Frequently Asked Questions (FAQ)

What is Sigmatech?

Sigma Tech 3.1  is a software for achieving objectives of QbD. It is useful for building quality into the process using DOE technique. The statistically designed  experimental data will be analysed by this software to build the mathematical model and provide various simulation techniques for optimal design of the process.  This software is useful for applications  in Analytical Research , Formulation, API ,  Chemical and Process R&D laboratories within the Pharmaceutical, Biotechnology and Chemical industries.

What is QbD ?

QbD is a concept called ‘Quality by Design’, which aims to build quality into processes by design. This implies

  • Quality cannot be improved by testing alone
  • QbQ enables building robustness in the process
  • QbD explains the steps to arrive at the finished process parameters
  • QbD requires to demonstrate the robustness of the  process
  • QbD approach results in design space, which is a wider range of process parameters
  • Manufacturing with in the approved design space provides opportunities to yield products without filing post-approval changes

What is DOE?

Design of Experiments (DOE) is a systematic, planned approach to solving problems  by gaining information through carefully planned statistically designed experiments. These experimental studies have adequate statistical properties to be able to

  • Accurately measure the effects of  process factors on the key response variable(s) (e.g. purity, impurity profile ,dissolution, content uniformity, etc.)
  • Determine if these factor effects are real (above the noise level) and if so to accurately quantify these effects.

Why do we need to go for DOE in process development?

  • The challenge facing corporations is to cut design and development time while producing low-cost, high quality products that are ready to perform. Many organizations are being challenged to cut delivery time in half or more.
  • By understanding and applying Experimental Designtechniques, scientists, researchers, and engineers typically obtain a 50% reduction in the time cycle required to conduct experiments. This translates into enhanced understanding of technologies, reduced design and development time, and decreased costs.
  • In regulated industries such as drugs and pharmaceutical industry, automobile industry and medical equipment manufacturing, the regulatory authorities have strongly recommended the use of DOE for the development of process and product.
  • Among the regulatory authorities, FDA issued guidelines   recommending the use of DOE for process development and submitting data to them for their approvals.
  • In contract research work, customers are asking to submit results of DOE methods
  • Below are the references for the details of various regulations that advocate the use of DOE for pharmaceutical process and product development

What happens if we do not use DOE in process development?

While developing the process, a process had to be developed quite often using a large number of variables (say about 7 to 10). Scientists usually use OFAT method (one factor at a time approach) in developing a process. Since the number of variables are quite large and adoption of OFAT method needs large number of experimental trials, time and resources, some of the variables are considered as not significant to the best of their knowledge. As a result, only 3 or 4 variables are tried in process development. This approach does not guarantee results.  Even some variables are not significant. Their interactions with other variables might be significant in influencing the results.

Also, the conventional methods as followed in process development cannot establish the consistency and reproducibility of the results. The interactions of the process variables are quite strong in many processes and they create havoc in the process leading to inconsistent results. Further, among the process variables, some will influence the average performance and some other will influence the variation in the results. Due to the inability of the OFAT method, the factors affecting the average performance and the variation in the results cannot be established and hence consistent and cost optimal results cannot be achieved. What ever is achieved with OFAT, the cost optimization cannot be proved.

Why is DOE not being followed in many Industries?

DOE methods were not part of the curriculum in many universities in the past.  Several engineers and scientists who attended the appreciation courses in academic sessions were not ready to use DOE due to its detailed mathematical calculations. As a result, OFAT method had been in use.

Some of the software packages that were made available later were not user friendly and were not in the sequence of process development steps. These factors made it difficult for the scientist and engineers to adopt these methods. Sigma Tech software is user friendly and can be used easily with little training. It is designed in the sequence of process development steps.

Hence, Swaroop Tech Services Pvt. Ltd has been trying to spread these DOE methods in the Corporate R&D s in industry, Professional Institutions and in academics by conducting various seminars and workshops through Sigma Tech software and guiding the Research Scholars through the use of Sigma Tech software in completing their project works.

What are the advantages of using DOE in process development?

  • At least, the process development cycle time and resources will be reduced by 50% by using DOE as compared to the OFAT
  • The interactions that significantly influence the results can be identified. This leads to improved results.
  • The factors that affect the variation in the results can be identified and a consistent and robust process can be designed to guarantee quality.
  • A cost effective optimal solution can be achieved.
  • When a large number of factors are confronted, they can be screened to find out the few most significant factors that matter for achieving the desired results using with least number of (say n + 1, where n is the number of variables) experiments.

Which organizations use DOE methods for process development?

  • Hoecshst Celanese
  • Glaxo
  • Pfizer
  • ICI
  • Teva API India
  • Freseneous Kabi-Oncology India
  • Divis Laboratories India
  • Ranbaxy Labs India
  • Reddys Labs India
  • NATCO India
  • Laurus India
  • Hindustan Levers India
  • Sudarshan Chemicals India
  • Crompton and Grieves India

What is AQbD?

AQbD means Analytical Quality by Design.  Food and Drug Administration (FDA) has approved a few new drug applications (NDA) with regulatory flexibility for quality by design (QbD) based analytical approach. The concept of QbD applied to analytical method development is known now as  AQbD  (analytical quality by design).

How does it benefit the Analytical Method Development?

Unlike current methods, analytical method developed using analytical quality by design (AQbD) approach reduces the number of out-of-trend (OOT) results and out-of-specification (OOS) results due to the robustness of the method within the region. It allows the analytical method for movement within method operable design region (MODR) and does not call for approval from Regulators as long as the parameters are changed within the MODR.

What happens if we use the current practice of Analytical  Method Development?

In current practice, the implemented analytical methods were based on one factor at a time (OFAT), in which one parameter alone is optimized for the expected response whilst others remained constant. This practice always yielded a narrow robust behavior of the method for instrumental variables used in method development phase. Hence the present strategy of analytical method (i.e., OFAT) development has high risk in method failure and always requires re-validation protocol after method transfer or alternative method development; thereby it has been increasing the cost of the method.