Economic implications of switching to the hexavalent infant vaccine in an immunization program in India

ABSTRACT

Combination vaccines can improve immunization coverage, timeliness, and acceptance by reducing the number of injections and simplifying program delivery. The hexavalent vaccine, which combines the pentavalent vaccine with inactivated polio vaccine (IPV), has been adopted in several countries to maintain polio immunity while streamlining routine immunization schedules. This study evaluates the economic implications of introducing the hexavalent vaccine into India’s national immunization program. Two introduction scenarios were assessed: replacement of pentavalent and IPV, and replacement of pentavalent, IPV, and the Diphtheria-Tetanus-Pertussis (DTP) first booster. The analysis considered costs from both government provider and household perspectives, capturing changes in program costs as well as time savings for families associated with fewer vaccine administrations. The results indicate that introducing the hexavalent vaccine would increase overall program costs under both scenarios, driven primarily by the higher price per dose of the hexavalent vaccine. However, the switch also yields operational efficiencies and time savings for caregivers during immunization visits. Importantly, the findings show that price reductions substantially improve the economic case for adoption. A 50% reduction in the unit price of the hexavalent vaccine would offset the additional program costs in the first scenario, while further price reductions could generate net cost savings in the second scenario. Overall, the study suggests that adoption of the hexavalent vaccine in India could support more efficient and user-friendly immunization delivery. Achieving economic benefits, however, will depend critically on procurement strategies that successfully lower vaccine prices.

Introduction

India’s national immunization program is one of the largest public health interventions, aiming to vaccinate 26 million infants and 29 million pregnant women annually.¹ This cost-effective intervention has saved the lives of many children under the age of five by protecting them against 12 vaccine-preventable diseases: diphtheria, pertussis, tetanus, polio, measles, rubella, tuberculosis, hepatitis B, meningitis and pneumonia caused by Haemophilus influenzae type B, rotavirus diarrhea, pneumococcal pneumonia, and Japanese encephalitis in endemic districts.

Two major milestones of the program in the past decade were the elimination of polio in 2014 and the elimination of maternal and neonatal tetanus in 2015. In recent years, several vaccines have been introduced to further protect children from life-threatening diseases, including the inactivated polio vaccine (IPV), the rotavirus vaccine, the measles-rubella vaccine, the pneumococcal conjugate vaccine, and the tetanus and diphtheria vaccine. Plans are underway to introduce a couple of more vaccines.¹ Innovations (Mission Indradhanush and Intensified Mission Indradhanush), system strengthening (electronic vaccine intelligence network), and capacity building helped improve the vaccine coverage from 62% in 2015–16 to 76.4% in 2019–2021.^2,3 However, the country is still far from reaching the 90% target of Immunization Agenda 2030.⁴

Combination vaccines, which protect against multiple diseases in a single injection, offer significant advantages in pediatric immunization programs.^5–9 They simplify vaccination schedules, improve coverage rates, and enhance timely compliance by reducing the number of clinic visits and injections required. This also makes the vaccination process more acceptable to parents, as it minimizes the pain and discomfort for the children.^5–8 Furthermore, combination vaccines help reduce logistical burdens and healthcare costs by streamlining storage, handling, and administration.⁹ Overall, they play a crucial role in ensuring higher immunization rates and better protection against preventable diseases in early childhood.

Pentavalent (diphtheria-tetanus-whole-cell pertussis, haemophilus influenzae type B, hepatitis B) was one such combination vaccine introduced in India’s national immunization program in 2011 and is being administered at 6, 10, and 14 weeks of age. This combination vaccine increased the coverage of the third dose of hepatitis B over the years. The coverage of the third dose of hepatitis B was only 6% when it was introduced in 2004, while the coverage of the third dose of diphtheria-tetanus-pertussis (DTP) was 63%.¹⁰ The coverage of hepatitis B remained low compared to DTP till pentavalent was introduced in a phased manner in 2011. In 2015, when pentavalent was scaled up throughout the country, the coverage of hepatitis B reached 85% along with 3rd dose of the DTP vaccine (DTP3).¹⁰

In 2013, the Strategic Advisory Group of Experts (SAGE) on immunization recommended a global switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) by April 2016.¹¹ To prepare for this switch, SAGE advised countries to introduce at least one dose of IPV into their routine immunization schedules at or after 14 weeks of age, in addition to the existing OPV doses.¹¹ Following this recommendation, India introduced a single full dose of IPV intramuscularly at 14 weeks in 2015. In response to the global IPV shortage in April 2016, SAGE recommended a dose-sparing strategy: administering two fractional doses of IPV (0.1 ml each) at 6 and 14 weeks, in place of a single full dose (0.5 ml) at 14 weeks.¹² India adopted this strategy, introducing two fractional IPV (fIPV) doses intradermally at 6 and 14 weeks in the routine immunization program to prevent stockouts. From 2023 onwards, fIPV is administered at 6 and 14 weeks and 9 months, which increases the number of injections.¹³

Although India continues to maintain high population immunity against all poliovirus types through OPV and fIPV, some concerns remain. The wastage rate of fIPV is significantly higher than the acceptable threshold of 10%.¹⁴ Combining IPV with the pentavalent vaccine increases opportunities to reduce the wastage rate while ensuring under-immunized children receive sufficient IPV doses. Therefore, the introduction of full-dose intramuscular IPV in the routine immunization, probably as a hexavalent vaccine, is a suitable option.

