Abstract
Background
In Italy, the financial reimbursement for labile blood components exchanged between Regions is regulated by national tariffs defined in 1991 and updated in 1993–2003. Over the last five years, the need for establishing standard costs of healthcare services has arisen critically. In this perspective, the present study is aimed at defining both the costs of production of blood components and the related prices, as well as the prices of plasma-derived medicinal products obtained by national plasma, to be used for interregional financial reimbursement.
Materials and methods
In order to analyse the costs of production of blood components, 12 out 318 blood establishments were selected in 8 Italian Regions. For each step of the production process, driving costs were identified and production costs were. To define the costs of plasma-derived medicinal products obtained by national plasma, industrial costs currently sustained by National Health Service for contract fractionation were taken into account.
Results
The production costs of plasma-derived medicinal products obtained from national plasma showed a huge variability among blood establishments, which was much lower after standardization. The new suggested plasma tariffs were quite similar to those currently in force. Comparing the overall costs theoretically sustained by the National Health Service for plasma-derived medicinal products obtained from national plasma to current commercial costs, demonstrates that the national blood system could gain a 10% cost saving if it were able to produce plasma for fractionation within the standard costs defined in this study.
Discussion
Achieving national self-sufficiency through the production of plasma-derived medicinal products from national plasma, is a strategic goal of the National Health Service which must comply not only with quality, safety and availability requirements but also with the increasingly pressing need for economic sustainability.
Keywords: sustainability, plasma, plasma-derived medicinal products, costs
Introduction
According to Law No. 219 of October 21st, 2005, which defines the “New discipline for blood transfusion activities and national production of plasma-derived medicinal products”1 and redesigns the structure of the national blood system, the Italian National Blood Centre (NBC), in agreement with the National Blood Technical Board, shall provide indications to the Ministry of Health and the Regional Health Authorities for the definition of the prices for interregional exchange of blood components (BCs) and of medicinal products obtained from the plasma for fractionation produced by Blood Establishments (BEs).
Prices for interregional exchange of BCs were defined for the first time in 19912 and subsequently updated in 19933, 19954, 19965 and 20036. According to article 2 of the State-Regions Agreement of 20036, the price of BCs represents the upper limit of gross costs attributable to all activities connected to the production process: blood donor recruitment, blood collection, processing, testing and storage.
Over the last ten years, significant changes have occurred within the Italian National Health Service (NHS). In particular, costs incurred by BEs are mainly linked to collective labour agreements, to the prices of goods and services, as well as to the introduction of additional mandatory blood testing. Moreover, a State-Regions Agreement of 20087 established new reimbursement fees that the Regional Health Authorities have to pay to blood donor associations for their activities of blood donor recruitment and retention and, where applicable, of blood and BC collection. Finally, in 2009 the Parliament approved a law on fiscal federalism8 which would change the healthcare funding system: resource allocation should shift from criteria based on historical costs to criteria based on standard costs of services.
In the light of these changes, in 2011 the NBC decided to start a collaboration with the Graduate School of Health Economics and Management of the Università Cattolica del Sacro Cuore of Rome, aimed at defining both the costs of production of BCs and the related prices, as well as the prices of plasma-derived medicinal products obtained from national plasma (nPMPs), both to be used for interregional financial reimbursement. Concerning nPMPs, the objective was to define tariffs that guarantee a balanced system covering the global costs of nPMP production. Currently, six nPMPs are obtained by contract fractionation (polyvalent immunoglobulin for intravenous administration, albumin, plasma-derived clotting factor - F - VIII and IX, antithrombin, prothrombin complex concentrates - PCCs), together with a marginal production of anti-hepatitis B virus immunoglobulin.
