Technical Update

June 2013

Comprehensive Economic Analysis of Improvest Adoption by the US Pork Industry

®

1,2

Brian Buhr, PhD, EconAnalytics, LLC Glynn Tonsor, PhD, Agri-Food Analytics, LLC Kelly Zering, PhD, North Carolina State University Dennis DiPietre, PhD, KnowledgeVentures, LLC Improvest® (gonadotropin releasing factor analogdiphtheria toxoid conjugate) is a FDA-approved veterinary prescription product developed by Zoetis that helps manage unpleasant aromas that can occur when pork from some male pigs is cooked. Improvest is a protein compound that works like an immunization to temporarily protect against off-odors in pork. Its related global brand, Improvac,® has been successfully used by pork producers in other countries for more than 10 years. FDA has determined that pork from pigs given Improvest is safe to eat and there are no residues that could affect human health. Regulatory authorities in more than 60 countries, including the European Union, Japan, South Korea, Russia, and China, have reached the same conclusion. Male pigs are given Improvest in the finish phase, eliminating the need for physical castration (PC). As a result, male swine are able to fully express their natural potential for feed-efficient growth, with all the inherent performance advantages of an intact male for the majority of the production cycle.

Bobby Cowles, DVM, MS, MBA; Paulo J. U. de Moraes, DVM, MBA Zoetis Inc., Madison, NJ 07940

Key Points A panel of economists estimated the impact of immunological castration (IC) vs physical castration (PC). They concluded that: n

IC barrows generate a potential increase of $5.32/head in net income (after product plus administration costs of $5.00/head).

n

This value is comprised of benefits due to: Cessation of physical castration (direct cost savings, fixed-costs dilution, increase in profit from saved pigs); Feed savings (heavier pigs with less feed); Increased revenue (heavier carcasses, higher average premium due to reduction in weight variation). l

l

l

n

The average optimal carcass weight for IC barrows is 10-12 lb heavier on live-weight basis (4-6 lb in carcass weight) over PC barrows when both are finished to their respective, different optimal carcass weight.

n

For packers, the expected estimated net total return from IC barrows averages $5.04/carcass.

n

These benefits from Improvest are consistent in multiple marketing scenarios, even in challenging market situations when optimal carcass weights are reduced.

Improvest Program ®

Use of Improvest involves a 2-dose regimen. The first dose should be administered after 9 weeks of age to prime the immunological system of the male pig. The second dose is then administered at least 4 weeks after the first, between 3 to 10 weeks before harvest of the immunologically

1

Improvest -managed barrows averaged 8.4% better F/G and 4.3% greater ADG. ®

Economics / Performance Overview

castrated (IC) barrows. This approach allows IC animals to express their naturally efficient growth potential, resulting in substantial feed savings per lb of gain compared to PC barrows. After the second dose, the male pig begins to eat substantially more feed per lb of gain and begins to increase the amount of fat in the carcass, thus attaining a desirable fat level for primal cut characteristics. Optimal marketing strategies take these factors into account, timing the immunizations and harvest of the animals to maximize profits while maintaining targeted carcass cutout characteristics.

The impact of immunological castration with Improvest on the performance of male swine has been extensively researched. Table 1 summarizes results of 12 US studies that compared the performance of contemporary IC barrows (Improvest) with that of PC barrows throughout the entire growing period.3 Improvest-managed barrows averaged 8.4% improvement in feed/gain (F/G), 4.3% greater average daily gain (ADG), and 0.047 inches (1.17 mm) less backfat. Based on research outcomes summarized in this Bulletin, producers adopting Improvest can increase net income by an average of $5.32 per

Table 1 — Summary of 12 US grower-finisher performance trials (Improvest change vs PC).3 Study number

