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Nov 02 2011

Project Management for Biotech Companies

In today’s fast paced, high pressure world of drug development there are multiple factors that can and do affect marketing success.  Large organizations understand the value that project management can contribute to a successful project.  The smaller companies tend to lag behind and often do not recognize that project management is not too complex or does not cost too much to fit into their smaller culture.  Project Management should not be considered as only a box of tools but a mindset on how to approach management of a project.  A small company can get huge payback just by incorporating basic project management into their processes.  Simple processes such as developing a project scope, identifying risks, and setting common goals for the project team performance can lead to benefits by shortening timelines, eliminating costly mistakes, and ensuring project success.  A cooperative alliance between a biotech company and a contract research organization (CRO), such as Cato Research, can help bridge any gap that may exist in the company’s experience level and ensure clear communication among all the team members through experienced project management.  Understanding the differences in the team’s work environments will lead to better communication and improve the overall performance.

Drug Development and Project Management:  Who are the team members and what do they do?

Project teams are multidisciplinary and the ability of the CRO to fit into the company’s corporate culture and fill in the areas where additional expertise is needed are vital in drug development.  In my experience, most biotechs stay “lean and mean” to avoid carrying excessive overhead costs which often means that not all disciplines are sufficiently covered inhouse.  Disciplines involved in most drug delivery programs usually include R&D, CMC (synthesis/manufacture), nonclinical, clinical, CMC (final formulation), and regulatory.  Each biotech is unique in the set of inhouse skills available, and by collaborating with the CRO, they can draw upon its multiple assets to fill in wherever additional help is needed for the particular drug and the regulatory pathway.  There are complex team dynamics that exist in any multidisciplinary project team.  Sources of conflict can develop due to the different work environments, the different priorities, or misunderstandings, and inadequate communication among the various team members.  Additionally, environmental diversity among the various team members may arise from the different motives, the distinct rewards/recognition, and the unique regulatory constraints that each team member faces in their specific area.

There are 2 key transitions where many conflicts tend to occur:  R&D to nonclinical and nonclinical to clinical.  There generally tends to be a complete change in personnel from one area to the next and even when there are some personnel overlaps there still may be confusion and misunderstandings.  The nonclinical scientists have likely never visited a clinical site or seen a subject dosed during a clinical trial.  Likewise, the clinical team has probably never stepped into a vivarium and certainly not a GLP quality toxicology animal room, and never done a necropsy.  Each of the three areas has their own perspective and area of expertise, but they must rely on each other to keep the project moving.  A good project manager can ensure that smooth transitions occur and that appropriate decisions are made to keep the project on the regulatory pathway for the drug.

R&D Perspective

The most common role found in a biotech company is the research scientist whose primary goal is to make new discoveries.  The R&D scientist generally works alone or in a small group and focuses at the cellular level to find and optimize a new drug and detect changes by developing in vitro models to use for discovery.  R&D tends to attract highly creative, innovative people that are risk takers.  There tends to be minimal regulatory restrictions, and they may never have seen a standard operating procedure (SOP) much less followed one in their work at the bench.  However, in my experience most biotechs now have multiple SOPs governing their activities, and all employees must signify that they have read and understood the company SOPs.  However, biotech company SOPs are not directed at bench research and do not specify how research is to be conducted.

Potential points of conflict with other team members:

  • Why do we have to make up the solution in the dark?
  • Why is there such a limited time between when the drug is made up and when it must be delivered?
  • Why can’t we change the order in which we dissolve the ingredients?
  • Why does it stick to everything?

Nonclinical Perspective

The nonclinical scientists use a team approach with the specific objective of determining if the drug is safe and what harmful side effects it may have.  Nonclinical personnel tend to be goal oriented, are in a structured work environment, and strive to eliminate risk.  They are required to follow Good Laboratory Practice (GLP) and company SOPs in their study design, animal care, environmental controls, and documentation.  Stringent FDA/ICH guidelines dictate the type of study to be done and extensive documentation of animal handling.  They are frequently faced with drug supply and formulation challenges:  limited quantity of drug (mixing multiple different batches), inconsistent quality, required to dissolve drug on site (with limited tools to accomplish this task), and the use of exotic vehicles (impossible to use in the clinic).  On the positive side, they have compliant subjects (homogenous population, no missed doses, no dropouts) and can conduct thorough post mortems (necropsy) to evaluate the effects of the drug on multiple organs.

