Transport of Immunobiologicals in Brazil: A Multiple Case Study

Abstract

Background: Immunobiologicals are thermolabile products that require strict storage and transportation conditions to maintain their immunogenic efficacy, particularly in countries where logistical and operational challenges are evident, such as Brazil. Methods: A holistic multiple case study, carried out in five regions of Brazil, in 2022, with 42 workers from different instances of the cold chain was conducted. As a source of evidence, data were collected through interviews and analysis of printed documents and analyzed using Thematic Content Analysis, using the analytical technique of cross-case synthesis. Results: The influence of geoclimatic diversity and transportation modes on immunobiological logistics was highlighted. Challenges and requirements were identified, as well as aspects of monitoring during transportation and distribution. Among the main challenges were long distances, poor road conditions, seasonality and the need to share vehicles due to the unavailability of exclusive transportation. Conversely, positive practices were highlighted, such as the use of air-conditioned vehicles, dataloggers and properly prepared thermal boxes. Conclusions: It is necessary to adopt mitigation strategies that consider regional inequalities and promote equity, through raising awareness among managers, investing in logistical infrastructure and expanding good practices in order to guarantee the universal and qualified distribution of immunobiologicals in the country.

1. Introduction

Immunobiologicals are thermolabile products that require strict storage conditions to maintain their immunogenic efficacy [1]. In order to guarantee stability from manufacture to administration, it is essential to use a system known as the cold chain, whose function is to maintain an adequate and constant temperature, avoiding loss of potency and compromised efficacy [2,3].

In Brazil, the cold chain is characterized by a vertical and hierarchical structure, made up of different organizational levels—a national central body, 27 state central bodies, 273 municipal central bodies and approximately 38,000 vaccination rooms—which make up the local level [4]. Each of these levels performs specific functions within the system, as well as common responsibilities, such as the storage and distribution of immunobiologicals. It should be noted, however, that the local level is the only one that does not carry out distribution [2].

The cold chain requires uninterrupted refrigeration in all of its operational stages, through the use of specific equipment which, over time, has been improved by technological innovations with the aim of optimizing the storage conditions of immunobiologicals [5]. To ensure that the appropriate temperature range is maintained, usually between +2 °C and +8 °C, various monitoring devices are used, such as infrared thermometers (laser sighting), data loggers and maximum, minimum and instant read thermometers [2,3]. In addition, recent research has focused on identifying and developing new technologies and processes capable of improving the effectiveness of the cold chain [6,7,8].

Breaches in the maintenance of the cold chain have been reported in various parts of the world [9,10,11,12,13,14]. Transport, considered one of the most critical stages in this chain, must follow the recommendations of the National Immunization Programs (PNI) [2,3,15], as well as the standards for transporting thermolabile medicines [16]. Failures at this stage can result in loss of efficacy of immunobiologicals, waste of resources and reduced confidence in immunization programs [11,13,14].

Temperature excursions have been identified during the transportation of immunobiologicals along the cold chain in various regions of the world [11,17,18,19], compromising the potency and efficacy of these products. In Brazil, studies show that transportation between different instances often fails to comply with the recommendations of the PNI [2], such as the use of air-conditioned vehicles or vehicles with the air conditioning on [20,21]. Although the Ministry of Health is responsible for regulating, monitoring, and ensuring the maintenance of the cold chain, resource constraints and operational challenges still hinder its effective implementation across different contexts [22].

During the transport of immunobiologicals, temperature excursions are widely identified in the literature as the primary failure of the cold chain. However, such excursions do not occur in isolation; rather, they are associated with a set of operational and logistical factors. Among operational failures, inadequate conditioning of reusable ice packs [23], improper conservation of insulated containers and the ice packs themselves during use [24], as well as inappropriate temperature monitoring practices, are particularly noteworthy.

Logistical failures, in turn, include the absence or limited availability of vehicles dedicated to the transport of immunobiologicals [21,25], the use of non-climate-controlled vehicles, the lack of thermometers for temperature control, and deficiencies in route planning and distribution flows, such as delays or deliveries performed outside the operating hours of health facilities [23]. Additionally, seasonality may significantly affect road conditions, constituting another relevant logistical challenge to maintaining the cold chain, especially in areas with poor transport infrastructure [26].

Nevertheless, most studies on the transport of immunobiologicals predominantly focus on the analysis of temperature excursions, without an integrated consideration of the logistical and operational factors involved, such as transport time, road conditions, training of the professionals involved, and the organization of distribution flows. Given that adequate cold chain maintenance is directly related to geographical, climatic, structural, and logistical factors, there is a clear need for studies that enable a comprehensive understanding of these different aspects within the context of immunobiological transport.

In this regard, the following guiding research question is proposed: Which factors influence the maintenance of the cold chain in the transport of immunobiologicals in Brazil?

The analysis of these factors may contribute to logistical optimization, preservation of the integrity and safety of immunobiologicals, cost reduction, and the strengthening of public health policies.

Accordingly, the present study aimed to understand the factors influencing the maintenance of the cold chain in the transport of immunobiologicals in Brazil.

2. Literature Review

The cold chain presents a similar structure across different countries, being vertically organized into levels responsible for the storage, conservation, and transportation of immunobiological products up to the local vaccination unit. Although variations may occur regarding nomenclature and the number of levels, the operational logic remains comparable [2,27].

