FDA: Drug Shortages Decline but Persist

The Food and Drug Administration has prevented at least 50 drug shortages so far this year, mainly as a result of manufacturers giving the agency early warning of impending problems, Dr. Sandra Kweder announced June 4.

Shortages persist, however, especially for key oncology therapies, according to Dr. Kweder, deputy director of the FDA Office of New Drugs, and oncologists who participated in a press briefing at the annual meeting of the American Society of Clinical Oncologists (ASCO) in Chicago.

Since the White House issued an executive order last Oct. 31 encouraging manufacturers to give the FDA "early notification" of potential disruptions, the agency, working with physicians, manufacturers, pharmacists, and others, has been able to avoid more than 150 drug shortages, Dr. Kweder said.

"Early notification by manufacturers of when they are having production difficulties makes a huge difference in our ability to prevent the public from bearing the burden of drug shortages," she said.

"The good news is that the frequency of drug shortages has begun to decline," agreed Dr. Richard Schilsky, chair of the ASCO Government Relations Committee and chief of the hematology/oncology section at the University of Chicago.

However, unpredictability still exists, which means that oncologists are "never sure when a generic is going to go out of supply," said Dr. Schilsky. "That creates a tremendous amount of uncertainty and anxiety for our patients."

Dr. Michael P. Link, ASCO president, said that several commonly used chemotherapy agents remain in short supply, including fluorouracil, nitrogen mustard, and paclitaxel. In addition, although a methotrexate shortage has been addressed, there is now a shortage of sodium bicarbonate, which is needed to give high-dose injections of the drug, said Dr. Link, chief of pediatric hematology/oncology at the Lucile Packard Children’s Hospital at Stanford (Calif.) University.

Shortages often lead to delays in treatment or less-than-desirable substitutions, said Dr. W. Charles Penley, the incoming ASCO Government Relations Committee chair. His practice – Tennessee Oncology in Nashville – is large enough that it generally has been able to locate products in short supply through its purchasing groups. But a leucovorin shortage last summer led him to switch some patients to oral capecitabine (Xeloda).

That drug is more expensive and is not tolerated well by some patients, he said.

And even that product almost went into short supply, Dr. Kweder said. There were some quality control issues that led the agency to temporarily import capecitabine while the manufacturer, Roche, fixed the problem, she said.

Manufacturing and quality control – especially for generic sterile injectables – continue to be behind many shortages, Dr. Kweder said. Sterility has been a consistent problem, with many products found to contain glass particles or metal shavings. She described a zero tolerance policy for such issues with injectables. "No patient should ever be exposed to risks of those sorts," she said.

When asked why generic injectables seem to be having more frequent quality control issues, Dr. Kweder said that the requirements and rules for good manufacturing have not changed over the years, but that the explosion of generic products in the last decade has perhaps put more pressure on manufacturers.

Dr. Schilsky and Dr. Penley said they were hopeful that legislation creating user fees for generic drugmakers would help address the shortage issue. Bills to reauthorize all FDA user fee programs have passed both the House and the Senate; differences are being hashed out in conference right now. The generic user fee – expected to add $1.5 billion to the FDA budget over the next few years – is expected to be retained. Experts expect the president to sign the final bill, said Dr. Schilsky.

The additional funds would give the FDA the ability to cut generic drug review times from the current 24-30 months to about 6-10 months, Dr. Kweder said.

It also would give the agency more resources to eradicate a current backlog of reviews and move more quickly on manufacturing issues, she said.

The legislation includes several additional items on ASCO’s wish list, including a requirement that manufacturers give the FDA early warning of impending shortages. But it does not include any penalties for noncompliance, said Dr. Schilsky.

The Food and Drug Administration has prevented at least 50 drug shortages so far this year, mainly as a result of manufacturers giving the agency early warning of impending problems, Dr. Sandra Kweder announced June 4.

Shortages persist, however, especially for key oncology therapies, according to Dr. Kweder, deputy director of the FDA Office of New Drugs, and oncologists who participated in a press briefing at the annual meeting of the American Society of Clinical Oncologists (ASCO) in Chicago.

Since the White House issued an executive order last Oct. 31 encouraging manufacturers to give the FDA "early notification" of potential disruptions, the agency, working with physicians, manufacturers, pharmacists, and others, has been able to avoid more than 150 drug shortages, Dr. Kweder said.

"Early notification by manufacturers of when they are having production difficulties makes a huge difference in our ability to prevent the public from bearing the burden of drug shortages," she said.

"The good news is that the frequency of drug shortages has begun to decline," agreed Dr. Richard Schilsky, chair of the ASCO Government Relations Committee and chief of the hematology/oncology section at the University of Chicago.

However, unpredictability still exists, which means that oncologists are "never sure when a generic is going to go out of supply," said Dr. Schilsky. "That creates a tremendous amount of uncertainty and anxiety for our patients."

Dr. Michael P. Link, ASCO president, said that several commonly used chemotherapy agents remain in short supply, including fluorouracil, nitrogen mustard, and paclitaxel. In addition, although a methotrexate shortage has been addressed, there is now a shortage of sodium bicarbonate, which is needed to give high-dose injections of the drug, said Dr. Link, chief of pediatric hematology/oncology at the Lucile Packard Children’s Hospital at Stanford (Calif.) University.

