The Role of Regulatory Affairs in Drug Compliance


Pharmaceutical companies face significant challenges in developing new, innovative medicines:

• Pharma R&D investment has increased 62 percent in the last decade, but the number of new drugs approved is 22 percent lower than the previous decade.
• The failure rate in phase III, the most expensive part of pharma R&D, is 40 percent.
• A Datamonitor study of 346 NDAs found that 42 percent of submissions received a complete response letter, resulting in a median delay in approval of 13 months.
• Cost cutting and the retirement of baby boomers with deep expertise have resulted in a shortage of in-house experts with the savvy to drive innovation and gain regulatory approvals.

External consultants can be a competent, efficient and unbiased means to address many of these challenges. Regulatory affairs, a key pharma function where most learning and expertise are gained on the job, is a prominent example. Few universities offer degrees in regulatory affairs, and an academic setting does not provide experience working directly with regulatory authorities on individual molecules. Actual work on drugs reveals nuanced differences by division, therapeutic area, drug class, and even FDA lead reviewer. This level of understanding is often critical in gaining approvals in a timely manner with an optimal prescribing label.

What aspects of development and submission are most advantageous for regulatory outsourcing?

In theory, companies can outsource almost any job function given enough planning and effective execution. Traditionally, companies outsource to gain capacity or competency. For example. a Regulatory Affairs CMC department has more work to do than people to do it, or a regulatory authority requires a response about a significant new adverse event in a therapeutic area that is not a strength for the company.

Another approach involves stage gate reviews and simulations. The beginning and end of each drug development phase involve critical assessments of trial results, plans for future development, plans for meetings with regulatory authorities, preparation of documents, and ultimately submissions. Expert consultants may help evaluate NDAs and BLAs before filing, prepare for advisory committee meetings, and hold mock advisory committees sessions. This work includes identification of gaps or suboptimal presentation of drug development results, recommendations on improvements, risk assessments, and mitigation strategies. For advisory committees, consultants may help prepare materials, coach clients on how to address issues, and serve as a mock advisory committee panel member to help the client practice. At the actual advisory committee meeting, external experts may act as coaches to the client company or participate directly.

Stage gate reviews and simulations often involve a team of external experts, such as regulatory strategy, medical, CMC, statistics, and pharmacovigilance. Although the expert consultants may find major deficiencies, more commonly they identify specific gaps and propose feasible approaches to address them. These stage gate reviews and simulations can have a significant impact on critical components of the developing regulatory approach.

How do you hire the right external experts?

Sources for consultants in all types of work include individual LLCs and large and small consulting companies. For stage gate reviews and simulations, finding a team who can meet all of the needs and work together effectively can add additional challenges. If the need is for submission work, keep in mind that many consultants have solid pharma career experience over one or two decades, but due to the high failure rate of drugs in early phases, they have not taken an NDA or BLA over the finish line. Knowing how to ensure a submission is fileable, reviewable, and approvable requires specific experience, not just extrapolation from early phase work. In addition, gaining approval for a new indication for a marketed product has some similarities to a new NDA or BLA, but is less complex and has fewer cross-functional challenges. In short, nothing substitutes for successful NDA and BLA experience. A seasoned regulatory consultant fortunate enough to have carried high potential molecules over the approval line will typically experience two to three approvals over a couple of decades, and former regulatory affairs directors and VPs with more.

In addition, stage gate review teams are often cross-functional, e.g. veteran pharmaceutical professionals from regulatory affairs, legal, medical, pre-clinical, pharmacology, pharmacovigilance, and manufacturing. These consultant teams must be able to work together.

How do you manage consultants for success?

Once a company has located and contracted with the right consulting talent, the challenge is how to manage effectively and use the consultant’s time efficiently. Under all outsourcing models, at least one central client company contact should be assigned to answer questions about work scope and provide resources such as access to data sets and reports. Most commonly, there is an in-house subject matter lead supported by an assistant for logistics. For teams of consultants, the need is for a client company project manager charged with planning, organizing and providing resources for the consultant team and linking each consultant to an in-house subject matter expert. If the consultants are hired from one outside consulting organization, then having an equivalent project management professional at the consulting company to work with the experts is necessary. All types of project management help ensure that the work will proceed on schedule and the consultants’ time will be used to do content work, not floundering in administrative and logistical issues. Face-to-face kick off meetings and end-of-project meetings are usually worth the expense. A great deal of other work can be done remotely. Simulations are typically conducted face-to-face.

Client companies should request feedback on the performance of the consultants from the project managers and in-house subject matter experts on a frequent basis and provide that feedback to the consultants or consulting organization. Rapid discontinuation of any consultant who is not getting the job done is in the best interest of all parties.

Finding seasoned, impartial consultants and setting up effective infrastructure will keep the work focused and productive, and the payoff in on-time approvals with optimal labels is worth it.