Hexavalent is the combined vaccine of pentavalent and IPV. Switching to the hexavalent vaccine will reduce the number of injections in the routine immunization schedule, which is expected to enhance acceptance among caregivers. A recent study involving stakeholders, including caregivers from eight Indian states, found that most caregivers preferred a maximum of three injectable vaccines per session.¹⁵ However, under the current schedule, children in some states receive up to four injections at 6 and 14 weeks, and 9 months of age. The switch to the hexavalent vaccine will help reduce this injection burden for beneficiaries. In the same study, stakeholders expressed their preference for combination vaccines. Thus, in addition to improving caregiver acceptance, the switch to a hexavalent vaccine is likely to have broader programmatic implications.

We estimated the economic consequences of switching to the hexavalent vaccine (diphtheria-tetanus-whole-cell pertussis, haemophilus influenzae type B, hepatitis B, IPV) by replacing pentavalent and fIPV vaccines in India’s national immunization program, keeping other vaccines intact. We assumed that the effectiveness of the pentavalent and IPV would remain the same when combined in the hexavalent vaccine.

Methods

The economic cost of the vaccine switch, including both direct expenditures and opportunity costs, was assessed from the perspectives of government providers and patients.¹⁶ Provider costs encompass vaccine and syringe prices (factoring in wastage rates), cold-chain requirements, and time spent on procurement, batch verification before dispatch, vaccine handling, record-keeping, and session delivery. For families, costs were measured primarily in terms of time saved at immunization sessions due to the reduced number of vaccine administrations.

Costs were estimated for two different scenarios

Scenario 1: Primary vaccination schedule at 6, 10, 14 weeks with hexavalent vaccine in place of pentavalent at 6,10,14 weeks and fIPV at 6, 14 weeks and 9 months.

Scenario 2: Primary vaccination schedule at 6, 10, 14 weeks with hexavalent vaccine in place of pentavalent at 6,10,14 weeks and fIPV at 6, 14 weeks and 9 months, and a booster schedule of hexavalent vaccine at 18 months replacing DTP vaccine.

Cost calculation methods

Vaccines and syringes

India’s birth cohort of 26,640,200 was considered for the cost estimation. The assumptions used for vaccine doses, unit prices, coverage, and wastage rates are presented in Table 1. In India, fractional IPV (fIPV) is used, which is 1/5 of a standard dose. Therefore, the price per dose of fIPV was used in the cost calculation. Vaccine costs were calculated using target, coverage, price per dose, and wastage rates. For syringes, a 10% wastage rate was assumed for all vaccines.

Table 1.

Assumptions on vaccine price, coverage, wastage rate, types, and price of syringe.

Vaccines	Coverage (%)a	Doses per vial	Price per dose (INR)b	Wastage rate (%)c	Type of syringe	Price per syringe (INR)
Pentavalent 1	92.4	10	46.8	4.75%	0.5 ml	1.98
Pentavalent 2	89.8	10	46.8	4.75%	0.5 ml	1.98
Pentavalent 3	90.6	10	46.8	4.75%	0.5 ml	1.98
IPV 1d	91.4	5	98.49	44.29%	0.1 ml	2.79
IPV 2d	89.2	5	98.49	44.29%	0.1 ml	2.79
IPV 3d	88.3	5	98.49	44.29%	0.1 ml	2.79
Hexavalent 1	92.4	10	236.55	4.75%	0.5 ml	1.98
Hexavalent 2	89.8	10	236.55	4.75%	0.5 ml	1.98
Hexavalent 3	90.6	10	236.55	4.75%	0.5 ml	1.98
DTP booster	88.3	10	8.52	10%	0.5 ml	1.98

^aDistrict-wise HMIS April 2023 to March 2024.^bPentavalent: https://mkp.gem.gov.in/pentavalent-vaccine-under-universal-immunization-programme-mohfw/pentavalent-vaccine-under-universal-immunization-programme-mohfw/p-5116877-67383635167-cat.html#variant_id=5116877-67383635167; IPV: https://mkp.gem.gov.in/drugs-and-pharmaceutical-productsold-immunomodulating-drugs-vaccines-and-antigens-and-toxoids-ip-vaccine-under-universal-immunization-programme-of-mohfw/search#/?q=ipv; Hexavalent: https://www.unicef.org/supply/documents/dtwp-hepb-ipv-hib-hexavalent-vaccine-price-data.^chttps://www.unicef.org/india/reports/national-vaccine-wastage-assessment.

^dIPV is fractional IPV (fIPV), i.e., 25 doses from a 5-dose vial. The price per dose of fIPV is INR 19.6984.

DTP: Diphtheria-Tetanus-Pertussis.

