there is any risk of contact, the use of suitable personal protection equipment (PPE) is mandatory, to ensure effective full-scale protection. PPE selection is commonly based on the findings and results of risk analysis, in addition to technical and organizational measures. These protective measures apply to all staff who come into contact with cytostatics, not just during production and preparation, but also during application, disposal, shipping and when being handled by cleaning and maintenance staff.

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Cleanroom Clothing or Chemical Protective Clothing

Both cleanroom clothing and chemical protective clothing need to meet the same basic criteria for use in a cleanroom: the material must be low-linting; the design must be sufficiently tight; and the danger of collecting particles on the surface of the garment must be minimized. To be suitable for dealing with cytostatics, such clothing must also be comfortable to wear, it must have good electrostatic charge derivation and sterilization must be possible. If, after taking all the relevant technical and organizational precautions, personnel are still exposed to a health risk--by exceeding the limit of airborne particles or the organic workplace tolerance value, for example --then the employer is legally obliged to provide personal protection equipment (PPE) (see Table IV). Cleanroom clothing does not qualify as personal protection equipment unless it has been certified as such under the PPE guidelines specified in the relevant European Directive. According to EU Directive 89/686, there are three classes of personal protection equipment that must be specified as such by manufacturers:

* Category I: low risk, for use in poor weather conditions, for example

* Category II: medium risk, such as high visibility clothing

* Category III: high risk, for protection from lethal hazards and from serious or irreversible damage to a person's health.

Chemical protective clothing comes under Category III and is divided into six tightness levels (Table III). Each of these tightness levels is linked to certain minimum requirements, which must be met both by the suit as a whole and by its material. Certification according to a certain protection type specifies the tightness of a suit against exposure to gas, liquid or dust. However, this does not automatically mean that the suit is 100% tight against such exposure. When choosing protective clothing, it is therefore advisable to check its type classification and the results of the type and material tests that can usually be found in the manufacturer's product description. Chemical protective clothing can be recognized by a product description, such as "Chemical Protective Clothing Cat. III, Type 4, 5, 6" and/or the specifications in the user instructions or on the inside label.

Protective Clothing: Gowns or Overalls?

A frequently asked question in connection with protective clothing is whether to opt for gowns or overalls. Gowns as working clothes for protection of the human body are generally known and used in the health service and are available in a range of different qualities. However, Carstens also discusses various alternatives that are especially suitable for protection against contamination from cytostatics. (8) First of all, protective clothing in the manufacturing and processing environment also serves to protect the product. If, for instance, Class A cleanroom requirements (a cytostatics workstation) are to be met in a Class B cleanroom (location of the workstation), then--according to Carstens--this standard can be fulfilled more easily with a combination of an overall, boots and hood than with a gown, bonnet and cleanroom shoes. Even though a gown may still achieve acceptable results in a manufacturing situation, it would certainly be unsuitable as protective clothing when unintended impurities need to be removed--at least if they take the form of large volumes of liquid or solids. Carstens says: "A long gown that protects the legs of a person when standing can then turn into a duster or mop when they squat down or bend forward to remove broken pieces or contaminated items. It follows that a spill kit must at least contain a sufficiently large overall and should generally be considered as a protective suit for cytostatic environments." In the same context, we must also ask under what circumstances protective clothing should be liquid-tight and whether particle-tight protection might not be sufficient in most cases.

Particle-Tight or Liquid-Tight?

Dealing with cases when the German Technical Regulations for Hazardous Substances (TRGS 525) merely specify liquid-tight PPE for extended cleaning activities at a cytostatic workstation and the removal of unintended contamination (spills), Carstens says: "Even while working at a workstation, it is possible for contamination to occur, for instance, from aerosols or drops on or near a person's legs, stomach or thighs." (4,8) When unwrapping and transferring cytostatics, protective clothing may become contaminated as a result of impurities on the primary packaging, caused, for instance, by substances coming off or becoming suspended while washing one's hands. Breakages may also cause major contamination issues. Thus, understandably, there are requirements for staff to extend the wearing of liquid-tight protective clothing into the manufacturing environment.