Potential points of conflict with other team members:

  • Why not use smaller animals?
  • Why so many animals?
  • Why so many repeat experiments?
  • Why not change the protocol to get better results?

CMC:  Drug Production

The CMC scientists must deal with all aspects of drug development starting with R&D and nonclinical to accommodate their needs and are under stringent requirements of Good Manufacturing Practice (GMP) to ensure cleanliness, reproducibility, document control, and worker and environmental safety.  They must also be vigilant about cost to maintain process efficiency, yield, and cost of goods.  CMC scientists play a crucial role in the transition to clinical and continue formulation development during the clinical studies.  Depending upon the type of drug, CMC scientists may encounter difficult physiochemical properties such as solubility, melting point, and stability issues.  Finally, scale-up will involve multiple rounds of trial and error to reduce synthesis steps, change starting materials, and change reaction conditions.  There are no standard patterns to follow as each drug is unique with its own physical properties and characteristics.

Potential points of conflict with other team members:

  • Why are you so stingy with the drug?
  • Why can’t you give us the exact delivery dates for drug supplies?
  • What can’t you deliver the drug on time?
  • Why are the capsules so big?

Clinical:  Inhouse Staff and Investigator Sites

The clinical scientists are concerned with patient treatment, laboratory tests, and assessing the data.  They are tasked with writing a clear, easy to follow protocol that will provide sufficient data to support the drug moving to the next phase of clinical study.  They need a long range view of the regulatory pathway best suited for their drug and how best to navigate the regulatory hurdles that may be encountered.  The clinical scientist also researches and identifies suitable investigator sites where the required trials will be conducted.

Potential points of conflict with other team members:

  • Why is the protocol so long?
  • Why are there so many exclusions?
  • Why is the screening period so short?
  • Why are there so many lab assessments?
  • Why are the sites so far away?

At the investigator site, the PI and the study staff look for feasible protocols that will cause no undue discomfort or inconvenience to subjects.  Their expectation is that the protocol is flawed not the subjects.  They want easy drug storage and dispensing and simple documentation.  The subjects in a clinical trial have high expectations that the drug is better than existing treatments and that bad things will not happen to them.  The investigator site staff are interested in new treatments for unmet needs, increasing their research credentials, and know best how to treat their patients.  They abide by Good Clinical Practice (GCP) that focus on ethics and safety.  They must be extremely flexible because they deal with protocols that are always different.  They frequently deal with uncontrolled variables.  They are constantly dealing with amendments for safety, efficacy, and enrollment.

In the clinical world, unlike nonclinical, the subjects have free will and must consent to participate in the study, do not always comply with the protocol, talk back, drop out, and have high expectations.  Clinical studies typically draw from a heterogeneous population and may include very sick patients, other diseases may be present, and concurrent medications will also be a consideration.  There will be limited post-mortem data so often the underlying reason for reaction or lack of reaction may not be clearly understood.  Since the subjects can talk and give descriptive details of drug effects, they can undergo more elaborate assessments than found in nonclinical studies.

Points of conflict with other team members:

  • Why isn’t enrollment going faster?
  • Why are there so many screen fails?
  • Why are there so many dropouts?
  • Why are there so many protocol amendments or deviations?

Goal of Project Management

A primary goal of project management should be to establish and follow a clear path for the project.  The FDA’s concept of the three dimensions of the critical path in drug development include:

  1. Safety – in vitro and animal models, animal and human testing, safety follow-up
  2. Medical utility – in vitro and computer model evaluation, in vitro and animal models, and human efficacy evaluation
  3. Industrialization – physical design, characterization and small scale production, manufacturing and scale-up, mass production

All three of these aspects must play an important role in the drug development process, and the project manager must consider them at all times.  The philosophy at Cato Research is “begin with the end in mind,” and this is paramount in a drug development project.  Because of the uncertainty in the process, the project manager must be prepared to switch directions or even back-up to ensure the overall success of the project.

For successful project management, the project manager should understand that all team members are motivated although with different objectives, rules, and rewards.  All team members want to do a good job but have different requirements and guidelines (GCP, GLP, GMP, and Regulatory requirements) but all want the same outcome.  Open communication is required to ensure clear understanding of each team member’s role and task in the drug development pathway.  The keys to successful project management are cooperation and communication from the biotech company, to the CRO, and to the investigator sites – all working together for the common goal of success in drug development.

This is a post by Kathy Grako, PhD, P.M.P.  Kathy is a Clinical Strategy Scientist in Cato Research‘s San Diego, CA office.