Table 4.
Manufacturing success rate and results from 75 PHPI lots by facility and for all facilities
| Center ID |
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| 1 (n = 9) | 2 (n = 4) | 3 (n = 17) | 4 (n = 15) | 5 (n = 7) | 6 (n = 12) | 7 (n = 6) | 8 (n = 5) | All facilities (N = 75) | |
| All CIT isolations* | |||||||||
| No. lots prepared | 57 | 27 | 44 | 39 | 35 | 58 | 19 | 37 | 324 |
| PHPI lots transplanted | 29 (50.9) | 12 (44.4) | 26 (59.1) | 22 (56.4) | 16 (45.7) | 32 (55.2) | 17 (89.5) | 9 (24.3) | 170 (52.5) |
| Protocol CIT-07 | |||||||||
| Donor characteristic | |||||||||
| Age (years) | 46 (9) | 50 (6) | 39 (19) | 37 (22) | 49 (27) | 43 (21) | 37 (7) | 53 (26) | 42 (19) |
| Height (cm) | 172.0 (5.0) | 167.8 (11.6) | 182.9 (7.0) | 180.0 (12.4) | 175.0 (14.9) | 175.1 (13.5) | 174.4 (9.8) | 172.7 (15.3) | 177.8 (12.7) |
| Weight (kg) | 85.0 (28.5) | 93.0 (28.1) | 113.4 (13.7) | 90.7 (28.0) | 113.0 (54.9) | 112.5 (16.6) | 113.6 (29.0) | 93.0 (32.0) | 107.0 (31.0) |
| BMI (kg/m2) | 27.1 (7.7) | 31.9 (5.6) | 34.7 (4.6) | 28.2 (11.2) | 36.0 (14.8) | 36.3 (5.2) | 38.4 (12.9) | 28.6 (13.6) | 33.4 (8.2) |
| Cold ischemic time (h) | 6.0 (5.4) | 8.5 (4.6) | 7.4 (2.5) | 6.7 (3.2) | 7.9 (2.7) | 8.9 (5.4) | 7.8 (0.7) | 7.8 (0.7) | 7.7 (3.4) |
| Product manufacture | |||||||||
| Final trimmed pancreas weight (g) | 95 (37) | 93 (46) | 109 (28) | 103 (40) | 101 (63) | 102 (64) | 112 (31) | 124 (19) | 106 (40) |
| Total packed tissue volume (mL) | 45 (6) | 45 (5) | 44 (14) | 45 (30) | 40 (46) | 39 (18) | 25 (1) | 40 (10) | 44 (16) |
| Postdigestion IPN | 865,000 (720,723) | 718,000 (404,000) | 1,183,000 (585,500) | 542,000 (556,000) | 421,250 (30,500) | 351,000 (145,524) | 548,500 (231,000) | 853,125 (111,250) | 537,500 (528,000) |
| Postdigestion IEQ | 732,250 (128,250) | 728,842 (314,642) | 1,074,360 (277,000) | 693,520 (615,069) | 613,534 (447,954) | 523,218 (359,927) | 787,250 (397,160) | 666,068 (93,080) | 708,470 (382,000) |
| Postdigestion index† | 1.10 (0.40) | 1.00 (0.20) | 0.95 (0.15) | 1.30 (0.10) | 1.30 (0.30) | 1.70 (1.40) | 1.55 (0.10) | 0.70 (0.00) | 1.20 (0.60) |
| Postpurification IPN | 451,750 (188,000) | 362,000 (177,000) | 506,000 (243,500) | 368,250 (216,000) | 268,750 (188,750) | 233,475 (150,900) | 350,750 (205,000) | 630,000 (80,000) | 390,500 (287,750) |
| Postpurification IEQ | 620,000 (258,506) | 641,275 (273,010) | 672,547 (226,290) | 556,181 (280,726) | 588,602 (338,136) | 503,459 (245,830) | 569,038 (438,968) | 492,736 (96,845) | 582,370 (267,931) |
| Postpurification index | 1.40 (0.50) | 1.70 (0.90) | 1.30 (0.40) | 1.50 (0.50) | 1.90 (0.70) | 1.95 (0.85) | 1.75 (0.70) | 0.90 (0.30) | 1.50 (0.60) |
| Postculture IPN | 396,000 (186,000) | 242,688 (115,188) | 265,250 (180,750) | 282,000 (145,750) | 197,000 (197,095) | 219,250 (103,500) | 210,500 (81,690) | 484,000 (223,510) | 276,000 (171,000) |
| Postculture IEQ | 469,400 (120,380) | 579,915 (139,065) | 637,280 (243,020) | 455,098 (235,652) | 402,600 (168,601) | 422,665 (284,797) | 598,874 (168,600) | 370,034 (43,550) | 490,174 (226,835) |
| Postculture (index) | 1.40 (0.50) | 1.55 (0.60) | 1.30 (0.90) | 1.30 (0.40) | 1.30 (0.40) | 1.85 (0.90) | 1.90 (0.40) | 0.80 (0.20) | 1.40 (0.70) |
