Producers of cosmetic products are legally obliged to comply with the principles and guidelines of good manufacturing practice (GMP). This requirement was formulated in the 6th amending directive to the Cosmetic Products Directive 76/768/EEC and anchored in German national law on 1 July 1997 in section 5 of the Cosmetics Ordinance (Kosmetikverordnung).

Compliance with the guidelines of good manufacturing practice should ensure that cosmetic products of constant quality are produced and tested in line with a defined quality standard. A Community guide to GMP for cosmetic products does not yet exist, but national and European guidelines are available. On the European level there are publications by COLIPA (1) and the Council of Europe (2). The SCCNFP (Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers) is expected to produce its recommendations by the end of 1999. In Germany the revised version of GMP for cosmetics (3) was published by the IKW (Industrieverband Körperpflege- und Waschmittel) in 1995 and supplemented by a self-assessment checklist (Checkliste zur Selbstbewertung (4)) in 1997.

Requirement to be satisfied by producers of cosmetic ingredients

The quality of cosmetic products largely depends on the quality of the starting materials. The guidelines of GMP for cosmetic products include the requirement that all starting materials should correspond to the agreed specifications and be of consistently good quality. This requirement applies equally to chemical and physical product parameters and microbial purity. Moreover the compatibility of the ingredients and the packaging must be ensured. The supplied containers must be clearly identifiable and bear the following information: product name, batch number, number of items, gross weight and tare weight. From this requirement with regard to quality, packaging and labeling, it is clear that producers of cosmetic ingredients must also comply with the principles and guidelines of GMP. Aspects such as the quality of the cosmetic ingredients, product and storage stability, adequate preservation and the compatibility of cosmetic ingredients and packaging are all checked during the development stage, and appropriate specifications of the cosmetic ingredients are defined. Production should be carried out in compliance with GMP to ensure that the defined level of quality is maintained and is not impaired in any way by the production process.

Main requirements of GMP

The GMP guidelines indicate that production should be carried out by qualified personnel in suitable premises with suitable equipment. Measurement and control instruments should be regularly calibrated and serviced. A comprehensive system of records should be established to provide documentation of the consistent good quality of production, storage and testing. All activities during production and testing should be recorded for each product and batch. Comprehensive documentation of the preparation and filling operations for each batch and the associated results of the quality testing of intermediate, bulk and finished products, as well as appropriate reserve samples, should enable the production history of each batch to be traced seamlessly if a complaint is received.

Like cosmetic products, cosmetic ingredients must be produced in a clean and perfectly hygienic environment to exclude any form of contamination. Production premises, equipment, instruments, storage tanks, containers, etc. should accordingly be maintained to a high standard of cleanliness. The equipment, containers and storage tanks used for production should be clearly labeled to minimize the risk of mix-ups between starting materials or batches.

Table 1
Documentation in conformity with GMP
·	Organigram with defined responsibilities
·	In-house processes
·	Process-related working procedures
·	Formulations
·	Production procedures
·	Batch-related production and filling reports
·	Quality testing records
·	Cleaning and disinfection instructions
·	Documentation of work performed
·	Hygiene plan
·	Waste disposal plan
·	Records of calibration and maintenance of control and measure- ment instruments
·	Documentation of personnel training courses
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Quality of starting materials/storage

Special attention should be devoted to the production of cosmetic ingredients that are susceptible to microbiological attack. Such ingredients must be handled with great care. Since they are usually preserved, the production process must be designed to ensure that the preservative action is not impaired at any stage of production or during storage.

A crucial requirement for the production of cosmetic ingredients with a low microorganism content is the use of starting materials with a low microorganism content. Incoming goods checks should therefore look at the microorganism content of critical materials as well as conformity with the defined chemical and physical specifications. Storage areas should be clean and dry and the stored materials should be clearly identifiable. The GMP guidelines also indicate that quarantined and released materials should be clearly separated and labeled. Next to the supplied starting materials, the microorganism count of the production water in particular is of crucial importance. In terms of volume, production water is often the main component of a formulation and for this reason it should be subjected to regular checks of its microorganism content. If necessary, one of a number of measures (bacterial filtration, ultraviolet irradiation, ozonization, etc.) can be taken to reduce the microorganism count to an acceptable level. The named methods can be monitored physically or chemically and should preferably incorporate an alarm system so that measures can be initiated immediately if any deviation from a threshold value is detected.

Requirements concerning production premises

In premises used for the production of cosmetic ingredients, the production areas should be clearly separated from all ancillary areas. All surfaces in the production areas should be smooth, permitting easy and effective cleaning and disinfection. Windows and doors should be kept closed to keep out dust, soil, birds, rodents, insects, etc. External ventilation systems should be fitted with appropriate filters and inspected at regular intervals. In particular, it is advisable to regularly check the microorganism content of the air if fluidized bed systems are used. It is advisable to use filters that are impermeable to both dust and microorganisms in ventilation systems for storage tanks. In addition, drums and small containers in the filling area should be protected from dust and soil during storage and filling.