Number of IC barrows

F/G (% change) a

ADG (% change) a

Dressing percentage change b

Loin depth change (mm) b

Backfat difference (mm) b

1

325

-7.26

3.45

-2.27

-1.00

-0.90

2

500

-13.33

2.87

-1.72

not measured

not measured

3

352

-7.54

2.12

-1.41

0.60

-0.90

4

408

-8.20

1.10

-2.53

0.60

-1.60

5a c

116

-13.69

6.76

-1.70

0.70

-2.45

5b

120

-8.08

9.74

-0.65

1.30

0.65

5c

187

-7.95

10.14

-0.30

2.95

0.95

6

245

-6.05

1.27

-3.60

-2.00

-3.20

7a c

200

-6.71

4.24

-2.01

1.50

-0.70

7b

200

-6.77

5.45

-1.76

2.00

-1.10

7c

200

-6.46

3.03

-1.26

2.60

-2.40

8

368

-8.84

1.18

not measured

not measured

not measured

Mean

-8.41

4.28

-1.75

0.93

-1.17

Weighted mean

-8.63

3.38

1.87

0.70

-1.24

Standard error

0.73

0.91

-0.27

0.48

0.42

Median

-7.75

3.24

-1.72

1.00

-1.00

95% confidence range d

-6.15 to -9.35

1.24 to 5.24

-2.32 to -1.12

-0.09 to 2.09

-2.11 to -0.23

a IC/PC b IC-PC

2

x 100

c Same

location but different marketing period around the median

d Range

Immunologically castrated males demonstrate consistent and predictable economic results.

Figure 2. Cumulative feed consumption of physical castrates and gilts compared to Improvest-managed males.

Days of age post-weaning

IC barrow (net after cost of product and implementation).1,2 The first obvious advantage of immunological castration with Improvest begins at the production facility, with adopting producers no longer needing to castrate male pigs. Elimination of physical castration can provide significant positive impacts on pre-weaning and postweaning mortality and morbidity while also saving the value of the labor and inputs associated with this practice. The authors estimate that the elimination of physical castration improves wean-to-finish net income by an average of $1.61/male pig marketed (direct cost savings from non-castration, dilution of fixed costs, and increased profit from saved pigs). Of course, adoption of Improvest also brings some expenses. The full cost of utilizing Improvest is estimated to be $5.00/male pig, which covers the cost of the product as well as inputs needed for administration and documentation. Farm staff will need to separate male and female pigs (e.g., separate pens at the minimum) to facilitate the administration, documentation, and certification of both Improvest doses.

200

161

171

141

151

121

131

101

0

111

100 81

161

171

141

151

121

131

101

111

81

91

61

71

41

51

21

31

0

1

1.00

91

2.00

300

61

3.00

400

71

After 2nd Improvest dose, males increase feed consumption and decrease feed efficiency to generate more fat in the carcass.

500

41

4.00

51

5.00

600

21

6.00

700

31

7.00

Physical castrates Improvest Gilts

800

1

8.00

Cumulative feed consumption (lb)

900

Physical castrates Improvest Gilts

11

Average daily feed intake (lb/hd)

9.00

11

Figure 1. Average daily feed intake of physical castrates and gilts compared to Improvest-managed males.

Days of age post-weaning

Intact males and PC barrows demonstrate very different patterns of feed consumption (Figures 1 and 2) and carcass lean accretion even though their growth rates are typically similar until the time of the second Improvest dose. Male pigs which have not been castrated but have received the first dose of Improvest consume feed and grow like untreated intact male hogs. This means F/G is dramatically improved compared to PC males and gilts, but growth rate is similar to PC barrows. Before administration of the second Improvest dose, the carcasses of Improvest-managed males are very lean compared to PC barrows. However, upon administration of the second dose, Improvest males increase feed consumption, decrease feed efficiency, and begin generating more fat in the carcass. Although feed efficiency declines after the second dose, it still remains better than PC barrows every week until 10 weeks post-second dose (see F/G improvements for study 5 in Table 1; study 5a= harvest 3 weeks after second dose, study 5b=9 weeks, study 5c=10 weeks post-second dose). Optimal harvest weight is determined by that which produces the greatest profits while maintaining the necessary fat (especially in belly cuts) essential to pork quality and value.