Cold chain space

We used the numbers of various cold-chain equipment at cold-chain points (CCPs), their storage volumes, unit prices, and storage volume per dose of pentavalent, IPV, DTP, and hexavalent to calculate cold-chain space cost. Cold chain-related assumptions are presented in Table 2.

Table 2.

Assumptions on cold chain.

Number of cold chain points in India	29,000
Number of ice-lined refrigerators − 45 liter	41,665
Price per 45-liter ice-lined refrigerator (INR)	80,000
Number of ice-lined refrigerators − 145 liter	13,660
Price per 145-liter ice-lined refrigerator (INR)	94,049
Cold chain volume per dose (cm3) of pentavalent	2.11
Cold chain volume per dose (cm3) of IPV	3.38
Cold chain volume per dose (cm3) of hexavalent	2.11
Cold chain volume per dose (cm3) of DTP	2.46

Sources: National Cold Chain Management Information System; https://www.gavi.org/our-alliance/market-shaping/product-information-vaccines-cold-chain-equipment.

Time costs for various activities

For calculating the time cost related to the procurement of vaccines, we considered the time spent by various categories of staff on the following activities: finalization of target children for each state, estimation of state-wise stock of one vaccine, preparing the indent, technical bid evaluation meeting, negotiation meeting with the manufacturers, consignee list preparation.

Before dispatching vaccines to various vaccine stores at the regional and state levels, designated program staff check each batch of every vaccine. We estimated the time required for batch verification of IPV, assuming that batch checking for the hexavalent vaccine would require the same amount of time as for the pentavalent and DTP vaccines. On average, 300 batches of IPV are being checked in a year, and checking four batches of IPV vaccine takes about 8 h for one person (personal communication with the concerned official).

There are 29,000 CCPs in India, which are managed by cold-chain handlers (CCHs).¹⁷ They receive vaccines from upper-level vaccine stores/CCPs and distribute them to lower-level CCPs or session sites. They maintain registers with the details of each vaccine receipt and distribution. Further, they enter each vaccine record in the electronic vaccine intelligence network (eVIN). We gathered data on the CCHs’ time spent on manual entry of receipt, distribution, and return vaccine information, electronic entry of vaccine information and their monthly gross average salaries from an earlier Indian study.¹⁸ Time use of CCHs for various activities is presented in Table 3.

Table 3.

Assumptions on time spent and hourly wage for various categories of staff.

Time spent by CCH for manual entry per vaccine receipt (mins)a	3
Time spent by CCH for the distribution and record-keeping of vaccines for the session sites (mins per vaccine)a	4
Time spent by CCH for manual entry of return vaccines for the session sites (mins per vaccine)a	6
Time spent by CCH for entering vaccine records in eVIN (mins per vaccine)a	2
CCH’s time cost per minute (INR)a	6.05
Number of ANMs as of March 2022b	207,587
Administration and reporting time per dose (minutes)c	6
ANM’s time cost per minute (INR)c	4.62
Total number of immunization sessionse	12 million
Parents’ time saved per session (minutes)d	6
Parents’ time cost per minute (INR)	0.37

^aThe authors estimated the time spent per vaccine for various categories of staff using data from Gurnani et al.¹⁸ and Chatterjee et al.^20bRural Health Statistics.^cIMI Cost study.^dAssuming minimum wage rate of India.^ehttps://pib.gov.in/PressReleasePage.aspx?PRID=2034080.

The auxiliary nurse midwives (ANMs) are responsible for childhood vaccination in India. We gathered information on the total number of ANMs from a government report,¹⁹ and their time administering vaccines and preparing vaccination reports, and their salaries from earlier studies.^20,21

To estimate the parents’ time spent on immunization, we only considered their time spent on one vaccine administration and record keeping, assuming there would be no additional travel time or expenses. This is because, in addition to the hexavalent vaccine, other scheduled vaccines, such as pneumococcal conjugate, rotavirus, and OPV, will also be administered. Therefore, parents would need to bring their children not only for the hexavalent vaccine, but also for other scheduled immunizations.

The time cost of each activity was estimated by multiplying the hours spent by different staff categories by their respective hourly wages. For estimating parents’ time cost at the immunization session, we used the hourly minimum wage rate of India as a proxy.²²

Costs of each component, i.e., vaccines, syringes, cold-chain space, staff and parents’ time, were estimated separately for pentavalent, IPV, and hexavalent. Cost savings were defined as the difference in the total cost of each component for pentavalent + IPV and hexavalent.

All costs were presented in 2024 Indian Rupee (INR) (1 US$ = INR 83.679).

