The Viva Puerto Rico Project

 

Some of These 101 Prescription Drugs – Made in Puerto Rico Before Hurricane Maria – May Soon Be Unavailable

With shortages looming, Insightus has identified the prescription drugs manufactured in Puerto Rico that the FDA refuses to name

26 October 2017 11:00 AM US Eastern

P
uerto Rico is home to prescription drug manufacturing facilities for pharmaceutical giants like Johnson & Johnson, Pfizer, Eli Lilly, Amgen, Bristol-Myers Squibb, AbbVie, Merck, Baxter, and others. With the island's infrastructure in tatters following Hurricane Maria those sites are now barely operational at best, leading the FDA to warn of possible impending drug shortages in mainland America.

So far, neither FDA nor the companies involved have provided a comprehensive list of the specific drugs that are manufactured in Puerto Rico (and that are thus at risk of shortages). By reviewing hundreds of government and industry documents we've assembled that list. It illustrates yet another reason why mainland Americans should care about Puerto Rican recovery: because the mainland and the island both depend on one another.





 
 

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America's Rapidly Emptying Drug Store: Hurricane-Ravaged Puerto Rico

When September's Hurricane Maria plunged the island of Puerto Rico and its 3.4 million American citizens into a post-apocalyptic existence without reliable electricity or drinkable water – conditions that remain today, more than a month later – one of the least-noted casualties of that death-blow was the island's largest manufacturing sector: pharmaceutical production.

The full implications of that disaster – and of the glacially slow pace of subsequent FEMA-led recovery efforts – now seem set to hit home for mainland Americans, who could soon face difficulties filling the prescriptions that many of our lives depend upon.

Thanks to a favorable U.S. tax code provision enacted in 1976, major pharmaceutical companies like Pfizer, Amgen, Bristol–Myers Squibb, Lilly, and Johnson & Johnson have large factories located across the island of Puerto Rico. But post–Maria those multimillion dollar facilities face the same impossible conditions that their workers' families also face at home: faltering electrical service, failing backup generators, trickling tap water, and unreliable transportation.

U.S. Food and Drug Administration head Scott Gottlieb painted a bleak picture of what that means for those pharmaceutical plants in a recent interview with Reuters:

A lot of companies say they're online, but they basically have one of five lines running at 20 percent or 80 percent or 50 percent [....] It's unclear when they are going to be able to bring that up to full capacity.
Underscoring the agency's concern, Gottlieb's FDA has announced that it is now closely monitoring "about 40 pharmaceutical and biological drug products for which a shortage could have substantial impact on the public health."

Unfortunately for American patients who rely on those drugs, so far neither FDA nor the companies involved are saying which drugs might soon be in short supply. In fact very few Americans - apparently even including reporters covering this emerging story - know which drugs are manufactured in Puerto Rico.

Mind The Gap

To address that lack of information, Insightus researchers have just completed a survey of hundreds of documents that identify drugs currently manufactured on the island. Sources used in our analysis included publicly available FDA (and foreign drug regulators') documentation, Securities and Exchange Commission filings, Federal Register notifications, drug package inserts, trade journals, court filings, scholarly studies, and other reliable sources.

Included in the resulting list of 101 Puerto Rico–manufactured pharmaceuticals (see table below) are 9 of America's top 20 bestselling drugs for 2016, including Humira (the #1 best-seller), Enbrel (#3), Remicade (#5), Januvia (#6), Lyrica (#8), Crestor (#9), Neulasta (#10), Xarelto (#14), and Eliquis (#16).

The most common applications for drugs on our made-in-Puerto-Rico list include:
 
Pain (12 drugs)
Diabetes (11)
Cancer and chemotherapy-related conditions (10)
Antibiotics and antifungals (9)
Cardiovascular (6)
Cholesterol control (6)
Depression (4)
Birth control (4)
Osteoporosis (4)
Anesthetics (3)
Crohn's disease (3)
Migraine (3)
Schizophrenia (3)
Antivirals (HIV and HCV) (3)
Arthritis (2)
Ulcerative colitis (2)
Attention deficit hyperactivity disorder (ADHD) (2)
Epilepsy (2)
The companies most represented in our list include:
 
Johnson & Johnson / Janssen (26)
Amgen (13)
Bristol-Myers Squibb (12)
AbbVie (10)
Eli Lilly (10)
Pfizer (8)
Merck (4)
Baxter (3)*
AstraZeneca (2)
Depomed (2)
Romark (2)

 
* The Baxter products listed here do not include the several bagged infusion products manufactured by Baxter in Puerto Rico, some of which were already in shortage prior to Hurricane Maria.
How We Identified Pharmaceuticals
Exposed to Puerto Rican Risk

Pharmaceutical companies are often hesitant to discuss their manufacturing and logistical operations, and the FDA cooperates by redacting such proprietary information from publicly available documents when requested to. Still, such details sometimes leak through into public information regarding drugs marketed in the U.S. and European Union.