In 2011, in Italy, 747,982 kilograms (kg) of plasma produced by BEs were sent to the contracted pharmaceutical industry for fractionation. The total amount was composed of 188,523 kg apheresis plasma (plasmapheresis plus multicomponent), 455,922 kg recovered plasma frozen within 6 hours of collection, 102,998 kg recovered plasma frozen between 7 and 72 hours of collection, and 539 kg of anti-hepatitis B plasma9. The mean weight of plasma units was 260 grams (g) for recovered plasma and 536 g for apheresis plasma (the latter value is obtained based on the following estimated weights: 350 g for a unit of multicomponent apheresis and 559 g for a unit of plasmapheresis plasma).
Materials and methods
In order to accurately analyse the costs of production of BCs, 12 out of 318 BEs were selected in 8 Italian Regions (Autonomous Province of Bolzano, Basilicata, Emilia-Romagna, Friuli-Venezia Giulia, Marche, Piedmont, Tuscany, Umbria). In line with Decree No. 68 of 201110, which regulates the application of the standard costs envisaged by Law No. 42 of 20098, BEs located in Regions with an official healthcare budget shortfall were excluded. All the remaining BEs were classified according to the number of units of whole blood (WB) collected in 2009 (small: 5,000–10,000, medium: 10,000–20,000, large: >20,000); BEs collecting less than 5,000 units were excluded. Other classification criteria were based on the collection of plasma and other BCs by apheresis (Table I). The 12 selected BEs were chosen, taking into account: i) the legal status of the structure in which BEs are located (general hospital, teaching hospital, health trust), ii) presence/absence of blood collection outsourcing to donors associations, iii) collection of both WB and apheresis BCs. For each class of values, BEs showing data around the mean were preferred to others. The 12 selected BEs were asked to fill in a complex questionnaire concerning their own costs of production of BCs in 2009, which was subsequently audited, revised and completed by individual on-site visits carried out by a healthcare economist belonging to the study team.
Table I.
Quantitative criteria used for the classification and selection of Blood Establishments.
| Blood Establishment size | Units of whole blood collected | Units of plasma collected by plasmapheresis | Units of blood components collected by apheresis |
|---|---|---|---|
| Small | [5,001–10,000] | [0–2,000] | [0–2,000] |
| Medium | [10,001–20,000] | [2,001–5,000] | [2,001–5,000] |
| Large | [more than 20,000] | [more than 5,000] | [more than 5,000] |
The costs of production of WB and BCs were calculated according to the methodology reported by the Decree of November 22nd, 1993, on the “Update of prices for blood component exchange and financial reimbursement among public healthcare services”3 and by the Decree of April 15th, 1994, on the “Definition of global criteria for hospital care tariff determination”11. In particular, for each step of the BC production process (collection, processing, testing) all driving costs such as personnel, devices, equipment and other items were surveyed. In this study distribution costs are not considered, while blood and BC storage costs are included.
Costs of production of WB and each BC were determined as the sum of the cost of the resources used during the manufacturing process. Unlike prices defined for commercial purposes, the tarrifs for public services such as healthcare are fixed in order to be equal to or lower than the global standard costs of production of the pertinent services/products.
The cost analysis of WB processing took into account the cost of a unit of WB collected and tested. Red blood cells, plasma and buffy coat were considered as co-products of WB, so that for each BC obtained by WB processing, a percentage contribution to global costs related to the production of WB was defined and applied to the sum of costs pertaining to blood collection, testing validation and processing. The percentage contribution was calculated taking into account all tariffs in force since 2003. Plasma frozen after 7 hours and before 72 hours of collection, which at present does not hold a tariff, was valued starting from the cost of production of fresh frozen plasma (FFP) recovered from WB.
