21 211 or 21 CFR Part 211 compliance requires the manager of any regulatory controlled manufacturing company to manufacture all medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorization and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this 21 211 compliance is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company’s suppliers and by the distributors.
To achieve 21 211 compliance there must be a comprehensively designed and correctly implemented system of Quality
Assurance Incorporating Good
Manufacturing Practice, and thus Quality
Control and Quality
Risk Management.It should be fully documented and its effectiveness monitored.
All parts of the Quality Assurance systems should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. There are additional legal responsibilities for the manager of the manufacturing authorization and for the authorized person(s). The basic concepts of Quality Assurance, Good Manufacturing Practice, Quality Control and Quality Risk Management are inter-related. They are described here in order to emphasis their relationships and their fundamental importance to the production and control of medicinal products.
Quality Assurance is a wide-ranging concept, which covers all matters, which individually or collectively influence the quality of a product. It is the sum and total of the organized arrangements made with the objective of ensuring that medicinal products are compliant with the requirements detailed in 21 211. Quality Assurance therefore incorporates Good Manufacturing Practice (GMP) plus other factors outside the scope of this Guide.
The system of Quality Assurance appropriate for the manufacture of medicinal products should ensure that:
Specifications describe in detail the
requirements with which the products or materials used or obtained
during manufacture have to conform. They serve as a basis for quality
evaluation. Manufacturing Formula, Processing and Packaging Instructions
state all the starting materials used and lay down all processing and
Procedures give directions for performing certain operations e.g.
cleaning, clothing, environmental control, sampling, testing, equipment
operations, as detailed in 21 CFR Part 211.
Records provide a history of each batch of product, including its
distribution, and also of all other relevant circumstances pertinent for
quality of the final product.
Documents should be designed, prepared, reviewed and
distributed with care. They should comply
with the relevant parts of the manufacturing and marketing authorization dossiers as detailed in 21 CFR Part 211.
Documents should be approved, signed and dated by appropriate and authorized persons.
Documents should have unambiguous
nature and purpose should be clearly stated. They should be laid out in
an orderly fashion and be easy to check. Reproduced documents should be
clear and legible. The reproduction of working documents from master
documents must not
allow any error to be introduced through the reproduction
Documents should be regularly reviewed
and kept up-to-date. When a document has been revised, systems should be
operated to prevent inadvertent use of superseded documents. As
detailed in Part 11 and 21 CFR Part
Documents should not be hand-written; although, where documents require the entry of data, these entries may be made in clear, legible, indelible handwriting. Sufficient space should be provided for such entries.
Any alteration made to the entry on a document should
be signed and dated; the alteration
should permit the reading of the original information. Where appropriate, the
reason for the alteration should be recorded.
The records should be made or completed at the time each action is taken
and in such a way that all significant activities concerning the manufacture of
medicinal products are traceable. They should be retained for at least one year
after the expiry date of the finished product.
Data may be recorded by electronic data processing
systems, photographic or other reliable means, but detailed procedures relating
to the system in use should be available and the accuracy of the records should
be checked. If documentation is handled by electronic data processing methods,
only authorized persons should be able to enter or modify data in the computer
and there should be a record of changes and deletions; access should be
restricted by passwords or other means and the result of entry of critical data
should be independently checked. Batch records electronically stored should be
protected by back-up transfer on magnetic tape, microfilm, paper or other means.
It is particularly important that the data are readily available throughout the
period of retention.