We identified such 'leaked' information using an automated search strategy to locate documents on the web containing a drug's brand name, plus 'Puerto Rico' or a Puerto Rican city name and 'PR', plus words related to 'manufacturing' or 'packaging'. Hits were then inspected to weed out false positives and old information (2007 was our minimum acceptable date). Among all the surviving references we chose only the single most current and authoritative to cite for each drug, in the table's numbered "Ref." column (below).

Finally, we checked our work by asking companies named in the table below to confirm or deny that their listed products are manufactured in whole or part in Puerto Rico. Their responses are summarized in the table's numbered "Note" column.


 
CONNECTING THE DOTS:
Understanding the Complicated
Origins of Modern Drugs

Manufacturing a modern prescription drug involves numerous steps, including chemically synthesizing the active ingredient (the so-called API), mixing it with inactive ingredients such as stabilizers and colors, formulating the final dosage form (pressing the tablets or filling the capsules or vials), packaging, warehousing and shipping.

Nowadays, a company specializing in chemical synthesis (a so-called contract manufacturer or CMO) might make the API, then ship it in bulk half-way around the world to a company that formulates the API into tablets, which a third company might package and a fourth would warehouse and distribute. The company whose name appears on the package (and in our table, below) – the marketer – might not be directly involved in any of those steps.

If any one of those steps currently occurs in Puerto Rico, that drug is at risk of post-Maria shortages. But some risks are greater than others. Synthesizing an API can't easily be moved to another factory overnight, but warehousing probably can. So a drug on our list may be at either higher or lower risk of Maria-caused shortages.

Other complexities should be kept in mind, too. Time is one of them. Some documents we cite here are current (for example, Janssen's Prescribing Information for Elmiron, dated 2017), but others are less so (such as the European Medicines Agency document for Takeda's Entyvio, dated 2014). In the many cases where marketers have declined to confirm whether such less-current documents still reflect pre-Maria 2017 conditions, we have assumed that they do.

Finally, a drug manufactured in Puerto Rico might also be manufactured at a second site elsewhere around the globe, thus reducing the threat of a shortage. In most cases the marketers we invited to comment declined to say if their drugs are also manufactured at additional off-island sites.

