Ciencia Aplicada Microbiologia Cosmeticos y Detergentes

8/13/2019 Ciencia Aplicada Microbiologia Cosmeticos y Detergentes

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11-2012

English EditionInternational Journal for Applied Science

Personal Care Detergents Specialties

W. Siegert

Microbiological Quality

Management for the

Production of Cosmeticsand Detergents


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COSMETICSPRESERVATIVES

W. Siegert*

Microbiological Quality Management for theProduction of Cosmetics and Detergents

The Target

Cosmetic products are not expected tobe aseptic; however, they must be com-pletely free of high-virulence microbialpathogens and the total number of aero-bic microorganisms per gram must below (4). Skin and mucous membranes areprotected from microbial attack by anatural mechanical barrier and variousdefence mechanisms (1). However, thesedefences may be damaged and a slighttrauma may be caused by the action ofsome cosmetics. This may increase thechance of a microbial infection. Such in-fections are of particular concern in cer-tain situations such as; when cosmeticsare used around the eyes, on mucousmembranes, on damaged skin, on chil-dren under 3 years, on the elderly andwith people showing compromised im-mune responses (1). Pathogens or oppor-tunistic pathogens whose incidence areof particular concern, especially in eye-area cosmetic products, include Staphy-

lococcus aureus, Streptococcus pyo-genes, Pseudomonas aeruginosa andother Pseudo-monasspecies also Kleb-siella pneumoniae (4). Pseudomonas

Producing microbiological faultless detergents and cosmetics requires

an integrated quality management system. This consists of good raw

material quality, hygienic design of production facilities, good pro-

duction hygiene and a validated preservative system.

The sustainable use of preservatives is optimised by the antimicrobial sta-

bilisation of detergents and cosmetics by utilisation of synergistic effects.Hazard analysis critical control point (HACCP) is a systematic preventive ap-

proach to safeguard microbiological faultless quality of products. The requi-

rements of ISO 22716 (Cosmetics Good Manufacturing Practices (GMP)

Guidelines on Good Manufacturing Practices) are demonstrated for the pro-

duction of aqueous products. Examples of proper hygienic design and ade-

quate hygiene measures are given, as well as a raw material and finished

product assessment according to ISO 29621 (Cosmetics Microbiology

Guidelines for the risk assessment and identification of microbiologically

low-risk products).

Introduction

Cosmetics Europe (2) PCPC (1) SCCS (3) US FDA (4)

Products specifically intended for children under 5 x 102 5 x 102 5 x 102 5 x 102

3 years (Category 1)

Products to be used in the eye area and on mucous 5 x 102 5 x 102 5 x 102 1 x 103

membranes (Category 1)

All other products (Category 2) 5 x 103 5 x 103 5 x 103 1 x 103

Table 1 Limits for the total viable count for aerobic mesophilic microorganisms in cosmetics [cfu/ml]


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SOFW-Journal | 138 | 11-2012 3


aeruginosa, Staphylococcus aureus andCandida albicans are considered themain potential pathogens in cosmeticproducts. These specific potentialpathogens must not be detectable in0.5 g or 0.5 ml of a cosmetic product ofCategory 1 and in 0.1 g or 0.1 ml of a cos-metic product of Category 2 (1).Table 1 shows the recommended limitsfor the total viable count of aerobicmesophilic microorganisms (1-4) fromdifferent guidelines.For household cleaning products fit foruse is the main demand, there is no le-gal demand for microbial cleanliness.

Nevertheless, in household products mi-crobial growth will negatively affect theproduct quality. Beside the health haz-ard of malodour there is potential cloud-ing or viscosity decrease (biodegradationof thickener) of the product. Bellying (gasformation e.g. by yeast growth) or con-traction (oxygen consumption by aero-bic growth) of the bottle could also beseen. Therefore following the same mi-crobial limits for household products asfor cosmetics is advisable.

Basic Conditions

Humidity, which means water, is avail-able in most products. It is the most im-portant factor for the multiplication ofmicroorganisms. Starting microbial cul-tures are always available from raw ma-terials through a range of sources suchas the used water, the production facili-ties and even from the air. Cosmeticproducts contain enough nutrients and

their storage at ambient temperature isnearly ideal for the growth of microor-ganisms.To produce microbial faultless products,an integrated microbiological qualitymanagement (MQM) is necessary. Thisincludes securing the microbiological pu-rity of the raw materials used, a validat-ed product formulation including thepreservation system, hygienic design andgood production hygiene.