3

Optimal live weights at market for Improvest -managed males should be 10-12 lb more than PC barrows. ®

Table 2 — Monthly average prices, Jan 2007 - Dec 2011.1

Item Corn (US#2, Cent. Ill., $/bu)

Average prices for feed and hogs (average) ± SD

High feed and high hog prices a (95th percentile) ± SD

$4.56 ± $1.37

$7.08 ± $2.13

Soybean mean (48%, Decatur, $/ton)

$314.88 ± $54.76

$398.70 ± $69.34

DDGS (Cent. Ill., 1% truck, $/ton)

$146.52 ± $36.31

$208.50 ± $51.66

$68.41 ± $13.60

$95.40 ± $18.97

$209.51 ± $45.61

$290.72 ± $69.89

Lean hog carcass (national avg., $/carcass cwt) Feed cost ($/ton) b a Value

at 95th percentile of reported prices - nearly equal to current prices and consistent. on diets derived from Zoetis trials. SD = standard deviation

b Based

Simulation Model of Profit Maximization Zoetis commissioned an independent panel of agricultural economists to explore management options for Improvest-adopting producers. The panel utilized a stochastic optimization approach which established how the optimal harvest weight of an IC barrow is likely to compare to that of a PC barrow on a national basis. The analysis estimated net returns to both producers and packers in a stochastic model of hog and pork production. Base price variables used for the analysis (Table 2) were derived from averages of monthly data over 5 years (2007-2011).

Market Weights An Improvest-managed male will typically reach profit optimization with a carcass weight 5 to 6 lb heavier than a PC barrow, without increasing days in the finisher. Improvest males have lower carcass yields due to the presence of the scrotum, testicles, and associated organs, as well as some other minor carcass changes. Thus, live weight at slaughter will likely be 10 to 12 lb heavier than a PC barrow. These estimates assume adequate pen space is provided so ADG suppression does not occur at these heavier weights (producers need to ensure stocking rates are appropriate). Results of the economic analysis presented here are not intended to predict the optimal weight for any individual or marketing group of US producers selling to any single packer. Rather, they represent the expected national average 4

difference between the likely profit-optimizing weights of PC and Improvest-managed males under a variety of production systems, feed ingredient prices, and packer buying schemes. A sensitivity analysis was conducted to estimate the optimal weights of IC vs PC barrows during periods when feed ingredient prices are high and pass-through of these costs to the hog price has not yet occurred. While the optimal weights of both types of animals are reduced under this scenario (as expected), the differential profitoptimization weight between IC and PC barrows remains essentially the same. Whenever market conditions are forcing average sell-weights down, producers need to pay special attention to the timing of the second Improvest dose to ensure that appropriate fat is allowed to accumulate on lighter carcasses, thereby meeting consumer preferences and avoiding erosion of carcass values (discounts). On average, Improvest-managed barrows are estimated to receive a $1.75/cwt premium over PC barrows when both are finished to their respective (but different) optimal carcass weights. This is primarily because Improvest carcasses are expected to offer a smaller coefficient of variation (smaller standard deviation relative to their different optimal carcass weights). This improvement in the average premium paid for Improvestmanaged males can be interpreted as a signal of enhanced value from the retail/consumer sectors of the production chain, mediated through the packer buying scheme.

Narrow ranges of carcass weights and lean percentages yield the highest premiums.

Carcass Value Quality premiums paid by packers are based on carcass composition. Figure 3 summarizes the premium and discount schedule used by a major US packer (representative of other packers) valued on a percent lean and weight basis. In addition, Figures 4 and 5 break-out specific examples of premiums/discounts for 207 lb carcass weight and 55% lean, to illustrate optimal premiums. In general, only narrow ranges of carcass weights and lean percentages yield the highest premiums. The key point is that premiums fall sharply when pigs are heavier or lighter. Therefore, in addition to optimal weights of Improvest-managed and PC pigs being affected by productivity and feed-cost changes, the optimum market weight will also be affected by packer quality payments or discounts related to carcass composition averages and variances.

used to simulate the likely value distribution differences between the 2 types of carcasses. Table 3 summarizes average producer and packer returns for Improvest-managed pigs compared to PC pigs (3 price scenarios). Using the average price scenario, the mean of total returns for the packer from an Improvestmanaged male was estimated to increase $9.75 compared to a PC barrow. After paying the producer $6.71 for the added weight and premium increase, a net improvement in returns of $3.04 was realized for the primal cuts. In addition, an Figure 3. Premium schedule of a major US packer based on carcass composition.