As expected considering the Italian organisation of BEs, the production process showed significant differences among BEs, especially related to the number of processed BCs and to the organisation and management, which can both imply huge differences in terms of production costs. As the main purpose was to define national tariffs, for each BE it was necessary to standardise the cost of production of BCs. In particular, 5 variables were considered for standardisation: i) where applicable, the costs of WB and apheresis BCs collected from pre-qualified blood donors, as at present blood donor pre-qualification is not envisaged as mandatory by the national legislation; ii) quota paid by the Regional Health Authorities whenever collection is outsourced to blood donor associations (data were normalised to 2008 national tariffs7); iii) only costs related to mandatory blood testing defined by the Decree of the Ministry of Health of 200512 and its subsequent updates were considered; iv) for personnel costs, the weighted average cost of work per unit produced was calculated for each professional involved in each step of the process; v) for other costs, only those related to waste disposal or to the entire blood production process were taken into account.
After having calculated the standard costs, the related tariffs were defined. In defining tariffs, a 20% increase was applied to the standard costs, which is the percentage most frequently, though discretionally, utilised in healthcare economics in order to take into account all costs not directly connected to the process but pertaining to the general management (i.e. indirect costs) of a healthcare service.
The principle on which the definition of national tariffs for nPMPs was based, is that the value of the products shall be equal to the costs of the system; hence, the latter are defined by the sum of plasma production costs and the cost of the fractionation service provided by the pharmaceutical industry.
Results
Data related to the costs of the production of a unit of WB (collected and tested) show a huge variability among BEs. They range from a minimum of 85.71 Euros (€) to a maximum of € 195.51 (Figure 1), with a weighted mean (W. Mean) of € 134.98 and a standard deviation (SD) of € 35.92.
Figure 1.
Cost of production of a unit of whole blood (450 mL ± 10%) in 12 Blood Establishments (A–N) (year 2009).
The variability of costs of production per unit calculated for the product “whole blood 450 mL ±10%” can be observed also as for plasma recovered from WB (Table II, Figures 2–3). Costs of recovered plasma vary from a minimum of € 10.89 to a maximum of € 26.55 per unit of plasma frozen within 6 hours of collection (W. Mean € 18.57, SD € 4.67) (Table II, Figure 2); from a minimum of € 11.54 to a maximum of € 24.16 per unit of plasma frozen between 7 and 72 hours of collection (W. Mean € 15.06, SD € 4.35) (Table II, Figure 3). The costs of production of both plasmapheresis plasma and multicomponent apheresis plasma show a higher variability than those observed for recovered plasma (Table III). Costs of plasmapheresis plasma vary from a minimum of € 115.62 to a maximum of € 296.08 per unit (W. Mean € 152.23, SD of € 54.99) (Figure 4). For multicomponent apheresis plasma, as well as the production costs surveyed at each BE, costs vary depending on the type of procedure (platelet and plasma apheresis, erythrocyte and plasma apheresis, etc.); hence, comprehensive values were determined, which range from a minimum of € 32.81 to a maximum of € 90.92 per unit (W. Mean € 47.76, SD of € 16.27).
Table II.
Costs of production of a unit of recovered plasma in 12 Blood Establishments (A–N) (year 2009).
| Blood component | Mean (Euro) | Weighted mean (Euro) | Minimum (Euro) | Maximum (Euro) | Standard deviation (Euro) |
|---|---|---|---|---|---|
| Recovered plasma frozen <6 hours | 19.27 | 18.57 | 10.89 | 26.55 | 4.67 |
| Recovered plasma frozen 7–72 hours | 18.47 | 15.06 | 11.54 | 24.13 | 4.35 |
Figure 2.
Cost of production of a unit of recovered plasma frozen within 6 hours of collection (average weight 260 g) in 12 Blood Establishments (A–N) (year 2009).
Figure 3.
Cost of production of a unit of recovered plasma frozen between 6 and 72 hours of collection (average weight 260 g) in 8 Blood Establishments (A–N) (year 2009).
Table III.