Optimising the Preservation

The use of biocides has enabled a shift to-wards products with greater biodegrad-

ability. It could be argued, the value ofbiocides to the quality of our lives is be-yond price. Their function is primarilypreventative, minimising waste of nat-ural and limited resources while reduc-ing exposure hazards of people to harm-ful microorganisms (5).To achieve a sustainable preservative useit is important to utilise synergistic ef-fects that minimise the biocidal activesconcentration used. An optimised dosageconcept offers additional benefits. Thefollowing products and application rec-ommendations illustrate this principle.

Detergents and cleansersMicrobial contamination of detergent canoccur during its manufacture. The ma-

jority of the contaminants are present inthe source of water and raw materialsbut also in equipment vessels and plumb-ing lines (tanks and pipes).The additionof a fast-acting preservative with longterm protection at the beginning of theproduction process to sanitise the waterused for bulk production is a solution tothis problem. The killing of bacteria bysuch a preservative must occur withina few minutes, the very best situationwould be adding it before other ingredi-ents (6). The principle of adding the full

amount of biocide during the first wateraddition to the vessel is shown in Fig. 1.From extensive research work, Bis(3-aminopropyl)dodecylamine (BDA) wasrecognised as an excellent enhancer fortodays standard soft preservatives basedon methylisothiazolinone (MIT) in com-bination with benzisothiazolinone (BIT).This combination of actives is able tomarkedly reduce the contact time nec-essary to sanitise the water within thenormal production process to a few min-utes (Fig. 2), without enlarged holdingtimes.

CosmeticsTo minimise the amount of preservativeactives in cosmetics different approach-es are used in the market:

Combinations of preservative actives

Addition of multifunctional actives toboost the antimicrobial effect

Addition of chelating agents

Combination of multifunctionalactives to achieve self-preserving sys-tems

By combining phenoxyethanol with themultifunctional cosmetic additive ethyl-

Fig. 1 Recommended process to control waterborne contamination


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hexylglycerin an enhanced efficacy isachieved (7). The combination of 90%phenoxyethanol and 10% ethylhexyl-glycerin (euxyl PE 9010) is a commonreplacement for the standard phenoxy-ethanol / paraben mixtures (8).Fig. 3 shows

the boosting effect of ethylhexylglyc-erin.

Further improvement is achievable byadding chelating agents (9). Fig. 4 showsthe boosting effect of the tetrasodium di-carboxymethyl glutamate (GLDA) on eu-xyl PE 9010. GLDA in combination withcitric acid gives a noticeably better effect,including an improved effectiveness against

fungi, than can be achieved with EDTA.

The boosting effect of GLDA is also utili-sable for self-preserving systems. Fig. 5displays an example of a self preservingwet wipe liquid.

Good Manufacturing Practices(GMP)

Why more than adding a preservativeis necessary?The preservative must be able to controlthe types of microorganisms most com-monly present in the intended applica-tion.

Preservatives are used for the protectionof consumers and the prevention ofproduct spoilage during the intendedand foreseeable use. However, they shouldnot replace good production hygiene.Contamination by microorganisms dur-ing production has to be avoided byrecognising and eliminating its sources.

ISO 22716In November 2007 the new guidance forGood Manufacturing Practices (GMP)for the cosmetics manufacturing indus-try ISO 22716 was published (10). It de-scribes the basic principles of how to ap-ply GMP in a facility that produces fin-ished cosmetic products.Since 1977 cosmetic products and theiringredients must be produced by cos-metic GMP rules. This is demanded in thesixth amendment (1993) of the CouncilDirective 76/768/EEC (11); but there wereno detailed legal guidelines about cos-metic GMP. Some associations published

guidelines: IKW (German Cosmetic, Toiletry, Per-

fumery and Detergent Association):Cosmetic GMP guidelines for theproduction of cosmetic products(updated several times last update1997)

Colipa (European Cosmetics Associa-tion): Cosmetic Good ManufacturingPractices (1994)

Council of Europe: Guidelines for

Good Manufacturing Practice of Cos-metic Products (1995)

The European Cosmetic Regulation 1223/2009 (12) was published on 30 Novem-

Fig. 2 Results of the germ count reduction test with parmetol MBX

Fig. 3 Germ count reduction of Pseudomonas aeruginosaand Aspergillus nigerintap water achieved by euxyl PE 9010 compared to the single components

Pseudomonas aeruginosa Aspergillus niger


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ber 2009 and came into force on 10 Jan-uary 2010. From 11 July 2013 most of theprovisions will be applicable, as the regu-lations are effective 42 months aftercoming into force. Article 8 of this regu-lation requires:

The manufacture of cosmetic prod-ucts shall comply with Good Manu-facturing Practice with a view to en-suring the objectives of Article 1

Compliance with Good Manufactur-ing Practice shall be presumed wherethe manufacture is in accordance withthe relevant harmonised standards,

the references of which have beenpublished in the Official Journal ofthe European Union.

