1€¦ · web viewgeneral principles of food hygiene (cac/rcp 1 – 1969, rev 4 – 2003. annex...

VERSION 32020-xx-xx

PROCESSDOCUMENT

BIOPROCESS

Quality and Safety System for Specialty Feed Ingredients

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FAMI-QS asblwww.fami-qs.org

BIOPROCESS DOCUMENT FOR PUBLIC CONSULTATION PD-01, Version 3

Deadline for comments: 2020-09-30

Table of Contents

1. Introduction..........................................................................22. Definitions............................................................................23. HACCP Programme...............................................................6

3.1. General requirements...................................................................................................6

3.2. HACCP Programme.......................................................................................................6

3.3. Assemble a HACCP team...............................................................................................7

3.4. Formulate the finished product description.................................................................7

3.5. Identify the intended use of the product......................................................................7

3.6. Construct a diagram of the process flow......................................................................8

3.7. Confirm the accuracy of the process flow diagram in situ............................................8

3.8. Identify and analyse the hazards..................................................................................8

3.9. Determine the CCP and control measure(s).................................................................9

3.10. Determine the target values and critical limits for the CCP......................................12

3.11. Construct monitoring procedures for the CCP..........................................................12

3.12. Determine corrective actions....................................................................................12

3.13. Verify the system......................................................................................................12

3.14. Draw up the necessary documentation....................................................................12

4. Requirements for Bioprocesses...........................................134.1. Description of the process..........................................................................................13

4.2. Flow chart of the process: example............................................................................14

4.3. Hazard Analysis, examples (non exhaustive list).........................................................15

4.4. Inputs for the Vulnerability assessment, when applicable example...........................19

5. References...............................................................................20

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1. Introduction

The FAMI-QS Process Documents are auditable documents established for each process described in Chapter 2 of the FAMI-QS Code of Practice. Such documents include the requirements for the evaluation of the feed safety hazards associated with the Operator's processes with the view of controlling their occurrence.

The Process Documents are required to be used by Operators and Certification Bodies to assure that they operate their programs in a consistent and equivalent manner.

According to FAMI-QS certification system code version 6.0, it is required for products coming from bioprocess to list the name and strain number of the microorganism used in the process. This applies to producers/manufacturers and traders.

2. Definitions

Adequate: The terminologies “adequate”, “where appropriate”, “where necessary”, or “sufficient” mean that it is up to the Operator in first instance to decide whether a requirement is necessary, appropriate, adequate or sufficient to achieve the objectives stated in this document. In determining whether a requirement is adequate, appropriate, necessary, or sufficient, account should be taken to the nature of the feed and of its intended use. (adopted from EC Guidance Document 2005 on Regulation 852/2004/EC and modified)

Antimicrobial Resistance (AMR): refers to micro-organisms – bacteria, fungi, viruses, and parasites – that have acquired resistance to antimicrobial substances (FAO ACTION PLAN ON ANTIMICROBIAL RESISTANCE 2016-2020)

Bacteria: microscopic, single-celled organisms that thrive in diverse environments

Batch: Unit of production from a single site using uniform production parameters or a number of such units, when produced in continuous order and stored together. It consists of an identifiable quantity of feed which is determined to have common characteristics, such as origin, variety, type of packing, packer, consignor or labelling. (COM(2008)124 final and Regulation 767/2009/EC in EU)

Calibration: The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements.

Carrier: Substance used to dissolve, dilute, disperse or otherwise physically modify a specialty feed ingredient in order to facilitate its handling, application or use without altering its technological function and without exerting any technological effect on the feed itself. (adapted from COM(2008)124 final & Regulation 767/2009/EC and adapted in EU)

Check/control: Monitor and measure processes against policies, objectives and requirements for the product and report results. The state wherein correct procedures are being followed and criteria are being met. (Codex Alimentarius)

Contamination: The undesired introduction of impurities/contaminant (chemical or microbiological nature or of foreign matter), into or onto a raw material, intermediate, and products covered by FAMI-QS scope during production, sampling, packaging or repackaging, storage or transport. (Codex Alimentarius and adapted)

Control Measure: Any action and activity that can be used to prevent or eliminate a feed/food safety hazard or reduce it to an acceptable level. (Codex Alimentarius and adapted)

Corrective Action: Any action to be taken when the results of monitoring at the CCP indicate loss of control. (Codex Alimentarius)

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Critical Control Point (CCP): A step at which control can be applied and that is essential to prevent or reduce a feed/food safety hazard or reduce it to an acceptable level. (Codex Alimentarius and adapted)

Critical Limit: Minimum or maximum value to which a biological, chemical (including radiological) or physical parameter must be controlled at a CCP to prevent, eliminate or reduce to an acceptable level the occurrence of the Feed Safety Hazard. (FDA)

Cross-Contamination: Contamination of a material or product with another material or product.

