The risk assessment of zoonoses
May 04 2023
and the literature search according to ISO 22442-3
The scope of the literature search and the data required depends on the source and origin of the animal material, the scope of the manufacturing process and the intended use of the medical device. Testing the removal and inactivation of bacteria, yeasts and fungi may already be covered by the normative requirements for sterilization. This must be checked on a case-by-case basis. Procedures for testing the removal and inactivation of parasites are not described in standards. If the literature research reveals gaps in the data, these must be filled by validated studies.
Who carries out the research?
The literature search should be carried out by persons who are appropriately qualified in the relevant field, are familiar with the state of the art and are able to demonstrate objectivity.
How does the research work?
The literature search begins with planning, which is recorded in a report. The literature research plan describes the methodology, the objective, the data sources used and the time period. The key points and acceptance criteria with which the data sources are searched for information are defined. The acceptance criteria include the relevance, equivalence and quality of the hits from the literature search in relation to the manufacturing process for the medical device in question. Criteria should also be defined according to which a literature reference is excluded from the evaluation (exclusion criteria, outside the specification).
Which data sources can be used?
Data sources can include medical and paramedical databases (PubMed, Livivo), technical publications from relevant standards committees, gray literature and other unpublished sources from experts in the field.
What data is relevant for the search?
To define the key points for the literature search, each individual production step - starting with the animal, its country of origin, the country of slaughter/processing, transport conditions and the individual process steps through to sterilization with a view to possible contamination with pathogens and inactivation/removal of pathogens - should be considered.
If the animals are born, reared, slaughtered and processed in the same country, the effort involved in researching the infection status is limited to this one country and the time required is limited (on average a few days to a week).
If the animals come from several countries or are reared in another country after birth and then transported to other countries for slaughter and further processing, the infection status must be considered for each of these countries and the associated risk assessed. This increases the material and time expenditure considerably. This is also due to the fact that the information on reportable infections in the WOAH's WAHIS database is not up to date and must therefore be supplemented by research in other databases. Additionally, infections that are not reportable are also significant. The period of publication is also relevant for the risk assessment and depends on various factors, such as the survivability of pathogens in the animal environment and the stability and storage of the medical devices until they come into contact with patients.
Each individual step of the manufacturing process can cause inactivation and removal of transmissible pathogens (e.g. temperature during transportation, concentration and pH of alkaline/acidic solutions and the duration of contact with the (intermediate) product). You should therefore be very familiar with the conditions at each manufacturing process step and the consistency of the (intermediate) products - even if this manufacturing process step takes place at your suppliers and subcontractors. If you know which manufacturing process steps (e.g. pH of the solutions used, high / very low temperatures) inactivate and remove the pathogens relevant for your medical device, you can derive the key points for the literature research on the inactivation and removal of transmissible pathogens. You should consider adding the effectiveness of each manufacturing process step to determine the overall effectiveness of inactivation and removal of transmissible pathogens during the entire manufacturing process. For approval in the EU, a log level reduction of at least 4 must be achieved.
How time-consuming is the research?
The time required increases in parallel with the number of defined key points and the number of hits. Even if a pre-evaluation of the relevance of the literature is carried out using the summaries, the literature search can take several days to several weeks. It is important to critically evaluate the data from the literature search - and to document this. An evaluation of the information in the summaries of the references is often not sufficient for this. You should therefore at least have the references defined as relevant available as full texts. This again increases the time required.
Furthermore, the costs can quickly exceed the budget defined for the risk assessment, as most literature is not available free of charge. If you have several medical devices of animal origin, it is helpful to create your own database on the relevant transmissible pathogens and inactivation methods in order to reduce the time required.
What happens to the results at the end?
The results of the literature search, the evaluation of the literature references and their conclusions should be summarized in a report. It should be noted that this literature search report should be part of the residual risk assessment report. Data gaps must be closed using validated procedures or changes to the process. If something changes in the manufacturing process (other countries of origin, new information) or if there are new findings on the pathogens, you must repeat the residual risk assessment and thus also the literature research. As there are regular publications on known and as yet unclassified pathogens, you should monitor the publications with regard to their relevance for your product and / or carry out a literature search on a regular basis.
Even if the ISO 22442 standard explicitly excludes products with components of human origin and other biological substances, the risk assessment of these materials follows similar aspects. Accordingly, ISO 22442 can be applied analogously to products with components of human origin and other biological substances, taking into account the specific legislation.
Conclusion and recommendation
While specific risk management and a residual risk assessment are in place, particularly for materials of biological origin with a high risk of transmitting viruses and TSE pathogens, there are often data gaps for the residual risk assessment with regard to other transmissible pathogens such as bacteria, yeasts, fungi and parasites. For medical devices that only partially consist of materials of biological origin or are only manufactured with these, there is often no specific risk management and/or residual risk assessment available.
Check your risk management now for your medical devices whose components include materials of biological origin:
- Check whether you need special risk management for your medical devices whose components include materials of biological origin.
- Check your specific risk management for completeness.
- Check whether the available data, certificates and attestations as well as the specifications of the manufacturing process are sufficient for the residual risk assessment.
- Find out what requirements you need to fulfill for special risk management and residual risk assessment and what timeframes and costs you will face.
- Plan literature research and, if necessary, studies at an early stage so as not to jeopardize the legally compliant marketing of your products.
We review your data on the manufacturing process and the entire supply chain, plan and carry out your literature research, assess the risks with regard to transmissible pathogens and hazards due to biological incompatibilities, prepare your residual risk assessment and show you which data still needs to be collected and how you can save time and costs in the process.
Optimize your risk management with us
Our experts will support you in developing an optimal, specific risk management system, carrying out the risk analysis including literature research, risk control and risk assessment. We help you to avoid time-consuming and cost-intensive efforts due to inactivation studies, delays and data gaps.
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