Guidelines for Cultivating Cannabis

for Medicinal Purposes

[Voorschriften voor de Verbouw
van Cannabis voor Medicinale Doeleinden]

Annex to the Regulation of the Minister of Health,

Welfare and Sport of 9 January 2003, GMT/BMC 2340685,
containing policy guidelines for the decision on applications
for Opium Act exemptions (Policy guidelines Opium Act exemptions)
(authorised English translation)

1. Introduction
2. General
3. Personnel and Training
4. Buildings and Facilities
5. Equipment
6. Seeds and Propagation Material
7. Cultivation
8. Harvesting

Provided courtesy of: Willem K. Scholten, MSc, Pharm, MPA, Office of Medicinal
Cannabis of the Pharmaceutical Affairs Directorate, Ministry of Health, Welfare and
Sport, P.O. Box 20350, NL-2500 EJ The Hague, Netherlands (E-mail: wk.scholten@
minvws.nl).
Journal of Cannabis Therapeutics, Vol. 3(2) 2003
http://www.haworthpress.com/store/product.asp?sku=J175
10.1300/J175v03n02_05 51
52 JOURNAL OF CANNABIS THERAPEUTICS

9. Primary Processing
10. Packaging
11. Storage and Distribution
12. Special Provisions for the Production of Cannabis Intended for
Processing into a Standardised Herbal Drug
13. Documentation
14. Safeguarding the Material

1. INTRODUCTION
Under certain conditions, the Dutch government permits the cultiva-
tion of cannabis for medicinal purposes. In the case of herbal drugs, the
cultivation method and primary processing of the plant determines the
ultimate properties of the active pharmaceutical ingredient. Starting
materials of herbal origin have a complex composition and can only be
characterised to a limited extent through chemical or biological analy-
sis. Therefore, an effective quality assurance system in the steps leading
up to the production of the active pharmaceutical ingredient is needed in
order to guarantee reproducible quality. These steps are cultivation,
harvesting and primary processing.
The following guidelines for cultivating, harvesting and primary pro-
cessing of cannabis constitute a quality assurance system that meets
these requirements. The Office of Medicinal Cannabis (Bureau voor
Medicinale Cannabis) will test on the basis of these requirements.
These guidelines have been derived from the general rules for Good
Agricultural Practice of the Working Group on Herbal Medicinal Prod-
ucts of the European Medicines Evaluation Agency (EMEA).
This is an authorised translation of the official version in Dutch.

2. GENERAL

2.1 These guidelines apply to the cultivation, harvesting and primary

processing of cannabis plants intended for medicinal use or the
preparation of medicinal drugs. These guidelines must be read in
connection with the European Good Manufacturing Practice (GMP)
guidelines for active pharmaceutical products. They apply to all
methods of production including organic cultivation. These guide-
 Guidelines 53

lines also provide additional standards for the production and pro-
cessing of herbal starting materials insofar as they identify the
critical production steps that are needed to ensure good, reproduc-
ible quality.
2.2 The main objective of these guidelines is to increase the reliability
of the medicines prepared from cannabis by establishing an appro-
priate quality standard for the herbal medicine cannabis. In partic-
ular, it is important that the cannabis:
• is produced hygienically to keep microbiological contamina-
tion to a minimum;
• is produced such that negative effects on the plants during
cultivation, processing and storage are kept to a minimum;
• is produced under conditions that ensure that the therapeutic
properties of the end product are constant and reproducible.