As mentioned earlier, Improvest-managed males produce a different carcass than PC males. Carcass cutout data collected by Zoetis in a trial utilized for the optimal weight estimations was employed by the consulting economists to evaluate the expected value of an Improvest-managed carcass compared to a PC barrow carcass. Carcass component price distributions (including the drop) were collected from USDA sources and

55% lean

0

-25

Carcass % lean

250

-40

243

-40

229

-35 214

-30

-35

199

-30

-20

185

-25

-15

170

-20

155

-15

-10

141

-10

-5

101

-5

40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63

Premium ($/carcass cwt)

0

5

207 lb

Premium ($/carcass cwt)

5

Figure 5. Premium schedule of a major US packer: by carcass weight at 55% lean.

121

Figure 4. Premium schedule of a major US packer: by lean % at 207 lb carcass weight.

Carcass weight (lb)

5

“Improvest is often thought of as a feed cost saving technology. However, the major benefit to producers is to market more pounds of pork with a similar feed cost, thereby increasing revenues relative to costs.” — Dr. Brian Buhr ®

retail, and the consumer, as well as any impacts on related markets for key meats which substitute for pork in the diet of US consumers (and by aggregation, the ‘rest of the world’). The economic ripples emanating from the initial effects reach out much farther than the industry in which they originate, and they move over an extended period of time until their full effect is realized. Initial effects produce impacts in markets which lead to many rounds of adjustments, not only in the originating market but in related markets as they all seek their new equilibriums.

increase in the drop (heavier livers, guts, and other organs) of $2.00 over the PC barrow was expected, thus yielding a total improvement of $5.04 in net returns per Improvest carcass.

Aggregate Analysis Once all of these estimates were complete, an aggregate economic analysis was generated that quantified the likely impact from all of the direct effects originating from Improvest adoption. The aggregate effects were measured across the entire pork chain, from production through processing,

Table 3 — Average values of producer and packer returns for Improvest (IC) over physical castration (PC) methods.1 3 price scenarios: Variable

Average prices for feed and hogs

High feed and high hog prices a

High feed and average hog prices a

(average)

(95th percentile)

(95th percentile)

IC b

PC

IC b

PC

IC b

PC

Carcass weight (lb) c

205.70

201.15

205.72

200.26

201.23

196.03

Live weight (lb) c

284.79

272.18

284.82

270.73

278.60

265.06

Net profit ($/head)

$75.64 d

$65.32

$104.91 d

$92.15

$49.70

$39.12

Improvest benefit ($/head)

$10.32 e

$0

$12.76

$0

$10.58 e

$0

Benefit due to non-castration

$1.61

$0

$2.11

$0

$1.16

$0

Benefit due to feed saving

$2.00

$0

$2.08

$0

$2.10

$0

Benefit due to revenue

$6.71

$0

$8.57

$0

$7.32

$0

Producer Impacts

Percent change in producer returns

15.80%

Packer Impacts

IC b

Cutout revenue ($/head)

$170.98

0

13.85%

0

27.05%

0

PC

IC b

PC

IC b

PC

$161.23

n/a

n/a

n/a

n/a

Benefit Improvest cutout ($/head)

$9.75

$0

n/a

n/a

n/a

n/a

Benefit over producer payment ($/head) f

$3.04

$0

n/a

n/a

n/a

n/a

Benefit drop credit ($/head)

$2.00

$0

n/a

n/a

n/a

n/a

Net benefit to packer ($/head)

$5.04

$0

n/a

n/a

n/a

n/a

0

n/a

n/a

n/a

n/a

Percent change in packer returns a High

3.13%

feed and high hog prices defined as those at the at 95th percentile (top 5%) of reported average prices. all scenarios and all variables, Improvest (IC) pigs were significantly different (P < 0.05) than physical castrates (PC). c In all cases, physical castrates are marketed at lighter weights than Improvest pigs. This results in both revenue and feed cost tradeoffs. The differences in benefit are due to relative feed and hog prices as well as how producers optimize weights under those conditions. d Net profit for the 95% increase in all prices is significantly different from average prices, primarily due to a higher relative increase in hog prices. e The change in Improvest benefit with 95 percentile feed prices and average hog prices is lower due to marketing at lower weights, but producers are optimizing profits, not the marginal value of Improvest. f Benefit over producer payment = benefit Improvest cutout – paid benefit to producer increased revenue ($3.04 = $9.75 – $6.71). n/a = not applicable since packer analysis was only estimated for the average price for feed and hogs. b In

6

ROI (estimated full benefits/costs) from Improvest adoption is estimated to be higher than 2:1. ®