Deviation: Failure to meet a critical limit. (Codex Alimentarius)

Documented Information: Information required to be controlled and maintained by an Operator and the medium on which it is contained. (ISO 9001:2015 and adapted)

Feed: Any substance or product, including specialty feed ingredients, whether processed, partially processed or unprocessed, intended to be used for oral feeding to animals. (Regulation 178/2002/EC and adapted in EU)

Feed Hygiene: The measures and conditions necessary to control hazards and to ensure fitness for animal consumption of a specialty feed ingredient(s) covered by FAMI-QS scope, taking into account its intended use. (Regulation 183/2005/EC in EU)

Feed Safety: High level of assurance that the feed (feedingstuff, feed material or products covered by FAMI-QS scope) will neither cause harm to the farm animals when prepared or consumed according to the intended use, nor to the final consumer. Throughout the document, the word ‘Safety’ is taken to have the same meaning as ‘Feed Safety’.

Feed Safety Hazard: Biological, chemical (including radiological) or physical agent in feed, with the potential to cause an adverse health effect in animals and/or humans. (Codex Alimentarius and adapted)

Bioprocess/Fermentation: is a metabolic process that produces chemical changes in organic substrates through the action of microorganisms such as bacteria and or fungi as well as eukaryotic cells or enzymes to make products useful to animals.Any metabolic process that releases energy from a sugar or other organic molecule, does not require oxygen or an electron transport system, and uses an organic molecule as the final electron acceptor.

Flow Diagram: A systematic representation of the sequence of steps or operations used in the production or manufacture of a particular feed or food item. (Codex Alimentarius and adapted)

Gene(s) of Concern: Gene(s) known to contribute to the production of toxic metabolites and antimicrobials of clinical relevance, or to AMR. For products with viablecells, other virulence factors are also included in this definition (EFSA Guidance on the characterisation of microorganisms used as feed additives or as production organisms, June 2018)

Genetically modified organism (GMO): is an organism in which one or more genes (called transgenes) have been introduced into its genetic material from another organism using recombinant DNA technology (FAO definition)

Good Manufacturing Practices (GMP): Processes and actions taken to maintain hygienic conditions throughout the food chain that provide the foundation for the HACCP Programme. Equivalent term: PRP (Pre-requisite Programme) (ISO 22000:2005)

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HACCP (Hazard Analysis and Critical Control Point) Programme: A system which identifies, evaluates, and controls hazards to feed and food safety. (Codex Alimentarius and modified)

Hazard Analysis: The process of collecting and evaluating information on hazards, and conditions leading to their presence, to decide which are significant for feed safety and therefore must be addressed in the HACCP Programme. (Codex Alimentarius)

Labelling: Means the attribution of any words, particulars, trademarks, brand name, pictorial matter or symbol to a feed by placing this information on any medium referring to or accompanying such feed, such as packaging, container, notice, label, document, ring, collar or the Internet, including for advertising purposes. (Regulation 767/2009/EC in EU)

Management System: Set of interrelated or interacting elements of an organisation to establish policies and objectives and processes to achieve those objectives. (ISO 9001:2015)

Manufacture/production: All operations encompassing receipt of materials, processing, packaging, repackaging, labelling, relabelling, quality control, release, storage, and distribution of products covered by FAMI-QS scope and related controls.

Microorganism: bacteria, viruses, yeasts, moulds, algae, parasitic protozoa, microscopic parasitic helminths, and their toxins and metabolites

Must: Compliance with a requirement which is mandatory for compliance with this standard (obligation to follow the exact requirement as stated by this document).

