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INCOME TAXES (Tables) | 12 Months Ended
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Dec. 31, 2021
Income Tax Disclosure [Abstract] |
Schedule of Benefit from Income Taxes Based on Loss Before Income Taxes | The benefit from income taxes was based on loss before income taxes as follows:
| Years Ended December 31
| 2021 |  | 2020 |  | 2019
U.S. Source | $ | (259,258) |  |  | $ | (162,939) |  |  | $ | (182,112) |
Non-U.S. Source | 183,908 |  |  | 120,617 |  |  | 87,301 |
Loss before income taxes | $ | (75,350) |  |  | $ | (42,322) |  |  | $ | (94,811) |
Schedule of Components of Provision for (Benefit From) Income Taxes | The U.S. and foreign components of the benefit from income taxes were as follows:
| Years Ended December 31,
| 2021 |  | 2020 |  | 2019
Provision for (benefit from) current income tax expense: |  |  |  |  |
Federal | $ | (2,038) |  |  | $ | (14,758) |  |  | $ | 5,127 |
State and local | 1,339 |  |  | 1,201 |  |  | 1,331 |
Foreign | 5,037 |  |  | 1,042 |  |  | 5,339 |
| 4,338 |  |  | (12,515) |  |  | 11,797 |
Provision for (benefit from) deferred income taxes: |  |  |  |  |
Federal | (29,895) |  |  | (45,038) |  |  | (58,311) |
State and local | (1,230) |  |  | (5,321) |  |  | (5,394) |
Foreign | 15,517 |  |  | (838,548) |  |  | (19,055) |
| (15,608) |  |  | (888,907) |  |  | (82,760) |
Benefit from income taxes | $ | (11,270) |  |  | $ | (901,422) |  |  | $ | (70,963) |
Schedule of Reconciliation of Statutory Federal Income Tax Rate to Company's Effective Income Tax Rate | The following is a reconciliation of the statutory federal income tax benefit to the Company’s effective tax rate:
| December 31,
| 2021 |  | 2020 |  | 2019
Federal statutory income tax benefit | $ | (15,824) |  |  | $ | (8,888) |  |  | $ | (19,911) |
State and local taxes | 509 |  |  | (3,264) |  |  | (2,784) |
Orphan Drug & General Business Credit | (29,363) |  |  | (44,114) |  |  | (43,124) |
Stock compensation expense | 7,859 |  |  | (1,101) |  |  | 239 |
Changes in the fair value of contingent consideration | — |  |  | — |  |  | (1,804) |
Foreign Source Income Subject to U.S. Tax | 16,878 |  |  | 6,266 |  |  | (52) |
Foreign tax rate differential (1) (2) | (16,971) |  |  | (16,238) |  |  | (30,639) |
Section 162(m) limitation | 6,304 |  |  | 9,571 |  |  | 8,294 |
Tax Reserves | 15,530 |  |  | 2,166 |  |  | 12,123 |
Intra-entity transfer of assets | (3,920) |  |  | (852,338) |  |  | — |
CARES Act carryback claim | — |  |  | (2,201) |  |  | — |
Valuation allowance/deferred benefit | 6,821 |  |  | 6,876 |  |  | 7,827 |
Other | 907 |  |  | 1,843 |  |  | (1,132) |
Effective income tax benefit | $ | (11,270) |  |  | $ | (901,422) |  |  | $ | (70,963) |
(1) For the year ended December 31, 2021, the foreign rate differential included foreign local tax expense which was at an effective rate lower than the U.S. statutory rate and includes the recognition of the valuation allowance against a portion of the deferred tax assets of the Company’s Dutch subsidiary of $9.3 million. (2) For the year ended December 31, 2019, the foreign rate differential included foreign local tax expense which was at an effective rate lower than the U.S. statutory rate and was offset by the benefit of the valuation allowance release against the deferred tax assets of the Company’s Dutch subsidiary of $29.6 million.
Schedule of Components of Net Deferred Tax Assets | The significant components of the Company’s net deferred tax assets were as follows:
| December 31,
| 2021 |  | 2020
Net deferred tax assets: |  |  |
Net operating loss carryforwards | $ | 25,936 |  |  | $ | 30,718 |
Tax credit carryforwards | 563,022 |  |  | 532,394 |
Accrued expenses, reserves, and prepaids | 72,759 |  |  | 66,889 |
Intangible assets | 875,311 |  |  | 873,575 |
Stock-based compensation | 50,910 |  |  | 47,011 |
Lease liabilities | 7,422 |  |  | 8,991 |
Inventory | 25,169 |  |  | 32,012 |
Other | 1,943 |  |  | 454 |
Valuation allowance | (109,176) |  |  | (93,075) |
Total deferred tax assets | 1,513,296 |  |  | 1,498,969 |
Joint venture basis difference | (1,665) |  |  | (1,164) |
Acquired intangibles | (1,250) |  |  | (1,364) |
Deferred revenue | — |  |  | (1,517) |
ROU assets | (6,808) |  |  | (8,280) |
Property, plant and equipment | (54,498) |  |  | (54,682) |
Total deferred tax liabilities | (64,221) |  |  | (67,007) |
Net deferred tax assets | $ | 1,449,075 |  |  | $ | 1,431,962 |
Summary of Expiration of not Utilized Net Operating Loss and Tax Credit Carryforwards | As of December 31, 2021, the Company had the following net operating loss and tax credit carryforwards, which if not utilized, will expire as follows:
Type |  | Amount |  | Year
Federal net operating loss carryforwards |  | $ | 4,147 |  |  | 2030-2033
Federal R&D and orphan drug credit carryforwards |  | $ | 592,710 |  |  | 2024-2041
State net operating loss carryforwards |  | $ | 230,500 |  |  | 2023-2041
Dutch net operating loss carryforwards |  | $ | 48,903 |  |  | Indefinite
Schedule of Reconciliation of Unrecognized Tax Benefits | A reconciliation of the beginning and ending amount of unrecognized tax benefits for the years ended December 31, 2021 and 2020, is as follows:
| December 31,
| 2021 |  | 2020
Balance at beginning of period | $ | 182,564 |  |  | $ | 168,748 |
Additions based on tax positions related to the current year | 23,499 |  |  | 16,481 |
(Deletions) Additions for tax positions of prior years | (786) |  |  | (2,527) |
Lapse of statute of limitations | (182) |  |  | (138) |
Balance at end of period | $ | 205,095 |  |  | $ | 182,564 |

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