The US Food and Drug Administration (FDA) needs to develop guidance on post-approval changes for complex generics, and to update its guidance on post-approval changes for non-complex generics as current versions are outdated, according to representatives of the generics industry.   The remarks were made during a panel on post-approval changes for complex generics on 9 November at the Association for Accessible Medicines’ (AAM) GRx+Biosim held a conference in Bethesda, ...

Regulators make benefit-risk decisions based on the three pillars of quality, safety, and efficacy. CMC is applied throughout the product development spectrum from the initial synthesis of a molecule to reach a hypothetical target, to commercial scale up and beyond. This article helps the reader navigate the CMC regulatory landscape and understand the multiple considerations needed in order to devise a strategy which is efficient with respect to cost and time to approval. ...

The five process groups of a process-based approach to project management are: Initiate, Plan, Execute, Monitor and Control, and Close, according to PMBOK. This article presents opportunities for using a project management framework when strategizing for CMC regulatory submission projects. The authors discuss PMBOK nomenclature, project performance domains, project constraints, process groups, examples of scenarios that may be encountered during a submission project, and t...

The US Food and Drug Administration (FDA) on Friday issued a question-and-answer guidance  to provide clarity to manufacturers on reporting post-approval changes to disposable manufacturing material.   The guidance covers changes made to new drug applications (NDAs), biologics license applications (BLAs) or abbreviated new drug applications (ANDAs) and applies to all manufacturing establishments, including those that perform functions under contract.   During the...

A global regulatory group is seeking industry participants for two pilot programs exploring a common regulatory framework for assessing manufacturing facilities in hybrid inspections and for reviewing postapproval changes.   The International Coalition of Medicines Regulatory Authorities (ICMRA) announced the pilots on 24 June. The group said that the pilots were prompted by its July workshop which “highlighted the need for more convergence on CMC [chemistry, manufac...

Both industry and clinicians asked the US Food and Drug Administration (FDA) for clarification related to the evaluation of cellular starting materials in its draft guidance on chimeric antigen receptor (CAR) T cell product development.   The public comments also sought more details on change management and how the guidance applies to other genetically modified products.   The draft guidance , issued on 15 March 2022, provides recommendations on chemistry, manufac...

CHICAGO – Several initiatives in the works among regulators and the pharmaceutical industry are gaining momentum to harmonize chemistry, manufacturing, and controls (CMC) information submitted in the Common Technical Document (CTD). One such effort is the formation of an industry consortium that is seeking to develop a structured content cloud-based CMC Module 3 template with input from regulators.   These plans were discussed on 20 June 2022 during the Drug Informatio...

The US Food and Drug Administration (FDA) on Thursday issued a final guidance to help manufacturers of certain biological products determine which types of changes to their products should be submitted in annual reports for changes expected to have a minimal impact on product quality. The final guidance differs from the draft in providing more examples of changes that can be submitted in annual reports; however, FDA rejected calls from industry to provide a timeframe for...

The US Food and Drug Administration (FDA) offered some advice to help ensure smoother reviews of abbreviated new drug application (ANDA) post-approval supplements and addressed how certain changes should be categorized at the 10 November meeting of the Association for Accessible Medicines” (AAM) GRx+Biosim conference.   Officials were asked to address common issues affecting ANDA post-approval chemistry, manufacturing and controls (CMC) submissions. Agency officials ...

When developing a regulatory submission for a gene or cellular therapy, it’s essential to keep the basics in mind, such as how to demonstrate the product’s identity, purity, and potency, Haroon Hashmi, PhD, told attendees at RAPS Convergence 2021.   “Even when we think about these complex technologies -- new emerging technologies -- certain regulatory principles always stay in place,” said Hashmi, senior vice president at Ziopharm Oncology, which has developed the Slee...

The US Food and Drug Administration (FDA) has reopened the comment period on its draft guidance implementing the International Council for Harmonization’s (ICH) Q12 guideline on postapproval chemistry, manufacturing and controls (CMC) changes for new and marketed pharmaceuticals and drug substances.   The additional time was requested by the Pharmaceutical Research and Manufacturers of America (PhRMA).   FDA announced in a pre-publication notice in the 8 Septembe...

The European Medicines Agency (EMA) on 1 July released for public consultation two draft guidelines to help sponsors of investigational medicinal products (IMPs) for new drugs and biologics decide whether manufacturing changes are considered a “substantial modification” needing prior approval.   These guidelines are connected to the EU regulation No. 536/2014 which came into force on 20 June 2014. The regulation defines a “substantial modification” as any change to a...