| Process recovery (IEQ/g trimmed pancreas) | |||||||||
| Postdigestion | 8,135 (2,300) | 6,531 (3,812) | 8,958 (2,876) | 6,270 (4,417) | 5,708 (2,919) | 4,720 (2,042) | 7,778 (3,064) | 6,422 (1,527) | 6,813 (3,672) |
| Postpurification | 5,877 (4,544) | 5,715 (3,029) | 6,601 (1,883) | 5,884 (3,942) | 5,442 (1,594) | 4,634 (1,614) | 6,201 (3,501) | 4,371 (1,160) | 5,471 (2,709) |
| Postculture | 4,925 (2,730) | 5,235 (1,845) | 5,749 (1,273) | 5,305 (2,614) | 4,525 (1,565) | 4,064 (662) | 5,662 (2,427) | 3,319 (1,154) | 4,730 (2,156) |
| Process yield (%) | |||||||||
| Postpurification | 73 (24) | 84 (6) | 77 (19) | 81 (25) | 106 (42) | 92 (31) | 84 (11) | 79 (13) | 82 (22) |
| Postculture | 81 (17) | 82 (17) | 91 (13) | 88 (11) | 80 (27) | 89 (20) | 96 (30) | 75 (8) | 86 (17) |
| Overall | 61 (25) | 71 (13) | 68 (17) | 71 (20) | 73 (25) | 85 (39) | 79 (7) | 60 (12) | 71 (22) |
| Final product release test results | |||||||||
| GSIR index (high-purity islets, preculture)‡ | 2.1 (0.7) | 1.6 (1.7) | 3.5 (3.9) | 2.3 (1.2) | 2.9 (3.7) | 2.1 (2.0) | 2.6 (2.9) | 2.0 (0.2) | 2.1 (2.0) |
| GSIR index (high-purity islets, postculture) | 2.6 (0.4) | 3.8 (2.7) | 2.2 (1.1) | 1.6 (1.1) | 2.9 (2.4) | 1.7 (1.8) | 2.2 (1.2) | 2.5 (0.7) | 2.3 (1.6) |
| Settled tissue volume (mL) | 5.0 (1.5) | 3.9 (1.7) | 6.0 (4.2) | 3.0 (4.0) | 2.9 (2.6) | 2.5 (1.1) | 3.9 (3.4) | 2.2 (0.8) | 4.0 (3.8) |
| Total transplant (IEQ) | 462,510 (119,531) | 573,116 (169,216) | 614,578 (190,868) | 467,135 (245,378) | 396,926 (166,745) | 406,982 (281,925) | 573,643 (178,843) | 366,390 (49,896) | 480,500 (231,139) |
| Islet quantity dose/batch (IEQ/kg recipient BW) | 6,535 (1,390) | 8,387 (2,943) | 7,813 (2,416) | 6,561 (3,338) | 5,924 (2,267) | 6,359 (1,903) | 9,035 (1,518) | 5,277 (1,892) | 6,694 (2,800) |
| Viability bag #1 | 97.00 (6.20) | 93.10 (7.50) | 89.80 (7.70) | 93.00 (1.00) | 96.24 (2.32) | 94.11 (3.48) | 100.00 (0.00) | 96.60 (4.90) | 93.80 (6.34) |
| Endotoxins (EU/kg recipient BW) | 0.07 (0.05) | 0.58 (0.38) | 0.66 (0.72) | 0.12 (0.54) | 0.02 (0.06) | 1.14 (1.53) | 3.41 (1.89) | 0.88 (0.20) | 0.44 (0.86) |
| Islet concentration total (IEQ/mL total settled tissue volume) | 78,512 (31,467) | 155,391 (141,985) | 89,580 (105,652) | 173,613 (101,180) | 134,813 (188,556) | 210,443 (178,965) | 146,832 (131,407) | 218,409 (110,943) | 134,813 (131,407) |
| Gram stain | All negative | All negative | All negative | All negative | All negative | All negative | All negative | All negative | All negative |
| Sterility | |||||||||
| Negative | 7 (77.8) | 4 (100) | 16 (94.1) | 15 (100) | 7 (100) | 11 (91.7) | 4 (66.7) | 5 (100) | 69 (92) |
| Positive | 2 (22.2) | 1 (5.9) | 1 (8.3) | 2 (33.3) | 6 (8) | ||||
| PHPI calculated microscopic purity (%) | 70 (3) | 63 (20) | 66 (14) | 60 (15) | 57 (27) | 75 (32) | 70 (32) | 80 (13) | 69 (17) |
Data are n (%) or median (IQR). EU, endotoxin units; IPN, islet particle number.
*The total number of lots includes Center 9, which did not manufacture PHPI for Protocol CIT-07.
†Postdigestion index: IPN values were available for 41 of 75 lots.
‡GSIR preculture result was for information only and not used for lot release.