When it comes to safe and reliable biological medicines, manufacturing matters

Managed care and hospital decision-makers should consider that biological drugs are different from traditional drugs in terms of their complexity and there is potential for problems to arise when manufacturing is not strictly controlled. Furthermore, biological medicines are more difficult to characterize, produce, and reproduce than most traditional pharmaceuticals. This, in turn, can affect the medicine’s quality, safety, or efficacy, and can ultimately impact the reliability of supply, according to a presentation at the Hematology/Oncology Pharmacy Association’s annual conference in Los Angeles, in March.

“A small change in the quality of the raw materials, temperature, or pH may modify the purity or potency of a biological medicine in an unexpected manner,” presenter John Petricciani, MD, former head of the FDA Office of Biologics, told Formulary.

In the case of shortages of sterile injectables, the main reason for the shortages are related to problems in quality control in manufacturing, according to Dr Petricciani. “Drug shortages can create significant public health concerns, as they may delay or deny needed care for patients when they involve drugs used to treat grievous illness, fight infectious diseases, or address other serious medical conditions,” he said.

According to FDA, there have been more than 160 biologic recalls related to issues with product quality, labeling, packaging, and distribution since 2004. However, shortages of biological medicines have been rare, despite manufacturing challenges. Currently there are 10 agents included on FDA’s Biologic Products Shortage list: 6 vaccines, 2 diagnostics, 1 antivenom, and 1 immune globulin. By contrast, more than 100 conventional products are listed on FDA’s Drug Shortage Index, including 82 sterile injectables.

“Overall, the biotech industry has a large pool of scientific expertise and technical experience, both of which may contribute to a very good track record in manufacturing performance,” Dr Petricciani said. “Along with that has been investment in manufacturing infrastructure and quality systems, as well as a willingness to go above and beyond regulatory standards.”

According to an American Hospital Association survey, which collected responses from 820 community hospitals, the problem of drug shortages has been so prominent that almost all hospitals (99.5%) experienced at least 1 drug shortage in the previous 6 months. What’s even more revealing is the fact that 87% of hospitals are coping with the problem on a very frequent basis, and the shortages involved multiple drugs in more than 90% of the hospitals.

These drug shortages have had a direct impact on patients by causing: delayed treatment (20%), failure to get the recommended treatment (10%), and even adverse outcomes in a small number of cases (3%). In addition, drug costs increased significantly, drug rationing was required, and tensions arose among hospital administrators, medical staff, and pharmacists because of these shortages.

However, it’s not just patients who are impacted by drug shortages. A survey from American Society of Health System Pharmacists shows that pharmacists were spending about 9 hours per week trying to manage the problem.

The problem of drug shortages is a growing concern in the United States. According to the U.S. Department of Health & Human Services, the problem of drug shortages has been growing in the United States, with a 3-fold increase in the total number of drug shortages during the 6-year period 2005 to 2010. Additionally, the number involving sterile injectables accounted for about 80% of the drug shortages in 2010 and 2011.

“Healthcare professionals have a responsibility to know what medicines they are purchasing and prescribing and need to better understand that manufacturing matters,” Dr Petricciani said. “If manufacturers of biological medicines see that prescribers and payers are demanding excellence in manufacturing, they may realize that their track record and reputation in this arena are more important than ever. This push could help ensure that potential problems remain very rare, even as biological agents become more common and accessible as treatment options. Ultimately, it is in the interest of patients, doctors, and the biopharmaceutical industry to follow regulatory guidance and best practices. Doing so minimizes the chances for problems, and helps to ensure that these new medicines will be available without interruption.”

Even organizations with significant expertise and manufacturing experience can face hurdles in dealing with the inherent complexity of biological medicine. “Maintaining a consistent supply of safe and effective biological medicines requires expert staff, advanced science, and sophisticated technology throughout the manufacturing process and supply chain. It also requires high standards for compliance with regulatory requirements and an organizational culture of quality,” Dr Petricciani said.

In the United States, FDA sets manufacturing requirements, licenses only those companies that can meet these requirements, and maintains a broad inspection program to safeguard the drug supply. “Compliance with regulations is among the most important steps that manufacturers can take to help ensure the quality of their biological medicines,” he said. “Physicians should consider asking about companies’ regulatory compliance history when deciding which medicine to prescribe.” 

A new educational initiative, Manufacturing Matters for Biological Medicines, is aimed at providing information about the manufacturing process for biological medicines and how the process can impact product quality and supply. For more information, visit www.buildingbiologics.com.