kSIST-TP FprCEN/TR 17612:2020

Algae and algae products - Specifications for pharmaceutical sector applications

This Technical Reports describes quality designations and indications for algae and directly derived products from algae production required for or by pharma producers and industry. It does not apply to Food and Feed sectors.
Note: This TRs does not provide instructions on existing handling of technical requirements in existing legislations.

Spezifikationen für Anwendungen im Nicht-Lebensmittel-/Futtermittelsektor

Algues et produits d’algues - Spécifications pour les applications dans le secteur pharmaceutique

Le présent document fournit une vue d’ensemble des recommandations relatives aux spécifications des produits ainsi que d’autres informations pertinentes pour les algues et produits d’algues dans les applications pharmaceutiques.
Le présent document ne s’applique pas aux applications de denrées alimentaires et d’aliments pour animaux.
Le présent document ne fournit pas d’instructions relatives aux exigences techniques requises selon les législations existantes.

Alge in izdelki iz alg - Specifikacije za uporabo v farmacevtski industriji

Standards Content (sample)

SLOVENSKI STANDARD
kSIST-TP FprCEN/TR 17612:2020
01-november-2020
Alge in izdelki iz alg - Specifikacije za uporabo v farmacevtski industriji
Algae and algae products - Specifications for pharmaceutical sector applications
Spezifikationen für Anwendungen im Nicht-Lebensmittel-/Futtermittelsektor
Ta slovenski standard je istoveten z: FprCEN/TR 17612
ICS:
11.120.01 Farmacija na splošno Pharmaceutics in general
kSIST-TP FprCEN/TR 17612:2020 en,fr,de

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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kSIST-TP FprCEN/TR 17612:2020
FINAL DRAFT
TECHNICAL REPORT
FprCEN/TR 17612
RAPPORT TECHNIQUE
TECHNISCHER BERICHT
September 2020
ICS
English Version
Algae and algae products - Specifications for
pharmaceutical sector applications
Spezifikationen für Anwendungen im Nicht-
Lebensmittel-/Futtermittelsektor

This draft Technical Report is submitted to CEN members for Vote. It has been drawn up by the Technical Committee CEN/TC

454.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,

Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,

Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and

United Kingdom.

Recipients of this draft are invited to submit, with their comments, notification of any relevant patent rights of which they are

aware and to provide supporting documentation.

Warning : This document is not a Technical Report. It is distributed for review and comments. It is subject to change without

notice and shall not be referred to as a Technical Report.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels

© 2020 CEN All rights of exploitation in any form and by any means reserved Ref. No. FprCEN/TR 17612:2020 E

worldwide for CEN national Members.
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Contents Page

European foreword ....................................................................................................................................................... 4

Introduction .................................................................................................................................................................... 5

1 Scope .................................................................................................................................................................... 6

2 Normative references .................................................................................................................................... 6

3 Terms and definitions ................................................................................................................................... 6

4 Product characteristics ................................................................................................................................. 8

4.1 Product purity .................................................................................................................................................. 8

4.1.1 General ................................................................................................................................................................ 8

4.1.2 Purity of microalgae and cyanobacteria ................................................................................................. 9

4.1.3 Purity of macroalgae ...................................................................................................................................... 9

4.1.4 Purity of algae derivatives or extracts ................................................................................................. 10

4.1.5 Methods of analysis ..................................................................................................................................... 11

4.2 Contamination ............................................................................................................................................... 11

4.2.1 General ............................................................................................................................................................. 11

4.2.2 Physical, biological and chemical contaminants .............................................................................. 11

4.2.3 Microbiological quality of algae and algae biomass ........................................................................ 12

4.2.4 Contaminants in algae and algal pharmaceutical ingredients .................................................... 13

4.3 Other product characteristics ................................................................................................................. 15

4.3.1 Identification ................................................................................................................................................. 15

4.3.2 Particle size .................................................................................................................................................... 15

