About the Industry
Through extensive research and development, the pharmaceutical industry continuously increases the therapeutic armamentarium available to treat an ever increasing number of clinical conditions.
Taking new ideas (often from a molecular stage), and developing these into useable products, the industry has the ability to treat patients not only in its own territories but to treat patients worldwide. Throughout product development the industry continuously monitors the safety of their drugs and monitors their safety while they are on the market.
As a pharmaceutical physician you can be involved in any stage of the development process from early drug discovery through toxicological evaluation, Phase I-IV clinical trials, marketing the product or even reviewing the safety of well established drugs. Although it’s good to know a little about all areas your job will mainly concentrate on one aspect (a bit like a specialist).
As a new entrant to the pharmaceutical industry you will most likely join the process when your company’s drug is in clinical development (being evaluated in healthy volunteers and/or patients) or the product is already on the market.
How does it work?
Before a drug can be marketed (i.e. advertised), a company needs to establish
A) does the drug work? and B) is the drug safe?
As it’s very rare that a drug is 100% efficacious, or 100% safe, the company has to prove that the benefit of the drug outweighs any associated risk before it will be granted a license to market that product.
The company therefore prospectively prepares a case for the product to present to the regulatory authorities (MHRA - UK, EMEA – Europe, FDA - USA). The company’s case (known as a marketing authorisation application, or new drug application in the US) must present evidence to prove that the clinical benefit gained from its product, in a defined patient population, outweighs any side effects potentially associated with its use.
To support the company’s case, the company will conduct pre-clinical and clinical studies to the highest standard (see ICH guidelines). The data will undergo intense scrutiny by the regulatory authorities so must be of excellent quality. Very few products that enter early clinical development will actually make it to the market.
Where does the pharmaceutical physician fit in?
Like medicine in the NHS, pharmaceutical medicine is divided into many “specialities”. To list just a few these can be, Medical Advisor/Medical Affairs, Clinical Development, Clinical Pharmacology, Regulatory Affairs, Drug Safety (Pharmacovigilance), Toxicology, Drug Discovery, Business Development or Pharmacoeconomics. Although these titles probably mean little to the new entrant, at the moment, I will try and give you an overview of the areas relevant to you.
I'll divide these into 3 areas;
1) Clinical Pharmacology 2) Clinical Development and 3) Medical Advisor/Affairs.
Clinical Pharmacology and Clinical Development predominantly work with the drug before it has been granted marketing approval by the regulatory authorities. Medical Affairs predominantly works with drugs that are on the market.
1. Clinical Pharmacology
Development starts by identifying a therapeutic target. Thousands of molecules may then be screened using automated techniques to find lead molecules that interact with the target.
Once a potential drug has been identified, and has undergone in-vitro evaluation, it will commence toxicology studies to assess the safety of the product.
If the drug satisfactorily passes toxicity testing, you are now ready to evaluate the safety, and the potential efficacy in man. The “first into man” studies are usually conducted in healthy volunteers and known as Phase I trials.
Normally you start with a very low dose and increase this in a stepwise fashion. These studies are needed to assess tolerance (side effect profile), potential therapeutic dosage, bioavailability (rate and extent of absorption) and metabolism in humans. Often you will hear the term pharmacokinetics used with Phase I.
Pharmacokinetics establishes how the body affects the drug (Absorption, Distribution, Metabolism and Excretion). This should not be confused with Pharmacodynamics which establishes how the drug effects the body (e.g. lowers BP).
The Clinical Pharmacologist works closely with the biochemists, toxicologists and other basic research scientists. They will also liaise with the Clinical Development team when they become involved.
Once you have established a safe starting dose, the first studies in patients can commence. Often a “proof of concept” trial is carried out. These early Phase II trials evaluate whether the drug is effective in patients with the disease, and also confirms the safety profile. Once this has been established the drug may now go into full clinical development.