101 Drugs Manufactured in Whole or Part in Puerto Rico Prior to Hurricane Maria
Mobile users: Click to view a full-screen version of this table
Note: Based on available evidence. The absence of a drug from this list does not necessarily indicate that it is not manufactured in Puerto Rico.
Brand Name Company Indications Active Ingredient Site Ref. Note
Brand Name Company Indications Active Ingredient Site Ref. Note
ABASRIA Eli Lilly Diabetes insulin glargine Carolina, PR 1 1
ACTONEL Allergan Osteoporosis risedronate sodium Manati, PR 3 1
ADVICOR AbbVie Cholesterol control niacin, lovastatin Barceloneta, PR 4 1
ALINIA (oral suspension) Romark HIV-associated infections nitazoxanide Manati, PR 5 1
ALINIA (tablets) Romark HIV-associated infections nitazoxanide Manati, PR 5 1
ARANESP Amgen Anemia darbepoetin alfa Juncos, PR 6 1
AVANDIA GlaxoSmithKline Diabetes rosiglitazone maleate Cidra, PR 8 1
AXERT Janssen Migraine almotriptan malate Gurabo, PR 9 1
BENADRYL Johnson & Johnson Allergy diphenhydramine HCl Las Piedras, PR 10 1
BIAXIN AbbVie Antibiotic clarithromycin Barceloneta, PR 11 1
BLINCYTO Amgen Cancer (leukemia) blinatumomab Juncos, PR 12 1
CARDURA XL Pfizer Hypertension doxazosin mesylate Barceloneta, PR 14 1
CELEBREX XL Pfizer Pain, inflammation celecoxib 15 1
CIALIS Eli Lilly Erectile dysfunction tadalafil 2 1
CONCERTA CR Janssen Attention deficit hyperactivity disorder methylphenidate 2 1
CORLANOR CR Amgen Cardiovascular ivabradine Juncos, PR 6 1
COUMADIN OSD Bristol-Myers Squibb Blood thinner coumadin Manati, PR 16 2
CRESTOR AstraZeneca Cholesterol control rosuvastatin Canovanas, PR 17 1
CYMBALTA Eli Lilly Depression; nerve pain duloxetine HCL 2 1
DAKLINZA Bristol-Myers Squibb Antiviral (Hepatitis C) daclatasvir 3
DEPAKOTE AbbVie Epilepsy; bipolar disorder; migraine divalproex sodium 18 1
ELIQUIS Bristol-Myers Squibb Cardiovascular apixaban Humacao, PR 19 2
ELMIRON Janssen Pain (bladder) pentosan polysulfate sodium Gurabo, PR 20 1
EMPLICITI Bristol-Myers Squibb Cancer (multiple myeloma) elotuzumab 3
ENBREL Amgen Arthritis etanercept Juncos, PR 6 1
ENTYVIO Takeda Ulcerative colitis; Crohns disease vedolizumab Barceloneta, PR 21 1,4
EPOGEN Amgen Anemia epoetin alpha Juncos, PR 6 1
EVISTA Eli Lilly Osteoporosis raloxifene HCl 22 1
FLUOXETINE Edgemont Depression fluoxetine HCl Manati, PR 23 1
FORANE Baxter Anesthesia isoflurane Guayama, PR 24 1
FORTEO Eli Lilly Osteoporosis teriparatide 22 1
GLUCOPHAGE Bristol-Myers Squibb Diabetes (Type 2) metformin HCl 3
GLUCOTROL XL Pfizer Diabetes (Type 2) glipizide 14 1
GRALISE Depomed Neuralgia gabapentin Manati, PR 25 1
HUMALOG Eli Lilly Diabetes insulin lispro Carolina, PR 26 1
HUMATROPE Eli Lilly Growth homone deficiency somatropin Carolina, PR 22 1
HUMIRA AbbVie Arthritis; Crohns disease; ulcerative colitis adalimumab Barceloneta, PR 27 1
INVEGA Janssen Schitzophrenia; depression paliperidone 2 1
INVOKAMET Janssen Diabetes (Type 2) canagliflozin, metformin HCl 15 1
INVOKANA Janssen Diabetes (Type 2) canagliflozin 15 1
JANUMET Merck Diabetes (Type 2) sitagliptin, metformin 2 1
JANUVIA Merck Diabetes (Type 2) sitagliptin Caguas, PR 28 1
JOLIVETTE Actavis Birth control norethindrone Manati, PR 29 1
K-TAB AbbVie Potassium deficiency potassium chloride Barceloneta, PR 30 1
KALETRA AbbVie Antiretroviral (HIV) lopinavir, ritonavir Barceloneta, PR 31 1
LEVAQUIN Janssen Antibiotic levofloxacin Gurabo, PR 32 1
LEVO-T Neolpharma Hypothyroidism levothyroxine sodium Caguas, PR 33 1