A baseline US adoption scenario was assumed to start with modest Improvest adoption rates which then accelerate to a final market adoption rate over a 10-year period (Improvest adoption in 4%, 17%, 34%, 50%, 58%, and 63% of male slaughter hogs in years 1-6, respectively, followed by consistent 65% Improvest use for years 7-10). From this baseline, several other sensitivity analyses were conducted assuming: • at the far-end of the spectrum, no adoption and a 15% loss in market share due to global competition from adopters in ‘rest of the world’; • an accelerated adoption profile which quickly moves from 0% adoption to 90% adoption by year 5 and which remains at that level for the duration of the 10-year analysis. In general, the baseline scenario increases the net present-value of total meat consumer surplus by $1802 million, with small losses to the beef and poultry sectors; and the net present-value of total societal surplus is expected to increase $3663 million. It is interesting to note that every part of the pork chain benefits from the adoption of Improvest, and every segment (hog producer, packers, and retail) are significantly worse-off in a US ‘no adoption’ scenario. In other words, global adoption of Improvest in the absence of US adoption will substantially reduce the ability of US pork producers to compete for global market share.

Important Safety Information: Pregnant women should not administer IMPROVEST. Women of childbearing age, as well as men, should exercise extreme caution when administering this product. Exercise special care to prevent accidental self-injection because of negative effects on reproductive physiology in both men and women. However, there is no risk associated with consuming pork from animals administered this product. IMPROVEST should not be used in female pigs, barrows, or male pigs intended for breeding.

Conclusions Based on their model assumptions, the panel of independent economists determined that producers who adopt Improvest can expect the optimal market weight of their animals to increase by an average of about 10 to 12 lb/head on a liveweight basis (4-6 lb/carcass) vs PC barrows. This outcome is consistent under a variety of cost and price scenarios. Furthermore, Improvest-managed males will attain this added weight without any additional days on feed, and the carcass will command a slightly improved premium value primarily due to increased uniformity. The expected improvement in net returns for US producers adopting Improvest (including costs and returns associated with increased production due to decreased pre-weaning mortality once castration stops) is $5.32/head after accounting for $5.00/head costs of Improvest use. This profit improvement for male pigs is derived as follows: n

$2.00/head feed savings at new optimal weight;

n

$6.71/head for higher optimal weight and carcass premium;

n

$1.61/head more wean-to-finish net income (direct cost savings from non-castration, dilution of fixed costs, increased profit from saved pigs);

n

= $10.32/head total of gross benefits;

n

-$5.00/head net cost of Improvest program;

n

$5.32/head more net profit/male pig marketed.

References 1. Buhr BL, Zering K, DiPietre D. A comprehensive, full chain and US meat sector economic analysis of the adoption of Improvest® by the US pork industry. Am Assoc Swine Vet 2013; 189-194. 2. Zoetis Inc. A comprehensive economic analysis of the adoption of an immunological alternative to physical castration by the US pork industry. Internal whitepaper, 2013. 3. Cowles B, Meeuwse D, Bradford J. Data summary of immunological castration impact in grow-finish performance of male pigs in USA. Am Assoc Swine Vet 2013; 375-376.