Transportation constitutes a critical stage in the cold chain logistics process, as it involves the movement of immunobiological products between different levels until reaching the end user. This displacement may occur by air, land, or water, depending on the geographic and infrastructural characteristics of the territory [2]. Failures in this process may compromise the quality and safety of immunobiological products, resulting in financial losses and public health risks [11,13].

In Brazil, the transportation of medicines and immunobiological products is regulated by legal frameworks that establish specific requirements to ensure product integrity, including appropriate temperature conditions, packaging, documentation, and shared responsibility among supply chain stakeholders, as provided for in Law No. 6360/1976 [28], Ordinance No. 802/1998 [29], and Collegiate Board Resolution No. 430/2020 [16], in addition to complementary guidelines issued by the Ministry of Health and the National Health Surveillance Agency.

The international literature reports recurrent failures during the transportation of immunobiological products, particularly related to temperature excursions. A systematic review identified multiple studies documenting exposure to temperatures below or above recommended limits during transportation [30]. Studies conducted in Mexico and India also reported significant thermal excursions during transfers between cold chain levels, with prolonged exposure outside the recommended range [11,31]. Problems related to inadequate conditioning of reusable ice packs and delivery delays have also been reported in different countries [23].

Beyond temperature monitoring, the adequacy of materials and equipment used in transportation is a determining factor in maintaining cold chain integrity. A study conducted in Kenya found that part of the cold boxes and reusable ice packs were unsuitable for use, compromising transport safety [24]. The availability of appropriate vehicles also represents a relevant challenge: a study in health facilities in the Kenyan capital indicated that only 1% had an exclusive vehicle for transporting immunobiological products, with frequent reliance on public transportation or alternative means [25].

In the Brazilian context, although consolidated regulations and technical guidelines exist, studies indicate weaknesses in the transportation of immunobiological products. Research conducted in the state of Minas Gerais identified inadequate implementation of cold chain procedures during transportation in a large proportion of evaluated municipalities, highlighting the absence of climate-controlled and exclusive vehicles, insufficient professional training, the use of cold boxes without thermometers, and the lack of systematic temperature monitoring during transport [21].

Despite the existence of specific regulations and evidence of operational failures, the national literature still presents limitations regarding comprehensive and comparative analyses of immunobiological transportation across different regional contexts. This gap reinforces the need for studies that deepen the understanding of logistical and structural challenges associated with this critical stage of the cold chain.

3. Materials and Methods

3.1. Research Design

This is a holistic multiple case study [32] carried out in different instances of the cold chain (state, regional, municipal, and local) in five regions of Brazil in 2022, derived from a larger project entitled Evaluation of the Cold Chain for the Conservation of Immunobiologicals in Brazil [33,34]. The multiple case study design enabled comparative analysis [32,35] across different regional and organizational contexts, while the holistic approach defined the unit of analysis as the maintenance of the cold chain in the transport of immunobiologicals in Brazil, encompassing all levels from the national to the local level (Figure 1). The guidelines of the Consolidated Criteria for Reporting Qualitative Research were followed [36].

3.2. Study Setting

Brazil has a territorial extension of 8,510,417.771 km², distributed between 26 states and the Federal District, with an estimated population of 212,583,750 inhabitants. The country is divided into five major regions: North, Northeast, Midwest, Southeast and South. The North has the largest territorial extension, with 3,850,593.10 km², while the South has the smallest, with 576,736.82 km² [37].

3.3. Data Collection

The selection of participants was based on the thematic study entitled Evaluation of the cold chain for the conservation of immunobiologicals in Brazil, which used a mixed methodological approach [33,34]. The first stage consisted of a cross-sectional study aimed at assessing the maintenance of the cold chain, using the Immunobiological Agent Conservation Assessment Scale (EACI) [38]. This phase included 280 randomly selected vaccination rooms in 80 municipalities in eight Brazilian states [33,34]. For the qualitative stage, the focus of this study, participants were selected from all regions of the country based on the EACI score stratification [38], which classifies cold chain maintenance as inadequate (0 to 9 points) or adequate (10 to 15 points) (Supplementary Material S1). Considering the scope of the thematic project’s focus, this work concentrated on issues related to the transportation of immunobiologicals between the different Brazilian instances, from the state to the local level.

All the state technical references in immunization, selected in the quantitative phase of the study [33,34], were invited to take part in the study, with the exception of one state, which chose not to take part in the qualitative stage. As inclusion criteria for participants in the qualitative data approach, individuals serving as technical references at the state, regional, and municipal levels were considered eligible. No exclusion criteria were applied, as the sampling strategy was based on exhaustion. The representatives of the regional and municipal levels and the professionals working in the vaccination rooms were selected by lottery, which was carried out during the quantitative stage of Amaral’s study [33,34]. In cases of refusal, a new draw was made. The sample for the qualitative stage consisted of 42 participants, distributed as follows: 7 state representatives, 11 regional representatives, 11 municipal representatives and 13 professionals directly affiliated with vaccination rooms across the five regions of Brazil.