Sensitivity analysis

We conducted a one-way sensitivity analysis by varying a few components to report the changes in final estimates. First, for the base-case analysis, we utilized the reported coverage rates of three doses of pentavalent and fIPV, assuming equivalent coverage for the hexavalent vaccine when estimating associated vaccine and syringe costs. In scenario 2, we considered the coverage of the DTP booster at 16–24 months and assumed comparable coverage for the hexavalent vaccine when used as a replacement. As part of the sensitivity analysis, we presented the estimated cost assuming 100% coverage of all vaccines. Second, we reported the changes in costs by varying the ANMs’ time to vaccinate and maintain a record of one vaccine. At the base case, we used an average of 6 min of ANMs’ time for this activity. However, as the ANMs’ efficiency differ, cost estimates were also presented using 2 and 4 min of ANMs’ time for vaccinating and maintaining the record of one antigen. Third, a study using a nationally representative sample of 255 various types of public health facilities across seven states in India estimated the delivery cost per dose of routine vaccination.²⁰ The delivery cost per dose of any antigen included various components: personnel expenses, travel and transportation costs, training, routine maintenance, overheads, as well as incentives for staff. Additionally, it accounted for the annualized value of capital expenditures, such as cold-chain infrastructure, facility buildings, and vehicles essential for vaccine storage and distribution.²¹ We utilized the delivery cost per dose, excluding vaccine and syringe costs from the study, and subsequently added the per-dose vaccine and syringe prices for pentavalent, IPV, DTP, and hexavalent to estimate the total delivery cost for each vaccine. We further added parents’ time at session sites, time spent on batch checking, and procurement in the total delivery cost estimation, as these were not considered in the published study. Finally, we reviewed the total number of doses procured and the total expenditure on pentavalent and IPV vaccines by the government of India since their introductions. We found that the expense per dose reduced by 50% within 2 y of the nationwide rollout, likely attributable to the large cohort size covered under the immunization program. Furthermore, as the majority of vaccines administered through India’s routine immunization program are domestically produced, unit prices are typically lower compared to those in other low- and middle-income countries.²⁰ Accordingly, we conducted a sensitivity analysis incorporating a 50% reduction in the price of the hexavalent vaccine and reported the corresponding change in overall costs.

Results

Scenario 1

Using the reported coverages of pentavalent, fIPV, and assuming the same coverage of hexavalent as pentavalent, the vaccine cost of switching to hexavalent will be INR 18,008 million (Table 4). Switching to the hexavalent vaccine is projected to result in total cost savings of INR 9,187 million, driven by reduced vaccine costs (pentavalent and IPV), fewer syringes, lower cold-chain storage requirements, and reduced time inputs from cold-chain handlers, auxiliary nurse midwives (ANMs), parents, and staff involved in procurement and vaccine batch verification.

Table 4.

Hexavalent vaccine price and changes in economic costs of hexavalent switch, 2024 Indian rupee (INR) million.

Cost components		Hexavalent price per dose (INR 237)	Hexavalent price per dose (INR 237)	Hexavalent price per dose (INR 118)	Hexavalent price per dose (INR 118)	Hexavalent price per dose (INR 93)	Hexavalent price per dose (INR 93)
Scenarios		Hexavalent replaces pentavalent + IPV	Hexavalent replaces pentavalent + IPV + DPT 1st Booster	Hexavalent replaces pentavalent + IPV	Hexavalent replaces pentavalent + IPV + DPT 1st Booster	Hexavalent replaces pentavalent + IPV	Hexavalent replaces pentavalent + IPV + DPT 1st Booster
Cost savings
Costs of pentavalent +IPV vaccines		5,599 (61%)	5,599 (61%)	5,599 (61%)	5,599 (61%)	5,599 (61%)	5,599 (61%)
Cost savings on syringes		220 (2%)	220 (2%)	220 (2%)	220 (2%)	220 (2%)	220 (2%)
Cold chain space saved		156 (2%)	172 (2%)	156 (2%)	172 (2%)	156 (2%)	172 (2%)
Cold chain handler time saved		820 (9%)	820 (9%)	820 (9%)	820 (9%)	820 (9%)	820 (9%)
ANM’s time saved at sessions		2,214 (24%)	2,214 (24%)	2,214 (24%)	2,214 (24%)	2,214 (24%)	2,214 (24%)
Parents’ time saved at sessions		178 (2%)	178 (2%)	178 (2%)	178 (2%)	178 (2%)	178 (2%)
Time saved for procurement		1 (0.01%)	1 (0.01%)	1 (0.01%)	1 (0.01%)	1 (0.01%)	1 (0.01%)
Time saved for batch checking		0.1 (0.001%)	0.1 (0.001%)	0.1 (0.001%)	0.1 (0.001%)	0.1 (0.001%)	0.1 (0.001%)
Total cost savings		9,187	9,203	9,187	9,203	9,187	9,203
Hexavalent vaccine cost		18,008	–	9,004	–	7,080	–
Hexavalent + DPT vaccine cost		–	23,630	–	11,705	–	9,156
Additional cost of the hexavalent switch		8,821	14,427	−183	2,502	–2,107	−46

Notes: All costs were calculated using the coverage rates of vaccines provided in Table 1. Cost-savings were defined as the difference in total cost of each component for the pentavalent + IPV and hexavalent vaccines. 1 US$ = INR 83.679.