Monitor: The act of conducting a planned sequence of observations or measurements of control parameters to assess whether a CCP is under control. (Codex Alimentarius)

Operator: The natural or legal persons responsible for ensuring that the requirements of food/feed law are met within the feed business under their control. (Regulation178/2002/EC and adapted in EU)

Organisation: Person or group of people that has its own functions with responsibilities, authorities and relationships to achieve its objectives. (ISO 9001:2015)

Plant cells: eukaryotic cells present in green plants, which are the basic unit of life in organisms of the kingdom Planta

Pre-requisite Programme (PRP): See ‘Good Manufacturing Practices (GMP)’

Preventive Action: Action to eliminate the cause of a potential nonconformity or other undesirable potential situation. Preventive action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence. (ISO 9000:2005)

Procedure: Operations to be performed, precautions to be taken and measures to be applied directly or indirectly related to the manufacturing of a material or products covered by FAMI-QS scope. (Modified from ICH Q7A). A specified way to carry out an activity or a process. (ISO 9000:2005)

Production organism: see “microorganism”

Quality: Degree to which a set of inherent characteristics fulfils requirements. (ISO 9000:2005)

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Raw Material: Any material which enters the manufacturing process of the products covered by the FAMI-QS scope.

Record: Written documents containing actual data. Document stating results achieved or providing evidence of activities performed. (ISO 9000:2005)

Recombinant DNA: A form of DNA that is created by combining two or more sequences that would not normally occur together (EFSA Guidance on the characterisation of microorganisms used as feed additives or as production organisms, June 2018)

Regulatory Requirement: Obligatory requirement specified by an authority mandated by a legislative body. (ISO 9000:2015)

Requirement: Need or expectation that is stated, generally implied or obligatory. (ISO 9000:2015)

Reworking / rework: Action on a nonconforming product to make it conform to the requirements. (ISO 9000:2005)

Risk: A function of the probability of an adverse health effect and the severity of that effect, consequential to a hazard. (Regulation 178/2002/EC in EU)

Safety: See ‘feed safety’.

Shelf Life: A defined time period for which a product fully complies with its specification, if stored appropriately.

Should: Means ”must” and the activities, descriptions or specifications accompanied by the word ”should” are intended to be mandatory, unless the manufacturer is able to demonstrate that the activity, description or specification is inapplicable or can be replaced by an alternative which must be demonstrated to provide at least an equivalent level of quality and safety assurance. (Operators are obligated to achieve the goal of the Process Document by appropriate means).

Site: Area in which animal feed is handled, together with any immediate surrounding area. (adapted from PAS 222)

Specialty Feed Ingredients: Any intentionally added ingredient not normally consumed as feed by itself, whether or not it has nutritional value, which affects the characteristics of feed or animals/ animal products and animal performance. (Codex Alimentarius and adapted).

Specification: A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material must conform to be considered acceptable for its intended use. ‘Compliance to specification’ means that the material, when tested according to the listed analytical procedures, meets the listed acceptance criteria. Document stating requirement. (ISO 9000:2005)

Step: A point, procedure, operation or stage in the food chain including raw materials, from primary production to final consumption. (Codex Alimentarius)

Sufficient: See “Adequate”.

Strain: genetic variant or subtype of a microorganism (e.g., virus or bacterium or fungus)

Top management: Person or group of people who directs and controls an organisation at the highest level. (ISO 9001:2015)

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Traceability: The ability to trace and follow a food, feed, food-producing animal or substance intended to be, or expected to be incorporated into a food or feed through all stages of production, processing and distribution. (Regulation 178/2002/EC in EU)

Undesirable substances: Any substance or product, with the exception of pathogenic agents, which is present in and/or on the product intended for the animal feed and which presents a potential danger to animal or human health or to the environment or could adversely affect livestock production. (Directive 2002/32/EC in EU)

Validation: Obtaining evidence that the control measures will be effective as designed. (ISO 22000:2005)

Verification: Obtaining evidence that implemented control measures/GMPs are effective by the application of methods, procedures, tests and other evaluations

Vulnerability: Activities to understand the exposure to vulnerabilities (as an act of feed fraud) in order to define and implement activities to reduce or mitigate the vulnerabilities. Where appropriate: See“Adequate”.

Yeast: eukaryotic single-celled microorganisms classified as members of the fungus kingdom.

3. HACCP Programme

HACCP Programme is a system that helps an operator identify feed safety hazards and evaluate the feed safety hazards associated with their product(s) and processes with the view of controlling their occurrence. The system enables the operator to implement, document, control and verify the effectiveness of the control measures.