4.3.3 Foreign matter .............................................................................................................................................. 16

4.3.4 Total ash, insoluble ash .............................................................................................................................. 16

4.3.5 Extractable matter ....................................................................................................................................... 16

4.3.6 Swelling index ............................................................................................................................................... 16

4.3.7 Bitterness value ............................................................................................................................................ 17

4.3.8 Loss on drying ............................................................................................................................................... 17

4.3.9 Water (for herbal drugs with high essential oil content) .............................................................. 17

4.3.10 Assay ................................................................................................................................................................. 17

5 Storage ............................................................................................................................................................. 18

6 Labelling .......................................................................................................................................................... 18

7 Product information documents ............................................................................................................ 18

7.1 General ............................................................................................................................................................. 18

7.2 Material Safety Data Sheet ........................................................................................................................ 18

7.3 Other relevant product information ..................................................................................................... 18

7.3.1 Origin ................................................................................................................................................................ 18

7.3.2 Strain origin ................................................................................................................................................... 19

7.3.3 Product origin ............................................................................................................................................... 19

7.4 Protected species ......................................................................................................................................... 19

7.5 Algae extracts ................................................................................................................................................ 19

8 Sustainable development .......................................................................................................................... 19

8.1 General ............................................................................................................................................................. 19

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8.2 United Nations sustainable development goals ................................................................................ 19

8.3 Sustainable development of macroalgae production ...................................................................... 20

8.4 Sustainable development of microalgae production ....................................................................... 20

9 Traceability ..................................................................................................................................................... 21

9.1 General ............................................................................................................................................................. 21

9.2 Chain of Custody ............................................................................................................................................ 21

10 Algae in EP and USP General monographs........................................................................................... 22

Annex A (informative) Regulatory framework ............................................................................................... 23

A.1 Regulatory framework in UE .................................................................................................................... 23

A.2 Regulatory framework outside UE ......................................................................................................... 23

Annex B (informative) Raw Material Specifications examples ................................................................. 24

B.1 Example of cyanobacterium biomass Specifications (Spirulina monograph) ........................ 24

B.2 Example of seaweed biomass Specifications (Fucus monograph) .............................................. 25

Annex C (informative) Technical Data Sheets (TDS) examples................................................................. 27

C.1 Example of microalga biomass Data Sheet .......................................................................................... 27

C.1.1 Description ...................................................................................................................................................... 27

C.1.2 Analytical data ............................................................................................................................................... 27

C.1.2.1 Physico-chemical characteristics............................................................................................................ 27

C.1.2.2 Microbiological characteristics ............................................................................................................... 28

C.1.3 Contaminants ................................................................................................................................................. 28

C.2 Example of cyanobacterium biomass Data Sheet ............................................................................. 28

C.2.1 Description ...................................................................................................................................................... 28

C.2.2 Analytical data ............................................................................................................................................... 29

C.2.2.1 Physico-chemical characteristics............................................................................................................ 29

C.2.2.2 Microbiological characteristics ............................................................................................................... 29

C.2.3 Contaminants ................................................................................................................................................. 29

Annex D (informative) Origin of algae products ............................................................................................ 30

D.1 Origin of algae strains ................................................................................................................................. 30

D.2 Origin of algae products ............................................................................................................................. 30

D.3 Origin Statement ........................................................................................................................................... 32

Annex E (informative) Algae extracts ................................................................................................................. 33

E.1 Algae extracts for pharmaceutical purposes ...................................................................................... 33

E.2 Solvent properties ........................................................................................................................................ 33

E.3 Solvent extraction vs CO -Extraction ..................................................................................................... 34

E.4 Algae biomass CO -Extraction .................................................................................................................. 34

Annex F (informative) Purity identification methods and gap analysis algae .................................... 36

Bibliography ................................................................................................................................................................. 38

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European foreword

This document (FprCEN/TR 17612:2020) has been prepared by Technical Committee CEN/TC 454

“Algae and algae products”, the secretariat of which is held by NEN.
This document is currently submitted to the Vote.