The majority of cost savings are attributable to the costs of pentavalent and IPV vaccines, accounting for 61% of total savings, followed by the time saved by ANMs at session sites due to the administration of one fewer injection (24%). The time saved by CCHs represents 9% of the savings, as they manage one fewer vaccine. However, transitioning from pentavalent and IPV to the hexavalent vaccine would incur an additional economic cost of INR 8,821 million because of the high price of the hexavalent vaccine (Table 4).

Scenario 2

When hexavalent replaces pentavalent, fIPV and DTP booster at 18 months, using reported coverages of all three vaccines and assuming the same coverage of hexavalent as pentavalent in the primary schedule and DTP booster, the additional vaccine cost of switching to hexavalent will be INR 23,630 million (Table 4). Total cost savings will be INR 9,203 million, leading to an economic cost of INR 14,427 million for the switch.

Sensitivity analyses

If the hexavalent vaccine price per dose is reduced by 50% following the trend observed for other recently introduced vaccines in the Indian immunization program, the additional vaccine cost would decrease from INR 18,008 million to INR 9,004 million for scenario 1 (Table 4). The total cost savings from the hexavalent switch were estimated at INR 9,187 million in this scenario. Therefore, at a 50% reduction in hexavalent vaccine price per dose, the benefit would outweigh the additional cost when the hexavalent vaccine replaces pentavalent and fIPV. However, the total cost of the switch would still be higher than the benefit in scenario 2, despite the vaccine price per dose being reduced by half. The benefits of switching to scenario 2, where the hexavalent vaccine replaces the pentavalent, fIPV, and DTP booster administered at 18 months, would outweigh the vaccine costs only if the price per dose of the hexavalent vaccine is reduced to INR 93 or lower (Table 4).

Using 100% coverage of all vaccines in scenario 1, the vaccine costs will increase from INR 18,008 million to INR 19,803 million. Cost savings will increase from INR 9,187 million to INR 9,803 million, leading to an additional economic cost of INR 10,000 million. For scenario 2, 100% coverage of all vaccines would lead to an additional cost of INR 16,352 million for the switch.

As the ANMs’ time spent was the major contributor to cost savings because of fewer vaccine administrations, we estimated the changes in cost savings by varying the time spent per antigen. Applying 2 min of ANMs’ time instead of 6 min for administering and recording one antigen, the ANMs’ time cost decreased from INR 2,214 million to INR 738 million, and total cost savings from INR 9,187 million to INR 7,593 million for scenario 1 and from INR 9,203 million to INR 7,603 million for scenario 2, leading to additional economic costs of INR 10,415 million and INR 16,022 million for scenario 1 and 2 respectively. If the ANMs spend 4 min per antigen, the additional cost will be INR 9,618 million for scenario 1 and INR 15,224 million for scenario 2.

Using the range of delivery costs per dose, excluding vaccine and syringe costs, reported in a published study for various Indian states (ranging from INR 88 to INR 197 in 2024 prices), we estimated the additional economic impact of switching to the hexavalent vaccine (see Table 5). We incorporated the vaccine and syringe costs for all four vaccines: pentavalent, IPV, DTP, and hexavalent, along with the two delivery cost estimates (INR 88 and INR 197 per dose). Based on a delivery cost of INR 88 per dose, the total projected cost savings amount to INR 21,927 million. When using the higher delivery cost of INR 197 per dose, the estimated savings increase significantly to INR 41,504 million under Scenario 1. This is because the hexavalent switch in scenario 1 will avoid the delivery costs of two vaccines: pentavalent and IPV. As the delivery cost per dose increases, delivering fewer doses will yield higher cost savings. Therefore, for states with high delivery costs per dose, switching to the hexavalent vaccine will lead to higher cost savings (Table 5). Using INR 88 per dose, the additional economic costs of the hexavalent switch will be INR 2,895 million, while the same will be (–) INR 8,379 when the delivery cost per dose is INR 197. We estimated that the states with delivery costs per dose, excluding vaccine and syringe cost of INR 116 and higher (in 2024 prices), will have negative incremental costs of the hexavalent switch, i.e., the cost savings from avoided delivery doses of pentavalent and IPV will be higher than the delivery cost of hexavalent for scenario 1.

Table 5.

Economic costs of hexavalent switch using delivery cost per dose, 2024 Indian rupee (INR) million.

Delivery cost per dose (INR)	88	197	88	197
Cost components	INR million	INR million	INR million	INR million
	Scenario 1		Scenario 2
Total delivery cost of pentavalent	10376	18680	10376	18680
Total delivery cost of IPV	11371	22645	11371	22645
Total delivery cost of hexavalent	24821	33125	33258	44384
Parents’ time saved at sessions	178	178	178	178
Time saved for batch checking	1	1	1	1
Time saved in procurement	0.1	0.1	0.1	0.1
Total cost saving	21927	41504	21927	41504
Additional cost	2895	−8379	11332	2880

Scenario 1: Primary vaccination schedule at 6, 10, 14 weeks with hexavalent vaccine in place of pentavalent at 6, 10, 14 weeks and fIPV at 6, 14 weeks and 9 months. Scenario 2: Primary vaccination schedule at 6, 10, 14 weeks with hexavalent vaccine in place of pentavalent at 6, 10, 14 weeks and fIPV at 6, 14 weeks and 9 months, and a booster schedule of hexavalent vaccine at 18 months replacing DTP vaccine. 1 US$ = INR 83.679.

