This article provides an overview of product safety with regard to the drug development process. For information on this topic for medical devices, please see Healthcare product safety: Medical devices.
Product safety is a major question to address during the drug development process. When undertaking drug development, the product safety profile of the investigational product must be properly evaluated to support the conduct of clinial studies and product licensing. This is because every single drug that affects the human body has some side effects. A drug can receive regulatory approval when its benefits (efficacy) outweigh its known risks (safety) for its intended use.1
The product safety information presented in a submission dossier (for regulatory review) is generally comprised of non-clinical and clinical information. To understand the safety assessment of a drug, one needs to understanding the drug itself and its intended use. In addition to the drug itself, factors such as the dosing regimen, treatment duration and route of administration can affect the data required to establish product safety.2
The cost of new drug development is high, with only about 3% to 5% of products that enter initial clinical evaluation becoming marketed drugs. It is estimated that just getting to the point of opening a clinical trial (for example, an Investigational New Drug Application [IND]) costs a minimum of $2.2 million, plus the cost of drug synthesis. Biological therapeutics are more expensive yet, with the estimated cost to reach IND at $4.5 million.2 Because of these financial implications, minimizing the drug development time and cost is essential. To this end, design and perform clinical studies according to regulatory standards.
Non-clinical safety assessments2,3 (such as all supportive toxicokinetic and metabolism activities and studies) are conducted to support:
The International Conference on Harmonisation (ICH) has published guidance documents* that include the following safety topics.3
In addition, the following joint safety/efficacy (multidisciplinary) guidance documents should be evaluated in support of the product safety information required for clinical studies:3
For drug products administered by routes other than oral, additional studies that address local tissue response to the administered clinical dosage are expected. These tests include studies such as:
As well, determine whether any local guidance documents apply to your product.
As with all drug products, adequate and well-controlled clinical studies are conducted to evaluate the product safety in human use. It is critical to include such information in your submission to support regulatory approval.
Drug safety evaluation is an ongoing activity as the premarket testing of drugs cannot detect all the problems that can occur with a drug, especially rare events (for example, those occurring in 1 in 10,000 people). Other problems such as medication errors and mix-ups with similar-sounding products are hard to foresee prior to regulatory approval. Thus, a vigorous program is needed after drugs are marketed to detect product safety problems and correct them as soon as possible.4
Compliance with any regional-specific requirements is critical to maintain your product licence and to protect public health. Such activities may include safety reporting, annual safety reports, post-approval studies, post-market surveillance studies and more. If the risk-benefit ratio changes, the product label may need to change, or the product may even need to be withdrawn to protect patient safety.
*Note: Guidance documents must reach Step 4 of the ICH process before they are ready for adoption by regulatory agencies.
The information presented in these articles is intended to outline the general processes, principles and concepts of the healthcare product development lifecycle. Since regulatory requirements are ever-changing, it is current only as of the date of publication and not intended to provide detailed instructions for product development. Every healthcare product is unique and therefore so is its associated product development lifecycle. Specific advice should be sought from a qualified healthcare or other appropriate professional.
Published: October 17, 2012