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[...]... product In this chapter, we will discuss the requirements for ophthalmic delivery systems in which a drug is incorporated in a carrier for its pharmacological effect on the human eye and is reviewed as a new drug product by the FDA’s Drug Center (CDER) V CLINICAL TESTING OF NEW OPHTHALMIC DRUG DELIVERY SYSTEMS A Human Versus Animal Testing Human drug products are often tested during development in animals... marketing approval The terms drug and new drug are inclusive of the drug substance and the drug product It is important to understand that a new drug is not just a newly discovered chemical or biological compound This can best be illustrated by several examples of when a drug can become a new drug for regulatory purposes: 1 The drug is a new derivative of a known molecule such as a prodrug of epinephrine 2... potential for Copyright © 2003 Marcel Dekker, Inc Regulatory Considerations 679 For oral drugs, the dose-response testing is a crucial parameter; however, it has not been a rigorous part of most topical ophthalmic drug- development programs The drug delivery researcher may find that these data are missing for his or her drug and needs to establish this relationship for optimization An example of this occurred... compliance for clinical trial manufacture (10) VI MARKETING NEW OPHTHALMIC DRUG DELIVERY SYSTEMS FOR HUMAN USE Once a manufacturer has obtained sufficient information from clinical trials in humans, safety testing in animals, and chemistry and manufacturing experience to establish that the new ophthalmic drug delivery system is safe and effective for its intended use, a New Drug Application is submitted to the... Copyright © 2003 Marcel Dekker, Inc Regulatory Considerations 669 application, $100 ,000 for each manufacturing facility, and $10, 000 for each product dosage form and strength Human drug applications that are exempt from user fees include those for clinical investigations, generic drug approvals, over-the-counter drug approvals, orphan drug approvals, and pediatric use approvals Fees may be waived in certain... study is intended to be used as part of the NDA to establish safety and effectiveness, it would be important to know if the FDA has any serious questions about the protocol before proceeding Ophthalmic drug clinical development generally follows three phases, particularly if the drug is a new molecule and this is its first introduction into humans Phase 1 for ophthalmic drugs usually is focused on the... previously approved drug has been discovered to have a new therapeutic use such as a nonsteroidal anti-inflammatory agent used to inhibit miosis during cataract surgery 3 A component of a drug is new for drug use such as an EVA polymer film to control the release of pilocarpine in the eye or a gel-forming polymer to extend the duration of IOP-lowering of timolol maleate 4 Two or more approved drugs are combined... Dekker, Inc 680 Roehrs and Krueger ophthalmic IND? In general, to begin clinical testing, FDA will require at least the same duration of testing in animals as proposed for human exposure The requirements will vary with the particular drug and the novelty of the particular delivery system The approach of one company in establishing the safety/toxicity profile of ophthalmic drugs and devices has recently... Kreuter (1978) Nanoparticles and nanocapsules—new dosage forms in the nanometer size range Pharm Acta Helv., 53:33–39 206 J Heller (1993) Polymers for controlled parenteral delivery of peptides and proteins Adv Drug Del Rev., 10: 163–204 207 W Lin, A G Coombes, M C Davies, S S Davis, and L Illum (1993) Preparation of sub -1 00 nm human serum albumin nanospheres using a pHcoacervation method J Drug Target.,... modification of the approved drug (21 CFR 314.430) For the new ophthalmic delivery system of an approved drug, the basic human clinical and animal safety studies would not have to be repeated but only referenced to the approved drug s NDA Full reports would only be required for demonstration of safety and efficacy of the new delivery system, i.e., the changes made to the approved drug A complete chemistry, . therapeutics: drug delivery and targeting. Adv. Drug Delivery Rev., 18:115–131. 167. J. W. Jaroszewski, and J. S. Cohen. (1991). Cellular uptake of antisense oli- godeoxynucleotides. Adv. Drug Delivery. pharmaceu- tical drug product will be essential. The commercial consideration for development of an ophthalmic drug delivery system is not limited to new therapeutic agents. Many existing ophthalmic drugs. T24 cells proliferation. EMBO J., 10: 1111–1118. 114. Y. Rojanasakul. (1996). Antisense oligonucleotide therapeutics: Drug delivery and targeting. Adv. Drug Delivery Rev., 18:115–131. 115. S.