Report By: ADAS Consulting Ltd

Defra Project NF0508

Report by: ADAS Consulting Ltd

Authors: R. Weightman, A. Lyne, D. Tiffin & P. Taylor

Date: 31st March 2005

HACCP Based Crop Assurance

Scheme for Medicinal Herbs

Technical annex to:

Defra Project NF0508

Exploiting the potential for UK pharmaceutical and medicinal herbs

through optimised process and production methods

ADAS Consulting Ltd,

Centre for Sustainable Crop Management,

Battlegate Rd,

Boxworth,

Cambs CB3 8NN.

Email:

Web:

ADAS Consulting LtdPage 1

Defra Project NF0508

Table of Contents

Background

Initial scope of the study

Issues which arose during the course of the study

The HACCP plan

HACCP Based Crop Assurance Scheme for Medicinal Herbs

1.Good Manufacturing Practice (GMP)

1.1. GMP Control Chart – Site, Structure and Facilities

1.2. GMP Control Chart – Supplier Quality Assurance, Specification, Traceability and Storage

1.3. GMP Control Chart – Equipment

1.4. GMP Control Chart – Chemicals

1.5. GMP Control Chart – Personnel

1.6. GMP Control Chart – Pest Control

2. Medicinal herbs production flowchart

3. MEDICINAL HERBS PRODUCTION HAZARD ANALYSIS

3.1. Hazard analysis – Crop Production

3.2. Hazard analysis – Primary processing of crop

3.3. Hazard analysis – Extraction of crop

3.4. Hazard analysis – Formulation of product

3.5. Hazard analysis – Packaging labelling and sale

4. HACCP Control charts

4.1. Crop production

4.2. Primary processing of crop

4.3 Extraction of crop

4.4. Formulation of product

4.5. Packaging, labelling and sale

5. Record keeping and documentation

6. Example Standard Operating procedures

Traceability

Product recall

Soil sampling for pH, nutrient and herbicide residue analysis

Steam distillation of plant material for production of essential oils and related products

7. References

Glossary of Abbreviations

BHTA / British Herb Trade Association
CCP / Critical Control Point
COLIPA / European Cosmetic, Toiletry and Perfumery Association
CoP / Code of Practice
CS / Consumer safety (hazard)
CTPA / UK Cosmetic, Toiletry and Perfumery Association
E / Environmental (hazard)
EC / European Commission
EMEA / European Medicines Agency
EU / European Union
EUROPAM / European Herb Growers Association
FACTS / Fertiliser Advisors and Certification Training Scheme
GAP / Good Agricultural Practice
GMP / Good Manufacturing Practice
HACCP / Hazard Analysis and Critical Control Point
HMPWP / Working Party on Herbal Medicinal Products
IATA / International Air Transport Association
L / Legal (hazard)
M / Microbiological (hazard)
MHRA / Medicines and Healthcare Products Regulatory Agency
Q / Quality
SCO2 / Supercritical carbon dioxide
SOP / Standard Operating Procedure
WHO / World Health Organisation

Acknowledgements

The authors would like to thank Helen Greenleaves of ADAS Arthur Rickwood for technical assistance, Mr Ken Goodjer for hosting visits to the facility of Norfolk Essential Oils, Welney, Norfolk and for invaluable discussions on herb production, and Mr Tony Gettins of Boots PLC for advice on legislative matters.

Background

To achieve a sustainable medicinal herbs industry in the UK, growers need to compete with imported products and raw materials, which have on numerous occasions, been reported to be of poor quality e.g. products contaminated with heavy metals; Dwivedi & Dey, 2002; Saper et al., 2004). One of the areas where UK growers can gain competitive advantage is through producing a safe product of superior quality, underpinned by a demonstration of first class traceability and crop assurance systems.

