The United States and European Union both attempt to control the safe testing and manufacture of medical devices and pharmaceutical products through Good Manufacturing Practices or GMPs. In general, these practices adhere to two primary ideas:
- Manufacturing processes should be clearly defined and controlled. All critical processes are validated to ensure consistency and compliance with specifications that the manufacturer has developed for the product.
- Manufacturing processes are controlled, and any changes to the process are evaluated before they are changed. Changes that have an impact on the quality of the product (the drug, or medical device) are carefully evaluated.
However, these GMPs are not nearly as helpful or as straightforward as they seem.
In the United States, one version of GMP’s are supervised and enforced by the FDA, while in the Europe, the European Union issues different GMP’s for pharmaceutical manufacturers. The World Health Organization also uses different GMP standards, primarily in the developing world.
Now with multiple standards coexisting and often conflicting with each other, GMPs have caused a good amount of confusion for many companies, especially ones who do business internationally and therefore must adhere to multiple standards, which can conflict with each other.
The situation is further complicated by the fact that FDA issues guidelines rather than rules.
“FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word ‘should’ in Agency guidance means that something is suggested or recommended, but not required.”
Because there are no hard rules governing GMPs from the FDA, manufacturers can never be certain that the practices they have followed will be approved by the FDA.
Such a lack of clear standards and conflicting guidelines has often led our clients to ask:
- Whose standard should we follow?
- How do we resolve conflicts between the various standards?
- How do we satisfy the FDA and understand what they want with their recommendations?
For some time, it has been difficult to address these questions. Fortunately, the International Standards Organization, commonly referred to as ISO, is bringing an element of consistency to these GMPs and has also created its own set of standards that are not region specific. For the last decade or so, ISO standards have begun to be used in addition or in place of FDA and EU standards to help resolve the discrepancy that often arises. Each year, the FDA is referencing more ISO standards in their documents, which makes it easier to understand what they are looking for, although the situation continues to be murky for companies operating internationally.
For example, the most recent version of ISO 14644 published, “ISO 14644-9:2012 establishes the classification of cleanliness levels on solid surfaces by particle concentration in cleanrooms and associated controlled environment applications. Recommendations on testing and measuring methods, as well as information about surface characteristics are also given.”
Therefore while progress has been made to clarify the applicable standards and how they are implemented, they continue to evolve and may still present difficulties when being interpreted and implemented. What is important to know is that when building a new pharmaceutical or medical device facility or updating an existing one, every effort should be made to work with a firm familiar with these standards to help you interpret and implement them correctly.
 FDA’s Guidance for Industry - Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice, http://www.fda.gov/downloads/Drugs/.../Guidances/ucm070342.pdf