LIPITOR Pfizer Cholesterol control atorvastatin calcium 34 1
LYRICA Pfizer Pain (neuropathic, fibromyalgia) pregabalin 15 1
MOTRIN Johnson & Johnson Pain, inflammation ibuprofen Las Piedras, PR 10 1
NEULASTA Amgen Infections assoc. w/ chemotherapy pegfilgrastim Juncos, PR 6 1
NEUPOGEN Amgen Infections assoc. w/ chemotherapy filgrastim Juncos, PR 6 1
NEURONTIN Pfizer Pain (neuralgia) gabapentin 2 1
NIASPAN AbbVie Hyperlipidemia niacin Barceloneta, PR 35 1
NPLATE Amgen Thrombocytopenia romiplostim Juncos, PR 6 1
NUCINTA ER Depomed Pain tapentadol Gurabo, PR 25 1
NULOJIX Bristol-Myers Squibb Kidney transplant belatacept Manati, PR 36 2
OPDIVO Bristol-Myers Squibb Cancer (metastatic melanoma) nivolumab Manati, PR 37 2
ORENCIA Bristol-Myers Squibb Arthritis (rheumatoid) abatacept Manati, PR 15 2
ORTHO MICRONOR Janssen Birth control norethindrone Manati, PR 38 1
ORTHO TRI-CYCLEN Janssen Birth control estrogen, progestin Manati, PR 39 1
ORTHO CYCLEN Janssen Birth control estrogen, progestin Manati, PR 40 1
PRAVACHOL Bristol-Myers Squibb Cholesterol control pravastatin sodium 3
PRAVASTATIN Bristol-Myers Squibb Cholesterol control pravastatin sodium 3
PREZISTA Janssen Antiretroviral (HIV) darunavir Gurabo, PR 41 1
PROLIA Amgen Osteoporosis denusamab Juncos, PR 6 1
PROPECIA Merck Hair loss finasteride Arecibo, PR 42 1
PROSCAR Merck Benign prostatic hyperplasia finasteride Arecibo, PR 2 1
RAZADYNE ER Janssen Alzheimers galantamine HBr Gurabo, PR 43 1
REGRANEX Janssen Diabetic ulcers becaplermin San German, PR 44 1
REMICADE Janssen Crohns disease infliximab 45 1
REPATHA Amgen Hyperlipidemia evolucomab Juncos, PR 6 1
RISPERDAL Janssen Schizophrenia risperidone Gurabo, PR 2 1
SENSIPAR Amgen Hyperparathyroidism cinacalcet Juncos, PR 6 1
SEVOFLURANE Baxter Anesthesia sevoflurane Guyama, PR 24 1
SIMCOR AbbVie Cholesterol control niacin, simvastatin Barceloneta, PR 47 1
SPORANOX Janssen Antifungal itraconazole Gurabo, PR 48 1
STRATTERA Eli Lilly Attention deficit hyperactivity disorder atomoxatine 49 1
SUPRANE Baxter Anesthesia desflurane Guyama, PR 24 1
SUSTIVA Briston-Myers Squibb Antiretrovial (HIV) efavirenz Humacao, PR 15 2
SYMBYAX Eli Lilly Depression, bipolar disorder olanzapine, fluoxetine HCl 22 1
SYNTHROID AbbVie Hypothyroidism levothyroxine sodium 2 1
TENORETIC Almatica Hypertension atenolol, chlorthalidone 50 1
TERAZOL 7 Janssen Antifungal (vaginal) terconazole Gurabo, PR 51 1
TERCONAZOLE CREAM 7 Watson Antifungal (vaginal) terconazole Manati, PR 52 1
TOPAMAX Janssen Epilepsy topiramate Gurabo, PR 53 1
TRILIPIX AbbVie hypertriglyceridemia fenofibric acid Barceloneta, PR 54 1
TYLENOL Johnson & Johnson pain, inflammation acetaminophen Las Piedras, PR 10 1
TYLENOL WITH CODEINE Janssen pain, inflammation acetaminophen, codeine Gurabo, PR 55 1
ULTRACET Janssen pain tramadol HCl, acetaminophen Gurabo, PR 56 1
ULTRAM Janssen pain tramadol HCl Manati, PR 57 1
VECTIBIX Amgen Cancer (colorectal) panitumumab Juncos, PR 6 1
XARELTO Janssen Blood thinner rivaroxaban Gurabo, PR 34 1
XGEVA Amgen Cancer (metastatic) denosumab Juncos, PR 6 1
XIGDUO XR AstraZeneca Diabetes (Type 2) dapagliflozin, metformin HCl 2 1
YERVOY Bristol-Myers Squibb Cancer (metastatic) ipilimumab Manati, PR 2 2
ZMAX ONE DOSE Pfizer Antibiotic azithromycin Vega Baja, PR 15 1
ZOMIG Impax Migraine zolmitriptan 15 1
ZYPREXA Eli Lilly Schizophrenia olanzapine 15 1
ZYRTEC Johnson & Johnson Antihistamine cetirizine HCl Las Piedras, PR 10 1
ZYVOX Pfizer antibiotic linezolid 15 1

