The chemistry, manufacturing, and control groups are responsible for documenting how the product and its raw materials are made and tested, and how the manufacturing processes are controlled. In the case of companies that work primarily with small molecules, these are people with experience in synthetic chemistry and classic analytical chemistry techniques. In the case of biotechnology products, these may be molecular biologists and protein chemists.
Proving that the company's manufacturing methods are not only controlled but are also reproducible is a major issue with the government, which requires that these processes be validated. Validation is a series of formal tests undertaken to prove that each important step in the process can be repeated with predictable results. Even if the process undergoes changes, it is important to show that the product that results is identical. This means that all of the equipment that must operate within very specific temperature and pressure ranges has been appropriately tested and recalibrated as needed, that the software that controls critical steps has been demonstrated to run reliably on the equipment it controls, and that changes to the software can only happen under specific and well-controlled circumstances.
The output from each person performing these tasks needs to be reported and documented to meet government requirements. When a product is to be produced commercially, the government inspects all of the documents to ensure that they do prove that the process and product are capable of reproducibly meeting the product specifications during the storage conditions specified in the marketing application. Some of these jobs fall within the regulatory world of compliance (Did people do what they said they had to do to make the product?), and some fall within the realm of documentation (Do we have all of the right reports containing the right information in the right format for the market in which we plan to sell our product?).
Preclinical development does the work needed to get the product into humans in the first place and it provides supporting data that show that the product can reasonably be expected to be safe even if a larger population is exposed to the product than in the definitive clinical trials. Typically, this group studies the pharmacology and pharmacokinetics (absorption, distribution, metabolism, and excretion) of the product in various animal species, and it provides toxicology data in various species. The amount and types of testing required for a drug is the subject of ongoing discussions between the United States, the European Union, and Japan and it is one area where harmonization of requirements is most likely to reduce the amount and kind of testing required at various stages of the drug development process.
For the preclinical group, regulatory input on the progress of the harmonization process and on the specific requirements for products in each therapeutic area is extremely important. This group also generates reports that must meet specific government requirements for content. These requirements must be taken into account when preclinical studies are designed, otherwise more studies will have to be conducted to provide the necessary information for the IND filing. Typically, the regulatory staff and the compliance group within regulatory work hand in hand at each stage of the process for key studies to make sure that the study and the final report meet government requirements.
The clinical group oversees the clinical trials for a product. Depending on the organization of the company and the regulatory group, this group may report to regulatory affairs, or regulatory affairs may report to them. This is another key group that is capable of making or breaking the entire company. More money is spent by this group than by any other group in the entire company, and it is their work that decides the fate of a product.
As with the preclinical group, the work of the clinical group is highly dependent on a series of regulations designed to protect the test subjects. The regulations that define this work are subject to harmonization between the different governments, but the reality is that most countries prefer to have testing done on their own particular population group before they will approve the local marketing of a new product. This can lead to a flurry of regulatory activities, due to the regulations that control shipping the product for testing across international boundaries, and shipping patient samples back to the company for analysis.
The government is keenly interested in each step of the clinical trial process, including the development of the protocols, enrollment of the clinical testing sites, development of the data reporting forms, verification of adherence by clinicians and nurses to the protocol, and data reporting, data entry, and adverse event reporting. Each step is subject to government inspection and thus each is intimately involved with regulatory affairs.
Once the data are locked into the data base and data verification is complete, the statisticians take over. This group grinds the data into various analyses, looking for not only the overall results, but results by sex, by race (genetic background can influence the pharmacokinetics and therefore the safety and efficacy of a drug), and by population subgroup. This analysis is again subject to review by the regulatory group, as is the final report generated from each clinical trial.
The compliance group is responsible for making sure that the preclinical and clinical studies were performed as specified by a protocol that was written to meet government requirements. Depending on the organization of the company involved, they also review the chemistry, manufacturing, and control groups to ensure that their protocols, data, and reports reflect written procedures to accurately report the results of the various studies performed.
Documentation is the most obvious of all of the regulatory responsibilities. It can be the most time-consuming, tedious, and exacting of those jobs as well. People involved in this work assemble format, file, and store for instant retrieval all of the documents needed by the government to support the various filings required for a product. While this part of regulatory can be dismissed by the uninitiated as rote and as not requiring much skill, it is also true that compliance puts together the document that ultimately decides the fate of the product. If the reports are lost or unreadable, if the pagination and indices are mixed up or inaccurate, a decade's work can be put aside by the government until the company provides a document that is complete, comprehensible, and able to be reviewed.
For each of these areas, depending on the size of the company, at least one person is responsible for each task. In some companies, there are dozens of people responsible for each of these areas. Other companies use contract organizations to provide most of the staff, and have only a few inside personnel to make sure that the functions are performed as needed.
