|
GMPs grew out of the
realization that end-point quality testing was insufficient to
assure the quality of the individual medication unit (the tablet,
the capsule, the vial) dispensed to the patient, but rather quality
needed to be assured at each step of the manufacturing process to be
as certain as possible that each dosage unit met its quality
specifications. Prior to this realization, pharmaceutical product
quality was assured by pharmacopoeal “end point” testing. |
Japan, Korea and the United States are the only
countries where the GMPs have been enshrined in law as legal
regulations. In the United States non-compliance with the GMPs during
manufacturing and testing, is taken by the courts as evidence that the
drug is adulterated, and hence cannot be marketed. For example, the US
GMPs mandate that when performing weighing operations (as well as for
other specified operations such as addition of chemicals to the
formulation) two people need to be present to perform the operation –
one to perform and one to watch and concur that all is correct. An FDA
inspector has no leeway to apply his own judgment during an inspection
when faced with one person performing the operation. The regulations are
the law, and the regulations mandate that two people be present
throughout the operation.
In other countries, a company having a valid
reason as to why there is only one person performing the activity can
reasonably discuss their rationale with the GMP inspector, and the
company will probably not receive a citation for non-compliance with the
GMPs.
|
While the US is generally
perceived by industry to be the toughest inspection agency due to
its inflexibility in interpretation of the regulations, the British
Commonwealth countries rank second due to their hiring practices for
inspectors. US inspectors typically do not have any background in
the healthcare manufacturing and food industries on joining the
agency – an FDA inspector being required to inspect all types of
facilities falling with FDA’s remit – but are entirely trained on
the job. Inspectors in the British Commonwealth countries only
inspect pharmaceutical manufacturing facilities and are not hired
unless they have 5 – 10 years of management experience within the
industry. Hence not only do these inspectors know what the
skeleton’s look like, they have the experience to understand where
the skeletons, if they exist, are most likely buried. American
companies inspected by the British MHRA would place the British at
the top of the above ranking; while European and Asian companies
place the Americans at the top. It often occurs that an American
company that has passed numerous FDA inspections will fail a British
MHRA inspection. Likewise a British company, with years of
compliance history to British GMPs will fail an FDA inspection. This
can and often is extremely embarrassing to both the company, and the
authorities, as evidenced by the failure of the British company
Fisons to pass an FDA inspection in 1994 which lead to questions in
the British House of Commons as to the effectiveness of the British
Department of Health and Social Services (a precursor to the crrent
MHRA) in doing its job.
It is
interesting to note the divide between approaches to GMP inspections
in Europe seems to be cultural, with countries that historically
were once part of the Holy Roman Empire (HRE) having a much looser
attitude to GMPs, GMP compliance and government regulations in
general, than the attitude of their Northern European neighbors, who
historically were outside the HRE. This is a concern that will
repeat itself when considering other multi-national agreements, as
explained later in this chapter when considering the potential for a
US-EU Memorandum of Understanding on Mutual Recognition of GMP
inspections. |
|