The Center for Drug Evaluation & Research’s announcement of the final approval for a new quality super office (the Office of Pharmaceutical Quality) is a milestone in Center Director Janet Woodcock’s decade-long effort to upgrade FDA’s approach to the regulation of drug quality – and the direct result of a two-year internal bureaucratic process to get the new structure approved and staffed.

FDA announced the official start date for OPQ – January 15 – in an October 16 email to staff. ([A#14141016007]) The new super office has been approved; while many functions are underway already, it technically starts operations (“stands up”) on January 5, 2015. That means it will have taken about 27 months between the announcement of the OPQ plan and the formal completion of the reorganization. Also see "CDER’s New Quality Office Still Awaiting Final Sign Offs" - Pink Sheet, 19 May, 2014.

It has taken a long time to reach formal sign off on the new structure, but that shouldn’t be mistaken for a sign that the change lacks importance. On the contrary, the amount of red tape involved in a restructuring on this scale should signal to industry just how critical a change the CDER director envisions with the move.

The top-line message for industry is that it is time for corporate organizations to assure FDA that they have a structure overseeing quality and interacting with FDA that places those issues at the same level and prominence that the agency has adopted for its quality group.

In other words, the quality organizations within biopharma companies should have similar importance, authority and senior management attention as the new FDA super office.

To reinforce the point about the importance of senior management commitment, Woodcock is remaining in charge of the new office as Acting Director in addition to her role as CDER director. Lawrence Yu, currently acting director of the Office of Pharmaceutical Science, will be the acting deputy director. Also see "FDA’s Woodcock to Head Office of Pharmaceutical Quality; New Details Emerge" - Pink Sheet, 23 December, 2013.

A striking opportunity for industry in the new structure is the chance to work cooperatively with a team of science/technology-oriented CDER staff through the new office on quality issues before those issues develop into compliance issues (policing and legal actions).

The creation of the super office also means that when a situation is referred from within that group to the agency’s compliance arm, it should serve as an even more significant benchmark of problems for the company in question. Effectively, when a situation transfers to FDA compliance staff, that will mean that the opportunity to work with the agency has passed.

FDA’s Objective: Foster “Culture of Quality” At Agency, In Industry

Woodcock’s short-hand for the change that she hopes the new center will help foster within FDA and throughout the biopharma sector is a “culture shift” from a “Culture of Compliance” to a “Culture of Quality.” She has stressed in recent public speeches that this reorganization offers the opportunity for FDA and industry to move from a “traffic-ticket” approach to reviewing manufacturing procedures to a broader assessment of quality issues and upgrades.

CDER Director Woodcock’s Introduction of the Office of Pharmaceutical Quality (OPQ)

OPQ will combine non-enforcement-related drug quality work into one super-office, creating “one quality voice” and improving our oversight of quality throughout the lifecycle of a drug product. This office will provide internal customers with a single drug quality assessment that captures the overall OPQ recommendation on approvability, and OPQ will provide feedback on quality deficiencies earlier in the review cycle.

OPQ’s structure provides for centralized functions for administrative activities, project management, training, quality management systems, and policy. OPQ creates a uniform drug quality program across all sites of manufacture, whether domestic or foreign, and across all drug product areas – new drugs, generic drugs, and over-the-counter drugs.

CDER originally hoped to have the new office approved and ready for final unveiling in September before the start of the new government fiscal year. CDER worked with the Product Quality Research Institute to hold an inaugural joint conference on “Evolving Product Quality” on Sept. 16-17. Woodcock keynoted the event with an address presumably planned to unveil the new organization, but instead serving as a preview or preamble rather than formal launch.

FDA “cannot create a culture of quality” by fiat throughout the industry, Woodcock acknowledged. That is clearly beyond the power of what a regulatory agency can do, the CDER director observed. “What FDA can do is organize our regulatory approach so that we can foster a culture of quality and at the same time do our duty, which is to test and intervene in instances where there is the potential for substandard products being out there.” Woodcock said she recognizes that “this is not just a culture shift for industry but also for FDA.”

Although the FDA/PQRI meeting was not an official unveiling of the new organization, it offered an opportunity for CDER to restate the objectives of its new quality organization, show off some of the new leaders and demonstrate the large number of people at FDA devoted to the new project. (See box.)