Costs of production of a unit of apheresis plasma in 12 Blood Establishments (year 2009).
| Blood component | Mean (Euro) | Weighted mean (Euro) | Minimum (Euro) | Maximum (Euro) | Standard deviation (Euro) |
|---|---|---|---|---|---|
| Plasmapheresis plasma | 197.09 | 152.23 | 115.62 | 296.08 | 54.99 |
| Multicomponent apheresis plasma | 60.02 | 47.76 | 32.81 | 90.82 | 16.27 |
Figure 4.
Cost of production of a unit of plasmapheresis plasma (average weight 559 g) in 12 Blood Establishments (A–N) (year 2009).
After standardisation, the costs of production of a unit of WB (collected and tested) still show some variability (Figure 5). Nevertheless, the latter is much lower when compared to the costs of production observed in the 12 BEs prior to standardisation. In particular, the W. Mean of standardised costs of production of a unit of WB is € 8 less and the SD is reduced by € 13.
Figure 5.
Standardised cost of production of a unit of whole blood (450 mL ± 10%) in 12 Blood Establishments (A–N) (year 2009).
Reduced variability of unitary costs after standardisation is also evident for recovered plasma (Table IV, Figures 6 and 7). Specifically, the SD was reduced by approximately € 2. Also for apheresis plasma, variability is lower after standardisation of the costs of production. For plasmapheresis plasma (Figure 8), the W. Mean is about € 9 less and the SD is halved; for multicomponent apheresis plasma, the W. Mean is about € 7 less and the SD is € 4 less (Table V).
Table IV.
Standardised costs of production of a unit of recovered plasma in 12 Blood Establishments (year 2009).
| Blood component | Mean (Euro) | Weighted mean (Euro) | Minimum (Euro) | Maximum (Euro) | Standard deviation (Euro) |
|---|---|---|---|---|---|
| Plasma frozen <6 hours | 17.69 | 17.20 | 14.39 | 23.25 | 2.67 |
| Plasma frozen 7–72 hours | 16.20 | 14.49 | 13.12 | 21.15 | 2.68 |
Figure 6.
Standardised cost of production of a unit of recovered plasma frozen within 6 hours of collection (average weight 260 g) in 12 Blood Establishments (A–N) (year 2009).
Figure 7.
Standardised cost of production of a unit of recovered plasma frozen between 6 and 72 hours of collection (average weight 260 g) in 8 Blood Establishments (A–N) (year 2009)
Figure 8.
Standardised cost of production of a unit of plasmapheresis plasma (average weight 559 g) in 12 Blood Establishments (A–N) (year 2009).
Table V.
Standardised costs of production of a unit of apheresis plasma in 12 Blood Establishments (year 2009).
| Blood component | Mean (Euro) | Weighted mean (Euro) | Minimum (Euro) | Maximum (Euro) | Standard deviation (Euro) |
|---|---|---|---|---|---|
| Plasmapheresis plasma | 168.09 | 143.07 | 121.20 | 205.85 | 28.43 |
| Multicomponent apheresis plasma | 54.35 | 54.14 | 38.53 | 81.08 | 12.11 |
Adding 20% to the respective standardised costs in order to suitably cover indirect costs and considering the tariffs currently in force (Table VI), the new suggested tariffs for plasma units were determined (Table VII). Taking into account the average weight per unit of recovered and apheresis plasma, the tariffs for plasma per kg are: € 302.86 for apheresis plasma (including both plasmapheresis and multicomponent apheresis), € 79.46 for recovered plasma frozen within 6 hours of collection, € 66.95 for recovered plasma frozen between 7 and 72 hours of collection.
Table VI.
Tariffs for plasma units currently in force (since 2003).
| Type of plasma (unit) | Tariff (Euro) |
|---|---|
| Plasma recovered from whole blood and frozen within 6 hours of collection | 20.00 |
| Plasma recovered from whole blood and frozen between 7 and 72 h of collection | - |
| Plasmapheresis plasma | 161.00 |
| Multicomponent apheresis plasma | 52.00 |
Table VII.
