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CMC Articles and Insights

Do Your Biologics Assays Tell the Whole Story?

Adherence to cGMP regulations assures the identity, potency, purity and quality of biologics or advanced therapeutics and helps ensure adequate control of manufacturing operations. A primary way to demonstrate these attributes for a biologic product under development is through assays. Stages of Assay Development Design

Analytical Testing Considerations for Gene Therapy Products

The FDA’s January 2020 guidance, Chemistry, Manufacturing and Control (CMC)[1] Information for Human Gene Therapy Investigational New Drug Applications (INDs), outlines the analytical methods that define the quality, safety and efficacy of gene therapy therapeutics. The analytical package, consisting of release, stability, and characterization tests,

CMC Considerations for Pre-IND Meetings

The pre-IND meeting is an opportunity for highly productive interactions between sponsors and the FDA, allowing for discussion of key material attributes and development strategy plus requests for Agency review and advice on specific topics. In general, such meetings are multidisciplinary and cover the regulatory,

Evaluating Impurities in New Drugs to Prevent Delays in Development

During the development of new small molecule drug products, developers must conduct impurity and degradant evaluation at several points in the program and to varying degrees. These evaluations include the active pharmaceutical ingredient (API), also known as the drug substance, and the drug product (formulated

What You Need to Know About ICH Q14 and ICH Q2(R2), Part 2

For researchers who are developing or working with analytical procedures, the new ICH Q14 Analytical Procedure Development and revised ICH Q2(R2) Validation of Analytical Procedures drafts represent foundational guidance documents. Together, they describe suggested development and validation activities for the lifecycle of an analytical procedure

What You Need to Know About ICH Q14 and ICH Q2(R2), Part 1

For researchers who are developing or working with analytical procedures, the new ICH Q14 Analytical Procedure Development and revised ICH Q2(R2) Validation of Analytical Procedures drafts represent foundational guidance documents. Together, they describe suggested development and validation activities for the lifecycle of an analytical procedure

Three Keys to a Successful Process Technology Transfer

The technology transfer of a manufacturing process to a contract development and manufacturing organization (CDMO) is a key step on the road to developing and commercializing biopharmaceutical products. Successfully executing this step is critical to clearing regulatory expectations, avoiding production delays, and delivering drugs to

PDUFA VII: Implications for Developers of Cell and Gene Therapies

One of the biopharmaceutical industry’s most closely watched forthcoming regulatory developments is the FDA’s imminent reauthorization of the Prescription Drug User Fee Act (PDUFA). PDUFA VII, as the reauthorization is commonly known, will cover the fiscal years 2023-2027. Many of the advancements included in PDUFA

Advancing from Research to Development: What Can Go Wrong?

The drug development process is a long journey, beginning with drug discovery, moving through nonclinical and clinical studies, and ultimately culminating in regulatory approval. With many steps in between, each as important as the next, multiple factors regarding development strategy and approach must be considered

Technology Transfer: What Is It, and How Is It Done?

Technology transfer is a critical step in any drug development program, occurring for various reasons and at different development stages. A sponsor may be looking for a contract development and manufacturing organization (CDMO) for clinical trial manufacturing; to transfer a manufacturing process to a larger,

Multidisciplinary Team Advances Immuno-Oncology Development

Developing a product from concept to commercialization is a multi-faceted and risky process. Particularly for complex programs, development plans must be customized based on real-world patient experience and optimized for a product’s post-approval success. A cross-disciplinary team is essential for crafting and assessing complex development

Quality Metrics – Coming Soon to Your Manufacturing Facility

The Food and Drug Administration (FDA) began requiring drug efficacy, in addition to safety, for approval in 1962 based on the Kefauver-Harris Amendment. Despite this requirement, many drugs that have been approved by FDA have limited efficacy (eg, drugs that treat cancer or Alzheimer’s disease).

New Generic Stability Requirements

After much delay, FDA just released the new guidance on the stability requirements to file and obtain approval of a generic drug product and API under 505j. The new requirements bring ANDAs closer in line with NDAs and ICH. The new requirements as summarized in

Drug Development Planned Like the Titanic

How many drug development companies leave it up to the CMO to design or execute their formulation and manufacturing without oversight? Like those who boarded the Titantic 100 years ago, they seem to trust the mantra that their contractor’s work is unsinkable. MAP Pharmaceuticals seemed

Labeling for Abuse-Deterrent Drugs

From a technological standpoint, it is understood that the goal of developing 505(b)(2) abuse-deterrent products is to make changes to the API or formulation of a drug that has abuse potential in such a way that it dissuades the abuser from wanting to use the

Target Product Profile

In any project development program an understanding of the program goal is critical to finding the shortest path to the final result. Generation of a Target Product Profile early in a development program facilitates reaching the goal of a marketed drug product. It provides a

Can and Should ANDA Labeling Differ from the RLD?

In the past two months, two appellate courts, the Fifth Circuit and the Eighth Circuit have handed down decisions which essentially state that generic pharmaceutical companies can be sued in state courts for failure-to-warn regarding serious side effects, where the generic companies had conformed their

Analytical Requirements for Oral Solutions

Analytical requirements for the NDA submission of an oral solution to the FDA are very similar to those requirements for any new drug product. The analytical methods that are used for the testing of an oral solution at the NDA stage of development should be

Comparability Protocols

What do you need to do when you need to change suppliers or manufacturing sites? Among the many choices is a formal FDA comparability protocol. Advance planning can improve the possibility that the FDA accepts your proposed change. One alternative that can streamline the process

Test Specifications for Stability Studies

Pivotal stability programs that are used to generate stability data for NDA submissions are different than research stability programs used to design the drug product, explore packaging configurations, etc. This is common sense, but we have seen instances of pivotal stability programs that have been

Multiple Dosage Strength Products – CMC Considerations

Developing a product with multiple strengths? How do you go about filing multiple strengths in an IND? How and when do you draft one CMC section covering multiple drug strengths for the same dosage form? Long-term drug development goals may include multiple strengths of a

Botanicals: What is the starting material for the API?

We typically work with small molecules of synthetic origin, but occasionally are retained to work with products that have active ingredients from botanical (plant) sources.  Lynn Gold, our VP of CMC provides the following discussion on how to define the starting material for the Active Pharmaceutical Ingredient (API).

One vs. Two Batches for Single-Dose and Multiple-Dose Studies

Today’s posting stems from a client question.  The client’s product candidate is an oral product that requires both single- and multiple dose pharmacokinetic studies. Question:  Do companies ever use one pivotal batch for single-dose (SD) study and another batch for the multi-dose (MD) study?  What

505(b)(2) NDA Labeling

A draft label be included with all NDA submissions. For a 505(b)(2) NDA, where do you get the information for this label? What labeling is required? What is labeling? Well, the “label” is what is on the immediate container of the drug product and can