Sharfstein used the Congressional hearing to "send the message" to manufacturers that FDA is significantly strengthening its
oversight and criminal enforcement. Deborah Autor, director of compliance at the Center for Drug Evaluation and Research (CDER),
said FDA's criminal investigative unit is examining whether J&J is criminally liable for McNeil's phantom recall and for the
company's slow response to FDA inspection citations. Sharfstein added that FDA plans to consider corporate structure when
enforcing the law, which would involve applying its experience at one facility to other operations run by the same company.
Companies need strong compliance programs in place, he said, noting that FDA prefers to see industry adhere to the rules than
to take enforcement action.
Manufacturers of older drug products in outdated facilities should take this advice seriously and modernize operations before
difficulties arise. Quality control problems that emerged at Genzyme last year led to a plant shutdown, dangerous shortages
in important treatments for rare diseases, and a contentious fight for control of the company. Genzyme CEO Henri Termeer almost
lost his job and had to add new members to his board of directors in June to placate investor Carl Icahn. Genzyme had already
been hit with FDA citations for GMP violations when the company discovered a virus in the bioreactors of its Allston Landing
facility last year, just when it was trying to scale up production to meet growing demand for new and existing therapies.
Additional fill-and-finish problems emerged later. The plant, which is more than 15 years old, had to close for several months
to undergo a $9-million decontamination process.
In addition to losing millions in revenue, Genzyme also has to finance a $150-million program to renovate and bring the facility
into compliance. Moreover, the company had to pay $175 million in fines for GMP violations and to accept an FDA consent decree
that requires third-party monitoring of operations to ensure that new production complies with regulations. Potentially more
damaging, FDA sped up its review and approval of competing therapies from two other firms to alleviate product shortages,
a move that may limit Genzyme's ability to regain market share.
All signs point to continued FDA emphasis on speedy and efficient company responses to citations of product quality violations.
In June, FDA's Center for Biologics Evaluation and Research (CBER) admonished Australian vaccine-maker CSL for failing to
fully correct manufacturing deficiencies found during an April 2010 inspection. In an untitled letter, FDA cited inadequate
testing of containers and closures as well as CSL's failure to investigate batch discrepancies or to establish testing procedures
to ensure conformity to standards. Even though this FDA communiqué was not an official Warning Letter, Mary Malarkey, director
of CBER's Office of Compliance and Biologics Quality, called for a meeting with CSL CEO Brian McNamee and his senior management
to discuss how the company will develop a corrective action plan to address its violations and to ensure the production of
safe, pure, and potent vaccines.
Although some members of Congress initially chastised FDA for failing to keep McNeil's adulterated children's medications
off the market, the agency came out looking pretty tough from the May Oversight Committee hearing. FDA was able to document
multiple efforts to compel McNeil compliance with quality standards, including frequent inspections of company facilities,
numerous reports and Warning Letters, and the meeting with corporate executives when previous efforts failed to produce results.
Sharfstein also made the case for stronger FDA regulatory and recall authority. The J&J recall was voluntary because, under
current policy, it's very difficult for FDA to compel a company to pull products from the market. Although most manufacturers
comply with FDA recall requests, there is often is a lag between when the company becomes aware of adverse events and quality
problems, and when that information reaches regulators. Several members of the House Committee indicated support for strengthening
FDA's powers, as did Rep. Rosa DeLauro (D-CT), chair of the House Appropriations subcommittee that oversees FDA's annual budget.
DeLauro sent a letter to Commissioner Hamburg complaining of McNeil's "reckless behavior" in disregarding GMPs at its facilities
and in marketing inconsistent and noncompliant cold medications for children. The Congresswoman suggested that FDA might benefit
from added authority to recall drugs and to require company monitoring of consumer complaints, and from more resources to
conduct more frequent inspections.
The need for multiple inspections of J&J plants over the past few years has raised the issue of whether manufacturers that
require repeat site audits should pay additional fees for the extra services. Reinspection user fees have been on FDA's wish
list for several years as a way to boost revenue. Some policymakers have proposed that FDA collect fees for all field inspections
as is done in Europe and many other countries. Such fees are not likely to be approved in the US, but asking violators to
pay more for reinspections and secondary reviews may gain support.
One likely possibility is for FDA to require more extensive pharmaceutical company monitoring of suppliers and contract manufacturers.
FDA holds the marketer of a finished drug responsible for ensuring that outside contractors comply with GMPs, but much of
that oversight currently involves review of data and reports on quality-control systems and product attributes. Now, the agency
is considering asking pharmaceutical companies to conduct on-site audits to confirm that contract manufacturers comply with
rules and standards.
As these options are being debated, the legal issues exposed by FDA attorneys could have a broad impact on industry. Pharmaceutical
companies are watching to see whether the agency brings criminal charges against J&J and McNeil, as well as enforcement action
under its "responsible corporate officer" doctrine. The latter could involve individual misdemeanor charges, which can carry
stiff fines and even prison terms.
Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634, email@example.com