Good Manufacturing Practice Guidance: Can We Make It Global?
Good Manufacturing and Distribution Practice is a necessary practice to ensure the overall safety and well being of society as a whole. The issue of whether it can be made global is simplistically complicated. Simplistic in the fact that, yes, globalization of Good Manufacturing Practice can be done and should be done, however complicated in the fact that while easy to agree to do, hard to actually implement or get other countries to all agree to a standard set of practices. Just about every country has some set of standardize practice and they are similar to varying degrees but they are not universal and while one country has a set of standards that are deemed exceptional there are othersâ?T that are deemed marginal at best which then requires other counties to employ their own standards. While this multiple checking is beneficial and can only improve quality control it is expensive and time consuming. If the three pharmaceutical industry regions can get together and form the International Conference on Harmonization and set a standard and greatly and contentiously improve the overall industry, it just greatly increases the likelihood that globalization of GMP is plausible and needs to be done.
The devolvement of new potential drugs is vital to the treatment of diseases and improving the quality of life for the worldâ?Ts population. With the research and development of these potential life saving drugs comes the testing and ultimately the distribution of these drugs. Over the past decades extensive research has gone into the best effective efficient and safest way to test these drugs. The whole process of Clinical trails has been examined under a microscope and the outcome has led to extensive rules and regulations both in the USA and other counties abroad. These rules and regulations are the corner stone of safety and they were created to ensure that the publicâ?Ts best interest is always first and foremost. With that being the priority, the leading countries have gotten together to globalize safety standards and to ensure compliance. It was the desire to improve standards and create harmonization among countries all while acting in the best interest of its people that has lead to the success of the International Conference on Harmonization. The success of the ICH just makes a case that globalization of GMP is possible and only serves to streamline the overall process and ensure efficiency and effectiveness and reduce overall errors, delay and repetitiveness.
Good Manufacturing Practice or GMP (also referred to as ‘cGMP’ or ‘current Good Manufacturing Practice’) is a term that is recognized worldwide for the control and management of manufacturing and quality control testing of foods and pharmaceutical products.5 â?oThe World Health Organization (WHO) version of GMP is used by pharmaceutical regulators and the pharmaceutical industry in more than one hundred countries worldwide, primarily in the developing world. The European Union’s GMP (EU-GMP) enforces more compliance requirements than the WHO GMP, as does the Food and Drug Administration’s version in the US. Similar GMPs are used in other countries, with Australia, Canada, Japan, Singapore and others having highly developed/sophisticated GMP requirementsâ?ť 5
Compliance with GMP principles ensures that medicinal products are consistently produced and controlled to appropriate quality standards. Unlike a number of EU member states, the UK does not require manufacturers to manufacture IMPs in accordance with the principles of GMP. However many UK manufacturers voluntarily follow the European legislation on the principles of GMP for manufacturing marketed products and the detailed guidance on IMPs. Currently, medicines manufactured for clinical trials are produced to a specification agreed by MHRA, but there is no certification or inspection of their manufacture.2
While many of most of the regions practice GMP and have various ethic and compliance committees in place, the standards by which these regulations are enforced and monitored vary greatly by country. The Food and Drug Administration (FDA) announced a new initiative that will greatly improve its overall regulation and monitoring of pharmaceutical manufacturing. The Pharmaceutical Current Good Manufacturing Practices, is â?ointended to modernize FDA’s regulation of pharmaceutical quality for veterinary and human drugs and select human biological products such as vaccines.â?ť 4
The FDA recognized the benefits and importance other countries have in the manufacturing of marketed products so it has reached out to the international community to expand its current paradigm. â?oThe FDA has increased its collaboration with international health and regulatory partners and will continue to actively collaborate with other regulatory authorities, in multilateral and international forums, to harmonize pharmaceutical quality standards or requirements to the fullest extent possible.â?ť 4
The ICH established an agreement with the FDA to create a plan that would harmonize the pharmaceutical manufacturing of marked products. This establishment involved the creation of two expert groups that serve to balance the risk and quality for a product. â?oIn November 2003, an agreement was reached by ICH to work on an internationally harmonized plan for developing a pharmaceutical quality system based on an integrated approach to risk management and science. FDA is developing bilateral and multilateral confidentiality agreements and specific information exchange agreements to facilitate these activities. To implement its vision, ICH established two Expert Working Groups (EWGs) on pharmaceutical development. The first (ICH Q8 EWG) seeks to incorporate elements of risk and quality by design throughout the life-cycle of the product. â?o 4
In the United Kingdom, The Medicines Inspectorate was established to ensure compliance with standard provisions set fourth for any applicant with licences in the UK.2 It was under the Therapeutic Substance Act that the Medicines Inspectorate now oversees the functions of the Department of Health (DH) Inspectorate, broadening its scope to biological products, and bestowing the authorization to inspect manufacturers in other countries that export products to the UK.2 It was not until 1991 that GMP and their manufacturing authorizations became universal within the European Community.