Ethnic medicines available in the UK are subjected to the same regulatory controls as ‘Western’ complementary medicines. Because of perceived deficiencies in consumer protection with respect to medicinal herbs, there is a draft European Directive 76/78/EEC (see Anon, 2002a) covering the marketing of traditional herbal medicinal products. Even though the legislation is still due to become effective at the time of preparing this report, it is advised that producers act as if it is in place now. One of the main requirements is the production of a quality dossier, demonstrating manufacture according to principles of good manufacturing practice (GMP). This underlines the need to develop and provide sound guidance on the principles of manufacture of medicinal herbal products

If medicinal herb producers wish to grow to a standard, currently they can use the generic crop assurance scheme for culinary herbs (Crop ID 38; Assured Crop Produce Ltd). However, in common with most crops assurance schemes in the UK, this does not cover production steps post-harvest (the last step in the flow chart is ‘harvest and storage’). When reviewed, there was seen to be a gap in the current crop assurance scheme, which needs to include drying, extraction, bottling, packing etc to cover the whole process. Therefore it was deemed desirable to develop a generic science based crop assurance scheme, specifically for medicinal herbs, and related products, which would extend to include on-farm processing.

Specific guidelines describing Good Agricultural Practice (GAP) for medicinal herbs, have been developed by the European Herb Growers Association (EUROPAM; Anon, 2003a). The UK has had input to these guidelines through the involvement of the British Herb Trade Association (BHTA). The EUROPAM guidelines in turn, form the basis of the paper released by the European Agency for the Evaluation of Medicinal products (EMEA) working party on Herbal Medicinal Products. EMEA described the points to consider with respect to: ‘Good agricultural and collection practice for starting materials of herbal origin’ (Anon 2002b). More recently, the World Health Organisation (WHO) have published draft guidelines on good manufacturing practices (GMP), in relation to the manufacture of herbal medicinal products (Anon, 2004). These are intended to complement those guidelines available for GMP for pharmaceutical products, and harmonisation of the various documents will undoubtedly occur over time.

While the above GAP guidelines contain much useful information, there is no documented evidence as to how the hazards were assessed. Clearly, the documents have been developed from contributions of a large group of stakeholders, and as a consequence some of the guidelines conflict. For example EUROPAM guidelines advise that fresh products (excluding basil) should be stored between 1 and 5 ○C (Anon, 2003a), whereas WHO guidelines advise storage between 2 and 8 ○C (Anon, 2004). These may be minor differences in practice, but highlight the fact that a grower cannot currently take one of these GAP guidelines, and use it as a robust working protocol.

The aim of the present study was to provide a generic protocol, based on a HACCP approach, which could be applied to any growers premises, to provide a framework for assessing those hazards, and provide a complete system which will allow for monitoring and documentation of a production system. It should be noted that production of crops, whether medicinal herbs or otherwise, should conform to the Codes of Good Agricultural Practice published by Defra (MAFF, 1998; Defra, 2001a,b).

The HACCP analysis presented here does not apply to any processes or harvesting relating to wild-crafting, but only production of cultivated crops in the UK. Further advice on Good Wildcrafting Practice can be found in the relevant EUROPAM paper (Anon, 2003b).

Initial scope of the study

The scope of the exercise for medicinal herbs was extended to include safety to consumers (e.g. control of pesticides, heavy metal contamination and mycotoxins), quality aspects (e.g. traceability) and environmental issues (e.g. use of pesticides), but excluded operator health and safety, except where these issues were covered under generic hazards such as staff training. Model procedures, work instructions and records were produced for all stages of production to assist businesses to adopt a fully effective system.

In terms of plant extraction, a number of different processes were considered, which are applied to the production of different medicinal products including distillation of essential oils, preparation of tinctures using cold alcohol (ethanol), organic solvent (e.g. hexane) extraction and supercritical carbon dioxide (SCO2) extraction. Of these, we have focussed on the production of essential oils only, for the following reasons:

Hexane extraction is a potentially dangerous process, and growers should not attempt this without extensive specialist training. Many extractions facilities exist in the UK, which can carry out toll manufacture, and growers interested in developing products based on organic solvent extraction are strongly advised to seek supply chain partners to work with. SCO2 extraction likewise, is a potentially hazardous process, using high-pressure gases. A high level of engineering competence is needed to manage an SCO2 extraction unit properly. Moreover, given the high capital cost involved, it makes more sense for growers to form co-operatives, and develop such facilities as part of a group, rather than trying to operate them individually.