The European committee for Standardization (CEN) was requested by the European Commission (EC) to

draft European standards or European standardization deliverables to support the implementation of

Article 3 or Directive 2009/28/EC for algae and algae products or intermediates. The request presented

as Mandate M/547, also contributes to the Communication on “Innovating for Sustainable Growth: A Bio

economy for Europe”.

The former working group CEN Technical Board Working Group 218 “Algae” was created in 2016 to

develop a work programme as part of the Mandate. The technical committee CEN/TC 454 “Algae and

algae products” was established to carry out the work program the secretariat of which is held by NEN.

CEN/TC 454 set up a number of topic specific working Groups listed below to develop standards for algae

and algae products.

This document has been prepared by Working Group 5 “Specifications for the pharmaceutical

applications sector” with the support of UNI as the secretariat, in close collaboration with the other

CEN/TC 454 working groups:
CEN/TC 454/WG 1 “Terminology”
CEN/TC 454/WG 2 “Identification”
CEN/TC 454/WG 3 “Productivity”
CEN/TC 454/WG 4 “Specifications for food/feed sectors applications”
CEN/TC 454/WG 6 “Product test methods”

Algae-based products and intermediates, in this TR referred to as ‘products’, are defined as whole

biomass, extracts or derivatives from algae, including a.o. algae oil and algal meal.

This document will allow the stakeholders to have access to a clear point of reference on the use of algae

in pharmaceutics.

Pharmacy had standards which date back to ancient Egypt; through the first pharmacopoeias which were

the Arab one, the Totum continens (Elhavi) of ar-Razi, and that of the Salerno medical school.

Then national Pharmacopoieas developed in Europe in the Eighteenth Century.

Today pharmacetical industry has the European Pharmacopoiea (EP) [1], being harmonized with

American (USP) [2]and Japanese (JP) [3] through ICH [4].
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Introduction

The interest in algae and algae-based products or intermediates as a renewable and sustainable source

of carbohydrates, proteins, lipids and pigments has increased significantly in Europe.

The purpose of this document prepared by WG 5 is to provide an overview on how quality indicating

parameters for algae and algae-based products and intermediates relevant for cosmetic applications can

be handled and to identify the need for any future standard developments for pharmaceutical

applications. Algae are highly available and used in many countries as fertiliser, biostimulant, animal feed,

medicine, cosmetic and food ingredients, and have different compounds depending on species.

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1 Scope

This document gives an overview of recommendations on product specifications, and other relevant

information, for algae and algae products for pharmaceutical applications.
This document does not apply to food and feed applications.

This document does not provide instructions on handling of technical requirements in existing

legislations.
2 Normative references

The following documents are referred to in the text in such a way that some or all of their content

constitutes requirements of this document. For dated references, only the edition cited applies. For

undated references, the latest edition of the referenced document (including any amendments) applies.

EN 16751, Bio-based products - Sustainability criteria
EN 16760, Bio-based products - Life Cycle Assessment

EN 16848, Bio-based products - Requirements for Business to Business communication of characteristics

using a Data Sheet

EN 16935, Bio-based products - Requirements for Business-to-Consumer communication and claims

EN 17399, Algae and algae products - Terms and definitions

prEN 17477:2020, Algae and algae products — Identification of the biomass of microalgae, macroalgae,

cyanobacteria and Labyrithulomycetes — Detection and identification with morphological and/or

molecular methods
3 Terms and definitions

For the purposes of this document, the terms and definitions given in EN 17399 and the following apply.