However, in scenario 2, i.e., when a fourth dose of hexavalent is added as a booster in place of DTP, the total delivery cost for hexavalent increases, and the cost savings would no longer outweigh the delivery costs (Table 5).

Discussion

Combination vaccines have been proven to improve immunization coverage, timeliness, and acceptability to parents while simplifying programmatic and logistical requirements.^5–9 Hexavalent is a six-in-one vaccine that combines pentavalent (diphtheria-tetanus-whole-cell pertussis, haemophilus influenzae type B, hepatitis B) and IPV. Starting from December 1, 2023, countries eligible for Gavi support can apply for switching to a hexavalent vaccine by replacing pentavalent and IPV.²³ As combination vaccines help improve coverage and more acceptable for parents, in this paper, we presented the economic implications of switching to the hexavalent vaccine in the Indian context under two scenarios: scenario 1: the hexavalent vaccine will replace pentavalent and fIPV at the primary schedule; scenario 2: the hexavalent vaccine will replace pentavalent and fIPV at the primary schedule and will also replace DTP booster given at 18 months.

The major cost implications of switching to hexavalent will be the vaccine itself, as the unit price per dose of hexavalent is 1.6 times higher than the combined price per dose of pentavalent and IPV. In India, fractional IPV is used; therefore, the unit price per dose of IPV is low. An analysis of government procurement data indicates that, after the nationwide introduction of multiple vaccines and the transition from Gavi-subsidized pricing to domestically negotiated procurement rates, the unit price per vaccine dose declined substantially. Specifically, the prices of pentavalent and IPV vaccines decreased by approximately 50% within 2 years of their national rollout. Applying this assumption for the hexavalent vaccine, i.e., a 50% price reduction per dose of the hexavalent vaccine, we found that the benefit from the hexavalent switch would outweigh the additional cost of the vaccine for scenario 1. However, if hexavalent also replaces the DTP booster (scenario 2), the price per dose of the hexavalent vaccine needs to be reduced to INR 93 for the benefits to outweigh the costs of the switch.

Other country studies have also noted higher vaccine costs in the case of hexavalent switch compared to the existing schedule; however, studies conducted in Argentina, Chile, and Peru found that a major cost-saving came from fewer adverse-event-related costs.^24–27 All these countries have switched from a pentavalent vaccine with whole-cell pertussis component (wP) plus IPV to a scheme with a hexavalent vaccine with acellular pertussis component (aP) and IPV. Therefore, those studies considered cost savings associated with hospitalizations, productivity loss of parents for adverse events management, and premature mortality. However, in our cost calculation, we considered the hexavalent vaccine containing whole-cell pertussis (wP), similar to the pentavalent vaccine, as studies have shown that wP vaccines confer stronger immunity than acellular pertussis (aP) vaccines. Additionally, wP vaccines offer better protection against colonization and transmission.^28,29 Therefore, we did not consider any adverse events because of the switch. We acknowledge that reducing the number of injection pricks may lead to fewer minor side effects, such as pain at the injection site; however, we did not quantify these minor events. Hence, our cost savings were much lower compared to other country studies.^24–27

Other studies have also accounted for parents’ travel expenses, time associated with vaccination visits, and productivity loss; however, these factors were not included in our analysis. In India’s immunization schedule, a pentavalent vaccine is given with rotavirus, OPV, IPV, and PCV vaccines. Therefore, the parents visit to get their children vaccinated with all scheduled doses. If IPV is merged with pentavalent (hexavalent), there will be no cost savings for travel and productivity loss, as they must bring their children for other scheduled doses. Their only time saved will be the time for vaccinating a child with IPV, hence, we only considered that in the cost estimation. However, the switch is expected to reduce vaccine hesitancy associated with multiple injections. A recent Indian study reported caregivers’ hesitancy about multiple injections in a single visit,¹⁵ which is one of the reasons for lower vaccine coverage and a contributing factor for vaccine-preventable disease outbreaks.

Our estimated cost using the delivery cost per dose from a published Indian study²¹ showed a lower additional economic cost of the switch for scenario 1. While our base-case scenario showed an incremental economic cost of INR 8,821 million for the switch, using INR 88 per dose of delivering routine vaccine showed an incremental cost of INR 2,895 million. The substantial difference in cost savings between the two approaches is primarily due to the delivery cost method of the published study, which accounted for all components related to routine vaccine delivery, some of which were not included in our cost estimation. For instance, we considered the time cost of ANMs for administering vaccines and maintaining records. However, the published study included additional personnel involved in immunization sessions, such as supervisors, Accredited Social Health Activists (ASHAs), and medical officers.²⁰ We did not consider the time saved for other staff at the session sites for the switch. Further, the switch could save staff time for activities such as monthly reporting and vaccine inventory checking, which were not included in our calculation. Replacing pentavalent and IPV with hexavalent will reduce waste management costs, which we could not estimate, but the published study did. Finally, we were unable to estimate the savings from capital items such as vehicles, vaccine vans, and cold-chain equipment at state and regional vaccine stores, as well as overhead costs like electricity. All those were included in estimating the delivery cost per dose in the published study. Therefore, using delivery cost per dose led to higher cost savings from the switch. However, when the fourth dose of hexavalent vaccine is added by replacing the DTP booster, the delivery cost would be higher than the benefits.