In contrast, the preparation of a tincture, is a process which can conceivably be carried out on-farm. However, there are strict guidelines in place regarding manufacture, and any end-user buying tinctures will expect a high standard of product assurance, including the employment by the producer, of a ‘medical herbalist’ to authenticate raw materials and batches of product. The producer must be able to identify the species used, and ensure that no weed species are present, which could lead to contamination with toxic components. For example ‘Fools parsley’ (Aethusa cynapium) is poisonous and is a member of the Umbelliferae, a plant family which contains many useful aromatic herbs and vegetables, including celery, coriander, parsnip, fennel etc (Cooper and Johnson, 1988).

Issues which arose during the course of the study

Products for human consumption

It was noted during the course of the study that certain secondary products of the essential oil extraction process e.g. the floral waters, or hydrosols are economically valuable products in their own right. They can be added to cosmetic bases, and sold direct to customers, or used as medicinal products, perfumes and aerosols ‘as-is’. Hydrosols are also promoted for human consumption (Catty, 2001). However, in the UK if a producer knowingly sells floral waters or related products for consumption, he/she must bear in mind that food law would apply i.e. in the UK, obligations under the Food Safety Act. Even if the product has no nutritional value, it is likely that, if it is not classed as a medicine or a cosmetic, then it will be classed as a food (Medicines and Healthcare products Regulatory Agency, MHRA; Anon, 2003c). Although the layman may assume that hydrosols are safe and stable because they contain anti-microbial compounds, we have found no data to support this assumption. Further research would be needed in order to validate this assumption. It is better therefore to take a precautionary approach and to specify (label) such products as not for human consumption. The HACCP analysis presented below only applies to non-food products.

Storage and shelf life

There are no clear guidelines for the storage of essential oils, or methods to assess their shelf life stability. Tisserand and Balacs (1995) state that oils should be stored in dark bottles to exclude light, and avoid light induced oxidative degradation. Shelf life is indicated at 1 year for oils kept at room temperature, and 2 years for oils kept in a refrigerator. Tisserand and Balacs note that small amounts of essential oil remaining in larger bottles should be transferred to smaller bottles, in order to prevent oxidation. However, when oils are mixed with a cosmetic cream base (in order to prepare a cosmetic product), shelf life of the final product will be determined by a combination of the shelf lives of the individual ingredients and the cleanliness of the environment in which the product was formulated. Producers are strongly advised to join the UK Cosmetic, Toiletry and Perfumery Association (CTPA; to gain further specific advice on determining shelf life information.

Selling direct to consumers

It was noted that with the advent of the internet, and with some encouragement in the light of industry restructuring, it is increasingly straightforward to set up, and sell, products over the internet, or through farmers markets.

If a grower decides to sell directly to consumers, he or she must pay attention to:

• Traceability (see EU Directive 178/2002/EC);
• Packing (cleanliness, storage);
• Labelling (follow European Cosmetic Industry guidelines (see EU Cosmetics Directive 76/768, and other Trading Standards requirements e.g. quantity declarations which are covered by weights and measures regulations);
• Avoiding contamination (segregation of raw material, active ingredients, finished formulations);
• Shelf life (microbial contamination, temperature, relative humidity, lighting) where products are stored;
• Shipping/transport (many essential oils are considered highly flammable – specialist training is required for packing, especially for international air freight under IATA regulations);
• Qualified staff (staff must be trained in appropriate standards of personal hygiene, as for food production processes). The EMEA guidelines (Anon, 2002b) describe in detail the importance of personnel training and education.

The EU Cosmetics Directive (76/768/EEC) is continually being updated and amended. At the time of preparing this report, seven council amendments are in place, and over 30 technical adaptations have been published. A summary can be found at ( Any producer wishing to enter these markets must inform the Department of Trade and Industry (DTI; and register as a cosmetic manufacturer, and is strongly advised to join the UK Cosmetic, Toiletry and Perfumery Association (CTPA; who will be able to provide specific advice on compliance with the relevant legislation. Other trade bodies which can offer valuable advice will include the British Essential Oil Association and the Aromatherapy Trade Council and the British Herb Trade Association.

