Guidance for Industry: Considerations for Developmental Toxicity Studies of Preventive and Therapeutic Vaccines for Infectious Disease Indications

The development of preventive and therapeutic vaccines against infectious diseases has become increasingly important in recent years. As these vaccines move through the regulatory process, it is crucial to consider potential risks associated with reproductive and developmental toxicity. In this article, we will discuss guidance for industry regarding developmental toxicity studies for vaccines and provide an overview of the current regulatory landscape.

Developmental toxicity testing has a rich history, dating back to the 1960s when guidelines were first established for reproduction studies (Goldenthal, 1966). These early guidelines were designed to ensure the safety of drugs for human use. In recent years, there have been several notable cases that highlight the importance of considering reproductive and developmental toxicity in drug development programs.

One such case is thalidomide, a medication that was withdrawn from the market in the 1960s due to its devastating effects on fetal development (Kelsey, 1997). The story of thalidomide serves as a reminder of the need for rigorous testing and regulatory oversight to prevent similar tragedies from occurring.

In response to these cases, regulatory authorities have developed guidelines to ensure that pharmaceutical companies conduct adequate reproductive and developmental toxicity testing. The International Conference on Harmonisation (ICH) S5(R2) is currently used for assessing potential developmental and reproductive toxicity in medicinal products (Tyl, 2006).

This chapter will provide an overview of the current regulatory considerations for reproductive and developmental toxicology testing specifically relating to pharmaceuticals and biopharmaceuticals. We will also discuss alternative methods for in vitro evaluations of reproductive and developmental toxicology, as well as consideration for evaluating Reproductive and Developmental Toxicity in nontraditional animal models.

The chapter incorporates reviews of the basic requirements for Conducting Fertility, Embryo–Fetal Development, and Prenatal and Postnatal Developmental Toxicology Studies as core components of pharmaceutical drug development programs. Additionally, we will discuss a brief history of the regulatory perspective of drugs, which provides background to the current study designs presented in this chapter.

In conclusion, the guidance for industry regarding developmental toxicity studies is crucial for ensuring the safe development and use of preventive and therapeutic vaccines against infectious diseases. By understanding the current regulatory landscape and the importance of reproductive and developmental toxicity testing, pharmaceutical companies can better ensure the safety of their products and prevent potential tragedies from occurring in the future.

References:

Goldenthal EJ (1966) Guidelines for reproduction studies for safety evaluation of drugs for human use.

Kelsey F (1997) From a speech “Denial of Approval for Thalidomide in the United States”.

Tyl RW (2006) Toxicology 707: advanced toxicology regulatory aspects of developmental and reproductive toxicology.

Lenz W (1988) A short history of thalidomide embryopathy.

Seidman LA, Warren N (2001) Pharmaceutical regulation in the United States: history and a case study.

Reversal of fortune: how a vilified drug became a life-saving agent in the “War” against cancer - Onco’Zine - The International Cancer Network (2013).

McFadyen RE (1976) Thalidomide in America: a brush with tragedy.

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