HNC Memo on Parenteral Nutrition Shortages
Parenteral nutrition (PN), otherwise known as intravenous (IV) nutrition, is provided to patients who are unable to eat or receive alternative methods of nutrition (i.e. enteral nutrition). PN solutions contain a unique combination of proteins, carbohydrates, fats, electrolytes, vitamins, and minerals to meet the patient’s specific nutritional needs. The United States has, for some time, been faced with a drastic parenteral nutrition drug shortage. According to the American Society for Parenteral and Enteral Nutrition (ASPEN), “almost 75% of active drug shortages are sterile injectables, which include PN components.” This poses a serious problem for patients who require PN either at the hospital or in their homes. Furthermore, healthcare facilities are forced to ration or reduce the use of these products and choose between patients in need, resulting in disrupted patient care and poor patient outcomes.
The Shortage Problem
In addition to the complexities with PN Medicare reimbursement that hinder some patients’ access to PN, there is a consistent shortage of components (such as amino acids, vitamins, electrolytes, zinc) needed to provide parenteral nutrition to all who need them in the U.S. These are specifically formulated nutrition solutions and may contain 40 or more individual ingredients, of which multiple components may simultaneously be in limited supply. There are several reasons the U.S. is in a constant ingredient shortage. For one, there are a small number of PN manufacturers in the U.S., not nearly enough manufacturers to meet the full U.S. market need. Until there are more manufacturers entering the PN market, the burden of producing enough solutions to meet U.S. need will fall on three companies. Additionally, as many of the primary PN manufacturers are based outside of the U.S., they are faced with redundant and time-consuming regulations from U.S. agencies when attempting to import PN products. PN solutions are regulated similarly to drugs and not as a nutrient. PN is not marketed, distributed or utilized similar to that of a drug and these solutions supply critical nutrition to those patients with the most complex nutritional needs who might be suffering medical diseases or conditions and/or malnutrition. Researching, formulating, and distributing these specialty products in the U.S. is expensive. When combined with additional barriers to get products in from overseas, many new companies do not have an incentive to enter the PN market.
Moreover, specific U.S. mandates require PN manufacturers to go through additional, extensive clinical trials on U.S. soil for certain products. Many of the clinical trials for these solutions are conducted overseas and have been on the market in Europe and in other countries for decades. These additional clinical trials, that mimic that of drug trials, prevents these well-established nutrients from entering the U.S. in a timely fashion. Additionally, there is less incentive to research and innovate, given it will be increasingly costly to bring the product to the U.S. Patient access should remain the top priority for those regulating PN solutions, supplies, and equipment.
The regulatory agencies are also under pressure to sort through the backlog of pending drug approvals. The agencies are paying particular attention to drugs deemed as “lifesaving” or those in which the shortage has garnered lots of public attention. PN solutions often fall into the background of the drug shortage debate despite these products saving the lives of many patients each day. PN gains most of its public attention for providing lifesaving nutrients to infants in the neonatal intensive care unit (NICU). These products also deliver nutrients to older adults who struggle to stay well-nourished and may suffer from complex disorders or medical conditions while in nursing homes, long-term care facilities, or other healthcare settings. We urge the U.S. Food and Drug Administration (FDA) to treat PN products with the same furor as they do with drugs, as these are also saving the lives of infants, adults, and older adults each day. Below, we discuss ways in which the FDA can partner with HNC and other stakeholders in the PN community to eliminate the elemental shortage in the U.S.
Potential Solutions for PN Shortage
HNC encourages consistent communication between FDA and relevant PN stakeholders to ensure all parties are notified when a shortage is identified and how the shortage will be remedied in the short term and long term. This would involve ramping up production and/or temporarily allowing products into the U.S. at a higher rate than previously done. If there is not increased communication between the parties, shortages can exacerbate and elements can be turned away for approvals due to unresolved questions or information. For example, when a natural disaster hit one of the three PN manufacturers’ production facilities in Puerto Rico, production of certain PN product and equipment grinded to a halt. During this time, the shortage was dire; healthcare providers struggled to treat patients and were forced to ration and dilute PN solutions to meet patient needs. There should be no situation in which healthcare professionals should have to choose which patients receive their specialized nutrition. There was a lack of communication and understanding between the parties in terms of the degree of severity of the products lost, which caused a delay in notifying other manufacturers to ramp up their production to meet the patient need. Increased communication and cooperation between FDA and stakeholders must occur on a regular basis to ensure status updates on PN production are received and processed and can be evaluated by the Agency to determine if there will be a shortage and how long it will last.
An improvement in the regulatory process for approving certain PN related medications for importation into the country is also necessary to improving the PN shortage long-term. We are encouraged that Commissioner Scott Gottlieb has made improving and streamlining the drug approval process a priority for FDA; we hope this priority continues under the new acting Commissioner Sharpless. We have seen FDA change their approval processes and expedite certain approvals due to a shortage. However, as PN is considered a nutrition support therapy and not a drug, they are often not treated with as much urgency by FDA as certain drugs despite their life saving nature. Utilizing PN is not a choice for patients but a necessity to stay alive and nourished due to a medical condition or disease, intensive surgery, or other situation requiring intravenous nutrition. FDA must continue to work to streamline the approval process for components that make up PN solutions due to the specially formulated nature of these solutions and how they are administered to patients.
Additionally, HNC recommends FDA regulate PN solutions as nutrients instead of drugs. The purpose of these solutions is to provide critical nutrition to patients intravenously as they cannot maintain a healthy nutritional status otherwise. PN clinical trials are not conducted with the intent that these solutions will act like or be marketed as drugs, yet they must follow protocols similar to that of drugs. Not only is the process of adhering to drug protocols and regulations expensive for companies to undergo, but PN therapies are meant to provide nutritional support for patients and not to alter a biological pathway, nor cure a disease or condition. By continuing to regulate PN similar to a drug rather than as nutrition support therapy, FDA is disincentivizing companies from entering the PN market due to the rigorous regulations around manufacturing PN solutions. In addition, these products are formulated as nutrition support therapies and have a significantly different market price and audience than drugs. Therefore, if companies are forced to comply fully with the requirements similar to that of developing a new drug but the price point of the final product is closer to that of a nutrition support therapy, it is not appealing to enter the PN market in the first place. As less manufacturers enter the PN market, competition dwindles, shortages occur frequently, and patients can lack access to essential PN.
Furthermore, the regulatory agencies must improve their process for screening and approving international facilities, which would expand the market of viable manufacturers who can distribute PN products in the U.S. Outdated import policies have created limited production capacities in the U.S., complex compliance issues, and additional barriers to entry for many manufacturers with the capability to formulate PN products. There are countless companies that produce these lifesaving therapies, but are barred from being distributed in the United States because they have not been certified by the FDA to produce products for direct distribution in the U.S. Many of these products have been on the market for decades in Europe and have undergone several clinical trials to determine their safety and effectiveness. We are encouraged that FDA has implemented new policies to review these facilities to improve streamlining safe products into the U.S., but there is still room for improvement.
Although we recognize the appeal of having manufacturers based and producing these products within the U.S., many established PN manufacturers originated and remain based in Europe. As manufacturers have yet to increase within the U.S., there needs to be acceptance of this European-made product in the U.S. market to ensure patients maintain access to PN. Improvements in the overseas facility inspections, drug approval process, and communication among PN stakeholders are steps towards solving the PN shortage. It will also lead to increased competition, which will lead to expanded market and increased patient choice and access, benefiting both healthcare providers and their patients. We are confident we can work with FDA to maintain the U.S.’ integrity for high quality imports, while improving the process that brings PN solutions into this country.