With the participants’ approval, a link to access the Free and Informed Consent Form was sent by email or through a messaging app. Data collection took place in two stages: a structured questionnaire prepared by the authors with information on sociodemographic characteristics, and individual synchronous interviews using the Google Meet platform (version 2022), based on a semi-structured script previously developed by the researchers (Supplementary Material S2). The interview script explored issues related to cold chain maintenance, and one was developed for each hierarchical level of the chain, taking into account the particularities of each instance (Supplementary Material S2), with a view to addressing the research problem, “Which factors influence the maintenance of the cold chain in the transport of immunobiologicals in Brazil?”. The interviews were recorded and transcribed in full. To guarantee the anonymity of the participants, an alphanumeric criterion was adopted, using the letter “E” (for interview), plus the sequential number of the interview, followed by the instance and the participant’s region (E1 State, North).

A total of 42 professionals from different segments of the cold chain participated in the study, representing all five regions of Brazil. Most participants were female (n = 36), with a predominance of nursing professionals (n = 31), followed by nursing technicians (n = 8), one veterinarian, one geographer, and one participant who did not report their professional background. Regarding length of experience in the vaccination field, 17 participants reported up to five years of experience, 11 reported between 6 and 15 years, and 13 reported more than 15 years of experience. Only one participant did not provide this information.

3.4. Data Analysis

As a source of evidence, we used data on the transportation of immunobiologicals, collected during the interviews, as well as the analysis of printed documents (forms, vaccine room training, standard operating procedures, contingency plan, among others) and images sent by the participants, defined as field notes. In addition, technical visits were made to two municipalities (adequate and inadequate), selected on the basis of the findings of Amaral’s study [33,34]. The triangulation of evidence was used to increase the credibility of the research, as it contributes to a deeper and more comprehensive explanation of the phenomenon under study [32], corroborating a study carried out by Eisenhardt [35].

The analysis of the research data was based on Thematic Content Analysis, following the phases: pre-analysis, exploration of the material and treatment of the results, inference and interpretation [39]. Exhaustive sampling led to literal replication of the data, as proposed by Yin [32], resulting in theoretical saturation of the concepts inherent to the established criteria for adequate and inadequate maintenance of the cold chain across the five regions of Brazil (Figure 2). Following this process, we grouped the units of similar and different records [32,40], naming with informants’ terms and analyzing the resulting set in the central categories of the research. All the interviews were included in the analysis, revealing patterns in their content (Supplementary Material S3). In addition, the analytical technique of cross-case synthesis [27,35] was used to compile the data, enabling detailed analysis. Similar results were then cross-referenced and differences identified, with the aim of gaining an in-depth understanding of the research object. Cross-synthesis was carried out initially, case by case and after crossing the cases [32], performing a systematic comparison, making it possible to synthesize and deepen the identified influencing factors [35].

The representativeness of this study is not statistical in nature, but rather analytical and theoretical, as participants from all regions of the country were included, encompassing different levels of the cold chain and vaccination rooms classified as having adequate or inadequate cold chain maintenance. These criteria were considered in achieving the theoretical saturation of the data. Furthermore, all 42 interviews available in the database of the larger project were used in full and exhaustively.

The study is part of a thematic project, entitled Evaluation of the cold chain for the conservation of immunobiologicals in Brazil and was approved by the Research Ethics Committees of the Ribeirão Preto Nursing School of the University of São Paulo (opinion no.: 4.610.079 and CAAE: 43322621.2.0000.5393); the Federal University of São João del-Rei, campus Centro-Oeste Dona Lindu (opinion no.: 4.747.228 and CAAE: 43322621.2.3001.5545); and the National Research Ethics Commission (opinion no.: 4.812.197 and CAAE: 43322621.2.3002.0008).

4. Findings

Data analysis revealed a central category related to the operational process of transporting immunobiologicals in Brazil, from which three subcategories emerged.

The first subcategory addresses the main challenges faced in ensuring that immunobiologicals reach their destination safely, considering factors such as seasonality and poor access road conditions.

4.1. Geoclimatic Diversity, Means of Transportation and Their Influence on the Transportation of Immunobiologicals

Considering the continental dimensions of the Brazilian territory, the extensive geographical distribution imposes significant logistical challenges, requiring the use of various modes of transportation, such as airplanes, cars, trucks, boats and speedboats, to ensure the delivery of immunobiologicals to all regions of the country.

“The municipalities that are part of, that are dependent on the polo de I (regional center), they are far away. Some can only be reached by road, but usually by boat or speedboat”

(E2 Regional, North).

“The Ministry of Health delivers them to us. [...] it comes by land in refrigerated trucks and sometimes it comes by air”

(E25 State, Midwest).

The transportation of immunobiologicals to more remote municipalities is difficult, requiring even more rigorous care, especially with regard to the use of suitable equipment to maintain the recommended temperature throughout the journey:

“How difficult our transportation is, from us (state center) to them (municipalities). There are also difficulties between them [...] there are municipalities where the distances are sometimes quite far from the regional headquarters”

(E1 State, North).

“The main difficulty is precisely distribution to the most difficult places to access. We find basic units (local level) that are far from the headquarters (municipal level). So we have to be more careful with the equipment we have”

(E8 Municipal, Northeast).

Some instances still face additional difficulties due to poor access roads. In addition, environmental factors such as rainfall and flooding have a significant influence on the trafficability of these roads, exacerbating logistical challenges, especially at certain times of the year:

“Our vaccine arrives by land and currently our road is not good [...] The road is really bad, so it usually takes a while. By car it’s taking about 4, almost 6 hours, by (truck). Sometimes it takes a little over 6 hours”

(E2 Regional, North).