3. PERSONNEL AND TRAINING

3.1 Training
3.1.1 Personnel must have received adequate botanical/horticultural
training before performing the tasks given to them.
3.1.2 Production personnel must be trained in the production tech-
niques used.
3.1.3 Primary processing procedures must comply with the regula-
tions on food hygiene.
3.2 Hygiene
3.2.1 All personnel entrusted with handling the herbal material must
maintain proper personal hygiene.
3.2.2 Persons suffering from infectious diseases transmittable via
food, including diarrhoea, or carriers of these diseases must be
forbidden access to areas where they could come into contact
with the herbal material.
3.2.3 Persons with open wounds, inflammations and skin-infections
must be suspended from areas where they could come into con-
tact with herbal material, unless they wear protective clothing or
gloves until they have recovered completely.
54 JOURNAL OF CANNABIS THERAPEUTICS

3.2.4 Personnel must be protected from contact with toxic or poten-

tially allergenic herbal material by means of adequate protective
clothing.

4. BUILDINGS AND FACILITIES

4.1 Buildings used in the processing of harvested crops must be clean,

well ventilated and must never be used for other activities.
4.2 Buildings must be designed in a manner that protects the crops
against pests and domestic animals.
4.3 The medicinal cannabis must be stored:
• in a suitable packaging;
• in rooms with concrete or similar floors which are easy to
clean;
• on pallets;
• at a sufficient distance from walls;
• well separated from other crops in order to prevent cross-
contamination.
Organic products must be stored separately from products not
grown organically.
4.4 Buildings where plant processing is carried out must have chang-
ing facilities, toilets and hand-washing facilities.

5. EQUIPMENT

5.1 Equipment used in plant cultivation and processing must be easy

to clean in order to eliminate the risk of contamination.
5.2 Equipment and machinery should be mounted such that they are
easily accessible. Machines used in fertiliser and pesticide appli-
cation must be calibrated regularly.
5.3 The equipment must be made from materials other than wood. If
wooden materials (such as pallets) are used, they must not come
into direct contact with chemicals and contaminated materials, in
order to prevent contamination of the herbal materials.
 Guidelines 55

5.4 Equipment and machinery used for harvesting must be clean and
in very good working condition. Machine parts that come into di-
rect contact with the harvested crop must be cleaned regularly and
must be free from oil and contamination, including residual plant
matter.

6. SEEDS AND PROPAGATION MATERIAL

6.1 Seeds and propagation material must be botanically identified as
to species, variety, chemotype and origin. The materials used must
be traceable. Starting material must be free from pests and disease
as much as possible in order to guarantee healthy growth.
6.2 Cuttings of female plants must be used as propagation material for
the production of cannabis.
6.3 During the entire production process (cultivation, harvest, drying,
packaging), the presence of male plants and different species, vari-
eties or different plant parts must be monitored. Any impurities
must be removed immediately.

7. CULTIVATION
7.1 Soil and fertilisation
7.1.1 Cannabis for medicinal purposes must not be grown on soil con-
taminated with sludge, heavy metals, pesticide residues or other
chemicals. Any chemicals used must therefore be kept to the
minimum effective dose.
7.1.2 Manure applied should be thoroughly composted and must be
devoid of human faeces. Irrigation should be controlled and ac-
cording to the needs of the cannabis plant. Fertilisers should be
used in such a way that leaching is reduced to a minimum.
7.2 Irrigation
7.2.1 Irrigation must be controlled and only as required by the canna-
bis plant.
7.2.2 Irrigation water must contain as few as possible contaminants
like faeces, heavy metals, herbicides, pesticides and toxicologi-
cally hazardous substances.
56 JOURNAL OF CANNABIS THERAPEUTICS

7.3 All tillage must be adapted to plant growth and requirements.

Using herbicides and pesticides must be avoided as far as possible.
Use and storage of pesticides must be in accordance with the recom-
mendations of the manufacturer and the relevant approval authori-
ties. Only qualified personnel are allowed to use such substances
using only approved material but not in a period preceding the har-
vest, as indicated by the buyer or producer.

