September 25, 2018
Authored and Edited by Y. Leon Lin; Shana K. Cyr, Ph.D.
On September 10, 2018, the FDA issued draft guidance on Post-approval Changes to Drug Substances, with recommendations regarding changes to drug substance manufacturing processes during the postapproval period. The guidance provides general considerations for assessing risk and change to the drug substance and product, as well as recommendations for the types of data to submit when proposing one or more changes in facility, scale, and equipment; specification; manufacturing process; starting materials; and container closure systems.
The guidance indicates that drug substance manufacturers must assess modifications throughout the manufacturing process to determine their associated risks. Risk assessment principles are outlined in the International Council for Harmonisation guidance for industry Q9 Quality Risk Management. Factors to consider in assessing risk may include experience of the facility and personnel involved, complexity of the involved manufacturing steps, physical and chemical stability of the involved material, complexity of the molecule, equivalence of the entire impurity profile, and comparability of physical properties when they may impact product performance or manufacturability.
Drug master file holders and drug substance manufacturers should assess the effects of the proposed manufacturing changes to the drug substance. According to the guidance, this can be done by comparing three consecutive pilot or commercial scale batches of pre- and post-modification material. Evaluating the change may include comparing impurities in intermediates or the drug substance, comparing the drug substance’s physical properties, or examining drug substance stability data. If drug substance equivalence cannot be established and the drug substance’s physical properties can affect manufacturability or performance of the drug product, the application holder must also assess the drug product made with the post-modified drug substance before distributing the product.
In addition to showing how the risk was evaluated, the risk assessment should explain how the accompanying data demonstrate that the risk was addressed or mitigated. Proposed changes should be supported by the documentation recommended in the guidance. Readers are encouraged to read the draft guidance, also available on the FDA’s website.
new drug application (NDA), New Animal Drug Application (NADA), FDA Guidance, Food and Drug Administration (FDA), drugs, veterinary pharmaceuticals
Copyright © 2018 Finnegan, Henderson, Farabow, Garrett & Dunner, LLP.
DISCLAIMER: Although we wish to hear from you, information exchanged in this blog cannot and does not create an attorney-client relationship. Please do not post any information that you consider to be personal or confidential. If you wish for Finnegan, Henderson, Farabow, Garrett & Dunner, LLP to consider representing you, in order to establish an attorney-client relationship you must first enter a written representation agreement with Finnegan. Contact us for additional information. One of our lawyers will be happy to discuss the possibility of representation with you. Additional disclaimer information.
Conference
2024 Licensing Executives Society USA – Canada Annual Meeting
October 20-23, 2024
New Orleans
Conference
4th Annual Passport to Proficiency on the Essentials of Hatch-Waxman and BPCIA
October 8-24, 2024
Virtual
Due to international data regulations, we’ve updated our privacy policy. Click here to read our privacy policy in full.
We use cookies on this website to provide you with the best user experience. By accepting cookies, you agree to our use of cookies. Please note that if you opt not to accept or if you disable cookies, the “Your Finnegan” feature on this website will be disabled as well. For more information on how we use cookies, please see our Privacy Policy.
Finnegan is thrilled to announce the launch of our new blog, Ad Law Buzz, devoted solely to breaking news, developments, trends, and analysis in advertising law.