“From my municipality to the regional office it’s 105 km, with a good road we used to get there in up to 2 hours, but now it’s 4 hours, 3 and a half hours. It depends, if it’s raining it’s 4 hours”

(E15 Municipal, Northeast).

“Sometimes it’s easy to get to the municipality because it’s flood season and sometimes it’s easy to get to the municipality because it’s dry. At other times, the journey is longer because it’s in flood or drought”

(E1 State, North).

Seasonality also has a direct impact on the local level, which, faced with adversity, adopts strategies to prevent losses of immunobiologicals. Among these measures is the practice of frequent transfers, weekly or even daily, to the municipal level, especially observed in locations in the Northeast region.

“Every Friday my vaccines go to the cold chain (the municipal office), and every Monday they go through this transportation. Because I get vaccinated practically every day, so it’s interesting that I have the vaccine at the clinic, but every week it goes through this route [...] because I don’t trust the structure. [...] Here in the city, any time the weather changes, the power goes out, so in order not to have to relocate out of hours, we think it’s safer to send it every Friday.”

(E12 Local, Northeast).

There is an interdependent relationship with state air transportation for the distribution of immunobiologicals destined for municipalities that are difficult to access, and in many cases this transportation is the only viable alternative:

“So when they hear that there’s an airplane, they try to call the representative so that they can take the immunobiologicals. We have a lot of difficulty with transportation, especially by air. [...] It’s only when they run into the issue of transportation, of not having a plane, that they really get stuck, without being able to get it”

(E1 Northern State).

It was found that some instances have exclusive means of transportation. On the other hand, there were instances where the availability of vehicles is limited, which compromises the regularity and conformity of transportation as recommended:

“That’s why we go in a special car, we don’t go in another car together with patients or another car that’s going to take care of other things there. We just go to pick them up and come back. It’s a specific car just for that [...]”

(E15 municipal Nordeste).

“Hence our logistical difficulties, because the transport that serves the base (regional level) is transport for all sectors, not just immunization. [...] These are the two vehicles we have at our disposal. When they are available”

(E19 Northeast Regional).

“It’s the car that’s available at the moment [...] it’s not necessarily always the car with air conditioning”

(E34 Municipal/Local Southeast).

In some municipalities, it is still common to use a single vehicle for multiple purposes during the same trip, such as the simultaneous transportation of patients and immunobiologicals:

“Sometimes, the municipality comes with a car that comes to bring patients and then it comes back at whatever time it can. So how are we going to guarantee the quality of these immunobiologicals? That temperature?”

(E18 Northeast Regional).

“We pick it up every week and there’s always one thing or another for us to pick up at the regional office or resolve”

(E8 Municipal Nordeste).

The second subcategory encompasses the need for a trained professional to accompany the transport of immunobiologicals, as well as the challenges related to the availability of such professionals.

4.2. Monitoring the Transportation and Distribution of Immunobiologicals

It emerged that immunobiologicals are transported in three different ways: exclusively by the driver or pilot; accompanied by a professional who is not part of the nursing team; or with the presence of a nurse or nursing technician:

“The representative of the municipality makes the delivery on the flight and from there it is brought to the municipality by the pilot, there is no specific professional accompanying, no. [...] It is the person responsible who makes the delivery (of vaccines), there is the driver and there is the person responsible for making the deliveries to the UBS (local instance). It’s not a specific professional. It’s not a nurse or a technician. Sometimes the technician goes, but not regularly”

(E3 Municipal, North).

“We always send a professional [...] to check the temperature, to check any emergency situation that might occur during transportation, so that he can get there and certify the material supply note together with the technician from the health region that is receiving these doses.”

(E4 State, Northeast).

“If it’s a small amount, only one driver goes, but if it’s a larger amount, COVID-19 vaccines, campaign vaccines, usually a nursing technician goes”

(E26 Regional, Midwest).

“The central office (regional level) takes it (to the municipal/local level). The driver arrives and a technician (nursing technician) comes, there are usually three of them, the driver and two more technicians”

(E31 Local, Southeast).

“No one comes to monitor the temperature, it’s just the driver, so there’s no control over the Ministry of Health’s trip”

(E39 State, South).

One of the reasons given for the lack of professional supervision during the transportation of immunobiologicals is the lack of human resources. In addition, the choice of alternative means of transportation is also related to the shortage of available drivers:

“Not even the municipality itself can send the coordinator or a nursing technician, because it will be taking away from the functions, which it has within the municipality, to come and get vaccine”

(E5 Regional, Northeast).

“When there were more staff here in the vaccine room, they always asked one of the nurses to come along, because then they could control the temperature. But now it’s a bit tight, so he (the driver) goes alone”

(E38 Local, Southeast).

“We’ve had the most difficulty with the professional driver [...] Because we only have one truck driver to do this transportation”

(E39 State, South).

To carry out the distribution of immunobiologicals, the professionals involved receive training, including the driver responsible for transportation between the different instances of the cold chain:

“Then we did a training session with the drivers, they receive the spreadsheet, they check it, the delivery person shows them and counts along with them. Oh... here’s two hundred doses of that, then he shows the paper, then he signs it”

(E6 Regional, Northeast).

“I now have a nursing technician for a year (2022). She’s helping a lot to monitor the receipt of vaccines, the deliveries [...] We’ve trained this person to check and she’ll pass anything different on to me”

(E32 State, Southeast).