In Australia their quality control is guided by strict regulations and their systems are extensively monitored to ensure compliance. Any product imported or exported out of the country must follow the same rigorous standards set fourth. This system, while strict, ensures a quality product. The Therapeutic Goods Act of 1989 required any manufacture wanting to manufacture a therapeutic good obtain a licence.â?ť It is an offence, carrying heavy penalties, to manufacture therapeutic goods for human use without a licence unless the manufacturer or goods are exempt from this requirement.â?ť 3 Obtaining a licence to manufacture therapeutic goods requires an applicant to demonstrate complete compliance with manufacturing principles, which is observed with an on site factory audit.
The TGA even extends to overseas manufacturers, who also must pass the same standards of GMP required by Australian manufactures if they expect their goods to be accepted into the country. These sponsors must provide proof in the form of documentation that their products are manufactured to the same standards as those deemed acceptable in Australia. In the event that a sponsor is unable or unwilling to provide such evidence, the TGA will conduct an onsite audit of the factory following the same SOP as it would if the factory was in Australia.
â?oCompliance with the Codes of GMP and / or Quality System requirements in Australia is ascertained by carrying out regular on-site audits. The purpose of the audits is to assess compliance with the relevant manufacturing standard, the conditions specified in the manufacturing licence and compliance with the relevant marketing authorizations. Each audit involves a detailed examination of the operations and procedures of the factory, and includes a detailed review of all processing activities, process validation, batch documentation and quality control testing. Product samples may be taken for testing by TGAL (Therapeutic Goods Administration Laboratories). The audit is concluded with an exit interview during which the manufacturer is provided with a summary of the findings of the audit. This summary is confirmed in writing at a later date by means of an audit report. The manufacturer is required to respond satisfactorily to the audit report before the audit is closed out. â?o 3
The UK Inspectorate currently carries out regular inspections in a number of countries, including USA, India, China and Japan both in connection with national requirements and on behalf of the European Medicines Agency (EMEA).
The Natural Health Products Directorate (NHPD) in Canada requires that before any site license will be given out, a location must meet all regulations of GMP set fourth by the NHPD, this includes any site that intends to manufacture, package, label or import products for sale in Canada.â?ťThey are also responsible to provide evidence that imported NHPs will be manufactured, packaged, labeled, imported, distributed and stored according to GMPs as set out in part 3 of the Regulations or their equivalent. â?o 1
Each of these countries are mere examples of the steps they are taking to ensure that manufactured products are met with the upmost quality and care. Some have gone as far as to require it for both its imports and exports of products. It just shows that countries worldwide are committed to the safety and quality of any and all products and that the overall safety of its citizens is top priority. To take this information and combine it with that of other countries can only improve the already effective system. Where one country is lacking another country, can add strength.
Each country can greatly benefit for each otherâ?Ts SOP and regulations. A more streamline process can ensure the ease of products reaching those people who need it without compromising the integrity or safety of the product. The process could be efficient and cost effective, eliminating the need for double and triple inspections and thus lessen the number of sample products needed to ensure compliance. Globalization of GMP will allow for better communication between the regions and will decrease the delay in response and having a central compliance committee will allow for a more effective monitoring system.
The biggest obstacle would be compliance and the enforcement of the new standards but that can be overcome with an agreed upon committee to head the monitoring. Every country involved would have a representative and from this a committee would be formed. This committee will set fourth and enforce the agreed upon new quality GMP standards and then be charged with the task of ensuring compliance. Established time lines, sanctions, penalties authorized personnel will be established from this committee. The success of this committee will greatly depend on the overall commitment and reliability of the countries involved. Each represented country must understand that their success of this project is dependent on their involvement and commitment of its success.
The globalization of GMP is a vison but not an impossible one, fore many countries have already shown their commitment to the overall quality and safety of manufactured products both imports and exports. Someone just needs to take the initiative and to get the ball rolling in making this vison an actual success. While the FDA has committed to working with the ICH on global GMP those countries involved and other countries as well need to take the initiative as well for this to be a major success. We have the idea and the resources, but itâ?Ts just a matter of using them to the benefit of our citizens.
Health Canada. (2007, August 20). Good Manufacturing Practices Guidance Document. Retrieved August 17, 2007, from http://www.hc-sc.gc.ca/
MHRA. (2007, January 02). Good Manufacturing & Distribution Practice. Retrieved August 15, 2007, from http://www.mhra.gov.uk/
Therapeutic Goods Administration. ( 2007, February 26 ). Good manufacturing practice for therapeutic goods. Retrieved August 17, 2007, from http://www.tga.gov.au/
U.S. Food and Drug Administation. ( 2006, July 28). Pharmaceutical CGMPs for the 21st century A Risk- Based Approach Final Report. Retrieved August 15, 2007, from http://www.fda.gov/
Wikipwdia The Free Encyclopedia. ( 2007, August 20). Good Manufacturing Practice. Retrieved August 17, 2007, from http://wikipedia.org