What matters is that the suit material should provide a reliable and protective barrier against both pure and dissolved cytostatics. Suit manufacturers need to specify such details about their suits, including the particle and liquid barriers of the workwear. Furthermore, as the focus is not only on personal protection, but also on product protection, the suit material should have a smooth surface that reduces the adhesion of particles and micro-organisms, and prevents linting as much as possible.

Disposable or Reusable Clothing?

Another point of discussion is whether or not to opt for protective clothing with a limited period of use (referred to as disposable protective clothing) or for reusable suits. The advantage of disposable suits is that a "new product" is available each time and that this suit has a proven and documented barrier effect. If clothing attracts unknown contaminants and is then removed, it may cause direct contamination to people and may also lead to the transfer of hazardous substances to other, hitherto uncontaminated objects, surfaces and environments.

Protective Suits: Product and Personal Protection

As well as providing product protection, Tyvek and Tychem protective clothing and accessories also meet the requirements of Category III chemical protective clothing and, as such, personal protection. To simplify the selection of suitable clothing, cytostatics can be classified according to their respective barrier requirements: (a) particles; (b) water-soluble; and (c) soluble in solvents. Obviously, however, this classification is only suitable as a guideline (Table V) and cannot replace a risk analysis. Generally speaking, the selection of suitable protective clothing always requires a detailed analysis of the hazardous substances and of the working environment. A range of factors, including concentration, temperature and pressure, substantially influences the barrier effect of protective clothing material. As well as looking at protection requirements, criteria such as comfort and environment-friendliness should also be considered when choosing protective clothing.

Tyvek and Tychem protective clothing is available in a range of models, such as a suit with a hood or collar, integrated socks, sewn or covered seams, thumb hole, etc. Accessories including sleeves, overboots, overshoes, lab gowns, aprons and back-fastening gowns, supplement the product range. The cost of waste disposal is not very high for users, as Tyvek and Tychem materials do not contain "critical" additives (those with halogen, for example) and can therefore be incinerated by local councils. Obviously, if clothing has been contaminated with hazardous substances, then it must be disposed of in the same way as the actual substances. The relevant national laws and regional regulations apply.

For more information

Ulrike Koster, Life Sciences Marketing Manager (Ulrike. Koster@lux.dupont.com) and Steve Marnach, Life Sciences Sales Specialist (Steve.Marnach@lux.dupont.com) DuPont Personal Protection Luxembourg (www.dpp-europe.com).

The DuPont Oval, DuPont[TM], The miracles of science[TM], Tyvek[R] and Tychem[R] are registered trademarks or trademarks of E.I. du Pont de Nemours and Company or its affiliates.

References

(1.) International Agency for Research on Cancer (IARC): IARC Monographs on the Evaluation of Carcinogenic Risks to Humans (www.iarc.fr).

(2.) TRGS 905: Verzeichnis Krebserzeugender, Erbgutverandernder oder Fortpflanzungsgefahrdender Stoffe (List of Carcinogenic, Mutagenic and Reprotoxic Substances), www.baua.de.

(3.) Suva Schweizerische Unfallversicherungsanstalt (Swiss National Accident Insurance Fund), Occupational Medicine Department: Sicherer Umgang mit Zytostatika (Safe Use of Cytostatics), www.suva.ch (Issue 6, June 2004, Lucerne Switzerland).

(4.) TRGS 525: Umgang mit Gefahrstoffen in Einrichtungen zur Humanmedizinischen Versorgung (Use of Hazardous Substances at Human Medical Facilities), www.baua.de.

(5.) ArbSchG: German Act on Conducting Occupational Safety Measures to Improve Health and Safety at Employees' Workplaces (http://de.osha.europa.eu).

(6.) GefStoffV: German Regulation on the Protection from Hazardous Substances (http://de.osha.europa.eu).