The third subcategory addresses the importance of complying with essential requirements to ensure the proper and safe transport of these products.

4.3. Challenges and Requirements for Transporting Immunobiologicals

Immunobiologicals require specific temperature and storage conditions during transportation between different instances. Among the precautions adopted are the use of equipment for continuous temperature monitoring and the availability of spare reusable ice reels:

“We manage to conserve and, generally, we already take two isopores, two thermal boxes, because then we don’t have any problems during this journey. Because these are trips in which we sometimes have to deal with other problems, we take this precaution [...]”

(E8 Municipal, Northeast).

“[...] We open the boxes, take out the datalogger, which is a little device that records temperature fluctuations during transportation, and give it to the driver”

(E33 Regional, Southeast).

“From the central office to the regional offices, we have a datalogger to monitor [...] we have this control up to the regional health offices”

(E39 State, South).

Another relevant aspect concerns the suitability of the vehicle used to transport immunobiologicals between the different instances, with the use of refrigerated or air-conditioned vehicles being particularly recommended:

“It (transportation) is done in those thermal containers and in small cars, which are also air-conditioned. They (municipal staff) take care to always send an air-conditioned car”

(E12 Local, Northeast).

“Our car doesn’t have air conditioning, it’s a car without air conditioning, it’s a Ranger (medium-sized vehicle)”

(E21 Municipal, Northeast).

“We have four refrigerated trucks. These trucks do the routes [...] We do half the regional routes one week and half the next”

(E25 State, Midwest).

“We have air-conditioning in the car, it’s not a van, that’s what it’s for, but inside the car we have air-conditioning which helps a lot”

(E37 Municipal/Local, Southeast).

In addition, the professionals carefully prepare the thermal box in order to ensure that the immunobiologicals are properly packaged during transportation:

“He arrives early, acclimatizes the ice packs (reusable ice reels), assembles the boxes, lets them reach temperature. As it’s close by, the temperature that leaves here usually reaches there”

(E35 Municipal, Southeast).

In a photographic record provided by technicians from the Northeast region, we can see the arrangement of reusable ice reels on a surface, as well as a polyurethane cooler equipped with a thermometer attached to one of its sides, registering a temperature of 3.2 °C (field note) (Supplementary Material S4).

In addition to properly assembling the cooler, when the regional authorities release the immunobiologicals to be picked up by the municipal authorities, the internal temperature of the cooler is checked, according to the recommendations, before it is handed over to the driver responsible for transportation:

“These containers come with thermometers on top, and we wait for the temperature of the container to start distributing the vaccine. Once it’s been placed in the Styrofoam according to what they’ve asked for, we close the Styrofoam, wait for the temperature to be right and send it to the municipality by the driver who comes to pick it up”

(E5 Regional, Northeast).

“They (the municipal office) come with a thermal box with a temperature control. We check it, see what time it left, what temperature it is, how long it takes to get to their municipality, and if necessary we add more icex (reusable ice reel) or remove it if the temperature is too low”

(E33 Regional, Southeast).

It was found that when the immunobiologicals are received, the professional in charge carries out a thorough check of the characteristics of the products, including the condition of the thermal box and temperature monitoring:

“Every time this immunobiological arrives, there is a form to fill in the temperature that was received to be sent to the state PNI (state body). There’s a team responsible for receiving it [...]. Then the thermal box is sealed and only opened by the nursing technician who is in the room (local instance), who monitors the temperature when she opens the box”

(E3 Municipal, North).

“We check the temperature that we’ve written down, there (municipal level) is a form that we write down as soon as we leave and another form that we fill in when we get here”

(E28 Local, Midwest).

Some authorities use forms to check when immunobiologicals are received, such as the voucher used by the Municipal Health Department of a municipality in the North region, which includes a temperature record, as well as a description of the immunobiologicals received and their respective quantities (field note).

In the northern region, it was found that the responsibility for maintaining the quality of immunobiologicals during transportation lies exclusively with the municipality:

“We guarantee our temperature here within the cold chain, now it’s gone we don’t know anymore”

(E2 Regional, North).

“When they (vaccines) are released by the state PNI (state body), the municipal health secretary signs an agreement taking responsibility for these immunobiologicals (transportation). Generally, at the weekend, from Friday onwards, he has to sign this form. Even if something unforeseen happens, he is responsible”

(E3 Municipal, North).

In the same region, the municipality has provided a form for requesting the withdrawal of supplies on Fridays or on the eve of public holidays, to be sent to the state body. In this context, the municipality assumes responsibility for the transportation and safety of the immunobiologicals (field note).

The municipal level in the Southeast region, during training on vaccination, clarifies responsibility for the quality of immunobiologicals, emphasizing that all the technicians involved in the cold chain are responsible for maintaining the quality of the immunobiologicals supplied to the population (field note).

During a technical visit to a municipal center in the Southeast region, specific precautions were observed, such as the use of a suitable, air-conditioned vehicle for transporting immunobiologicals, as well as the presence of a driver trained exclusively for this purpose (visit notes).

The lack of adequate preventive maintenance and the delay in carrying out corrective maintenance on the vehicles used to transport immunobiologicals have an impact on distribution between the instances in the Northeast region:

“Although we have a truck that does this service, but for bureaucratic reasons maintenance ends up being more difficult. So the truck spends some time at a standstill until it’s up and running again [...] Because it’s no good just going in for maintenance when it breaks down, it has to be preventative.”

