FDA Calls for Top-Down Commitment to Quality

She showed that the Agency is serious about addressing some of the issues that the FDA's Center for Drug Evaluation and Research (CDER) director Janet Woodcock and FDA economist Marta Wosinska brought up in their 2012 article in Clinical Pharmacology and Therapeutics.

Quality will be a top priority at the FDA, said Hamburg, and CDER will be creating a new Office of Pharmaceutical Quality to mobilize resources to “improve consistency and regulatory certainty across the drug quality review, with the end goal of patient safety first and foremost.”

“We must have systems in place that are capable of continual quality surveillance,” she said, emphasizing that new requirements were not needed, just monitoring compliance with existing ones.

Generics currently account for 85 percent of the medicine prescribed in the US, she noted. "Year in and year out, we say much about safety and efficacy. But without product quality, none of us can feel confident that the product will be either safe or effective… and, unfortunately, we’ve seen far too many quality lapses throughout the pharmaceutical industry over the past few years."

Hamburg emphasized the fact that commitment to quality must come from the top down, from the CEO to the line operator. “The industry must build robust quality and risk management systems into all levels of its operations.”

She recalled the early days of the generic drugs industry, and how important it was for manufacturers to gain the public’s trust. “It takes time to build your reputation,” she said, “but, unfortunately, it takes only a few lapses to potentially damage it.”

Dr. Hamburg was clear that both name-brand and generic manufacturers had quality problems, enumerating some of the actual issues (e.g., glass contamination, leaking IV bags, endotoxin contamination). “These are not the norm, but they are warning signals that we can and must do more.”

She connected quality problems to current drug shortages, which have increased five-fold over the past seven years.

The Agency has asked the public to contribute ideas on how to solve the quality and supply dilemma. To access a written transcript of her speech, click here.

There is no doubt that both name-brand and generics manufacturers have had their share of lapses over the past few years. But generics are extremely lean with thin margins. Could that lead to sanctioned shortcut-taking (on a more widespread level than what some of you have already pointed to in pharma in general)?

Some prickly areas for generics:

• API loading can be highly variable, although the FDA is OK with that. (After all, it’s only something we ingest, not something where consistency is really important, like wall paint.) For an "oldie but goodie" interview with the FDA's Gary Buehler on bioequivalency issues, click here.
  
  
• Less attention may be paid to quality management systems overall, and the individual links in API supply chains.
  
  
• There may be less consideration of consistency in blending, granulating, and tableting -- or close monitoring of amorphous vs. crystalline forms of API. As Emil Ciurczak notes, crystallinity affects drug uptake and peak blood levels, especially in poorly dissolved or absorbed APIs.
  
  
• With bioequivalents (already established in many countries), there may be questions of whether they were tested in clinics or via USP monograph comparisons in the lab, according to Ciurczak -- not to mention the verification that data were submitted to both the EMA and the FDA.

It was important to hear an industry leader emphasize product quality. Dr. Hamburg’s speech was long overdue, and an important reminder of priorities: public safety and health. As she reminded her audience, “At the end of the day, the major responsibility is not on FDA but on industry.”