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Blog: Regulatory Requirements for Early Phase Drug Product Development

Supporting a compound from discovery to clinical phases and potentially commercial phases requires an immense amount of time, energy, and money. Regulatory management is paramount during the drug development pipeline funnel, and recognizing Current Good Manufacturing Practices (CGMPs) is the foundation of drug safety and efficacy.

Every country has its own regulatory authority, responsible for enforcing rules and regulations and issuing guidelines for drug development, licensing, registration, manufacturing, marketing, and labeling of pharmaceutical products.[1]

Some of the regulatory bodies include:

  • EMEA (Europe) – European Medicines Evaluation Agency
  • FDA (US) – Food and Drug Administration
  • HC (Canada) – Health Canada
  • PMDA (Japan) – Pharmaceuticals and Medical Devices Agency
  • MHRA (UK) – Medicines and Healthcare products Regulatory Agency
  • ANVISA (Brazil) – Brazilian Health Regulatory Agency
  • TGA (Australia) – Therapeutic Goods Administration
  • TMMDA (Turkey) – Turkish Medicines and Medical Devices Agency

The following international organizations are also instrumental in ensuring drug safety and efficacy:

  • WHO – World Health Organization
  • PIC/S – Pharmaceutical Inspection Co-operation Scheme
  • ICH – International Conference on Harmonization
  • ISO – International Organization for Standardization
  • PDA – Parenteral Drug Association
  • ISPE – International Society for Pharmaceutical Engineering

Drug discovery is the process of identifying potential new medicines. It involves a wide range of scientific disciplines, including biology, chemistry and pharmacology, bioinformatics, and others. Thousands of potential compounds are identified and screened during this early phase of development.

Drug discoveries and associated therapeutic indications are identified through a number of facets, including experience, serendipity, knowledge of diseases/medicine, synthetic chemistry, and pharmaceutical modification. They may provide new insights into a disease process that allow researchers to design a product to halt, significantly reduce, or reverse the effects of a disease or condition. Often, tests of molecular compounds (in vitro screening) are conducted to find possible beneficial effects against any of a large number of diseases. Drug discoveries may also occur from existing treatments that have unanticipated effects, giving rise to physicians prescribing medications off of label indications. Additionally, they can arise using new technologies, like targeted drug delivery systems. These emerging new technologies support mechanisms to target medical products to specific sites within the body, manipulate genetic material, or increase the concentration of product reaching a targeted area of the body relative to the rest of the body.

Regulatory agencies have minimal oversight of drug discovery studies, yet do provide certain requirements and clear documentation to achieve milestone during this process. Basic exploratory studies are carried out to determine whether a test article has potential utility or to determine the physical or chemical characteristics of a material do not need to comply with Good Laboratory Practices (GLP) or Good Manufacturing Practices (GMP).

The objective of preclinical studies is to determine the safe dose of a drug and to measure its toxicity, typically through model systems such as in vitro, in vivo, or ex vivo. Pharmacology studies are performed to assess the potential efficacy and mechanism of action, including pharmacokinetics to determine the way the body absorbs, distributes, metabolizes, and excretes the drug (ADME), and pharmacodynamics to assess the mechanisms of action of the drugs on the body. Computer modeling is a method that is gaining more interest to predict drug metabolism. While this computer modeling technique, in silico, is gaining support, it’s still in the early phase of industry adoption.

Additionally, pharmacovigilance is integral and required to be defined during preclinical studies. Safety data and risk assessment studies investigate adverse effects of new drugs, including mutagenicity, general toxicology, safety pharmacology, carcinogenicity, and teratogenicity. These studies are conducted on animal models to predict drug behavior in humans. The ultimate goal of these studies is to determine the non-observed adverse effect level (NOAEL) from the general toxicity studies to appropriately mitigate patient risks that may eventually allow for the baseline transition from animal studies to human clinical trials.

Moving forward from drug discovery to nonclinical/preclinical studies, GLP principles regulate the organizational process and the conditions under which nonclinical health and environmental safety studies are planned, performed, monitored, recorded, reported, and archived. Important guidances for these type of studies include:

  • 21 CFR Part 58.1: Good Laboratory Practice for Nonclinical Laboratory Studies
  • ICH Guideline: M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (2010)
  • ICH Guideline: S6(R1) Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals (2012)

As GLP studies are used to support applications for research or marketing permits, they must adhere to fundamental requirements set forth by regulatory agencies. The following list examines necessary steps for nonclinical/preclinical safety studies.[2]

  • Assignment of study director
  • Establishment of an independent Quality Assurance Unit (QAU) to review and sign off on data for every GLP study
  • Maintenance of a master schedule
  • Establishment of Standard Operating Procedures (SOPs)
  • Written protocol for each study
  • Audit of every study conducted
  • Facilities large enough and with the right construction to secure the integrity of a study and to avoid cross contamination
  • People trained and qualified for the job
  • Test and control articles with the right quality
  • Instruments calibrated and well maintained 
  • Data acquired, processed, and archived to assure integrity of data
  • Final report to be issued

In conclusion, although regulatory oversight is less stringent during the drug discovery phase, regulatory requirements must be considered during early development of drug products. Following the drug discovery phase is the preclinical phase, which evaluates safety factors of the drug as well as drug behavior in the host organism. Although these products are not administered to patients and are therefore not subject to GMP regulations, it is imperative that the data collected in preclinical studies is accurate. This data will be used to support regulatory filings, and to determine if the drug is safe to administer in human trials. Regulatory oversight and guidance of products in later phases of development, clinical trials, registration, and process validation as well as commercially marketed drugs, is vital to help ensure pharmaceutical companies are appropriately monitoring release drugs products to patients that are both safe and efficacious.


Technical Contributors

Jonna Clark
Jonna Clark supports Alcami's drug development programs from preclinical to commercial phases of development and for laboratory training programs. She has over 18 years of experience in the pharmaceutical industry with extensive experience in analytical development and is an instructor at the University of North Carolina Wilmington, teaching courses in Good Manufacturing Practices (GMP) and Quality Control (QC) laboratory techniques. Jonna holds Bachelor of Science degrees in Biochemistry and Chemistry from NC State University, and a Master’s degree in Chemistry from the University of North Carolina Wilmington.

Andrea Young
Andrea Young is the Manager of Regulatory Affairs at Alcami. She has over 20 years of experience in the pharmaceutical industry, and has spent ten years providing both internal and external support for regulatory-related matters. She also has considerable experience in Quality processes and procedures. Andrea has a Bachelor of Science degree in Biology from St. Bonaventure University, and an MBA from the University of North Carolina Wilmington.

[1] For a comprehensive list, visit


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