(E7 Regional, Northeast).

“Difficulty, we currently have 3 vehicles at our disposal, but we have some obstacles in relation to the maintenance of these vehicles [...] because they are cars that are always having some problem in terms of maintenance, breakdowns [...] and because the sector is very large I need the cars to do other activities”

(E21 Municipal, Northeast).

4.4. Cross-Case Synthesis

Using the cross-case synthesis methodology [32], it was possible to identify similarities and contrasts between the five Brazilian regions (

Table 1. Cross-section of cases from the five major regions of Brazil.

Cross-Synthesis of the Five Multiple Cases: Similar Characteristics and Particularities in the Five Brazilian Regions	Brazilian Regions
Dependence on government aircraft for transportation	North
Difficulty of access in remote areas	North
Seasonality impacting positively or negatively on transportation	North, Northeast
Sharing vehicles on the same trip to transport immunobiologicals and other demands	North, Northeast
Difficulty in finding vehicles to transport immunobiologicals	North, Northeast, Southeast
Transportation accompanied by a professional in addition to the driver at some point between the state and local levels	North, Northeast, Midwest and Southeast
Shortage of refrigerated truck drivers	South
Transportation unaccompanied by health professionals or technicians, only by drivers	North, Northeast, Southeast and South
Need for different means of transportation (land, air, river)	North, Midwest
Use of vehicles suitable for transporting immunobiologicals (refrigerated or air-conditioned)	Midwest, Northeast, Southeast
Training of distribution professionals, including drivers	North, Northeast, Southeast
Institutions facing difficulties in having professionals accompanying transportation	Northeast (regional and municipal), Southeast (local), South
Lack of maintenance of transport vehicles	North, Northeast
Transfer of responsibility for maintaining the temperature of the vaccine from the state/region to municipal transportation	North

). The analysis reveals disparities in the transportation of immunobiologicals, with problems related to accessibility and seasonality standing out in the North and Northeast. On the other hand, the Southeast, Midwest and South have more consolidated structures, although they still face operational and logistical challenges, such as the availability of vehicles, transportation exclusively by drivers and temperature monitoring. Despite the regional particularities, there is a continuous effort to train and improve practices related to the transportation of immunobiologicals throughout the country.

The analysis of the data allowed the elaboration of a descriptive infographic of the transport of immunobiologicals in each of the five Brazilian regions (Figure 3):

4.4.1. North Region

The transport of immunobiologicals from the National Center to the North region occurs by air and, between the instances of this region, there are several means: land, air and river. Currently, it has a single regional instance that serves five municipalities, and the others are served by the state instance which sends the immunobiologicals to the regional by land, using trucks. In addition to the driver, a professional accompanies transport, but the conditions of the highways and roads are precarious. The regional informs the municipalities of the arrival of the products and they carry out their withdrawal. However, the municipalities do not have exclusive transportation for immunobiologicals, and this transportation is used for other purposes. In addition, the main means of transport for the municipalities is the river. In the other municipalities, in general, transport is carried out by air, and transport is carried out only by the pilot, without the presence of a health professional. After that, the municipality transports the immunobiologicals to the vaccination rooms in a small vehicle accompanied by a professional responsible for the delivery, not specific to the nursing team.

4.4.2. Northeast Region

The immunobiologicals arrive in the Northeast region by air transport and are taken to the state level by a third-party company, at the service of the Ministry of Health. Subsequently, the state instance forwards the immunobiologicals to the regional instances by means of an air-conditioned truck, which may or may not be accompanied by professionals, depending on the state. In addition, some roads that connect the different instances of the cold chain are in precarious condition and are affected by seasonality. When the immunobiologicals arrive at the regional offices, the municipalities travel to carry out the removal using their own vehicles. This transport, most of the time, is accompanied by technical professionals, nurses or mid-level professionals. There are also situations in which the municipality takes advantage of the transport of immunobiologicals for other purposes. Upon arrival at the municipal instance, this transport occurs in two ways: the instance delivers the immunobiologicals directly to the vaccination room, or the vaccination room picks up the immunobiologicals at the instance. This process is accompanied by professionals.

4.4.3. Midwest Region

The national authority sends the immunobiologicals to the state level in two ways: by air and by land. When shipped by land, they are transported in refrigerated trucks. Then, they are sent to the regional instance in refrigerated large vehicles (trucks), accompanied by a professional. When they arrive at the regional, they are directed to the municipal instance in small air-conditioned vehicles. When there is a greater demand, a nursing technician accompanies the transport. The municipal authority then distributes the immunobiologicals to the vaccination rooms in small air-conditioned vehicles, with a technician from the network accompanying them.

4.4.4. Southeast Region

The immunobiologicals are sent to the state level by a third-party company, in large refrigerated vehicles, such as trucks. Some states have regional instances, while others do not. They can be forwarded to the regional or directly to the municipalities. During this process, there is no follow-up by a professional from the nursing team or from the secondary level. After arriving at the regional level, the municipalities travel to pick up their immunobiologicals in small air-conditioned vehicles, and this transport can be outsourced and accompanied by a nursing technician, depending on the municipality. Afterwards, the vaccination rooms pick up their immunobiologicals in air-conditioned vehicles, usually without accompaniment. However, a small part receives the immunobiologicals directly in the vaccination room through air-conditioned vehicles, with a professional accompanying them. In municipalities that are not covered by a regional instance, immunobiologicals are sent from the state instance directly to the vaccination rooms by means of small refrigerated vehicles, with a technical professional from the network accompanying, which may be a nursing technician.

