Pharmaceutical Industry

My recent interest in the Pharmaceutical Industry has allowed me to explore learn a great deal about the manufacturing processes and regulatory guidelines in different countries. I would like to share what i have learned about Good Manufacturing Practices(GMP) in the Pharmaceutical Industry.

 

Good Manufacturing Practices (GMP)

Guidelines and standards are important in any industry you work in but nowhere does it get updated and changed more so than in the Pharmaceutical Industry. Designing a modern, compliant pharmaceutical facility is difficult enough within a demanding and competitive industry but constantly changing standards and increasing complexity of regulations make it even tougher¹.

 

 Overview

According to the World Health Organisation(WHO): “GMP or good manufacturing practice is a part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to the intended use as required by the marketing authorisation.” The general guiding principle behind GMP is that quality should built into the product and not just into a finished product. So the product not only meets the final specification but has been made using the same procedures under the same conditions under the same conditions each and every time. There is a term for ensuring quality is built into the design of pharmaceutical products, Quality by Design (QbD), which is probably the hottest topic in the industry now since GSK has successfully demonstrated a continuous production process. I will have to talk more on QbD on another article and place the link here**.

This would mean that we have to control the quality of the starting materials, the facility and its systems should be top notch as well as maintaining quality of production at all stages. Apart from these, quality should be ensured during testing of the product and all materials must have adequate storage facilities.

GMP covers all aspects of manufacturing process and I am going to list out below what GMP inspectors are typically looking for:

1.                   A well-defined manufacturing process

2.                   Validated critical manufacturing steps

3.                   Suitable premises for storage and transport of materials

4.           Qualified and trained production, quality control personnel

4.                   Adequate laboratory facilities

5.                   Approved written procedures and instructions

6.                   Records all steps taken

7.                   Full traceability of product

8.                   Systems for recall and investigation of complaints

If we look at a typical project stages in the Pharmaceutical industry, we can locate the stages in which certain guidelines and regulations kick in. For example see the figure below for an overview:

Regulatory driven manufacturing requirements cover various issues including facilities design, product delivery and validation issues.

 

Regulatory Issues

Although different countries have their own regulatory bodies, the most widely used (accepted) are the FDA, EU and Japan regulations because these regions house major pharmaceutical manufacturers and represent the largest proportion of the market combined. While FDA’s current GMPs provide minimal guidance by outlining facility requirements and requirements for documentation of manufacturing procedures, the FDA also issues regulations in the code of federal register (CFR) 21. These regulations are summarised in the table below:


 

No.	CFR Regulations
21 CFR 210	Current Good Manufacturing Practices in Manufacturing, Processing, Packaging or General Holding of Drugs
21 CFR 211	Current Good Manufacturing Practices for Finished Pharmaceuticals
·  Part C	Building and Facilities
·  Part D	Equipment
21 CFR 600	General Biological Products
21 CFR 820	Quality Systems Regulations

Future Implications

GMP guideline is constantly evolving with technology to accommodate rising demand for quality and value products. The future of global pharmaceutical industry is going to be “dynamic and highly responsive to marketing and regulatory forces”¹. There will be higher expectations from manufacturing facilities to keep up with economic and regulatory requirements in order to maintain flexibility, safety, value and speed to market. Good design practices will apply to all manufacturers as they try to achieve business objectives and at the same time conform to globally harmonised guidelines which address an increasingly safety and quality conscious community. 

 

Reference/Further Reading:

[1] Good Design Practices for GMP Pharmaceutical Facilities: Drugs and the pharmaceutical industry, Andrew A. Signore, Terry Jacobs Vol. 146 [2005]

[2] Good Manufacturing Practices for Pharmaceuticals: A plan for Total Quality Control, Sidney H. Willig, Murray M. Tuckerman and William S. Hatchings IV, [2^nd / 3^rd Edition]

[3] Modern Pharmaceutics, edited by Gilbert S. Banker and Christopher T.  Rhodes

[4] Pharmaceutical Process Validation, edited  by Bernard T. Loftus and Robert A. Nash

[5] Handbook of Pharmaceutical Granulation Technology, edited by Dilip M. Parikh

[6] Automation and Validation of Information in Pharmaceutical Processing, edited by Joseph F. deSpautz

[7] Pharmaceutical Process Engineering, Anthony J. Hickey and David Ganderton*