Microbial Quality Assurance in Pharmaceuticals, Cosmetics, and Toiletries

R. Baird, Sally F. Bloomfield

• Publisher: CRC Press
• Year: 2017
• ISBN:
  9781135743628
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Microbiology
• Index: Biological Sciences

The importance of quality assurance in the production, storage and use of manufactured preparations is widely recognized. This book encapsulates the issues involved in the manufacture of non-steriles, such as creams, ointments, herbal remedies, shampoos, soaps and toiletry products (as opposed to sterile drugs and injectible products). Knowledge of the microbial limits is expanded, new standards are included, and coverage of the preservation issues of dosage forms is widened to include semi-solids and liquid preparations. This edition also contains new regulations regarding preservative efficacy testing and covers pharmacopoeial and industry regulations and guidelines. Rapid methods are also discussed, now more common in cosmetic and toiletry practice, in their pharmaceutical capacity.

PART ONE

Identifying the issues

1

Control of microbial contamination in cosmetics, toiletries and non-sterile pharmaceuticals

SALLY F. BLOOMFIELD

Chelsea Department of Pharmacy, King’s College London, University of London, Manresa Road, London SW3 6LX

In the manufacture of cosmetics, toiletries and all types of pharmaceuticals, quality assurance represents a major consideration. This book is particularly concerned with one aspect of quality, namely the assurance that products are not contaminated with organisms which might affect their safety, efficacy or acceptability to the consumer or patient.

One obvious approach to this problem is to ensure that all products are manufactured either as sterile products or as ‘single-use’ packs. For cosmetics and toiletries and many pharmaceuticals, this is neither appropriate nor commercially viable and alternative means of microbial quality assurance are therefore sought. During product manufacture, microbial contamination is mainly controlled by the application of good manufacturing practice (GMP) whilst the maintenance of quality during storage and use (also the responsibility of the manufacturer) is achieved largely by the inclusion of preservatives but also by product design and by product formulation and packaging.

In practice, the presence of micro-organisms in pharmaceuticals, cosmetics and toiletries constitutes a potential hazard for two reasons. These aspects are reviewed in chapter 2. Firstly, it may result in spoilage of the product - the metabolic versatility of microorganisms is such that almost any formulation ingredient may undergo degradation in the presence of a suitable micro-organism. Alternatively, it may constitute an infection hazard to the consumer or patient, although here we have to bear in mind that the degree of hazard will vary considerably from one situation to another according to the intended use of the product (oral, topical, application to the eye, etc.) by the patient or consumer.

In attempting to define acceptable standards or limits for microbial contamination for non-sterile products, it is therefore extremely difficult to establish what levels and types of contamination represent a hazard and what can be considered as safe.

If the problem is examined from a historical point of view it is found that, prior to about 1960, although products were manufactured under hygienic conditions with the inclusion of a preservative, there was little evidence of the rigorous approach which is currently adopted. During the 1960s, following increasing numbers of reports of infection outbreaks associated with contaminated products (see chapter 2), there was a general realization of the need for improvements in microbial quality assurance for all types of products.

In order to assess how this might be achieved, a number of studies were initiated to obtain a general picture of the quality of products being manufactured at that time. Some of the studies were official or national studies as in Sweden and Denmark (Kallings et al. 1966; Ulrich, 1968), whilst others were independent surveys. The investigations included cosmetics and toiletries as well as pharmaceuticals. In the UK, two official studies of pharmaceuticals were initiated, one by the Public Health Laboratory Service to study hospital medicaments, the other by the Royal Pharmaceutical Society of Great Britain (RPSGB) to study all types of products (Anon. 1971a, 1971b). The results of all these surveys are reviewed in chapter 15.

Having established the nature and extent of the problem, the next step was to try to control it; the various official bodies had to decide the extent to which manufacturers should be asked to limit microbial contamination in their produces and how the standards should be applied. Inevitably, the limits varied from one country and one situation to another. Accepted limits may be ‘in-house’ limits or, for pharmaceuticals, may be applied via the pharmacopoeia or licensing systems. The various official, unofficial and ‘in-house’ standards which have been developed over the last 20 or so years are outlined in chapter 15.