4.4.5. South Region

The transport of immunobiologicals to the South region follows a specific process: the national level is responsible for delivering, mainly by land, the immunobiologicals to the state level. Then, these are sent to the regional instance in large vehicles, without refrigeration. The municipalities then withdraw their immunobiologicals at the regional level and deliver them to the vaccination rooms. It should be noted that this transport between instances is carried out only by the driver, without the accompaniment of a professional.

5. Discussion

The analysis showed factors that influence the cold chain in the transport of immunobiologicals and regional disparities in Brazil, highlighting the complexity of ensuring the integrity of these products in an extensive and heterogeneous territory. The long distances between the instances of the cold chain, especially in the North and Northeast regions, are a relevant challenge. Monitoring by a trained professional was pointed out as essential, although there are difficulties in making this available. Requirements such as monitoring up to the local instance, adequate packaging and use of appropriate vehicles are also highlighted, in view of limitations such as unavailability and insufficient maintenance of means of transport. These findings are discussed below in terms of their theoretical implications, practical contributions, and limitations.

5.1. Implications for Theory

Brazil, with its extensive territorial area of approximately 8.5 million km² [37], has only one national center responsible for the distribution of immunobiologicals to states and municipalities [4]. This configuration requires, in certain regions, the use of modes of transport other than the land modal such as river transport in the North region, as pointed out in a previous study [41]. To mitigate the impacts of long distances and seasonality, innovative solutions have been developed, including the use of unmanned aerial vehicles (drones) and route and cost optimization algorithms, which have shown promising results [42,43], especially in hard-to-reach areas.

From a theoretical standpoint, these findings contribute to the literature on health logistics and cold chain management by demonstrating how geographic scale, climate variability, and infrastructure constraints interact to shape distribution performance in decentralized health systems.

The results also showed that seasonality directly influences the transport of immunobiologicals, and can both facilitate and hinder transport routes, especially in relation to waterway transport. Thus, statistical models aimed at analyzing water levels, with the ability to predict periods of drought and flood at certain intervals, can contribute to the improvement of navigability conditions that help the strategic planning of transport [44]. In addition, the Brazilian Ministry of Health has developed specific recommendations for transportation during extramural vaccination activities, considering factors such as seasonality and distance [15].

The conditions of transport of immunobiologicals can be affected by hydrometeorological events, such as heavy rainfall, floods, landslides, and erosive processes [26], which can lead to shortages of these inputs and negatively influence vaccination coverage [45]. A study conducted in Madagascar showed that, during the rainy seasons, there were interruptions in the supply of vaccines, with a direct impact on vaccination coverage, which reached 43% in affected regions, compared to 70% in unaffected regions [45].

In the Brazilian context, this vulnerability is aggravated by the precariousness of the road infrastructure, since 67% of the highways have inadequate conservation conditions, according to the National Transport Confederation [46]. In this sense, it is assumed that the obstacles related to the transport of immunobiologicals have contributed to the reduction in vaccination coverage, evidenced by more accentuated drops in the North and Northeast regions, especially for vaccines against poliomyelitis [47] and MMR vaccines (measles, mumps, and rubella) [48].

The climate crisis tends to intensify the challenges faced by the cold chain, especially in the transport and storage of immunobiologicals. Thus, the relevance and need for studies such as the present one are evident, which contribute to the understanding of the impacts of climate change on immunization logistics and to the strengthening of health systems. The study also advances discussions on resilience in public health supply chains by incorporating climate-related risks as structural determinants of cold chain performance. Such an approach is aligned with the Sustainable Development Goals (SDGs), especially SDG 3—Good Health and Well-Being and SDG 13—Action Against Global Climate Change.

5.2. Implications for Practice

From a practical perspective, the findings highlight priority areas for strengthening cold chain transport management in Brazil and similar settings.

The availability of vehicles for the transport of immunobiologicals, as well as their use for other purposes, was reported in the study as a critical factor for the maintenance of the cold chain. This finding reflects a reality observed in different regions of Brazil [21,34]. In Minas Gerais, it was found that 58.5% of the municipalities did not have exclusive transportation for this purpose [21]. Similarly, a study conducted in Kenya found that only 1% of health facilities had an official vehicle for transporting immunobiologicals, while most resorted to alternative means, such as public transport, buses, vans, taxis, motorcycles, ambulances, and even walking, which can compromise the temperature control required to ensure the efficacy of immunobiologicals [2].

The present study pointed out that in the Northeast, Midwest and Southeast regions of Brazil, transportation is mostly carried out in air-conditioned or refrigerated vehicles, in accordance with the standards established by the PNI. However, research indicates that the lack of this type of resource is still a reality in several countries [21,24].

A negative point pointed out by the participants of this study was the absence of preventive maintenance and the delay in carrying out corrective maintenance of vehicles, in disagreement with Collegiate Board Resolution No. 430/2020, which provides for the obligation of proper maintenance of these vehicles [16]. Such negligence compromises the availability of vehicles and hinders the logistics of distributing immunobiologicals. The systematic adoption of preventive maintenance is essential, as it allows the early identification of failures and contributes to the reduction in operating costs.