REFERENCES:
1. European Medicines Agency (2014): Assessment report: Abasria (2014)
2. Food and Drug Administration Philippines (2017): Provisional List of Comparator Products for in vivo and/or in vitro Equivalence Studies
3. Allergan (2015): Prescribing Information: Actonel
4. AbbVie (2013): Prescribing Information: Advicor
5. Federal Register (2017): Notification of Proposed Production Activity; Romark Global Pharma
6. Forbes (2017): Amgen Puerto Rico staff keeping plant open despite personal losses from Hurricane Maria
7. [deleted]
8. U.S. FDA (2017): September 2017 - Approved drug product list
9. Janssen (2017): Prescribing information: Axert
10. Communications of the IIMA (2013): McNeil Healthcare, Puerto Rico: FDA case study
11. AbbVie (2017): Prescribing information: Biaxin
12. U.S. FDA (2014): BLA Accelerated Approval - Blincyto
13. [deleted]
14. Caribbean Business (2017): Pfizer to downsize operations in Barceloneta beyond 2017
15. Pharma Boardroom (2016): Made in Puerto Rico
16. Pharmaceutical Technology (2011): Bristol-Myers Squibb, Puerto Rico
17. PharmExec (2016): Country Report: Puerto Rico
18. AbbVie (2017): Prescribing Information: Depakote
19. U.S. FDA (2016): Approval Package for Eliquis
20. Janssen (2017): Prescribing Information: Elmiron
21. European Medicines Agency (2014): Summary of product characteristics: Entyvio
22. News Is My Business (2013): Lilly to invest $200M in Puerto Rico insulin production
23. Almatica Pharma (2017): Medication guide: Fluoxetine
24. Baxter International (2008): Baxter Annual Report 2008, p. 19
25. in-Pharma Technologist (2017): Depomed warns of Nucynta ER delays citing damage to Puerto Rico CMO
26. Pharmaceutical Technology (2010): Eli Lilly Humalog manufacturing facility, Carolina, Puerto Rico
27. Chicago Tribune (2015): AbbVie get incentive to expand in Puerto Rico
28. U.S. Dept. of Commerce (2007): FTZ 7 - Request for manufacturing authority, Merck Sharpe & Dohme Quimica de Puerto Rico
29. Actavis (2015): Prescribing information: Jolivette
30. AbbVie (2017): Prescribing information: K-Tab
31. AbbVie (2017): Prescribing information: Kaletra
32. Federal Court of Canada (2016): Janssen v. Teva; Public judgment and reasons
33. News Is My Business (2017): Neolpharma Group to invest #35M in Caguas expansion
34. Fierce Pharma (2017): Shortages of drugs and saline reported as Puerto Rico hurricane damage lingers
35. AbbVie (2016): Prescribing Information: Niaspan
36. U.S. FDA (2011): Approval letter: Nulojix
37. U.S FDA (2014): Approval letter: Opdivo
38. Janssen (2017): Prescribing Information: Ortho Micronor
39. Janssen (2017): Prescribing Information: Ortho Tri-Cyclen
40. Janssen (2015): Prescribing Information: Ortho-Cyclen
41. Fierce Pharma (2017): EMA gives nod to Janssen for continuous manufacturing of HIV drug
42. Lawyers and Settlements (2016): Propecia manufacturer hit with citations while Propecia impotence lawsuits continue
43. U.S. FDA (2015): Prescribing Information: Razadyne
44. Janssen (2008): Prescribing Information: Regranex
45. SSR (2017): Reliance on Puerto Rico manufacturing, by major pharmaceutical firm
46. GlaxoSmithKline (2012): Prescribing Information: Rescriptor
47. AbbVie (2013): Prescribing Information: Simcor
48. Janssen (2015): Prescribing Information: Sporanox
49. New Zealand Medicines and Medical Devices Safety Authority (2016): Product detail: Strattera
50. Almatica (2016): Prescribing Information: Tenoretic
51.Janssen (2014): Prescribing Information: Terazol 7
52. Watson (2010): Prescribing Information: Terconazole 0.8%
53. Janssen (2014): Prescribing Information: Topamax
54. AbbVie (2016): Prescribing Information: Trilipix
55. Janssen (2017): Prescribing Information: Tylenol With Codeine
56. Janssen (2017): Prescribing Information: Ultracet
57. Janssen (2017): Prescribing Information: Ultram
NOTES:
1. The company declined an invitation by Insightus to confirm or deny the Puerto Rico origin of this drug.
 
2. A company spokesperson confirmed the Puerto Rico origin of this drug.
 
3. Our research did not uncover evidence of the manufacture of this drug in Puerto Rico, but a company spokesperson volunteered that information to Insightus.
 
4. In response to our invitation to confirm or deny the Puerto Rican origin of Entyvio, a Takeda spokesperson stated "we have no Takeda-owned or operated manufacturing operations or warehousing on the island." When presented with evidence (Reference 21) that Entyvio is manufactured for Takeda by AbbVie in Barceloneta, PR, the spokesperson offered no further comment. According to a recent report, "Analysts have projected blockbuster-level sales for Entyvio by 2020, and Takeda sees it hitting at least twice that. In the company's 2015 year-end financial presentation, Takeda wrote that Entyvio is "on the way to over $2 billion in peak sales" and reported that Entyvio's third quarter sales made it the company's No. 4 selling drug."

 

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