The reference to the harmonised standardISO 22716 was published on 21.4.2011 inthe Official Journal of the EuropeanUnion (13).

Basic requirements

ISO 22716 gives guidelines for the pro-duction, control, storage, and shipmentof cosmetic products. Related to micro-bial quality the main requirements are:

Cosmetic GMP regulations must befollowed in all areas of production, forall cosmetic products and for all busi-nesses (large or small)

Ensure adequate professional qualifi-cations of the person who is respon-sible for the production

Provision of suitable premises

Sufficient staff with appropriate

training Documentation of the activities and

inspections during production

Requirements for a good production

hygiene

Personnel hygiene 3.5.1 of ISO 22716 describes the de-mands for personnel hygiene Hygieneprogrammes should be established andadapted to the needs of the plant. Theserequirements should be understood and

followed by every person whose activi-ties take them into production, controland storage areas. Additionally the train-ing document ISO/TR 24475 (15) states

Fig. 4 Boosting effect of the tetrasodium dicarboxymethyl glutamate (GLDA) oneuxyl PE 9010

Fig. 5 Self preserving wet wipe liquid


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The personnel represent a permanentsource of potential errors and contami-nations and therefore need to have un-dergone appropriate training in accor-dance with their level of responsibility.Hands are an often underestimated riskof transmission of microorganisms. Fig. 6shows a typical contamination of a hand.If direct contact with products, raw ma-terials, production equipment, or pack-aging material occurs, a hand sanitisingis recommended, preferably with an al-coholic rub in.

Cleaning and sanitisation of premises

and equipmentFor cleaning and disinfection the follow-ing items have to be taken into account:

Premises used for the productionshould be maintained in a clean con-dition

Cleaning and, if necessary, sanitisa-tion should be carried out to achieve

the objective of protecting each prod-uct

Cleaning and, if necessary, sanitisingagents to be used should be specifiedand effective

There should be cleaning and, if nec-essary, sanitisation programmes cor-

responding to specific needs of eacharea

All equipment should be subject to anappropriate cleaning and, if neces-sary, sanitisation programme

Cleaning and sanitising agents shouldbe specified and effective

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Fig. 6 Contact slides from a hand show the importance of hand disinfection

Fig. 7 : Example of an individual hygiene plan


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Where equipment is assigned to con-tinuous production or production ofsuccessive batches of the same prod-uct, equipment should be cleaned and,if necessary, sanitised at appropriateintervals.

For the production of aqueous productslike shampoo, lotions, gels etc. sanitisa-tion is necessary because these productsallow the proliferation of microorganism.

Hygiene plan

The sanitisation procedures includingthe sanitising agents should be described

in an individual hygiene plan (Fig. 7).

Hygienic design

The ISO 22716 requires the principle:Equipment should be suitable for theintended purpose and capable of beingcleaned and, if necessary, sanitised andmaintained. ISO/TR 24475 states: Ifthere are ridges or unreachable corners,there is a risk of contamination of theprevious manufacturing run mixing withthe current batch. Hygienic design prin-ciples ensure that the machines can becleaned quickly and safely. The followingstandards help to specify the demands:

ISO 14159; Safety of machinery - Hy-giene requirements for the design ofmachinery (16).

DIN EN 1672-2; Food processing ma-chinery - Basic concepts - Part 2: Hy-giene requirements (17).

Fig. 8 shows an example from ISO 14159

about the design of tanks or container.

Availability of relevant documents(ISO 22716)An essential demand of GMP is thedocumentation. Relevant documenta-tion should be available at each stage ofmanufacturing operations. Manufactur-ing operations should be carried out ac-cording to manufacturing documenta-tion, including detailed manufacturingoperations for each stage, such as addi-

tion of raw materials, temperatures,speeds, mixing times, sampling, cleaningand sanitising of equipment, and bulkproduct transfer.

Before starting any manufacturing op-erations, it should be ensured that:

All documentation relevant to themanufacturing operations isavailable

All raw materials are available andreleased

Suitable equipment is available foruse, in working order, cleaned andsanitised

Clearance of the area has beenperformed to avoid mixing withmaterials from previous operations

Critical Control Points (CCPs)

The identification, evaluation, and con-trol of a product safety hazards is thegoal to achieve a safe production process.Its important to find out the criticalcontrol points to establish critical limits,monitoring procedures, and correctiveactions.