Another relevant finding refers to the lack of follow-up by a qualified professional during transport between the instances of the cold chain in some regions of Brazil, in disagreement with the recommendations of the Ministry of Health, which establish the need for follow-up by a properly trained technician [2]. In order to qualify the continuous monitoring of transport and support the management of the cold chain, technologies for remote supervision in real time have been developed. These technologies include digital temperature sensors, such as thermocouples and devices capable of performing spot and continuous measurements, as well as systems for recording, verifying, and analyzing the flow of vaccines from production to health services. Such systems allow the issuance of alerts in the event of temperature deviations, helping managers in strategic decision-making [49,50,51].

An essential precaution for the identification of possible changes that occur during transport is to check the conditions of the immunobiologicals at the time of receipt. The study showed that this practice occurs in at least one instance of the cold chain in each region of Brazil. Considering that transportation is the most critical stage of the entire cold chain, it is essential that it be carried out under continuous monitoring, with systematic temperature recording and the use of monitors attached to the bottles, as control and safety strategies [1].

One aspect that stood out in the study was the adoption of essential precautions in the transport of immunobiologicals, such as correct packaging and temperature verification before delivery to the person responsible for transport, fundamental steps for maintaining temperature during transport. International evidence indicates different results: research carried out in Kenya demonstrated adequate knowledge of professionals about the correct packaging of ice coils [24] while research in Tigray, Ethiopia, and Uganda has identified inappropriate practices, such as incorrect placement of these coils in coolers [13,52]. In addition, alternatives to ice coils are being tested, as well as new storage and transport devices, which are promising options to qualify cold chain maintenance [7,8].

The findings indicate operational gaps in planning, monitoring, and resource allocation along the transport segment of the cold chain. From a logistical perspective, these gaps are reflected in limitations related to vehicle availability, route organization, and the continuity of professional supervision during transport. The results highlight the relevance of standardized procedures, such as the preparation, implementation, and monitoring of standard operating procedures, as mechanisms to reduce failures and preserve the integrity of immunobiologicals throughout the cold chain.

From an operational perspective, the findings suggest the need for measurable indicators to support transport performance, such as frequency of temperature excursions, availability of dedicated vehicles, preventive maintenance compliance rates, and presence of trained personnel during transport.

Failures in the transport of immunobiologicals, evidenced in the research, can compromise their effectiveness, exposing the population to potential outbreaks of vaccine-preventable diseases. The supply of immunobiologicals with compromised quality has been pointed out as one of the factors associated with these outbreaks [10]. This scenario underscores the importance of clear and effective regulations, as well as the application of penalties in cases of non-compliance or the adoption of incentives to encourage compliance with these standards [53].

Although this study did not aim to evaluate the cost of the cold chain, evidence from the Brazilian context indicates that investments related to monitoring, preventive maintenance, and qualified human resources represent a substantial share of cold chain expenditures. A recent economic evaluation conducted at the municipal level in Brazil showed that nonmedical direct costs accounted for more than 60% of total cold chain costs, with human resources representing over 70% of overall expenditures, followed by expenses related to refrigeration equipment and transport logistics [54]. Furthermore, the literature indicates that failures in cold chain transport may lead to vaccine losses corresponding to a significant proportion of procurement costs, whereas investments in monitoring technologies and preventive maintenance are generally classified as low- to medium-cost interventions when compared with the financial losses associated with vaccine wastage and the costs of outbreak response [5,49,55,56].

5.3. Limitations of the Study and Future Research Directions

Although this nationally representative study contextualizes the cold chain in Brazil, regional differences and contextual specificities may limit direct generalization to other countries with different geographic and infrastructural characteristics.

In addition, the study did not include direct measurement of temperature deviations during transport nor a detailed cost-effectiveness assessment of proposed interventions.

Future research could explore longitudinal monitoring of transport performance indicators, comparative analyses across countries, and economic evaluations of digital monitoring technologies and preventive maintenance strategies to further strengthen theoretical and operational models of cold chain management.

6. Final Considerations

Regional inequalities in the transport of immunobiologicals in Brazil highlight the logistical challenges of preserving cold chain integrity in a vast and heterogeneous territory marked by climatic, geographical, structural, financial, and administrative differences. The results show that the logistics of transporting these inputs are unevenly distributed nationwide, reflecting operational vulnerabilities related to transport modes, infrastructure conditions, vehicle availability, monitoring practices, and preventive maintenance.

The findings indicate that certain regions face additional challenges in maintaining the cold chain, particularly those with more precarious infrastructure and greater logistical constraints, reinforcing the relevance of the equity principle within the context of the PNI. In this sense, the identification of these disparities underscores the importance of initiatives aimed at strengthening local capacities, including the training of professionals involved, the expansion and adequacy of transport resources, and improvements in logistical infrastructure, especially in more vulnerable regions.

Without proposing specific normative or policy measures, this study contributes by identifying critical logistical factors that affect the performance of immunobiological transport and by indicating operational elements that can be monitored, measured, and optimized throughout the cold chain. These findings provide support for future analyses focused on cost-effectiveness, governance arrangements, and the implications of logistics management for vaccination coverage.