8. HARVESTING
8.1 Harvesting must be done when the plants have reached the best
quality for the intended use.
8.2 Male, damaged, and dead plants must be removed.
8.3 Harvesting must take place under the best possible conditions,
avoiding wet soil or extremely high air humidity. If harvesting oc-
curs in wet conditions, additional care needs to be taken to avoid
the adverse effects of moisture.
8.4 During harvesting, care must be taken that no other species or can-
nabis variety get mixed with the cannabis crop.
8.5 The harvested crop must not come into direct contact with the soil.
Directly after harvesting, it must be prepared for transport in clean,
dry conditions (e.g., sacks, baskets, boxes).
8.6 All containers must be clean and free from any residues from pre-
vious harvests; containers that are not in use must be kept in dry
conditions, free of pests and inaccessible to domestic animals.
8.7 Mechanical damage and compacting of the herbal drug that could
result in undesirable quality changes must be avoided. In this re-
spect, take care to avoid:
• overfilling sacks/containers;
• stacking sacks/containers too high.
8.8 Freshly harvested herbal material must be delivered to the pro-
cessing facility as quickly as possible in order to prevent thermal
degradation.
8.9 The harvested crop must be protected from pests and domestic ani-
mals.
 Guidelines 57

9. PRIMARY PROCESSING
9.1 Primary processing includes washing, cutting before drying, de-
contamination from pests, freezing, distillation, drying, etc.
9.2 On arrival at the processing facility, the harvested crop must be di-
rectly unloaded and unpacked. Prior to processing, the material
must not be exposed to direct sunlight (except in cases that specifi-
cally require this) and must be protected from rain.
9.3 Drying
9.3.1 Drying crops directly on the ground or under direct sunlight
must be avoided.
9.3.2 Uniform drying speed and prevention of mold growth must be
assured.
9.3.3 In the case that plant material is dried in the open air, it must be
spread in a thin layer. To ensure good air circulation the drying
racks must be placed at sufficient distance to the floor.
9.3.4 In the case plant material is not dried in the open air optimal drying
circumstances like temperature and drying time must be chosen.
9.4 Waste bins must be available and must be emptied and cleaned daily.

10. PACKAGING
10.1 Following repeated controls and removal of any sub-standard ma-
terial or undesired objects, the product must be packaged in clean,
dry and preferably new packaging. The label must be clear, firmly
fixed and made from non-toxic material.
10.2 Reusable packaging material must be well cleaned and dried prior
to use.
10.3 Packaging material must be stored in a clean, dry place that is free
of pests and inaccessible to domestic animals. The packaging ma-
terial must not contaminate the product.

11. STORAGE AND DISTRIBUTION

11.1 Dried, packaged products and extracts must be stored in a dry,
well-ventilated building in which daily temperature fluctuations
58 JOURNAL OF CANNABIS THERAPEUTICS

are limited and good ventilation is ensured. Fresh products must be

stored between 1°C and 5°C; frozen products must be kept at tem-
peratures below ⫺18°C (or below ⫺20°C for long-term storage).
11.2 In the event of bulk transport, it is important to ensure dry condi-
tions. To prevent mould formation or fermentation, it is advisable
to use ventilated containers, transport vehicles and other venti-
lated facilities.
11.3 Decontamination of the storage area to combat pests must be car-
ried out only where necessary and by authorised personnel only.
11.4 When frozen storage or saturated steam is used for pest control,
the moisture content of the product must be controlled after treat-
ment.

12. SPECIAL PROVISIONS FOR THE PRODUCTION

OF CANNABIS INTENDED FOR PROCESSING
INTO A STANDARDISED HERBAL DRUG

12.1 Herbs
12.1.1 In these guidelines, a herbal medicine is understood to mean any
medicine that contains exclusively herbal drugs or herbal prepa-
rations as active ingredients.
12.1.2 Herbal drugs are plants or parts of plants in an unprocessed state
which are used for medicinal or pharmaceutical purposes. A
herbal drug or a preparation is regarded as one active substance
in its entirety whether or not the constituents with therapeutic ac-
tivity are known.
12.1.3 Herbal drug preparations are comminuted or powdered herbal
drugs, extracts, tinctures, fatty or essential oils, expressed juices,
processed resins or gums, etc., prepared from herbal drugs, and
preparations that are produced through fractionation, purifica-
tion or concentration.
12.1.4 In departure from the above, chemically defined isolated con-
stituents or their mixtures are not considered herbal drug prepa-
rations.
12.1.5 Herbal drug preparations may contain other components such as
solvents, diluents and preservatives.
 Guidelines 59