(7.) PSA BV: Health and Safety Regulation for the Use of Personal Protection Equipment at Work (Article 1 in implementation of the EC Directive on the EC Framework Directive on Occupational Safety), http://de.osha.europa.eu.

(8.) G. Carstens, "Personliche Schutzausrustung (Personal Protection Equipment)" in QuapoS 3--Quality Standards for Oncological Pharmacy Services with Commentary (Institute for Applied Healthcare Sciences [IFAHS eV] for the Deutsche Gesellschaft fur Onkologische Pharmazie [DGOP eV]) as the result of the 11th Convention on Oncological Pharmacy (January 2003).
Table I: Classification of cytostatics according to carcinogenic
effect (IARC and EU Directive 67/548, Annex VI)

Category     Carcinogenic Effect on People            Examples

Category 1   Carcinogenic: Substances with a known    Cyclophosphamid
             carcinogenic effect on people. There     Melphalan
             is sufficient evidence to establish a    Thiotepa
             causal link between human exposure to    Treosulfan
             a substance and the development of
             cancer. Cyclophosphamid

Category 2   May be or is likely to be                Cisplatin
             carcinogenic: Substances that should     Dacarbazin
             be considered to be carcinogenic to      Mitomycin
             people. There is sufficient evidence
             to presume that human exposure to a
             substance may result in the
             development of cancer. This
             presumption is generally based on
             suitable long- term animal trials or
             other relevant information.

Category 3   Not classifiable as carcinogenic:        5-Fluorouracil
             Substances that cause concern for        6-Mercaptopurin
             people owing to possible carcinogenic    Methotrexat
             effects but in respect of which the
             available information is not adequate
             to make a satisfactory assessment.
             There is some evidence from
             appropriate animal trials, but this is
             insufficient to place the substance in
             Category 2.

Table II: Examples of measures to avoid the contamination of people
during the production and preparation of cytostatics."

Types of measures      Examples of measures

Technical              Suitable morns and furnishings
                       Production and preparation in a suitably safe
                         workplace or an insulated environment
                       Use of technical aids such as pressure relief
                         and transmission systems

Organizational         Standard operating procedures must be written
                         and made available to the workforce
                       Suitable working methods to prevent the release
                         of cytostatics
                       Regular workplace-specific instructions
                         concerning dangers and precautions
                       Observance of a ban for pregnant and
                         breastfeeding women

Personal Precautions   Wear suitable protective gloves
                       Wear suitable protective clothing
                       Wear a respirator (at least protection level P
                         2) or goggles/visors in certain situations,
                         such as cleaning activities

Health and Safety      Examinations by occupational physicians

Table III: Definition of protective clothing types: chemical
protective clothing Category III.

Type     Description                                    Standard

Type 1   Gas-proof                                      EN 943-1
                                                        EN 943-2
Type 2   Not gas-proof                                  EN 943-1
Type 3   Protection from pressurization with liquid     EN 14605
           chemicals
Type 4   Protection from liquid aerosols                EN 14605
Type 5   Protection from solid airborne particles       EN ISO 13982-1
Type 6   Limited protection from liquid mists           EN 13034

Table IV: Employer's obligations concerning the use of PPE under
German legislation and regulations.

Law Regulation            Extract

ArhSchG (German           Section 3: fundamental Duties of the Employer
Occupational Health
and Safety Act) (5)       (1) The employer shall take whatever
                          measures are required for occupational
                          health and safety with due regard to the
                          circumstances that affect the health and
                          safety of employees at work. The employer
                          shall check measures for their effectiveness
                          and, where necessary, adjust them to changes
                          in circumstances. In doing so, the employer
                          shall aim to improve the protection of
                          employees' heath and safety.

                          (2) To plan and conduct the measures
                          specified in Subsection 1, the employer
                          shall take care to ensure the following,
                          with due regard to the type of work and the
                          number of employees: 1. Ensure suitable
                          organization and supply the required
                          resources; 2. Ensure that, where necessary,
                          the relevant measures are observed in all
                          activities, that they form part of
                          operational manayement structures and that
                          employees meet their obligations to co-
                          operate.