3.1. General requirements

The HACCP Programme is a required system to identify, evaluate, and control hazards related to feed safety. It is required for the Operator to have an effective Good Manufacturing Practices (GMPs) in place to manage the daily tasks of good hygienic practice(s). The Good Manufacturing Practices (GMPs) are the backbone of any quality or safety system and without it no management program is likely to be successful.

Documents should specify how Good Manufacturing Practices (GMPs) are managed. Documented information about verifications and modifications of the Good Manufacturing Practices (GMPs) must be maintained.

There is a dedicated chapter for Good Manufacturing Practices (GMPs) in the FAMI-QS Code of Practice (Chapter 7) providing requirements with a goal of maintaining feed safety and quality.

3.2. HACCP Programme

HACCP Programme consists of the following 7 principles:

1) Conduct a hazard analysis;2) Determine the critical control points (CCPs);3) Establish critical limits;4) Establish a system to monitor the control of each CCP;

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5) Establish the corrective action to be taken if controls should fail;6) Establish a procedure to verify that all the aspects of the HACCP Programme are working effectively;7) Document all procedures and records to demonstrate the HACCP Programme is working effectively.

Based on 7 principles, the implementation of HACCP Programme follows a logical sequence of 12 steps, including the above 7 principles.

3.3. Assemble a HACCP team

The Operator must form a multi-disciplinary team that will have responsibility for establishing, developing, implementing, maintaining and reviewing the HACCP Programme. It is vital that this group has the full support of the top management. The team must include people who are very familiar with the products, processes and associated hazards.

The HACCP team leader must:

a) Appoint (where possible) and manage a HACCP team and organise its work;b) ensure relevant training, and periodic retraining of the HACCP team members;c) arrange for periodic, at least yearly, review of the HACCP plan(s);d) report to the top management on the effectiveness of the HACCP programme.

Note: The responsibility of the HACCP team leader may include liaison with external parties on matters relating to the Feed Safety and Quality Management system.

3.4. Formulate the finished product description

Full and detailed information regarding each product is required in order to assess hazards presented by the process or delivery to the end user. The Operator must consider:

composition (e.g. raw materials, ingredients, additives, etc.); physico-chemical (and or radiological) characteristics related to feed/food safety; processing; packaging; storage and distribution conditions; required shelf life; instructions for use; any microbiological or chemical criteria applicable.

3.5. Identify the intended use of the product

The product specification must detail the target groups for which it is intended. It should also specify the animal species, directions for use, storage and shelf life guaranteed and other information required for its use or compliance with relevant requirements.

3.6. Construct a diagram of the process flow

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The Operator must draw up a process flow diagram for each product group. This diagram should indicate the steps taken to produce the product and should include details of by-products, intermediate products, storage, transport etc. One block in the process flow should reflect each step in the process.

The diagram should, while including the necessary details, be clear with unambiguous terms. A very basic example is given here:

3.7. Confirm the accuracy of the process flow diagram in situ

After the flow chart diagram is drawn up, the Operator must make sure it is accurate by checking it against the actual operating process in its facility.

3.8. Identify and analyse the hazards

The Operator must use the diagram to access potential hazards at each process step from the perspective of:

a) Chemical (including radiological): Pesticides, lubricants, dioxins, heavy metals, cleaning agents, radionuclides, etc. b) Biological: Undesirable microorganisms such as pathogenic bacteria, fungi, viruses and other parasitesc) Physical: Foreign bodies such as glass, wood, jewellery, stones, etc.

For example, for Step 1, the Operator’s first consideration should always be, “How good is the material being supplied to me?”

The Operator must consider the chemical (including radiological), biological and physical hazards associated with each material entering on site. Potential chemical (including radiological), biological and physical hazards must be considered for each subsequent step in the process, in each case taking the particular circumstances with regard to the step into account.

When conducting a hazard analysis, the following must be considered:

a) the likelihood of hazards occurring;

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b) the severity of their adverse health effects.

3.9. Determine the CCP and control measure(s)

After the hazard identification, it is important to evaluate whether or not a hazard is significant. I f a hazard needs a specific control and there is no point further down stream in the process that can reduce it, this step is a Critical Control Point (CCP). If the correct application of the Operator’s prerequisite programs prevents or reduces the hazard to an acceptable level, then the step in question is not a CCP. Useful questions the Operator can ask itself when establishing CCPs are:

a) ‘If I do not control this hazard, is the safety of the end user compromised?’b) ‘If I do not apply controls to this hazard at this step, are there other controls further on in the process that

will ensure animal or consumer safety?’