Shortages often lead to delays in treatment or less-than-desirable substitutions, said Dr. W. Charles Penley, the incoming ASCO Government Relations Committee chair. His practice – Tennessee Oncology in Nashville – is large enough that it generally has been able to locate products in short supply through its purchasing groups. But a leucovorin shortage last summer led him to switch some patients to oral capecitabine (Xeloda).

That drug is more expensive and is not tolerated well by some patients, he said.

And even that product almost went into short supply, Dr. Kweder said. There were some quality control issues that led the agency to temporarily import capecitabine while the manufacturer, Roche, fixed the problem, she said.

Manufacturing and quality control – especially for generic sterile injectables – continue to be behind many shortages, Dr. Kweder said. Sterility has been a consistent problem, with many products found to contain glass particles or metal shavings. She described a zero tolerance policy for such issues with injectables. "No patient should ever be exposed to risks of those sorts," she said.

When asked why generic injectables seem to be having more frequent quality control issues, Dr. Kweder said that the requirements and rules for good manufacturing have not changed over the years, but that the explosion of generic products in the last decade has perhaps put more pressure on manufacturers.

Dr. Schilsky and Dr. Penley said they were hopeful that legislation creating user fees for generic drugmakers would help address the shortage issue. Bills to reauthorize all FDA user fee programs have passed both the House and the Senate; differences are being hashed out in conference right now. The generic user fee – expected to add $1.5 billion to the FDA budget over the next few years – is expected to be retained. Experts expect the president to sign the final bill, said Dr. Schilsky.

The additional funds would give the FDA the ability to cut generic drug review times from the current 24-30 months to about 6-10 months, Dr. Kweder said.

It also would give the agency more resources to eradicate a current backlog of reviews and move more quickly on manufacturing issues, she said.

The legislation includes several additional items on ASCO’s wish list, including a requirement that manufacturers give the FDA early warning of impending shortages. But it does not include any penalties for noncompliance, said Dr. Schilsky.

The Food and Drug Administration has prevented at least 50 drug shortages so far this year, mainly as a result of manufacturers giving the agency early warning of impending problems, Dr. Sandra Kweder announced June 4.

Shortages persist, however, especially for key oncology therapies, according to Dr. Kweder, deputy director of the FDA Office of New Drugs, and oncologists who participated in a press briefing at the annual meeting of the American Society of Clinical Oncologists (ASCO) in Chicago.

Since the White House issued an executive order last Oct. 31 encouraging manufacturers to give the FDA "early notification" of potential disruptions, the agency, working with physicians, manufacturers, pharmacists, and others, has been able to avoid more than 150 drug shortages, Dr. Kweder said.

"Early notification by manufacturers of when they are having production difficulties makes a huge difference in our ability to prevent the public from bearing the burden of drug shortages," she said.

"The good news is that the frequency of drug shortages has begun to decline," agreed Dr. Richard Schilsky, chair of the ASCO Government Relations Committee and chief of the hematology/oncology section at the University of Chicago.

However, unpredictability still exists, which means that oncologists are "never sure when a generic is going to go out of supply," said Dr. Schilsky. "That creates a tremendous amount of uncertainty and anxiety for our patients."

Dr. Michael P. Link, ASCO president, said that several commonly used chemotherapy agents remain in short supply, including fluorouracil, nitrogen mustard, and paclitaxel. In addition, although a methotrexate shortage has been addressed, there is now a shortage of sodium bicarbonate, which is needed to give high-dose injections of the drug, said Dr. Link, chief of pediatric hematology/oncology at the Lucile Packard Children’s Hospital at Stanford (Calif.) University.

Shortages often lead to delays in treatment or less-than-desirable substitutions, said Dr. W. Charles Penley, the incoming ASCO Government Relations Committee chair. His practice – Tennessee Oncology in Nashville – is large enough that it generally has been able to locate products in short supply through its purchasing groups. But a leucovorin shortage last summer led him to switch some patients to oral capecitabine (Xeloda).

That drug is more expensive and is not tolerated well by some patients, he said.

And even that product almost went into short supply, Dr. Kweder said. There were some quality control issues that led the agency to temporarily import capecitabine while the manufacturer, Roche, fixed the problem, she said.

Manufacturing and quality control – especially for generic sterile injectables – continue to be behind many shortages, Dr. Kweder said. Sterility has been a consistent problem, with many products found to contain glass particles or metal shavings. She described a zero tolerance policy for such issues with injectables. "No patient should ever be exposed to risks of those sorts," she said.

When asked why generic injectables seem to be having more frequent quality control issues, Dr. Kweder said that the requirements and rules for good manufacturing have not changed over the years, but that the explosion of generic products in the last decade has perhaps put more pressure on manufacturers.

Dr. Schilsky and Dr. Penley said they were hopeful that legislation creating user fees for generic drugmakers would help address the shortage issue. Bills to reauthorize all FDA user fee programs have passed both the House and the Senate; differences are being hashed out in conference right now. The generic user fee – expected to add $1.5 billion to the FDA budget over the next few years – is expected to be retained. Experts expect the president to sign the final bill, said Dr. Schilsky.

The additional funds would give the FDA the ability to cut generic drug review times from the current 24-30 months to about 6-10 months, Dr. Kweder said.

It also would give the agency more resources to eradicate a current backlog of reviews and move more quickly on manufacturing issues, she said.

The legislation includes several additional items on ASCO’s wish list, including a requirement that manufacturers give the FDA early warning of impending shortages. But it does not include any penalties for noncompliance, said Dr. Schilsky.