The Answers May be in What Is Not Stated – Drug Substance and Drug Product Manufacturers – Partnering to Improve the Process

An interesting session during the GRx+Biosims conference held in Bethesda on November 4, 2019 addressed Drug Substance and Drug Product Manufacturers – Partnering to Improve the Process.  The presentations from the FDA, as well as industry, acknowledged that the adequacy of drug master files (DMFs) for APIs in one cycle has been a lot more challenging compared to that of the first-cycle approval of ANDAs.  

Keeping an Eye on The Ultimate Goal – How to Ensure Success In Developing Complex Generics

One of the popular sessions in GRx+Biosims Conference held in Bethesda on November 4, 2019 was about Developing Complex Generic Products – How to Ensure Success. The session involved presentation and discussion by FDA and industry. Both sides agreed that the most important factor in assuring success in the development of complex generic is communication,

Nitrosamines – Expensive Witch Hunt or Very Broad Safety Concern?

I have recently touched upon the subject of nitrosamines in drug products as part of a blog on Extraneous Peaks. (here)  The concern about nitrosamines in drug products continues to grow, and it will be a significant challenge for the regulators and pharmaceutical industry to establish meaningful policies and procedures to ensure there are no safety concerns for marketed products. 

Proactive Evaluation of Possible Genotoxic Impurities During the Early Stages of Drug Development

Aloka Srinivasan, Vice President, Regulatory Practice at Lachman Consultants recently wrote an article for PharmTech, detailing the Proactive Evaluation of Possible Genotoxic Impurities During the Early Stages of Drug Development. The article provides a direction for identifying genotoxic impurities early in the drug development process, regulating genotoxic impurities at acceptable levels in the API or [...]
Old Way x New Way Crossroad

Are All Methods Equivalent?

The use of alternate methods, especially for USP methods, some of which are rather old, has long been a question that both the industry and the FDA have contemplated.  Alternate methods can be easier to use and, in some instances, more accurate and reliable.  But how can you demonstrate that an alternate method is indeed equivalent to an existing method?

Continuous Manufacturing and its Regulatory Challenge

So, what is the buzz about continuous manufacturing (CM)? What benefits does it bring to the manufacturer and what are the regulatory challenges? The author of this Contract Pharma article, José L. Toro, Ph.D. of Lachman Consultants, discusses the current thinking on the benefits of CM and the regulatory hurdles a manufacturer has to overcome. [...]
Printout of a DNA sequence chromatogram

Extraneous Chromatographic Peaks – What’s a Lab to Do?

Recently, the United States Pharmacopeia and National Formulary (USP-NF) announced a three-month public consultation period on a proposal to change the approach to impurity reporting thresholds for drug products and drug substance monographs[i].  This activity is part of the USP-NF’s ongoing efforts to ensure that monographs reflect technical advances and current regulatory expectations. 

Bioanalytical Laboratories:  What to Do with Variable Internal Standard Response?

For all Sponsors submitting INDs, NDAs, ANDAs, BLAs, and supplements, and the bioanalytical laboratories analyzing and reporting the data to support these submissions, the FDA just issued its Guidance for Industry, “Evaluation of Internal Standard Responses During Chromatographic Bioanalysis: Questions and Answers.”  The Q&A guidance contains five questions, along with the Agency’s current thinking on each topic. 

Laboratory Instrument Calibration – Are You Covered?

It is paramount that a Quality Control laboratory has a calibration and preventative maintenance program for the laboratory instrumentation so that there is assurance that the instrumentation continues to be “fit for purpose” and that there is confidence in the accuracy and reliability of all analytical instruments.  There should be a controlled, comprehensive list of the instrumentation within the laboratory,

More is Not Always Better – Extra Testing

When it comes to ice cream and desserts, I must admit the more the better in my opinion.  The same, however, doesn’t hold true for laboratory testing and the resultant data.  All testing performed and data generated must be accountable to ensure the integrity of the data.  Performing extra testing, even if with all good intentions,

Ready or Not Here They Come – Lab Regulatory Inspections

Like death and taxes, eventually every pharmaceutical testing laboratory will get a regulatory agency inspection.  The anticipation of a regulatory inspection will instill great angst even within the most compliant laboratories.  The anticipated inspection might be a periodic inspection, but most often is a Pre-Approval Inspection (PAI).  The anxiety about an impending inspection often triggers a request for an independent third-party audit of the facility including the laboratory.

More Time Needed for Comments on Continuous Manufacturing Draft Guidance  

The pre-publication page of the Federal Register Notice posted today (here) a reopening of the comment period for the draft guidance Quality Considerations for Continuous Manufacturing which was originally released February 27, 2019.  That guidance can be found here  .

While some (but not too many) firms have embraced the concept of continuous manufacturing,

USP Chapter <197> Spectroscopy Identification Tests – Controlling Your Identities!

This post was co-authored by Thu Truong, J.D., Senior Associate, Science and Technology Group, and Ron George, Ph.D, Director, Science and Technology Group

Prior to USP 42 – NF 37 (effective April 30, 2019), USP Chapter <197>, Spectroscopy Identification Tests, stated, “The IR absorption spectrum of a substance, compared with that obtained concomitantly for the corresponding USP Reference Standard,

The Treasure Map to Biosimilarity Just Got More Granular

The FDA’s recently published draft guidance titled Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and other Quality-Related Considerations (here) is a significant improvement over the withdrawn 2012 guidance (i.e., Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product) that it replaced.  The increased level of detail and wider breadth of topics gives a significantly better view of the information that the Agency wishes to see in a BLA for a biosimilar product. 

Generics and the News – Bad Start to the Week or Just Business as Usual?

From the news stories on the price fixing suits, to the reported revelations about quality in the generic drug industry, or to the publication of a book titled “Bottle of Lies”, it has not been a good start to the news cycle for the generic drug industry this week.  The report on price fixing was met with a response to 60 Minutes May 12,