Any product, which is likely to be ingested, or applied to the skin or any other part of the body, must be produced with as much care, and attention to hygiene as a food product. This is because the skin, oral cavities, eyes etc, to which medicinal and personal care products may be applied, are routes through which chemicals can enter the body. Moreover, when skin is damaged, cuts and abrasions can provide infection routes for pathogenic micro-organisms. For this reason, EUROPAM (Anon, 2003a) note that all processing procedures should confirm to both EU-Guidelines on Food Hygiene (i.e. 178/2002/EC), to the General principles for Food Hygiene of the Codex Alimentarius, as well as the European Directive on Good Manufacturing Practice. These principles may not always be familiar to a primary producer. For this reason, we stress, particularly though the generic hazard controls in the HACCP analysis, that certain hygiene prerequisites must be in place if growers wish to enter this market place.

Selling to commercial companies

In addition to the points above, with respect to selling direct to consumers, should growers want to supply an extractor, end-user (e.g. retailer, formulator), or pharmaceutical company, they will have to follow the strict guidelines prescribed by the particular customer. Initial production should follow guidelines for GAP, as advised by the EU and the World Health Organisation (see WHO, 2004). Key areas which must be addressed by the producer, are as follows:

• Cleanliness of equipment and buildings;
• Batch processing records;
• Conformation of labelling/packaging to European and national labelling regulations;
• Organic products stored in accordance with national organic regulations and EU Directives;
• Maintenance of documentation covering all parts of the production process;
• Copies of all documents to be stored for a minimum of 7 years from the harvest date.

The above are currently guidelines only. The following additional information will be described in the suppliers’ manual of the relevant customer:

• Material Safety Data Sheets (MSDS: typically 16 sections, covering all aspects of product safety);
• Certificates of analysis/conformance;
• Packaging material;
• Environmental codes of practice.

For a new plant product, separate and additional requirements will be in place, for example provision of information on safety and toxicology, and data on the reproducibility of different batches of raw material.

The HACCP scheme developed here should provide a framework, whereby growers can adapt the crop assurance scheme, and meet all the above requirements, if demanded by the customer.

Outline of HACCP schemes – key requirements

Hazard Analysis and Critical Control Point is a system used by food businesses to ensure food safety. The general principles of HACCP are described by Codex Alimentarius (2003)

There are seven underlying principles to observe, when carrying out a HACCP analysis:

1.Conduct a hazard analysis.

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2.Determine the Critical Control Points (CCPs).

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3. Establish critical limits for the CCPs

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4.Establish a system to monitor control of the CCPs

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5. Develop corrective actions to be taken when monitoring indicates that a particular CCP is not under control

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6.Establish procedures for verification to confirm that the HACCP system is working effectively

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7.Establish documentation concerning all procedures and records appropriate to these principles and their application

The HACCP plan

The following items are presented in the HACCP plan:

Generic hazards

Hygiene prerequisites – encompassed in Good Manufacturing Practice and Product Recall. The fundamental basis upon which a quality assurance system must be built.

Production flowchart

Outlining the production steps

Hazard analysis

Record of the hazard analysis process. In some cases, we could not define controls as CCPs e.g. control of fungal growth leading to production of mycotoxins. This probably requires a CCP, but as we currently have little data on mycotoxin levels in herbs we cannot set limits, and so cannot define as a CCP.

Control charts

Listing only the Critical Control Points (CCP’s) and the process-specific controls, control measures and corrective actions. We have not listed responsibilities, but in practice, this would be required (e.g. farm manager, foreman, secretary etc)

Record keeping and documentation

Suggested SOP’s and associated records that would form the basis of a quality management system have been listed.

Example Standard Operating Procedures

1. Soil sampling
2. Steam distillation
3. Traceability
4. Product recall

HACCP validation

When a HACCP system has been prepared, it is essential that it is validated in the business where it was designed to function to ensure that it accurately describes the practices, that it is effective, and that it is practical. If these criteria are not met, then either the HACCP system or the business practice should be changed, and documentation updated.