Cleaning and disinfection

Equipment used for production, filling and storage should be regularly cleaned and disinfected to prevent microbial contamination. Written cleaning and disinfection procedures should be drawn up for this purpose, indicating the products to be used and the necessary concentrations and exposure times. Cleaning and disinfection operations should be documented.

Cleaning and disinfection measures can only be carried out effectively if the production equipment is capable of being cleaned. This means that it must be designed so that it can be emptied completely and has no “dead”, non-rinsable sections. The cleaning and disinfection agents must be able to access all parts of all surfaces that come into contact with the product. Equipment that does not meet these basic requirements can only be satisfactorily cleaned by dismantling the critical sections.

Avoidance of cross-contamination

When materials and products are transported from non-clean zones into production and filling areas, it should not be possible for microorganisms to accompany them. Moreover, the establishment of plant-specific rules of personal hygiene is advisable. Employees should be instructed about washing and, if necessary, disinfecting their hands; suitable work clothing; not smoking, eating or drinking in the workplace; rules of behavior governing illness or injury, coughing and sneezing, etc., so that at least the minimal requirements of personal hygiene are satisfied and, in this way, personnel-related sources of risk are minimized.

Filling of finished products/finished product checks

Filling equipment, like production equipment, should be regularly cleaned and disinfected. To avoid contamination, the drums and other containers that are used must have a low microorganism content. Special protective measures should be taken, in particular, when filling tank trucks. Tank trucks should be properly cleaned and steam-treated before they are filled. Insistence on the provision of a cleaning certificate has proven worthwhile. Tank trucks cannot usually be filled in clean areas, and such operations are generally performed outdoors. For this reason it is advisable to use a disinfected filler hose and to fit the manhole of the tank truck with a special cover to keep out soil.

Sensitive cosmetic ingredients should be subjected to microbiological checks before they are released for delivery. Samples should be taken from the full containers or tank trucks under clean-room conditions. The documented test results and reference samples should be available in case complaints are received.

Documentation and personnel training

To avoid potential sources of error it is advisable to draw up specific procedures for the individual production areas. The content and purpose of these procedures should be explained to production personnel during training courses, in order to achieve acceptance of the described measures. The guideline shown in Table 2 can be used as a basis for systematically safeguarding the production process.

As well as the initially mentioned documentation of all defined processes, documentation of the personnel training courses has also proven worthwhile. When an audit is carried out, only comprehensive documentation can prove what measures were taken to protect cosmetic ingredients.

Table 2
Guidelines for safeguarding the production of cosmetic ingredients
1.	Draft hygiene measures for storage, production and filling areas
2.	Draft rules of behavior for personnel in each production area
3.	Draft hygiene measures for handling starting materials
	- Instructions on procedures for incoming goods and storage of   goods delivered in drums and sacks
	- Hygiene measures for weighing starting materials handling   instruments and containers and proper labeling, as well as   instructions on handling cracked containers.
4.	Measures and checks for monitoring production water
	- Checks (physical, microbiological) to monitor the water quality   and the efficiency of the method used to reduce the microorgan-   ism count in the production and filling areas and in the zones   where containers and equipment are cleaned.
5.	Production premises
	- Define the frequency with which cleaning and disinfection have   to be carried out on equipment used to produce cosmetic ingre-   dients and to transfer them to intermediate storage tanks
	- Draw up a cleaning procedure, specifying the method, the pro-   ducts to be used, their concentrations and the exposure times.
	- Draw up a code of behavior for personnel who handle products   that are susceptible to microbiological attack.
	- Define maximal residence times for batches that are susceptible   to microbiological attack.
6.	Filling area
	- Define the frequency with which cleaning and disinfection have   to be carried out on filling equipment
	- Draw up a cleaning procedure, specifying the method, the prod-   ucts to be used, their concentrations and the exposure times.
	- Hygiene measures when handling drums, containers, etc.
	- Hygiene measures when filling tank trucks
7.	Measures for microbiological product release
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References

(1) COLIPA (1988, 1994) Cosmetic good manufacturing practice. Brussels
(2) Council of Europe (1955): Guidelines for good manufacturing practice of cosmetic products (GMPC). Strasbourg
(3) Industrieverband Körperpflege- und Waschmittel e.V. (1992, 1995): Kosmetik GMP. Leitlinien zur Herstellung kosmetischer Mittel. Frankfurt a. M.
(4) Industrieverband Körperpflege- und Waschmittel e.V. (1997): Kosmetik-GMP. Checkliste zur Selbstbewertung. Frankfurt a. M.

Dipl. Ing. Regine Scholtyssek

Dipl. Ing. Regine Scholtyssek, formerly head of the Microbiological Department of Hans Schwarzkopf GmbH, is now active in the field of Biology/Product Safety at Henkel KGaA. Here, she is mainly in charge of Schwarzkopf & Henkel Cosmetic in terms of microbiological issues.