FDA had over 100 people at the conference out of a total of about 300. The large industry contingent was also important as a sign of the development of teams within companies that are emerging to interact with the new OPQ.

The investiture of the OPQ super office represents a significant and sustained bureaucratic triumph for Woodcock. To arrive at the structure, she had to extract a number of functions from existing organizations within CDER (primarily chemistry and analytical functions) and to arrive at an agreement with the separate FDA-wide inspectional organization (Office of Regulatory Affairs).

In an announcement of the final approval for the new super office to CDER staff, Woodcock alluded to the reorganization as “being especially complex.”

The negotiations for CDER to get more authority and control over drug inspections were a bigger challenge for Woodcock since it positioned CDER up against a long-entrenched part of FDA’s culture and structure – the inspection force. The first signs of success in moving the control over drug inspections more into the purview of CDER occurred last year, when Commissioner Margaret Hamburg announced a review of the Office of Regulatory Affairs with the goal of organizing around specific product expertise rather than the more traditional regional inspection groups.

Leadership Team and Office Structure Within OPQ

Office of Program and Regulatory Operations (OPRO)

Acting Director: Giuseppe Randazzo
Deputy Director: Michael Smedley

Office of Policy for Pharmaceutical Quality (OPPQ)

Acting Director: Ashley Boam
Acting Deputy Director: Brian Hasselbalch

Office of Biotechnology Products (OBP)

Director: Steve Kozlowski
Deputy Director: Jeffrey C. Baker

Office of New Drug Products (ONDP)

Acting Director: Sarah Pope Miksinski
Deputy Director: Scott Furness

Office of Lifecycle Drug Products (OLDP)

Acting Director: Susan Rosencrance
Acting Deputy Director: Glen Smith

Office of Testing and Research (OTR)

Acting Director: Lucinda (Cindy) Buhse
Deputy Director: (Vacant)

Office of Process and Facilities (OPF)

Acting Director: Christine Moore
Acting Deputy Director: Dave Doleski

Office of Surveillance (OS)

Acting Director: Theresa Mullin
Acting Deputy Director: Russ Wesdyk

Source: Email to CDER staff

Hamburg announced the results of that review October 7, shortly before the final approval of OPQ. The next step on the pharmaceutical side will be the development of a five year “action plan,” due in 12 months.

“Core elements of Action Plans may include increased specialization, de-layered management structures and processes involving ORA and the Centers, jointly developing training programs, new work planning models, strategic enforcement approaches with aligned and updated compliance programs and policy, strategic import approaches, laboratory optimization, and coordination of internal and external communication on the Action Plan to ensure that FDA speaks with one voice on the policies and operations related to the pharmaceuticals program.”

New Template For Inspections Planned For this Year

In her PQRI speech, Woodcock referred a number of times to the change in relations with ORA. She talked about the agreement between CDER and ORA on new approaches going forward – toward “One Quality Voice.” Among the notable changes that Woodcock is seeking in inspections is a new template for inspection reports and observations that allows for more commentary on the general state of a facility – including strengths as well as weaknesses – rather than a list of rote violations.

The “template” approach has been evolving along with the OPQ project; Woodcock initially described the idea as a “report card” on quality to help industry better benchmark its performance.

“We are working with ORA for the templates for inspection. We want to move from a ‘traffic ticket’ approach to an assessment of the state of the facility,” Woodcock said. She predicted that FDA will be implementing the new templates within the year.

“Our new inspectional assessment will include the good things too,” Woodcock said. “We do not just want to know observations; we want to understand how people are doing. You might be doing well in quality management except you are not investing adequately in capital investments and rebuilding and [upgrading] operating equipment.” She said she wants that type of information captured so that FDA has that information available the next time the agency visits.

CDER and ORA are also working on an approach to get inspectors involved in parts of the original drug reviews so that the inspection force will be more knowledgeable about specific products and processes. That is further away, “probably a couple of years.” Woodcock stressed, however, that ORA is “on board on this.” Further, CDER wants ORA to develop a cadre of inspectors who specialize in pharma operations. That will be the core focus of the Program Alignment action plan.

