Pharmaceuticals - Fundamentals of Industrial Chemistry: Pharmaceuticals, Polymers, and Business - page 168

it is operating properly. Performance qualification is done to ensure that the
equipment operates correctly in the actual operating environment. Traceabil-
ity is important so raw materials must be controlled and traceable to products.
Batch records and equipment use records should show ingredients, equip-
ment, containers, labeling, and personnel. Lot or batch numbering is the key
to traceability.
To be cGMP compliant, there must be Good Documentation Practices
(GDP). It is important to write things down in permanent indelible black
ink, to leave no doubt, and to sign and date the entry. Correction fluid should
not be used. If there is an error: draw a line through without obscuring the
original entry; make the correction; sign and date the correction.
When the FDA inspects a facility and finds situations of objectionable con-
ditions or practices, at the conclusion of the inspection they issue a Form 483.
This represents a list of GMP concerns in the judgment of the inspector. By
monitoring 483s, which are public record, companies can maintain currency
in GMP. Warnings letters can also be issued by the FDA. They represent
concerns not only of an investigator, but of District and/or Center compliance
officers. Possible repercussions include product recall, seizure, injunction,
monetary fine, debarment, disqualification, license suspension or revoca-
tion, prosecution, or denial of access to United States market for foreign
suppliers.
Drug development can be divided into different stages. Initially, there is the
discovery activity. The discovery activity is not governed by regulatory stan-
dard [23]. In the next stage, toxicology and safety pharmacology studies, with
a potential extension to pharmokinetics and bioavailability are done. These
studies can be termed non-clinical or preclinical because they are not done
with humans. The primary purpose of this stage is safety and it requires com-
pliance with Good Laboratory Practices (GLP). Subsequent stages involve
clinical studies with humans. Here Good Clinical Practice (GCP) is required.
Also at this stage, and through the lifetime of the drug, all manufacturing must
be done according to cGMP. In the commercial manufacturing of an approved
drug, the quality control labs are governed by cGMP and not by GLP. GLP
is described in part 58 of Title 21. This part is divided into 11 subparts with
each subpart describing an aspect of GLP.
GLP can be broken down into six requirements [24]:
1. Responsibilities should be defined for the sponsor management, study
management, and quality assurance unit.
2. All routine work should follow SOPs.
3. Facilities should be large enough and constructed to ensure the integrity
of the study.
4. Test and control articles should have the right quality and instruments
should be calibrated and well maintained.
5. People should be trained or otherwise qualified for the job.