Common methods for the determination of the CCps are decision matrix and decision tree. Other methods can be used like failure mode and effect analysis (FMEA).

One of the methods is using a decision matrix, that will help the Operator to decide how severe the potential hazard is and how likely it is to occur. It is based on the concept that the significance is the result of the probability that a hazard will occur and the severity if it occurs.

The matrix can be simple or more sophisticated. Three different examples are shown below.

Example a)

Four significance levels can be determined with the evaluation model.In the event of significance level 1, no measures are necessary. In case of significance level 2, periodic measures – often activities to be performed just once or minimal review – have to be carried out. Significance level 3 requires general control measures, such as hygiene programs, maintenance and calibration, purchasing procedures, etc.In the event of risk level 4, specific control measures are necessary for that particular situation.

Example b)

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Significance level 1: no need for measuresSignificance level 2: once-only periodical measuresSignificance level 3: general control measures, control of points of attentionSignificance level 4: specific control measures - control at critical control points (CCPs)

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Example c)

Another and simpler matrix is shown below.

The other approach to determine CCPs is to use a decision tree (see figure below, which indicates, by means of four questions, a logic approach). The figure below is an example of a decision tree; other logical approaches may be used.

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*) Proceed to the next identified hazard in the described process

**) Acceptable and unacceptable levels need to be determined within the overall objectives of the HACCP Programme

The number of CCPs will depend on the Operator’s system. The Operator can monitor a few key CCPs much more effectively than a vast array.Once a hazard that needs a specific control is identified, the Operator must identify the process step where the control measure should be associated.

Critical limits must:

a) be established to ensure that the identified acceptable level of the feed safety hazard in the end product is not exceeded;

b) be measurable (quantitatively and qualitatively) and the rationale for their determination must be supported by scientific or other documented information.

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3.10. Determine the target values and critical limits for the CCP

The operator must establish a critical limit and can establish target or action limits. These limits must comply with all legislative obligations but if there are no legal limits, one’s own research (analytical; bibliographic) and experience should be used to strike the right balance between safety and operability.

3.11. Construct monitoring procedures for the CCP

For each CCP, a monitoring system must be established to demonstrate that the critical limits are controlled. The system must include all scheduled measurements or observations relative to the critical limit(s).

The monitoring system must consist of documented information including procedures, instructions and records and should include, but are not limited to the following:

c) measurements or observations that provide results within an adequate time frame;d) monitoring devices used;e) applicable calibration methods;f) monitoring frequency;g) monitoring results;h) responsibilities and authorities for monitoring and evaluation of all data.

When monitoring procedures are based on subjective data, e.g. visual inspection of products and/or processes, they must be supported by instructions or specifications. Training must be given to the persons with responsibility for the monitoring activities.

The monitoring procedure and frequency of monitoring must be capable of determining when the critical limits have been exceeded in time for the product to be isolated, before it leaves the immediate control of the operator.

3.12. Determine corrective actions

These are the decisions that must be taken once a critical limit has been breached. For example, a faulty raw material or finished good may be placed on hold, reworked, destroyed, etc. A written procedure must be in place that details how this process should be undertaken and someone must have the responsibility for this process.

3.13. Verify the system

The system must be verified periodically to ensure it is effective and up to date. This review should cover all aspects of the HACCP Programme including the prerequisites, deviations and customer complaints. All records of this review should be documented and be part of the company’s internal audit schedule.

3.14. Draw up the necessary documentation

The HACCP programme must be maintained as documented information and must include the following:

a) information for each identified Critical Control Points (CCP);

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b) feed safety hazard(s) to be controlled at the CCP;c) control measure(s);d) critical limit(s);e) monitoring procedure(s);f) corrections and corrective action(s) to be taken if critical limits are exceeded;g) verification procedure(s);h) list of responsibilities, designated responsible personnel, including for certain authorisations;i) records of monitoring and verification procedures.

4. Requirements for Bioprocesses

4.1. Description of the process

Bioprocessing uses biological material or its components to obtain the desired product. Bioprocessing is mainly based on upstream processes to produce biological material (cell culture, fermentation) and downstream processes which include recovery, separation/purification of the desired material/intermediate products, and possible preservations steps such as drying/freeze-drying and formulation.

