A Technical Article by Colin Ellis (Managing Director, Hanningfield)

What is GMP?

GMP or ‘Good Manufacturing Practice’ is the area of quality assurance which ensures that medicinal (and some food) products are consistently produced and controlled to the quality standards appropriate for their intended use and as required by the product specification. In this respect, GMP is concerned with both quality control and production.

“The FDA inspects manufacturing facilities worldwide using scientifically and cGMP-trained individuals whose job it is to evaluate whether the company is following the cGMP regulations.” GMP regulations are enforceable by law and require that manufacturers, processors, and packagers of pharmaceuticals, medical devices, and some types of food products take proactive steps to ensure that their products are pure, effective and safe to use.

"The FDA ensures cGMP standards are upheld."

GMP regulations address all issues that concern record keeping, hygiene, personnel qualifications, cleanliness, equipment verification and the handling of complaints. These regulations in turn protect the consumer from purchasing a product which is ineffective or potentially life threatening. Failure of manufacturers to comply with GMP regulations can result in very serious consequences such as seizure, recall, fines and ultimately imprisonment.

The main aim of GMP is to consistently produce high quality medicines or medical devices that meet the international standards required for responsibly managed healthcare. Processes used in manufacture are carefully controlled, and any changes to the process must be evaluated. Changes that have an impact on the quality of the finished product are also validated as required and checked for compliance and consistency with the product specifications.

GMP requirements are not definitive instructions on how to manufacture specific products. GMP forms a series of general principles that must be observed during manufacturing. When a company is setting up its quality program and manufacturing process, there may be many ways to comply with GMP requirements. It is the company’s responsibility to determine the most effective and efficient quality process. This provides much flexibility, but also requires that the manufacturer interpret the requirements in a manner which makes sense for each individual business.

GMP is sometimes referred to as ‘cGMP’ or ‘Current GMP’ reminding manufacturers that they must employ technologies and systems which are up to date in order to comply with the relevant regulations. Systems and equipment adopted to prevent contamination and errors in the past may be considered less than adequate by current standards.

The Basic Rules of GMP

• Operators must be adequately trained to carry out and document procedures.

• Instructions and procedures should be written in clear and unambiguous language. These instructions are often referred to as ‘SOP’s’ or ‘Standard Operating Procedures’.

• Records must be kept, (manually or by instrumentation), during manufacture which proves that all the steps required by the defined procedures and instructions were taken and that the quantity and quality of the drug was as expected.

"GMP is as much about procedures and operator training, as it is about equipment usage."

• Any deviations from the standard procedure found during the keeping of production records must be investigated and documented.

• Records of manufacture (including distribution) that enable the complete history of a batch to be traced must be kept and retained in a comprehensible and readily accessible form.

• Care must be taken to ensure the distribution of the drugs minimizes any risk to their quality.

• A system must be in place for recalling any batch of drug from sale or supply.

• Complaints about marketed drugs must be examined and the causes of quality defects investigated.

• Appropriate measures must be taken with respect to the recall of defective drugs to prevent any future recurrence.

Equipment Design and Manufacture

GMP also applies to the design and manufacture of process equipment. Although this area of GMP is not strictly covered by legislation, it is the responsibility of the equipment manufacturer to understand the importance of hygienic design and the training of competent staff to design and construct equipment that meets the specific needs of the end user and comply with GMP requirements. Documentation also has to be provided to give evidence of competence and materials used in construction.

"GMP also applies to equipment manufacture"

The following points should be considered in the design and construction of process equipment intended for use in GMP regulated industries;

• Design must avoid where possible ledges, dirt traps and flat surfaces where excess dust layers can build up.

• All equipment should be easy to clean and ideally be dismantled without the use of tools.

• Materials of construction must meet the required specification and evidence of materials used should be available. In some cases thorough traceability may be required through mill certificates or other means of identification.

In general most end users will provide a detailed specification or URS (user requirement specification) which will provide in detail the exact requirements in terms of materials, surface finishes and material certification. Competency of the manufacturers ability is also often required which may include evidence of a recognised quality system and proof of staff competency for areas such as design, welding, electrical and other areas of equipment construction.

Hopefully this has helped to shed some light on GMP. If you have any questions whatsoever, I would be delighted to answer them.