7

(Gonadotropin Releasing Factor AnalogDiphtheria Toxoid Conjugate, 0.2 mg/mL) Sterile Solution for Injection CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. DESCRIPTION: IMPROVEST is a sterile solution containing Gonadotropin Releasing Factor Analog-Diphtheria Toxoid Conjugate. Each mL contains 0.2 mg Gonadotropin Releasing Factor Analog-Diphtheria Toxoid Conjugate, 150 mg of diethylaminoethyl-dextran hydrochloride, 1 mg chlorocresol, sodium hydroxide as needed to adjust pH and water for injection. INDICATIONS FOR USE: IMPROVEST is indicated for the temporary immunological castration (suppression of testicular function) and reduction of boar taint in intact male pigs intended for slaughter. DOSAGE AND ADMINISTRATION: IMPROVEST should be administered via subcutaneous injection into the post auricular region of the neck. A safety injector should be used, preferably one which has a dual safety system providing both a needle guard and a mechanism to prevent accidental operation of the trigger. Each intact male pig should receive two 2-mL doses of IMPROVEST. The first dose should be administered no earlier than 9 weeks of age. The second dose should be administered at least 4 weeks after the first dose. Pigs should be slaughtered no earlier than 3 weeks and no later than 10 weeks after the second dose. In case of misdosing, the animal should be re-dosed immediately. CONTRAINDICATIONS: Do not use IMPROVEST in intact male pigs intended for breeding because of the disruption of reproductive function. Not approved for use in female pigs and barrows. WARNINGS: WITHDRAWAL PERIODS: No withdrawal period is required when used according to labeling. Not for Human Use. Keep Out of Reach of Children. USER SAFETY WARNINGS: Warning for person administering IMPROVEST: Accidental self injection could affect reproductive physiology of both men and women and may adversely affect pregnancy. Pregnant women should not administer this product. Women of childbearing age should exercise extreme caution when handling this product. Special care should be taken to avoid accidental self injection and needle stick injury when administering the product. Protective clothing including, but not limited to, safety glasses and gloves should be worn. Use a safety injector, preferably one which has a dual safety system providing both a needle guard and a mechanism to prevent accidental operation of the trigger. In case of eye contact, rinse immediately with copious amounts of water. In case of skin contact, wash immediately with soap and water. The product should be stored safely out of the reach of children. As a reminder, it is the prescribing veterinarian's responsibility to inform drug administrators of the user safety warnings associated with IMPROVEST. Advice to the user in the event of accidental self injection: In the event of accidental self injection, wash the injury thoroughly with clean running water. Seek prompt medical attention and take the package leaflet with you. Do not administer the product, and/or any other product with a similar action, in the future. Advice to the physician: Accidental self injection could affect reproductive physiology of both men and women and may adversely affect pregnancy. If self injection with IMPROVEST is suspected, reproductive physiology should be monitored by assay of testosterone or estrogen levels (as appropriate). The risk of a physiological effect is greater after a second or subsequent accidental injection than after a first injection. The patient should be advised not to administer IMPROVEST, and/or any other product with a similar action, in the future.

For orortotoobtain ofofthetheMaterial For customer customer service, service,totoreport reportsuspected suspectedadverse adversereactions reactions obtaina acopy copy Material Safety Safety Data Data Sheet Sheet (MSDS) (MSDS) call call 1-888-963-8471. 1-800-366-5288. PRECAUTIONS: Subcutaneous injection in intact male pigs can cause a transient local injection site reaction that may result in trim loss at slaughter. ADVERSE REACTIONS: The field study observations from field effectiveness studies were consistent with the observations made during the target animal safety studies of transient inflammation at the injection sites. IMPROVEST did not cause unusual clinical signs or an unexpected frequency or severity of injection site reactions. Adverse events, as reported, were not uniquely attributable to IMPROVEST. TARGET ANIMAL SAFETY: Margin of Safety: The safety of two doses of IMPROVEST was evaluated in intact male swine. Thirty 9-week old intact boars received two subcutaneous doses of IMPROVEST in the same location 14 days apart. The boars received one of three treatments: Saline Control (12-mL), IMPROVEST at the intended dose (2-mL, 1X), or IMPROVEST at 6 times the intended dose (12-mL, 6X). Boars were clinically monitored daily. In addition, observation and measurement of injection sites, body weight, quantitative feed consumption, hematology, and clinical chemistry analyses were also obtained. A complete postmortem examination was conducted on each boar