The typical process consists of production of biological material by microorganisms or cell culture. The microorganism, itself can also be the product. The microorganisms are grown (fermented) on raw materials and nutrients such as carbon- and nitrogen sources together with micronutrients. After a growth step, the microorganisms may produce the intended product and then this product is separated from the cells (or cells are opened for intracellular products); when the microorganism is the product, the microorganism is separated from the growth media. After separation (or cell opening) the product is processed in a recovery step (typically by precipitation, filtration, centrifugation, chromatography, etc. and or washing of the cells). Finally the product may be formulated by: mixing with stabilizers or attachment to carriers and granulation, spray-drying, freeze-drying, immobilization, etc..

Different processes may be used to produce biological products. The flow chart below (4.2) describes a typical set of processes which may be involved in the feed production and the subsequent hazard analyses (4.3) and vulnerability/points of interest for assesment (4.4), as an example on how to analyse the process. Flow chart(s), hazard analyses and vulnerability/points of interest for assessment shall be established for the actual individual operator’s process(es).

4.2. Flow chart of the process: example

- Depository cell Bank (well identified and maintained culture collection) - Preparation of raw material

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Strain(s)/production organism(s)

Fermentation/Biomass productionRaw materials

Raw materials

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Non exhaustive list of steps, others might be included based on the product

- Inactivation (deactivation) of the production strain/stopping of the biomass production (not necessarily rendering it dead)

Non exhaustive list of steps, others might be included based on the product - Filtration

- Inactivation of the production organism - Washing and removal of solid/liquid

Non exhaustive list of steps, others might be included based on the product - Cell disruption/disintegration (opening)

- Washing/removal of impurity(ies) - Precipitation/Flocculation

- Concentration - Refining - Filtration/Centrifugation

- Drying - Crystallization - Cryoprotection

- Intermediate/Storage - Chemical reaction(s)

Non exhaustive list of steps, others might be included based on the product - Blending/Mixing - Granulation - Immobilisation

- Drying

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Separation of Product/microorganism

Substance recovery/ Purification

Storage, Packaging and Labelling

Formulation

Shipment/Transportation

Raw materials

Raw materials (carriers)

Raw materials

Packaging materials, labels

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4.3. Hazard Analysis, examples (non exhaustive list)PROCESS STEPS PROCESS DESCRIPTION HAZARD DESCRIPTION EXAMPLES OF CONTROL AND PREVENTIVE MEASURES

Production organism(s)/ strain(s)

Production organism(s)/ strain(s)

use of unwanted/incorrect strain (absence of characterisation)

Purity and strain identity check prior to the use, through established internal procedureYield check during fermentation (take sample and compare with reference sample, via microscopy) against internal established levelsName and strain number obtained from an official depository authority (proved via a copy of official certificate) and legislation of destination countries

Production of toxins and virulence factors and occurrence of phenotypic antibiotic resistance caused by improper characterization of the strain

Strain characterization (sequence analyses, antimicrobial susceptibility for bacteria, antimicrobial resistance factors via genetic analysis) toxin and virulence factors production (via literature study, tests in lab to ensure safety of the strain (e.g. potential production of toxins))

Contaminated production strain (Mix up or contamination of production strain)

Depository cell bank and purity check procedures

Yield check during fermentation

Selection of raw materials for processing

Use of incorrect raw materials Clear labelling/verification of raw materials

Poor performance of final productVerification of fermentation, processing aids and formulation raw materials

unwanted chemicals from raw materials due to contamination or wrong grade of raw materials

Supplier and raw materials assessment combined with receiving inspection, periodic analysis and process controls like sieving and infection control

Physical debris in raw materials

Raw materials infected with pathogenic and/or toxin producing organisms

Radiological hazards resulting from accidental contamination, e.g., contamination arising from accidental release from a nuclear facility or from damage to a nuclear facility from a natural disaster

Monitoring of accidental releases of radiological hazards and verification of the possible impact on raw materials during manufacturing, storage, transport

Fermentation/Biomass production

Propagation of production strain(s) and formation of the intended product in growth medium

Growth of pathogenic/ toxin forming organisms (mainly) during fermentation

Processing of rules to avoid and or check for any contamination (sterilization, hygienic procedures, checks for contamination, maintenance of equipment)

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PROCESS STEPS PROCESS DESCRIPTION HAZARD DESCRIPTION EXAMPLES OF CONTROL AND PREVENTIVE MEASURES

