Regulatory/GMP Compliance

FDA is working more closely with foreign regulators to keep abreast of drug and vaccine quality issues in their regions.

Whether it's for manufacturing drugs, characterizing cell substrates, or regulating new technology, quality systems provide a needed framework.

This article shows how Probabilistic Tolerance Intervals of the form, "We are 99% confident that 99% of the measurements will fall within the calculated tolerance limits" can be used to set acceptance limits using production data that are approximately Normally distributed. If the production measurements are concentrations of residual compounds that are present in very low concentrations, it may be appropriate to set acceptance limits by fitting a Poisson or an Exponential Distribution.

The first part of this article, published in the September 2006 issue, discussed general strategies for validation extensions to other test method components, laboratories and even different test methods.1This second part provides practical tips on how to maintain test method suitability long after the formal completion of analytical method validation (AMV) studies.

It is important to ensure that flow decay during processing is comparable to that observed during retention studies.

While not yet finalized and adopted, ICH Q10 represents some of the most current thinking with respect to pharmaceuticals manufacturing and control.

Development reports document process development and support the design of validation experiments, yet in many firms training is not provided nor are expectations established. This article describes how project managers can help scientists master the art of report-writing.

SOPs are written job aids that detail the procedure of how to do a specific job task correctly.

The concept of design space has started a minor revolution in our industry.

Reserve samples of test and control articles must be retained for at least one stability time point after the completion of the study.

The challenge is to determine the optimal frequency for preventive maintenance and the optimal frequency and tolerances for calibration readings.

Taking a purist stance is always tempting. It can, however, have unintended consequences.

Companies faced with real or threatened FDA sanctions are usually least prepared to react effectively.

Increasingly, pharmaceutical companies have recognized that software development is not their core competency.

Good risk management tools dictate how much assay performance characteristics can deviate from ideal.

There is growing support for new partnership arrangements that seek to expand drug research by reducing the financial risk for manufacturers.

Understand your company's requirements, define responsibilities,and manage your team effectively.

Is it possible to reconcile phage therapy, which is inherently variable, with requirements for tight product characterization and control?

FDA did not gain any real teeth for regulating unsafe and ineffective products until a national health disaster in 1937 roused a public outcry.

In 2005, 10 biopharma- ceuticals gained marketing approval in the US or Europe, although only five of them were genuinely new molecular entities.

Case studies were run to test Process Analytical Technology applications for protein refolding, diafiltration, and cation exchange chromatography. It is shown that it is feasible to design control schemes that rely on measurement of product quality attributes and thereby enable real-time decisions.

Federal regulations are broad and open to interpretation. Most have not caught up with advancements in technology.

Disposables require less space than conventional equipment, and they can be assembled offsite into complete process trains.

A novel calibration approach was developed that not only calibrates the X-axis, but also calibrates the peak shape.

For decades now, it has been said that "the process is the product" for biologics. Great care and consistency must be applied in their upstream manufacture-during fermentation, harvest, and early purification-to preserve their complex structure, which confers their activity and specificity. As the product moves to late-stage purification, however, the relative concentration of impurities and altered product forms is diminished. Also, the final dosage form of most large molecule biopharmaceuticals is the relatively simple liquid formulation of parenteral dosage form. In contrast, manufacturing the solid dosage forms common for small-molecule drugs involves more complex processes, such as mixing dry powders, granulation, manufacturing controlled-release matrices, and tableting.