This study has several strengths that enhance its relevance for immunization policy and program decision-making. First, policy-relevant analysis for a large national program: This study provides timely and directly actionable evidence for India’s national immunization program by evaluating the economic implications of introducing a hexavalent vaccine at national scale, making the findings highly relevant for policy and procurement decision-making. Second: comprehensive costing perspective. Costs were assessed from both the government provider and household perspectives, capturing not only vaccine and delivery costs but also operational processes and caregiver time savings. This comprehensive approach offers a more complete understanding of the economic trade-offs associated with the combination vaccine introduction. Third: comparison of realistic implementation scenarios.

By evaluating two plausible introduction scenarios, the analysis reflects real-world policy options and allows decision-makers to compare alternative programmatic pathways rather than a single hypothetical scenario. Fourth: identification of key cost drivers and price thresholds. The study clearly identifies vaccine price as the primary driver of costs and quantifies the price reductions required for the hexavalent vaccine to become cost-neutral or cost-saving, providing valuable guidance for procurement negotiations and market-shaping strategies. Finally, focus on both efficiency and service delivery outcomes. In addition to economic outcomes, the study highlights operational efficiencies and reductions in burdens on caregivers, reinforcing the broader value of combination vaccines beyond cost considerations.

Despite the strengths of the study, the following limitations merit comment. First, for the vaccine procurement process, we considered the time cost of immunization division staff and officials at the national level; however, we did not account for the time of the upper-level government officials, which underestimated the cost savings. Second, for calculating the time cost of the parents, we assumed that either parent would accompany their children, and their time cost was calculated using the minimum wage rate of India, which probably underestimated the cost savings.

Conclusions

Replacing the pentavalent, fIPV, and DTP booster with the hexavalent vaccine in the Indian routine immunization program would lead to higher vaccine acquisition costs. The increased cost would be partially offset by lower delivery costs per dose and cost savings from syringes, cold-chain space, and time of various staff involved in procurement, vaccine handling, and administration. Based on past trends of vaccine price reductions, a 50% decrease in the hexavalent vaccine’s price per dose would result in benefits from the switch outweighing the additional vaccine costs for scenario 1. A further reduction of the price per dose of the hexavalent vaccine would lead to higher cost savings from the switch under scenario 2 as well. Therefore, the study provides valuable insight into the economic impact of the switch, supporting evidence-based policymaking.

Biographies

Pawan Kumar currently serves as the Additional Commissioner-in charge of Immunization Division & Maternal Health Division at the Ministry of Health & Family Welfare, Government of India. A seasoned public health professional, he brings over 25 years of experience in healthcare management, encompassing planning, policy development, implementation, monitoring, and supervision at the National, State, & District levels. Throughout his career, Dr Kumar has successfully published and presented over 95 research papers in prestigious national and international journals and conferences and executed more than 30 major projects at both the national and state levels, significantly contributing to India’s public health landscape. Moreover, he is also the Life member of many professional bodies like IAPSM, IPHA, IMA, AGI, ISHWM, ACHHA, AHA, IEA, EFI and IAE. Dr Kumar’s outstanding contributions have been widely recognized. Presently, Dr Pawan Kumar is driving the implementation of zero dose implementation plan of India to meet the goal of reducing 30% burden of zero dose children in the country by 2026 with the support of concerned States and implementing partners. Dr Kumar is steering the development of new National Vaccine Policy & National Immunization Strategy for the country. Some of his recent achievements include the launch of the world’s largest electronic immunization registry (U-WIN).

Kapil Singh is a public health professional with more than 15 years of experience in policy, planning, administration, and implementation of public health programs. Over the years, he has specialized in health systems strengthening including immunization systems improvement and introduction of new vaccines. Currently, he is working as a Health Specialist-New Vaccines at UNICEF, India and supporting the introduction of the HPV vaccine & TCV in the National Immunization Programme of India. Before joining UNICEF, he supported the Universal Immunization Programme of India as a WHO-Technical Officer for New Vaccine Introduction. Previously, he has worked as the country focal point for Gavi, the Vaccine Alliance, COVAX, and APVAX. Dr Kapil has supported the National Government in planning and implementing the COVID-19 vaccination, developing the new Gavi-India partnership and India’s Zero Dose Implementation Plan. His contribution in the field of immunization program is also reflected in the peer-reviewed publications, development of various guidelines & training modules related to Immunization. He has also supported the Union Health Minister of India in his capacity as the Gavi Board member and senior officers of the ministry as the Gavi Programme & Policy Committee (PPC) member to represent the SEARO WPRO constituency of Gavi.