Surveillance and Broad Database on Manufacturing Facilities Is Key Feature

One of the most ambitious projects in the new product quality super office is a broad surveillance function: the Office of Surveillance to be headed by one of Woodcock’s top managers for special projects, Theresa Mullin. Mullin will be Acting Director of the Office of Surveillance in the new super office.

For the past two years, Mullin has been heading the ambitious effort to establish a repeatable, ongoing series of structured meetings to bring patient voices representing different diseases into the new drug FDA review process negotiated as part of PDUFA V. ([A#2014500092])

Woodcock told the mid-September PQRI meeting that CDER was rushing to put the finishing touches on the “1.0” version of the heart of the new surveillance effort – the “Pharmaceutical Platform.” She called the agency’s effort to increase operations on the post-marketing quality side a “bigger challenge” than the coordination of the quality control aspects of premarket review activities for brand and generic drugs within the new super office.

The surveillance project began with an “artisanal,” hand-built inventory of all of the pharmaceutical production facilities that make drug products and components for the US market. Woodcock said that after creating the inventory of facilities, “what we want to attach to that” for each facility “is all the information about that facility.”

“The Pharmaceutical Platform will have all of the products in it,” Woodcock said. It will contain “the inventory of facilities and it will have verified data about them: any EIRs [establishment inspection reports]; field alerts, recalls.” Through the combined information, FDA will be able to get an accurate picture and history on any facility.

The Pharmaceutical Platform also will be our workforce management tool and will incorporate information from the agency’s attempt to work out a system of metrics with the industry for measuring the performance of facilities and benchmarking individual facilities versus the agency norms. Woodcock noted at PQRI that the discussion of developing these metrics over the past two years has already had a salutary impact on industry production and quality control.

Another major organizational innovation within the new super office is an attempt to formalize the relationship between quality review functions for NDAs (handled by the Office of New Drug Products under Acting Director Sarah Pope Miksinski) and subsequent ANDAs and generic drugs (handled by the Office of Lifecycle Drugs under Acting Director Susan Rosencrance).

Woodcock’s decision to integrate the generic drug chemistry reviews into the new office served as one of the earliest indicators of the importance of this reorganization: the decision helped precipitate the departure of Gregory Geba as head of the Office of Generic Drugs, leaving that organization without a permanent director just as the Generic Drug User Fee Act came into effect. Also see "Growing Pains for Generic Drugs: OGD Gains Respect, But Loses Geba" - Pink Sheet, 21 March, 2013.

The identification of the former “generic” chemistry group as the “lifecycle” division also indicates an important emphasis in the evolving quality paradigm. The issues related to “new products” are important, but have nothing to do with the “brand” identity of the sponsor. Similarly, the issues related to older, well established products are not limited to the involvement of a new “generic” supplier.

Woodcock said the organization change is meant to reflect the greater attention that the agency is paying to the “hand-off” and the “accumulated information” on the quality control/manufacturing review functions for new drugs to generics.

“At CDER,” Woodcock told PQRI, “we are changing the way we do premarket review. We are trying to assure that new and generic drugs are held to the same quality standards. We are going to do that through the lifecycle approach to review where we start with the new drug and then the NDA is handed off to the lifecycle group and then we will also review generics against background info on the new drugs.”

Miksinski underscored one of the key issues that she will face as head of “new products” in OPQ in a unique fashion at the PQRI event, inviting Office of Hematology & Oncology Products Director Richard Pazdur to address a breakout workshop. She used that session to highlight the critical need to assure that manufacturing and quality issues are at the forefront of discussions about accelerated development pathways for breakthrough therapies.

The “lifecycle” head, Rosencrance, previously was Acting Deputy Director for generic drug chemistry in the Office of Pharmaceutical Sciences. She has been part of the management effort to bring on a large group of new chemists to handle ANDA reviews as part of the Generic Drug User Fee program and new review targets: 65 chemists were hired in fiscal 2013 and 113 added in the just-ended fiscal 2014.

Importantly, FDA is not yet taken an analogous approach on the biologic product side. Biological and biosimilar manufacturing issues for the therapeutics under CDER’s purview will stay under the management of Office of Biotechnology Products Director Steve Kozlowski, who will continue in that role in the new organization.

CDER Office of Product Quality Ready To Go: New Structure Sends Strong Signal To Industry

More from Manufacturing

More from Compliance