Suggested tariffs for plasma units.
| Type of plasma (unit) | Tariff (Euro) |
|---|---|
| Plasma recovered from whole blood frozen within 6 hours of collection | 20.64 |
| Plasma recovered from whole blood frozen between 7 and 72 hours of collection | 17.39 |
| Plasmapheresis plasma | 171.68 |
| Multicomponent apheresis plasma | 54.14 |
According to the above-reported data, the Italian global costs of plasma intended for fractionation account for € 100,219,354, of which € 57,096,076 are attributable to the costs of apheresis plasma, € 36,227,562 to the costs of recovered plasma frozen within 6 hours of collection, and € 6,895,716 to the costs of recovered plasma frozen between 7 and 72 hours of collection. Some technical discretional choices were taken in determining the above-reported costs. These concerned the allocation of industrial costs for the production of nPMPs. Moreover, data were calculated valuing the whole potential production of FVIII, while for FIX and prothrombin complex concentrates the respective amounts of the products actually given back to Regions were considered.
Table VIII shows the consumption of nPMPs in Italy in 2011 and the equivalent commercial prices for all products obtained from national plasma. The analysis demonstrates that if Italy had to buy the nPMPs on the market at current commercial prices it would spend € 233,203,003. This amount would be reduced to € 217,166,867 provided the price of both FVIII and FIX is € 200 per 1,000 international units (I.U.), as currently in place in the international market.
Table VIII.
Consumption of plasma-derived medicinal products and value of national plasma (year 2011).
| Product | g/I.U. bought on the market at the expense of NHS | Mean costs (€)per g/I.U. | g/IU obtained from national plasma | Value of national plasma (equivalent to commercial prices in €) |
|---|---|---|---|---|
| Albumin (g) | 9,536,670 | 3 | 16,852,260 | 50,556,780.00 |
| IVIg (g) | 775,023 | 49.95 | 2,541,228 | 126,934,313.63 |
| ATIII (IU) | 40,941,500 | 0.28 | 74,517,000 | 20,864,760.00 |
| PCC (IU) | 1,861,500 | 0.29 | 21,844,000 | 6,334,760.00 |
| FVIII (IU) | 33,454,500 | 0.54 | 46,168,500 | 24,930,990.00 |
| FIX (IU) | 3,338,500 | 0.47 | 7,620,000 | 3,581,400.00 |
|
| ||||
| Total | 233,203,003.63 (VAT incl.) | |||
Source: Istisan Report 12–53, 201213.
Legend g: grams; I.U.: international units; NHS: National Health Service; €: Euro; IVIg: polyvalent immunoglobulin for intravenous administration; ATIII: antithrombin III; PCC: prothrombin complex concentrates; FVIII: plasma-derived clotting factor VIII; FIX: plasma-derived clotting factor IX; VAT: value added tax.
According to the assumption that the definition of national tariffs for nPMPs must be based on the principle that the value of the products shall be equal to the pertinent costs of the system, the total costs of the Italian system account for € 208,363,568, of which € 100,222,303 are attributable to plasma production at standardised costs (including indirect costs), and € 108,141,265 to the fractionation service.
In line with the data above, the suggested tariffs for nPMPs are reported in Table IX. These tariffs, given the number of vials per single nPMP obtained by contract fractionation, produce the expected value of € 208,363,568, corresponding to the total cost of the system.
Table IX.
Suggested tariffs for plasma-derived medicinal products obtained by national plasma (nPMP) and corresponding values (in Euros) according to 2011 plasma-derived medicinal products production (number of vials).