Degradation of the intended product(s) including into undesirable substances

Control of the process to ensure repeatability

Monitoring of product stability and undesirable substances

Chemical or physical contamination from equipment including contaminants from wear and tear (pieces of glasses, metals, etc.…….), migration of metals and plastic monomers from contact materials

Preventive maintenance program (preventive maintainance program and analyses), sieves

Selection of suitable contact materials


Separation of product/ microorganism

and Recovery/ Purification

Separation of intended product from the rest of the broth (production organism, organic and inorganic growth medium)

Presence of DNA/gene of concerns/unwanted cells in final intended products

Procedures to measure the absence of viable cells from production strain(s) (by e.g. plating and counting)

Sequence analyses and/or specific PCR methods to measure the absence of DNA/gene of concern in final intended product(s)

Growth of contaminating micro organisms due to favourable pH and temperature conditions

Heat treatment / sterilization of equipment / cleaning in place / pH / temperature conditions monitoring and verification to ensure sterile conditions

Risk analyses of raw materials

Procedure of inoculation of fermentor with inoculum; to ensure no contamination

Contamination with pathogenic and/or toxin producing organisms from environment, personnel or pests

Product processing procedures including handling, opening and personal hygiene, disease control, pest control, contamination checks

Risk analyses of raw materialsContamination from personnel, pathogenic/toxin producing organisms pests or birds during handling and or opening.

Contamination from cleaning agents, lubricants, utilities (water, steam, air)

Preventive maintenance program (e.g. to prevent oil leaks)

Risk analyses with requirements to utilities (filtering of air, use of oil suitable for feed products etc.), including analyses of water (well or municipal), water use for steam and growth medium on a regular basis

Use of oil suited for food (feed) grade production

Physical, chemical, biological and radiological hazards from utilities (water supply/or other solvents, steam, air……..)

Risk analyses of utilities including analyses of water source (well or municipal) and other solvents on a regular basis

Regular check of report(s) from water companies

Cleaning program

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Chemical or physical contamination from equipments, including wear and tear (Pieces of glasses, metals, …….and migration of metals and plastic monomers from contact materials (also as during intermediate storage)

Preventive maintenance program (preventive maintainance program and analyses)

Risk analyses, instructions and use of proper contact materials

FormulationFormulating with additives, stabilizer, aids, carriers, preservatives etc.

Granulation

Contaminants from cleaning agents, lubricants, process air, utilities

Physical, chemical, biological and radiological hazards from utilities (water supply/or other solvents, air……..)

Utilities requirements (filtering of air, use of oil suitable for feed products etc.)

Analyses or verification of reports on water source (well or municipal) and other solvents on a regular basis.

Preventive maintenance program

Use of food grade lubricant/grease

Physical, chemical, biological and radiological hazards from use of contaminated water supply

Analyses or verification of reports on water source (well or municipal) on a regular basis.

Physical contamination from equipment, personnel, pests or birds during handling and opening Processing procedures and personal hygiene, pest control,

contamination checks, maintenance programsContamination from pathogenic and/or toxin producing organisms from environment, personnel or pests

Presence of residues due to carry-over potential risk that carriers might be contaminated with undesirable substances. E.g. mycotoxin, heavy metals, dioxins etc. These could be leading to non-compliancy.

Preventive measures to control carry-over, cleaning, CIP,and analyses

Incorrect addition of formulating agents leading to reduced product & microbial stability

Adequate dosing system (dosing and weighing tolerance shall be considered) / Stability testing

Non-uniform distribution of ingredients/raw material

Validation and regular testing of the mixer/mixing efficiency

Formulation homogeneity (e.g. dispersion of micro ingredients) and particle size shall be considered


Packaging and Labelling

Packaging of the products in bags, boxes, drums, etc.