2. Clinical Development.
Following phase I, products are then usually tested in a relatively small number of patients. This is normally carried out in the hospital environment, and designed to show efficacy, find the optimal dose/dosing regime (late phase II) and evaluate short-term safety for humans. Phase III studies are large-scale investigations on as many as several thousand patients, to further establish the safety and efficacy of your product. All clinical studies must be carried out in accordance with ICH-Good Clinical Practice (GCP) guidelines.
Much time, thought and effort goes into designing Phase III trials and as a Pharmaceutical Physician you will be key in the decision making. You will review and analyse the data produced before and liaise with Key Opinion Leaders (KOL’s); statisticians; data management teams; and your regulatory colleagues. You may also involve the marketing team.
When the trial commences your work doesn’t stop there. Although as a rule you will not have hands on involvement with the study, you will be in contact with the investigators, your company’s project management team and your safety officers (which may also be you). In smaller companies you may be looking after the study budget.
The Clinical Development Physician can have several trials running at any one time. The clinical development program may be affected by any of these results so it’s important to have good managerial skills and have a strategic mind.
Following completion of successful Phase III studies, you are ready to submit your application/dossier (present your case) to the regulatory authorities (MHRA-UK, FDA-US, MHW-Japan, etc). The dossier (known now as the Common Technical Document) can be quite sizable but you will mainly have input into the clinical sections. You will also be involved in compiling answers to any queries that are raised by the concerned authorities.
If the regulatory authorities are satisfied with the evidence presented to them, and happy the benefit outweighs any risk, they will permit the company to market the product for the approved indication/s, in that territory (e.g. Europe, US). Often this is referred to as “marketing approval” or “granted a license”.
3. Medical Advisor/Affairs
Medical Advisors become experts on their products and the therapeutic areas their drugs are used in. They are required to have a high degree of commercial awareness and not only advise their company but also advise outside leading Clinical Physicians and Pharmacists. To be effective, the Medical Advisor has to recognise both the clinical needs of the patients and the commercial needs of the company.
Clinical trials don't stop once a drug is on the market. Trials to find out more about its therapeutic profile and other indications the drug may be used for need to be conducted (Phase IV). The medical affairs team may “brain storm” ideas, analysing their drugs key strengths over their competitors. This will often lead to clinical trials focused on showing these strengths, providing a competitive edge for your product.
The drug still needs to be continually monitored for any safety concerns (post marketing surveillance). This may be undertaken in large “post-marketing” studies. It is important that the medical affairs physician is up to date with any changes to a drugs risk/benefit profile. Spontaneously reported adverse drug reactions must also be monitored, although this will be more by the pharmacovigilance department than medical affairs, the medical affairs physician must keep up to date with these.
As a pharmaceutical physician, working in medical affairs, you may be responsible for reviewing product literature and promotional material, and ensuring these are factually accurate. You will provide medical direction to marketing strategy and be involved with educating company representatives. There is a Code of Practice set out by The Association of the British Pharmaceutical Industry (ABPI) which establishes the guidelines for promotional activities of pharmaceutical products. You will, with time, become very familiar with this.
Contract Research Organisations (CRO’s)
When pharmaceutical companies wish to conduct studies requiring resources immediately that they do not have internally e.g. worldwide studies, or require a specialised facility to undertake the work e.g. Phase I unit, the most effective way to do this is to contract the work out to an organisation already set up to carry this out.
These organisations are in a position to deliver results in the shortest possible timeframe. They are known as Contract Research Organisations and provide excellent experience to the “would be” Pharmaceutical Physician.
Working for a CRO will provide experience in the operational aspects of conducting clinical trials, and allows the physician to develop their managerial skills. The roles are primarily concerned with patient safety but provide insight into the development of drugs.
This only touches on the surface of available roles, but hopefully goes some way to helping your decision as to whether the pharmaceutical industry is right for you. Pharmaceutical Medicine is a rewarding career allowing you to treat patients worldwide.
For further information, and an individual discussion about your needs, click here to contact Synapse Medical Resourcing today.
For some further reading click here for an article in the British Medical Journal.