| nPMP | Tariff (Euro) | N. of vials produced from national plasma | Value of products (Euro) |
|---|---|---|---|
| Albumin (10 g) | 28.00 | 1,883,556 | 52,739.578 |
| IVIg (5 g) | 213.00 | 538,159 | 114,627,858 |
| ATIII (1000 IU) | 200.00 | 82,251 | 16,450,103 |
| PCC (500 IU) | 110.00 | 47,836 | 5,261,999 |
| FVIII (1000 IU) | 200.00 | 86,703 | 17,340,678 |
| FIX (1000 IU) | 200.00 | 9,717 | 1,943,352 |
|
| |||
| Total | 208,363,568 | ||
Legend nPMP: national plasma-derived medicinal product; N.: number; g: grams; IU: international units; IVIg: polyvalent immunoglobulin for intravenous administration; ATIII: antithrombin III; PCC: prothrombin complex concentrates; FVIII: plasma-derived clotting factor VIII; FIX: plasma-derived clotting factor IX.
Discussion
The high variability of the surveyed costs of production of a unit of WB (collected and tested) can be attributed to the lack of homogeneity in the volume of activity of BEs and to several differences in the local organisation of processes. The latter might be specifically related to: i) blood donor recruitment policies (e.g. blood donor pre-qualification implies significant additional costs in terms of both medical workload and testing), ii) the organisational level of collection (public only, blood donor association only, integrated), as public blood collection is potentially more costly than collection outsourced to blood donors associations, iii) blood testing costs, concerning both the type and number of tests performed and the organisation of testing laboratories.
The variability of costs of production per unit found for WB can be observed also for recovered plasma. In this case, differences are mainly attributable to the mix of FFP used for therapeutic purposes and plasma intended for fractionation.
The variability detected for the costs of all types of apheresis plasma, particularly for plasmapheresis plasma, is most probably related to the very different organisational approaches used for apheresis collection in Italy, which, in general, suffer from significant inefficiency (Figure 9). Other factors that might explain this variability are essentially those already identified for the production of WB.
Figure 9.
Spread and efficiency of apheresis in Italy (year 2009).
Source: SIdEM-SIMTI apheresis register, 200914.
After standardisation, the costs of production of WB still show some variability. Nevertheless, the latter is much lower when compared to the costs of production observed in the 12 BEs prior to standardisation. Reduced variability of unitary costs after standardisation is also evident for recovered and apheresis plasma. Hence, as expected, the costs of production of WB and BCs are more homogeneous after standardisation.
The new suggested plasma unit tariffs of are quite similar to the tariffs in force since 2003, with the exception of plasmapheresis plasma, whose new tariff is about € 10 higher than the previous one.
The suggested tariffs per kg of plasma show that Italy could compete with the international commercial market only for recovered plasma, which is currently sold at € 70–80 per kg15. The Italian standardised costs of apheresis plasma production are about three times higher than the commercial prices currently in place. The latter estimate cannot be referenced as it is based on data which are diffusely known but have never been officially disclosed by plasma fractionators, for understandable reasons.
Notwithstanding the very high costs of apheresis plasma, the national system of nPMP production would allow a cost saving of 10.65% compared to commercial costs of equivalent products. Even hypothesising that the price of both FVIII and FIX on the Italian market is reduced to € 200 per 1,000 I.U., the system would still allow a cost saving of 4.05%. Most importantly, if the average weight of a unit of plasmapheresis plasma were significantly higher than the current one, and apheresis collection were more efficiently organised and managed, savings could be significantly higher.
Conclusions
A strategic goal of the NHS is to achieve national self-sufficiency for an appropriate set of medicinal products through the production of nPMPs. This production must comply with quality, safety and availability requirements but also with economic sustainability; the latter is critically dependent on the capacity of producing plasma for fractionation at competitive standard costs.
On the basis of a total cost comparison and of a hypothesised value of national products on the market, the production of nPMPs in Italy can be sustainable only if standard costs of BC production are appropriately pursued and maintained and apheresis collection is deeply re-organised at the regional level.
Acknowledgements
The Authors are most thankful to the Directors and Staff of the 12 Blood Establishments who very actively collaborated in this study. Their identity is herewith not disclosed according to the agreements made for the development of the study.
Footnotes
The Authors declare no conflicts of interest.
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