hange is good because it encourages self-development. Without it, there would be no progress. Change is always challenging,
but the pharma industry is growing and surviving because it is accepting such changes in regulatory requirements and markets.
The last two decades have witnessed many changes including:
- Regulators supporting industry by introducing compliance initiatives, such as PAT and quality risk management (QRM).
- More stringent regulations; for example, the introduction of cGMP by FDA.
- The compliance efforts made by the industry.
- An increased quality awareness among manufacturers to strengthen the business.
- The industry's shift towards total quality management to ensure product safety, quality and efficiency.
- A stronger focus on effective clinical trials.
- Steps towards harmonization of regulatory compliance, and the advancement of International Conference on Harmonization (ICH)
Quality topics — Q7a, Q8, Q9 and Q10.
- Improved communication between regulators in different countries.
- Analytical equipment that is 21 CFR Part 11 compliant.
- Improved auditing processes.
- Introduction of e-filing process and common technical documents.
- Progress in paperless operations (i.e., electronic documentation systems).
- Evolution of new markets, such as Brazil, China, India, Indonesia, Mexico, Russia and Turkey (E7).
- Increased outsourcing for R&D, manufacturing, testing and clinical trials activity.
Indeed, the most important change the global pharma industry has witnessed is FDA's introduction of two new initiatives: QRM
and PAT.
QRM. FDA introduced this in 2003. It is a systematic approach for assessing, controlling, communicating and reviewing the quality
of a drug product during its life cycle. ICH, the European Agency for the Evaluation of Medicinal Products (EMEA) and the
World Health Organisation (WHO) have also now introduced QRM. The four major steps involved in QRM are:
- Risk assessment: this covers identification, analysis and evaluation of risks.
- Risk control: this takes care of controls, reduction and acceptance of risks.
- Risk communications: sharing information on risk among all stakeholders
- Risk reviews: results of risk management processes are to be reviewed to identify what can be learned from the experience.
The benefits of PAT
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The primary principle of QRM is to evaluate the risk to quality and how it is linked to the protection of patients. Documentation
and efforts must also balance the level of scientific-based risk. The approach is beneficial as it saves time, energy and
money. It can also avoid problems and issues in manufacturing, and ensure compliance and quality of products.
FDA has suggested various management methods to minimize the risks of noncompliance. They help to provide a scientific and
practical approach to decision making by providing documented, transparent and reproducible methods to accomplish QRM (see
sidebar "Methods to accomplish QRM").
Methods to accomplish QRM
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PAT. This FDA initiative was introduced in September 2004 to help the industry understand its manufacturing processes. Dr Ajaz
Husain, former FDA Deputy Director, and architect of PAT, believed that it would take the industry to a "desired state", as
process understanding is a foundation for innovation and continuous improvement in R&D and manufacturing. It is now a part
of cGMP, and ICH also emphasizes the need to adopt an integrated, quality by design (QbD) approach to ensure an effective
quality manufacturing system. PAT has huge benefits (see sidebar "The benefits of PAT") and ensures the continuous control of processes and the timely availability
of quality products to market, which results in satisfied customers. This is a step towards real time release. Additionally,
PAT improves profit after tax because of increased productivity, and minimum reworking and rejections of products.
There are many ways to implement PAT. Some of them are:
- Developing an integrated science- and technology-based platform in the organization.
- Creating awareness of QbD and science by design across all aspects of a product's life cycle.
- Understanding each step of the manufacturing process before implementation.
- Developing a culture of 'right first time and every time'.
These can be supported by the following road map:
- Training and knowledge of PAT and its benefits for all concerned, including the finance head whose final clearance is needed
for investments.
- Identify which technologies will be used.
- Focusing on the complete process — from API to finished product.
- Manufacturing with Six Sigma mentality.
What advice would you like to give to the next generation of pharmaceutical scientists?
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Ideally, a PAT team should be developed that involves manufacturing, R&D, quality assurance, quality control (QC) and regulatory
departments. Additionally, a strategic initiative leader should be identified who can successfully implement PAT. Trust and
mutual understanding will help the team to work quickly together, and good coordination is necessary for effective performance.
Depending on the product, the team will decide which PAT tools should be utlilized. Various options are available to help
measure or analyse the products on-line, such as near infrared, colour imaging techniques and Raman spectroscopy. Although regulatory agencies have done an excellent job by introducing initiatives, such as QRM and PAT, that set the standard
for compliance in the industry, I also believe that the industry would appreciate a global regulatory cGMP system. Today,
various agencies have different requirements and it is time consuming and expensive to cope with the mixed demands. If agencies
could speed up review and inspection processes, it could mean the faster approval and launch of a new product. Current approval
time is 15–24 months, which could potentially be reduced to 12–15 months.