In examining the methods which are currently adopted for controlling microbial contamination in pharmaceuticals, cosmetics and toiletries, it can be seen that in general these have been developed from specific recommendations laid out in the original RPSGB working party report and the report of a joint working party representing the Toilet Preparations Federation and the Society of Cosmetic Chemists (Anon. 1970). The recommendations of the RPSGB were then further developed and incorporated into the UK Guide to Good Manufacturing Practice (Anon. 1983). As a result of European harmonization, the UK guide has been superseded by the European Guide to Good Manufacturing Practice (Anon. 1992, 1993a). Recommendations relating to the manufacture of cosmetics and toiletries are outlined in a document published by the Cosmetic and Toiletry Products Association (Anon. 1993b).

If we refer to these recommendations, we find that they divide into three groups: recommendations related to GMP, recommendations related to formulation of the product, and recommendations which related to the inclusion of preservatives. In the following chapters of this book, each of these aspects is considered in detail. The problems of applying these various principles to microbial quality assurance of two specific groups of products, namely powder, tablet and capsule formulations, and hair and skin products is also discussed in chapters 7 and 8 respectively.

As far as GMP is concerned, the main concerns are with the microbial quality of the raw materials (particularly water) and with all aspects of the manufacturing process, the processing environment and equipment, the process itself and the personnel operating the process. These aspects are discussed in chapters 3 and 4.

As far as product formulation is concerned, any number of physicochemical factors can affect the fate of micro-organisms which enter a product. These factors include the conditions of water activity, pH and osmotic pressure within the product, the availability of nutrient material, the product storage temperature, and so on. In practice, it is found that some types of products are virtually ‘self-preserving’ such that residual contamination occurring during manufacture (or use) is reduced to undetectably low levels during storage. In the pharmaceutical industry, there has been some tendency to overlook this aspect and to rely almost entirely on chemical preservatives. With increasing concern over possibilities of toxic side effects associated with chemical preservatives, it is important to consider carefully the possibilities of ‘self-preservation or natural preservation’ of products. This aspect is discussed in chapter 5.

The third aspect relates to the inclusion of chemical preservatives. Although the microbial quality of products should be achieved by GMP, it may be necessary in certain types of product to include a preservative to protect the product against residual contamination introduced during manufacture and any further microbial contamination which might occur during use. It is clearly understood, however, that the function of the preservative must not be to cover bad manufacturing practice but to ensure that the product remains in a satisfactory condition during storage and use.

In solving problems related to chemical preservation, there are four main questions which have to be considered. Under what conditions is the inclusion of a preservative justified? What constitutes adequate preservation? What preservatives are available to meet our requirements? How do we establish that a product is effectively preserved?

In deciding under what conditions the inclusion of a preservative is justified, for some situations the indications are obvious whilst in others there may be room for disagreement. Thus, for example, in tablet film coating where working schedules demand advance preparation of film coating solutions, although the inclusion of preservatives in these solutions might be considered as an admission of bad manufacturing practice, in practice this is considered acceptable to prevent microbial growth which would otherwise occur during the unavoidable holding period prior to the film coating process. In addition to this, although tablets are assumed to be self-preserving, the question has been raised as to whether preservatives should be included to prevent incidents of mould growth which occur from time to time. Problems associated with control of microbial contamination in powders, tablets and capsules are discussed in chapter 8.

Secondly, it is necessary to consider what constitutes adequate preservation. As far as pharmaceuticals are concerned, it appears that the licensing authorities currently allow themselves to be guided by criteria defined in the British Pharmacopoeia (BP), European Pharmacopoeia (EP) and United States Pharmacopoeia (USP) tests for preservative efficacy (Anon. 1993c, 1993d, 1995). If one asks how such standards have arisen, it would be difficult to get a precise answer. It would be comforting to believe that they represent a definitive knowledge of the required activity to protect the product and user against the appropriate hazard, but in practice, as mentioned earlier, such information is not available, nor is it ever likely to be. In effect, the criteria appear to be based on a knowledge of what is achievable in relation to the range of available preservatives and a working knowledge of preservative efficacy in manufactured products. In recognition of the problems of deciding what constitutes adequate preservation, and the fact that this may vary from product to product according to its nature and intended use, the BP test states that, at present, compliance with the test is not rigidly demanded; deviation is acceptable where it is adequately justified by bacteriological and othe...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• Preface
• PART ONE IDENTIFYING THE ISSUES
• PART TWO CONTROL IN MANUFACTURE
• PART THREE CONTROL THROUGH PRESERVATION
• PART FOUR MICROBIOLOGICAL CONTROL: METHODS AND STANDARDS
• Index