Contaminants from unsuitable packaging (e.g. not suited for feed products) Selection of suitable packaging/risk analyses of packaging materials

Contamination with foreign material during the packaging process Packaging via dedicated production lines and packaging machines (metal detection)

Cleaning and inspection procedures

Usage of new and/or clean packaging materials

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Identify the products with the right label identification according to the applicable legislation and to be able to track and trace the products in cases it is necessary

Innacurate labelling and identification of the product leading to improper usage of the product or unabling to do a complete recall in case of incident

Labelling procedures

Batch identification system check

Labelling-identification, traceability and legislation of destination countries

Storage Storage of products

Microbiological and chemical contaminations due to the exposure to weather conditions/open air

Training and education of employees

Weatherproof storage facilities

Cross contamination with other undesirable materials during movent of goods

Effective segregation of different materials, particularly when stored on floors

Cleanout procedures between different types of products

Separation of storage areas/clear segregation for feed and non-feed materials

Deterioration of the product due to poor stock rotation

Expiry control, e.g that the process management system prevents sale of expired products

Proper stock rotation (e.g first in first out)

Storage under temperatures that lead to premature product deterioration

Temperature control to prevent microbial growth

Warehousing procedures to ensure hygiene and temperature control according to recommended storage conditions

Infestation by rodents/ parasites/birds Pest Control Programme in place


Shipment of packed goods or in bulk

Shipment of packed goods Possible contamination with foreign materials, pests or other goods in case the packaging gets damaged

Contractual agreements with transporters to ensure hygiene and temperature control according to recommended transport conditions

Check of cleaning certificates

Inspection before loading /dedicated transport

Sole use of certified and registered transporters according the requirements

Notification of any problems during transport

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Bulk shipment Possible contamination by previous loads

Contractual agreements with transporters to ensure hygiene and temperature control according to the recommended transport conditions

Inspection before loading /dedicated transport

Info about previous load(s) and request for cleaning certificates

Sole use of certified and registered transporters according the requirements

Guidance proposed: ICH Q6B (ICH Website) QPS-Qualified Presumption of Safety (EU-EFSA Website last updates) GRAS-Generally Recognized as safe (USA-FDA Website last updates) Guidance on the assessment of bacterial susceptibility to antimicrobials of human and veterinary importance (EFSA Journal 2012;10(6):2740) Guidance on the characterisation of microorganisms used as feed additives or as production organisms (EFSA Journal 2018;16(3):5206)

4.4. Inputs for the Vulnerability assessment, when applicable example1

PROCESS STEPS PROCESS DESCRIPTION DESCRIPTION OF POINT OF INTEREST EXAMPLE OF CHECKS

Production organism/ strain

Production organism/ strainSelection of non compliant strain (for the intented use or non-authorised in the country where the product is placed on the market)

Check of Regulatory status of the microorganisms (according to applicable regulation of the country where the product is to be placed on the market, e.g. reference to an application dossier and regulation of authorisation when applicable)Verification that the microorganism used in production and the one stated in the approval and/or licence letter are in alignment.

Selection of raw materials for processing Selection of non compliant raw material and processing aids

Consideration of the respective regulatory framework in the country where the product is to be placed on the market


1 In regard to regulatory requirements, see the feed fraud prevention and defence module

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Separation of product/ microorganism

and Recovery/ Purification

Separation of intended product from the rest of the broth (production organism, organic and inorganic growth medium)

Presence of recombinant DNA/unwanted cells in final intended product(s), if applicable

Absence of detectable recombinant DNA by methods according to requirements in the country where the product is to be placed on the market

Enumeration (e.g. plating and counting) of the viable cells

Formulation

Formulating of additives with formulation aids, carriers, preservatives etc.

Granulation

N/A (see raw materials) Consideration of the regulations in the country where the product is to be placed on the market


Packaging and Labelling

Packaging of the products in bags, boxes, drums, etc. Packaging not compliant with feed legislation Consideration of the regulations in the country where the product

is to be placed on the market

Identify the products with the right label identification according to the applicable legislation

Innacurate labelling and identification of the product leading to non compliant usage of the product Consideration of the regulations in the country where the product


Storage and Transport Storage and transport of products Non compliant storage and transport rules Consideration of the regulations in the country where the product


Guidance proposed: EC Regulation (EU-EC Website) Guidance on the characterisation of microorganisms used as feed additives or as production organisms (EU-EFSA Website last updates doi:

10.2903/j.efsa.2018.5206)

5. ReferencesFormal guidance on the implementation of HACCP principles is available from the Codex Alimentarius (www.codexalimentarius.net).

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General principles of Food Hygiene (CAC/RCP 1 – 1969, Rev 4 – 2003. Annex on Hazard Analysis Critical Control Point (HACCP) System and Guidelines for its Application.)EN ISO 22000:2005 on Food safety management systems - Requirements for any organization in the food chain.

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