Critical raw materialsAll water and water-containing raw ma-terials may be microbially polluted. Therisk can be assessed as follows:

Highly concentrated material isless critical

Water-free but water soluble com-pounds are normally considered to besafe

Water insoluble compounds may beaccompanied by a small water phasee.g. from condensing water

Even white oil or natural oil can becontaminated if proper hygiene is notensured (regular draining)

As guideline ISO 29621 Guidelines forthe risk assessment and identification of

microbiologically low-risk products (14)is helpful. The rules for finished productscan be also applied to raw materials.Fig. 9 shows some examples of microbi-ologically low-risk products from ISO29621.

The total amount of preservativeThe total amount of preservative is thesum of:

The preservative added to the

water phase

The preservative added to theoil phase

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Fig. 8 Design of a container or tank to optimise the draining


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The preservative added to thefinished product

The preservative added to a premix

The preservative in the raw materials

The producer should know which andhow much preservative is in the raw ma-terials. If the preservative in the raw ma-terial changes the preservation of thefinished product may fail.

How to make sure the preservative isreally added?

From our experience one of the mainreasons of the failure of a preservative ina cosmetic product which has passed thepreservative test is just to forget to addit. A manual dosing should be performedon the basis of the four-eye principle.To guarantee this it is recommend thatone person is weighing the small com-pounds and provide a set of these rawmaterials for each batch. In the produc-tion another person should control anddose them to the batch. For automaticdosing mass flow-meters are recom-mended. Volumetric systems are less safeand dependent on the temperature. Forthese at least an alarm for an emptydosage system is necessary because thesesystems will also measure air.

Critical processA hot process e.g. at 80 C will eliminatemost contamination from the water andraw materials. In contrast to this a coldprocess cannot eliminate this risk whichmeans that the raw material quality willbe a more critical factor.Also highly viscous systems are more dif-ficult to cope with. Often a preservativecannot be added at the end of theprocess which limits the possible selec-tion of preservatives. Furthermore thematerial may be filled at a higher tem-perature which leads to an increased for-mation of condensing water. A preser-vative which provides head space pro-tection becomes more important.

Critical downtimeLong cold unpreserved phases (> 3 h)should be prevented during the produc-tion process. The staff has to be trained

that even during unplanned downtimethis is guaranteed. We recommend in-stalling special quality control checks ifa longer period occurs by accident. Atypical mistake which leads to longerunpreserved phases is to add the waterto a vessel the day before production tobe quicker at the start of next day in thefirst batch. If the water is preserved ofcourse this can be done, but unpreservedstorage should never happen.

Critical contamination control of bacillus spec.Bacteria spores are difficult to kill. Tem-peratures above 100 C are needed to killthem. Chemically, high amounts of form-aldehyde or glutaraldehyde can kill bac-terial spores as well as oxidising agentslike chlorine, hydrogen peroxide or per-acetic acid. Preservatives control onlythe vegetative form of bacillus species,but do not kill their spores. To prevent

bacillus contamination in a cosmeticproduct they should not be present inthe raw materials. Especially critical arethe raw materials derived from roots,leaves, or mud. Of course any multipli-cation of bacillus species in pre-solutionshas to be prevented. This can be man-aged by the addition of normal preser-vatives. Bacillus spores should also notbe brought in during the productionprocess. That means no soil or dustshould get into the product.

Change controlAny changes in the formulation, in theraw material quality, in the production

process or in the batch size have to beanalysed if they might have an influenceon the microbial stability of the formu-lation.Supposed minor changes can have se-vere influence on the susceptibility tomicrobial growth. For example a perfumecomposition can be a synergist to thepreservative system. One glycol will re-duce the active water value more thananother. An extract can contain a bioci-dal compound which another will notcontain.The same INCI name does not necessari-ly mean the same compatibility. Impuri-ties often lead to more incompatibilitiesthen the chemical itself. For example thechange from carbomer in powder formto a liquid form has shown dramatic ef-fects. The liquid material contained sul-phite impurities from the polymerisationprocess, which destroyed the isothiazoli-nones being used for the preservation ofthe end product. Also sulphonates based

on the production process can containhigh amounts of sulphite.Different pH values of raw materials haveto be adjusted in the finished product.Otherwise the stability can be influencedor pH value can get out of activity lim-its of the preservative actives.The upgrading of a formulation to a big-ger batch size is not only critical for thegalenic properties of emulsions. The big-ger batch size leads to a longer heatingperiod which means a good sanitation ofraw material contamination but a possi-

ble destruction of biocides. The longercooling period can lead to growing con-ditions for microbes before the preser-vative is added but also to a better dis-

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Fig. 9 Examples of low-risk products


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tribution of the preservative in the wa-ter phase caused by the longer stirringtime.Normally a microbiological challenge testis done during the development of a for-mulation. A re-validation should be per-formed with the first production batch.Each change should be secured by a newmicrobiological test.