GefStoffV (German         Section 14: Provision of Information and
Hazardous                 Instructions to Employees
Substances Act) (6)
                          (1) The employer shall ensure that employees
                          have access to written operating
                          instructions as specified in Sentence 2,
                          that such instructions take account of the
                          hazard appraisal and that they are written
                          in a form and language that can be
                          understood by the employees. Operating
                          instructions shall contain at least the
                          following minimum details:

                          1. Information concerning hazardous
                          substances occurring at the workplace, such
                          as the names of such substances, their
                          labels and their health and safety hazards.

                          2. Information on suitable precautions and
                          measures that must be conducted by each
                          employee for their own protection and for
                          the protection of other employees at work,
                          in particular:

                          a) hygiene regulations

                          b) information on measures required to
                          prevent exposure

                          c) information on wearing and using personal
                          protection equipment and protective
                          clothing, etc.

PPE User Regulation (7)   Section 1: Scope

                          (1) This regulation applies to the provision
                          of personal protection equipment by the
                          employer and to the use of such equipment by
                          employees at work.

                          (2) Personal protection equipment within the
                          meaning of this regulation is any equipment
                          used or wan by employees to protect
                          themselves against dangers to their health
                          and safety as well as any supplementary
                          equipment used for the same purpose in
                          combination with the said personal
                          protection equipment.

                          (3) The following items do not quality as
                          personal protection equipment within The
                          meaning of Subsection 2:

                          1. Working clothes and uniforms that do not
                          specifically serve to protect the health and
                          safety of employees.

                          Section 2: Provision and Use

                          (1) Notwithstanding its duties under
                          Sections 3, 4 and 5 of the German
                          Occupational Heath and Safety Act, the
                          employer may only choose personal protection
                          equipment and make the same available to its
                          employees if such equipment meets the
                          requirements detailed in the regulation
                          governing the circulation of personal
                          protection equipment.

Table V: Guidelines for protection from cytostatics.

                    Particles                   Liquid

                              <1                           Not
            >1 [micro] m   [micro]m   Water-soluble   water-soluble

Tyvek            *
Tychem C                      *             *
Tychern F                     *                             *

Table VI: List of requirements for protective clothing and DuPont
protective clothing materials.

                  Protective Clothing
                  Requirements

Personal          Protection from liquid
Protection        hazardous substances

                  Protection from solid
                  hazardous substances

                  Protection from organic
                  hazardous substances

                  Reliable electrostatic
                  charge derivation

Product           High abrasion resistance to
Protection        prevent release of fibres

                  High particle barrier of
                  material and tight seams

                  Low particle emission
                  of material

                  Sterilizable

Wearing Comfort   Must allow body to
                  transmit heat; safe to
                  work with, perfect fit

                  Safe to work with,
                  perfect fit

Environmentally
Friendly

                  Tyvek            Tychem C        Tychem F

Personal          Inorganic        Inorganic       Organic and
Protection        chemicals at     chemicals       highly
                  low                              concentrated
                  concentrations                   inorganic
                                                   chemicals

                  Particles >1     Particles <1
                  [micro]m         [micro]m

                  Limited, only    Protection from contaminated
                  protects from    particles and liquids; meets
                  contaminated     standard requirements in
                  particles        highest performance classes
                                   (EN 14126)

                  Materials are antistatic

Product                 *
Protection

                        *          100% particle-tight

                        *

                        *

Wearing Comfort   Air and steam    Particle-tight and therefore
                  permeability     100% air-tight and
                                   steam-tight

                        *

Environmentally   Contains no halogen compounds and therefore
Friendly          may be disposed of without leaving residues
                  that would pose hazards to the environment or
                  human health. Obviously, this does not apply
                  to contaminated protective clothing.
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Title Annotation:cleanrooms
Author:Koster, Ulrike
Publication:Pharma
Article Type:Report
Geographic Code:4EULU
Date:Sep 1, 2009
Words:2942
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