Medical Writers in the pharmaceutical or medical device industry usually work within Clinical Development or Pharmacovigilance, authoring documents required by regulatory agencies to prepare for marketing authorization of a drug/device and for the post-marketing phase.
After years of writing clinical regulatory documents such as study reports, investigator’s brochures, overviews and summaries, I became curious about what goes on before a drug enters a “first-in-human” trial. So I applied for a position in our company’s Preclinical Development department and got to find out!
Here, I would like to share:
- what preclinical research involves and why it is required
- who compiles the necessary documentation
- how the Medical Writer can contribute to a smooth submission process
- my experience working within a preclinical team
Preclinical research and requirements
Studies in test tubes (in vitro) and animals (in vivo) are necessary to predict the human response to a drug and minimize the risk of adverse reactions. Therefore, such experiments take place after the discovery phase and before and alongside clinical testing. Using animal species and disease models that best correlate with human physiology and disease generates data which are helpful in 1) assessing a product's safety and efficacy, and 2) determining a safe starting dose for a Phase 0 or 1 clinical trial.
So which types of studies are conducted at this stage in drug development?
- Pharmacodynamics (PD) studies which assess the biological effect of a drug and its mechanism of action.
- Pharmacokinetics (PK) studies which follow the movement of a drug around the body, including its absorption, distribution, metabolism, and excretion (ADME).
- PD/PK modelling which combines the above two. PD assessment might include safety pharmacology investigating potential unwanted PD effects on the respiratory and cardiovascular systems, CNS, gastrointestinal and renal systems.
- Toxicology (safety) studies which are designed to detect adverse effects a drug may have after a single dose (for dose-finding) and after repeated dosing (to establish the no observable adverse effect level or NOAEL). If relevant, the following are also investigated: local tolerance, toxicokinetics, target organs to support clinical monitoring, immunogenicity or the ability of a product to provoke an immune response, long-term genotoxic or carcinogenic potential, and adverse effects on reproduction and pre-and post-natal development.
The most commonly used animal species for these assessments are rodents (mice, rats) and dogs, and sometimes nonhuman primates (e.g. macaques), rabbits, or pigs. Regulatory authorities require safety testing in at least two mammalian species, including one nonrodent species, before approving a first-in-human clinical study. Thankfully, alternative methods (in vitro, in silico, etc) are being developed to reduce the number of animals used and to make testing less expensive and more accurate.
Regulatory documentation
Preclinical documentation is not much different to that of clinical. Just like clinical research data are collected into clinical study reports (CSR) and summarized in the appropriate modules of the Common Technical Document (CTD), preclinical data are presented in preclinical study reports and discussed in summary documents in the CTD. The Nonclinical Overview and Summary are located in modules 2.4 and 2.6, and study reports in Module 4.
There is usually no dedicated medical writing team within Preclinical Development. Because the material is more scientific than in Clinical, study reports are written by in-house scientists or CROs, depending on where the study was performed, with in-depth knowledge of the therapeutic area in question.
The Nonclinical Overview and Summary might be authored by a specialized team within a company’s Toxicology department. This team is composed of members with various educational backgrounds ranging from scientists to certified toxicologists and regulatory affairs experts.
Robust preclinical data are critical for presubmission meetings where they are presented in comprehensive briefing packages, and for the Investigational Medicinal Product Dossier (IMPD; EU) and Investigational New Drug file (IND; USA, Japan). The preclinical Regulatory/Toxicology team also provides input to documents prepared by Clinical Development and Pharmacovigilance, i.e. the investigator’s brochure, risk assessments, periodic safety update and benefit-risk reports, and product labels.
And this is where the Medical Writer can contribute.
The Medical Writer
As in clinical medical writing, the ability to convey scientific data in a clear and concise manner is crucial. Therefore, in addition to knowledge of drug development, international regulatory guidelines, and Good Laboratory Practice (GLP), excellent writing and editing skills are key.
The Medical Writer can facilitate the drug development and approval process by effectively presenting and communicating the often highly complex data in preclinical dossiers. Study reports might be written by scientists who are non-native speakers of English or less concerned with phrasing, and thus could require considerable editing when transferring the information into regulatory documents.
Liaising with departments outside Pharmacology and Toxicology is also part of the job. Some preclinical sections of the CTD require input from experts in Research, Quality, and Clinical. So being able to build positive relationships with these outside functions is an asset.
While a background in pharmacology, pharmacokinetics, or toxicology is helpful, it is not a must. New terms and concepts, despite being challenging, can be learned. Without a science degree, however, some aspects of the work might take a little getting used to.
My Experience
While my own transition from Clinical to Preclinical was relatively smooth, I was faced with some uncomfortable facts about animal testing. Not only normal species but also gene modified animals are bred for experimentation, making these animals prone to the disease studied. The description of side effects of some drugs, e.g. for cancer, at this early stage can also be difficult to digest. Many study reports refer to the killing of laboratory animals as “sacrifice” or “euthanasia”. While all animals are put to death in a humane manner (and all study procedures carried out in accordance with the Animal Welfare Act), I would not agree with these euphemisms.
Apart from these few niggles, my experience within Preclinical in my company was most rewarding. The presence of veterinarians in the department makes for a down-to-earth working approach. Communication between the preclinical functions was refreshingly friendly and uncomplicated - a major benefit when needing input into submission documents!
Unfortunately, preclinical development seems to be less highly valued by companies than clinical, as evidenced by less visibility and lower salaries in these departments. On the plus side, because most drugs that undergo preclinical testing do not make it to humans (only 1 in 1,000 are entered into Phase 1), there is a broader range of products to learn about.
Conclusion
Preclinical research is highly innovative and involves many different types of studies and technologies. Therefore, by editing preclinical study reports and presenting the results in summary documents, the Medical Writer can gain greater insight into drug development and into new therapeutic areas. The task of compiling data from diverse functions and departments gives the writer a key position in the regulatory submission process. And thus, I highly recommend getting started in this fascinating field!