Arindam Ray is a medical epidemiologist with about 30 years of experience in public health management, particularly in urban health care, population studies, disease surveillance and immunization. Following his tenure under the Government of West Bengal, he joined the World Health Organization in 2000. He was the National Monitoring and Evaluation Focal Person at WHO country office, India, before joining the Gates Foundation in 2014. At the Foundation, India office, he looks after new vaccine initiatives, immunization systems, disease surveillance and modeling, Gavi projects and polio legacy work. He represents the Foundation at the global urban immunization workgroup, GAVI Asia-Pacific Regional Work Group, WHO SEAR RITAG, India Expert Committees on Rotavirus Vaccine, Pneumococcal Conjugate Vaccine, HPV vaccine, Typhoid conjugate vaccine and Polio & MR India Expert Advisory Groups.

Amrita Kumari is a medical doctor and public health specialist with over 11 years of experience in the development sector. Her expertise encompasses the design, implementation, and oversight of public health programs, focusing on child and adolescent health. Dr Amrita offers substantial proficiency in epidemiology, immunization, monitoring and evaluation, medical training, and healthcare research. Her career in public health commenced at the National Health System Resource Centre (NHSRC), the think tank of the Ministry of Health and Family Welfare, where she contributed to the implementation of the Adverse Events Following Immunization (AEFI) system at both national and state levels. Since then, she has continued to collaborate closely with the Ministry of Health and Family Welfare (MoHFW), supporting planning, capacity building, implementation, monitoring, and data analysis to strengthen immunization programs. Dr Amrita’s notable accomplishments at John Snow India Pvt Ltd include leading program implementation initiatives, managing the COVID-19 vaccination control room, introducing new vaccines, and ensuring vaccine safety. Beyond her work in immunization, Dr Amrita has worked under Technical Support Unit-Adolescent Health at Jhpiego, providing technical guidance to the Adolescent Health Division to facilitate effective management and timely execution of the Rashtriya Kishor Swasthya Karyakram (RKSK) across all states.

Susmita Chatterjee is an economist and the Program Head of Health Economics at the George Institute for Global Health, India. She is a conjoint faculty member of the University of New South Wales, Australia; research fellow of the Partnership for Economic Policy, Kenya; and adjunct faculty of St John’s National Academy of Health Sciences, India. With a PhD from Calcutta University, India, and post-doctoral research at Mahidol University, Thailand, and the University of San Francisco, USA, her expertise lies in health service costing, economic burden studies, health financing, and economic evaluations. Her work spans economic evaluations in immunization, tuberculosis, and mental health. Dr Chatterjee has co-authored key resources, including a vaccine economics curriculum developed in collaboration with Johns Hopkins University and international partners, a costing manual for provider payments by the Joint Learning Network in the USA, and a health economics handbook on vaccines published by Oxford University Press.

Homero Hernandez has over 20 years of experience in public health, starting with the Global Drug Facility of the Stop TB Partnership in 2005. In 2010, he took up a position in the Immunization and Vaccine Development (IVD) unit of the WHO’s South-East Asia Regional Office (SEARO), based in New Delhi, India. He provided technical support to India, Indonesia, Myanmar, Nepal, Bangladesh, and Bhutan as part of the regional team focused on priority countries of the WHO Southeast Asia Region. In 2014, Homero started a new position in the Gavi Alliance as Senior Country Officer responsible for managing Gavi support to eligible countries in the Americas (Bolivia, Cuba, Guyana, Honduras, Haiti, Nicaragua). In 2020, Homero became the new Senior Country Manager responsible for India, focusing on evolving priorities related to India’s manufacturing role and critical partner for Covax Facility and developing a new strategic partnership between Gavi and India for 2022–2026. This support involved managing a funding envelope of 250 million dollars to implement innovative strategies to reduce zero-dose children and introduce HPV and TCV vaccines. Homero has a bachelor’s degree in international business from the European University and a master’s in health systems management from the University of Liverpool.

Arup Deb Roy is a medical graduate (MBBS) with a master’s (MD) in Community Medicine. He has close to two decades of experience in public health. He started as a Surveillance Medical Officer with the WHO’s Polio project and supported various states, including the remote northeastern states, to strengthen AFP surveillance and supplementary immunization activities to stop polio transmission. Later, as a State Routine Immunization Officer, he supported states in improving routine immunization activities. He is the country lead at JSI India, where he manages the new vaccine introduction portfolio. He has worked closely with the Immunization Division, MoHFW, to provide technical support in the introduction and scale-up of new vaccines like the Rotavirus vaccine (RVV) and the Pneumococcal conjugate vaccine (PCV) and other vaccines in the UIP. For over a decade, he has been working closely with the Ministry of Health and Family Welfare (MoHFW) and all states on strengthening the universal immunization programme (UIP), especially the introduction of new vaccines.

Disclosure statement

No potential conflict of interest was reported by the author(s).