**2.2 Sample processing and quality controls**

*Human Blood Group Systems and Haemoglobinopathies*

transferences) and their corresponding checkpoints.

overlapped checkpoints.

**and preservation**

obtained, and processing and storage facilities. Attending to the complexity of the project, a specific workflow is implemented after process definition identifying every factor involved in (site, staff, equipment, method, materials, samples and

**2. Harmonization of sample collection and derivative preservation**

To guarantee the integrity of biomarkers to be tested and to avoid bias, pre-analytical variables must be carefully considered [6]. In fact, many studies are being conducted to elucidate the effects of pre-analytical variables on analytical profiles. In this sense, a study has been recently published to determine acceptable delays to fixation for formalin-fixed paraffin-embedded (FFPE) tissue samples [7]. In order to mitigate their impact in the complex frame of multicenter projects, biobanks contribute through supervised materials and sample handling and continuous and

**2.1 Centralized preparation of consumables for sample collection, processing** 

With the objective to ensure the consistency in sample collection, stabilization, and preservation, specific kits with the consumables necessary for only a donation are defined in function of pre-analytical requirements of obtaining samples and derivatives (**Figure 1**). A careful selection of collection devices is critical here since differences in biomarker testing have been reported [8, 9]. Consumables such as modified cards (IsoCode cards or FTA cards) for blood spot collection, in addition to multibarrier pouches with desiccant packs for room-temperature transportation and future conservation, could be also included for traceability purposes [10]. For

*Consumables included for sample collection, stabilization, and preservation in representative kits, classified by* 

**168**

**Figure 1.**

*the corresponding protocol and derivatives obtained.*

Evidence-based standard operating procedures (SOPs) are elaborated for sample processing taking the sample requirements provided by the testing laboratories into consideration. The number and volume of samples necessary for analytical assays and the type of derivative, anticoagulant or preservative must be identified in order to choose the most appropriate and approachable option of prospective collection of samples providing high-quality biomarkers useful for downstream applications [11]. Additional requirements from guides [12] or previous scientific publications [13] are also taken into account in relation with specific sample collection and derivative stabilization. Preservation delay and resources available for long-term storage will influence the selection of the collection device as well. In fact, roomtemperature storage alternatives have been proposed [14]. When the same sample allows obtaining different derivatives (i.e., blood for plasma, buffy coat, and RBCs), protocols will adjust the number and type of collection tubes or devices to minimize the quantity of sample collected from the donor. On the other hand, the number of aliquots of liquid samples must be set in function of the different analyses to be performed avoiding unnecessary freeze-thaw cycles.

These pre-analytical conditions of samples and derivatives will determine where each process (collection, initial sample processing, provisional cryopreservation of derivatives, long-term storage, testing) will be performed depending on the recruitment site, the biobank, and the analytical laboratory locations and facilities. Accordingly, transportation of samples at the corresponding temperature should be organized [15] following the international recommendations.

Obtaining of specific derivatives such as nucleic acid isolation may be centralized in the biobank or testing laboratories in order to avoid bias. In the same sense, reactive batches must be controlled. When possible, automation of processes must be implemented to avoid traceability errors and decreasing hands on time. Samples should be handled following validation of standard operating protocols by using samples not belonging to the particular project, specifically collected and approved for this purpose by an ethical committee.

The quality of samples must be evaluated after processing by means of a comprehensive analysis of quality indicators [16]. Because of the current lack of qualification tools for each type of derivative and pre-analytical variable, numerous studies are trying to identify new markers to assess the fitness-for-purpose of samples. Thus, new scores and indicators have been proposed for the quality of samples in relation with the impact derived from the pre-analytical phase [17–23]. In the same way, participation in external quality assurance (EQA) schemes like the EQA program developed by the International Society for Biological and Environmental

Repositories (ISBER) focused on sample processing and testing evaluation [24]; it is a highly recommended complementary tool for the internal quality control (IQC). Biobank collaboration through international working groups focused on standardization of sample processing, and biological sample quality control will contribute to the implementation of the last innovations in the field as well.
