Changing Quality and cGMP Environment - A Pharma Industry Insight
Dr B V Sivakumar,
Chief Scientific Officer,
Enaltec Labs

This article discusses the urgent need for the up-gradation of Quality Assurance parameters to meet the stringent FDA norms and cGMP requirements, for the pharma companies to help elevate their product quality and check reputational injury.

In 2013, the Pharma industry will experience substantial drug patent expirations, with more than 40 brandname products losing patent protection with an estimated value of USD 35 billion in annual sales. In five years the patent expiration and the estimate market opening for the generic manufacturers is expected to increase up to USD 100 billion.

While this is one side of the coin - a news of rejoice to the generic players, there's another side of the coin that is fading out its shine. Now, you ponder what's making the other side fading!

Nowadays, the everyday news about pharmaceutical industry is more about big blockbuster companies failing faces and succumbing to compliance issues, many companies getting clamped down further to legal action against adulterated/misbranded drug products in the supply chain. Yes, compliance issues. Coping up with the continuously changing, constantly advancing quality environment is one of the challenges that pharma industry is facing today. As a matter of fact, "Comply or face action" is the FDA's jargon now a days. It is becoming more so evident from the stumbling statistics of number of Warning letters issued out to companies globally by FDA - As of yet approximately 350 warning letters were issued to companies globally this year.

Interestingly, FDA has obtained approval from the Indian government in the month of March 2013 to add seven more drug investigators to its Indian offices, which would increase the number of FDA officials operating from India to 19 from its current head count of 12.

Now that enough is said about the compliance issues prevalent in the pharmaceutical industry, what are the actual changes in cGMP environment that has happened and is happening in the industry and how does one upgrade the quality system and effectively monitor its sustenance to stay GMP compliant.

Before getting in to what are the current changing landscapes in the quality environment, it is important to introspect on one's thought and be clarified about what "GMP" is in the eyes of FDA and what exactly is the expectation that FDA has on drug substance/product manufacturers.

FDA keeps it simple, when it says cGMP is "establishing strong Quality- management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories that assure the identity, strength, quality, and purity of drug products.

Also, it feels that this formal system of controls at a pharmaceutical company, if adequately put to practice, will help prevent instances of contamination, mix-ups, deviations, failures, and errors assuring that drug products meet their quality standards. It's clear, simple and straight is what you say after reading these lines. Yes it is a CLEAR, SIMPLE and STRAIGHT thought about GMP. Then what's 'the' thing that drives the industry crazy is the little 'c' thing to the GMP which makes it cGMP. And yes from the primitive ages we know 'c' in cGMP stands for 'Current', but what actually this 'c' means has remained a mystery most of the times. What is the changing quality landscape in the development and manufacture of drug substance and products? Looking at the trend and regulations in the recent years it is evident the quality approach is moving towards product and process lifecycle management and continual improvement in quality systems. This shift in the quality approach has brought in some quality concepts with increased daily prominence and that one listens to day in day out in the current pharmaceutical quality environment.

Here are the big 5s in the league - Lifecycle approach in Process validation , Quality Risk Management, Pharmaceutical Quality Systems, Quality by Design (QbD) and Process Analytical Technology. The need for having quality knowledge right from the design/development stage throughout the lifecycle of a molecule or a drug product has yielded to this transition.

Ever since the expectation for the life cycle management has pitched in, the regulations and quality guidelines binding the manufacturers have also taken their course. To get an insight on how the new regulations come up one could understand that, with the need of having better product and process knowledge right from the development stage rose the necessity of evaluating the potential product and process risks, quantifying it and subsequently mitigating it (ICH Q9); the requirement of putting forth life cycle approach to the process validation has resulted in changing the view point about quality and design space from our early development milestone; with more emphasis on Life cycle approach and defining quality right from the development phase evolved the concept of QbD, which imbibes concepts from ICH Q8 and ICH Q9.

These quality tools which enable manufacturers to enter into the market are reliable while some are still trying to enter into the market early with limited process and product knowledge and later getting outstripped by the advantage of being there early.

Letís have a close look at the latest sensation in the pharmaceutical quality assurance - "Pharmaceutical Quality Systems". Some of you might wonder as to why it is being called here the latest sensation, while these concepts have been well-known to the industry since decades. You are right; the concepts were known since ages, if one might relate to the concepts of ISO 9001 series, while the recent prominence after FDAs increasing interest towards this has brought it to the lime light.

ICH Q10 is not only the latest fad but it also represents the cultural change in the quality environment. Its comprehensive model can be implemented throughout the different stages of a product life cycle (including development) which is putting it favorable in the middle among other GMPs.

One might ask, if this puts other GMP regulations to the back seat? No Ė would be the answer. The harmonised model of a pharmaceutical quality system throughout the lifecycle of a product is intended for integrated use with other applicable GMP regulations and requirements.

The quality system elements and management responsibilities described in this guideline when implemented synergistically with the quality risk management and PAT are intended to encourage the use of science and risk based approaches at each lifecycle stage, thereby promoting continual improvement across the entire product lifecycle.

Implementation of the quality tools discussed above facilitates the manufacturer to align with the changing quality environment thereby accomplishing three major objectives:
  • Achieve product & process realisation.
  • Establish and maintain a state of control throughout the life cycle .
  • Facilitate continual improvement.
With the increasing quality tools & regulations and the amount of data mining required right from the development stage through the lifecycle of the product, the prominence of statistical analysis of data is growing in to the pharmaceutical sector deliberating to pull in personnel with competencies from other areas like statisticians etc.

As regulations and best practices in industry change, monitoring or implementation of these changes into the Quality System will ensure that the organisational structures, processes, procedures and resources used to manufacture pharmaceutical products remain in compliance throughout the product lifecycles; pharmaceutical development, technology transfer, commercial manufacturing and continual improvement.

While the regulations are growing and industry is striving to continue producing quality medicines for better patient safety and health, on a positive note, known for making cheaper and equal quality generic versions of expensive well-known drugs, India enjoys about 10 per cent share in the finished-dose product market in the US.