Summary

According to the EU rapid alert system fordangerous consumer products (RAPEX)

contamination of cosmetics such as ba-by shampoo, cream, make-up, tooth-paste or shower gel has increased in thepast few years (18).It must be the aim of all manufacturersto ensure that their products are safe inall respects under normal and reasonablyforeseeable conditions of use. Contami-nating microorganisms may be harmfulto the consumer and may cause spoilageof the product. It is, therefore, necessaryto limit them. This can be achieved by:

Use of microbiologically satisfactoryraw materials

Use of good plant hygiene andmanufacturing practices

Hygienic design

Use of a validated preservative system

A microbiological quality management(MQM) is legally requested at least for

the production of cosmetics, but alsostrongly recommended for the produc-tion of cleaning products. The ISO 22716guidelines provide guidance regardingGood Manufacturing Practices.

References

(1) SCCS, Notes of Guidance for Testing of Cos-

metic Ingredients and Their Safety Evaluation7th Revision

(2) COLIPA, Guidelines on Microbial Quality

Management, (MQM) Edition of 1997

(3) CTFA, Microbiology Guidelines 2007, Section

12 Establishing Microbial Quality of Products

(4) FDA, Bacteriological Analytical Manual Chap-

ter 23 Microbiological Methods for Cosmet-

ics, C. Interpretation

(5) The European Producer of Antimicrobial Sub-

stances (EPAS), a Sector Group of Cefic, Ben-

efit of Biocides

(6) W. Siegert, A. Gckel, S. Carstens, A New Ap-

proach to Prevent Waterborne Contamina-

tion in Detergent Production, SOWF Journal

6-2011

(7) W. Beilfuss, M. Leschke, K. Weber, A New Con-

cept to Boost the Preservative Efficacy of

Phenoxyethanol, SOFW Journal11-2005

(8) M. Leschke, S. Wstermann, A Reliable Alter-

native for Traditional Preservative Systems,

SOFW Journal 4-2006

(9) W. Siegert, Can New Biodegradable Complex-ing Agents Replace Tetrasodium EDTA to

boost Preservatives? SOFW Journal 1/2 2008

(10) ISO 22716; Cosmetics Good Manufacturing

Practices (GMP) Guidelines on Good Manu-

facturing Practices

(11) COUNCIL DIRECTIVE of 27 July 1976 on the

approximation of the laws of the Member

States relating to cosmetic products (76/768/

EEC, consolidated http://eur-lex.europa.eu/

LexUriServ/LexUriServ.do?uri=CONSLEG: 1976

L0768:20111118:EN:PDF

(12) Regulation (EC) No 1223/2009 of the Euro-pean parliament and the council of Europe of

30 November 2009 on cosmetic products

http://eur-lex.europa.eu/LexUriServ/LexUri

Serv.do?uri=OJ:L:2009:342:0059:0209:EN:

PDF

(13) Official Journal of the European Union 2011/

C 123/04, Commission communication in the

framework of the implementation of Regula-

tion (EC) No 1223/2009 of the European Par-liament and of the Council on cosmetic prod-

ucts http://eur-lex.europa.eu/LexUriServ/Lex

UriServ.do?uri=OJ:C:2011:123:0003:0004:EN:

PDF

(14) ISO 29621, Cosmetics Microbiology Guide-

lines for the risk assessment and identifica-

tion of microbiologically low-risk products

(15) ISO/TR 24475, Cosmetics Good Manufac-

turing Practices General training document

(16) ISO 14159; Safety of machinery Hygiene re-

quirements for the design of machinery

(17) EN 1672-2; Food processing machinery Ba-

sic concepts Part 2: Hygiene requirements

(18) Bundesinstitut fr Risikobewertung (BfR),

Keime in Duschgel, Stellungnahme Nr. 036/

2009

* Authors address:

Wolfgang SiegertSchlke & Mayr GmbHRobert-Koch-Strae 2

22851 NorderstedtGermany

Email: [email protected]

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Ciencia Aplicada Microbiologia Cosmeticos y Detergentes