14 days after the second injection. IMPROVEST, administered subcutaneously at the label dose (2-mL) resulted in mild transient injection site reactions at the 1X dose and caused clinical signs of systemic inflammation at 6X the intended dose. The signs of inflammation included depression, stiffness of the neck lasting up to five days, reduction in feed intake, and lower body weights. Multiple swollen joints and associated lameness, which may be signs of systemic inflammation, were observed in one 6X boar. Evaluation of blood work revealed increased white blood cell counts (eosinophilia and neutrophilia); slight increases in total serum protein (above normal reference range in 50% of the 6X boars) and globulin (above the normal reference range in 40% of the 6X boars); and slight decreases in serum albumin in 6X boars. Injection sites for the 6X boars showed clinically detectable firmness persisting in all animals for 14 days after the second injection. Pain and sensitivity at the injection site persisted for up to five days, and erythema and heat were more prominent in the 6X boars than in the 1X boars. Mild to moderate chronic inflammation and discoloration in the subcutaneous tissues at the injection site were observed. In all IMPROVEST treated boars, atrophy of testes, prostate, and bulbourethral glands were observed as expected consequences associated with the intended effect of the drug. At the label 2-mL dose, IMPROVEST may cause transient injection site inflammation. Injection Site Safety: Injection site safety was evaluated following the injection of IMPROVEST into healthy 17-week old boars. The treated boars received two 2-mL doses of IMPROVEST into the same injection site location 28 days apart, while the control boars received saline. Daily monitoring included clinical evaluation and observation and measurement of injection sites. Two days after the second injection, postmortem observations of injection sites were conducted. All clinical signs of observable injection site swelling were resolved within 24 hours, and pain on palpation resolved by 48 hours post-injection. Firmness persisted for up to 11 days after the first injection in 10% of boars. Gross injection site alterations consisted of subcutaneous edema with tan or red discoloration. Two 2-mL injections of IMPROVEST, administered 28 days apart into the same location resulted in transient injection site reactions following each injection and resulted in discoloration of tissue at the injection site which was observable approximately 48 hours after the second injection. Field Safety: During the conduct of the nine location field effectiveness study, IMPROVEST did not cause unusual clinical signs or an unexpected frequency or severity of injection site reactions. The field safety observations from this study were consistent with the observations made during the target animal safety studies of transient inflammation at the injection sites. Adverse events, as reported, were not uniquely attributable to IMPROVEST. EFFECTIVENESS: IMPROVEST is an injectable sterile solution containing an incomplete analog of natural gonadotropin releasing factor (GnRF) conjugated to diphtheria toxoid in an adjuvanted formulation. Immunization with a two dose regimen of IMPROVEST, with a four week interval between doses, stimulates the pig’s immune system to produce antibodies which can neutralize its own GnRF. Pigs given an initial dose of IMPROVEST are immunologically primed but do not produce sufficient antibodies to have any physiological effect. Following receipt of the second dose, the pig’s immune system responds with a strong antibody response. These antibodies bind to and neutralize circulating GnRF in the bloodstream. Neutralization of GnRF blocks the hypothalamic-pituitary-gonadal endocrine axis, thereby suppressing testicular function, including both sex hormone production and reproductive capability, thereby providing temporary immunological castration in these injected boars. Evidence of temporary immunological castration was provided in a series of studies showing that within 1-2 weeks after the second injection of IMPROVEST, anti-GnRF antibody levels increase significantly. With this rise in anti-GnRF antibodies, the levels of gonadal sex hormones were substantially reduced, the size of the testes, and spermatogenesis suppressed, as was the expression of typical male behaviors (aggression and sexual, e.g., mounting). Full immunological castration was demonstrated to last from 3 to 10 weeks after the second dose. IMPROVEST injected boars will start to return to full reproductive function at a variable period after this time, as evidenced by increases in male sex hormones, testicle size, and intact male behavior. IMPROVEST should not be used in boars intended for breeding purposes. Evidence to assess the acceptability of pork from IMPROVEST treated pigs was provided through a series of consumer taste panels using consumers deemed sensitive to the taste of “tainted” meat. The presence of boar taint was evaluated on the basis of pork aroma and flavor and not by chemical analysis. Four consumer taste panel studies were conducted to demonstrate the difference of pork generated from IMPROVEST treated boars and intact boars. A surgically castrated male group was not evaluated during these studies. In these four studies, 767 sensitive consumers evaluated cooked pork loin samples from IMPROVEST treated and intact boars. These pigs were raised to market weight, injected with IMPROVEST as per product labelling and slaughtered 3 to 10 weeks after receipt of the second IMPROVEST injection. The consumers found the aroma and flavor of pork from the IMPROVEST injected pigs to be more acceptable than from the intact boars in all four studies. STORAGE INFORMATION: Store under refrigeration at 2°-8°C (36°-46°F). Once broached, product may be stored under refrigeration for 28 days. Store bottles in carton until used. Protect from light. Protect from freezing. HOW SUPPLIED: IMPROVEST is available in the following package sizes: 20 mL bottle, 100 mL bottle, 250 mL bottle, 500 mL bottle. NADA # 141-322, Approved by FDA

Revised: January 2013

Revised: September 2011

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NADA # 141-322, Approved by FDA

PAA035383