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— ISO Online browsing platform: available at http://www.iso.org/obp
— IEC Electropedia: available at http://www.electropedia.org/
3.1
algae and algae products

functional group of organisms consisting of microalgae, macroalgae, cyanobacteria, labyrinthulomycetes

and products derived thereof
3.2
Raw Material Specification
RMS

several pages technical dossier about the product, usually prepared by manufacturer, directed to provide

all product approval information to the customer and usually attached to commercial contract

Note 1 to entry: Examples of RMS for some algae categories are attached as Annex B.

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3.3
Technical Data Sheet
TDS

one (few) page technical document showing the technical (biochemical) parameters adopted to

characterize the product and therefore being the paradigm of the Certificate of Analysis (CoA)

Note 1 to entry: TDS includes ranges of different parameters used to define the product characteristics or

applicable regulatory limits.

Note 2 to entry: Models of TDS for some algae categories are attached as Annex C.

3.4
Certificate of Analysis
CoA

one (few) page document issued from laborator(ies) and reporting test results for a specific lot, usually

in front of TDS parameters, including references to test method
3.5
Material Safety Data Sheet
MSDS or SDS

document issued with the aim of providing information about product compliance in respect of human

health and safety at the workplace and protection of the environment
3.6
sustainable development

development that meets the environmental, social and economic needs of the present without

compromising the ability of future generations to meet their own needs
3.7
algae as herbal raw material

whole, fragmented or cut algae, in an unprocessed state, usually in dried form but sometimes fresh,

precisely defined by the botanical scientific name according to the binomial system (genus, species,

strain, (variety) and author
3.8
extracts

concentrated preparations of liquid, solid or intermediate consistency, usually obtained from dried algae

matter

Note 1 to entry: For some preparations, the matter to be extracted undergo a preliminary treatment, for example,

inactivation of enzymes, grinding or defatting.
3.9
algal drug preparations

products obtained by subjecting herbal drugs to treatments such as extraction, distillation, expression,

fractionation, purification, concentration or fermentation, including comminuted or powdered herbal

drugs, tinctures, extracts, essential oils, expressed juices and processed exudates

3.10
active principles of algal origin
substances having proven clinical activity
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3.11
pesticides

any substances or mixture of substances intended for preventing, destroying or controlling any pest,

unwanted species of plants or animals causing harm during or otherwise interfering with the production,

processing, storage and transport or marketing of vegetable drugs

Note 1 to entry: Pesticides include substances intended for use as growth-regulators, defoliants or desiccants and

any substance applied to crops either before or after harvest to protect the commodity from deterioration during

storage and transport.
4 Product characteristics
4.1 Product purity
4.1.1 General

The product characteristics specified from 4.2 to 4.6 should comply with the relevant Pharmacopeia (e.g.

European Pharmacopea (EP) [1], US Pharmacopea (USP) [2] and Japanese Pharmacopea (JP) [3]),

depending on the product final destination Country. This condition is applicable to algae and algae

products extracts.

In case the product characteristics are referred to algae and algae products raw materials, the compliance

applies after processing (extraction, refining).

The product purity is defined by the percentage of specific component in the total amount of product or,

in case of whole algae biomass, by species/strain amount as percentage of the total dry weight of the

product. Any other substances should be specified in the technical data sheet.

The purity percentage is specified by mass fraction (kg/kg). When this is not possible according to the

3 3

state in which the product is presented, it can be expressed by volume fraction (m /m ) or cell fraction

(cell counts/all cell counts) or their corresponding concentrations if more appropriate.

The presence of GMO material in algae and algae products is to be considered as impurity (ref to EU Reg

on GMO).

The presence of not organic material in organic algae and algae products is to be considered as impurity

(ref to EU Reg on organic production).

NOTE 1 Purity is referred to contractual limits. Purity is generally not directly related to contamination since the

latter is often of small extent and does not affect the amount of required substance.

NOTE 2 Purity is related to species identification and test methods. For methods on the identification of species

refer to prEN 17477:2020.

When a product is not pure, this impurity can be detected by different types of detection methods listed

in Table 1.