12.2 If the cannabis is intended for processing into a standardised

herbal medicine, the cannabis must be cultivated under such stand-
ardised conditions that the content of the constituents is constant.
Protocols of the operations committed during the cultivation must
be kept available.
12.3 The content of the main constituents, which includes ∆-9-tetra-
hydrocannabinol (∆-9-THC) and cannabidiol (CBD), is deter-
mined quantitatively. For a selection of the other constituents,
fingerprinting with a suitable technique, such as GC-MS, GC,
HPLC or TLC will suffice.
12.4 Unless it is proven that omitting the standardisation of one of the
following elements results in a constant and reproducible product,
at least the following must be standardised during cultivation:
a. cultivar of the cannabis plant;
b. cultivation substrate;
c. day length;
d. light intensity;
e. colour temperature of the lighting;
f. atmospheric humidity;
g. temperature;
h. ventilation;
i. plant age at the time of harvesting;
j. time of day of harvesting.
12.5 Unless it is proven that omitting the standardisation of one of the
following elements results in a constant and reproducible product,
at least the following must be standardised during drying:
a. atmospheric humidity;
b. temperature;
c. ventilation;
d. drying time.

13. DOCUMENTATION

13.1 All processes and procedures which may affect the quality of the
product must be recorded in the documentation for each batch.
The following in particular must documented:
60 JOURNAL OF CANNABIS THERAPEUTICS

a. the location of cultivation and the name of the cultivator in

charge;
b. details on crops previously grown at that location;
c. nature, origin and quantity of the herbal starting materials;
d. the chemicals and other substances used during cultivation,
such as fertilisers, pesticides and herbicides;
e. standard cultivation conditions, if applicable;
f. particular circumstances which occurred during cultivation,
harvesting and production which may affect the chemical
composition, such as plant diseases or temporary departure
from standard cultivation conditions, particularly during the
harvesting period;
g. nature and quantity of the yield;
h. date or dates, and time or times of day when harvesting oc-
curred;
i. drying conditions;
j. measures for pest control.
13.2 Analysis reports of soil analysis must be kept available in the dos-
sier
13.3 Location
13.3.1 All batches originating from one location must be clearly la-
belled (e.g., with a batch number). This must be done as early on
in the process as possible.
13.3.2 Batches originating from different geographic locations may
only be combined if guaranteed to be the same, and that the mix-
ture is homogenous. Mixing of batches must be documented.
13.3.3 It must be recorded in the documentation for each batch that the
cultivation, harvest and primary processing procedures were in
accordance with these requirements.
13.3.4 All parties involved in the production process must demand that
their suppliers document all relevant stages and elements of the
production process for each batch.
13.3.5 Audit results must be recorded in an audit report. The audit re-
port and concomitant analysis reports and other documents must
be kept for at least ten years.
 Guidelines 61

14. SAFEGUARDING THE MATERIAL

14.1 The buildings in which the cannabis is cultivated, processed, pack-

aged and stored must be sufficiently secured. This means that
there must be security in force and that only authorised personnel
is allowed access to the buildings.
14.2 The personnel involved in the production process of cannabis
must be authorised for that purpose by the employer. When con-
cluding the supply contract, the supplier designates authorised
persons and indicates how this will be verified.
14.3 There must be a balanced administration of the cannabis.
14.4 Waste must be stored in such a way that theft is impossible. If
waste is collected in bags it must be stored in a lockable container
(for instance a pressing container) immediately.