Macroscopical/microscopical characterization includes features, which distinguish the algae material

from potential non-specified substances. Identification tests need to be specifically validated for algae

and are usually a combination of methods depending on the algae species. Identification tests include

macroscopical characters, microscopical characters, chromatographic procedures and physicochemical

analysis. Automated tools might help like cell counters or cell flow cytometers.

The development of tests based on nucleic acids characteristics (microsatellites, NGS, barcoding, RAPD,

AFLP, etc.) to be sequenced from product samples would provide simple and fast tools for the

identification of multiple targeted species and would help to indicate the presence of other nucleic acids

than those of the algal material. In general, there is a lack of algae databases for the identification of

foreign matter.
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Currently these tests are not yet standardized and available for routine testing. Therefore, quality

assurance methods aimed at reduction / prevention of risk of impurity like good farming practices (GFP),

good manufacturing practices (GMP), traceability and Chain of Custody systems are essential to monitor

the level of purity for algae and algae products.

An overview of the currently available methods for qualitative and quantitative determination of algae

purity is shown in Table 1. The reliability of these different methods depends on the complexity of the

species and impurities and are not necessarily sufficient for each case.
The following substances affecting the purity of a product can be addressed:

— Physical foreign matter (i.e. (micro) plastic fragments, wires from fishing nets and ropes, feathers

from birds, shells);

— Other algae (including toxin-producing cyanobacteria), bacteria or organic materials (i.e. grass,

proteins or oils from other species);

— Algae from other location then stated (i.e. from Asia instead of Europe). Most promising test to detect

the presence of algae from other regions then stated, is the use of stable isotopes. However, first

databases with the characterization of isotopes from different regions need to be established.

Macroscopic examination is suitable for determining the presence of particles of foreign matter in whole

or cut (macro)algae. Foreign matter are all materials which are not part of the (macro)algae biomass.

Additional aids (like UV-light, sieving, centrifugation) might be helpful to find the foreign matter.

The algae harvesting and farming company should provide the purity on a CoA for each batch of algae.

4.1.2 Purity of microalgae and cyanobacteria

Microscopy is a suitable tool for microalgae, cyanobacteria and all powdered materials. Reduction of

particle size or powdering materials can hide the presence of non-specified substances and make it more

difficult to detect. Also diluted samples cannot be qualified and need a quantification step.

The determination of purity in fresh sample can be possible using inverted microscopy (Utermöhl

technique according to EN 15204) to determine the microalgae and cyanobacteria biovolume. This

European Standard describes the necessary methods for measuring cell dimensions and for the

calculation of cell or counting unit volumes to estimate the biovolume (wet weight biomass) in

phytoplankton samples. This method has been successfully used by French spirulina producers to

monitor the quality and purity of their biomass.

Where available, methods based on nucleic acid analysis of specific species, fingerprinting or

metabarcoding (using 1 or 2 markers) may provide information on purity of any algae powder.

Currently these methods are not yet available for routine tests.
4.1.3 Purity of macroalgae

By their very nature, macroalgae growing in the wild may be found to grow interspersed with other

species. Therefore, it is not always practical to obtain a harvest of macroalgae that is 100 % pure.

Macroscopic examination is suitable for determining the presence of foreign matter in whole or cut

macroalgae. This applies also to algae cultivated in tanks.

Visual inspection is suitable for freshly harvested algae as the intact cells can be recognized as a whole.

When the holdfast is removed, or when epiphytic organisms are present on the surface visual inspection

may not be sufficient to identify the species after harvesting. For ground algae, cells are disrupted and

algae type can no longer be recognized nor be quantified.
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Microscopy is indispensable for all powdered materials. Reduction of particle size or powdering

materials can hide the presence of non-specified substances and make it more difficult to detect. Also

diluted samples cannot be qualified and need a quantification step.

The most reliable way to monitor the purity of macroalgae is for companies to assess the freshly

harvested raw materi
...